ObjectiveTo investigate whether vitamin D supplementation is associated with lower mortality in adults.DesignSystematic review and meta-analysis of randomised controlled trials.Data sourcesMedline, Embase, and the Cochrane Central Register from their inception to 26 December 2018.Eligibility criteria for selecting studiesRandomised controlled trials comparing vitamin D supplementation with a placebo or no treatment for mortality were included. Independent data extraction was conducted and study quality assessed. A meta-analysis was carried out by using fixed effects and random effects models to calculate risk ratio of death in the group receiving vitamin D supplementation and the control group.Main outcome measuresAll cause mortality.Results52 trials with a total of 75 454 participants were identified. Vitamin D supplementation was not associated with all cause mortality (risk ratio 0.98, 95% confidence interval 0.95 to 1.02, I2=0%), cardiovascular mortality (0.98, 0.88 to 1.08, 0%), or non-cancer, non-cardiovascular mortality (1.05, 0.93 to 1.18, 0%). Vitamin D supplementation statistically significantly reduced the risk of cancer death (0.84, 0.74 to 0.95, 0%). In subgroup analyses, all cause mortality was significantly lower in trials with vitamin D3 supplementation than in trials with vitamin D2 supplementation (P for interaction=0.04); neither vitamin D3 nor vitamin D2 was associated with a statistically significant reduction in all cause mortality.ConclusionsVitamin D supplementation alone was not associated with all cause mortality in adults compared with placebo or no treatment. Vitamin D supplementation reduced the risk of cancer death by 16%. Additional large clinical studies are needed to determine whether vitamin D3 supplementation is associated with lower all cause mortality.Study registrationPROSPERO registration number CRD42018117823.

No abstract

IMPORTANCEAlthough corticosteroids are widely used for adults with sepsis, both the overall benefit and potential risks remain unclear.OBJECTIVE To conduct a systematic review and meta-analysis of the efficacy and safety of corticosteroids in patients with sepsis. DATA SOURCES AND STUDY SELECTION MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception until March 20, 2018, and updated on August 10, 2018. The terms corticosteroids, sepsis, septic shock, hydrocortisone, controlled trials, and randomized controlled trial were searched alone or in combination. Randomized clinical trials (RCTs) were included that compared administration of corticosteroids with placebo or standard supportive care in adults with sepsis.DATA EXTRACTION AND SYNTHESIS Meta-analyses were conducted using a random-effects model to calculate risk ratios (RRs) and mean differences (MDs) with corresponding 95% CIs. Two independent reviewers completed citation screening, data abstraction, and risk assessment. MAIN OUTCOMES AND MEASURES Twenty-eight-day mortality.RESULTS This meta-analysis included 37 RCTs (N = 9564 patients). Eleven trials were rated as low risk of bias. Corticosteroid use was associated with reduced 28-day mortality (RR, 0.90; 95% CI, 0.82-0.98; I 2 = 27%) and intensive care unit (ICU) mortality (RR, 0.85; 95% CI, 0.77-0.94; I 2 = 0%) and in-hospital mortality (RR, 0.88; 95% CI, 0.79-0.99; I 2 = 38%). Corticosteroids were significantly associated with increased shock reversal at day 7 (MD, 1.95; 95% CI, 0.80-3.11) and vasopressor-free days (MD, 1.95; 95% CI, 0.80-3.11) and with ICU length of stay (MD, −1.16; 95% CI, −2.12 to −0.20), the sequential organ failure assessment score at day 7 (MD, −1.38; 95% CI, −1.87 to −0.89), and time to resolution of shock (MD, −1.35; 95% CI, −1.78 to −0.91). However, corticosteroid use was associated with increased risk of hyperglycemia (RR, 1.19; 95% CI, 1.08-1.30) and hypernatremia (RR, 1.57; 95% CI, 1.24-1.99). CONCLUSIONS AND RELEVANCEThe findings suggest that administration of corticosteroids is associated with reduced 28-day mortality compared with placebo use or standard supportive care. More research is needed to associate personalized medicine with the corticosteroid treatment to select suitable patients who are more likely to show a benefit.

While observational studies have shown an association between vitamin D insufficiency and diabetes, it is unclear whether intervention with vitamin D supplements can lower the risk of type 2 diabetes mellitus (T2DM). PURPOSETo assess whether vitamin D supplementation reduces the risk of T2DM in people with prediabetes. DATA SOURCESWe searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to 5 July 2019. STUDY SELECTIONWe included randomized controlled trials assessing vitamin D supplementation versus placebo in relation to new-onset T2DM in people with prediabetes. DATA EXTRACTIONWe screened studies and extracted data from published trials independently. DATA SYNTHESISWe identified eight eligible trials with a total of 4,896 subjects. Vitamin D supplementation significantly reduced the risk of T2DM (risk ratio [RR] 0.89 [95% CI 0.80-0.99]; I 2 5 0%). Benefit was found in nonobese subjects (RR 0.73 [95% CI 0.57-0.92]) but not in obese subjects (RR 0.95 [95% CI 0.84-1.08]) (P interaction 5 0.048). The reversion of prediabetes to normoglycemia occurred in 116 of 548 (21.2%) participants in the vitamin D group and 75 of 532 (14.1%) in the control group. Vitamin D supplementation increased reversion rate of prediabetes to normoglycemia (RR 1.48 [95% CI 1.14-1.92]; I 2 5 0%.) LIMITATIONSDefinitions of prediabetes and new-onset diabetes in eligible studies were different, and long-term data on outcomes of T2DM prevention were lacking. CONCLUSIONSIn persons with prediabetes, vitamin D supplementation reduces the risk of T2DM and increases the reversion rate of prediabetes to normoglycemia. The benefit of the prevention of T2DM could be limited to nonobese subjects. Individual participant data meta-analyses are needed to confirm these findings.

The syntheses of MeN=P(MeNCH#H&N (4), [HRNP(MeNCH2CH2)3N](CF3C02) (R = Ph, S(CF3-C02); R = Me, 6(CF3C02)), [MePhNP(MeNCH2CH2)3N]I (7(I)), the stable azide adduct MeN3P(MeNCH2CH2)3N (S), and [HRNP(NMe2)3] (CF3C02) (R = Ph, 9(CF$02) are reported. Equilibria measured by 31P NMR spectroscopy reveal the relative ordering of basicity:The unusually strong basicities of the polycyclic cage bases (e.g., those of 1 and 4 are ca. 17 and more than 3 pKb units stronger than DBU, respectively) and the stability of adduct 8 is rationalized on the basis of partial transannulation from the bridgehead nitrogen to phosphorus which effectively delocalizes positive charge. The structure of S(CF3C02) determined by X-ray means is also reported, revealing a transannular distance of 2.559(4) A which is facilitated by a widened average MeN-P-NMe bond angle of 114.9(2)'.