Observations from the IMPROVE trial concerning the clinical care of patients with ruptured abdominal aortic aneurysm.

BACKGROUND: Single-centre series of the management of patients with ruptured abdominal aortic aneurysm (AAA) are usually too small to identify clinical factors that could improve patient outcomes. METHODS: IMPROVE is a pragmatic, multicentre randomized clinical trial in which eligible patients with a clinical diagnosis of ruptured aneurysm were allocated to a strategy of endovascular aneurysm repair (EVAR) or to open repair. The influences of time and manner of hospital presentation, fluid volume status, type of anaesthesia, type of endovascular repair and time to aneurysm repair on 30-day mortality were investigated according to a prespecified plan, for the subgroup of patients with a proven diagnosis of ruptured or symptomatic AAA. Adjustment was made for potential confounding factors. RESULTS: Some 558 of 613 randomized patients had a symptomatic or ruptured aneurysm: diagnostic accuracy was 91·0 per cent. Patients randomized outside routine working hours had higher operative mortality (adjusted odds ratio (OR) 1·47, 95 per cent confidence interval 1·00 to 2·17). Mortality rates after primary and secondary presentation were similar. Lowest systolic blood pressure was strongly and independently associated with 30-day mortality (51 per cent among those with pressure below 70 mmHg). Patients who received EVAR under local anaesthesia alone had greatly reduced 30-day mortality compared with those who had general anaesthesia (adjusted OR 0·27, 0·10 to 0·70). CONCLUSION: These findings suggest that the outcome of ruptured AAA might be improved by wider use of local anaesthesia for EVAR and that a minimum blood pressure of 70 mmHg is too low a threshold for permissive hypotension

Endovascular or open repair strategy for ruptured abdominal aortic aneurysm: 30 day outcomes from IMPROVE randomised trial

Objective To assess whether a strategy of endovascular repair (if aortic morphology is suitable, open repair if not) versus open repair reduces early mortality for patients with suspected ruptured abdominal aortic aneurysm. Design Randomised controlled trial. Setting 30 vascular centres (29 UK, 1 Canadian), 2009-13. Participants 613 eligible patients (480 men) with a clinical diagnosis of ruptured aneurysm. Interventions 316 patients were randomised to the endovascular strategy (275 confirmed ruptures, 174 anatomically suitable for endovascular repair) and 297 to open repair (261 confirmed ruptures). Main outcome measures 30 day mortality, with 24 hour and in-hospital mortality, costs, and time and place of discharge as secondary outcomes. Results 30 day mortality was 35.4% (112/316) in the endovascular strategy group and 37.4% (111/297) in the open repair group: odds ratio 0.92 (95% confidence interval 0.66 to 1.28; P=0.62); odds ratio after adjustment for age, sex, and Hardman index 0.94 (0.67 to 1.33). Women may benefit more than men (interaction test P=0.02) from the endovascular strategy: odds ratio 0.44 (0.22 to 0.91) versus 1.18 (0.80 to 1.75). 30 day mortality for patients with confirmed rupture was 36.4% (100/275) in the endovascular strategy group and 40.6% (106/261) in the open repair group (P=0.31). More patients in the endovascular strategy than in the open repair group were discharged directly to home (189/201 (94%) v 141/183 (77%); P<0.001). Average 30 day costs were similar between the randomised groups, with an incremental cost saving for the endovascular strategy versus open repair of £1186 (€1420; $1939) (95% confidence interval −£625 to £2997). Conclusions A strategy of endovascular repair was not associated with significant reduction in either 30 day mortality or cost. Longer term cost effectiveness evaluations are needed to assess the full effects of the endovascular strategy in both men and women

Validity and reliability of fitbit flex for step count, moderate to vigorous physical activity and activity energy expenditure

Objectives: To examine the validity and reliability of the Fitbit Flex against direct observation for measuring steps in the laboratory and against the Actigraph for step counts in free-living conditions and for moderate-to-vigorous physical activity (MVPA) and activity energy expenditure (AEE) overall. Methods: Twenty-five adults (12 females, 13 males) wore a Fitbit Flex and an Actigraph GT3X+ during a laboratory based protocol (including walking, incline walking, running and stepping) and free-living conditions during a single day period to examine measurement of steps, AEE and MVPA. Twenty-four of the participants attended a second session using the same protocol. Results: Intraclass correlations (ICC) for test-retest reliability of the Fitbit Flex were strong for walking (ICC = 0.57), moderate for stair stepping (ICC = 0.34), and weak for incline walking (ICC = 0.22) and jogging (ICC = 0.26). The Fitbit significantly undercounted walking steps in the laboratory (absolute proportional difference: 21.2%, 95%CI 13.0-29.4%), but it was more accurate, despite slightly over counting, for both jogging (6.4%, 95%CI 3.7-9.0%) and stair stepping (15.5%, 95%CI 10.1-20.9%). The Fitbit had higher coefficients of variation (Cv) for step counts compared to direct observation and the Actigraph. In free-living conditions, the average MVPA minutes were lower in the Fitbit (35.4 minutes) compared to the Actigraph (54.6 minutes), but AEE was greater from the Fitbit (808.1 calories) versus the Actigraph (538.9 calories). The coefficients of variation were similar for AEE for the Actigraph (Cv = 36.0) and Fitbit (Cv = 35.0), but lower in the Actigraph (Cv = 25.5) for MVPA against the Fitbit (Cv = 32.7). Conclusion: The Fitbit Flex has moderate validity for measuring physical activity relative to direct observation and the Actigraph. Test-rest reliability of the Fitbit was dependant on activity type and had greater variation between sessions compared to the Actigraph. Physical activity surveillance studies using the Fitbit Flex should consider the potential effect of measurement reactivity and undercounting of steps

Characteristics of the Early Immune Response Following Transplantation of Mouse ES Cell Derived Insulin-Producing Cell Clusters

Background The fully differentiated progeny of ES cells (ESC) may eventually be used for cell replacement therapy (CRT). However, elements of the innate immune system may contribute to damage or destruction of these tissues when transplanted. Methodology/Principal Findings Herein, we assessed the hitherto ill-defined contribution of the early innate immune response in CRT after transplantation of either ESC derived insulin producing cell clusters (IPCCs) or adult pancreatic islets. Ingress of neutrophil or macrophage cells was noted immediately at the site of IPCC transplantation, but this infiltration was attenuated by day three. Gene profiling identified specific inflammatory cytokines and chemokines that were either absent or sharply reduced by three days after IPCC transplantation. Thus, IPCC transplantation provoked less of an early immune response than pancreatic islet transplantation. Conclusions/Significance Our study offers insights into the characteristics of the immune response of an ESC derived tissue in the incipient stages following transplantation and suggests potential strategies to inhibit cell damage to ensure their long-term perpetuation and functionality in CRT

HealtheSteps™ Study Protocol: a pragmatic randomized controlled trial promoting active living and healthy lifestyles in at-risk Canadian adults delivered in primary care and community-based clinics

Abstract Background Physical inactivity is one of the leading causes of chronic disease in Canadian adults. With less than 50% of Canadian adults reaching the recommended amount of daily physical activity, there is an urgent need for effective programs targeting this risk factor. HealtheSteps™ is a healthy lifestyle prescription program, developed from an extensive research base to address risk factors for chronic disease such as physical inactivity, sedentary behaviour and poor eating habits. HealtheSteps™ participants are provided with in-person lifestyle coaching and access to eHealth technologies delivered in community-based primary care clinics and health care organizations. Method/Design To determine the effectiveness of Healthesteps™, we will conduct a 6-month pragmatic randomized controlled trial with integrated process and economic evaluations of HealtheSteps™ in 5 clinic settings in Southwestern Ontario. 110 participants will be individually randomized (1:1; stratified by site) to either the intervention (HealtheSteps™ program) or comparator (Wait-list control). There are 3 phases of the HealtheSteps™ program, lasting 6 months each. The active phase consists of bi-monthly in-person coaching with access to a full suite of eHealth technology supports. During the maintenance phase I, the in-person coaching will be removed, but participants will still have access to the full suite of eHealth technology supports. In the final stage, maintenance phase II, access to the full suite of eHealth technology supports is removed and participants only have access to publicly available resources and tools. Discussion This trial aims to determine the effectiveness of the program in increasing physical activity levels and improving other health behaviours and indicators, the acceptability of the HealtheSteps™ program, and the direct cost for each person participating in the program as well as the costs associated with delivering the program at the different community sites. These results will inform future optimization and scaling up of the program into additional community-based primary care sites. Trial registration NCT02413385 (Clinicaltrials.gov). Date Registered: April 6, 2015

The genome of the emerging barley pathogen Ramularia collo-cygni

Background Ramularia collo-cygni is a newly important, foliar fungal pathogen of barley that causes the disease Ramularia leaf spot. The fungus exhibits a prolonged endophytic growth stage before switching life habit to become an aggressive, necrotrophic pathogen that causes significant losses to green leaf area and hence grain yield and quality. Results The R. collo-cygni genome was sequenced using a combination of Illumina and Roche 454 technologies. The draft assembly of 30.3 Mb contained 11,617 predicted gene models. Our phylogenomic analysis confirmed the classification of this ascomycete fungus within the family Mycosphaerellaceae, order Capnodiales of the class Dothideomycetes. A predicted secretome comprising 1053 proteins included redox-related enzymes and carbohydrate-modifying enzymes and proteases. The relative paucity of plant cell wall degrading enzyme genes may be associated with the stealth pathogenesis characteristic of plant pathogens from the Mycosphaerellaceae. A large number of genes associated with secondary metabolite production, including homologs of toxin biosynthesis genes found in other Dothideomycete plant pathogens, were identified. Conclusions The genome sequence of R. collo-cygni provides a framework for understanding the genetic basis of pathogenesis in this important emerging pathogen. The reduced complement of carbohydrate-degrading enzyme genes is likely to reflect a strategy to avoid detection by host defences during its prolonged asymptomatic growth. Of particular interest will be the analysis of R. collo-cygni gene expression during interactions with the host barley, to understand what triggers this fungus to switch from being a benign endophyte to an aggressive necrotroph

The immediate management of the patient with rupture: open versus endovascular repair (IMPROVE) randomised controlled trial for abdominal aortic aneurysm: clinical and health economic evaluation

Background: Ruptured abdominal aortic aneurysm is a common vascular emergency. The mortality from emergency endovascular repair may be much lower than the 40-50% reported for open surgery. Objectives: To assess whether a strategy of endovascular repair versus open repair reduces 30-day and mid-term mortality (costs and cost-effectiveness) for patients with suspected ruptured abdominal aortic aneurysm. Design: Randomised controlled trial, with computer-generated telephone randomisation of patients in a 1:1 ratio, using variable block size, stratified by centre, without blindin