Critical illness myopathy and trajectory of recovery in acute kidney injury requiring continuous renal replacement therapy: a prospective observational trial protocol.

INTRODUCTION: Acute kidney injury requiring renal replacement therapy (AKI-RRT) is common in the intensive care unit (ICU) and is associated with significant morbidity and mortality. Continuous RRT (CRRT) non-selectively removes large amounts of amino acids from plasma, lowering serum amino acid concentrations and potentially depleting total-body amino acid stores. Therefore, the morbidity and mortality associated with AKI-RRT may be partly mediated through accelerated skeletal muscle atrophy and resulting muscle weakness. However, the impact of AKI-RRT on skeletal muscle mass and function during and following critical illness remains unknown. We hypothesise that patients with AKI-RRT have higher degrees of acute muscle loss than patients without AKI-RRT and that AKI-RRT survivors are less likely to recover muscle mass and function when compared with other ICU survivors. METHODS AND ANALYSIS: This protocol describes a prospective, multicentre, observational trial assessing skeletal muscle size, quality and function in ICU patients with AKI-RRT. We will perform musculoskeletal ultrasound to longitudinally evaluate rectus femoris size and quality at baseline (within 48 hours of CRRT initiation), day 3, day 7 or at ICU discharge, at hospital discharge, and 1-3 months postdischarge. Additional skeletal muscle and physical function tests will be performed at hospital discharge and postdischarge follow-up. We will analyse the effect of AKI-RRT by comparing the findings in enrolled subjects to historical controls of critically ill patients without AKI-RRT using multivariable modelling. ETHICS AND DISSEMINATION: We anticipate our study will reveal that AKI-RRT is associated with greater degrees of muscle loss and dysfunction along with impaired postdischarge recovery of physical function. These findings could impact the in-hospital and postdischarge treatment plan for these patients to include focused attention on muscle strength and function. We intend to disseminate findings to participants, healthcare professionals, the public and other relevant groups via conference presentation and publication without any publication restrictions. TRIAL REGISTRATION NUMBER: NCT05287204.

A Tool to Assess Competence in Critical Care Ultrasound Based on Entrustable Professional Activities.

Background: Existing assessment tools for competence in critical care ultrasound (CCUS) have limited scope and interrupt clinical workflow. The framework of entrustable professional activities (EPAs) is well suited to developing an assessment tool that is comprehensive and readily integrated into the intensive care unit (ICU) training environment. Objective: This study sought to design an EPA-based tool to assess competence in CCUS for pulmonary and critical care fellows and to assess the validity and reliability of the tool. Methods: Eight experts in CCUS met to define the core EPAs for CCUS. A nominal group technique was used to reach consensus. An assessment tool was created based on the EPAs with a modified Ottawa entrustability scale. Trained faculty evaluated pulmonary and critical care fellows using this tool in the ICU over a 6-month study period at a single institution. An assessment of validity of the EPA-based tool is made with four sources of validity evidence: content, response process, reliability, and relation to other variables. Reliability and response process data were generated using generalizability theory analysis to estimate sources of variance in entrustment scores. Analysis of response process validity and validity by relation to other variables was performed using regression models. Results: Fifty-four assessments were recorded during the study period, conducted on 23 trainees by 13 faculty. Content validity of the tool was demonstrated using expert consensus and published guidelines from critical care societies to define the EPAs. Response process validity was demonstrated by the low variance in entrustment scores due to evaluators (0.086 or 6%) and high agreement between score and trainee self-assessment (regression coefficient, 0.82; P < 0.0001). Reliability was demonstrated by the high "true" variance in entrustment score attributable to the trainee: 0.674 or 45%. Validity by relation to other variables was demonstrated using regression analysis to show correlation between entrustment score and the number of times a fellow has performed an EPA (regression coefficient, 0.023; P < 0.0001). Conclusion: An EPA-based assessment tool for competence in CCUS was created. We obtained sufficient validity evidence on three of the diagnostic EPAs. Procedural EPAs were infrequently assessed, limiting generalizability in this subgroup.

Development and Validation of a Novel Instrument to Measure the Community Well-Being of Residency Programs.

PURPOSE: To develop and validate the Residency Community Well-Being (RCWB) instrument, a novel instrument to measure the subjective community well-being of an individual residency program, and to explore differences in RCWB scores between demographic groups. METHOD: An initial questionnaire to measure a residency program's community well-being was developed after literature review. Items were pilot tested, and the questionnaire was reviewed by experts in the fields of residency education, survey design, and sociology. The questionnaire was administered electronically between March and July 2021 to U.S. residents in 18 specialties recruited through convenience and snowball sampling using social media, a listserv, and personal emails to residency program leaders. Three previously validated instruments were administered as well to examine criterion validity: the Professional Fulfillment Index, the Brief Inventory of Thriving, and a single-item burnout measure. Data were analyzed with descriptive statistics, and exploratory factor analysis was performed using principal axis factoring with direct oblimin rotation to reduce the items and identify subscales. RESULTS: Of the 366 participants who opened and started the survey, 219 completed it (completion rate: 59.8%). Most respondents were women (133, 60.7%), 26-30 years old (132, 60.3%), and White (149, 68.0%). Three subscales emerged with 18 items: program leadership, structures, and practices (PLSP); resident interpersonal relationships (RIR); and resident mistreatment (RM). The Cronbach's alphas were 0.96 for PLSP, 0.92 for RIR, 0.82 for RM, and 0.95 for the overall RCWB. RCWB score positively correlated with professional fulfillment ( r = .52, P < .001) and thriving ( r = .45, P < .001) and inversely correlated with burnout ( r = -.39, P < .001). CONCLUSIONS: The RCWB instrument demonstrates strong internal consistency and content and criterion validity that shows that a residency program's subjective community well-being is primarily composed of program leadership quality, supportive interpersonal relationships, and the absence of mistreatment.

Development and Evaluation of Resident-Championed Point-of-Care Ultrasound Curriculum for Internal Medicine Residents.

Introduction: Point-of-care ultrasound (POCUS) is a powerful clinical tool that has seen widespread adoption, including in Internal Medicine (IM), yet standardized curricula designed by trained faculty are scant. To address the demand for POCUS education at our institution, we created a resident-championed curriculum with support from skilled faculty across multiple specialties. Our objective was to teach postgraduate year (PGY)-3 IM residents the basics of POCUS for evaluation of the pulmonary, cardiac, and abdominal systems through resident-developed workshops. The goal of acquisition of these skills was for resident education and to inform decisions to pursue further patient testing. Methods: Three half-day workshops were created to teach residents how to obtain and interpret ultrasound images of the pulmonary, cardiac, and abdominal systems. Workshops were comprised of didactic teaching and practical ultrasound instruction with expert supervision of clinicians within and outside of IM. Residents were asked to complete a written survey before and after each workshop to assess confidence, knowledge, and likelihood of future POCUS use. Results: Across the three workshops (pulmonary, cardiac, and abdominal), 66 sets of pre- and post-workshop surveys (32 pulmonary, 25 cardiac, and 9 abdominal) were obtained and analyzed. Confidence in and knowledge regarding POCUS use increased significantly across all three workshops. Likelihood of future use increased in the cardiac workshop. Conclusions: We implemented a resident-championed POCUS curriculum that led to improved attitudes and increased knowledge of POCUS for PGY-3 IM residents.

Engagement and Retention in HIV Care for Transgender Women: Perspectives of Medical and Social Service Providers in New York City.

Transgender women are less likely to engage in HIV care and adhere to antiretroviral medications than other at-risk populations. Health care and social service providers, in addition to consumers, have experiences that can elucidate barriers and facilitators to care and inform interventions. Guided by the social/ecological model, we conducted interviews with 19 providers working with transgender women. At the health systems level, perceived barriers included lack of care accessibility and security, providers' misunderstanding of the transgender community, and lack of cultural competency of information systems and staff. At the community level, barriers included HIV stigma. At the family level, barriers included rejection and housing instability. At the individual level, barriers included conflicts between HIV- and transgender care, medication side effects, competing priorities, mental health issues and substance abuse, and low health literacy. Facilitators included provider competence in transgender health, improved access to care, and patient empowerment. Findings indicate the need for an integrated care model.

Higher locoregional recurrence rate for triple-negative breast cancer following neoadjuvant chemotherapy, surgery and radiotherapy.

BACKGROUND: Breast cancer subtype, determined by expression of estrogen/progesterone receptor (ER/PR) and human epidermal growth factor receptor (HER)-2, is predictive for prognosis. The importance of subtype to locoregional recurrence (LRR) following neoadjuvant chemotherapy (NAC) is unknown, particularly after adjuvant radiotherapy (RT). METHODS: We retrospectively identified 160-breast cancer patients registered at Columbia University Medical Center from 1999 to 2012 treated with NAC, surgery and adjuvant RT. RESULTS: Patients were grouped by receptor status: hormone receptor positive (HR+) [(ER or PR+)/HER2-; n = 75], HER2+ (n = 46), or triple-negative (TNBC) [ER (-) PR (-) HER2 (-); n = 36]. The median follow-up was 28 months. 92.0% received an anthracycline-taxane based NAC and 80.4% of HER2+ patients received trastuzumab. All underwent surgical resection followed by RT. 15.6% had a pathologic complete response (pCR): 26% of HER2+, 5% of HR+, and 25% of TN. The actuarial rate of DM was 13.8% for the entire cohort, with equivalent rates by subtypes in non-pCR patients. The overall rate of LRR was 8%. However, the LRR rate was significantly higher for TNBC patients (22.2%) than HER2+ (5.6%) (p = 0.025) or HR+ (3.0%) (p = 0.037) in non-pCR group. In the pCR group, two patients had recurrence; one LRR and one a DM, both had TNBC. All LRR occurred in or near the radiation field. CONCLUSIONS: TNBC patients with < pCR to NAC have a significantly higher LRR rate as compared to other subtypes even with surgery and adjuvant RT. Our data support a need to further intensify local therapy in TNBC patients.

Titanium(IV) complexes with N,N'-dialkyl-2,3-dihydroxyterephthalamides and 1-hydroxy-2(1H)-pyridinone as siderophore and tunichrome analogues.

The aqueous chemistry of Ti(IV) with biological ligands siderophores and tunichromes is modeled by using N,N'-dialkyl-2,3-dihydroxyterephthalamides (alTAMs), analogues of catecholamide-containing biomolecules, and 1-hydroxy-2(1H)-pyridinone (1,2-HOPO), an analogue of hydroxamate-containing biomolecules. Both types of ligands stabilize Ti(IV) with respect to hydrolytic precipitation, and afford tractable complexes. Complexes with the methyl derivative of alTAM, meTAM, are characterized by using mass spectrometry and UV/vis spectroscopy. Complexes with etTAM are characterized by the same techniques as well as X-ray crystallography, cyclic voltammetry, and spectropotentiomeric titration. The ESI mass spectra of these complexes in water show both 1:2 and 1:3 metal/ligand species. The X-ray crystal structure of a 1:2 complex, K(2)[Ti(etTAM)(2)(OCH(3))(2)].2CH(3)OH (1), is reported. The midpoint potential for reduction of 1 dissolved in solution is -0.98 V. A structure for a 1:3 Ti/etTAM species, Na(2)[Ti(etTAM)(3)] demonstrates the coordination and connectivity in that complex. Spectropotentiometric titrations in water reveal three metal-containing species in solution between pH 3 and 10. 1,2-HOPO supports Ti(IV) complexes that are stable and soluble in aqueous solution. The bis-HOPO complex [Ti(1,2-HOPO)(2)(OCH(3))(2)] (5) was characterized by X-ray crystallography and by mass spectrometry in solution, and the tris-HOPO dimer [(1,2-HOPO)(3)TiOTi(1,2-HOPO)(3)] (6) was characterized by X-ray crystallography. Taken together, these experiments explore the characteristics of complexes that may form between siderophores and tunichromes with Ti(IV) in biology and in the environment, and guide efforts toward new, well characterized aqueous Ti(IV) complexes. By revealing the identities and some characteristics of complexes that form under a variety of conditions, these studies further our understanding of the complicated nature of aqueous titanium coordination chemistry.