Robert M. Rodriguez

OBJECTIVE: To determine whether the administration of recombinant human erythropoietin (rHuEPO) to critically ill patients in the intensive care unit (ICU) would reduce the number of red blood cell (RBC) transfusions required. DESIGN: A prospective, randomized, double-blind, placebo-controlled, multicenter trial. SETTING: ICUs at three academic tertiary care medical centers. PATIENTS: A total of 160 patients who were admitted to the ICU and met the eligibility criteria were enrolled in the study (80 into the rHuEPO group; 80 into the placebo group). INTERVENTIONS: Patients were randomized to receive either rHuEPO or placebo. The study drug (300 units/kg of rHuEPO or placebo) was administered by subcutaneous injection beginning ICU day 3 and continuing daily for a total of 5 days (until ICU day 7). The subsequent dosing schedule was every other day to achieve a hematocrit (Hct) concentration of >38%. The study drug was given for a minimum of 2 wks or until ICU discharge (for subjects with ICU lengths of stay >2 wks) up to a total of 6 wks (42 days) postrandomization. MEASUREMENTS AND MAIN RESULTS: The cumulative number of units of RBCs transfused was significantly less in the rHuEPO group than in the placebo group (p<.002, Kolmogorov-Smirnov test). The rHuEPO group was transfused with a total of 166 units of RBCs vs. 305 units of RBCs transfused in the placebo group. The final Hct concentration of the rHuEPO patients was significantly greater than the final Hct concentration of placebo patients (35.1+/-5.6 vs. 31.6+/-4.1; p<.01, respectively). A total of 45% of patients in the rHuEPO group received a blood transfusion between days 8 and 42 or died before study day 42 compared with 55% of patients in the placebo group (relative risk, 0.8; 95% confidence interval, 0.6, 1.1). There were no significant differences between the two groups either in mortality or in the frequency of adverse events. CONCLUSIONS: The administration of rHuEPO to critically ill patients is effective in raising their Hct concentrations and in reducing the total number of units of RBCs they require.

BACKGROUND: The COVID-19 pandemic disrupted the United States (US) medical education system with the necessary, yet unprecedented Association of American Medical Colleges (AAMC) national recommendation to pause all student clinical rotations with in-person patient care. This study is a quantitative analysis investigating the educational and psychological effects of the pandemic on US medical students and their reactions to the AAMC recommendation in order to inform medical education policy. METHODS: The authors sent a cross-sectional survey via email to medical students in their clinical training years at six medical schools during the initial peak phase of the COVID-19 pandemic. Survey questions aimed to evaluate students' perceptions of COVID-19's impact on medical education; ethical obligations during a pandemic; infection risk; anxiety and burnout; willingness and needed preparations to return to clinical rotations. RESULTS: Seven hundred forty-one (29.5%) students responded. Nearly all students (93.7%) were not involved in clinical rotations with in-person patient contact at the time the study was conducted. Reactions to being removed were mixed, with 75.8% feeling this was appropriate, 34.7% guilty, 33.5% disappointed, and 27.0% relieved. Most students (74.7%) agreed the pandemic had significantly disrupted their medical education, and believed they should continue with normal clinical rotations during this pandemic (61.3%). When asked if they would accept the risk of infection with COVID-19 if they returned to the clinical setting, 83.4% agreed. Students reported the pandemic had moderate effects on their stress and anxiety levels with 84.1% of respondents feeling at least somewhat anxious. Adequate personal protective equipment (PPE) (53.5%) was the most important factor to feel safe returning to clinical rotations, followed by adequate testing for infection (19.3%) and antibody testing (16.2%). CONCLUSIONS: The COVID-19 pandemic disrupted the education of US medical students in their clinical training years. The majority of students wanted to return to clinical rotations and were willing to accept the risk of COVID-19 infection. Students were most concerned with having enough PPE if allowed to return to clinical activities.

OBJECTIVE: To determine the effects of accidental injury of varying severity on interleukin (IL)-1 alpha, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha), and endotoxin release. DESIGN: Prospective, multi-unit, longitudinal study. SETTING: Emergency Departments and intensive care units of two university hospitals. PATIENTS: Trauma patients after mild, moderate, and severe injury (Injury Severity Score of < or = 10, 11 to 24, and > or = 25, respectively). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma cytokine and endotoxin concentrations were measured over a 5-day period, starting within 2 hrs of accidental injury. An enzyme-linked immunosorbent assay was used to determine plasma concentrations of IL-1 alpha, IL-6, IL-8, and TNF-alpha. Plasma endotoxin concentrations were measured using a chromogenic limulus amebocyte assay. Preresuscitation samples obtained immediately on arrival in the Emergency Department, and within 2 hrs of injury, demonstrated significant increases of IL-6 and IL-8 concentrations in the severe injury group, in contrast to minimal increases seen after mild or moderate injury. Analysis of serial postresuscitation samples demonstrated rapid increases in IL-6 and IL-8 concentrations within 12 hrs of injury. IL-6 and IL-8 remained increased for 24 hrs after injury, then decreased markedly from their peak values during the next 24 hrs. Increased circulating concentrations of these cytokines continued to be present for > 5 days in the severely injured patients. IL-6 and IL-8 concentrations were only minimally increased in patients 8 and 24 hrs after moderate injury. Endotoxin and IL-1 alpha were not found in any samples, including those samples obtained serially from severely injured patients. No patient at any time point had TNF-alpha concentrations of > 35 pg/mL. CONCLUSIONS: These results demonstrate that severe injury produces rapid, large increases in circulating concentrations of IL-6 and IL-8 that may contribute to the frequent development of the adult respiratory distress syndrome and multiple organ system failure in this clinical setting.