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Burns K.E.,Li Ka Shing Knowledge Institute
The Cochrane database of systematic reviews

Noninvasive positive-pressure ventilation (NPPV) provides ventilatory support without the need for an invasive airway. Interest has emerged in using NPPV to facilitate earlier removal of an endotracheal tube and to decrease complications associated with prolonged intubation. We evaluated studies in which invasively ventilated adults with respiratory failure of any cause (chronic obstructive pulmonary disease (COPD), non-COPD, postoperative, nonoperative) were weaned by means of early extubation followed by immediate application of NPPV or continued IPPV weaning. The primary objective was to determine whether the noninvasive positive-pressure ventilation (NPPV) strategy reduced all-cause mortality compared with invasive positive-pressure ventilation (IPPV) weaning. Secondary objectives were to ascertain differences between strategies in proportions of weaning failure and ventilator-associated pneumonia (VAP), intensive care unit (ICU) and hospital length of stay (LOS), total duration of mechanical ventilation, duration of mechanical support related to weaning, duration of endotracheal mechanical ventilation (ETMV), frequency of adverse events (related to weaning) and overall quality of life. We planned sensitivity and subgroup analyses to assess (1) the influence on mortality and VAP of excluding quasi-randomized trials, and (2) effects on mortality and weaning failure associated with different causes of respiratory failure (COPD vs. mixed populations). We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 5, 2013), MEDLINE (January 1966 to May 2013), EMBASE (January 1980 to May 2013), proceedings from four conferences, trial registration websites and personal files; we contacted authors to identify trials comparing NPPV versus conventional IPPV weaning. Randomized and quasi-randomized trials comparing early extubation with immediate application of NPPV versus IPPV weaning in intubated adults with respiratory failure. Two review authors independently assessed trial quality and abstracted data according to prespecified criteria. Sensitivity and subgroup analyses assessed (1) the impact of excluding quasi-randomized trials, and (2) the effects on selected outcomes noted with different causes of respiratory failure. We identified 16 trials, predominantly of moderate to good quality, involving 994 participants, most with chronic obstructive pulmonary disease (COPD). Compared with IPPV weaning, NPPV weaning significantly decreased mortality. The benefits for mortality were significantly greater in trials enrolling exclusively participants with COPD (risk ratio (RR) 0.36, 95% confidence interval (CI) 0.24 to 0.56) versus mixed populations (RR 0.81, 95% CI 0.47 to 1.40). NPPV significantly reduced weaning failure (RR 0.63, 95% CI 0.42 to 0.96) and ventilator-associated pneumonia (RR 0.25, 95% CI 0.15 to 0.43); shortened length of stay in an intensive care unit (mean difference (MD) -5.59 days, 95% CI -7.90 to -3.28) and in hospital (MD -6.04 days, 95% CI -9.22 to -2.87); and decreased the total duration of ventilation (MD -5.64 days, 95% CI -9.50 to -1.77) and the duration of endotracheal mechanical ventilation (MD - 7.44 days, 95% CI -10.34 to -4.55) amidst significant heterogeneity. Noninvasive weaning also significantly reduced tracheostomy (RR 0.19, 95% CI 0.08 to 0.47) and reintubation (RR 0.65, 95% CI 0.44 to 0.97) rates. Noninvasive weaning had no effect on the duration of ventilation related to weaning. Exclusion of a single quasi-randomized trial did not alter these results. Subgroup analyses suggest that the benefits for mortality were significantly greater in trials enrolling exclusively participants with COPD versus mixed populations. Summary estimates from 16 trials of moderate to good quality that included predominantly participants with COPD suggest that a weaning strategy that includes NPPV may reduce rates of mortality and ventilator-associated pneumonia without increasing the risk of weaning failure or reintubation. Source

Jaqaman K.,Harvard University | Grinstein S.,Li Ka Shing Knowledge Institute
Trends in Cell Biology

There is mounting evidence that the plasma membrane is highly dynamic and organized in a complex manner. The cortical cytoskeleton is proving to be a particularly important regulator of plasmalemmal organization, modulating the mobility of proteins and lipids in the membrane, facilitating their segregation, and influencing their clustering. This organization plays a critical role in receptor-mediated signaling, especially in the case of immunoreceptors, which require lateral clustering for their activation. Based on recent developments, we discuss the structures and mechanisms whereby the cortical cytoskeleton regulates membrane dynamics and organization, and how the nonuniform distribution of immunoreceptors and their self-association may affect activation and signaling. © 2012 Elsevier Ltd. Source

Withrow D.,Queens University | Alter D.A.,Li Ka Shing Knowledge Institute
Obesity Reviews

In the last decade, the prevalence of obesity has increased significantly in populations worldwide. A less dramatic, but equally important increase has been seen in our knowledge of its effects on health and the burden it places on healthcare systems. This systematic review aims to assess the current published literature on the direct costs associated with obesity. A computerized search of English language articles published between 1990 and June 2009 yielded 32 articles suitable for review. Based on these articles, obesity was estimated to account for between 0.7% and 2.8% of a country's total healthcare expenditures. Furthermore, obese individuals were found to have medical costs that were approximately 30% greater than their normal weight peers. Although variations in inclusion/exclusion criteria, reporting methods and included costs varied widely between the studies, a lack of examination of how and why the excess costs were being accrued appeared to be a commonality between most studies. Accordingly, future studies must better explore how costs accrue among obese populations, in order to best facilitate health and social policy interventions. © 2010 The Authors. obesity reviews © 2010 International Association for the Study of Obesity. Source

Although seemingly diverse, the tissue injury at sites of diabetic complications, whether in the heart, kidneys or eyes, shares the common histopathological feature of endothelial cell loss, a consequence of both increased cell death and deficient regeneration. In medium-sized and larger arteries the loss of the protective lining contributes to the atherosclerotic process, while at sites of microvascular disease endothelial cell loss leads to capillary rarefaction and ischemia. The pathophysiology of these changes and their consequences on organ structure and function in diabetes are reviewed, and the potential for endothelial regenerative strategies to enhance repair and ameliorate the long-term complications of diabetes is explored. Source

Slutsky A.S.,Li Ka Shing Knowledge Institute
American journal of respiratory and critical care medicine

Mechanical ventilation is a life-saving therapy that catalyzed the development of modern intensive care units. The origins of modern mechanical ventilation can be traced back about five centuries to the seminal work of Andreas Vesalius. This article is a short history of mechanical ventilation, tracing its origins over the centuries to the present day. One of the great advances in ventilatory support over the past few decades has been the development of lung-protective ventilatory strategies, based on our understanding of the iatrogenic consequences of mechanical ventilation such as ventilator-induced lung injury. These strategies have markedly improved clinical outcomes in patients with respiratory failure. Source

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