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Introduction Antibiotics are time-critical in the management of sepsis. When infectious organisms are unknown, patients are treated with empiric antibiotics to include coverage for gram-negative organisms, such as antipseudomonal cephalosporins and penicillins. However, in observational studies, some antipseudomonal cephalosporins (eg, cefepime) are associated with neurologic dysfunction while the most common antipseudomonal penicillin (piperacillin–tazobactam) is associated with acute kidney injury (AKI). No randomised control trials have compared these regimens. This manuscript describes the protocol and analysis plan for a trial designed to compare the effects of antipseudomonal cephalosporins and antipseudomonal penicillins among acutely ill patients receiving empiric antibiotics.Methods and analysis The Antibiotic Choice On ReNal outcomes trial is a prospective, single-centre, non-blinded randomised trial being conducted at Vanderbilt University Medical Center. The trial will enrol 2500 acutely ill adults receiving gram-negative coverage for treatment of infection. Eligible patients are randomised 1:1 to receive cefepime or piperacillin–tazobactam on first order entry of a broad-spectrum antibiotic covering gram-negative organisms. The primary outcome is the highest stage of AKI and death occurring between enrolment and 14 days after enrolment. This will be compared between patients randomised to cefepime and randomised to piperacillin–tazobactam using an unadjusted proportional odds regression model. The secondary outcomes are major adverse kidney events through day 14 and number of days alive and free of delirium and coma in 14 days after enrolment. Enrolment began on 10 November 2021 and is expected to be completed in December 2022.Ethics and dissemination The trial was approved by the Vanderbilt University Medical Center institutional review board (IRB#210591) with a waiver of informed consent. Results will be submitted to a peer-reviewed journal and presented at scientific conferences.Trial registration number NCT05094154.

Introduction: Hepatitis C virus (HCV), the leading cause of advanced liver disease, has enormous economic burden. Identification of patients at risk of treatment failure could lead to interventions that improve cure rates.Objectives: Our goal was to develop and evaluate a prediction model for HCV treatment failure.Methods: We analyzed HCV patients initiating direct-acting antiviral therapy at four United States institutions. Treatment failure was determined by lack of sustained virologic response (SVR) 12 weeks after treatment completion. From 20 patient-level variables collected before treatment initiation, we identified a subset associated with treatment failure in bivariate analyses. In a derivation set, separate predictive models were developed from 100 bootstrap samples using logistic regression. From the 100 models, variables were ranked by frequency of selection as predictors to create four final candidate models, using cutoffs of ≥80%, ≥50%, ≥40%, and all variables. In a validation set, predictive performance was compared across models using area under the receiver operating characteristic curve.Results: In 1,253 HCV patients, overall SVR rate was 86.1% (95% CI = 84.1%, 88.0%). The AUCs of the four final candidate models were: ≥80% = 0.576; ≥50% = 0.605; ≥40% = 0.684; all = 0.681. The best performing model (≥40%) had significantly better predictive ability than the ≥50% (p = 0.03) and ≥80% models (p = 0.02). Strongest predictors of treatment failure were older age, history of hepatocellular carcinoma, and private (vs. government) insurance.Conclusion: This study highlighted baseline factors associated with HCV treatment failure. Treatment failure prediction may facilitate development of data-driven clinical tools to identify patients who would benefit from interventions to improve SVR rates.

Barriers remain in the hepatitis C virus (HCV) cascade of care (CoC), limiting the overall impact of direct acting antivirals. This study examines movement between the stages of the HCV CoC and identifies reasons why patients and specific patient populations fail to advance through care in a real world population. We performed a single-center, ambispective cohort study of patients receiving care in an outpatient infectious diseases clinic between October 2015 and September 2016. Patients were followed from treatment referral through sustained virologic response. Univariate and multivariate analyses were performed to identify factors related to completion of each step of the CoC. Of 187 patients meeting inclusion criteria, 120 (64%) completed an evaluation for HCV treatment, 119 (64%) were prescribed treatment, 114 (61%) were approved for treatment, 113 (60%) initiated treatment, 107 (57%) completed treatment, and 100 (53%) achieved a sustained virologic response. In univariate and multivariate analyses, patients with Medicaid insurance were less likely to complete an evaluation and were less likely to be approved for treatment. Treatment completion and SVR rates are much improved from historical CoC reports. However, linkage to care following referral continues to be a formidable challenge for the HCV CoC in the DAA era. Ongoing efforts should focus on linkage to care to capitalize on DAA treatment advances and improving access for patients with Medicaid insurance.