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ObjectiveTo compare the rate of moderate to severe exacerbations between triple therapy and dual therapy or monotherapy in patients with chronic obstructive pulmonary disease (COPD).DesignSystematic review and meta-analysis of randomised controlled trials.Data sourcesPubMed, Embase, Cochrane databases, and clinical trial registries searched from inception to April 2018.Eligibility criteriaRandomised controlled trials comparing triple therapy with dual therapy or monotherapy in patients with COPD were eligible. Efficacy and safety outcomes of interest were also available.Data extraction and synthesisData were collected independently. Meta-analyses were conducted to calculate rate ratios, hazard ratios, risk ratios, and mean differences with 95% confidence intervals. Quality of evidence was summarised in accordance with GRADE methodology (grading of recommendations assessment, development, and evaluation).Results21 trials (19 publications) were included. Triple therapy consisted of a long acting muscarinic antagonist (LAMA), long acting β agonist (LABA), and inhaled corticosteroid (ICS). Triple therapy was associated with a significantly reduced rate of moderate or severe exacerbations compared with LAMA monotherapy (rate ratio 0.71, 95% confidence interval 0.60 to 0.85), LAMA and LABA (0.78, 0.70 to 0.88), and ICS and LABA (0.77, 0.66 to 0.91). Trough forced expiratory volume in 1 second (FEV1) and quality of life were favourable with triple therapy. The overall safety profile of triple therapy is reassuring, but pneumonia was significantly higher with triple therapy than with dual therapy of LAMA and LABA (relative risk 1.53, 95% confidence interval 1.25 to 1.87).ConclusionsUse of triple therapy resulted in a lower rate of moderate or severe exacerbations of COPD, better lung function, and better health related quality of life than dual therapy or monotherapy in patients with advanced COPD.Study registrationProspero CRD42018077033.

IntroductionIt has been suggested that vitamin D is effective to prevent mortality. However, there is no consistent conclusion that the effects of vitamin D supplementation on all-cause mortality are associated with duration of treatment. We conducted a meta-analysis regarding this issue in an effort to provide a more robust answer.MethodsA comprehensive search in a number of databases, including MEDLINE, Embase and The Cochrane Central Register of Controlled Trials, was conducted for collecting randomized controlled trials (RCTs) on vitamin D supplementation preventing mortality. Two investigators independently screened the literature according to the inclusive and exclusive criteria and the relative data were extracted. Data analysis was performed by using Review Manager 5.0 software.ResultsData from forty-two RCT s were included. Vitamin D therapy significantly decreased all-cause mortality with a duration of follow-up longer than 3 years with a RR (95% CI) of 0.94 (0.90–0.98). No benefit was seen in a shorter follow-up periods with a RR (95% CI) of 1.04 (0.97–1.12). Results remain robust after sensitivity analysis. The following subgroups of long-term follow-up had significantly fewer deaths: female only, participants with a mean age younger than 80, daily dose of 800 IU or less, participants with vitamin D insufficiency (baseline 25-hydroxyvitamin D level less than 50 nmol/L) and cholecalciferol therapy. In addition, the combination of vitamin D and calcium significantly reduced mortality and vitamin D alone also had a trend to decrease mortality in a longer time follow up.ConclusionsThe data suggest that supplementation of vitamin D is effective in preventing overall mortality in a long-term treatment, whereas it is not significantly effective in a treatment duration shorter than 3 years. Future studies are needed to identify the efficacy of vitamin D on specific mortality, such as cancer and cardiovascular disease mortality in a long-term treatment duration.

Data on the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on fracture risk are conflicting. Here, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effects of DPP-4 inhibitors. Electronic databases were searched for relevant published articles, and unpublished studies presented at ClinicalTrials.gov were searched for relevant clinical data. Eligible studies included prospective randomized trials evaluating DPP-4 inhibitors versus placebo or other anti-diabetic medications in patients with type 2 diabetes. Study quality was determined using Jadad scores. Statistical analyses were performed to calculate the risk ratios (RRs) and 95% confidence intervals (CIs) using fixed-effects models. There were 62 eligible RCTs with 62,206 participants, including 33,452 patients treated with DPP-4 inhibitors. The number of fractures was 364 in the exposed group and 358 in the control group. The overall risk of fracture did not differ between patients exposed to DPP-4 inhibitors and controls (RR, 0.95; 95% CI, 0.83–1.10; P = 0.50). The results were consistent across subgroups defined by type of DPP-4 inhibitor, type of control, and length of follow-up. The study showed that DPP-4 inhibitor use does not modify the risk of bone fracture compared with placebo or other anti-diabetic medications in patients with type 2 diabetes.