Metformin for sepsis-associated AKI: a protocol for the Randomized Clinical Trial of the Safety and FeasibiLity of Metformin as a Treatment for sepsis-associated AKI (LiMiT AKI).

INTRODUCTION: Acute kidney injury (AKI) is a common complication of sepsis associated with increased risk of death. Preclinical data and observational human studies suggest that activation of AMP-activated protein kinase, an ubiquitous master regulator of energy that can limit mitochondrial injury, with metformin may protect against sepsis-associated AKI (SA-AKI) and mortality. The Randomized Clinical Trial of the Safety and FeasibiLity of Metformin as a Treatment for sepsis-associated AKI (LiMiT AKI) aims to evaluate the safety and feasibility of enteral metformin in patients with sepsis at risk of developing SA-AKI. METHODS AND ANALYSIS: Blind, randomised, placebo-controlled clinical trial in a single-centre, quaternary teaching hospital in the USA. We will enrol adult patients (18 years of age or older) within 48 hours of meeting Sepsis-3 criteria, admitted to intensive care unit, with oral or enteral access. Patients will be randomised 1:1:1 to low-dose metformin (500 mg two times per day), high-dose metformin (1000 mg two times per day) or placebo for 5 days. Primary safety outcome will be the proportion of metformin-associated serious adverse events. Feasibility assessment will be based on acceptability by patients and clinicians, and by enrolment rate. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board. All patients or surrogates will provide written consent prior to enrolment and any study intervention. Metformin is a widely available, inexpensive medication with a long track record for safety, which if effective would be accessible and easy to deploy. We describe the study methods using the Standard Protocol Items for Randomized Trials framework and discuss key design features and methodological decisions. LiMiT AKI will investigate the feasibility and safety of metformin in critically ill patients with sepsis at risk of SA-AKI, in preparation for a future large-scale efficacy study. Main results will be published as soon as available after final analysis. TRIAL REGISTRATION NUMBER: NCT05900284.

Characterizing intensive care unit rounding teams using meta-data from the electronic health record.

PURPOSE: Teamwork is an important determinant of outcomes in the intensive care unit (ICU), yet the nature of individual ICU teams remains poorly understood. We examined whether meta-data in the form of digital signatures in the electronic health record (EHR) could be used to identify and characterize ICU teams. METHODS: We analyzed EHR data from 27 ICUs over one year. We linked intensivist physicians, nurses, and respiratory therapists to individual patients based on selected EHR meta-data. We then characterized ICU teams by their members' overall past experience and shared past experience; and used network analysis to characterize ICUs by their network's density and centralization. RESULTS: We identified 2327 unique providers and 30,892 unique care teams. Teams varied based on their average team member experience (median and total range: 262.2 shifts, 9.0-706.3) and average shared experience (median and total range: 13.2 shared shifts, 1.0-99.3). ICUs varied based on their network's density (median and total range: 0.12, 0.07-0.23), degree centralization (0.50, 0.35-0.65) and closeness centralization (0.45, 0.11-0.60). In a regression analysis, this variation was only partially explained by readily observable ICU characteristics. CONCLUSIONS: EHR meta-data can assist in the characterization of ICU teams, potentially providing novel insight into strategies to measure and improve team function in critical care.

Adoption and Deadoption of Medications to Treat Hospitalized Patients With COVID-19.

OBJECTIVES: The COVID-19 pandemic was characterized by rapidly evolving evidence regarding the efficacy of different therapies, as well as rapidly evolving health policies in response to that evidence. Data on adoption and deadoption are essential as we learn from this pandemic and prepare for future public health emergencies. DESIGN: We conducted an observational cohort study in which we determined patterns in the use of multiple medications to treat COVID-19: remdesivir, hydroxychloroquine, IV corticosteroids, tocilizumab, heparin-based anticoagulants, and ivermectin. We analyzed changes both overall and within subgroups of critically ill versus Noncritically ill patients. SETTING: Data from Optum's deidentified Claims-Clinical Dataset, which contains multicenter electronic health record data from U.S. hospitals. PATIENTS: Adults hospitalized with COVID-19 from January 2020 to June 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 141,533 eligible patients, 34,515 (24.4%) required admission to an ICU, 14,754 (10.4%) required mechanical ventilation, and 18,998 (13.4%) died during their hospitalization. Averaged over the entire time period, corticosteroid use was most common (47.0%), followed by remdesivir (33.2%), anticoagulants (19.3%), hydroxychloroquine (7.3%), and tocilizumab (3.4%). Usage patterns varied substantially across treatments. For example, hydroxychloroquine use peaked in March 2020 and leveled off to near zero by June 2020, whereas the use of remdesivir, corticosteroids, and tocilizumab all increased following press releases announcing positive results of large international trials. Ivermectin use increased slightly over the study period but was extremely rare overall (0.4%). CONCLUSIONS: During the COVID-19 pandemic, medication treatment patterns evolved reliably in response to emerging evidence and changes in policy. These findings may inform efforts to promote optimal adoption and deadoption of treatments for acute care conditions.

Ocular metastasis of colorectal cancer: An uncommon presentation of a common malignancy.

Approximately 20% of patients with colorectal cancer have metastatic disease at time of diagnosis, and another 25-35% develop metastases during the course of their disease. Liver, peritoneum, and lungs are the most common sites of metastases. We report the case of a 60-year-old female who presented with ocular metastasis 4 years after her initial curative-intent treatment for T3N1M0 rectal adenocarcinoma. After local eye radiation therapy, she received palliative systemic chemotherapy and enjoyed a good quality of life for 32 months before succumbing to progressive disease. Ocular metastasis of colorectal cancer is rare. When present, it usually occurs in the setting of diffuse hematogenous spread. In addition to local therapy, systemic chemotherapy should also be considered.