IMPORTANCE Observational studies have reported an association between low serum vitamin D levels and elevated risk of cardiovascular disease (CVD) events, but such studies cannot prove causation because of possible unmeasured confounding.OBJECTIVE We conducted a meta-analysis of randomized clinical trials that tested the association of vitamin D supplementation with reduced CVD events and all-cause mortality.

Introduction Treatment of chronic obstructive pulmonary disease (COPD) is evolving specially with triple inhaler therapy. Objectives To perform a meta‐analysis to ascertain the safety and efficacy of triple inhaler therapy consisting of an inhaled‐glucocorticoid (ICS), long‐acting muscarinic antagonist (LAMA) and long‐acting beta2‐agonist (LABA) when compared with dual therapy (ICS‐LABA or LAMA‐LABA). Methods We performed an electronic database search to include randomized controlled trials (RCTs) comparing between triple and dual inhalers. Pooled rate‐ratio (RR) or odds‐ratio (OR) for dichotomous data and weighted mean difference (MD) for continuous data were calculated with their corresponding 95% confidence interval (CI). Results Our study included 12 RCTs totaling 19,322 patients, mean age of 65 ± 8.2 years and 68.2% were male. Pooled analysis demonstrated a significant reduction in moderate‐to‐severe COPD exacerbations with triple therapy (RR 0.75; 95% CI 0.69‐0.83; P < 0.01). Additionally, triple therapy caused significant increase in trough FEV1 (MD 0.09 L; 95% CI 0.07‐0.12; P < 0.01), significant reduction in the mean St. George's Respiratory Questionnaire (SGRQ) score (MD −1.67; 95% CI −2.02‐ −1.31; P < 0.01), and more patients experienced ≥ 4 points reduction of SGRQ score (OR 1.27; 95% CI 1.19‐1.35; P < 0.01). Triple therapy was associated with an increased risk of pneumonia when compared to LABA/LAMA (OR 1.25; 95% 1.03‐1.97; P = 0.03) but there were no significant differences in other adverse events between triple and dual inhalers. Conclusions Among patients with moderate‐to‐severe COPD, triple inhaler therapy was associated with a reduction of moderate‐to‐severe COPD exacerbations, improved lung function and improved quality of life when compared to dual inhaler therapy but with an increased pneumonia risk.

Classic or large duct primary sclerosing cholangitis (PSC) is part of the PSC spectrum. It is diagnosed on clinical and biochemical findings of cholestasis supported by biliary tree changes on cholangiography, forgoing the need for an invasive liver biopsy. The spectrum contains various PSC variants with distinct clinical courses and outcomes. We present a case of small duct PSC, a rare variant that manifested insidiously with clinical and objective cholestasis but appeared negative on diagnostic cholangiography. Eventually, a liver biopsy was obtained that revealed chronic bilious disease of the small and microscopic ducts with simultaneous changes consistent with liver cirrhosis. Despite presenting like its classical counterpart, small duct PSC can remain undetectable on cholangiography due to the diminutive size of the bile ducts requiring histological confirmation. In contrast to classic PSC, small duct PSC portends a much better prognosis. However, it eventually progresses to the classic form or end-stage liver disease, requiring patients to receive timely surveillance and transplantation referrals. Due to the limited understanding of this disease process, patients with similar presentations often pose a diagnostic dilemma due to the clinical and cholangiographic mismatch. This case aims to reaffirm that a negative cholangiography does not rule out the PSC spectrum and that small duct disease is a rare but growing entity. The paucity in cases emphasizes the importance of isolated reports in guiding workup and management, especially since surveillance schedules and transplantation guidelines have not been formally established.