Meta-Analysis of Long-Term Vitamin D Supplementation on Overall Mortality

<div><p>Introduction</p><p>It 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.</p> <p>Methods</p><p>A 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.</p> <p>Results</p><p>Data 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.</p> <p>Conclusions</p><p>The 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.</p> </div

Risk ratio of fatal adverse events by subgroup.

<p>NSCLC, non– small cell lung cancer; SCLC, small cell lung cancer; RR, risk ratio; PFS, progression-free survival; NA, not applicable.</p

An Updated Meta-Analysis of Fatal Adverse Events Caused by Bevacizumab Therapy in Cancer Patients

<div><p>Background</p><p>The risk of fatal adverse events (FAEs) due to bevacizumab-based chemotherapy has not been well described; we carried out an updated meta-analysis regarding this issue.</p><p>Methods</p><p>An electronic search of Medline, Embase and The Cochrane Central Register of Controlled Trials was conducted to investigate the effects of randomized controlled trials on bevacizumab treatment on cancer patients. Random or fixed-effect meta-analytical models were used to evaluate the risk ratio (RR) of FAEs due to the use of bevacizumab.</p><p>Results</p><p>Thirty-four trials were included. Allocation to bevacizumab therapy significantly increased the risk of FAEs; the RR was 1.29 (95% CI:1.05–1.57). This association varied significantly with tumor types (<i>P</i> = 0.002) and chemotherapeutic agents (<i>P</i> = 0.005) but not with bevacizumab dose (<i>P</i> = 0.90). Increased risk was seen in patients with non–small cell lung cancer, pancreatic cancer, prostate cancer, and ovarian cancer. However, FAEs were lower in breast cancer patients treated with bevacizumab. In addition, bevacizumab was associated with an increased risk of FAEs in patients who received concomitant agents of taxanes and/or platinum.</p><p>Conclusion</p><p>Compared with chemotherapy alone, the addition of bevacizumab was associated with an increased risk of FAEs among patients with special tumor types, particularly when combined with chemotherapeutic agents such as platinum.</p></div

Study flow diagram.

<p>Study flow diagram.</p

Study flow diagram.

<p>Study flow diagram.</p

Characteristics of studies included in primary analysis.

<p>*Number of patients for safety analysis; NSCLC, non– small cell lung cancer; SCLC, small cell lung cancer.</p

Sensitivity analysis (fixed effect model): A, studies under 3 years; B, studies over 3 years.

<p>Sensitivity analysis (fixed effect model): A, studies under 3 years; B, studies over 3 years.</p

Fatal adverse events by specific type.

<p>Fatal adverse events by specific type.</p

Risk ratio of fatal adverse events in cancer participants treatment with bevacizumab compare with control.

<p>Risk ratio of fatal adverse events in cancer participants treatment with bevacizumab compare with control.</p

Primary analysis (fixed effect model): A, studies under 3 years; B, studies over 3 years.

<p>Primary analysis (fixed effect model): A, studies under 3 years; B, studies over 3 years.</p