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BACKGROUND Both balanced crystalloids and saline are used for intravenous fluid administration in critically ill adults, but it is not known which results in better clinical outcomes. METHODS In a pragmatic, cluster-randomized, multiple-crossover trial conducted in five intensive care units at an academic center, we assigned 15,802 adults to receive saline (0.9% sodium chloride) or balanced crystalloids (lactated Ringer’s solution or Plasma-Lyte A) according to the randomization of the unit to which they were admitted. The primary outcome was a major adverse kidney event within 30 days — a composite of death from any cause, new renal-replacement therapy, or persistent renal dysfunction (defined as an elevation of the creatinine level to ≥200% of baseline) — all censored at hospital discharge or 30 days, whichever occurred first. RESULTS Among the 7942 patients in the balanced-crystalloids group, 1139 (14.3%) had a major adverse kidney event, as compared with 1211 of 7860 patients (15.4%) in the saline group (marginal odds ratio, 0.91; 95% confidence interval [CI], 0.84 to 0.99; conditional odds ratio, 0.90; 95% CI, 0.82 to 0.99; P = 0.04). In-hospital mortality at 30 days was 10.3% in the balanced-crystalloids group and 11.1% in the saline group (P = 0.06). The incidence of new renal-replacement therapy was 2.5% and 2.9%, respectively (P = 0.08), and the incidence of persistent renal dysfunction was 6.4% and 6.6%, respectively (P = 0.60). CONCLUSIONS Among critically ill adults, the use of balanced crystalloids for intravenous fluid administration resulted in a lower rate of the composite outcome of death from any cause, new renal-replacement therapy, or persistent renal dysfunction than the use of saline. (Funded by the Vanderbilt Institute for Clinical and Translational Research and others; SMART-MED and SMART-SURG ClinicalTrials.gov numbers, NCT02444988 and NCT02547779.)

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Key PointsQuestionDoes prior COVID-19 vaccination reduce hospitalizations for COVID-19, and among patients hospitalized for COVID-19, does prior vaccination reduce disease severity?FindingsIn a case-control study that included 4513 hospitalized adults in 18 US states, hospitalization for a COVID-19 diagnosis compared with an alternative diagnosis was associated with an adjusted odds ratio (aOR) of 0.15 for full vaccination with an authorized or approved mRNA COVID-19 vaccine. Among adults hospitalized for COVID-19, progression to death or invasive mechanical ventilation was associated with an aOR of 0.33 for full vaccination; both ORs were statistically significant.MeaningVaccination with an mRNA COVID-19 vaccine was significantly less likely among patients with COVID-19 hospitalization and with disease progression, consistent with risk reduction among vaccine breakthrough infections.