Comparative efficacy of chemoimmunotherapy versus immunotherapy for advanced non-small cell lung cancer: A network meta-analysis of randomized trials.

BACKGROUND: To the authors' knowledge, in the absence of head-to-head trials, it is unclear whether chemoimmunotherapy provides an additional overall survival (OS) benefit compared with immunotherapy alone in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). The authors conducted a systematic literature review and network meta-analysis (NMA) to compare the efficacy of chemoimmunotherapy versus ICI. METHODS: MEDLINE, Excerpta Medica dataBASE (EMBASE), Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception to April 2020. Phase 3 trials evaluating the efficacy of first-line ICI or chemoimmunotherapy and reporting efficacy outcomes (OS, progression-free survival [PFS], and the overall response rate [ORR]) stratified by programmed death-ligand 1 (PD-L1) status were included. NMA with a Bayesian random effects model was performed. RESULTS: A total of 12 eligible trials comprising 7845 patients were included. In patients who were negative for PD-L1 (tumor proportion score [TPS] <1%), NMA comparing chemoimmunotherapy with dual-agent ICI failed to demonstrate a statistically significant difference with regard to OS, PFS, or the ORR. In patients with low PD-L1 (TPS 1%-49%), there was no statistically significant difference observed between chemoimmunotherapy compared with either single-agent ICI or dual-agent ICI with regard to OS or the ORR. In patients with high PD-L1 (TPS ≥50%), chemoimmunotherapy was found to be associated with an improved PFS and ORR compared with single-agent ICI, but not with dual-agent ICI. No differences in OS were observed with chemoimmunotherapy when compared with either single-agent or dual-agent ICIs. CONCLUSIONS: Although chemoimmunotherapy appears to improve the ORR and PFS in patients with PD-L1-high tumors when compared with single-agent ICI, it does not appear to confer an OS benefit over single-agent or dual-agent ICI for patients with advanced NSCLC regardless of PD-L1 status. Prospective trials are needed to validate these findings.

Early Colonoscopy Does Not Improve Outcomes of Patients With Lower Gastrointestinal Bleeding: Systematic Review of Randomized Trials.

BACKGROUND & AIMS: Guidelines recommend colonoscopy evaluation within 24 hours of presentation or admission in patients with high-risk or severe acute lower gastrointestinal bleeding (LGIB). Meta-analyses of the timing of colonoscopy have relied primarily on observational studies that had major potential for bias. We performed a systematic review of randomized trials to determine optimal timing of colonoscopy for patients hospitalized with acute LGIB. METHODS: We searched publication databases through July 2019 and abstracts from gastroenterology meetings through November 2019 for randomized trials of patients with acute LGIB or hematochezia. We searched for studies that compared early colonoscopy (within 24 hours) with elective colonoscopy beyond 24 hours and/or other diagnostic tests. Our primary outcome was further bleeding, defined as persistent or recurrent bleeding after index examination. Secondary outcomes included mortality, diagnostic yield (identifying source of bleeding), endoscopic intervention, and any primary hemostatic intervention (endoscopic, surgical, or interventional radiologic). We performed dual independent review, data extraction, and risk of bias assessments. We performed the meta-analysis using a random-effects model. RESULTS: Our final analysis included data from 4 randomized trials. Further bleeding was not decreased among patients who received early vs later, elective colonoscopy (relative risk [RR] for further bleeding with early colonoscopy, 1.57; 95% CI. 0.74-3.31). We did not find significant differences in the secondary outcomes of mortality (RR, 0.93; 95% CI, 0.05-17.21), diagnostic yield (RR, 1.09; 95% CI, 0.99-1.21), endoscopic intervention (RR, 1.53; 95% CI, 0.67-3.48), or any primary hemostatic intervention (RR, 1.33; 95% CI, 0.92-1.92). CONCLUSIONS: In a meta-analysis of randomized trials, we found that colonoscopy within 24 hours does not reduce further bleeding or mortality in patients hospitalized with acute LGIB. Based on these findings, patients hospitalized with acute LGIB do not generally require early colonoscopy.

Clinical practice guideline adherence before and after implementation of the HEARTFELT (HEART Failure Effectiveness & Leadership Team) intervention.

HEART Failure Effectiveness & Leadership Team (HEARTFELT) is a multifaceted intervention designed to improve adherence with the American College of Cardiology/American Heart Association practice guidelines for heart failure (HF). The purpose of this study was to assess differences in clinician adherence with clinical practice guidelines before and after implementation of HEARTFELT. A quasi-experimental, untreated control group design with separate pretest/posttest samples was employed at a community hospital in Connecticut. The untreated historical control group included patients aged 65 years or older with HF and a nonequivalent comparison group of patients with stroke. The posttest samples included patients with the diagnosis of HF and stroke admitted after implementation of the HEARTFELT intervention. The HEARTFELT intervention included automated pathway in electronic medical record (order sets, interdisciplinary plan of care, self-management plan), access to evidence for clinicians and patients, HF self-management education tools, and ongoing discipline-specific feedback regarding adherence. Data were analyzed using parametric and nonparametric methods. The HEARTFELT intervention significantly improved clinician adherence with addressing all self-management categories in the electronic medical record (P = .000) and adherence with self-management education given to the patient in writing at discharge (P = .000). There were no significant differences in adherence with medical interventions (P = .39). While guideline adherence is associated with less practice variation and improved processes, methods of integration into practice in community hospital settings have been largely unexplored. The multifaceted HEARTFELT intervention is promising for its potential to integrate evidence at the point of care, to reduce unwarranted variation in practice, and ultimately to improve the outcomes of individuals with HF.