Network Meta-Analysis of Randomized Controlled Trials: Efficacy and Safety of UDCA-Based Therapies in Primary Biliary Cirrhosis

Major ursodeoxycholic acid (UDCA)-based therapies for primary biliary cirrhosis (PBC) include UDCA only, or combined with either methotrexate (MTX), corticosteroids (COT), colchicine (COC), or bezafibrate (BEF). As the optimum treatment regimen is unclear and warrants exploration, we aimed to compare these therapies in terms of patient mortality or liver transplantation (MOLT) and adverse events (AE).PubMed, the Cochrane Library, and Scopus were searched for randomized controlled trials up to August 31, 2014. We estimated the hazard ratios (HRs) for MOLT and odds ratios (ORs) for AE. A sensitivity analysis based on the dose of UDCA was also executed.Thirty-one eligible articles were included. Compared with COT plus UDCA, UDCA (HR 0.38, 95% confidence interval [CI] 0.09–1.39), BEF plus UDCA (HR 0.29, 95% CI 0.02–4.83), COC plus UDCA (HR 0.39, 95% CI 0.07–2.25), MTX plus UDCA (HR 0.28, 95% CI 0.05–1.63), or OBS (HR 0.49, 95% CI 0.11–2.01) all provided an increased risk of MOLT. With respect to drug AE profile, although not differing appreciably, BEF plus UDCA was associated with more AEs compared with UDCA (OR 3.16, 95% CI 0.59–20.67), COT plus UDCA (OR 2.27, 95% CI 0.15–33.36), COC plus UDCA (OR 1.00, 95% CI 0.09–12.16), MTX plus UDCA (OR 2.03, 95% CI 0.23–17.82), or OBS (OR 3.00, 95% CI 0.53–20.75). The results of sensitivity analyses were highly consistent with previous analyses.COT plus UDCA was the optimal UDCA-based regimen for both MOLT and AEs. BEF plus UDCA was most likely to cause AEs, whereas monotherapy with UDCA and coadministriation of COT plus UDCA appeared to be associated with the fewest AEs for PBC treatment.     

Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep

Pulmonary hypertension of the newborn (PHN) constitutes a critical condition with severe cardiovascular and neurological consequences. One of its main causes is hypoxia during gestation, and thus, it is a public health concern in populations living above 2500 m. Although some mechanisms are recognized, the pathophysiological facts that lead to PHN are not fully understood, which explains the lack of an effective treatment. Oxidative stress is one of the proposed mechanisms inducing pulmonary vascular dysfunction and PHN. Therefore, we assessed whether melatonin, a potent antioxidant, improves pulmonary vascular function. Twelve newborn sheep were gestated, born, and raised at 3600 meters. At 3 days old, lambs were catheterized and daily cardiovascular measurements were recorded. Lambs were divided into two groups, one received daily vehicle as control and another received daily melatonin (1 mg/kg/d), for 8 days. At 11 days old, lung tissue and small pulmonary arteries (SPA) were collected. Melatonin decreased pulmonary pressure and resistance for the first 3 days of treatment. Further, melatonin significantly improved the vasodilator function of SPA, enhancing the endothelial‐ and muscular‐dependent pathways. This was associated with an enhanced nitric oxide‐dependent and nitric oxide independent vasodilator components and with increased nitric oxide bioavailability in lung tissue. Further, melatonin reduced the pulmonary oxidative stress markers and increased enzymatic and nonenzymatic antioxidant capacity. Finally, these effects were associated with an increase of lumen diameter and a mild decrease in the wall of the pulmonary arteries. These outcomes support the use of melatonin as an adjuvant in the treatment for PHN.     

Challenges facing HIV-positive persons who use drugs and their families in Vietnam

It is hypothesized that persons who use drugs (PWUD) in Vietnam who are also HIV-positive may face additional challenges in psychosocial outcomes, and these challenges may extend to their family members. In this study, we examined depressive symptoms, stigma, social support, and caregiver burden of HIV-positive PWUD and their family members, compared to the outcomes of HIV-negative PWUD and their family members. Baseline, 3-month, and 6-month assessment data were gathered from 83 PWUD and 83 family members recruited from four communes in Phú Th? Province, Vietnam. For PWUD, although we observed a general decline in overall stigma over time for both groups, HIV-positive PWUD consistently reported significantly higher overall stigma for all three periods. Depressive symptoms among family members in both groups declined over time; however, family members of HIV-positive PWUD reported higher depressive symptoms across all three periods. In addition, family members of HIV-positive PWUD reported lower levels of tangible support across all three periods. Caregiver burden among family members of HIV-positive PWUD increased significantly over time, whereas the reported burden among family members of HIV-negative PWUD remained relatively unchanged. The findings highlight the need for future interventions for PWUD and family members, with targeted and culturally specific strategies to focus on the importance of addressing additional stigma experienced by PWUD who are HIV-positive. Such challenges may have direct negative impact on their family members' depressive symptoms, tangible support, and caregiver burden.