Citations

Introduction The World Health Organization (WHO) endorses male circumcision as an effective human immunodeficiency virus (HIV) prevention intervention in settings where the expected impact is greatest, including Sub-Saharan Africa. Data on cost implications of early infant male circumcision (EIMC) are limited. The ShangRing (SR) is a WHO pre-qualified device for circumcision. We sought to perform a comprehensive cost assessment alongside a randomized controlled trial (RCT) of the SR versus the standard of care Mogen clamp (MoC) for EIMC to enable future scale-up towards a cost-effective HIV prevention strategy. Methods We collected resource utilization and economic data as part of an RCT of infants aged 0–60 days old undergoing EIMC in Kenya, Tanzania, and Uganda. Cost data for both the SR and MoC included baseline facility costs, direct costs, and indirect costs. The Decision Makers Program Planning Tool v1.0 was used to perform a direct cost comparison of these two devices. The Goals model was used to compare the costs of EIMC in 2023 using the present value of money to circumcise an adolescent male 15 years from now. Results A total of 1,378 infant males underwent circumcision, 689 via SR and 689 via MoC. The overall cost of a single EIMC in Kenya, Tanzania, and Uganda were 61.30 United States Dollars ($), $47.14, and $64.59 respectively for the SR, and $56.38, $50.43, and $58.57 respectively for the MoC. In Kenya, EIMC would be less expensive based on nominal present costs in 2023 compared to waiting for adolescent circumcision at age 15 years in 2038. This finding is reversed in Tanzania and Uganda. Conclusions The overall cost of EIMC via SR versus MoC is comparable in an RCT. With scale-up utilizing lower level personnel, the cost of SR may be further reduced. The SR is an attractive alternative for future EIMC initiatives in Sub-Saharan Africa to further reduce HIV burden.

Aging occurs heterogeneously across organs, leading to progressive tissue dysfunction. Cellular senescence is a stress response triggered by age-associated insults, yet the mechanisms regulating senescence and organ aging remain incompletely understood. Here, we defined a role for lysine-specific demethylase 1 (LSD1) in DNA damage–mediated senescence and organ aging. LSD1 was upregulated in aged organs and senescent cells. In response to natural aging or ionizing radiation–induced DNA damage, LSD1 interacted with and demethylated ATM at lysine 3,016, as confirmed using a newly generated ATM-K3016me antibody. This modification sustained ATM phosphorylation, amplified DNA damage signaling, and delayed checkpoint recovery, promoting senescence and organ aging. Inhibition of LSD1 accelerated ATM dephosphorylation via WIP1, enhanced DNA repair, reduced senescence and DNA damage, and prevented irradiation-induced hair graying. Elimination of senescent cells with senolytics reduced LSD1 protein in aged organs, indicating a feedback loop between LSD1 and senescence. Mechanistically, LSD1 underwent autophagosome-lysosome degradation through interaction with LC3 and Beclin1, and autophagy impairment during DNA damage contributed to LSD1 accumulation in senescent cells. This study revealed LSD1 as a key regulator of DNA damage–induced senescence and organ aging and suggested that targeting LSD1 may attenuate senescence, delay organ aging, and prevent hair graying.

Background Poor financial literacy and financial behaviors negatively affect the wellness and professional duties of residents and fellow physicians. Major financial missteps can create significant personal stress, leading to worsening wellness and burnout. There are currently no available comprehensive financial literacy curricula for residents and fellows for educators to use to address this gap. Methods We created and assessed the educational impact of a comprehensive 4-module curriculum that covers fundamental personal finance topics which are universally applicable to all physicians regardless of their medical and surgical specialty. We delivered the entire curriculum 6 times between November 2023 and December 2024 to anesthesia residents, internal medicine residents, and critical care fellows. We assessed their self-reported baseline financial behaviors and their knowledge and self-efficacy with core financial topics using pretest and posttest surveys. Results For the 4 modules respectively, 66 (25%), 39 (15%), 44 (17%), and 35 (13%) of 260 possible trainees completed surveys. Self-efficacy significantly increased for creating a financial plan (p<0.001), investing (p<0.001), designing a debt payoff strategy (p=0.005), selecting an asset allocation (p<0.001), selecting optimal asset locations (p<0.001), and selecting appropriate health (p<0.001)/life (p<0.001)/disability (p<0.001) insurance plans. Resident knowledge significantly increased from pretest to posttest for all 4 modules: Financial Plan & Basics of Investing (p<0.001), Budgeting & Debt Management (p=0.010), Retirement Accounts & Asset Allocation (p<0.001), and Insurance (p<0.001). Mean trainee satisfaction with the overall curriculum on a 5-point scale (1-low, 5-high) was 4.2 (standard deviation 0.8). Conclusions We identified poor baseline financial literacy and behaviors in our resident and fellow physicians. This prioritized curriculum effectively adapted to the needs of multiple different training programs and was highly desired by trainees. This curriculum increased their knowledge and self-efficacy with several key topics in personal finance.

Introduction Ultra-marathon races present a prolonged cardiopulmonary physiological stress but the magnitude, persistence, and impact of race environment on respiratory function are incompletely understood. The aim of this study is to observe the effect of ultra-marathon trail races on both lung function and airway impedance. Methods Fifty-seven individuals (49/8, M/F) participated in either the Courmayeur-Champex-Chamonix (CCC ® , 101.5km), Ultra Trail du Mont-Blanc (UMTB ® , 171.5 km), or the Hong Kong 100 (HK, 100 km) races. Participant demographics were measured pre-race and included: age (40.7±10.3 yrs); height (175.5±7.1 cm), body mass (69.7±8.3 kg). Spirometry, airway impedance (via forced oscillation technique, FOT), maximal inspiratory (MIP) and expiratory pressure (MEP), and exhaled nitric oxide (ExNO) were assessed before, immediately (18–4 hours after), and 188–24 hours post-race. Mixed effects analysis with Dunnett’s post-hoc correction were conducted to evaluate the effects of race and time. Results Results demonstrated significant effects of time for: forced vital capacity (FVC), forced expiratory flow over one second (FEV 1 ), peak expiratory flow (PEF), forced expiratory flow between 25-75% (FEF25-75), forced expiratory flow at 25% and at 50% (FEF 25 and FEF 50 , respectively), MIP, MEP, airway reactance (X) at all frequencies from FOT (X 5 , X 11 , X 19 ), respiratory rate, and ExNO (all p &lt;0.05). A significant effect of race was also observed for ExNO ( p =0.002). Discussion Findings indicate declines in lung function and airway impedance immediately after ultra-marathon races, some of which, persisted up to 24 hours post-race. Further investigations are required to better understand the etiology of changes in lung function following ultra-endurance events.

Abstract Objectives Embedded pragmatic clinical trials (ePCTs) are conducted as part of routine clinical care and therefore use data collected from real-world data sources, such as electronic health record systems and administrative claims. A common approach for using these types of data across all phases of trial conduct is to create a computable phenotype (an explicitly defined data query data, including specified data types, data codes, and logical parameters) to capture patients with a clinical condition, exposure, symptom, characteristic, treatment, or outcome of interest. Materials and Methods The Electronic Health Record (EHR) Core Working Group of the NIH Pragmatic Trials Collaboratory captured the experiences of investigators in developing, adapting, and applying computable phenotype definitions in their studies. Results Four case studies describe different approaches to developing and using computable phenotypes in pragmatic trials. Discussion We recommend: (1) developing computable phenotypes as part of a team with multiple areas of expertise; (2) appropriate validation; (3) dissemination of salient details regarding phenotype creation; and (4) capturing and reporting any modifications made to phenotypes during the conduct of the trial. Conclusion A range of issues and decisions influence how computable phenotypes are developed and used in pragmatic clinical trials. Multidisciplinary teams that understand the context of the data, including the reason the data are collected and potential sources of bias, are best suited for the development and validation of phenotypes for ePCTs.

Abstract Background Breast cancer is etiologically heterogeneous, but which risk factors differ in their associations across tumor subtypes remains unclear. We conducted a large, pooled analysis to evaluate independent, dose-response associations between breast cancer risk factors and quantitative tumor features. Methods Analyses of 15,731 invasive breast cancers from 24 studies evaluated associations (p-trend) between reproductive and hormonal factors, body mass index (BMI), alcohol, smoking, and family history in relation to quantitative immunohistochemistry measures on tissue microarrays (ER, PR, HER2, KI67, TP53) and tumor grade. Analyses in a subset of 10 population-based studies estimated subtype-specific odds ratios (ORs) comparing cases to controls. A Bayesian False Discovery Probability (BFDP) &lt;0.2 was used to identify associations with strong statistical evidence. Results Nulliparity and later age at menopause were associated with higher ER-positivity (p-trend=0.021 and 0.001, respectively), with corresponding OR[ER+] (95% CI) = 1.49 (1.16-1.90) for nulliparous vs. parous and 1.07 (1.03-1.11) per 5 years. Current combined menopausal hormone therapy (MHT) use was associated with lower grade (p-trend&lt;0.001), with OR [grade1] = 3.37 (2.69-4.21) for current vs. never users. Higher BMI was associated with lower ER-positivity and higher grade in premenopausal women (p-trend&lt;0.001 and &lt;0.001), with OR[ER+] = 0.80 (0.74-0.87) and OR[grade1] = 0.75 (0.63-0.88) per 5 units, and with higher PR-positivity and higher grade in postmenopausal women (p-trend&lt;0.001 and &lt;0.001), with OR[PR+] = 1.08 (1.03-1.14) and OR[grade 3] = 1.10 (1.04-1.17) per 5 units. Conclusion This pooled analysis of 15,731 cases showed that nulliparity, age at menopause, MHT, and BMI have independent, dose-response associations with ER, PR, and grade, clarifying patterns of etiologic heterogeneity. Associations with HER2, KI67 and TP53, or other risk factors did not meet our threshold for strong evidence.

ABSTRACT Key performance indicators (KPIs) are quantifiable measures that describe critical success factors of an organization. Their vital role in ensuring the delivery of quality health care services necessitates the development of KPIs relevant to inpatient clinical pharmacy practice. This opinion paper from the American College of Clinical Pharmacy (ACCP) Clinical Administration Practice and Research Network (CADM PRN) describes the rationale, methodology, and outcomes of a consensus process to identify a focused set of inpatient/acute care clinical pharmacy KPIs. Leveraging a modified Delphi approach, the CADM PRN convened an Expert Panel of clinical pharmacy leader members to build a consensus‐driven set of KPIs reflecting clinical, operational, patient‐centered, and financial contributions of clinical pharmacists in the inpatient/acute care setting. From a previous ACCP White Paper, a total of 15 KPIs were identified across four domains: (1) clinical practice and patient safety, (2) clinical outcomes and readmissions, (3) medication education and patient engagement, and (4) financial and operational value. The CADM PRN posits that the establishment and implementation of standardized KPIs are essential for measuring and demonstrating the value of clinical pharmacy services in modern health care, offers pragmatic, consensus‐based KPIs for evaluating clinical pharmacy services supporting resource justification, and advancing the visibility and impact of pharmacists in acute care practice. As hospitals shift toward value‐based care, robust KPI frameworks will be critical for optimizing patient outcomes, supporting financial sustainability, and justifying appropriate staffing. Future efforts should focus on pilot testing, addressing implementation barriers, and achieving broader acceptance for KPIs across the profession.

Cardiac arrest is a leading cause of global mortality, with low survival rates despite advances in resuscitation science. Reported survival ranges from 8% to 34% for out-of-hospital and in-hospital cardiac arrest. Extracorporeal cardiopulmonary resuscitation (ECPR) has emerged as a rescue therapy for patients unresponsive to conventional CPR, leveraging veno-arterial extracorporeal membrane oxygenation (ECMO) to provide artificial circulation, gas exchange, and maintenance of organ perfusion in the absence of spontaneous native circulation. Successful ECPR depends on minimizing time to ECMO initiation and selecting appropriate patients. While several aspects are consistent across countries, ECPR protocols vary in logistics, team composition, cannulation methods, and monitoring, which may influence patient-important outcomes such as survival and neurological recovery. This narrative review explores current global practices in ECPR, and identifies opportunities for standardization while recognizing elements that should remain context specific.