Objective To determine the magnitude of all-cause mortality risk in patients with antineutrophil cytoplasmic antibodies-associated vasculitis (AAV) compared with the general population through a meta-analysis of observational studies. Methods We searched Medline and Embase databases from their inception to April 2015. Observational studies that met the following criteria were assessed by two researchers: (1) clearly defined AAV identified by either the American College of Rheumatology 1990 classification criteria or the 2012 Chapel Hill Consensus Conference disease definitions, and (2) reported standardised mortality ratios (SMR) and 95% CI. We calculated weighted-pooled summary estimates of SMRs (meta-SMRs) for all-cause mortality using random-effects model, tested for publication bias and heterogeneity. Results Ten studies met the inclusion criteria, comprising 3338 patients with AAV enrolled from 1966 to 2009, and a total of 1091 observed deaths. Overall, we found a 2.7-fold increased risk of death in patients with AAV when compared with the general population (meta-SMR: 2.71 (95% CI 2.26 to 3.24)). Analysis on studies that included only granulomatosis with polyangiitis cases also indicated a similar mortality risk (meta-SMR: 2.63 (95% CI 2.02 to 3.43)). There was no significant publication bias or small-study effect. Subgroup analyses showed that mortality risks were higher in older cohorts, with a trend towards improvement over time (ie, those with their midpoint of enrolment periods that were between 1980–1993 and 1994–1999, vs 2000–2005). Conclusion Published data indicate there is a 2.7-fold increase in mortality among patients with AAV compared with the general population.

Environmental temperature is an important factor exerting pervasive influence on neuronal morphology and synaptic physiology. In theDrosophilabrain, axonal arborization of mushroom body Kenyon cells was enhanced when flies were raised at high temperature (30°C rather than 22°C) for several days. Isolated embryonic neurons in culture that lacked cell–cell contacts also displayed a robust temperature-induced neurite outgrowth. This cell-autonomous effect was reflected by significantly increased high-order branching and enlarged growth cones. The temperature-induced morphological alterations were blocked by the Na⁺channel blocker tetrodotoxin and a Ca²⁺channel mutation but could be mimicked by raising cultures at room temperature with suppressed K⁺channel activity. Physiological analyses revealed increased inward Ca²⁺currents and decreased outward K⁺currents, in conjunction with a distal shift in the site of action potential initiation and increased prevalence of TTX-sensitive spontaneous Ca²⁺transients. Importantly, the overgrowth caused by both temperature and hyperexcitability K⁺channel mutations were sensitive to genetic perturbations of cAMP metabolism. Thus, temperature acts in a cell-autonomous manner to regulate neuronal excitability and spontaneous activity. Presumably, activity-dependent Ca²⁺accumulation triggers the cAMP cascade to confer the activity-dependent plasticity of neuronal excitability and growth.

There is increasing evidence that community-based treatment of drug resistant tuberculosis (DRTB) is a feasible and cost-effective alternative to centralized, hospital-based care. Although several large programs have reported favourable outcomes from community-based treatment, to date there has been no systematic assessment of community-based DRTB treatment program outcomes. The objective of this study was to synthesize available evidence on treatment outcomes from community based multi-drug resistant (MDRTB) and extensively drug resistant tuberculosis (XDRTB) treatment programs.