Sex-Specific Clinical Outcomes of the PACT-HF Randomized Trial

BACKGROUND: Transitional care may have different effects in males and females hospitalized for heart failure. We assessed the sex-specific effects of a transitional care model on clinical outcomes following hospitalization for heart failure. METHODS: In this stepped-wedge cluster randomized trial of adults hospitalized for heart failure in Ontario, Canada, 10 hospitals were randomized to a group of transitional care services or usual care. Outcomes in this exploratory analysis were composite all-cause readmission, emergency department visit, or death at 6 months; and composite all-cause readmission or emergency department visit at 6 months. Models were adjusted for stepped-wedge design and patient age. RESULTS: Among 2494 adults, mean (SD) age was 77.7 (12.1) years, and 1258 (50.4%) were female. The first composite outcome occurred in 371 (66.3%) versus 433 (64.1%) males (hazard ratio [HR], 1.04 [95% CI, 0.86-1.26]; P=0.67) and in 326 (59.9%) versus 463 (64.8%) females (HR, 0.83 [95% CI, 0.69-1.01]; P=0.06) in the intervention and usual care groups, respectively (P=0.012 for sex interaction). The second composite outcome occurred in 357 (63.8%) versus 417 (61.7%) males (HR, 1.03 [95% CI, 0.85-1.24]; P=0.76) and 314 (57.7%) versus 450 (63.0%) females (HR, 0.81 [95% CI, 0.67-0.99]; P=0.037) in the intervention and usual care groups, respectively (P=0.024 for sex interaction). The sex differences were driven by a reduction in all-cause emergency department visits among females (HR, 0.66 [95% CI, 0.51-0.87]; P=0.003), but not males (HR, 1.10 [95% CI, 0.85-1.43]; P=0.46), receiving the intervention (P<0.001 for sex interaction). CONCLUSIONS: A transitional care model offered a reduction in all-cause emergency department visits among females but not males following hospitalization for heart failure. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02112227

Changes in timber haul emissions in the context of shifting forest management and infrastructure

<p>Abstract</p> <p>Background</p> <p>Although significant amounts of carbon may be stored in harvested wood products, the extraction of that carbon from the forest generally entails combustion of fossil fuels. The transport of timber from the forest to primary milling facilities may in particular create emissions that reduce the net sequestration value of product carbon storage. However, attempts to quantify the effects of transport on the net effects of forest management typically use relatively sparse survey data to determine transportation emission factors. We developed an approach for systematically determining transport emissions using: 1) -remotely sensed maps to estimate the spatial distribution of harvests, and 2) - industry data to determine landscape-level harvest volumes as well as the location and processing totals of individual mills. These data support spatial network analysis that can produce estimates of fossil carbon released in timber transport.</p> <p>Results</p> <p>Transport-related emissions, evaluated as a fraction of transported wood carbon at 4 points in time on a landscape in western Montana (USA), rose from 0.5% in 1988 to 1.7% in 2004 as local mills closed and spatial patterns of harvest shifted due to decreased logging on federal lands.</p> <p>Conclusion</p> <p>The apparent sensitivity of transport emissions to harvest and infrastructure patterns suggests that timber haul is a dynamic component of forest carbon management that bears further study both across regions and over time. The monitoring approach used here, which draws only from widely available monitoring data, could readily be adapted to provide current and historical estimates of transport emissions in a consistent way across large areas.</p

Restoring immune tolerance in neuromyelitis optica: Part I.

Neuromyelitis optica (NMO) and spectrum disorder (NMO/SD) represent a vexing process and its clinical variants appear to have at their pathogenic core the loss of immune tolerance to the aquaporin-4 water channel protein. This process results in a characteristic pattern of astrocyte dysfunction, loss, and demyelination that predominantly affects the spinal cord and optic nerves. Although several empirical therapies are currently used in the treatment of NMO/SD, none has been proven effective in prospective, adequately powered, randomized trials. Furthermore, most of the current therapies subject patients to long-term immunologic suppression that can cause serious infections and development of cancers. The following is the first of a 2-part description of several key immune mechanisms in NMO/SD that might be amenable to therapeutic restoration of immune tolerance. It is intended to provide a roadmap for how potential immune tolerance restorative techniques might be applied to patients with NMO/SD. This initial installment provides a background rationale underlying attempts at immune tolerization. It provides specific examples of innovative approaches that have emerged recently as a consequence of technical advances. In several autoimmune diseases, these strategies have been reduced to practice. Therefore, in theory, the identification of aquaporin-4 as the dominant autoantigen makes NMO/SD an ideal candidate for the development of tolerizing therapies or cures for this increasingly recognized disease

Restoring immune tolerance in neuromyelitis optica: Part II

Neuromyelitis optica spectrum disorder (NMO/SD) and its clinical variants have at their core the loss of immune tolerance to aquaporin-4 and perhaps other autoantigens. The characteristic phenotype is disruption of astrocyte function and demyelination of spinal cord, optic nerves, and particular brain regions. In this second of a 2-part article, we present further perspectives regarding the pathogenesis of NMO/SD and how this disease might be amenable to emerging technologies aimed at restoring immune tolerance to disease-implicated self-antigens. NMO/SD appears to be particularly well-suited for these strategies since aquaporin-4 has already been identified as the dominant autoantigen. The recent technical advances in reintroducing immune tolerance in experimental models of disease as well as in humans should encourage quantum leaps in this area that may prove productive for novel therapy. In this part of the article series, the potential for regulatory T and B cells is brought into focus, as are new approaches to oral tolerization. Finally, a roadmap is provided to help identify potential issues in clinical development and guide applications in tolerization therapy to solving NMO/SD through the use of emerging technologies. Each of these perspectives is intended to shine new light on potential cures for NMO/SD and other autoimmune diseases, while sparing normal host defense mechanisms