Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

6ª Diretriz de monitorização ambulatorial da pressão arterial e 4ª diretriz de monitorização residencial da pressão arterial

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The impact of patient-related nonmodifiable factors on perioperative outcomes following radical cystectomy with enhanced recovery protocol

Background: Enhanced recovery after surgery (ERAS) protocols decrease the length of hospital stay (LOS) and complications following radical cystectomy (RC). However, the impact of non-modifiable patient factors to postoperative outcome is unclear. This study aimed to identify nonmodifiable patient and disease factors predictive of post-RC outcomes with ERAS protocols. Methods: We reviewed our institutional review board-approved prospectively maintained bladder cancer database. Patients with primary urothelial bladder cancer who underwent open RC with ERAS protocol between 2012 and 2016 were identified. Patient demographic and disease-relevant variables were reviewed. Factors predictive of LOS, 30- and 90-day complications and readmission were assessed using univariate and multivariable analyses. Results: A total of 289 patients with a median age of 70 years were included, of whom 80.6% were male, 33.6% had Charlson comorbidity index ⩾2. Median LOS was 4 days and 21.1% received intraoperative transfusion. The 30-day complication and readmission rates were 58.8% and 16.6%, respectively. Age >70 ( p = 0.02), Charlson comorbidity index ⩾2 ( p = 0.005), and intraoperative transfusion ( p = 0.03) were significantly associated with LOS. Intraoperative transfusion was significantly associated with 30-day complication and readmission ( p = 0.008, p = 0.005, respectively). No factor was found to be significantly associated with 90-day complication or readmission. Conclusions: With ERAS protocol, non-modifiable patient and disease factors influence outcomes after RC. Risk adjustment for these factors is important for patient counseling, quality assessment and future reimbursement

Machine learning models for predicting post-cystectomy recurrence and survival in bladder cancer patients.

Currently in patients with bladder cancer, various clinical evaluations (imaging, operative findings at transurethral resection and radical cystectomy, pathology) are collectively used to determine disease status and prognosis, and recommend neoadjuvant, definitive and adjuvant treatments. We analyze the predictive power of these measurements in forecasting two key long-term outcomes following radical cystectomy, i.e., cancer recurrence and survival. Information theory and machine learning algorithms are employed to create predictive models using a large prospective, continuously collected, temporally resolved, primary bladder cancer dataset comprised of 3503 patients (1971-2016). Patient recurrence and survival one, three, and five years after cystectomy can be predicted with greater than 70% sensitivity and specificity. Such predictions may inform patient monitoring schedules and post-cystectomy treatments. The machine learning models provide a benchmark for predicting oncologic outcomes in patients undergoing radical cystectomy and highlight opportunities for improving care using optimal preoperative and operative data collection