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Randomized controlled trials (RCTs) have compared mechanical endovascular therapy (MET) in addition to intravenous tissue plasminogen activator (IVtPA) to IVtPA alone for the management of acute ischemic stroke (AIS). Direct comparative studies between individual METs are not available. In lieu of head-to-head randomized control trials, we performed an adjusted indirect treatment comparison (ITC) meta-analysis to assess the comparative efficacy and safety of different METs, Solitaire+IVtPA and Penumbra+IVtPA in AIS patients.We searched MEDLINE, the Cochrane Central Register of Controlled Trials and Embase from January 1, 2005 through April 1, 2017 for RCTs in AIS patients, comparing a single MET+IVtPA to IVtPA alone and reporting shift in ordinal modified Rankin Scale (mRS) score at 90 days. Secondary endpoints included 90 day mortality and symptomatic intracranial hemorrhage (sICH). Endpoints were pooled using traditional random effects meta-analysis methods, producing odds ratios and 95% confidence intervals. Adjusted ITCs using pooled estimates were then performed. Three studies (SWIFT PRIME, EXTEND-IA, THERAPY) were included; two evaluating the Solitaire stent retriever and one the Penumbra system. Traditional meta-analysis demonstrated that each MET+IVtPA resulted in increased odds of improving ordinal mRS score vs. IVtPA alone, but did not alter the odds of death or sICH. Adjusted ITC showed no significant difference between the METs for any outcome.No significant difference in efficacy or safety between the Solitaire and Penumbra devices was observed.

In a recent PLOS ONE paper, we conducted an evidence-based analysis of current versus historical fire regimes and concluded that traditionally defined reference conditions of low-severity fire regimes for ponderosa pine (Pinus ponderosa) and mixed-conifer forests were incomplete, missing considerable variability in forest structure and fire regimes. Stevens et al. (this issue) agree that high-severity fire was a component of these forests, but disagree that one of the several sources of evidence, stand age from a large number of forest inventory and analysis (FIA) plots across the western USA, support our findings that severe fire played more than a minor role ecologically in these forests. Here we highlight areas of agreement and disagreement about past fire, and analyze the methods Stevens et al. used to assess the FIA stand-age data. We found a major problem with a calculation they used to conclude that the FIA data were not useful for evaluating fire regimes. Their calculation, as well as a narrowing of the definition of high-severity fire from the one we used, leads to a large underestimate of conditions consistent with historical high-severity fire. The FIA stand age data do have limitations but they are consistent with other landscape-inference data sources in supporting a broader paradigm about historical variability of fire in ponderosa and mixed-conifer forests than had been traditionally recognized, as described in our previous PLOS paper.

Dry forests at low elevations in temperate-zone mountains are commonly hypothesized to be at risk of exceptional rates of severe fire from climatic change and land-use effects. Their setting is fire-prone, they have been altered by land-uses, and fire severity may be increasing. However, where fires were excluded, increased fire could also be hypothesized as restorative of historical fire. These competing hypotheses are not well tested, as reference data prior to widespread land-use expansion were insufficient. Moreover, fire-climate projections were lacking for these forests. Here, I used new reference data and records of high-severity fire from 1984-2012 across all dry forests (25.5 million ha) of the western USA to test these hypotheses. I also approximated projected effects of climatic change on high-severity fire in dry forests by applying existing projections. This analysis showed the rate of recent high-severity fire in dry forests is within the range of historical rates, or is too low, overall across dry forests and individually in 42 of 43 analysis regions. Significant upward trends were lacking overall from 1984-2012 for area burned and fraction burned at high severity. Upward trends in area burned at high severity were found in only 4 of 43 analysis regions. Projections for A.D. 2046-2065 showed high-severity fire would generally be still operating at, or have been restored to historical rates, although high projections suggest high-severity fire rotations that are too short could ensue in 6 of 43 regions. Programs to generally reduce fire severity in dry forests are not supported and have significant adverse ecological impacts, including reducing habitat for native species dependent on early-successional burned patches and decreasing landscape heterogeneity that confers resilience to climatic change. Some adverse ecological effects of high-severity fires are concerns. Managers and communities can improve our ability to live with high-severity fire in dry forests.

There is widespread concern that fire exclusion has led to an unprecedented threat of uncharacteristically severe fires in ponderosa pine (Pinus ponderosa Dougl. ex. Laws) and mixed-conifer forests of western North America. These extensive montane forests are considered to be adapted to a low/moderate-severity fire regime that maintained stands of relatively old trees. However, there is increasing recognition from landscape-scale assessments that, prior to any significant effects of fire exclusion, fires and forest structure were more variable in these forests. Biota in these forests are also dependent on the resources made available by higher-severity fire. A better understanding of historical fire regimes in the ponderosa pine and mixed-conifer forests of western North America is therefore needed to define reference conditions and help maintain characteristic ecological diversity of these systems. We compiled landscape-scale evidence of historical fire severity patterns in the ponderosa pine and mixed-conifer forests from published literature sources and stand ages available from the Forest Inventory and Analysis program in the USA. The consensus from this evidence is that the traditional reference conditions of low-severity fire regimes are inaccurate for most forests of western North America. Instead, most forests appear to have been characterized by mixed-severity fire that included ecologically significant amounts of weather-driven, high-severity fire. Diverse forests in different stages of succession, with a high proportion in relatively young stages, occurred prior to fire exclusion. Over the past century, successional diversity created by fire decreased. Our findings suggest that ecological management goals that incorporate successional diversity created by fire may support characteristic biodiversity, whereas current attempts to "restore" forests to open, low-severity fire conditions may not align with historical reference conditions in most ponderosa pine and mixed-conifer forests of western North America.

ObjectiveTo conduct a systematic review of economic models of newer anticoagulants for stroke prevention in atrial fibrillation (SPAF).Patients and methodsWe searched Medline, Embase, NHSEED and HTA databases and the Tuft's Registry from January 1, 2008 through October 10, 2012 to identify economic (Markov or discrete event simulation) models of newer agents for SPAF.ResultsEighteen models were identified. Each was based on a lone randomized trial/new agent, and these trials were clinically and methodologically heterogeneous. Dabigatran 150 mg, 110 mg and sequentially-dosed were assessed in 9, 8, and 9 models, rivaroxaban in 4 and apixaban in 4. Warfarin was a first-line comparator in 94% of models. Models were conducted from United States (44%), European (39%) and Canadian (17%) perspectives. Models typically assumed patients between 65-73 years old at moderate-risk of stroke initiated anticoagulation for/near a lifetime. All models reported cost/quality-adjusted life-year, 22% reported using a societal perspective, but none included indirect costs. Four models reported an incremental cost-effectiveness ratio (ICER) for a newer anticoagulant (dabigatran 110 mg (n = 4)/150 mg (n = 2); rivaroxaban (n = 1)) vs. warfarin above commonly reported willingness-to-pay thresholds. ICERs vs. warfarin ranged from $3,547-$86,000 for dabigatran 150 mg, $20,713-$150,000 for dabigatran 110 mg, $4,084-$21,466 for sequentially-dosed dabigatran and $23,065-$57,470 for rivaroxaban. Apixaban was found economically-dominant to aspirin, and dominant or cost-effective ($11,400-$25,059) vs. warfarin. Indirect comparisons from 3 models suggested conflicting comparative cost-effectiveness results.ConclusionsCost-effectiveness models frequently found newer anticoagulants cost-effective, but the lack of head-to-head trials and the heterogeneous characteristics of underlying trials and modeling methods make it difficult to determine the most cost-effective agent.