Effects of Community Exercise Therapy on Metabolic, Brain, Physical, and Cognitive Function Following Stroke : A Randomized Controlled Pilot Trial

© The Author(s) 2014.Peer reviewedPostprintPostprin

Exercise Induces Peripheral Muscle But Not Cardiac Adaptations After Stroke: A Randomized Controlled Pilot Trial

Objective To explore the physiological factors affecting exercise-induced changes in peak oxygen consumption and function poststroke. Design Single-center, single-blind, randomized controlled pilot trial. Setting Community stroke services. Participants Adults (N=40; age>50y; independent with/without stick) with stroke (diagnosed >6mo previously) were recruited from 117 eligible participants. Twenty participants were randomized to the intervention group and 20 to the control group. No dropouts or adverse events were reported. Interventions Intervention group: 19-week (3times/wk) progressive mixed (aerobic/strength/balance/flexibility) community group exercise program. Control group: Matched duration home stretching program. Main Outcome Measures (1) Pre- and postintervention: maximal cardiopulmonary exercise testing with noninvasive (bioreactance) cardiac output measurements; and (2) functional outcome measures: 6-minute walk test; timed Up and Go test, and Berg Balance Scale. Results Exercise improved peak oxygen consumption (18±5 to 21±5mL/(kg⋅min); P<.01) and peak arterial-venous oxygen difference (9.2±2.7 to 11.4±2.9mL of O2/100mL of blood; P<.01), but did not alter cardiac output (17.2±4 to 17.7±4.2L/min; P=.44) or cardiac power output (4.8±1.3 to 5.0±1.35W; P=.45). A significant relation existed between change in peak oxygen consumption and change in peak arterial-venous oxygen difference (r=.507; P<.05), but not with cardiac output. Change in peak oxygen consumption did not strongly correlate with change in function. Conclusions Exercise induced peripheral muscle, but not cardiac output, adaptations after stroke. Implications for stroke clinical care should be explored further in a broader cohort

Tolerability of the Low-Affinity, Use-Dependent NMDA Antagonist AR-R15896AR in Stroke Patients

Background and Purpose—AR-R15896AR is a use-dependent, low-affinity blocker of the NMDA ion channel with neuroprotective effects in animal models of focal cerebral ischemia. This study aimed to establish the highest safe and tolerated loading and maintenance dosing regimen of AR-R15896AR in acute ischemic stroke patients and to determine the associated plasma concentrations of AR-R15896AR.Methods—This was a 4-part, multicenter, randomized, double-blind, placebo-controlled study in 175 patients (mean age, 69 years) within 24 hours of acute stroke symptom recognition. Ascending 60-minute intravenous infusion loading doses of AR-R15896AR were initially examined (100, 150, 200, 250, or 300 mg or placebo in 3:1 randomization, n=36 treated); in part 2, 250, 275, or 300 mg was compared with placebo (n=33). In part 3, a 250-mg loading dose was followed by 9 maintenance doses of 60, 75, 90, 105, or 120 mg every 8 hours versus placebo in 3:1 randomization (n=59); subsequently, in part 4, maintenance doses of 90, 105, and 120 mg after the 250-mg loading dose were directly randomized against placebo (n=42). Safety, tolerability, and pharmacokinetics were the primary end points; NIHSS at 1 week and Barthel and modified Rankin scores at 1 month were also recorded, but the study was neither designed nor powered to assess efficacy.Results—Rates for mortality and serious adverse events (SAE) were similar in active and placebo groups (9% mortality and 23% SAE for all active combined versus 11% mortality and 33% SAE for placebo). Adverse events associated with AR-R15896AR were dizziness, vomiting, nausea, stupor, and some agitation/hallucination. Withdrawal from treatment occurred only in response to loading doses with AR-R15896AR: placebo, 3 of 46 (7%); 250 mg, 11 of 89 (12%); 275 mg, 1 of 8 (12.5%); and 300 mg, 3 of 15 (20%). No significant difference in outcome was observed between groups. Plasma concentrations of AR-R15896AR were 1524±536 ng/mL at the end of the 250-mg loading infusion and were 1847±478 ng/mL at steady state after the 9 maintenance doses of 120 mg.Conclusions—The maximum tolerated loading infusion of AR-R15896AR in this study was 250 mg over a period of 1 hour. Subsequent maintenance infusions of 120 mg every 8 hours were well tolerated. With these doses, putative neuroprotective concentrations of 1240 ng/mL are attained by the loading dose and are satisfactorily maintained thereafter. The loading dose may be improved further by adjustment on an individual patient basis, but tolerability issues remain

Cosmological Aspects of Rolling Tachyon

We examine the possibility of rolling tachyon to play the dual roll of inflaton at early epochs and dark matter at late times. We argue that enough inflation can be generated with the rolling tachyon either by invoking the large number of branes or brane world assisted inflation. However, reheating is problematic in this model.Comment: RevTeX 4 pages, Talk delivered in PASCOS held at TIFR (Mumbai) from 3rd Jan to 9th Jan. To appear in the proceedings of PASCOS to be published in a special issue of Praman

Multivariable analysis of outcome predictors and adjustment of main outcome results to baseline data profile in randomized controlled trials: Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST)

&lt;p&gt;&lt;b&gt;Background and Purpose:&lt;/b&gt; The Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy (SITS-MOST) unadjusted results demonstrated that intravenous alteplase is well tolerated and that the effects were comparable with those seen in randomized, controlled trials (RCTs) when used in routine clinical practice within 3 hours of ischemic stroke onset. We aimed to identify outcome predictors and adjust the outcomes of the SITS-MOST to the baseline characteristics of RCTs.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; The study population was SITS-MOST (n=6483) and pooled RCTs (n=464) patients treated with intravenous alteplase within 3 hours of stroke onset. Multivariable, backward stepwise regression analyses (until P&#8804;0.10) were performed to identify the outcome predictors for SITS-MOST. Variables appearing either in the final multivariable model or differing (P&#60;0.10) between SITS-MOST and RCTs were included in the prediction model for the adjustment of outcomes. Main outcome measures were symptomatic intracerebral hemorrhage, defined as National Institutes of Health Stroke Scale deterioration &#8805;1 within 7 days with any hemorrhage (RCT definition), mortality, and independency as defined by modified Rankin Score of 0 to 2 at 3 months.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; The adjusted proportion of symptomatic intracerebral hemorrhage for SITS-MOST was 8.5% (95% CI, 7.9 to 9.0) versus 8.6% (6.3 to 11.6) for pooled RCTs; mortality was 15.5% (14.7 to 16.2) versus 17.3% (14.1 to 21.1); and independency was 50.4% (49.6 to 51.2) versus 50.1% (44.5 to 54.7), respectively. In the multivariable analysis, older age, high blood glucose, high National Institutes of Health Stroke Scale score, and current infarction on imaging scans were related to poor outcome in all parameters. Systolic blood pressure, atrial fibrillation, and weight were additional predictors of symptomatic intracerebral hemorrhage. Current smokers had a lower rate of symptomatic intracerebral hemorrhage. Disability before current stroke (modified Rankin Score 2 to 5), diastolic blood pressure, antiplatelet other than aspirin, congestive heart failure, patients treated in new centers, and male sex were related to high mortality at 3 months.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; The adjusted outcomes from SITS-MOST were almost identical to those in relevant RCTs and reinforce the conclusion drawn previously in the unadjusted analysis. We identified several important outcome predictors to better identify patients suitable for thrombolysis.&lt;/p&gt

The stroke ‘Act FAST’ campaign: Remembered but not understood?

Background: The stroke awareness raising campaign &lsquo;Act FAST' (Face, Arms, Speech: Time to call Emergency Medical Services) has been rolled out in multiple waves in England, but impact on stroke recognition and response remains unclear. Purpose: The purpose of this study was to test whether providing knowledge of the FAST acronym through a standard Act FAST campaign leaflet increases accurate recognition and response in stroke-based scenario measures. Methods: This is a population-based, cross-sectional survey of adults in Newcastle upon Tyne, UK, sampled using the electoral register, with individuals randomized to receive a questionnaire and Act FAST leaflet (n&thinsp;=&thinsp;2500) or a questionnaire only (n&thinsp;=&thinsp;2500) in 2012. Campaign message retention, stroke recognition, and response measured through 16 scenario-based vignettes were assessed. Data were analyzed in 2013. Results: Questionnaire return rate was 32&middot;3% (n&thinsp;=&thinsp;1615). No differences were found between the leaflet and no-leaflet groups in return rate or demographics. Participants who received a leaflet showed better campaign recall (75&middot;7% vs. 68&middot;2%, P&thinsp;=&thinsp;0&middot;003) and recalled more FAST mnemonic elements (66&middot;1% vs. 45&middot;3% elements named correctly, P&thinsp;&lt;&thinsp;0&middot;001). However, there were no between-group differences for stroke recognition and response to stroke-based scenarios (P&thinsp;&gt;&thinsp;0&middot;05). Conclusions: Despite greater levels of recall of specific &lsquo;Act FAST' elements among those receiving the Act FAST leaflet, there was no impact on stroke recognition and response measures

Evolution in agriculture: the application of evolutionary approaches to the management of biotic interactions in agro-ecosystems

Anthropogenic impacts increasingly drive ecological and evolutionary processes at many spatio-temporal scales, demanding greater capacity to predict and manage their consequences. This is particularly true for agro-ecosystems, which not only comprise a significant proportion of land use, but which also involve conflicting imperatives to expand or intensify production while simultaneously reducing environmental impacts. These imperatives reinforce the likelihood of further major changes in agriculture over the next 30–40 years. Key transformations include genetic technologies as well as changes in land use. The use of evolutionary principles is not new in agriculture (e.g. crop breeding, domestication of animals, management of selection for pest resistance), but given land-use trends and other transformative processes in production landscapes, ecological and evolutionary research in agro-ecosystems must consider such issues in a broader systems context. Here, we focus on biotic interactions involving pests and pathogens as exemplars of situations where integration of agronomic, ecological and evolutionary perspectives has practical value. Although their presence in agro-ecosystems may be new, many traits involved in these associations evolved in natural settings. We advocate the use of predictive frameworks based on evolutionary models as pre-emptive management tools and identify some specific research opportunities to facilitate this. We conclude with a brief discussion of multidisciplinary approaches in applied evolutionary problems

Factors that influence clinicians’ decisions to offer intravenous alteplase in acute ischemic stroke patients with uncertain treatment indication:Results of a discrete choice experiment

Background: Treatment with intravenous alteplase for eligible patients with acute ischemic stroke is underused, with variation in treatment rates across the UK. This study sought to elucidate factors influencing variation in clinicians’ decision-making about this thrombolytic treatment. Methods: A discrete choice experiment using hypothetical patient vignettes framed around areas of clinical uncertainty was conducted with UK-based clinicians. Mixed logit regression analyses were conducted on the data. Results: A total of 138 clinicians completed the discrete choice experiment. Seven patient factors were individually predictive of increased likelihood of immediately offering IV alteplase (compared to reference levels in brackets): stroke onset time 2 h 30 min [50 min]; pre-stroke dependency mRS 3 [mRS 4]; systolic blood pressure 185 mm/Hg [140 mm/Hg]; stroke severity scores of NIHSS 5 without aphasia, NIHSS 14 and NIHSS 23 [NIHSS 2 without aphasia]; age 85 [68]; Afro-Caribbean [white]. Factors predictive of withholding treatment with IV alteplase were: age 95 [68]; stroke onset time of 4 h 15 min [50 min]; severe dementia [no memory problems]; SBP 200 mm/Hg [140 mm/Hg]. Three clinician-related factors were predictive of an increased likelihood of offering IV alteplase (perceived robustness of the evidence for IV alteplase; thrombolyzing more patients in the past 12 months; and high discomfort with uncertainty) and one with a decreased likelihood (high clinician comfort with treating patients outside the licensing criteria). Conclusions: Both patient- and clinician-related factors have a major influence on the use of alteplase to treat patients with acute ischemic stroke. Clinicians’ views of the evidence, comfort with uncertainty and treating patients outside the license criteria are important factors to address in programs that seek to reduce variation in care quality regarding treatment with IV alteplase. Further research is needed to further understand the differences in clinical decision-making about treating patients with acute ischemic stroke with IV alteplase

Witness Response at Acute Onset of Stroke: A Qualitative Theory-Guided Study

Background: Delay in calling emergency medical services following stroke limits access to early treatment that can reduce disability. Emergency medical services contact is mostly initiated by stroke witnesses (often relatives), rather than stroke patients. This study explored appraisal and behavioural factors that are potentially important in influencing witness behaviour in response to stroke. Methods and Findings: Semi-structured interviews with 26 stroke witnesses were transcribed and theory-guided content analysed was undertaken based on the Common Sense Self-Regulation Model (appraisal processes) and Theory Domains Framework (behavioural determinants). Response behaviours were often influenced by heuristics-guided appraisal (i.e. mental rules of thumb). Some witnesses described their responses to the situation as &lsquo;automatic' and &lsquo;instinctive', rather than products of deliberation. Potential behavioural influences included: environmental context and resources (e.g. time of day), social influence (e.g. prompts from patients) and beliefs about consequences (e.g. 999 accesses rapid help). Findings are based on retrospective accounts and need further verification in prospective studies. Conclusions: Witnesses play a key role in patient access to emergency medical services. Factors that potentially influence witnesses' responses to stroke were identified and could inform behavioural interventions and future research. Interventions might benefit from linking automatic/instinctive threat perceptions with deliberate appraisal of stroke symptoms, prompting action to call emergency medical services