Noninvasive Ventilation Practice Patterns for Acute Respiratory Failure in Canadian Tertiary Care Centres: A Descriptive Analysis

BACKGROUND: The extent of noninvasive ventilation (NIV) use for patients with acute respiratory failure in Canadian hospitals, indications for use and associated outcomes are unknown.OBJECTIVE: To describe NIV practice variation in the acute setting.METHODS: A prospective observational study involving 11 Canadian tertiary care centres was performed. Data regarding NIV indication, mode and outcomes were collected for all adults (>16 years of age) treated with NIV for acute respiratory failure during a four-week period (between February and August 2011). Logistic regression with site as a random effect was used to examine the association between preselected predictors and mortality or intubation.RESULTS: A total of 330 patients (mean [± SD] 30±12 per centre) were included. The most common indications for NIV initiation were pulmonary edema (104 [31.5%]) and chronic obstructive pulmonary disease (99 [30.0%]). Significant differences in indications for NIV use across sites, specialty of ordering physician and location of NIV initiation were noted. Although intubation rates were not statistically different among sites (range 10.3% to 45.4%), mortality varied significantly (range 6.7% to 54.5%; P=0.006). In multivariate analysis, the most significant independent predictor of avoiding intubation was do-not-resuscitate status (OR 0.11 [95% CI 0.03 to 0.37]).CONCLUSION: Significant variability existed in NIV use and associated outcomes among Canadian tertiary care centres. Assignment of do-not-resuscitate status prevented intubation.Peer Reviewe

Novel mutations and decreased expression of the epigenetic regulator TET2 in pulmonary arterial hypertension

Background: Pulmonary arterial hypertension (PAH) is a lethal vasculopathy. Hereditary cases are associated with germline mutations in BMPR2 and 16 other genes; however, these mutations occur in 86% of PAH patients. Tet2-knockout mice spontaneously developed PAH, adverse pulmonary vascular remodeling, and inflammation, with elevated levels of cytokines, including interleukin-1β. Long-term therapy with an antibody targeting interleukin-1β blockade resulted in regression of PAH.Conclusions: PAH is the first human disease related to potential TET2 germline mutations. Inherited and acquired abnormalities of TET2 occur in 0.39% of PAH cases. Decreased TET2 expression is ubiquitous and has potential as a PAH biomarker