Importance Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear.Objective To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids.Data Sources Twenty-eight databases from inception to April 2015. Study SelectionRandomized clinical trials of cannabinoids for the following indications: nausea and vomiting due to chemotherapy, appetite stimulation in HIV/AIDS, chronic pain, spasticity due to multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, or Tourette syndrome. Data Extraction and SynthesisStudy quality was assessed using the Cochrane risk of bias tool. All review stages were conducted independently by 2 reviewers. Where possible, data were pooled using random-effects meta-analysis. Main Outcomes and MeasuresPatient-relevant/disease-specific outcomes, activities of daily living, quality of life, global impression of change, and AEs.Results A total of 79 trials (6462 participants) were included; 4 were judged at low risk of bias. Most trials showed improvement in symptoms associated with cannabinoids but these associations did not reach statistical significance in all trials. Compared with placebo, cannabinoids were associated with a greater average number of patients showing a complete nausea and vomiting response (47% vs 20%; odds ratio [OR], 3.82 [95% CI, 1.55-9.42]; 3 trials), reduction in pain (37% vs 31%; OR, 1.41 [95% CI, 0.99-2.00]; 8 trials), a greater average reduction in numerical rating scale pain assessment (on a 0-10-point scale; weighted mean difference [WMD], −0.46 [95% CI, −0.80 to −0.11]; 6 trials), and average reduction in the Ashworth spasticity scale (WMD, −0.12 [95% CI, −0.24 to 0.01]; 5 trials). There was an increased risk of short-term AEs with cannabinoids, including serious AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination. Conclusions and RelevanceThere was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term AEs.
Meta-analysis: Its strengths and limitations REVIEW ■ ABSTRACTNowadays, doctors face an overwhelming amount of information, even in narrow areas of interest. In response, reviews designed to summarize the large volumes of information are frequently published. When a review is done systematically, following certain criteria, and the results are pooled and analyzed quantitatively, it is called a meta-analysis. A well-designed meta-analysis can provide valuable information for researchers, policymakers, and clinicians. However, there are many critical caveats in performing and interpreting them, and thus many ways in which meta-analyses can yield misleading information. ■ KEY POINTSMeta-analysis is an analytical technique designed to summarize the results of multiple studies.By combining studies, a meta-analysis increases the sample size and thus the power to study effects of interest.
View references (28)Background Programmed death 1 (PD-1) programmed death-ligand 1 (PD-L1) inhibitors show significant clinical activity in non-small cell lung carcinoma (NSCLC). However, they are often associated with potentially fatal immune-mediated pneumonitis. Preliminary reports of trials suggest a difference in the rate of pneumonitis with PD-1 and PD-L1 inhibitors. We sought to determine the overall incidence of pneumonitis and differences according to type of inhibitors and prior chemotherapy use. Methods MEDLINE, Embase, and Scopus databases were searched up to November 2016. Rates of pneumonitis of any grade and grade ≥ 3 from all clinical trials investigating nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab as single agents in NSCLC were collected. The incidence of pneumonitis across trials was calculated using DerSimonian-Laird random effects models. We compared incidences between PD-1 and PD-L1 inhibitors and between treatment naive and previously treated patients. Results Nineteen trials (12 with PD-1 inhibitors [n = 3,232] and 7 with PD-L1 inhibitors [n = 1,806]) were identified. PD-1 inhibitors were found to have statistically significant higher incidence of any grade pneumonitis compared with PD-L1 inhibitors (3.6%; 95% CI, 2.4%-4.9% vs 1.3%; 95% CI, 0.8%-1.9%, respectively; P =.001). PD-1 inhibitors were also associated with higher incidence of grade 3 or 4 pneumonitis (1.1%; 95% CI, 0.6%-1.7% vs 0.4%; 95% CI, 0%-0.8%; P =.02). Treatment naive patients had higher incidence of grade 1 through 4 pneumonitis compared with previously treated patients (4.3%; 95% CI, 2.4%-6.3% vs
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