Prospective clinical trials and novel therapies in the medical management of severe alcohol-associated hepatitis.
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ABSTRACT:
SUBMITTER: Pimienta M
PROVIDER: S-EPMC9745256 | biostudies-literature | 2022 Dec
REPOSITORIES: biostudies-literature
Publications
Prospective clinical trials and novel therapies in the medical management of severe alcohol-associated hepatitis.
Pimienta Michael M Tien Christine C Terrault Norah A NA
Clinical liver disease 20221212 6
Content available: Author Interview and Audio Recording. ...[more]
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Project description:IntroductionSevere blunt trauma is a leading cause of premature death and handicap. However, the benefit for the patient of pre-hospital management by emergency physicians remains controversial because it may delay admission to hospital. This study aimed to compare the impact of medical pre-hospital management performed by SMUR (Service Mobile d'Urgences et de Réanimation) with non-medical pre-hospital management provided by fire brigades (non-SMUR) on 30-day mortality.MethodsThe FIRST (French Intensive care Recorded in Severe Trauma) study is a multicenter cohort study on consecutive patients with severe blunt trauma requiring admission to university hospital intensive care units within the first 72 hours. Initial clinical status, pre-hospital life-sustaining treatments and Injury Severity Scores (ISS) were recorded. The main endpoint was 30-day mortality.ResultsAmong 2,703 patients, 2,513 received medical pre-hospital management from SMUR, and 190 received basic pre-hospital management provided by fire brigades. SMUR patients presented a poorer initial clinical status and higher ISS and were admitted to hospital after a longer delay than non-SMUR patients. The crude 30-day mortality rate was comparable for SMUR and non-SMUR patients (17% and 15% respectively; P = 0.61). After adjustment for initial clinical status and ISS, SMUR care significantly reduced the risk of 30-day mortality (odds ratio (OR): 0.55, 95% CI: 0.32 to 0.94, P = 0.03). Further adjustments for the delay to hospital admission only marginally affected these results.ConclusionsThis study suggests that SMUR management is associated with a significant reduction in 30-day mortality. The role of careful medical assessment and intensive pre-hospital life-sustaining treatments needs to be assessed in further studies.
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Project description:ImportanceThe benefits of prophylactic antibiotics for hospitalized patients with severe alcohol-related hepatitis are unclear.ObjectiveTo determine the efficacy of amoxicillin-clavulanate, compared with placebo, on mortality in patients hospitalized with severe alcohol-related hepatitis and treated with prednisolone.Design, setting, and participantsMulticenter, randomized, double-blind clinical trial among patients with biopsy-proven severe alcohol-related hepatitis (Maddrey function score ≥32 and Model for End-stage Liver Disease [MELD] score ≥21) from June 13, 2015, to May 24, 2019, in 25 centers in France and Belgium. All patients were followed up for 180 days. Final follow-up occurred on November 19, 2019.InterventionPatients were randomly assigned (1:1 allocation) to receive prednisolone combined with amoxicillin-clavulanate (n = 145) or prednisolone combined with placebo (n = 147).Main outcome and measuresThe primary outcome was all-cause mortality at 60 days. Secondary outcomes were all-cause mortality at 90 and 180 days; incidence of infection, incidence of hepatorenal syndrome, and proportion of participants with a MELD score less than 17 at 60 days; and proportion of patients with a Lille score less than 0.45 at 7 days.ResultsAmong 292 randomized patients (mean age, 52.8 [SD, 9.2] years; 80 [27.4%] women) 284 (97%) were analyzed. There was no significant difference in 60-day mortality between participants randomized to amoxicillin-clavulanate and those randomized to placebo (17.3% in the amoxicillin-clavulanate group and 21.3% in the placebo group [P = .33]; between-group difference, -4.7% [95% CI, -14.0% to 4.7%]; hazard ratio, 0.77 [95% CI, 0.45-1.31]). Infection rates at 60 days were significantly lower in the amoxicillin-clavulanate group (29.7% vs 41.5%; mean difference, -11.8% [95% CI, -23.0% to -0.7%]; subhazard ratio, 0.62; [95% CI, 0.41-0.91]; P = .02). There were no significant differences in any of the remaining 3 secondary outcomes. The most common serious adverse events were related to liver failure (25 in the amoxicillin-clavulanate group and 20 in the placebo group), infections (23 in the amoxicillin-clavulanate group and 46 in the placebo group), and gastrointestinal disorders (15 in the amoxicillin-clavulanate group and 21 in the placebo group).Conclusion and relevanceIn patients hospitalized with severe alcohol-related hepatitis, amoxicillin-clavulanate combined with prednisolone did not improve 2-month survival compared with prednisolone alone. These results do not support prophylactic antibiotics to improve survival in patients hospitalized with severe alcohol-related hepatitis.Trial registrationClinicalTrials.gov Identifier: NCT02281929.
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