Creation of a sustainable longitudinal women in Leadership Development (WILD) curriculum focused on graduate medical education trainees.

BACKGROUND: Although women comprise the majority of medical students, gender disparities emerge early and remain at the highest levels of academia. Most leadership courses focus on faculty or students rather than women graduate medical education (GME) trainees. AIM: To promote the leadership development of women GME trainees through empowerment, community building, networking and mentorship, and concrete leadership skills development. SETTING: University of California, San Francisco. PARTICIPANTS: 359 women residents and fellows from 41 specialties. PROGRAM DESCRIPTION: A longitudinal curriculum of monthly workshops designed to support leadership development for women trainees. Sessions and learning objectives were designed via needs assessments and literature review. PROGRAM EVALUATION: A mixed-methods evaluation was performed for 3 years of WILD programming. Quantitative surveys assessed participant satisfaction and fulfillment of learning objectives. Structured interview questions were asked in focus groups and analyzed qualitatively. DISCUSSION: 23% of invited participants attended at least one session from 2018 to 2021, despite challenging trainee schedules. Surveys demonstrated acceptability and satisfaction of all sessions, and learning objectives were met at 100% of matched sessions. Focus groups highlighted positive impact in domains of community-building, leadership skills, mentorship, and empowerment. This program has demonstrated WILD's longitudinal sustainability and impact for women trainees.

The Utilization and Impact of Live Interactive and Store-and-Forward Teledermatology in a Veterans Affairs Medical Center During the COVID-19 Pandemic.

Introduction: Teledermatology has emerged as a promising method of continuing dermatologic care during the coronavirus 2019 (COVID-19) pandemic, including in the Department of Veterans Affairs (VA). Analysis of the utilization and impact of teledermatology within the San Francisco Veterans Affairs Health Care System (SFVAHCS) may elucidate the ways that teledermatology programs can continue to be optimized. Methods: We conducted a retrospective analysis of live interactive encounters, Veterans Affairs Video Connect (VVC), store-and-forward telehealth (SFT), and face-to-face (FTF) consultations, performed within the SFVAHCS from March 2020 to December 2020. To assess utilization, we analyzed numbers of encounters throughout 2020. To assess impact, we analyzed primary diagnoses for each encounter and rates of recommendations for medications and lesion biopsies. Additionally, we assessed diagnostic accuracy associated with each teledermatology type by measuring concordance between teledermatologists' clinical diagnoses and histopathological diagnoses. Results: Two thousand two hundred fifty FTF, 347 VVC, and 470 SFT encounters were conducted from March to December 2020. More female patients utilized VVC, and patients who utilized VVC were younger than SFT and FTF users (p < 0.01). SFT was utilized more by patients from rural areas (p < 0.01). Diagnoses addressed were significantly different between VVC and SFT. A majority of VVC encounters involved referrals for inflammatory conditions; primary diagnoses associated with SFT consultations were most frequently neoplasms. Comparison of VVC and SFT outcomes showed that more VVC visits resulted in a medication recommendation, while more SFT consultations resulted in a biopsy recommendation. Conclusions: Teledermatology contributed to meeting patient needs throughout 2020 and created an impact on clinical management. Patient characteristics, diagnoses, and type of impact associated with encounters varied between SFT and VVC. This analysis provides insight into teledermatology utilization within the VA system and can contribute to efforts to improve the quality of teledermatology care for veterans.

Point-of-care motion capture and biomechanical assessment improve clinical utility of dynamic balance testing for lower extremity osteoarthritis.

Musculoskeletal conditions impede patient biomechanical function. However, clinicians rely on subjective functional assessments with poor test characteristics for biomechanical outcomes because more advanced assessments are impractical in the ambulatory care setting. Using markerless motion capture (MMC) in clinic to record time-series joint position data, we implemented a spatiotemporal assessment of patient kinematics during lower extremity functional testing to evaluate whether kinematic models could identify disease states beyond conventional clinical scoring. 213 trials of the star excursion balance test (SEBT) were recorded by 36 subjects during routine ambulatory clinic visits using both MMC technology and conventional clinician scoring. Conventional clinical scoring failed to distinguish patients with symptomatic lower extremity osteoarthritis (OA) from healthy controls in each component of the assessment. However, principal component analysis of shape models generated from MMC recordings revealed significant differences in subject posture between the OA and control cohorts for six of the eight components. Additionally, time-series models of subject posture change over time revealed distinct movement patterns and reduced overall postural change in the OA cohort compared to the controls. Finally, a novel metric quantifying postural control was derived from subject specific kinematic models and was shown to distinguish OA (1.69), asymptomatic postoperative (1.27), and control (1.23) cohorts (p = 0.0025) and to correlate with patient-reported OA symptom severity (R = -0.72, p = 0.018). Time series motion data have superior discriminative validity and clinical utility than conventional functional assessments in the case of the SEBT. Novel spatiotemporal assessment approaches can enable routine in-clinic collection of objective patient-specific biomechanical data for clinical decision-making and monitoring recovery.

Demographic Characteristics of Participants in Rheumatoid Arthritis Randomized Clinical Trials: A Systematic Review.

Importance: Racial/ethnic minority groups, women, and elderly people experience a disproportionate burden of disease in rheumatoid arthritis (RA), making it particularly important to examine drug therapies in these populations. Despite a national health agenda to improve representation of diverse populations in randomized clinical trials (RCTs), there have been few large-scale analyses examining RCT demographic characteristics within rheumatology and none focusing on RA. Objective: To characterize the representation of racial/ethnic minority groups, women, and elderly people through a comprehensive systematic review of RA RCTs. Data Sources: A literature search of PubMed's MEDLINE database was conducted to identify RA RCTs in adults 19 years and older published in English between January 1, 2008, and January 1, 2018. Study Selection: Randomized double-blind RCTs examining any systemic, disease-modifying therapy were included. Secondary analyses of previously published RCTs were excluded. Of 1195 identified records, 240 articles (20.1%) met final selection criteria. The analysis focused on RCTs with at least 1 US-based site. Data Extraction and Synthesis: Data were extracted and synthesized according to the PRISMA guidelines for systematic reviews. Studies were screened for eligibility criteria. Demographic data on the age, sex, and race/ethnicity of RCT participants were extracted. Data analysis was conducted from October 25, 2018, to March 15, 2019. Main Outcomes and Measures: Representation of race/ethnicity and sex, defined as the proportion of total participants that belonged to each racial/ethnic group or sex. Trends in proportions over time were examined and compared with US demographic data. Results: A total of 240 RCTs with 77 071 participants were included. Of 126 RCTs with at least 1 US-based site (52.5%), the enrollment of minority racial/ethnic groups was significantly lower than their representation within the US Census population (16% vs 40%; P < .001), and the enrollment of men was significantly lower than the incidence of RA in men nationally (20.4% vs 28.6%; P < .001). There was no trend toward improved representation of racial/ethnic minority groups or men over time. Conclusions and Relevance: Given the disproportionate burden of RA among racial/ethnic minority groups, it is imperative that policy makers better incentivize the inclusion of racial/ethnic minority groups in RA RCTs.

Protein Kinase G Activation Reverses Oxidative Stress and Restores Osteoblast Function and Bone Formation in Male Mice With Type 1 Diabetes.

Bone loss and fractures are underrecognized complications of type 1 diabetes and are primarily due to impaired bone formation by osteoblasts. The mechanisms leading to osteoblast dysfunction in diabetes are incompletely understood, but insulin deficiency, poor glycemic control, and hyperglycemia-induced oxidative stress likely contribute. Here we show that insulin promotes osteoblast proliferation and survival via the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signal transduction pathway and that PKG stimulation of Akt provides a positive feedback loop. In osteoblasts exposed to high glucose, NO/cGMP/PKG signaling was reduced due in part to the addition of O-linked N-acetylglucosamine to NO synthase-3, oxidative inhibition of guanylate cyclase activity, and suppression of PKG transcription. Cinaciguat-an NO-independent activator of oxidized guanylate cyclase-increased cGMP synthesis under diabetic conditions and restored proliferation, differentiation, and survival of osteoblasts. Cinaciguat increased trabecular and cortical bone in mice with type 1 diabetes by improving bone formation and osteocyte survival. In bones from diabetic mice and in osteoblasts exposed to high glucose, cinaciguat reduced oxidative stress via PKG-dependent induction of antioxidant genes and downregulation of excess NADPH oxidase-4-dependent H2O2 production. These results suggest that cGMP-elevating agents could be used as an adjunct treatment for diabetes-associated osteoporosis.

Sulfheme formation during homocysteine S-oxygenation by catalase in cancers and neurodegenerative diseases.

Accumulating evidence suggests that abnormal levels of homocysteine are associated with vascular dysfunctions, cancer cell proliferation and various neurodegenerative diseases. With respect to the latter, a perturbation of transition metal homeostasis and an inhibition of catalase bioactivity have been reported. Herein, we report on some of the molecular bases for the cellular toxicity of homocysteine and demonstrate that it induces the formation of sulfcatalase, an irreversible inactive state of the enzyme, without the intervention of hydrogen sulfide. Initially, homocysteine reacts with native catalase and/or redox-active transition metal ions to generate thiyl radicals that mediate compound II formation, a temporarily inactive state of the enzyme. Then, the ferryl centre of compound II intervenes into the unprecedented S-oxygenation of homocysteine to engender the corresponding sulfenic acid species that further participates into the prosthetic heme modification through the formation of an unusual Fe(II) sulfonium. In addition, our ex cellulo studies performed on cancer cells, models of neurodegenerative diseases and ulcerative colitis suggest the likelihood of this scenario in a subset of cancer cells, as well as in a cellular model of Parkinson's disease. Our findings expand the repertoire of heme modifications promoted by biological compounds and point out another deleterious trait of disturbed homocysteine levels that could participate in the aetiology of these diseases.