Background:Predicting which individuals with M. tuberculosis (M. tb) infection will progress to active disease remains challenging. We evaluated whether a pragmatic serial, quantitative ESAT6-CFP10 (EC) antigen-based skin test strategy improves risk stratification for targeted prevention in a large-scale prospective cohort. Methods:We enrolled 73,761 contacts identified during school-based tuberculosis outbreaks in Jiangsu, China, from 2020 to 2024. Participants underwent baseline EC test, chest radiography, and symptom screening. EC-negative individuals were retested after 8-12 weeks. Incident tuberculosis was identified through active surveillance and registry linkage. We compared single vs. serial test strategies using Cox models, receiver operating characteristic (ROC) curves and precision-recall (PR) curves. Findings:Among 73,761 close contacts, 108 had prevalent tuberculosis and 190 developed incident cases (overall incidence 151.2 per 100,000 person-years). EC response size predicted incident tuberculosis in a steep, dose-dependent manner. Each 1-mm increase in the maximum response diameter was associated with a 7% higher hazard. The serial test strategy, utilizing the maximum response from two measurements, substantially outperformed single test [C-statistic: 0.806 vs. 0.722]. At the ≥5 mm threshold, this combined strategy yielded a sensitivity of 65.0% and specificity of 96.1%. The subgroup of recent converters had a PPV of 3.4% (95% CI: 2.8-4.1), corresponding to an NNT of approximately 30, and a hazard ratio (HR) of 45.12 (95% CI: 32.50-62.63). Preventive treatment completion was strongly protective (aHR 0.17; 95% CI: 0.11-0.25). Interpretation:The "test twice, take maximum" EC strategy provides superior risk stratification for tuberculosis prevention. This approach identifies high-risk contacts for targeted intervention. Despite limited sensitivity, these results suggest that quantitative EC skin testing can provide a practical alternative for programmatic risk stratification. In settings where IGRAs are constrained by cost or infrastructure, this approach may enable more efficient targeting of preventive treatment. Funding:National Natural Science Foundation of China (82504476, 82473693, 82574173); Jiangsu Province Preventive Medicine Research Project (Ym2023039); The Special Scientific Research Project for Talent Introduction of the First Affiliated Hospital of Wannan Medical College (KY2960YR2530); Jiangsu Province Postgraduate Research and Innovation Project (KYCX24_2061).

Importance:Tuberculosis preventive therapy is central to reducing tuberculosis, and foreign-born individuals account for most US tuberculosis cases. Current US Preventive Services Task Force guidance recommends testing and treating all foreign-born individuals regardless of age or time since immigration, yet the risks of disease progression and of treatment-related harm are not uniform across these groups. Objective:To evaluate the cost-effectiveness and health outcomes of tuberculosis infection treatment strategies among immigrants from high-burden settings, stratified by age and time since immigration. Design:Decision analytical model using individual-level microsimulation (Markov model) over a 30-year horizon, with deterministic and probabilistic (second-order Monte Carlo) sensitivity analyses. Costs and outcomes were discounted at 3%. Setting:US TB and primary care clinics (healthcare-sector perspective), using observed data from the Boston Medical Center/Boston Public Health Commission tuberculosis clinic and published literature. Participants:A simulated cohort of 10 000 IGRA-positive, foreign-born adults from high tuberculosis incidence settings (excluding immunosuppressed individuals), modeled as recent or non-recent (immigrated 25 years earlier) immigrants at ages 35 and 65 years. Interventions:Rifampin daily for 4 months, isoniazid daily for 9 months, or no preventive therapy. Main Outcomes and Measures:Costs, disability-adjusted life-years (DALYs), incident tuberculosis cases and deaths, treatment completion, and incremental cost-effectiveness ratios (ICERs), with the proportion of simulations in which each strategy was optimal at a willingness-to-pay threshold of $50 000 per DALY averted. Results:Among recent immigrants, rifampin was the dominant strategy at ages 35 and 65 years (optimal in 88.5% and 93.9% of simulations), yielding the fewest tuberculosis cases (119.44 and 82.31 per 10 000) and the highest treatment completion (71.4% and 67.7%). Among non-recent immigrants, rifampin remained the dominant strategy (optimal in 53.41% of simulations), followed by no treatment. In 65-year-olds who did not immigrate recently, no treatment was optimal in 94.7% of simulations. ICERs for treatment versus no treatment were unfavorable ($193 600 and $412 857 per DALY averted for rifampin and isoniazid, respectively, at age 65). Conclusions and Relevance:In this decision analytical model, rifampin was cost-effective for recent immigrants, whereas no treatment was optimal for older immigrants with remote arrival date. Age and time since immigration may help risk-stratify tuberculosis infection treatment and reduce unnecessary treatment in lower-risk populations.

This review highlights the current state of molecular diagnostic modalities to detect invasive fungal infections, with a focus on molds in immunocompromised children and adults. Molecular diagnostics may also be utilized to detect antifungal drug resistance. Although both pathogen-specific and pathogen-agnostic assays may be beneficial in more rapidly identifying fungal infection with less invasive sampling in high-risk populations, the clinical implementation and interpretation of these tests must consider several important factors, including anatomic site and type of specimen, host characteristics, use of antifungal prophylaxis, and timing of specimen collection.

Sexual dysfunction is a prevalent and often under-addressed concern among prostate cancer survivors, significantly affecting quality of life for patients and their partners. The True North Sexual Health and Rehabilitation eClinic (SHAReClinic) is a virtual, biopsychosocial intervention developed to improve access to sexual health support for prostate cancer survivors and their partners. This study used a qualitative descriptive design to examine barriers and facilitators influencing the integration of SHAReClinic into oncology care across nine Canadian health care centres. Semi-structured interviews were conducted with 17 knowledge users, including health care providers and institutional leaders. Data were analyzed using a hybrid deductive–inductive thematic approach guided by the Consolidated Framework for Implementation Research (CFIR) 2.0. Participants described SHAReClinic as a much-needed resource, particularly in the absence of standardized sexual health pathways in oncology care. The virtual format was seen as accessible and well suited to addressing sensitive topics. However, limited funding, lack of institutional support, and workflow integration challenges emerged as primary barriers to implementation. Findings offer practical, theory-informed guidance for integrating SHAReClinic into oncology care and highlight key considerations for developing sustainable and scalable survivorship care models.

Treatment of erectile dysfunction is based on pharmacotherapy for most patients. To review the current data on pharmacotherapy for erectile dysfunction based on efficacy, psychosocial outcomes, and safety outcomes. A review of the literature was undertaken by the committee members. All related articles were critically analyzed and discussed, and consensus statements were developed after presentation at the 2024 ICSM. Eight recommendations are provided with the corresponding level of evidence and grade of recommendation. The management of erectile dysfunction should be personalized to address the psychosocial needs and expectations of both the patient and their partner. PDE5 inhibitors remain the first-line treatment for most men, while intracavernosal injections, vacuum erection devices, and penile prostheses serve as second-line options, with treatment decisions guided by patient preferences. Key recommendations are summarized in table 1.

BACKGROUND A total of 700 000 US children and adolescents are estimated to have latent tuberculosis (TB) infection. Identifying facilitators and barriers to engaging in TB infection care is critical to preventing pediatric TB disease. We explored families’ and clinicians’ perspectives on pediatric TB infection diagnosis and care. METHODS We conducted individual interviews and small group discussions with primary care and subspecialty clinicians, and individual interviews with caregivers of children diagnosed with TB infection. We sought to elicit facilitators and barriers to TB infection care engagement. We used applied thematic analysis to elucidate themes relating to care engagement, and organized themes using a cascade-grounded pediatric TB infection care engagement framework. RESULTS We enrolled 19 caregivers and 24 clinicians. Key themes pertaining to facilitators and barriers to care emerged that variably affected engagement at different steps of care. Clinic and health system themes included the application of risk identification strategies and communication of risk; care ecosystem accessibility; programs to reduce cost-related barriers; and medication adherence support. Patient- and family-level themes included TB knowledge and beliefs; trust in clinicians, tests, and medical institutions; behavioral skills; child development and parenting; and family resources. CONCLUSIONS Risk identification, education techniques, trust, family resources, TB stigma, and care ecosystem accessibility enabled or impeded care cascade engagement. Our results delineate an integrated pediatric TB infection care engagement framework that can inform multilevel interventions to improve retention in the pediatric TB infection care cascade.

Background: Managing health care acquired and device-associated intracranial infections in young children can be challenging given adverse antibiotic side effects and difficulties in achieving adequate central nervous system (CNS) antibiotic concentrations. Ceftaroline is a cephalosporin with a favorable safety profile and activity against methicillin-resistant Staphylococci and several Gram-negative organisms. Published data on the use of ceftaroline for CNS infections in children and adults are limited. Methods: We describe a 2-month-old infant with ventriculo-subgaleal shunt-associated methicillin-resistant Staphylococcus epidermidis ventriculitis, which was successfully treated with ceftaroline, in addition to vancomycin and rifampin. We conducted a scoping review of English-language literature retrieved from PubMed, EMBASE and Web of Science that assessed the use of ceftaroline for CNS infections. Results: We identified 22 articles for inclusion in our review, which described 92 unique patients, of whom 2 were <21 years old. Ceftaroline was commonly used in conjunction with other antibiotics to treat infections caused by Staphylococcus aureus, coagulase-negative Staphylococci and Streptococcus pneumoniae. Most case reports described clinical success with ceftaroline, though small case series and cohort studies yielded mixed efficacy assessments. Adverse effects attributed to ceftaroline were rare and included reversible myelosuppression, eosinophilia, hepatotoxicity and nephrotoxicity. Pharmacokinetic/pharmacodynamic studies suggested similar CNS penetration through inflamed meninges as other beta lactam antibiotics. Conclusions: We identified a growing body of published evidence supporting the use of ceftaroline in combination with other agents for the treatment of CNS infections. In absence of clinical trials, additional real-world data are needed to define the efficacy and safety of ceftaroline for children and adults with CNS infections.

Abstract Introduction Peyronie's disease (PD) affects about 10% of men and is often studied using traditional monolayer fibroblast monolayer cultures and limited animal models, which do not adequately replicate the complex cellular interactions of PD. We have developed an advanced three-dimensional (3D) cellular model named PD.SPHERE using a novel 'micro-gravity' cell culture technique from human PD tissues. Significant advancements in the culturing protocol have improved the morphology and physiopathology of these models, providing an essential platform for in vitro treatment screening. Objective The aim is to refine the culturing protocol for generating PD.SPHEREs that more accurately mimics the morphological and physiological features of PD plaques and to assess the efficacy of these refined models as tools for treatment screening. Methods Fibroblasts from human PD tissues were isolated and cultured using the 'micro-gravity' technique with modifications. The PD fibroblast cells were cultured and propagated in a non-adhesive 96-well plate, with and without 10 ng/ml transforming growth factor-beta (TGF-β) supplementation, under micro-gravity conditions. The plates were then placed on an orbital shaker inside the incubator and incubated at 37°C with 5% CO2 and 95% relative humidity. We confirmed the appropriate morphology and cellular compositions, including α-smooth muscle actin (α-SMA) and cellular collagen, using microscopic assays. The refined 3D model was subsequently used to evaluate the effects of collagenase from Clostridium histolyticum (CCH) and actinidin, a collagenase-like enzyme derived from kiwi fruits. Results Our findings from the refined 3D model revealed significant changes in cellular morphology. Specifically, PD.SPHEREs developed from cells that were not initially supplemented with TGF-β, but were later cultured in micro-gravity with TGF-β supplementation, and PD.SPHEREs from cells both propagated and cultured with TGF-β were approximately 2.3 and 3.5 times larger, respectively, than those PD.SPHEREs propagated and cultured entirely without TGF-β (P < 0.0001). The collagen content was significantly highest (P < 0.01) in PD.SPHEREs that were both propagated and cultured with TGF-β, compared to all other groups. The refined model was susceptible to both CCH and actinidin. The size and collagen content of the refined PD.SPHEREs significantly decreased (P < 0.05) following treatment with CCH and actinidin. Conclusions The advancements made in the culturing protocol of PD.SPHEREs represent a significant improvement in the modeling of PD for in vitro studies. Our results demonstrate the critical role of TGF-β in the growth and morphology of PD.SPHEREs. The increase in sized collagen content of the spheroids when cultured in the presence of TGF-β suggests that this factor plays a substantial role in cellular proliferation and cellular matrix accumulation, which are key aspects of PD pathogenesis. Furthermore, the increased collagen content in PD.SPHEREs cultured with TGF-β aligns with the known pathophysiology of PD, where collagen accumulation contributes to plaque formation and disease progression. This finding underscores the utility of our model in replicating key pathological features of PD and supports the potential of PD.SPHERE as an effective tool for screening and evaluating the efficacy of treatments aimed at modulating these pathological processes. Disclosure No.

In the United States, tuberculosis (TB) screening is recommended for pregnant individuals with TB risk factors. We conducted a retrospective study of perinatal TB infection testing and treatment in a tertiary health system. Of 165 pregnant individuals with positive TB infection tests, only 9% completed treatment within 4.6 years of follow-up.

BACKGROUND Leaving the hospital against medical advice (AMA) reflects a breakdown in the family-clinician relationship and creates ethical dilemmas in inpatient pediatric care. There are no national data on frequency or characteristics of leaving AMA from US children's hospitals.METHODS We performed a retrospective cohort study of hospital discharges for children under 18 years old from January 1, 2018 to December 31, 2022 in 43 children's hospitals in the Pediatric Health Information System (PHIS) database. The primary outcome was leaving AMA. Exposures were demographic, geographic, and clinical characteristics. We used multivariable mixed effects logistic regression models to assess independent factors associated with leaving AMA and all-cause 14-day hospital readmission.RESULTS Among 3 672 243 included inpatient encounters, 2972 (0.08%) ended in leaving AMA. Compared with non-Hispanic white patients, non-Hispanic Black patients had higher odds of leaving AMA (adjusted odds ratio [aOR] 1.31 [95% confidence interval (CI) 1.19-1.44]), whereas Hispanic patients (aOR 0.66 [95% CI 0.59-0.75]) had lower odds of leaving AMA. Hospitalizations for patients with noncommercial insurance were more likely to end in leaving AMA. Leaving AMA was associated with increased odds of 14-day inpatient readmission (aOR 1.41 [95% CI 1.24-1.61]) compared with patients who did not leave AMA. There was substantial interhospital variability in standardized rates of leaving AMA (range 0.18-2.14 discharges per 1000 inpatient encounters).CONCLUSIONS Approximately 1 in 1235 inpatient encounters ended in leaving AMA. Non-Hispanic Black patients had increased odds of leaving AMA. Leaving AMA was associated with increased odds of 14-day readmission.