Spotlight on unmet needs in stroke prevention: The PIONEER AF-PCI, NAVIGATE ESUS and GALILEO trials.

PubMed

Hemmrich, Melanie; Peterson, Eric D; Thomitzek, Karen; Weitz, Jeffrey I

2016-09-28

Atrial fibrillation (AF) is a major healthcare concern, being associated with an estimated five-fold risk of ischaemic stroke. In patients with AF, anticoagulants reduce stroke risk to a greater extent than acetylsalicylic acid (ASA) or dual antiplatelet therapy (DAPT) with ASA plus clopidogrel. Non-vitamin K antagonist oral anticoagulants (NOACs) are now a widely-accepted therapeutic option for stroke prevention in non-valvular AF (NVAF). There are particular patient types with NVAF for whom treatment challenges remain, owing to sparse clinical data, their high-risk nature or a need to harmonise anticoagulant and antiplatelet regimens if co-administered. This article focuses on three randomised controlled trials (RCTs) that are investigating the utility of rivaroxaban, a direct, oral, factor Xa inhibitor, in additional areas of stroke prevention where data for anticoagulants are lacking: oPen-label, randomized, controlled, multicentre study explorIng twO treatmeNt stratEgiEs of Rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment (PIONEER AF-PCI); New Approach riVaroxoban Inhibition of factor Xa in a Global trial vs Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS); and Global study comparing a rivAroxaban-based antithrombotic strategy to an antipLatelet-based strategy after transcatheter aortIc vaLve rEplacement to Optimize clinical outcomes (GALILEO). Data from these studies present collaborative efforts to build upon existing registrational Phase III data for rivaroxaban, driving the need for effective and safe treatment of a wider range of patients for stroke prevention.

Exclusion of patients with concomitant chronic conditions in ongoing randomised controlled trials targeting 10 common chronic conditions and registered at ClinicalTrials.gov: a systematic review of registration details.

PubMed

Buffel du Vaure, Céline; Dechartres, Agnès; Battin, Constance; Ravaud, Philippe; Boutron, Isabelle

2016-09-27

To systematically assess registration details of ongoing randomised controlled trials (RCTs) targeting 10 common chronic conditions and registered at ClinicalTrials.gov and to determine the prevalence of (1) trial records excluding patients with concomitant chronic condition(s) and (2) those specifically targeting patients with concomitant chronic conditions. Systematic review of trial registration records. ClinicalTrials.gov register. All ongoing RCTs registered from 1 January 2014 to 31 January 2015 that assessed an intervention targeting adults with coronary heart disease (CHD), hypertension, heart failure, stroke/transient ischaemic attack, atrial fibrillation, type 2 diabetes, chronic obstructive pulmonary disease, painful condition, depression and dementia with a target sample size ≥100. From the trial registration records, 2 researchers independently recorded the trial characteristics and the number of exclusion criteria and determined whether patients with concomitant chronic conditions were excluded or specifically targeted. Among 319 ongoing RCTs, despite the high prevalence of the concomitant chronic conditions, patients with these conditions were excluded in 251 trials (79%). For example, although 91% of patients with CHD had a concomitant chronic condition, 69% of trials targeting such patients excluded patients with concomitant chronic condition(s). When considering the co-occurrence of 2 chronic conditions, 31% of patients with chronic pain also had depression, but 58% of the trials targeting patients with chronic pain excluded patients with depression. Only 37 trials (12%) assessed interventions specifically targeting patients with concomitant chronic conditions; 31 (84%) excluded patients with concomitant chronic condition(s). Despite widespread multimorbidity, more than three-quarters of ongoing trials assessing interventions for patients with chronic conditions excluded patients with concomitant chronic conditions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Returning to Paid Employment after Stroke: The Psychosocial Outcomes In StrokE (POISE) Cohort Study

PubMed Central

Hackett, Maree L.; Glozier, Nick; Jan, Stephen; Lindley, Richard

2012-01-01

Objectives To determine which early modifiable factors are associated with younger stroke survivors' ability to return to paid work in a cohort study with 12-months of follow-up conducted in 20 stroke units in the Stroke Services NSW clinical network. Participants Were aged >17 and <65 years, recent (within 28 days) stroke, able to speak English sufficiently to respond to study questions, and able to provide written informed consent. Participants with language or cognitive impairment were eligible to participate if their proxy provided consent and completed assessments on the participants' behalf. The main outcome measure was return to paid work during the 12 months following stroke. Results Of 441 consented participants (average age 52 years, 68% male, 83% with ischemic stroke), 218 were in paid full-time and 53 in paid part-time work immediately before their stroke, of whom 202 (75%) returned to paid part- or full-time work within 12 months. Being male, female without a prior activity restricting illness, younger, independent in activities of daily living (ADL) at 28 days after stroke, and having private health insurance was associated with return to paid work, following adjustment for other illnesses and a history of depression before stroke (C statistic 0·81). Work stress and post stroke depression showed no such independent association. Conclusions Given that independence in ADL is the strongest predictor of return to paid work within 12 months of stroke, these data reinforce the importance of reducing stroke-related disability and increasing independence for younger stroke survivors. Trial Registration Australian New Zealand Clinical Trials Registry ANZCTRN 12608000459325 PMID:22848610

Observed Cost and Variations in Short Term Cost-Effectiveness of Therapy for Ischemic Stroke in Interventional Management of Stroke (IMS) III.

PubMed

Simpson, Kit N; Simpson, Annie N; Mauldin, Patrick D; Palesch, Yuko Y; Yeatts, Sharon D; Kleindorfer, Dawn; Tomsick, Thomas A; Foster, Lydia D; Demchuk, Andrew M; Khatri, Pooja; Hill, Michael D; Jauch, Edward C; Jovin, Tudor G; Yan, Bernard; von Kummer, Rüdiger; Molina, Carlos A; Goyal, Mayank; Schonewille, Wouter J; Mazighi, Mikael; Engelter, Stefan T; Anderson, Craig; Spilker, Judith; Carrozzella, Janice; Ryckborst, Karla J; Janis, L Scott; Broderick, Joseph P

2017-05-08

Examination of linked data on patient outcomes and cost of care may help identify areas where stroke care can be improved. We report on the association between variations in stroke severity, patient outcomes, cost, and treatment patterns observed over the acute hospital stay and through the 12-month follow-up for subjects receiving endovascular therapy compared to intravenous tissue plasminogen activator alone in the IMS (Interventional Management of Stroke) III Trial. Prospective data collected for a prespecified economic analysis of the trial were used. Data included hospital billing records for the initial stroke admission and subsequent detailed resource use after the acute hospitalization collected at 3, 6, 9, and 12 months. Cost of follow-up care varied 6-fold for patients in the lowest (0-1) and highest (20+) National Institutes of Health Stroke Scale category at 5 days, and by modified Rankin Scale at 3 months. The kind of resources used postdischarge also varied between treatment groups. Incremental short-term cost-effectiveness ratios varied greatly when treatments were compared for patient subgroups. Patient subgroups predefined by stroke severity had incremental cost-effectiveness ratios of $97 303/quality-adjusted life year (severe stroke) and $3 187 805/quality-adjusted life year (moderately severe stroke). Detailed economic and resource utilization data from IMS III provide powerful evidence for the large effect that patient outcome has on the economic value of medical and endovascular reperfusion therapies. These data can be used to inform process improvements for stroke care and to estimate the cost-effectiveness of endovascular therapy in the US health system for stroke intervention trials. URL: http://www.clinicaltrials.gov. Registration number: NCT00359424. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

MIDAS (Modafinil in Debilitating Fatigue After Stroke): A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial.

PubMed

Bivard, Andrew; Lillicrap, Thomas; Krishnamurthy, Venkatesh; Holliday, Elizabeth; Attia, John; Pagram, Heather; Nilsson, Michael; Parsons, Mark; Levi, Christopher R

2017-05-01

This study aimed to assess the efficacy of modafinil, a wakefulness-promoting agent in alleviating post-stroke fatigue ≥3 months after stroke. We hypothesized that 200 mg of modafinil daily for 6 weeks would result in reduced symptoms of fatigue compared with placebo. This single-center phase 2 trial used a randomized, double-blind, placebo-controlled, crossover design. The key inclusion criterion was a multidimensional fatigue inventory score of ≥60. Patients were randomized to either modafinil or placebo for 6 weeks of therapy, then after a 1 week washout period swapped treatment arms for a second 6 weeks of therapy. The primary outcome was the multidimensional fatigue inventory; secondary outcomes included the Montreal cognitive assessment, the Depression, Anxiety, and Stress Scale (DASS), and the Stroke-Specific Quality of Life (SSQoL) scale. The multidimensional fatigue inventory is a self-administered questionnaire with a range of 0 to 100. Treatment efficacy was assessed using linear regression by estimating within-person, baseline-adjusted differences in mean outcomes after therapy. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000350527). A total of 232 stroke survivors were screened and 36 were randomized. Participants receiving modafinil reported a significant decrease in fatigue (multidimensional fatigue inventory, -7.38; 95% CI, -21.76 to -2.99; P <0.001) and improved quality of life (SSQoL, 11.81; 95% CI, 2.31 to 21.31; P =0.0148) compared with placebo. Montreal cognitive assessment and DASS were not significantly improved with modafinil therapy during the study period ( P >0.05). Stroke survivors with nonresolving fatigue reported reduced fatigue and improved quality of life after taking 200 mg daily treatment with modafinil. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368268. Unique identifier: ACTRN12615000350527. © 2017 The Authors.

ESCAPS study protocol: a feasibility randomised controlled trial of ‘Early electrical stimulation to the wrist extensors and wrist flexors to prevent the post-stroke complications of pain and contractures in the paretic arm’

PubMed Central

Fletcher-Smith, Joanna C; Walker, Dawn-Marie; Sprigg, Nikola; James, Marilyn; Walker, Marion F; Allatt, Kate; Mehta, Rajnikant; Pandyan, Anand D

2016-01-01

Introduction Approximately 70% of patients with stroke experience impaired arm function, which is persistent and disabling for an estimated 40%. Loss of function reduces independence in daily activities and impacts on quality of life. Muscles in those who do not recover functional movement in the stroke affected arm are at risk of atrophy and contractures, which can be established as early as 6 weeks following stroke. Pain is also common. This study aims to evaluate the feasibility of a randomised controlled trial to test the efficacy and cost-effectiveness of delivering early intensive electrical stimulation (ES) to prevent post-stroke complications in the paretic upper limb. Methods and analysis This is a feasibility randomised controlled trial (n=40) with embedded qualitative studies (patient/carer interviews and therapist focus groups) and feasibility economic evaluation. Patients will be recruited from the Stroke Unit at the Nottingham University Hospitals National Health Service (NHS) Trust within 72 h after stroke. Participants will be randomised to receive usual care or usual care and early ES to the wrist flexors and extensors for 30 min twice a day, 5 days a week for 3 months. The initial treatment(s) will be delivered by an occupational therapist or physiotherapist who will then train the patient and/or their nominated carer to self-manage subsequent treatments. Ethics and dissemination This study has been granted ethical approval by the National Research Ethics Service, East Midlands Nottingham1 Research Ethics Committee (ref: 15/EM/0006). To our knowledge, this is the first study of its kind of the early application (within 72 h post-stroke) of ES to both the wrist extensors and wrist flexors of stroke survivors with upper limb impairment. The results will inform the design of a definitive randomised controlled trial. Dissemination will include 2 peer-reviewed journal publications and presentations at national conferences. Trial registration number ISRCTN1648908; Pre-results. Clinicaltrials.gov ID: NCT02324634. PMID:26729394

Randomized clinical trial comparing percutaneous closure of patent foramen ovale (PFO) using the Amplatzer PFO Occluder with medical treatment in patients with cryptogenic embolism (PC-Trial): rationale and design

PubMed Central

2011-01-01

Background Several studies have shown an association of cryptogenic stroke and embolism with patent foramen ovale (PFO), but the question how to prevent further events in such patients is unresolved. Options include antithrombotic treatment with warfarin or antiplatelet agents or surgical or endovascular closure of the PFO. The PC-Trial was set up to compare endovascular closure and best medical treatment for prevention of recurrent events. Methods The PC-Trial is a randomized clinical trial comparing the efficacy of percutaneous closure of the PFO using the Amplatzer PFO occluder with best medical treatment in patients with cryptogenic embolism, i.e. mostly cryptogenic stroke. Warfarin for 6 months followed by antiplatelet agents is recommended as medical treatment. Randomization is stratified according to patients age (<45 versus ≥45 years), presence of atrial septal aneurysm (ASA yes or no) and number of embolic events before randomization (one versus more than one event). Primary endpoints are death, nonfatal stroke and peripheral embolism. Discussion patients were randomized in 29 centers of Europe, Canada, and Australia. Randomization started February 2000. Enrollment of 414 patients was completed in February 2009. All patients will be followed-up longitudinally. Follow-up is maintained until the last enrolled patient is beyond 2.5 years of follow-up (expected in 2011). Trial Registration Trial listed in ClinicalTrials.gov as NCT00166257 and sponsored by AGA Medical, Plymouth, MN, USA PMID:21356042

Protocol for the Locomotor Experience Applied Post-stroke (LEAPS) trial: a randomized controlled trial

PubMed Central

Duncan, Pamela W; Sullivan, Katherine J; Behrman, Andrea L; Azen, Stanley P; Wu, Samuel S; Nadeau, Stephen E; Dobkin, Bruce H; Rose, Dorian K; Tilson, Julie K

2007-01-01

Background Locomotor training using body weight support and a treadmill as a therapeutic modality for rehabilitation of walking post-stroke is being rapidly adopted into clinical practice. There is an urgent need for a well-designed trial to determine the effectiveness of this intervention. The objective of the Locomotor Experience Applied Post-Stroke (LEAPS) trial is to determine if there is a difference in the proportion of participants who recover walking ability at one year post-stroke when randomized to a specialized locomotor training program (LTP), conducted at 2- or 6-months post-stroke, or those randomized to a home based non-specific, low intensity exercise intervention (HEP) provided 2 months post-stroke. We will determine if the timing of LTP delivery affects gait speed at 1 year and whether initial impairment severity interacts with the timing of LTP. The effect of number of treatment sessions will be determined by changes in gait speed taken pre-treatment and post-12, -24, and -36 sessions. Methods/Design We will recruit 400 adults with moderate or severe walking limitations within 30 days of stroke onset. At two months post stroke, participants are stratified by locomotor impairment severity as determined by overground walking speed and randomly assigned to one of three groups: (a) LTP-Early; (b) LTP-Late or (c) Home Exercise Program -Early. The LTP program includes body weight support on a treadmill and overground training. The LTP and HEP interventions are delivered for 36 sessions over 12 weeks. Primary outcome measure include successful walking recovery defined as the achievement of a 0.4 m/s gait speed or greater by persons with initial severe gait impairment or the achievement of a 0.8 m/s gait speed or greater by persons with initial moderate gait impairment. LEAPS is powered to detect a 20% difference in the proportion of participants achieving successful locomotor recovery between the LTP groups and the HEP group, and a 0.1 m/s mean difference in gait speed change between the two LTP groups. Discussion The goal of this single-blinded, phase III randomized clinical trial is to provide evidence to guide post-stroke walking recovery programs. Trial registration NCT00243919. PMID:17996052

Multidisciplinary transmural rehabilitation for older persons with a stroke: the design of a randomised controlled trial.

PubMed

Vluggen, Tom P M M; van Haastregt, Jolanda C M; Verbunt, Jeanine A; Keijsers, Elly J M; Schols, Jos M G A

2012-12-31

Stroke is one of the major causes of loss of independence, decreased quality of life and mortality among elderly people. About half of the elderly stroke patients discharged after rehabilitation in a nursing home still experience serious impairments in daily functioning one year post stroke, which can lead to difficulties in picking up and managing their social life. The aim of this study is to evaluate the effectiveness and feasibility of a new multidisciplinary transmural rehabilitation programme for older stroke patients. A two group multicentre randomised controlled trial is used to evaluate the effects of the rehabilitation programme. The programme consists of three care modules: 1) neurorehabilitation treatment for elderly stroke patients; 2) empowerment training for patient and informal caregiver; and 3) stroke education for patient and informal caregiver. The total programme has a duration of between two and six months, depending on the individual problems of the patient and informal caregiver. The control group receives usual care in the nursing home and after discharge. Patients aged 65 years and over are eligible for study participation when they are admitted to a geriatric rehabilitation unit in a nursing home due to a recent stroke and are expected to be able to return to their original home environment after discharge. Data are gathered by face-to-face interviews, self-administered questionnaires, focus groups and registration forms. Primary outcomes for patients are activity level after stroke, functional dependence, perceived quality of life and social participation. Outcomes for informal caregivers are perceived care burden, objective care burden, quality of life and perceived health. Outcome measures of the process evaluation are implementation fidelity, programme deliverance and the opinion of the stroke professionals, patients and informal caregivers about the programme. Outcome measures of the economic evaluation are the healthcare utilisation and associated costs. Data are collected at baseline, and after six and 12 months. The first results of the study will be expected in 2014. International Standard Randomised Controlled Trial Register Number ISRCTN62286281, The Dutch Trial Register NTR2412.

Acupuncture treatment for ischaemic stroke in young adults: protocol for a randomised, sham-controlled clinical trial

PubMed Central

Chen, Lifang; Fang, Jianqiao; Jin, Xiaoming; Keeler, Crystal Lynn; Gao, Hong; Fang, Zhen; Chen, Qin

2016-01-01

Introduction Stroke in young adults is not uncommon. Although the overall incidence of stroke has been recently declining, the incidence of stroke in young adults is increasing. Traditional vascular risk factors are the main cause of young ischaemic stroke. Acupuncture has been shown to benefit stroke rehabilitation and ameliorate the risk factors for stroke. The aims of this study were to determine whether acupuncture treatment will be effective in improving the activities of daily living (ADL), motor function and quality of life (QOL) in patients of young ischaemic stroke, and in preventing stroke recurrence by controlling blood pressure, lipids and body weight. Methods and analysis In this randomised, sham-controlled, participant-blinded and assessor-blinded clinical trial, 120 patients between 18 and 45 years of age with a recent (within 1 month) ischaemic stroke will be randomised for an 8-week acupuncture or sham acupuncture treatment. The primary outcome will be the Barthel Index for ADL. The secondary outcomes will include the Fugl-Meyer Assessment for motor function; the World Health Organization Quality of Life BREF (WHOQOL-BREF) for QOL; and risk factors that are measured by ambulatory blood pressure, the fasting serum lipid, body mass index and waist circumference. Incidence of adverse events and long-term mortality and recurrence rate during a 10-year and 30-year follow-up will also be investigated. Ethics and dissemination Ethics approval was obtained from the Ethics Committee of The Third Affiliated Hospital of Zhejiang Chinese Medical University. Protocol V.3 was approved in June 2013. The results will be disseminated in a peer-reviewed journal and presented at international congresses. The results will also be disseminated to patients by telephone during follow-up calls enquiring on the patient's post-study health status. Trial registration number ChiCTR-TRC- 13003317; Pre-results. PMID:26739742

Using wireless technology in clinical practice: does feedback of daily walking activity improve walking outcomes of individuals receiving rehabilitation post-stroke? Study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Regaining independent ambulation is the top priority for individuals recovering from stroke. Thus, physical rehabilitation post-stroke should focus on improving walking function and endurance. However, the amount of walking completed by individuals with stroke attending rehabilitation is far below that required for independent community ambulation. There has been increased interest in accelerometer-based monitoring of walking post-stroke. Walking monitoring could be integrated within the goal-setting process for those with ambulation goals in rehabilitation. The feedback from these devices can be downloaded to a computer to produce reports. The purpose of this study is to determine the effect of accelerometer-based feedback of daily walking activity during rehabilitation on the frequency and duration of walking post-stroke. Methods Participants will be randomly assigned to one of two groups: feedback or no feedback. Participants will wear accelerometers daily during in- and out-patient rehabilitation and, for participants in the feedback group, the participants’ treating physiotherapist will receive regular reports of walking activity. The primary outcome measures are the amount of daily walking completed, as measured using the accelerometers, and spatio-temporal characteristics of walking (e.g. walking speed). We will also examine goal attainment, satisfaction with progress towards goals, stroke self-efficacy, and community-integration. Discussion Increased walking activity during rehabilitation is expected to improve walking function and community re-integration following discharge. In addition, a focus on altering walking behaviour within the rehabilitation setting may lead to altered behaviour and increased activity patterns after discharge. Trial registration ClinicalTrials.gov NCT01521234 PMID:23865593

Innovative STRoke Interactive Virtual thErapy (STRIVE) online platform for community-dwelling stroke survivors: a randomised controlled trial protocol

PubMed Central

Bird, Marie-Louise; Muthalib, Makii

2018-01-01

Introduction The STRoke Interactive Virtual thErapy (STRIVE) intervention provides community-dwelling stroke survivors access to individualised, remotely supervised progressive exercise training via an online platform. This trial aims to determine the clinical efficacy of the STRIVE intervention and its effect on brain activity in community-dwelling stroke survivors. Methods and analysis In a multisite, assessor-blinded randomised controlled trial, 60 stroke survivors >3 months poststroke with mild-to-moderate upper extremity impairment will be recruited and equally randomised by location (Melbourne, Victoria or Launceston, Tasmania) to receive 8 weeks of virtual therapy (VT) at a local exercise training facility or usual care. Participants allocated to VT will perform 3–5 upper limb exercises individualised to their impairment severity and preference, while participants allocated to usual care will be asked to maintain their usual daily activities. The primary outcome measures will be upper limb motor function and impairment, which will be assessed using the Action Research Arm Test and Upper Extremity Fugl-Meyer, respectively. Secondary outcome measures include upper extremity function and spasticity, as measured by the box and block test and Modified AshworthScale, respectively, and task-related changes in bilateral sensorimotor cortex haemodynamics during hand reaching and wrist extension movements as measured by functional near-infrared spectroscopy. Quality of life will be measured using the Euro-Quality of Life-5 Dimension-5 Level Scale, and the Motor Activity Log-28 will be used to measure use of the hemiparetic arm. All measures will be assessed at baseline and immediately postintervention. Ethics and dissemination The study was approved by the Deakin University Human Research Ethics Committee in May 2017 (No. 2017–087). The results will be disseminated in peer-reviewed journals and presented at major international stroke meetings. Trial registration number ACTRN12617000745347; Pre-results. PMID:29317414

Protocol for a prospective interventional trial to develop a diagnostic index test for stroke as a cause of vertigo, dizziness and imbalance in the emergency room (EMVERT study)

PubMed Central

Bardins, Stanislavs; Müller, Hans-Helge; Jahn, Klaus; Zwergal, Andreas

2017-01-01

Introduction Identifying stroke as a cause of acute vertigo, dizziness and imbalance in the emergency room is still a clinical challenge. Many patients are admitted to stroke units, but only a minority will have strokes. This imposes a heavy financial burden on the healthcare system. The aim of this study is to develop a diagnostic index test to identify patients with a high risk of having a stroke as the cause of acute vertigo and imbalance. Methods and analysis Patients with acute onset of vertigo, dizziness, postural imbalance or double vision within the last 24 hours lasting for at least 10 min are eligible to be included in the study. Patients with clinically proven peripheral or central aetiology will be excluded. In the emergency room, all enrolled patients will undergo standardised neuro-ophthalmological/physiological testing (including video-oculography, mobile posturography, measurement of subjective visual vertical) (EMVERT block 1). Within 10 days, standardised MRI will be performed as a reference test to identify stroke (EMVERT block 2). Data from EMVERT block 2 will be compared with results from block 1 in order to devise a diagnostic index test with a high specificity and sensitivity to predict the risk of stroke in the emergency room. Ethics and dissemination The study was approved by the ethics committee of the University of Munich and will be conducted according to the Guideline for Good Clinical Practice, the Federal Data Protecting Act and the Helsinki Declaration of the World Medical Association in its recent version. Study results are expected to be published in international peer-reviewed journals and will be presented at international conferences. Trial registration number German Clinical Trial Register: DRKS00008992; Universal trial number: U1111-1172-8719); pre-results. PMID:29018076

A structured reading algorithm improves telemetric detection of atrial fibrillation after acute ischemic stroke.

PubMed

Kallmünzer, Bernd; Breuer, Lorenz; Hering, Christiane; Raaz-Schrauder, Dorette; Kollmar, Rainer; Huttner, Hagen B; Schwab, Stefan; Köhrmann, Martin

2012-04-01

Anticoagulation is a highly effective secondary prevention in patients with cardioembolic stroke and atrial fibrillation/flutter (AF). However, the condition remains underdiagnosed, because paroxysmal AF may be missed by diagnostic tests in the acute phase. In this study, the sensitivity of AF detection was assessed for serial electrocardiographic recordings and continuous stroke unit telemetric monitoring with or without a structured algorithm to analyze telemetric data (SEA-AF). Three hundred forty-six consecutive patients with acute ischemic stroke were prospectively included and subjected to standard telemetric monitoring. In addition, telemetric data were separately analyzed following SEA-AF, consisting of a structured evaluation of episodes with high risk for AF and a chronological beat-to-beat screening of the full registration. Serial electrocardiograms were conducted in 24-hour intervals. Median effective telemetry monitoring time was 75.5 hours (interquartile range 64-86 hours). Overall, AF was diagnosed in 119 of 346 patients (34.4%). The structured reading algorithm was the most sensitive method to detected AF. Conventional telemetry and serial electrocardiographic assessments were less effective. However, only 35% of patients with previously documented paroxysmal AF and negative baseline electrocardiogram demonstrated AF episodes during monitoring. Continuous stroke unit telemetry using SEA-AF shows a significantly higher detection rate for AF compared with daily electrocardiographic assessments and standard telemetry without structured reading. The low overall probability to detect paroxysmal AF with either method during the first days after stroke demonstrates the urgent need for complementary diagnostic strategies such as long-term monitoring and frequent follow-up assessments. Clinical Trial Registration- URL: www.clinicaltrials.gov. Unique identifier: NCT01177748.

The Stroke Oxygen Study (SO2S) - a multi-center, study to assess whether routine oxygen treatment in the first 72 hours after a stroke improves long-term outcome: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Mild hypoxia is common in stroke patients and may have significant adverse effects on the ischemic brain after stroke. The use of oxygen treatment is rapidly increasing in European stroke units but is not without side effects. It impedes early mobilization, could pose an infection risk, and may encourage the formation of toxic free radicals, leading to further damage to the ischemic brain. In the Stroke Oxygen Pilot Study (2 or 3 L/min for 72 hours) neurological recovery at one week was better in the oxygen group than in controls, and after correction for difference in baseline stroke severity and prognostic factors, there was a trend to better outcome with oxygen at six months. Oxygen was as effective in mild as in severe strokes. Oxygen saturation is lower at night than during the day, and episodes of oxygen desaturation are common during sleep. Nocturnal oxygen supplementation is likely to reduce the burden of hypoxia without interfering with daytime mobilization and rehabilitation. Before wider use of oxygen supplementation becomes established it is important to obtain better evidence on which patients benefit from such treatment. Methods Participants will be randomized to one of three groups: the first will receive continuous oxygen for 72 hours (at a rate of 2 or 3 L/min depending on baseline oxygen saturation), the second group will receive nocturnal oxygen only (at a rate of 2 or 3 L/min depending on baseline oxygen saturation) and the third group will not receive any oxygen (control). A baseline assessment is performed at randomization and a one-week follow-up completed. Outcome data at three, six and twelve months will be obtained via a questionnaire sent to the patient by the trial center. Discussion This study will provide evidence on the effectiveness of oxygen supplementation for the treatment of stroke and whether nocturnal oxygen is a potentially beneficial therapy regimen. Trial registration This trial is registered with the ISRCTN register ID number ISRCTN52416964 PMID:24684940

Detailed analysis of periprocedural strokes in patients undergoing intracranial stenting in Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS).

PubMed

Fiorella, David; Derdeyn, Colin P; Lynn, Michael J; Barnwell, Stanley L; Hoh, Brian L; Levy, Elad I; Harrigan, Mark R; Klucznik, Richard P; McDougall, Cameron G; Pride, G Lee; Zaidat, Osama O; Lutsep, Helmi L; Waters, Michael F; Hourihane, J Maurice; Alexandrov, Andrei V; Chiu, David; Clark, Joni M; Johnson, Mark D; Torbey, Michel T; Rumboldt, Zoran; Cloft, Harry J; Turan, Tanya N; Lane, Bethany F; Janis, L Scott; Chimowitz, Marc I

2012-10-01

Enrollment in the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) trial was halted due to the high risk of stroke or death within 30 days of enrollment in the percutaneous transluminal angioplasty and stenting arm relative to the medical arm. This analysis focuses on the patient and procedural factors that may have been associated with periprocedural cerebrovascular events in the trial. Bivariate and multivariate analyses were performed to evaluate whether patient and procedural variables were associated with cerebral ischemic or hemorrhagic events occurring within 30 days of enrollment (termed periprocedural) in the percutaneous transluminal angioplasty and stenting arm. Of 224 patients randomized to percutaneous transluminal angioplasty and stenting, 213 underwent angioplasty alone (n=5) or with stenting (n=208). Of these, 13 had hemorrhagic strokes (7 parenchymal, 6 subarachnoid), 19 had ischemic stroke, and 2 had cerebral infarcts with temporary signs within the periprocedural period. Ischemic events were categorized as perforator occlusions (13), embolic (4), mixed perforator and embolic (2), and delayed stent occlusion (2). Multivariate analyses showed that higher percent stenosis, lower modified Rankin score, and clopidogrel load associated with an activated clotting time above the target range were associated (P ≤ 0.05) with hemorrhagic stroke. Nonsmoking, basilar artery stenosis, diabetes, and older age were associated (P ≤ 0.05) with ischemic events. Periprocedural strokes in SAMMPRIS had multiple causes with the most common being perforator occlusion. Although risk factors for periprocedural strokes could be identified, excluding patients with these features from undergoing percutaneous transluminal angioplasty and stenting to lower the procedural risk would limit percutaneous transluminal angioplasty and stenting to a small subset of patients. Moreover, given the small number of events, the present data should be used for hypothesis generation rather than to guide patient selection in clinical practice. Clinical Trial Registration Information- URL: http://clinicaltrials.gov. Unique Identifier: NCT00576693.

Results of the Intravascular Cooling in the Treatment of Acute Stroke 2 Trial (ICTuS-2)

PubMed Central

Lyden, Patrick; Hemmen, Thomas; Grotta, James; Rapp, Karen; Ernstrom, Karin; Rzesiewicz, Teresa; Parker, Stephanie; Concha, Mauricio; Syed, Hussain; Agarwal, Sachin; Meyer, Brett; Jurf, Julie; Altafullah, Irfan; Raman, Rema

2016-01-01

Background and Purpose Therapeutic hypothermia (TH) is a potent neuroprotectant approved for cerebral protection after neonatal hypoxia-ischemia and cardiac arrest. TH for acute ischemic stroke is safe and feasible in pilot trials. We designed a study protocol to provide safer, faster TH in stroke patients. Methods Safety procedures and 4°C saline infusions for faster cooling were added to the Intravascular Cooling Treatment in Acute Stroke (ICTuS) trial protocol. A femoral venous intravascular cooling catheter following intravenous rt-PA in eligible patients provided 24 hours cooling followed by a 12 hour re-warm. Serial safety assessments and imaging were performed. The primary endpoint was 3-month modified Rankin score 0,1. Results Of the intended 1600 subjects, 120 were enrolled before the study was stopped. Randomly, 63 were to receive hypothermia (HY) plus anti-shivering treatment and 57 normothermia (NT). Compared to prior studies, cooling rates were improved with a cold saline bolus, without fluid overload. The intention-to-treat primary outcome of 90-day mRS 0,1 occurred in 33% HY and 38% NT subjects, OR (95% CL) of 0.81 (0.36, 1.85). Serious adverse events occurred equally. Mortality was 15.9% HY and 8.8% NT subjects, OR (95% CL) of 1.95 (0.56, 7.79). Pneumonia occurred in 19% HY vs. 10.5% in NT subjects, OR (95% CL) of 1.99 (0.63, 6.98). Conclusion Intravascular TH was confirmed to be safe and feasible in rt-PA treated acute ischemic stroke patients. Protocol changes designed to reduce pneumonia risk appeared to fail, although the sample is small. Clinical trial registration clinicaltrials.gov NCT 01123161. PMID:27834742

Did a quality improvement collaborative make stroke care better? A cluster randomized trial

PubMed Central

2014-01-01

Background Stroke can result in death and long-term disability. Fast and high-quality care can reduce the impact of stroke, but UK national audit data has demonstrated variability in compliance with recommended processes of care. Though quality improvement collaboratives (QICs) are widely used, whether a QIC could improve reliability of stroke care was unknown. Methods Twenty-four NHS hospitals in the Northwest of England were randomly allocated to participate either in Stroke 90:10, a QIC based on the Breakthrough Series (BTS) model, or to a control group giving normal care. The QIC focused on nine processes of quality care for stroke already used in the national stroke audit. The nine processes were grouped into two distinct care bundles: one relating to early hours care and one relating to rehabilitation following stroke. Using an interrupted time series design and difference-in-difference analysis, we aimed to determine whether hospitals participating in the QIC improved more than the control group on bundle compliance. Results Data were available from nine interventions (3,533 patients) and nine control hospitals (3,059 patients). Hospitals in the QIC showed a modest improvement from baseline in the odds of average compliance equivalent to a relative improvement of 10.9% (95% CI 1.3%, 20.6%) in the Early Hours Bundle and 11.2% (95% CI 1.4%, 21.5%) in the Rehabilitation Bundle. Secondary analysis suggested that some specific processes were more sensitive to an intervention effect. Conclusions Some aspects of stroke care improved during the QIC, but the effects of the QIC were modest and further improvement is needed. The extent to which a BTS QIC can improve quality of stroke care remains uncertain. Some aspects of care may respond better to collaboratives than others. Trial registration ISRCTN13893902. PMID:24690267

Endovascular therapy for acute ischaemic stroke: the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) randomised, controlled trial

PubMed Central

Muir, Keith W; Ford, Gary A; Messow, Claudia-Martina; Ford, Ian; Murray, Alicia; Clifton, Andrew; Brown, Martin M; Madigan, Jeremy; Lenthall, Rob; Robertson, Fergus; Dixit, Anand; Cloud, Geoffrey C; Wardlaw, Joanna; Freeman, Janet; White, Philip

2017-01-01

Objective The Pragmatic Ischaemic Thrombectomy Evaluation (PISTE) trial was a multicentre, randomised, controlled clinical trial comparing intravenous thrombolysis (IVT) alone with IVT and adjunctive intra-arterial mechanical thrombectomy (MT) in patients who had acute ischaemic stroke with large artery occlusive anterior circulation stroke confirmed on CT angiography (CTA). Design Eligible patients had IVT started within 4.5 hours of stroke symptom onset. Those randomised to additional MT underwent thrombectomy using any Conformité Européene (CE)-marked device, with target interval times for IVT start to arterial puncture of <90 min. The primary outcome was the proportion of patients achieving independence defined by a modified Rankin Scale (mRS) score of 0–2 at day 90. Results Ten UK centres enrolled 65 patients between April 2013 and April 2015. Median National Institutes of Health Stroke Scale score was 16 (IQR 13–21). Median stroke onset to IVT start was 120 min. In the intention-to-treat analysis, there was no significant difference in disability-free survival at day 90 with MT (absolute difference 11%, adjusted OR 2.12, 95% CI 0.65 to 6.94, p=0.20). Secondary analyses showed significantly greater likelihood of full neurological recovery (mRS 0–1) at day 90 (OR 7.6, 95% CI 1.6 to 37.2, p=0.010). In the per-protocol population (n=58), the primary and most secondary clinical outcomes significantly favoured MT (absolute difference in mRS 0–2 of 22% and adjusted OR 4.9, 95% CI 1.2 to 19.7, p=0.021). Conclusions The trial did not find a significant difference between treatment groups for the primary end point. However, the effect size was consistent with published data and across primary and secondary end points. Proceeding as fast as possible to MT after CTA confirmation of large artery occlusion on a background of intravenous alteplase is safe, improves excellent clinical outcomes and, in the per-protocol population, improves disability-free survival. Trial registration number NCT01745692; Results. PMID:27756804

Exploring threats to generalisability in a large international rehabilitation trial (AVERT)

PubMed Central

Bernhardt, Julie; Raffelt, Audrey; Churilov, Leonid; Lindley, Richard I; Speare, Sally; Ancliffe, Jacqueline; Katijjahbe, Md Ali; Hameed, Shahul; Lennon, Sheila; McRae, Anna; Tan, Dawn; Quiney, Jan; Williamson, Hannah C; Collier, Janice; Dewey, Helen M; Donnan, Geoffrey A; Langhorne, Peter; Thrift, Amanda G

2015-01-01

Objective The purpose of this paper is to examine potential threats to generalisability of the results of a multicentre randomised controlled trial using data from A Very Early Rehabilitation Trial (AVERT). Design AVERT is a prospective, parallel group, assessor-blinded randomised clinical trial. This paper presents data assessing the generalisability of AVERT. Setting Acute stroke units at 44 hospitals in 8 countries. Participants The first 20 000 patients screened for AVERT, of whom 1158 were recruited and randomised. Model We use the Proximal Similarity Model, which considers the person, place, and setting and practice, as a framework for considering generalisability. As well as comparing the recruited patients with the target population, we also performed an exploratory analysis of the demographic, clinical, site and process factors associated with recruitment. Results The demographics and stroke characteristics of the included patients in the trial were broadly similar to population-based norms, with the exception that AVERT had a greater proportion of men. The most common reason for non-recruitment was late arrival to hospital (ie, >24 h). Overall, being older and female reduced the odds of recruitment to the trial. More women than men were excluded for most of the reasons, including refusal. The odds of exclusion due to early deterioration were particularly high for those with severe stroke (OR=10.4, p<0.001, 95% CI 9.27 to 11.65). Conclusions A model which explores person, place, and setting and practice factors can provide important information about the external validity of a trial, and could be applied to other clinical trials. Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN12606000185561) and Clinicaltrials.gov (NCT01846247). PMID:26283667

Virtual reality for the rehabilitation of the upper limb motor function after stroke: a prospective controlled trial

PubMed Central

2013-01-01

Background Recent evidence has demonstrated the efficacy of Virtual Reality (VR) for stroke rehabilitation nonetheless its benefits and limitations in large population of patients have not yet been studied. Objectives To evaluate the effectiveness of non-immersive VR treatment for the restoration of the upper limb motor function and its impact on the activities of daily living capacities in post-stroke patients. Methods A pragmatic clinical trial was conducted among post-stroke patients admitted to our rehabilitation hospital. We enrolled 376 subjects who had a motor arm subscore on the Italian version of the National Institutes of Health Stroke Scale (It-NIHSS) between 1 and 3 and without severe neuropsychological impairments interfering with recovery. Patients were allocated to two treatments groups, receiving combined VR and upper limb conventional (ULC) therapy or ULC therapy alone. The treatment programs consisted of 2 hours of daily therapy, delivered 5 days per week, for 4 weeks. The outcome measures were the Fugl-Meyer Upper Extremity (F-M UE) and Functional Independence Measure (FIM) scales. Results Both treatments significantly improved F-M UE and FIM scores, but the improvement obtained with VR rehabilitation was significantly greater than that achieved with ULC therapy alone. The estimated effect size of the minimal difference between groups in F-M UE and FIM scores was 2.5 ± 0.5 (P < 0.001) pts and 3.2 ± 1.2 (P = 0.007) pts, respectively. Conclusions VR rehabilitation in post-stroke patients seems more effective than conventional interventions in restoring upper limb motor impairments and motor related functional abilities. Trial registration Italian Ministry of Health IRCCS Research Programme 2590412 PMID:23914733

Troponin elevation in acute ischemic stroke (TRELAS) - protocol of a prospective observational trial

PubMed Central

2011-01-01

Background Levels of the cardiac muscle regulatory protein troponin T (cTnT) are frequently elevated in patients with acute ischemic stroke and elevated cTnT predicts poor outcome and mortality. The pathomechanism of troponin release may relate to co-morbid coronary artery disease and myocardial ischemia or, alternatively, to neurogenic cardiac damage due to autonomic activation after acute ischemic stroke. Therefore, there is uncertainty about how acute ischemic stroke patients with increased cTnT levels should be managed regarding diagnostic and therapeutic workup. Methods/Design The primary objective of the prospective observational trial TRELAS (TRoponin ELevation in Acute ischemic Stroke) is to investigate the frequency and underlying pathomechanism of cTnT elevation in acute ischemic stroke patients in order to give guidance for clinical practice. All consecutive patients with acute ischemic stroke admitted within 72 hours after symptom onset to the Department of Neurology at the Campus Benjamin Franklin of the University Hospital Charité will be screened for cTnT elevations (i.e. >= 0.05 μg/l) on admission and again on the following day. Patients with increased cTnT will undergo coronary angiography within 72 hours. Diagnostic findings of coronary angiograms will be compared with age- and gender-matched patients presenting with Non-ST-Elevation myocardial infarction to the Department of Cardiology. The primary endpoint of the study will be the occurrence of culprit lesions in the coronary angiogram indicating underlying co-morbid obstructive coronary artery disease. Secondary endpoints will be the localization of stroke in the cerebral imaging and left ventriculographic findings of wall motion abnormalities suggestive of stroke-induced global cardiac dysfunction. Discussion TRELAS will prospectively determine the frequency and possible etiology of troponin elevation in a large cohort of ischemic stroke patients. The findings are expected to contribute to clarify pathophysiologic concepts of co-morbid cardiac damage in ischemic stroke patients and also to provide a basis for clinical recommendations for cardiac workup of such patients. Trial registration clinicaltrials.gov NCT01263964 PMID:21824425

Effect of adding upper limb rehabilitation to botulinum toxin-A on upper limb activity after stroke: Protocol for the InTENSE trial.

PubMed

Lannin, Natasha A; Ada, Louise; English, Coralie; Ratcliffe, Julie; Crotty, Maria

2018-01-01

Rationale Although clinical practice guidelines recommend that management of moderate to severe spasticity include the use of botulinum toxin-A in conjunction with therapy, there is currently no evidence to support the addition of therapy. Aims To determine the effect and cost-benefit of adding evidence-based movement training to botulinum toxin-A. Sample size estimate A total of 136 participants will be recruited in order to be able to detect a between-group difference of seven points on the Goal Attainment Scale T-score with 80% power at a two-tailed significance level of 0.05. Methods and design The InTENSE trial is a national, multicenter, Phase III randomized trial with concealed allocation, blinded assessment and intention-to-treat analysis. Stroke survivors who are scheduled to receive botulinum toxin-A in any muscle(s) that cross the wrist because of moderate to severe spasticity after a stroke greater than three months ago, who have completed formal rehabilitation and have no significant cognitive impairment will be randomly allocated to receive botulinum toxin-A plus evidence-based movement training or botulinum toxin-A alone. Study outcomes The primary outcomes are goal attainment (Goal Attainment Scaling) and upper limb activity (Box and Block Test) at three months (end of intervention) and at 12 months (beyond the intervention). Secondary outcomes are spasticity, range of motion, strength, pain, burden of care and health-related quality of life. Direct costs, personal costs and health system costs will be collected at 12 months. Discussion The results of the InTENSE trial are anticipated to directly influence intervention for moderate to severe spasticity after stroke. Trial Registration ANZCTR12615000616572.

Protocol for process evaluation of a randomised controlled trial of family-led rehabilitation post stroke (ATTEND) in India

PubMed Central

Liu, Hueiming; Lindley, Richard; Alim, Mohammed; Felix, Cynthia; Gandhi, Dorcas B C; Verma, Shweta J; Tugnawat, Deepak Kumar; Syrigapu, Anuradha; Ramamurthy, Ramaprabhu Krishnappa; Pandian, Jeyaraj D; Walker, Marion; Forster, Anne; Anderson, Craig S; Langhorne, Peter; Murthy, Gudlavalleti Venkata Satyanarayana; Shamanna, Bindiganavale Ramaswamy; Hackett, Maree L; Maulik, Pallab K; Harvey, Lisa A; Jan, Stephen

2016-01-01

Introduction We are undertaking a randomised controlled trial (fAmily led rehabiliTaTion aftEr stroke in INDia, ATTEND) evaluating training a family carer to enable maximal rehabilitation of patients with stroke-related disability; as a potentially affordable, culturally acceptable and effective intervention for use in India. A process evaluation is needed to understand how and why this complex intervention may be effective, and to capture important barriers and facilitators to its implementation. We describe the protocol for our process evaluation to encourage the development of in-process evaluation methodology and transparency in reporting. Methods and analysis The realist and RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) frameworks informed the design. Mixed methods include semistructured interviews with health providers, patients and their carers, analysis of quantitative process data describing fidelity and dose of intervention, observations of trial set up and implementation, and the analysis of the cost data from the patients and their families perspective and programme budgets. These qualitative and quantitative data will be analysed iteratively prior to knowing the quantitative outcomes of the trial, and then triangulated with the results from the primary outcome evaluation. Ethics and dissemination The process evaluation has received ethical approval for all sites in India. In low-income and middle-income countries, the available human capital can form an approach to reducing the evidence practice gap, compared with the high cost alternatives available in established market economies. This process evaluation will provide insights into how such a programme can be implemented in practice and brought to scale. Through local stakeholder engagement and dissemination of findings globally we hope to build on patient-centred, cost-effective and sustainable models of stroke rehabilitation. Trial registration number CTRI/2013/04/003557. PMID:27633636

Methodological issues in the design and evaluation of supported communication for aphasia training: a cluster-controlled feasibility study

PubMed Central

Horton, Simon; Clark, Allan; Barton, Garry; Lane, Kathleen; Pomeroy, Valerie M

2016-01-01

Objective To assess the feasibility and acceptability of training stroke service staff to provide supported communication for people with moderate–severe aphasia in the acute phase; assess the suitability of outcome measures; collect data to inform sample size and Health Economic evaluation in a definitive trial. Design Phase II cluster-controlled, observer-blinded feasibility study. Settings In-patient stroke rehabilitation units in the UK matched for bed numbers and staffing were assigned to control and intervention conditions. Participants 70 stroke rehabilitation staff from all professional groups, excluding doctors, were recruited. 20 patients with moderate-severe aphasia were recruited. Intervention Supported communication for aphasia training, adapted to the stroke unit context versus usual care. Training was supplemented by a staff learning log, refresher sessions and provision of communication resources. Main outcome measures Feasibility of recruitment and acceptability of the intervention and of measures required to assess outcomes and Health Economic evaluation in a definitive trial. Staff outcomes: Measure of Support in Conversation; patient outcomes: Stroke and Aphasia Quality of Life Scale; Communicative Access Measure for Stroke; Therapy Outcome Measures for aphasia; EQ-5D-3L was used to assess health outcomes. Results Feasibility of staff recruitment was demonstrated. Training in the intervention was carried out with 28 staff and was found to be acceptable in qualitative reports. 20 patients consented to take part, 6 withdrew. 18 underwent all measures at baseline; 16 at discharge; and 14 at 6-month follow-up. Of 175 patients screened 71% were deemed to be ineligible, either lacking capacity or too unwell to participate. Poor completion rates impacted on assessment of patient outcomes. We were able to collect sufficient data at baseline, discharge and follow-up for economic evaluation. Conclusions The feasibility study informed components of the intervention and implementation in day-to-day practice. Modifications to the design are needed before a definitive cluster-randomised trial can be undertaken. Trial registration number ISRCTN37002304; Results. PMID:27091825

Intensive versus Guideline Blood Pressure and Lipid Lowering in Patients with Previous Stroke: Main Results from the Pilot ‘Prevention of Decline in Cognition after Stroke Trial’ (PODCAST) Randomised Controlled Trial

PubMed Central

Scutt, Polly; Blackburn, Daniel J.; Ankolekar, Sandeep; Krishnan, Kailash; Ballard, Clive; Burns, Alistair; Mant, Jonathan; Passmore, Peter; Pocock, Stuart; Reckless, John; Sprigg, Nikola; Stewart, Rob; Wardlaw, Joanna M.; Ford, Gary A.

2017-01-01

Background Stroke is associated with the development of cognitive impairment and dementia. We assessed the effect of intensive blood pressure (BP) and/or lipid lowering on cognitive outcomes in patients with recent stroke in a pilot trial. Methods In a multicentre, partial-factorial trial, patients with recent stroke, absence of dementia, and systolic BP (SBP) 125–170 mmHg were assigned randomly to at least 6 months of intensive (target SBP <125 mmHg) or guideline (target SBP <140 mmHg) BP lowering. The subset of patients with ischaemic stroke and total cholesterol 3.0–8.0 mmol/l were also assigned randomly to intensive (target LDL-cholesterol <1.3 mmol/l) or guideline (target LDL-c <3.0 mmol/l) lipid lowering. The primary outcome was the Addenbrooke’s Cognitive Examination-Revised (ACE-R). Results We enrolled 83 patients, mean age 74.0 (6.8) years, and median 4.5 months after stroke. The median follow-up was 24 months (range 1–48). Mean BP was significantly reduced with intensive compared to guideline treatment (difference –10·6/–5·5 mmHg; p<0·01), as was total/LDL-cholesterol with intensive lipid lowering compared to guideline (difference –0·54/–0·44 mmol/l; p<0·01). The ACE-R score during treatment did not differ for either treatment comparison; mean difference for BP lowering -3.6 (95% CI -9.7 to 2.4), and lipid lowering 4.4 (95% CI -2.1 to 10.9). However, intensive lipid lowering therapy was significantly associated with improved scores for ACE-R at 6 months, trail making A, modified Rankin Scale and Euro-Qol Visual Analogue Scale. There was no difference in rates of dementia or serious adverse events for either comparison. Conclusion In patients with recent stroke and normal cognition, intensive BP and lipid lowering were feasible and safe, but did not alter cognition over two years. The association between intensive lipid lowering and improved scores for some secondary outcomes suggests further trials are warranted. Trial Registration ISRCTN ISRCTN85562386 PMID:28095412

Cluster randomized trials utilizing primary care electronic health records: methodological issues in design, conduct, and analysis (eCRT Study)

PubMed Central

2014-01-01

Background There is growing interest in conducting clinical and cluster randomized trials through electronic health records. This paper reports on the methodological issues identified during the implementation of two cluster randomized trials using the electronic health records of the Clinical Practice Research Datalink (CPRD). Methods Two trials were completed in primary care: one aimed to reduce inappropriate antibiotic prescribing for acute respiratory infection; the other aimed to increase physician adherence with secondary prevention interventions after first stroke. The paper draws on documentary records and trial datasets to report on the methodological experience with respect to research ethics and research governance approval, general practice recruitment and allocation, sample size calculation and power, intervention implementation, and trial analysis. Results We obtained research governance approvals from more than 150 primary care organizations in England, Wales, and Scotland. There were 104 CPRD general practices recruited to the antibiotic trial and 106 to the stroke trial, with the target number of practices being recruited within six months. Interventions were installed into practice information systems remotely over the internet. The mean number of participants per practice was 5,588 in the antibiotic trial and 110 in the stroke trial, with the coefficient of variation of practice sizes being 0.53 and 0.56 respectively. Outcome measures showed substantial correlations between the 12 months before, and after intervention, with coefficients ranging from 0.42 for diastolic blood pressure to 0.91 for proportion of consultations with antibiotics prescribed, defining practice and participant eligibility for analysis requires careful consideration. Conclusions Cluster randomized trials may be performed efficiently in large samples from UK general practices using the electronic health records of a primary care database. The geographical dispersal of trial sites presents a difficulty for research governance approval and intervention implementation. Pretrial data analyses should inform trial design and analysis plans. Trial registration Current Controlled Trials ISRCTN 47558792 and ISRCTN 35701810 (both registered on 17 March 2010). PMID:24919485

Botulinum toxin therapy for treatment of spasticity in multiple sclerosis: review and recommendations of the IAB-Interdisciplinary Working Group for Movement Disorders task force.

PubMed

Dressler, Dirk; Bhidayasiri, Roongroj; Bohlega, Saeed; Chahidi, Abderrahmane; Chung, Tae Mo; Ebke, Markus; Jacinto, L Jorge; Kaji, Ryuji; Koçer, Serdar; Kanovsky, Petr; Micheli, Federico; Orlova, Olga; Paus, Sebastian; Pirtosek, Zvezdan; Relja, Maja; Rosales, Raymond L; Sagástegui-Rodríguez, José Alberto; Schoenle, Paul W; Shahidi, Gholam Ali; Timerbaeva, Sofia; Walter, Uwe; Saberi, Fereshte Adib

2017-01-01

Botulinum toxin (BT) therapy is an established treatment of spasticity due to stroke. For multiple sclerosis (MS) spasticity this is not the case. IAB-Interdisciplinary Working Group for Movement Disorders formed a task force to explore the use of BT therapy for treatment of MS spasticity. A formalised PubMed literature search produced 55 publications (3 randomised controlled trials, 3 interventional studies, 11 observational studies, 2 case studies, 35 reviews, 1 guideline) all unanimously favouring the use of BT therapy for MS spasticity. There is no reason to believe that BT should be less effective and safe in MS spasticity than it is in stroke spasticity. Recommendations include an update of the current prevalence of MS spasticity and its clinical features according to classifications used in movement disorders. Immunological data on MS patients already treated should be analysed with respect to frequencies of MS relapses and BT antibody formation. Registration authorities should expand registration of BT therapy for spasticity regardless of its aetiology. MS specialists should consider BT therapy for symptomatic treatment of spasticity.

Functional strength training and movement performance therapy produce analogous improvement in sit-to-stand early after stroke: early-phase randomised controlled trial.

PubMed

Kerr, A; Clark, A; Cooke, E V; Rowe, P; Pomeroy, V M

2017-09-01

Restoring independence in the sit-to-stand (STS) task is an important objective for stroke rehabilitation. It is not known if a particular intervention, strength training or therapy focused on movement performance is more likely to improve STS recovery. This study aimed to compare STS outcomes from functional strength training, movement performance therapy and conventional therapy. Randomised controlled trial. Acute stroke units. Medically well patients (n=93) with recent (<42 days) stroke. The mean age of patients was 68.8 years, mean time post ictus was 33.5 days, 54 (58%) were male, 20 showed neglect (22%) and 37 (40%) had a left-sided brain lesion. Six weeks of either conventional therapy, functional strength training or movement performance therapy. Subjects were allocated to groups on a random basis. STS ability, timing, symmetry, co-ordination, smoothness and knee velocity were measured at baseline, outcome (after 6 weeks of intervention) and follow-up (3 months after outcome). No significant differences were found between the groups. All three groups improved their STS ability, with 88% able to STS at follow-up compared with 56% at baseline. Few differences were noted in quality of movement, with only symmetry when rising showing significantly greater improvement in the movement performance therapy group; this benefit was not evident at follow-up. Recovery of the STS movement is consistently good during stroke rehabilitation, irrespective of the type of therapy experienced. Changes in quality of movement did not differ according to group allocation, indicating that the type of therapy is less important. Clinical trial registration number NCT00322192. Copyright © 2016 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Telmisartan on top of antihypertensive treatment does not prevent progression of cerebral white matter lesions in the prevention regimen for effectively avoiding second strokes (PRoFESS) MRI substudy.

PubMed

Weber, Ralph; Weimar, Christian; Blatchford, Jon; Hermansson, Karin; Wanke, Isabel; Möller-Hartmann, Claudia; Gizewski, Elke R; Forsting, Michael; Demchuk, Andrew M; Sacco, Ralph L; Saver, Jeffrey L; Warach, Steven; Diener, Hans-Christoph; Diehl, Anke

2012-09-01

High blood pressure is one of the main risk factors for cerebral white matter lesions (WMLs). There is limited evidence from one randomized trial that blood pressure-lowering is able to slow WML progression. We investigated whether telmisartan prevents WML progression in the imaging substudy of the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. This predefined substudy comprised 771 patients (mean age, 65 years) with recent ischemic stroke of noncardioembolic origin who received telmisartan or placebo during a mean follow-up of 27.9 (SD, 7.6) months and had 2 evaluable MRI examinations after index stroke and at study closeout. All MRI scans were centrally adjudicated for progression of periventricular and subcortical WML by 2 neuroradiologists blinded to treatment allocation. Mean blood pressure was 3.0/1.3 mm Hg lower with telmisartan compared with placebo at follow-up MRI. There was no statistically significant difference in progression of the mean periventricular WML score (least squares mean difference, 0.14; 95% CI, -0.12 to 0.39; P=0.29) and mean subcortical WML diameter (least squares mean difference, -0.35 mm; 95% CI, -1.00 to 0.31 mm; P=0.30) during follow-up between patients on telmisartan and placebo. Treatment with telmisartan on top of existing antihypertensive medication did not result in significant blood pressure-lowering and did not prevent the progression of WML in patients with a recent ischemic stroke in this patient cohort. Our analysis is limited by the relatively short follow-up period. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique Identifier: NCT00153062.

Effects of Computer-Aided Interlimb Force Coupling Training on Paretic Hand and Arm Motor Control following Chronic Stroke: A Randomized Controlled Trial

PubMed Central

Lin, Chueh-Ho; Chou, Li-Wei; Luo, Hong-Ji; Tsai, Po-Yi; Lieu, Fu-Kong; Chiang, Shang-Lin; Sung, Wen-Hsu

2015-01-01

Objective We investigated the training effects of interlimb force coupling training on paretic upper extremity outcomes in patients with chronic stroke and analyzed the relationship between motor recovery of the paretic hand, arm and functional performances on paretic upper limb. Design A randomized controlled trial with outcome assessment at baseline and after 4 weeks of intervention. Setting Taipei Veterans General Hospital, National Yang-Ming University. Participants Thirty-three subjects with chronic stroke were recruited and randomly assigned to training (n = 16) and control groups (n = 17). Interventions The computer-aided interlimb force coupling training task with visual feedback included different grip force generation methods on both hands. Main Outcome Measures The Barthel Index (BI), the upper extremity motor control Fugl-Meyer Assessment (FMA-UE), the Motor Assessment Score (MAS), and the Wolf Motor Function Test (WMFT). All assessments were executed by a blinded evaluator, and data management and statistical analysis were also conducted by a blinded researcher. Results The training group demonstrated greater improvement on the FMA-UE (p<.001), WMFT (p<.001), MAS (p = .004) and BI (p = .037) than the control group after 4 weeks of intervention. In addition, a moderate correlation was found between the improvement of scores for hand scales of the FMA and other portions of the FMA UE (r = .528, p = .018) or MAS (r = .596, p = .015) in the training group. Conclusion Computer-aided interlimb force coupling training improves the motor recovery of a paretic hand, and facilitates motor control and enhances functional performance in the paretic upper extremity of people with chronic stroke. Trial Registration ClinicalTrials.gov NCT02247674. PMID:26193492

Angioplasty and stenting for patients with symptomatic intracranial atherosclerosis: study protocol of a randomised controlled trial

PubMed Central

Cui, Xiao-Ping; Lin, Min; Mu, Jun-Shan; Ye, Jian-Xin; He, Wen-Qing; Fu, Mao-Lin; Li, Hua; Fang, Jia-Yang; Shen, Feng-Feng; Lin, Hang

2016-01-01

Introduction Whether adding percutaneous transluminal angioplasty and stenting (PTAS) to background medical treatment is effective for decreasing the incidence of stroke or death in patients with symptomatic intracranial atherosclerosis (ICAS) is still controversial. We perform a randomised controlled trial to examine the effectiveness and safety of an improved PTAS procedure for patients with ICAS. Methods and analysis A randomised controlled trial will be conducted in three hospitals in China. Eligible patients with ICAS will be randomly assigned to receive medication treatment (MT) plus PTAS or MT alone. The MT will be initiated immediately after randomisation, while the PTAS will be performed when patients report relief of alarm symptoms defined as sudden weakness or numbness. All patients will be followed up at 30 days, 3 and 12 months after randomisation. The primary end point will be the incidence of stroke or death at 30 days after randomisation. Secondary outcomes will be the incidence of ischaemic stroke in the territory of stenosis arteries, the incidence of in-stent restenosis, the Chinese version of the modified Rankin Scale and the Chinese version of the Stroke-Specific Quality of Life (CSQoL). Ethics and dissemination The study protocol is approved by institutional review boards in participating hospitals (reference number FZ20160003, 180PLA20160101 and 476PLA2016007). The results of this study will be disseminated to patients, physicians and policymakers through publication in a peer-reviewed journal or presentations in conferences. It is anticipated that the results of this study will improve the quality of the current PTAS procedure and guide clinical decision-making for patients with ICAS. Trial registration number NCT02689037 PMID:27852711

Metformin and sitAgliptin in patients with impAired glucose tolerance and a recent TIA or minor ischemic Stroke (MAAS): study protocol for a randomized controlled trial.

PubMed

Osei, Elizabeth; Fonville, Susanne; Zandbergen, Adrienne A M; Brouwers, Paul J A M; Mulder, Laus J M M; Lingsma, Hester F; Dippel, Diederik W J; Koudstaal, Peter J; den Hertog, Heleen M

2015-08-05

Impaired glucose tolerance is present in one third of patients with a TIA or ischemic stroke and is associated with a two-fold risk of recurrent stroke. Metformin improves glucose tolerance, but often leads to side effects. The aim of this study is to explore the feasibility, safety, and effects on glucose metabolism of metformin and sitagliptin in patients with TIA or minor ischemic stroke and impaired glucose tolerance. We will also assess whether a slow increase in metformin dose and better support and information on this treatment will reduce the incidence of side effects in these patients. The Metformin and sitAgliptin in patients with impAired glucose tolerance and a recent TIA or minor ischemic Stroke trial (MAAS trial) is a phase II, multicenter, randomized, controlled, open-label trial with blinded outcome assessment. Non-diabetic patients (n = 100) with a recent (<6 months) TIA, amaurosis fugax or minor ischemic stroke (modified Rankin scale ≤ 3) and impaired glucose tolerance, defined as 2-hour post-load glucose levels between 7.8 and 11.0 mmol/L after repeated standard oral glucose tolerance test, will be included. Patients with renal or liver impairment, heart failure, chronic hypoxic lung disease stage III-IV, history of lactate acidosis or diabetic ketoacidosis, pregnancy or breastfeeding, pancreatitis and use of digoxin will be excluded. The patients will be randomly assigned in a 1:1:2 ratio to metformin, sitagliptin or "no treatment." Patients allocated to metformin will start with 500 mg twice daily, which will be slowly increased during a 6-week period to a twice daily dose of 1000 mg. Patients allocated to sitagliptin will be treated with a daily fixed dose of 100 mg. The study has been registered as NTR 3196 in The Netherlands Trial Register. Primary outcomes include percentage still on treatment, percentage of (serious) adverse events, and the baseline adjusted difference in 2-hour post-load glucose levels at 6 months. This study will give more information about the feasibility and safety of metformin and sitagliptin as well as the effect on 2-hour post-load glucose levels at 6 months in patients with TIA or ischemic stroke and impaired glucose tolerance. NTR3196 , Date of registration: 15 December 2011.

Cardiovascular rehabilitation soon after stroke using feedback-controlled robotics-assisted treadmill exercise: study protocol of a randomised controlled pilot trial

PubMed Central

2013-01-01

Background After experiencing a stroke, most individuals also suffer from cardiac disease, are immobile and thus have low endurance for exercise. Aerobic capacity is seriously reduced in these individuals and does not reach reasonable levels after conventional rehabilitation programmes. Cardiovascular exercise is beneficial for improvement of aerobic capacity in mild to moderate stroke. However, less is known about its impact on aerobic capacity, motor recovery, and quality-of-life in severely impaired individuals. The aim of this pilot study is to explore the clinical efficacy and feasibility of cardiovascular exercise with regard to aerobic capacity, motor recovery, and quality-of-life using feedback-controlled robotics-assisted treadmill exercise in non-ambulatory individuals soon after experiencing a stroke. Methods/Design This will be a single-centred single blind, randomised control trial with a pre-post intervention design. Subjects will be recruited early after their first stroke (≤20 weeks) at a neurological rehabilitation clinic and will be randomly allocated to an inpatient cardiovascular exercise programme that uses feedback-controlled robotics-assisted treadmill exercise (experimental) or to conventional robotics-assisted treadmill exercise (control). Intervention duration depends on the duration of each subject’s inpatient rehabilitation period. Aerobic capacity, as the primary outcome measure, will be assessed using feedback-controlled robotics-assisted treadmill-based cardiopulmonary exercise testing. Secondary outcome measures will include gait speed, walking endurance, standing function, and quality-of-life. Outcome assessment will be conducted at baseline, after each 4-week intervention period, and before clinical discharge. Ethical approval has been obtained. Discussion Whether cardiovascular exercise in non-ambulatory individuals early after stroke has an impact on aerobic capacity, motor recovery, and quality-of-life is not yet known. Feedback-controlled robotics-assisted treadmill exercise is a relatively recent intervention method and might be used to train and evaluate aerobic capacity in this population. The present pilot trial is expected to provide new insights into the implementation of early cardiovascular exercise for individuals with severe motor impairment. The findings of this study may guide future research to explore the effects of early cardiovascular activation after severe neurological events. Trial registration This trial is registered with the Clinical Trials.gov Registry (NCT01679600). PMID:24053609

Provider perceptions of barriers to the emergency use of tPA for Acute Ischemic Stroke: A qualitative study

PubMed Central

2011-01-01

Background Only 1-3% of ischemic stroke patients receive thrombolytic therapy. Provider barriers to adhering with guidelines recommending tPA delivery in acute stroke are not well known. The main objective of this study was to describe barriers to thrombolytic use in acute stroke care. Methods Twenty-four hospitals were randomly selected and matched into 12 pairs. Barrier assessment occurred at intervention sites only, and utilized focus groups and structured interviews. A pre-specified taxonomy was employed to characterize barriers. Two investigators independently assigned themes to transcribed responses. Seven facilitators (three emergency physicians, two nurses, and two study coordinators) conducted focus groups and interviews of emergency physicians (65), nurses (62), neurologists (15), radiologists (12), hospital administrators (12), and three others (hospitalists and pharmacist). Results The following themes represented the most important external barriers: environmental and patient factors. Important barriers internal to the clinician included familiarity with and motivation to adhere to the guidelines, lack of self-efficacy and outcome expectancy. The following themes were not substantial barriers: lack of awareness of the existence of acute stroke guidelines, presence of conflicting guidelines, and lack of agreement with the guidelines. Conclusions Healthcare providers perceive environmental and patient-related factors as the primary barriers to adherence with acute stroke treatment guidelines. Interventions focused on increasing physician familiarity with and motivation to follow guidelines may be of highest yield in improving adherence. Improving self-efficacy in performing guideline concordant care may also be useful. Trial Registration ClinicalTrials.gov identifier: NCT00349479 PMID:21548943

The network of Shanghai Stroke Service System (4S): A public health-care web-based database using automatic extraction of electronic medical records.

PubMed

Dong, Yi; Fang, Kun; Wang, Xin; Chen, Shengdi; Liu, Xueyuan; Zhao, Yuwu; Guan, Yangtai; Cai, Dingfang; Li, Gang; Liu, Jianmin; Liu, Jianren; Zhuang, Jianhua; Wang, Panshi; Chen, Xin; Shen, Haipeng; Wang, David Z; Xian, Ying; Feng, Wuwei; Campbell, Bruce Cv; Parsons, Mark; Dong, Qiang

2018-07-01

Background Several stroke outcome and quality control projects have demonstrated the success in stroke care quality improvement through structured process. However, Chinese health-care systems are challenged with its overwhelming numbers of patients, limited resources, and large regional disparities. Aim To improve quality of stroke care to address regional disparities through process improvement. Method and design The Shanghai Stroke Service System (4S) is established as a regional network for stroke care quality improvement in the Shanghai metropolitan area. The 4S registry uses a web-based database that automatically extracts data from structured electronic medical records. Site-specific education and training program will be designed and administrated according to their baseline characteristics. Both acute reperfusion therapies including thrombectomy and thrombolysis in the acute phase and subsequent care were measured and monitored with feedback. Primary outcome is to evaluate the differences in quality metrics between baseline characteristics (including rate of thrombolysis in acute stroke and key performance indicators in secondary prevention) and post-intervention. Conclusions The 4S system is a regional stroke network that monitors the ongoing stroke care quality in Shanghai. This project will provide the opportunity to evaluate the spectrum of acute stroke care and design quality improvement processes for better stroke care. A regional stroke network model for quality improvement will be explored and might be expanded to other large cities in China. Clinical Trial Registration-URL http://www.clinicaltrials.gov . Unique identifier: NCT02735226.

RApid Primary care Initiation of Drug treatment for Transient Ischaemic Attack (RAPID−TIA): study protocol for a pilot randomised controlled trial

PubMed Central

2013-01-01

Background People who have a transient ischaemic attack (TIA) or minor stroke are at high risk of a recurrent stroke, particularly in the first week after the event. Early initiation of secondary prevention drugs is associated with an 80% reduction in risk of stroke recurrence. This raises the question as to whether these drugs should be given before being seen by a specialist – that is, in primary care or in the emergency department. The aims of the RAPID-TIA pilot trial are to determine the feasibility of a randomised controlled trial, to analyse cost effectiveness and to ask: Should general practitioners and emergency doctors (primary care physicians) initiate secondary preventative measures in addition to aspirin in people they see with suspected TIA or minor stroke at the time of referral to a specialist? Methods/Design This is a pilot randomised controlled trial with a sub-study of accuracy of primary care physician diagnosis of TIA. In the pilot trial, we aim to recruit 100 patients from 30 general practices (including out-of-hours general practice centres) and 1 emergency department whom the primary care physician diagnoses with TIA or minor stroke and randomly assign them to usual care (that is, initiation of aspirin and referral to a TIA clinic) or usual care plus additional early initiation of secondary prevention drugs (a blood-pressure lowering protocol, simvastatin 40 mg and dipyridamole 200 mg m/r bd). The primary outcome of the main study will be the number of strokes at 90 days. The diagnostic accuracy sub-study will include these 100 patients and an additional 70 patients in whom the primary care physician thinks the diagnosis of TIA is possible, rather than probable. For the pilot trial, we will report recruitment rate, follow-up rate, a preliminary estimate of the primary event rate and occurrence of any adverse events. For the diagnostic study, we will calculate sensitivity and specificity of primary care physician diagnosis using the final TIA clinic diagnosis as the reference standard. Discussion This pilot study will be used to estimate key parameters that are needed to design the main study and to estimate the accuracy of primary care diagnosis of TIA. The planned follow-on trial will have important implications for the initial management of people with suspected TIA. Trial registration ISRCTN62019087 PMID:23819476

Update of the Preventive Antibiotics in Stroke Study (PASS): statistical analysis plan.

PubMed

Westendorp, Willeke F; Vermeij, Jan-Dirk; Dippel, Diederik W J; Dijkgraaf, Marcel G W; van der Poll, Tom; Prins, Jan M; Vermeij, Frederique H; Roos, Yvo B W E M; Brouwer, Matthijs C; Zwinderman, Aeilko H; van de Beek, Diederik; Nederkoorn, Paul J

2014-10-01

Infections occur in 30% of stroke patients and are associated with unfavorable outcomes. Preventive antibiotic therapy lowers the infection rate after stroke, but the effect of preventive antibiotic treatment on functional outcome in patients with stroke is unknown. The PASS is a multicenter, prospective, phase three, randomized, open-label, blinded end-point (PROBE) trial of preventive antibiotic therapy in acute stroke. Patients are randomly assigned to either ceftriaxone at a dose of 2 g, given every 24 h intravenously for 4 days, in addition to standard stroke-unit care, or standard stroke-unit care without preventive antibiotic therapy. The aim of this study is to assess whether preventive antibiotic treatment improves functional outcome at 3 months by preventing infections. This paper presents in detail the statistical analysis plan (SAP) of the Preventive Antibiotics in Stroke Study (PASS) and was submitted while the investigators were still blinded for all outcomes. The primary outcome is the score on the modified Rankin Scale (mRS), assessed by ordinal logistic regression analysis according to a proportional odds model. Secondary analysis of the primary outcome is the score on the mRS dichotomized as a favorable outcome (mRS 0 to 2) versus unfavorable outcome (mRS 3 to 6). Secondary outcome measures are death rate at discharge and 3 months, infection rate during hospital admission, length of hospital admission, volume of post-stroke care, use of antibiotics during hospital stay, quality-adjusted life years and costs. Complications of treatment, serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs) are reported as safety outcomes. The data from PASS will establish whether preventive antibiotic therapy in acute stroke improves functional outcome by preventing infection and will be analyzed according to this pre-specified SAP. Current controlled trials; ISRCTN66140176. Date of registration: 6 April 2010.

The cost effectiveness of an early transition from hospital to nursing home for stroke patients: design of a comparative study

PubMed Central

2010-01-01

Background As the incidence of stroke has increased, its impact on society has increased accordingly, while it continues to have a major impact on the individual. New strategies to further improve the quality, efficiency and logistics of stroke services are necessary. Early discharge from hospital to a nursing home with an adequate rehabilitation programme could help to optimise integrated care for stroke patients. The objective is to describe the design of a non-randomised comparative study evaluating early admission to a nursing home, with multidisciplinary assessment, for stroke patients. The study is comprised of an effect evaluation, an economic evaluation and a process evaluation. Methods/design The design involves a non-randomised comparative trial for two groups. Participants are followed for 6 months from the time of stroke. The intervention consists of a redesigned care pathway for stroke patients. In this care pathway, patients are discharged from hospital to a nursing home within 5 days, in comparison with 12 days in the usual situation. In the nursing home a structured assessment takes place, aimed at planning adequate rehabilitation. People in the control group receive the usual care. The main outcome measures of the effect evaluation are quality of life and daily functioning. In addition, an economic evaluation will be performed from a societal perspective. A process evaluation will be carried out to evaluate the feasibility of the intervention as well as the experiences and opinions of patients and professionals. Discussion The results of this study will provide information about the cost effectiveness of the intervention and its effects on clinical outcomes and quality of life. Relevant strengths and weaknesses of the study are addressed in this article. Trial registration Current Controlled Trails ISRCTN58135104 PMID:20504313

Biomarkers and perfusion – training-induced changes after stroke (BAPTISe): protocol of an observational study accompanying a randomized controlled trial

PubMed Central

2013-01-01

Background Physical activity is believed to exert a beneficial effect on functional and cognitive rehabilitation of patients with stroke. Although studies have addressed the impact of physical exercise in cerebrovascular prevention and rehabilitation, the underlying mechanisms leading to improvement are poorly understood. Training-induced increase of cerebral perfusion is a possible mediating mechanism. Our exploratory study aims to investigate training-induced changes in blood biomarker levels and magnetic resonance imaging in patients with subacute ischemic stroke. Methods/design This biomarker-driven study uses an observational design to examine a subgroup of patients in the randomized, controlled PHYS-STROKE trial. In PHYS-STROKE, 215 patients with subacute stroke (hemorrhagic and ischemic) receive either 4 weeks of physical training (aerobic training, 5 times a week, for 50 minutes) or 4 weeks of relaxation sessions (5 times a week, for 50 minutes). A convenience sample of 100 of these patients with ischemic stroke will be included in BAPTISe and will receive magnetic resonance imaging (MRI) scans and an additional blood draw before and after the PHYS-STROKE intervention. Imaging scans will address parameters of cerebral perfusion, vessel size imaging, and microvessel density (the Q factor) to estimate the degree of neovascularization in the brain. Blood tests will determine several parameters of immunity, inflammation, endothelial function, and lipometabolism. Primary objective of this study is to evaluate differential changes in MRI and blood-derived biomarkers between groups. Other endpoints are next cerebrovascular events and functional status of the patient after the intervention and after 3 months assessed by functional scores, in particular walking speed and Barthel index (co-primary endpoints of PHYS-STROKE). Additionally, we will assess the association between functional outcomes and biomarkers including imaging results. For all endpoints we will compare changes between patients who received physical fitness training and patients who had relaxation sessions. Discussion This exploratory study will be the first to investigate the effects of physical fitness training in patients with ischemic stroke on MRI-based cerebral perfusion, pertinent blood biomarker levels, and functional outcome. The study may have an impact on current patient rehabilitation strategies and reveal important information about the roles of MRI and blood-derived biomarkers in ischemic stroke. Trial registration NCT01954797. PMID:24330706

Telerehabilitation to improve outcomes for people with stroke: study protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background In New Zealand, around 45,000 people live with stroke and many studies have reported that benefits gained during initial rehabilitation are not sustained. Evidence indicates that participation in physical interventions can prevent the functional decline that frequently occurs after discharge from acute care facilities. However, on-going stroke services provision following discharge from acute care is often related to non-medical factors such as availability of resources and geographical location. Currently most people receive no treatment beyond three months post stroke. The study aims to determine if the Augmented Community Telerehabilitation Intervention (ACTIV) results in better physical function for people with stroke than usual care, as measured by the Stroke Impact Scale, physical subcomponent. Methods/design This study will use a multi-site, two-arm, assessor blinded, parallel randomised controlled trial design. People will be eligible if they have had their first ever stroke, are over 20 and have some physical impairment in either arm or leg, or both. Following discharge from formal physiotherapy services (inpatient, outpatient or community), participants will be randomised into ACTIV or usual care. ACTIV uses readily available technology, telephone and mobile phones, combined with face-to-face visits from a physiotherapist over a six-month period, to help people with stroke resume activities they enjoyed before the stroke. The impact of stroke on physical function and quality of life will be assessed, measures of cost will be collected and a discrete choice survey will be used to measure preferences for rehabilitation options. These outcomes will be collected at baseline, six months and 12 months. In-depth interviews will be used to explore the experiences of people participating in the intervention arm of the study. Discussion The lack of on-going rehabilitation for people with stroke diminishes the chance of their best possible outcome and may contribute to a functional decline following discharge from formal rehabilitation. Best practice guidelines recommend a prolonged period of rehabilitation, however this is expensive and therefore not undertaken in most publicly funded centres. An effective, cost-effective, and preference-sensitive therapy using basic technology to assist programme delivery may improve patient autonomy as they leave formal rehabilitation and return home. Trial registration ACTRN12612000464864 PMID:23216861

Outcomes in advanced heart failure patients with left ventricular assist devices for destination therapy.

PubMed

Park, Soon J; Milano, Carmelo A; Tatooles, Antone J; Rogers, Joseph G; Adamson, Robert M; Steidley, D Eric; Ewald, Gregory A; Sundareswaran, Kartik S; Farrar, David J; Slaughter, Mark S

2012-03-01

The HeartMate II (HMII) destination therapy (DT) trial demonstrated significant improvements in outcomes in continuous-flow left ventricular assist devices compared with patients implanted with the pulsatile-flow HeartMate XVE. The primary hypothesis of the current study is that trial patients enrolled after the initial data cohort would have better clinical outcomes. Two hundred eighty-one patients who underwent HMII for DT from May 2007 to March 2009 (Mid Trial [MT] group) were compared with the initial 133 HMII patients from March 2005 to May 2007 (Early Trial [ET] group). Patient entry criteria were the same during the 2 time periods. Survival, adverse events, and quality of life were compared between the 2 groups. Baseline characteristics were similar between the groups. Compared with the ET group, patients in the MT group had reduced adverse event rates for bleeding requiring transfusions (1.66 versus 1.13 events per patient-year, P<0.001), sepsis (0.38 versus 0.27, P=0.025), device-related infections (0.47 versus 0.27, P<0.001), and hemorrhagic stroke (0.07 versus 0.03, P=0.01). Other event rates were similar between groups including ischemic stroke (0.06 versus 0.05 events per patient-year, P=0.57). Survival at 1 year in the MT group was 73% versus 68% in the ET group (P=0.21). Additionally, there was a significant reduction in deaths caused by hemorrhagic stroke (P=0.01). Quality of life improvements were significant in both the groups (P<0.001). The benefit of DT therapy with the HMII is confirmed in subsequent trial patients, with improved adverse event rates and a strong trend for improvements in survival. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00121485.

Rationale and Study Design for a Single-Arm Phase IIa Study Investigating Feasibility of Preventing Ischemic Cerebrovascular Events in High-Risk Patients with Acute Non-disabling Ischemic Cerebrovascular Events Using Remote Ischemic Conditioning

PubMed Central

Liu, Shi-Meng; Zhao, Wen-Le; Song, Hai-Qing; Meng, Ran; Li, Si-Jie; Ren, Chang-Hong; Ovbiagele, Bruce; Ji, Xun-Ming; Feng, Wu-Wei

2018-01-01

Background: Acute minor ischemic stroke (AMIS) or transient ischemic attack (TIA) is a common cerebrovascular event with a considerable high recurrence. Prior research demonstrated the effectiveness of regular long-term remote ischemic conditioning (RIC) in secondary stroke prevention in patients with intracranial stenosis. We hypothesized that RIC can serve as an effective adjunctive therapy to pharmacotherapy in preventing ischemic events in patients with AMIS/TIA. This study aimed to investigate the feasibility, safety, and preliminary efficacy of daily RIC in inhibiting cerebrovascular/cardiovascular events after AMIS/TIA. Methods: This is a single-arm, open-label, multicenter Phase IIa futility study with a sample size of 165. Patients with AMIS/TIA receive RIC as an additional therapy to secondary stroke prevention regimen. RIC consists of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of cuffs on bilateral upper limbs twice a day for 90 days. The antiplatelet strategy is based on individual physician's best practice: aspirin alone, clopidogrel alone, or combination of aspirin and clopidogrel. We will assess the recurrence rate of ischemic stroke/TIA within 3 months as the primary outcomes. Conclusions: The data gathered from the study will be used to determine whether a further large-scale, multicenter randomized controlled Phase II trial is warranted in patients with AMIS/TIA. Trial Registration: ClinicalTrials.gov, NCT03004820; https://www.clinicaltrials.gov/ct2/show/NCT03004820. PMID:29363651

Novel proteins associated with risk for coronary heart disease or stroke among postmenopausal women identified by in-depth plasma proteome profiling

PubMed Central

2010-01-01

Background Coronary heart disease (CHD) and stroke were key outcomes in the Women's Health Initiative (WHI) randomized trials of postmenopausal estrogen and estrogen plus progestin therapy. We recently reported a large number of changes in blood protein concentrations in the first year following randomization in these trials using an in-depth quantitative proteomics approach. However, even though many affected proteins are in pathways relevant to the observed clinical effects, the relationships of these proteins to CHD and stroke risk among postmenopausal women remains substantially unknown. Methods The same in-depth proteomics platform was applied to plasma samples, obtained at enrollment in the WHI Observational Study, from 800 women who developed CHD and 800 women who developed stroke during cohort follow-up, and from 1-1 matched controls. A plasma pooling strategy, followed by extensive fractionation prior to mass spectrometry, was used to identify proteins related to disease incidence, and the overlap of these proteins with those affected by hormone therapy was examined. Replication studies, using enzyme-linked-immunosorbent assay (ELISA), were carried out in the WHI hormone therapy trial cohorts. Results Case versus control concentration differences were suggested for 37 proteins (nominal P < 0.05) for CHD, with three proteins, beta-2 microglobulin (B2M), alpha-1-acid glycoprotein 1 (ORM1), and insulin-like growth factor binding protein acid labile subunit (IGFALS) having a false discovery rate < 0.05. Corresponding numbers for stroke were 47 proteins with nominal P < 0.05, three of which, apolipoprotein A-II precursor (APOA2), peptidyl-prolyl isomerase A (PPIA), and insulin-like growth factor binding protein 4 (IGFBP4), have a false discovery rate < 0.05. Other proteins involved in insulin-like growth factor signaling were also highly ranked. The associations of B2M with CHD (P < 0.001) and IGFBP4 with stroke (P = 0.005) were confirmed using ELISA in replication studies, and changes in these proteins following the initiation of hormone therapy use were shown to have potential to help explain hormone therapy effects on those diseases. Conclusions In-depth proteomic discovery analysis of prediagnostic plasma samples identified B2M and IGFBP4 as risk markers for CHD and stroke respectively, and provided a number of candidate markers of disease risk and candidate mediators of hormone therapy effects on CHD and stroke. Clinical Trials Registration ClinicalTrials.gov identifier: NCT00000611 PMID:20667078

Efficacy of interventions to improve physical activity levels in individuals with stroke: a systematic review protocol

PubMed Central

Aguiar, Larissa Tavares; Martins, Júlia Caetano; Nadeau, Sylvie; Britto, Raquel Rodrigues; Teixeira-Salmela, Luci F; Faria, Christina D C M

2017-01-01

Introduction Stroke is a leading health problem worldwide and an important cause of disability. Stroke survivors show low levels of physical activity, and increases in physical activity levels may improve function and health status. Therefore, the aims are to identify which interventions that have been employed to increase physical activity levels with stroke survivors, to verify their efficacy and to identify the gaps in the literature. Methods and analysis A systematic review of randomised controlled trials that investigated the efficacy of interventions aiming at increasing physical activity levels of stroke survivors will be conducted. Electronic searches will be performed in the MEDLINE, Physiotherapy Evidence Database (PEDro), Excerpta Medica (EMBASE), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) and Scientific Electronic Library Online (SCIELO) databases. Hand searches of the reference lists of the included studies or relevant reviews will also be employed. Two independent reviewers will screen all the retrieved titles, abstracts and full texts. A third reviewer will be referred to solve any disagreements. The quality of the included studies will be assessed by the PEDro Rating Scale. This systematic review will also include a qualitative synthesis. Meta-analyses will be performed, if the studies are sufficiently homogeneous. This review will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The quality of the evidence regarding physical activity will be assessed, according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Discussion This systematic review will provide information on which interventions are effective for increasing physical activity levels of stroke survivors. This evidence may be important for clinical decision-making and will allow the identification of gaps in the literature that may be useful for the definition of future research goals and the planning of new trials. Trial registration number CRD42016037750. PMID:28057651

Identifying continence options after stroke (ICONS): a cluster randomised controlled feasibility trial.

PubMed

Thomas, Lois H; Watkins, Caroline L; Sutton, Christopher J; Forshaw, Denise; Leathley, Michael J; French, Beverley; Burton, Christopher R; Cheater, Francine; Roe, Brenda; Britt, David; Booth, Joanne; McColl, Elaine

2014-12-23

Urinary incontinence (UI) affects half of patients hospitalised after stroke and is often poorly managed. Cochrane systematic reviews have shown some positive impact of conservative interventions (such as bladder training) in reducing UI, but their effectiveness has not been demonstrated with stroke patients. We conducted a cluster randomised controlled feasibility trial of a systematic voiding programme (SVP) for the management of UI after stroke. Stroke services were randomised to receive SVP (n = 4), SVP plus supported implementation (SVP+, n = 4), or usual care (UC, n = 4).Feasibility outcomes were participant recruitment and retention. The main effectiveness outcome was presence or absence of UI at six and 12 weeks post-stroke. Additional effectiveness outcomes included were the effect of the intervention on different types of UI, continence status at discharge, UI severity, functional ability, quality of life, and death. It was possible to recruit patients (413; 164 SVP, 125 SVP+, and 124 UC) and participant retention was acceptable (85% and 88% at six and 12 weeks, respectively). There was no suggestion of a beneficial effect on the main outcome at six (SVP versus UC: odds ratio (OR) 0.94, 95% CI: 0.46 to 1.94; SVP+ versus UC: OR: 0.62, 95% CI: 0.28 to 1.37) or 12 weeks (SVP versus UC: OR: 1.02, 95% CI: 0.54 to 1.93; SVP+ versus UC: OR: 1.06, 95% CI: 0.54 to 2.09).No secondary outcomes showed a strong suggestion of clinically meaningful improvement in SVP and/or SVP+ arms relative to UC at six or 12 weeks. However, at 12 weeks both intervention arms had higher estimated odds of continence than UC for patients with urge incontinence. The trial has met feasibility outcomes of participant recruitment and retention. It was not powered to demonstrate effectiveness, but there is some evidence of a potential reduction in the odds of specific types of incontinence. A full trial should now be considered. ISRCTN Registry, ISRCTN08609907, date of registration: 7 July 2010.

A cluster randomized trial to assess the effect of clinical pathways for patients with stroke: results of the clinical pathways for effective and appropriate care study

PubMed Central

2012-01-01

Background Clinical pathways (CPs) are used to improve the outcomes of acute stroke, but their use in stroke care is questionable, because the evidence on their effectiveness is still inconclusive. The objective of this study was to evaluate whether CPs improve the outcomes and the quality of care provided to patients after acute ischemic stroke. Methods This was a multicentre cluster-randomized trial, in which 14 hospitals were randomized to the CP arm or to the non intervention/usual care (UC) arm. Healthcare workers in the CP arm received 3 days of training in quality improvement of CPs and in use of a standardized package including information on evidence-based key interventions and indicators. Healthcare workers in the usual-care arm followed their standard procedures. The teams in the CP arm developed their CPs over a 6-month period. The primary end point was mortality. Secondary end points were: use of diagnostic and therapeutic procedures, implementation of organized care, length of stay, re-admission and institutionalization rates after discharge, dependency levels, and complication rates. Results Compared with the patients in the UC arm, the patients in the CP arm had a significantly lower risk of mortality at 7 days (OR = 0.10; 95% CI 0.01 to 0.95) and significantly lower rates of adverse functional outcomes, expressed as the odds of not returning to pre-stroke functioning in their daily life (OR = 0.42; 95 CI 0.18 to 0.98). There was no significant effect on 30-day mortality. Compared with the UC arm, the hospital diagnostic and therapeutic procedures were performed more appropriately in the CP arm, and the evidence-based key interventions and organized care were more applied in the CP arm. Conclusions CPs can significantly improve the outcomes of patients with ischemic patients with stroke, indicating better application of evidence-based key interventions and of diagnostic and therapeutic procedures. This study tested a new hypothesis and provided evidence on how CPs can work. Trial registration ClinicalTrials.gov ID: [NCT00673491]. PMID:22781160

Changing practice in the assessment and treatment of somatosensory loss in stroke survivors: protocol for a knowledge translation study.

PubMed

Cahill, Liana S; Lannin, Natasha A; Mak-Yuen, Yvonne Y K; Turville, Megan L; Carey, Leeanne M

2018-01-23

The treatment of somatosensory loss in the upper limb after stroke has been historically overshadowed by therapy focused on motor recovery. A double-blind randomized controlled trial has demonstrated the effectiveness of SENSe (Study of the Effectiveness of Neurorehabilitation on Sensation) therapy to retrain somatosensory discrimination after stroke. Given the acknowledged prevalence of upper limb sensory loss after stroke and the evidence-practice gap that exists in this area, effort is required to translate the published research to clinical practice. The aim of this study is to determine whether evidence-based knowledge translation strategies change the practice of occupational therapists and physiotherapists in the assessment and treatment of sensory loss of the upper limb after stroke to improve patient outcomes. A pragmatic, before-after study design involving eight (n = 8) Australian health organizations, specifically sub-acute and community rehabilitation facilities. Stroke survivors (n = 144) and occupational therapists and physiotherapists (~10 per site, ~n = 80) will be involved in the study. Stroke survivors will be provided with SENSe therapy or usual care. Occupational therapists and physiotherapists will be provided with a multi-component approach to knowledge translation including i) tailoring of the implementation intervention to site-specific barriers and enablers, ii) interactive group training workshops, iii) establishing and fostering champion therapists and iv) provision of written educational materials and online resources. Outcome measures for occupational therapists and physiotherapists will be pre- and post-implementation questionnaires and audits of medical records. The primary outcome for stroke survivors will be change in upper limb somatosensory function, measured using a standardized composite measure. This study will provide evidence and a template for knowledge translation in clinical, organizational and policy contexts in stroke rehabilitation. Australian New Zealand Clinical Trials Registry (ANZCTR) retrospective registration ACTRN12615000933550 .

The economic impact of stroke in The Netherlands: the €-restore4stroke study

PubMed Central

2012-01-01

Background Stroke has a considerable socio-economic impact worldwide and is the leading cause of disabilities in the Western world. Economic studies of stroke focus merely on physical aspects and clinical interventions. To our current knowledge there is no comprehensive economic study investigating the economic impact of stroke including psychological and social aspects. The €-Restore4Stroke project, part of a large comprehensive research programme Restore4Stroke, aims to investigate the total economic impact of stroke in the Netherlands. Methods Two trial-based economic evaluation studies will be conducted within the €-Restore4Stroke project: one focussing on a self-management intervention and one on an augmented cognitive behavioural therapy intervention. Both include cost-effectiveness analyses and cost-utility analyses as primary research methods. Furthermore, a cost-of-illness study investigating costs after stroke attached to a cohort study and a record linkage study in which four databases are linked to investigate patterns of health care consumption before and after stroke, are embedded in €-Restore4Stroke. All studies will be performed from a societal perspective. The primary outcome measure for the cost-effectiveness analysis is the increase in health status on the primary outcome scales. Within the cost-utility analysis, the primary outcome measure is quality-adjusted life years (QALYs) for which an indirect preference-based technique will be used. In the self-management study we will also look at the estimation of health effects on informal caregivers. Cost outcomes in the cost-of-illness study will be computed with a cost questionnaire and linkage of several databases will be used to derive outcomes in the record linkage study, Discussion €-Restore4Stroke will provide new insights and evidence for the economic impact of psychosocial consequences after stroke. Besides being innovative in various ways (i.e. focussing on the chronic phase after stroke and including personal factors as possible determinants of long-term re-integration including quality of life in a prospective longitudinal design), a major strength of €-Restore4Stroke is that we include impact on informal caregivers. The outcomes of this study will provide health care decision makers with valuable and necessary information regarding stroke care related decisions. Trial registration NTR3051 (RCT Self-management), NTR2999 (RCT Augmented Cognitive Behavioural Therapy) PMID:22329910

A prospective controlled study: Minimally invasive stereotactic puncture therapy versus conventional craniotomy in the treatment of acute intracerebral hemorrhage

PubMed Central

2011-01-01

Background Spontaneous intracerebral hemorrhage (ICH) is a devastating form of stroke with the high mortality twofold to sixfold higher than that for ischemic stroke. But the treatment of haematomas within the basal ganglia continues to be a matter of debate among neurologists and neurosurgeons. The purpose of this study is to judge the clinical value of minimally invasive stereotactic puncture therapy (MISPT) on acute ICH. Methods A prospective controlled study was undertaken. The clinical trial was in compliance with the WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects. According to the enrollment criterion, there were 168 acute ICH cases analyzed, of which 90 cases were performed by MISPT ( MISPT group, MG) and 78 cases by Conventional craniotomy (CC group, CG), by means of compare of Glasgow Coma Scale(GCS) score, postoperative complications(PC) and rebleeding incidence(RI), moreover, long-term outcome of 1 year postoperation judged by Glasgow Outcome Scale (GOS), Barthel Index (BI), modified Rankin Scale (mRS) and case fatality(CF). Results MG patients showed obvious amelioration in GCS score compared with that of CG. The total incidence of PC in MG decreased obviously compared with that of CG. The incidences of rebleeding in MG and CG were 10.0% and 15.4% respectively. There was no obvious difference between CFs of MG and CG. For three parameters representing long-term outcome, the GOS, BI and mRS in MG were ameliorated significantly than that of CG. Conclusion These data suggested that the advantage of MISPT was displayed in minute trauma and safety, and seemed to be feasible and to had a trend towards improved long-term outcome. Trial Registration The Australian New Zealand Clinical Trials Registry (ANZCTR), the registration number:ACTRN12610000945022. PMID:21699716

Gothenburg very early supported discharge study (GOTVED) NCT01622205: a block randomized trial with superiority design of very early supported discharge for patients with stroke

PubMed Central

2013-01-01

Background Stroke is the disease with the highest costs for hospital care and also after discharge. Early supported discharge (ESD) has shown to be efficient and safe and the best results with well-organised discharge teams and patients with less severe strokes. The aim is to investigate if very early supported discharge (VESD) for stroke patients in need for on-going individualised rehabilitation at home is useful for the patient and cost effective. Methods/design A randomized controlled trial comparing VESD with ordinary discharge. Inclusion criteria: confirmed stroke, >18 years of age, living within 30 min from the stroke unit, on day 2 0–16 points on the National institute of health stroke scale (NIHSS) and 50–100 points on the Barthel Index (BI), with BI 100 then the patient can be included if the Montreal Cognitive Assessment is < 26. Exclusion criteria are: NIHSS >16, BI < 50, life expectancy < 1 year, inability to speak or to communicate in Swedish. The inclusion occurs on day 4 and in block randomization of 20 and with blinded assessor. Primary outcome: levels of anxiety and depression. Secondary outcomes: independence, security, level of function, quality of health, needs of support in activities of daily living and caregiver burden. Power calculation is based on the level of anxiety and with a power of 80%, p-value 0.05 (2 sided test) 44 persons per group are needed. Data is gathered on co-morbidity, re-entry to hospital, mortality and a health economic analysis. Interviews will be accomplished with a strategic sample of 15 patients in the intervention group before discharge, within two weeks after homecoming and 3 months later. Interviews are also planned with 15 relatives in the intervention group 3 months after discharge. Discussion The ESD studies in the Cochrane review present hospital stays of a length that no longer exist in Sweden. There is not yet, to our knowledge, any study of early supported discharge with present length of hospital stay. Thus it is not clear if home rehabilitation nowadays without risks, is cost effective, or with the same patient usefulness as earlier studies. Trial registration ClinicalTrials.gov NCT01622205 PMID:23800106

Tai Chi-based exercise program provided via telerehabilitation compared to home visits in a post-stroke population who have returned home without intensive rehabilitation: study protocol for a randomized, non-inferiority clinical trial

PubMed Central

2014-01-01

Background The incidence of strokes in industrialized nations is on the rise, particularly in the older population. In Canada, a minority of individuals who have had a stroke actually receive intensive rehabilitation because most stroke patients do not have access to services or because their motor recovery was judged adequate to return home. Thus, there is a considerable need to organize home-based rehabilitation services for everyone who has had a stroke. To meet this demand, telerehabilitation, particularly from a service center to the patient’s home, is a promising alternative approach that can help improve access to rehabilitation services once patients are discharged home. Methods/Design This non-inferiority study will include patients who have returned home post-stroke without requiring intensive rehabilitation. To be included in the study, participants will: 1) not be referred to an Intensive Functional Rehabilitation Unit, 2) have a Rankin score of 2 or 3, and 3) have a balance problem (Berg Balance Scale score between 46 and 54). Participants will be randomly assigned to either the teletreatment group or the home visits group. Except for the delivery mode, the intervention will be the same for both groups, that is, a personalized Tai Chi-based exercise program conducted by a trained physiotherapist (45-minute session twice a week for eight consecutive weeks). The main objective of this research is to test the non-inferiority of a Tai Chi-based exercise program provided via telerehabilitation compared to the same program provided in person at home in terms of effectiveness for retraining balance in individuals who have had a stroke but do not require intensive functional rehabilitation. The main outcome of this study is balance and mobility measured with the Community Balance and Mobility Scale. Secondary outcomes include physical and psychological capacities related to balance and mobility, participants’ quality of life, satisfaction with services received, and cost-effectiveness associated with the provision of both types of services. Study/trial registration ClinicalTrials.gov: NCT01848080 PMID:24479760

PreSSUB II: The prehospital stroke study at the Universitair Ziekenhuis Brussel II

PubMed Central

Espinoza, Alexis Valenzuela; Van Hooff, Robbert-Jan; De Smedt, Ann; Moens, Maarten; Yperzeele, Laetitia; Nieboer, Koenraad; Hubloue, Ives; De Keyser, Jacques; Dupont, Alain; De Wit, Liesbet; Putman, Koen; Brouns, Raf

2015-01-01

Rationale Stroke is a time-critical medical emergency requiring specialized treatment. Prehospital delay contributes significantly to delayed or missed treatment opportunities. In-ambulance telemedicine can bring stroke expertise to the prehospital arena and facilitate this complex diagnostic and therapeutic process. Aims This study evaluates the efficacy, safety, feasibility, reliability and cost-effectiveness of in-ambulance telemedicine for patients with suspicion of acute stroke. We hypothesize that this approach will reduce the delay to in-hospital treatment by streamlining the diagnostic process and that prehospital stroke care will be improved by expert stroke support via telemedicine during the ambulance transportation. Design PreSSUB II is an interventional, prospective, randomized, open-blinded, end-point, single-center trial comparing standard emergency care by the Paramedic Intervention Team of the Universitair Ziekenhuis Brussel (control) with standard emergency care complemented with in-ambulance teleconsultation service by stroke experts (PreSSUB). Study Outcomes The primary efficacy endpoint is the call-to-brain imaging time. Secondary endpoints for the efficacy analysis include the prevalence of medical events diagnosed and corrected during in-ambulance teleconsultation, the proportion of patients with ischemic stroke receiving recanalization therapy, the assessment of disability, functional status, quality of life and overall well-being. Mortality at 90 days after stroke is the primary safety endpoint. Secondary safety analysis will involve the registration of any adverse event. Other analyses include assessment of feasibility and reliability and a health economic evaluation. PMID:27847888

Combining Standard Conventional Measures and Ecological Momentary Assessment of Depression, Anxiety and Coping Using Smartphone Application in Minor Stroke Population: A Longitudinal Study Protocol

PubMed Central

Vansimaeys, Camille; Zuber, Mathieu; Pitrat, Benjamin; Join-Lambert, Claire; Tamazyan, Ruben; Farhat, Wassim; Bungener, Catherine

2017-01-01

Context: Stroke has several consequences on survivors’ daily life even for those who experience short-lasting neurological symptoms with no functional disability. Depression and anxiety are common psychological disorders occurring after a stroke. They affect long-term outcomes and quality of life but they are difficult to diagnose because of the neurobiological consequences of brain lesions. Current research priority is given to the improvement of the detection and prevention of those post-stroke psychological disorders. Although previous studies have brought promising perspectives, their designs based on retrospective tools involve some limits regarding their ecological validity. Ecological Momentary Assessment (EMA) is an alternative to conventional instruments that could be a key in research for understanding processes that underlined post-stroke depression and anxiety onset. We aim to evaluate the feasibility and validity of anxiety, depression and coping EMA for minor stroke patients. Methods: Patients hospitalized in an Intensive Neuro-vascular Care Unit between April 2016 and January 2017 for a minor stroke is involved in a study based on an EMA methodology. We use a smartphone application in order to assess anxiety and depression symptoms and coping strategies four times a day during 1 week at three different times after stroke (hospital discharge, 2 and 4 months). Participants’ self-reports and clinician-rates of anxiety, depression and coping are collected simultaneously using conventional and standard instruments. Feasibility of the EMA method will be assessed considering the participation and compliance rate. Validity will be the assessed by comparing EMA and conventional self-report and clinician-rated measures. Discussion: We expect this study to contribute to the development of EMA using smartphone in minor stroke population. EMA method offers promising research perspective in the assessment and understanding of post-stroke psychological disorders. The development of EMA in stroke population could lead to clinical implications such as remotely psychological follow-ups during early supported discharge. Trial registration: European Clinical Trials Database Number 2014-A01937-40 PMID:28747895

Intravenous thrombolysis guided by a telemedicine consultation system for acute ischaemic stroke patients in China: the protocol of a multicentre historically controlled study

PubMed Central

Yuan, Ziwen; Wang, Bo; Li, Feijiang; Wang, Jing; Zhi, Jin; Luo, Erping; Liu, Zhirong; Zhao, Gang

2015-01-01

Introduction The rate of intravenous thrombolysis with tissue-type plasminogen activator or urokinase for stroke patients is extremely low in China. It has been demonstrated that a telestroke service may help to increase the rate of intravenous thrombolysis and improve stroke care quality in local hospitals. The aim of this study, also called the Acute Stroke Advancing Program, is to evaluate the effectiveness and safety of decision-making concerning intravenous thrombolysis via a telemedicine consultation system for acute ischaemic stroke patients in China. Methods and analysis This is a multicentre historically controlled study with a planned enrolment of 300 participants in each of two groups. The telestroke network consists of one hub hospital and 14 spoke hospitals in underserved regions of China. The usual stroke care quality in the spoke hospitals without guidance from the hub hospital will be used as the historical control. The telemedicine consultation system is an interactive, two-way, wireless, audiovisual system accessed on portable devices. The primary outcome is the percentage of patients treated with intravenous thrombolysis within 4.5 h of stroke onset. Ethics and dissemination The project has been approved by the Institutional Review Board of Xijing Hospital. The results will be published in scientific journals and presented to local government and relevant institutes. Trial registration number NCT02088346 (12 March 2014). PMID:25979867

Virtual Reality Therapy for Adults Post-Stroke: A Systematic Review and Meta-Analysis Exploring Virtual Environments and Commercial Games in Therapy

PubMed Central

Lohse, Keith R.; Hilderman, Courtney G. E.; Cheung, Katharine L.; Tatla, Sandy; Van der Loos, H. F. Machiel

2014-01-01

Background The objective of this analysis was to systematically review the evidence for virtual reality (VR) therapy in an adult post-stroke population in both custom built virtual environments (VE) and commercially available gaming systems (CG). Methods MEDLINE, CINAHL, EMBASE, ERIC, PSYCInfo, DARE, PEDro, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews were systematically searched from the earliest available date until April 4, 2013. Controlled trials that compared VR to conventional therapy were included. Population criteria included adults (>18) post-stroke, excluding children, cerebral palsy, and other neurological disorders. Included studies were reported in English. Quality of studies was assessed with the Physiotherapy Evidence Database Scale (PEDro). Results Twenty-six studies met the inclusion criteria. For body function outcomes, there was a significant benefit of VR therapy compared to conventional therapy controls, G = 0.48, 95% CI = [0.27, 0.70], and no significant difference between VE and CG interventions (P = 0.38). For activity outcomes, there was a significant benefit of VR therapy, G = 0.58, 95% CI = [0.32, 0.85], and no significant difference between VE and CG interventions (P = 0.66). For participation outcomes, the overall effect size was G = 0.56, 95% CI = [0.02, 1.10]. All participation outcomes came from VE studies. Discussion VR rehabilitation moderately improves outcomes compared to conventional therapy in adults post-stroke. Current CG interventions have been too few and too small to assess potential benefits of CG. Future research in this area should aim to clearly define conventional therapy, report on participation measures, consider motivational components of therapy, and investigate commercially available systems in larger RCTs. Trial Registration Prospero CRD42013004338 PMID:24681826

SALGOT - Stroke Arm Longitudinal study at the University of Gothenburg, prospective cohort study protocol

PubMed Central

2011-01-01

Background Recovery patterns of upper extremity motor function have been described in several longitudinal studies, but most of these studies have had selected samples, short follow up times or insufficient outcomes on motor function. The general understanding is that improvements in upper extremity occur mainly during the first month after the stroke incident and little if any, significant recovery can be gained after 3-6 months. The purpose of this study is to describe the recovery of upper extremity function longitudinally in a non-selected sample initially admitted to a stroke unit with first ever stroke, living in Gothenburg urban area. Methods/Design A sample of 120 participants with a first-ever stroke and impaired upper extremity function will be consecutively included from an acute stroke unit and followed longitudinally for one year. Assessments are performed at eight occasions: at day 3 and 10, week 3, 4 and 6, month 3, 6 and 12 after onset of stroke. The primary clinical outcome measures are Action Research Arm Test and Fugl-Meyer Assessment for Upper Extremity. As additional measures, two new computer based objective methods with kinematic analysis of arm movements are used. The ABILHAND questionnaire of manual ability, Stroke Impact Scale, grip strength, spasticity, pain, passive range of motion and cognitive function will be assessed as well. At one year follow up, two patient reported outcomes, Impact on Participation and Autonomy and EuroQol Quality of Life Scale, will be added to cover the status of participation and aspects of health related quality of life. Discussion This study comprises a non-selected population with first ever stroke and impaired arm function. Measurements are performed both using traditional clinical assessments as well as computer based measurement systems providing objective kinematic data. The ICF classification of functioning, disability and health is used as framework for the selection of assessment measures. The study design with several repeated measurements on motor function will give us more confident information about the recovery patterns after stroke. This knowledge is essential both for optimizing rehabilitation planning as well as providing important information to the patient about the recovery perspectives. Trial registration ClinicalTrials.gov: NCT01115348 PMID:21612620

Mobilisation of Hematopoietic CD34+ Precursor Cells in Patients with Acute Stroke Is Safe - Results of an Open-Labeled Non Randomized Phase I/II Trial

PubMed Central

Kraemer, Mathias; Schormann, Thorsten; Schlachetzki, Felix; Schuierer, Gerhard; Luerding, Ralph; Hennemann, Burkhard; Orso, Evelyn; Dabringhaus, Andreas; Winkler, Jürgen; Bogdahn, Ulrich

2011-01-01

Background Regenerative strategies in the treatment of acute stroke may have great potential. Hematopoietic growth factors mobilize hematopoietic stem cells and may convey neuroprotective effects. We examined the safety, potential functional and structural changes, and CD34+ cell–mobilization characteristics of G-CSF treatment in patients with acute ischemic stroke. Methods and Results Three cohorts of patients (8, 6, and 6 patients per cohort) were treated subcutaneously with 2.5, 5, or 10 µg/kg body weight rhG-CSF for 5 consecutive days within 12 hrs of onset of acute stroke. Standard treatment included IV thrombolysis. Safety monitoring consisted of obtaining standardized clinical assessment scores, monitoring of CD34+ stem cells, blood chemistry, serial neuroradiology, and neuropsychology. Voxel-guided morphometry (VGM) enabled an assessment of changes in the patients' structural parenchyma. 20 patients (mean age 55 yrs) were enrolled in this study, 5 of whom received routine thrombolytic therapy with r-tPA. G-CSF treatment was discontinued in 4 patients because of unrelated adverse events. Mobilization of CD34+ cells was observed with no concomitant changes in blood chemistry, except for an increase in the leukocyte count up to 75,500/µl. Neuroradiological and neuropsychological follow-up studies did not disclose any specific G-CSF toxicity. VGM findings indicated substantial atrophy of related hemispheres, a substantial increase in the CSF space, and a localized increase in parenchyma within the ischemic area in 2 patients. Conclusions We demonstrate a good safety profile for daily administration of G-CSF when begun within 12 hours after onset of ischemic stroke and, in part in combination with routine IV thrombolysis. Additional analyses using VGM and a battery of neuropsychological tests indicated a positive functional and potentially structural effect of G-CSF treatment in some of our patients. Trial Registration German Clinical Trial Register DRKS 00000723 PMID:21887230

Exercise Training and Recreational Activities to Promote Executive Functions in Chronic Stroke: A Proof-of-Concept Study

PubMed Central

Liu-Ambrose, Teresa; Eng, Janice J

2015-01-01

Background Stroke survivors represent a target population in need of intervention strategies to promote cognitive function and prevent dementia. Both exercise and recreational activities are promising strategies. We assessed the effect of a six-month exercise and recreation program on executive functions in adults with chronic stroke. Methods A six-month ancillary study within a multi-centre randomized trial. Twenty-eight chronic stroke survivors (i.e., ≥ 12 months since an index stroke) were randomized to one of two experimental groups: intervention (INT; n=12) or delayed intervention (D-INT; n=16). Participants of the INT group received a six-month community-based structured program that included two sessions of exercise training and one session of recreation and leisure activities per week. Participants of the D-INT group received usual care. The primary outcome measure was the Stroop Test, a cognitive test of selective attention and conflict resolution. Secondary cognitive measures included set shifting and working memory. Mood, functional capacity, and general balance and mobility were additional secondary outcome measures. Results Compared with the D-INT group, the INT group significantly improved selective attention and conflict resolution (p=0.02), working memory (p=0.04), and functional capacity (p=0.02) at the end of the six-month intervention period. Improved selective attention and conflict resolution was significantly associated with functional capacity at six months (r=0.39; p=0.04). Conclusions This is the first randomized study to demonstrate that an exercise and recreation program can significantly benefit executive functions in community-dwelling chronic stroke survivors who are mildly cognitively impaired – a population at high-risk for dementia and functional decline. Thus, clinicians should consider prescribing exercise and recreational activities in the cognitive rehabilitation of chronic stroke survivors. Clinical Trial Registration http://clinicaltrials.gov. Unique identifier: NCT01085240. PMID:25440324

Clinical trial registration in physical therapy journals: a cross-sectional study.

PubMed

Babu, Abraham Samuel; Veluswamy, Sundar Kumar; Rao, Pratiksha Tilak; Maiya, Arun G

2014-01-01

Clinical trial registration has become an important part of editorial policies of various biomedical journals, including a few physical therapy journals. However, the extent to which editorial boards enforce the need for trial registration varies across journals. The purpose of this study was to identify editorial policies and reporting of trial registration details in MEDLINE-indexed English-language physical therapy journals. This study was carried out using a cross-sectional design. Editorial policies on trial registration of MEDLINE-indexed member journals of the International Society of Physiotherapy Journal Editors (ISPJE) (Journal of Geriatric Physical Therapy, Journal of Hand Therapy, Journal of Neurologic Physical Therapy, Journal of Orthopaedic and Sports Physical Therapy, Journal of Physiotherapy [formerly Australian Journal of Physiotherapy], Journal of Science and Medicine in Sport, Manual Therapy, Physical Therapy, Physical Therapy in Sport, Physiotherapy, Physiotherapy Research International, Physiotherapy Theory and Practice, and Revista Brasileira de Fisioterapia) were reviewed in April 2013. Full texts of reports of clinical trials published in these journals between January 1, 2008, and December 31, 2012, were independently assessed for information on trial registration. Among the 13 journals, 8 recommended trial registration, and 6 emphasized prospective trial registration. As of April 2013, 4,618 articles were published between January 2008 and December 2012, of which 9% (417) were clinical trials and 29% (121/417) of these reported trial registration details. A positive trend in reporting of trial registration was observed from 2008 to 2012. The study was limited to MEDLINE-indexed ISPJE member journals. Editorial policies on trial registration of physical therapy journals and a rising trend toward reporting of trial registration details indicate a positive momentum toward trial registration. Physical therapy journal editors need to show greater commitment to prospective trial registration to make it a rule rather than an option.

Enhancing activities of daily living of chronic stroke patients in primary health care by modified constraint-induced movement therapy (HOMECIMT): study protocol for a cluster randomized controlled trial

PubMed Central

2013-01-01

Background Stroke leads to constant rehabilitation needs even at the chronic stage. However, although many stroke patients receive physical or occupational therapy in primary health care, treatment prescriptions do not generally specify therapeutic goals; in particular, participation is not established as an explicit therapeutic goal in the ambulatory setting. The primary aim of this study is to evaluate the efficacy of a therapy regimen for chronic stroke patients (modified ‘constraint-induced movement therapy (CIMT) at home’) with impaired hand or arm function with regard to the prerequisites of participation in everyday activities: a sufficient arm and hand function. ‘CIMT at home’ will be compared with conventional physical and occupational therapy (‘therapy as usual’). Methods/design The study is a parallel cluster randomized controlled trial with therapy practices as clusters (n = 48). After written consent from the patients (n = 144), the therapists will be randomly assigned to treat either the intervention or the control group. Blinded external assessors will evaluate the patients using standardized outcome measures before and after the intervention, and six months later. The two coprimary endpoint assessments of arm and hand function as prerequisites for participation (defined as equal involvement in activities of daily living) are the motor activity log (quality of arm and hand use) and the Wolf motor function test (arm and hand function). These assessments are made four weeks post-treatment and relativized to baseline performance. Changes in primary outcomes will be analyzed with mixed models, which consider the hierarchical structure of the data and will be adjusted to the baseline measurements and sex. The primary analysis will be the comparison of the two randomized groups, with respect to the adjusted averages for each of the two coprimary endpoints. To keep an overall significance level of 5%, the two endpoints will be tested at the significance level of 5% each in hierarchical order. Discussion A modification of the CIMT, feasible in the patients’ homes (CIMT at home), appears to be a promising therapeutic approach in the ambulatory care of chronic stroke patients. With proven efficacy and practicality, a participation-oriented, stroke-specific treatment would be available in primary care. Trial registration ClinicalTrials.gov NCT01343602 PMID:24124993

Mortality and morbidity during and after Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial: results by sex.

PubMed

Oparil, Suzanne; Davis, Barry R; Cushman, William C; Ford, Charles E; Furberg, Curt D; Habib, Gabriel B; Haywood, L Julian; Margolis, Karen; Probstfield, Jeffrey L; Whelton, Paul K; Wright, Jackson T

2013-05-01

To determine whether an angiotensin-converting enzyme inhibitor (lisinopril) or calcium channel blocker (amlodipine) is superior to a diuretic (chlorthalidone) in reducing cardiovascular disease incidence in sex subgroups, we carried out a prespecified subgroup analysis of 15 638 women and 17 719 men in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Total follow-up (active treatment + passive surveillance using national administrative databases to ascertain deaths and hospitalizations) was 8 to 13 years. The primary outcome was fatal coronary heart disease or nonfatal myocardial infarction. Secondary outcomes included all-cause mortality, stroke, combined cardiovascular disease (coronary heart disease death, nonfatal myocardial infarction, stroke, angina, coronary revascularization, heart failure [HF], or peripheral vascular disease), and end-stage renal disease. In-trial rates of HF, stroke, and combined cardiovascular disease were significantly higher for lisinopril compared with chlorthalidone, and rates of HF were significantly higher for amlodipine compared with chlorthalidone in both men and women. There were no significant treatment sex interactions. These findings did not persist through the extension period with the exception of the HF result for amlodipine versus chlorthalidone, which did not differ significantly by sex. For both women and men, rates were not lower in the amlodipine or lisinopril groups than in the chlorthalidone group for either the primary coronary heart disease outcome or any other cardiovascular disease outcome, and chlorthalidone-based treatment resulted in the lowest risk of HF. Neither lisinopril nor amlodipine is superior to chlorthalidone for initial treatment of hypertension in either women or men. Clinical Trial Registration- clinicaltrials.gov; Identifier: NCT00000542.

ASPREE-NEURO study protocol: A randomized controlled trial to determine the effect of low-dose aspirin on cerebral microbleeds, white matter hyperintensities, cognition, and stroke in the healthy elderly.

PubMed

Ward, Stephanie A; Raniga, Parnesh; Ferris, Nicholas J; Woods, Robyn L; Storey, Elsdon; Bailey, Michael J; Brodtmann, Amy; Yates, Paul A; Donnan, Geoffrey A; Trevaks, Ruth E; Wolfe, Rory; Egan, Gary F; McNeil, John J

2017-01-01

Rationale Cerebral microbleeds seen on brain magnetic resonance imaging are markers of small vessel disease, linked to cognitive dysfunction and increased ischemic and hemorrhagic stroke risk. Observational studies suggest that aspirin use may induce cerebral microbleeds, and associated overt intracranial hemorrhage, but this has not been definitively resolved. Aims ASPREE-NEURO will determine the effect of aspirin on cerebral microbleed development over three years in healthy adults aged 70 years and over, participating in the larger 'ASPirin in Reducing Events in the Elderly (ASPREE)' primary prevention study of aspirin. Sample size Five hundred and fifty-nine participants provide 75% power (two-sided p value of 0.05) to determine an average difference of 0.5 cerebral microbleed per person after three years. Methods and design A multi-center, randomized placebo-controlled trial of 100 mg daily aspirin in participants who have brain magnetic resonance imaging at study entry, one and three years after randomization and who undergo cognitive testing at the same time points. Study outcomes The primary outcome is the number of new cerebral microbleeds on magnetic resonance imaging after three years. Secondary outcomes are the number of new cerebral microbleeds after one year, change in volume of white matter hyperintensity, cognitive function, and stroke. Discussion ASPREE-NEURO will resolve whether aspirin affects the presence and number of cerebral microbleeds, their relationship with cognitive performance, and indicate whether consideration of cerebral microbleeds alters the risk-benefit profile of aspirin in primary prevention for older people. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12613001313729.

Exercise-induced changes in cardiovascular function after stroke: a randomized controlled trial

PubMed Central

Tang, Ada; Krassioukov, Andrei V; Madden, Kenneth M; Mohammadi, Azam; Tsang, Michael YC; Tsang, Teresa SM

2015-01-01

Background and aims Cardiovascular co-morbidities are prevalent after stroke, with heart disease, hypertension and impaired glucose tolerance present in the majority of cases. Exercise has the potential to mediate cardiovascular risk factors commonly present in people with stroke. This single-blinded randomized controlled trial compared the effects of high versus low intensity exercise on fitness, cardiovascular risk factors, and cardiac function after stroke. Methods Fifty participants (age 50–80y, >1y post-stroke) were randomized to a high-intensity Aerobic Exercise (AE) or low-intensity non-aerobic Balance/Flexibility (BF) program (6 months, 3 60-minute sessions/week). Outcomes assessed by VO2peak (primary outcome), arterial stiffness, ambulatory capacity, hemodynamics and cardiac function using echocardiography, and lipid, glucose and homocysteine levels. Assessors were blinded to group allocation. Results Twenty-three (92%) of 25 AE group participants (withdrawals unrelated to the intervention) and all BF group participants completed the program. One BF group participant experienced 2 non-injurious falls during class. No other adverse events occurred. There were no changes in VO2peak in either group (AE 16.9±7 to 17.4±7 ml•kg−1•min−1 vs. BF 16.9±6 to 16.6±5 ml•kg−1•min−1, P=0.45), but AE group demonstrated greater improvement in right atrial emptying fraction (AE 30±22 to 37±22% vs. BF 35±20 to 31±20%, P=0.04). Both groups demonstrated improvements in lipid profiles, glucose and homocysteine levels, and ambulatory capacity (P<0.04). Conclusions This was the first study to examine the effects of aerobic exercise after stroke on cardiovascular hemodynamics. High-intensity exercise improved right-sided function and early myocardial relaxation. Low-intensity exercise may also benefit plasma lipid, glucose and inflammatory markers, and ambulatory capacity. This study is an important step towards understanding mechanisms by which exercise may reduce cardiovascular risk and function. Clinical Trial Registration Information http://www.clinicaltrials.gov. Unique identifier: NCT01189045 PMID:24148695

Combined Cognitive-Motor Rehabilitation in Virtual Reality Improves Motor Outcomes in Chronic Stroke - A Pilot Study.

PubMed

Faria, Ana L; Cameirão, Mónica S; Couras, Joana F; Aguiar, Joana R O; Costa, Gabriel M; Bermúdez I Badia, Sergi

2018-01-01

Stroke is one of the most common causes of acquired disability, leaving numerous adults with cognitive and motor impairments, and affecting patients' capability to live independently. Virtual Reality (VR) based methods for stroke rehabilitation have mainly focused on motor rehabilitation but there is increasing interest toward the integration of cognitive training for providing more effective solutions. Here we investigate the feasibility for stroke recovery of a virtual cognitive-motor task, the Reh@Task, which combines adapted arm reaching, and attention and memory training. 24 participants in the chronic stage of stroke, with cognitive and motor deficits, were allocated to one of two groups (VR, Control). Both groups were enrolled in conventional occupational therapy, which mostly involves motor training. Additionally, the VR group underwent training with the Reh@Task and the control group performed time-matched conventional occupational therapy. Motor and cognitive competences were assessed at baseline, end of treatment (1 month) and at a 1-month follow-up through the Montreal Cognitive Assessment, Single Letter Cancelation, Digit Cancelation, Bells Test, Fugl-Meyer Assessment Test, Chedoke Arm and Hand Activity Inventory, Modified Ashworth Scale, and Barthel Index. Our results show that both groups improved in motor function over time, but the Reh@Task group displayed significantly higher between-group outcomes in the arm subpart of the Fugl-Meyer Assessment Test. Improvements in cognitive function were significant and similar in both groups. Overall, these results are supportive of the viability of VR tools that combine motor and cognitive training, such as the Reh@Task. Trial Registration: This trial was not registered because it is a small clinical study that addresses the feasibility of a prototype device.

Prospective, Multi-Centre, Single-Arm Study of Mechanical Thrombectomy using Solitaire FR in Acute Ischemic Stroke-STAR

PubMed Central

Pereira, Vitor M; Gralla, Jan; Davalos, Antoni; Bonafé, Alain; Castaño, Carlos; Chapot, Rene; Liebeskind, David S; Nogueira, Raul G; Arnold, Marcel; Sztajzel, Roman; Liebig, Thomas; Goyal, Mayank; Besselmann, Michael; Moreno, Alfredo; Schroth, Gerhard

2013-01-01

Background and Purpose Mechanical thrombectomy using stent retriever devices have been advocated to increase revascularization in intracranial vessel occlusion. We present the results of a large prospective study on the use of the Solitaire FR in patients with acute ischemic stroke. Methods STAR was an international, multicenter, prospective, single-arm study of Solitaire FR thrombectomy in patients with large vessel anterior circulation strokes treated within 8 hours of symptom onset. Strict criteria for site selection were applied. The primary endpoint was the revascularization rate (3TICI 2b) of the occluded vessel as determined by an independent core lab. The secondary endpoint was the rate of good functional outcome (defined as 90-day modified Rankin scale (mRS) 0–2). Results A total of 202 patients were enrolled across 14 comprehensive stroke centers in Europe, Canada and Australia. The median age was 72 years, 60% were female patients. The median National Institute of Health Stroke Scale (NIHSS) was 17. Most proximal intracranial occlusion was the internal carotid artery in 18%, the middle cerebral artery in 82%. Successful revascularization was achieved in 79.2% of patients. Device and/or procedure related severe adverse events were found in 7.4%. Favorable neurological outcome was found in 57.9%. The mortality rate was 6.9%. Any intracranial hemorrhagic transformation was found in 18.8% of patients, 1.5% were symptomatic. Conclusions In this single arm study, treatment with the Solitaire™ FR device in intracranial anterior circulation occlusions results in high rates of revascularization, low risk of clinically relevant procedural complications, and good clinical outcomes in combination with low mortality at 90 days. Clinical Trial Registration This study is registered with ClinicalTrials.gov, number NCT01327989. PMID:23908066

Combined Cognitive-Motor Rehabilitation in Virtual Reality Improves Motor Outcomes in Chronic Stroke – A Pilot Study

PubMed Central

Faria, Ana L.; Cameirão, Mónica S.; Couras, Joana F.; Aguiar, Joana R. O.; Costa, Gabriel M.; Bermúdez i Badia, Sergi

2018-01-01

Stroke is one of the most common causes of acquired disability, leaving numerous adults with cognitive and motor impairments, and affecting patients’ capability to live independently. Virtual Reality (VR) based methods for stroke rehabilitation have mainly focused on motor rehabilitation but there is increasing interest toward the integration of cognitive training for providing more effective solutions. Here we investigate the feasibility for stroke recovery of a virtual cognitive-motor task, the Reh@Task, which combines adapted arm reaching, and attention and memory training. 24 participants in the chronic stage of stroke, with cognitive and motor deficits, were allocated to one of two groups (VR, Control). Both groups were enrolled in conventional occupational therapy, which mostly involves motor training. Additionally, the VR group underwent training with the Reh@Task and the control group performed time-matched conventional occupational therapy. Motor and cognitive competences were assessed at baseline, end of treatment (1 month) and at a 1-month follow-up through the Montreal Cognitive Assessment, Single Letter Cancelation, Digit Cancelation, Bells Test, Fugl-Meyer Assessment Test, Chedoke Arm and Hand Activity Inventory, Modified Ashworth Scale, and Barthel Index. Our results show that both groups improved in motor function over time, but the Reh@Task group displayed significantly higher between-group outcomes in the arm subpart of the Fugl-Meyer Assessment Test. Improvements in cognitive function were significant and similar in both groups. Overall, these results are supportive of the viability of VR tools that combine motor and cognitive training, such as the Reh@Task. Trial Registration: This trial was not registered because it is a small clinical study that addresses the feasibility of a prototype device. PMID:29899719

ANNALS OF THE NEW YORK ACADEMY OF SCIENCES

PubMed Central

Hanna, Michael S; Mohan, Puneet; Knabb, Robert; Gupta, Elora; Frost, Charles; Lawrence, John H

2014-01-01

The factor Xa inhibitor apixaban is one of the novel anticoagulants to emerge as alternatives to long-standing standards of care that include low-molecular-weight heparin and warfarin. The development of apixaban reflects a strategy to optimize the clinical pharmacology profile, dosing posology, trial designs, and statistical analyses across multiple indications, and to seek alignment with global health authorities. The primary objective of dose selection was to maintain balance between efficacy and bleeding risk. Twice-daily dosing of apixaban, rather than once daily, was chosen to lower peak concentrations and reduce fluctuations between peak and trough levels. Our discussion here focuses on the use of apixaban for stroke prevention in nonvalvular atrial fibrillation (NVAF). Supporting this indication, a pair of registrational trials was conducted that enrolled the full spectrum of patients who, by guidelines, were eligible for anticoagulation. In the AVERROES study of patients who were unsuitable for warfarin therapy, apixaban was superior to aspirin in reducing the risk of stroke or systemic embolism (SSE), without a significant increase in major bleeding (MB). In the ARISTOTLE (Apixaban for Reduction In STroke and Other ThromboemboLic Events in Atrial Fibrillation) study, apixaban was superior to warfarin on the rates of SSE, MB, and all-cause mortality. Overall, these studies have demonstrated a substantially favorable benefit–risk profile for apixaban over warfarin and aspirin in NVAF. PMID:25377080

Promoting Optimal Physical Exercise for Life (PROPEL): aerobic exercise and self-management early after stroke to increase daily physical activity—study protocol for a stepped-wedge randomised trial

PubMed Central

Mansfield, Avril; Brooks, Dina; Tang, Ada; Taylor, Denise; Inness, Elizabeth L; Kiss, Alex; Middleton, Laura; Biasin, Louis; Fleck, Rebecca; French, Esmé; LeBlanc, Kathryn; Aqui, Anthony; Danells, Cynthia

2017-01-01

Introduction Physical exercise after stroke is essential for improving recovery and general health, and reducing future stroke risk. However, people with stroke are not sufficiently active on return to the community after rehabilitation. We developed the Promoting Optimal Physical Exercise for Life (PROPEL) programme, which combines exercise with self-management strategies within rehabilitation to promote ongoing physical activity in the community after rehabilitation. This study aims to evaluate the effect of PROPEL on long-term participation in exercise after discharge from stroke rehabilitation. We hypothesise that individuals who complete PROPEL will be more likely to meet recommended frequency, duration and intensity of exercise compared with individuals who do not complete the programme up to 6 months post discharge from stroke rehabilitation. Methods and analysis Individuals undergoing outpatient stroke rehabilitation at one of six hospitals will be recruited (target n=192 total). A stepped-wedge design will be employed; that is, the PROPEL intervention (group exercise plus self-management) will be ‘rolled out’ to each site at a random time within the study period. Prior to roll-out of the PROPEL intervention, sites will complete the control intervention (group aerobic exercise only). Participation in physical activity for 6 months post discharge will be measured via activity and heart rate monitors, and standardised physical activity questionnaire. Adherence to exercise guidelines will be evaluated by (1) number of ‘active minutes’ per week (from the activity monitor), (2) amount of time per week when heart rate is within a target range (ie, 55%–80% of age-predicted maximum) and (3) amount of time per week completing ‘moderate’ or ‘strenuous’ physical activities (from the questionnaire). We will compare the proportion of active and inactive individuals at 6 months post intervention using mixed-model logistic regression, with fixed effects of time and phase and random effect of cluster (site). Ethics and dissemination To date, research ethics approval has been received from five of the six sites, with conditional approval granted by the sixth site. Results will be disseminated directly to study participants at the end of the trial, and to other stake holders via publication in a peer-reviewed journal. Trial registration number NCT02951338; Pre-results. PMID:28667222

Clinical characteristics, precipitating factors, management and outcome of patients with prior stroke hospitalised with heart failure: an observational report from the Middle East

PubMed Central

Khafaji, Hadi A R; Sulaiman, Kadhim; Singh, Rajvir; AlHabib, Khalid F; Asaad, Nidal; Alsheikh-Ali, Alawi; Al-Jarallah, Mohammed; Bulbanat, Bassam; AlMahmeed, Wael; Ridha, Mustafa; Bazargani, Nooshin; Amin, Haitham; Al-Motarreb, Ahmed; AlFaleh, Hussam; Elasfar, Abdelfatah; Panduranga, Prashanth; Al Suwaidi, Jassim

2015-01-01

Objectives The purpose of this study is to report the prevalence, clinical characteristics, precipitating factors, management and outcome of patients with prior stroke hospitalised with acute heart failure (HF). Design Retrospective analysis of prospectively collected data. Setting Data were derived from Gulf CARE (Gulf aCute heArt failuRe rEgistry), a prospective multicentre study of consecutive patients hospitalised with acute HF in 2012 in seven Middle Eastern countries and analysed according to the presence or absence of prior stroke; demographics, management and outcomes were compared. Participants A total of 5005 patients with HF. Outcome measures In-hospital and 1-year outcome. Results The prevalence of prior stroke in patients with HF was 8.1%. Patients with stroke with HF were more likely to be admitted under the care of internists rather than cardiologists. When compared with patients without stroke, patients with stroke were more likely to be older and to have diabetes mellitus, hypertension, atrial fibrillation, hyperlipidaemia, chronic kidney disease, ischaemic heart disease, peripheral arterial disease and left ventricular dysfunction (p=0.001 for all). Patients with stroke were less likely to be smokers (0.003). There were no significant differences in terms of precipitating risk factors for HF hospitalisation between the two groups. Patients with stroke with HF had a longer hospital stay (mean±SD days; 11±14 vs 9±13, p=0.03), higher risk of recurrent strokes and 1-year mortality rates (32.7% vs 23.2%, p=0.001). Multivariate logistic regression analysis showed that stroke is an independent predictor of in-hospital and 1-year mortality. Conclusions This observational study reports high prevalence of prior stroke in patients hospitalised with HF. Internists rather than cardiologists were the predominant caregivers in this high-risk group. Patients with stroke had higher risk of in-hospital recurrent strokes and long-term mortality rates. Trial registration number NCT01467973. PMID:25908674

How is rehabilitation with and without an integrated self-management approach perceived by UK community-dwelling stroke survivors? A qualitative process evaluation to explore implementation and contextual variations

PubMed Central

Jones, Fiona; McKevitt, Christopher; Riazi, Afsane; Liston, Matthew

2017-01-01

Objective Self-management programmes could support long-term needs after stroke and using methods integrated into rehabilitation is one option. To explore theoretical assumptions and possible mechanisms of implementation a process evaluation was delivered alongside a cluster trial which has demonstrated feasibility of an integrated self-management programme (Bridges SMP) in community-dwelling stroke survivors. This paper aims to show the extent to which experiences from stroke survivors receiving rehabilitation in control (usual care) and intervention (integrated self-management) sites reflected the differences in rehabilitation received and whether their understandings aligned with the self-management approach employed. Design Semistructured qualitative interviews carried out as part of a process evaluation analysed thematically. Setting Study was based in South London; all interviews were carried out in participants' home setting. Participants 22 stroke participants recruited; 12 from integrated self-management sites and 10 from usual care sites. Results All participants revealed shared appreciation of knowledge and support from therapists but subtle differences emerged between sites in respect to perceptions about responsibility, control and how previous experiences were used. Accounts depicted a variance regarding who had structured and planned their rehabilitation, with greater flexibility about content and involvement perceived by participants from the integrated self-management sites. They also provided accounts and experiences which aligned with principles of the intervention, such as self-discovery and problem-solving. Conclusions The findings reflect our theoretical assumptions and possible mechanisms of implementation that rehabilitation with a focus on supporting self-management is reflected in accounts and understandings of stroke survivors. Taken together with our previous research this justifies evaluating the effectiveness of Bridges SMP in a larger sample to further contribute to an understanding of the functioning of the intervention, implementation, contextual factors and mechanisms of impact. Trial registration number ISRCTN42534180; Post-results. PMID:28373253

Efficiency of physical therapy on postural imbalance after stroke: study protocol for a systematic review and meta-analysis

PubMed Central

Hugues, A; Di Marco, J; Janiaud, P; Xue, Y; Pires, J; Khademi, H; Cucherat, M; Bonan, I; Gueyffier, F; Rode, G

2017-01-01

Introduction Stroke frequently results in balance disorders, leading to lower levels of activity and a diminution in autonomy. Current physical therapies (PT) aiming to reduce postural imbalance have shown a large variety of effects with low levels of evidence. The objectives are to determine the efficiency of PT in recovering from postural imbalance in patients after a stroke and to assess which PT is more effective. Methods and analysis We will search several databases from inception to October 2015. Only randomised controlled trials assessing PT to recover from poststroke postural imbalance in adults will be considered. Outcome measures will be the Berg Balance Scale (BBS), the Postural Assessment Scale for Stroke (PASS), the ‘weight-bearing asymmetry’ (WBA), the ‘centre of pressure’ (COP) and the ‘limit of stability’ (LOS). WBA, COP and LOS are measured by a (sitting or standing) static evaluation on force plate or another device. Two independent reviewers will screen titles, abstracts and full-text articles, evaluate the risk of bias and will perform data extraction. In addition to the outcomes, measures of independence will be analysed. This study will aim at determining the effects of PT on the function (WBA, COP, LOS), the activity (BBS, PASS) and the independence of patients. Subgroup analyses will be planned according to the location of brain lesion (hemispheric, brainstem or cerebellum), the time since stroke (early, late, chronic), the PT (type, main aim (direct effect or generalisation), overall duration), the type of approaches (top-down or bottom-up) and the methodological quality of studies. Ethics and dissemination No ethical statement will be required. The results will be published in a peer-reviewed journal. This meta-analysis aims at managing the rehabilitation after postural imbalance by PT after a stroke. Trial registration number Prospero CRD42016037966;Pre-results. PMID:28137928

A Randomized Factorial Trial of Vitamins C, E, and Beta-Carotene in the Secondary Prevention of Cardiovascular Events in Women

PubMed Central

Cook, Nancy R.; Albert, Christine M.; Gaziano, J. Michael; Zaharris, Elaine; MacFadyen, Jean; Danielson, Eleanor; Buring, Julie E.; Manson, JoAnn E.

2007-01-01

Background Randomized trials have largely failed to support an effect of antioxidant vitamins on risk of cardiovascular disease (CVD). Few trials have examined interactions among antioxidants, and no previous trial has examined the individual effect of vitamin C on CVD. Methods WACS tested the effects of vitamins C (500 mg daily), E (600 IU every other day), and beta-carotene (50 mg every other day) on the combined outcome of myocardial infarction (MI), stroke, coronary revascularization, or CVD death among 8,171 female health professionals at increased risk in a 2×2×2 factorial design. Participants were 40 years or older with a prior history of CVD or three or more CVD risk factors, and were followed an average 9.4 years, from 1995-96 to 2005. Results 1,450 women experienced one or more CVD outcomes. There was no overall effect of vitamin C (RR=1.02, 95% CI=0.92-1.13, p=0.71), vitamin E (RR=0.94, 95% CI=0.85-1.04, p=0.23), or beta-carotene (RR=1.02, 95% CI=0.92-1.13, p=0.71) on the primary combined endpoint, or on the individual secondary outcomes of MI, stroke, coronary revascularization, or CVD death. A marginally significant reduction in the primary outcome with active vitamin E was observed among the pre-specified subgroup of women with prior CVD (RR=0.89, 95% CI=0.79-1.00, p=0.04; p-interaction=0.07). There were no significant interactions between agents for the primary endpoint, but those randomized to both active vitamin C and E experienced fewer strokes (p for interaction=0.03). Conclusion There were no overall effects of vitamins C, E or beta-carotene on cardiovascular events among women at high risk for CVD. Trial Registration clinicaltrials.gov Identifier: NCT00000541 PMID:17698683

More outcomes than trials: a call for consistent data collection across stroke rehabilitation trials.

PubMed

Ali, M; English, C; Bernhardt, J; Sunnerhagen, K S; Brady, M

2013-01-01

Stroke survivors experience complex combinations of impairments, activity limitations, and participation restrictions. The essential components of stroke rehabilitation remain elusive. Determining efficacy in randomized controlled trials (RCTs) is challenging; there is no commonly agreed primary outcome measure for rehabilitation trials. Clinical guidelines depend on proof of efficacy in RCTs and meta-analyses. However, diverse trial aims, differing methods, inconsistent data collection, and use of multiple assessment tools hinder comparability across trials. Consistent data collection in acute stroke trials has facilitated meta-analyses to inform trial design and clinical practice. With few exceptions, inconsistent data collection has hindered similar progress in stroke rehabilitation research. There is an urgent need for the routine collection of a core dataset of common variables in rehabilitation trials. The European Stroke Organisation Outcomes Working Group, the National Institutes of Neurological Disorders and Stroke Common Data Elements project, and the Collaborative Stroke Audit and Research project have called for consistency in data collection in stroke trials. Standardizing data collection can decrease study start up times, facilitate data sharing, and inform clinical guidelines. Although achieving consensus on which outcome measures to use in stroke rehabilitation trials is a considerable task, perhaps a feasible starting point is to achieve consistency in the collection of data on demography, stroke severity, and stroke onset to inclusion times. Longer term goals could include the development of a consensus process to establish the core dataset. This should be endorsed by researchers, funders, and journal editors in order to facilitate sustainable change. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

Statistical analysis plan of the head position in acute ischemic stroke trial pilot (HEADPOST pilot).

PubMed

Olavarría, Verónica V; Arima, Hisatomi; Anderson, Craig S; Brunser, Alejandro; Muñoz-Venturelli, Paula; Billot, Laurent; Lavados, Pablo M

2017-02-01

Background The HEADPOST Pilot is a proof-of-concept, open, prospective, multicenter, international, cluster randomized, phase IIb controlled trial, with masked outcome assessment. The trial will test if lying flat head position initiated in patients within 12 h of onset of acute ischemic stroke involving the anterior circulation increases cerebral blood flow in the middle cerebral arteries, as measured by transcranial Doppler. The study will also assess the safety and feasibility of patients lying flat for ≥24 h. The trial was conducted in centers in three countries, with ability to perform early transcranial Doppler. A feature of this trial was that patients were randomized to a certain position according to the month of admission to hospital. Objective To outline in detail the predetermined statistical analysis plan for HEADPOST Pilot study. Methods All data collected by participating researchers will be reviewed and formally assessed. Information pertaining to the baseline characteristics of patients, their process of care, and the delivery of treatments will be classified, and for each item, appropriate descriptive statistical analyses are planned with comparisons made between randomized groups. For the outcomes, statistical comparisons to be made between groups are planned and described. Results This statistical analysis plan was developed for the analysis of the results of the HEADPOST Pilot study to be transparent, available, verifiable, and predetermined before data lock. Conclusions We have developed a statistical analysis plan for the HEADPOST Pilot study which is to be followed to avoid analysis bias arising from prior knowledge of the study findings. Trial registration The study is registered under HEADPOST-Pilot, ClinicalTrials.gov Identifier NCT01706094.

Sight Impairment registration due to stroke-A small yet significant rise?

PubMed

Bunce, Catey; Zekite, Antra; Wormald, Richard; Rowe, Fiona

2017-12-01

In the United Kingdom, when an individual's sight falls to and remains at a certain threshold, they may be offered registration as sight impaired. Recent analysis of causes of registrable sight impairment in England/Wales indicated that visual impairment due to stroke had increased as a proportionate cause of sight loss. We aim to assess whether there is evidence of an increase in incidence of certification for sight impairment due to stroke in England/Wales between 2008 and 2014. The number of certifications with a main cause of sight impairment being stroke was obtained from the Certifications Office London. Directly standardized rates per 100,000 were computed with 95% confidence intervals and examined. Poisson regression was used to assess evidence of trend over time. In the year ending 31st March 2008, 992 people were newly certified with stroke with an estimated DSR of 2.1 (2.0 to 2.2) per 100,000 persons at risk. In the year ending March 31st 2014, there were 1310 certifications with a DSR of 2.5 (2.4 to 2.7). Figures were higher for men than women. Poisson regression indicated an estimated incidence rate ratio of 1.03 per year with 95% confidence intervals of 1.028 to 1.051, P  < .001. These data suggest a small but statistically significant increase in the incidence of certifiable visual impairment due to stroke between 2008 and 2014. Figures are, however, considerably lower than estimated, perhaps suggesting that more should be done to address the visual needs of those who have suffered stroke.

Effects of substituting a portion of standard physiotherapy time with virtual reality games among community-dwelling stroke survivors

PubMed Central

2013-01-01

Background Evidence indicates that the continuation of therapy among community-dwelling stroke survivors improves physical function. Community rehabilitation programmes often face limitations in terms of resources. It is imperative to include new motivational interventions to encourage some level of non-clinician management. The aim of this study was to determine whether there were any changes in physical function and activities of daily living when substituting a portion of the standard physiotherapy time with virtual reality games among community-dwelling stroke survivors. Methods In this controlled trial, the experimental group received 30 minutes of virtual reality balance games in addition to 90 minutes of standard physiotherapy. The control group continued with their two hours of routine standard physiotherapy. Both groups received 12 therapy sessions: two-hour sessions twice per week for six continuous weeks. Changes in physical function, activities of daily living and balance ability were assessed using the Timed Up and Go test, 30-second Sit to Stand test, Timed Ten-Metre Walk test, Six-Minute Walk test and the Barthel Index, and static balance was assessed using a probalance board. Results Twenty-eight participants completed post-intervention assessments. The results showed a significant within-subject effect on the Timed Up and Go test: F (1, 26) = 5.83, p = 0.02; and the 30-second Sit to Stand test; F (1, 26) = 13.50, p = 0.001. The between-subject effect was not significant (p > 0.05) for any of the outcome measurements. Conclusion Substituting a portion of the standard physiotherapy time with virtual reality games was equally effective in maintaining physical function outcomes and activities of daily living among community-dwelling stroke survivors. Trial Registration Australia and New Zealand Clinical Trials Register, ACTRN12613000478718 PMID:24330250

Absence of Cortical Vein Opacification Is Associated with Lack of Intra-arterial Therapy Benefit in Stroke.

PubMed

Jansen, Ivo G H; van Vuuren, Annemieke B; van Zwam, Wim H; van den Wijngaard, Ido R; Berkhemer, Olvert A; Lingsma, Hester F; Slump, Cornelis H; van Oostenbrugge, Robert J; Treurniet, Kilian M; Dippel, Diederik W J; van Walderveen, Marianne A A; van der Lugt, Aad; Roos, Yvo B W E M; Marquering, Henk A; Majoie, Charles B L M; van den Berg, René

2018-02-01

Purpose To assess the degree of cortical vein opacification in patients with internal carotid artery or middle cerebral artery (MCA) stroke and to evaluate the relationship with treatment benefit from intra-arterial therapy (IAT). Materials and Methods Written informed consent was obtained from all patients in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands. From the trial's database, all patients (recruited from December 2010 until March 2014) with baseline computed tomographic (CT) angiograms were retrospectively included. Enhancement of the vein of Labbé, sphenoparietal sinus, and superficial middle cerebral vein was graded by one neuroradiologist, as follows: 0, not visible; 1, moderate opacification; and 2, full opacification. The sum for the ipsilateral hemisphere was calculated, resulting in the cortical vein opacification score (COVES) (range, 0-6). Primary outcome was the modified Rankin Scale score at 90 days. Association with treatment according to full cortical vein score and different dichotomized cutoff points was estimated with ordinal logistic regression. Interobserver agreement was assessed by two separate observers who reviewed 100 studies each. Results In total, 397 patients were analyzed. Interaction of the cortical vein score with treatment was significant (P = .044) when dichotomized COVES was 0 versus more than 0. The adjusted odds ratio for shift toward better functional outcome was 1.0 (95% confidence interval [CI]: 0.5, 2.0) for a COVES of 0 (n = 123) and 2.2 (95% CI: 1.6, 4.1) for a COVES greater than 0 (n = 274). The multirater κ value was 0.73. Conclusion In this study, patients with acute middle cerebral artery stroke with absence of cortical vein opacification in the affected hemisphere (COVES = 0) appeared to have no benefit from IAT, whereas patients with venous opacification (COVES >0) were shown to benefit from IAT. © RSNA, 2017 Clinical trial registration nos. NTR(1804) and ISRCTN10888758 Online supplemental material is available for this article.

Clinical trial registration in oral health journals.

PubMed

Smaïl-Faugeron, V; Fron-Chabouis, H; Durieux, P

2015-03-01

Prospective registration of randomized controlled trials (RCTs) represents the best solution to reporting bias. The extent to which oral health journals have endorsed and complied with RCT registration is unknown. We identified journals publishing RCTs in dentistry, oral surgery, and medicine in the Journal Citation Reports. We classified journals into 3 groups: journals requiring or recommending trial registration, journals referring indirectly to registration, and journals providing no reference to registration. For the 5 journals with the highest 2012 impact factors in each group, we assessed whether RCTs with results published in 2013 had been registered. Of 78 journals examined, 32 (41%) required or recommended trial registration, 19 (24%) referred indirectly to registration, and 27 (35%) provided no reference to registration. We identified 317 RCTs with results published in the 15 selected journals in 2013. Overall, 73 (23%) were registered in a trial registry. Among those, 91% were registered retrospectively and 32% did not report trial registration in the published article. The proportion of trials registered was not significantly associated with editorial policies: 29% with results in journals that required or recommended registration, 15% in those that referred indirectly to registration, and 21% in those providing no reference to registration (P = 0.05). Less than one-quarter of RCTs with results published in a sample of oral health journals were registered with a public registry. Improvements are needed with respect to how journals inform and require their authors to register their trials. © International & American Associations for Dental Research.

Value of the CHA2DS2-VASc score and Fabry-specific score for predicting new-onset or recurrent stroke/TIA in Fabry disease patients without atrial fibrillation.

PubMed

Liu, Dan; Hu, Kai; Schmidt, Marie; Müntze, Jonas; Maniuc, Octavian; Gensler, Daniel; Oder, Daniel; Salinger, Tim; Weidemann, Frank; Ertl, Georg; Frantz, Stefan; Wanner, Christoph; Nordbeck, Peter

2018-05-24

To evaluate potential risk factors for stroke or transient ischemic attacks (TIA) and to test the feasibility and efficacy of a Fabry-specific stroke risk score in Fabry disease (FD) patients without atrial fibrillation (AF). FD patients often experience cerebrovascular events (stroke/TIA) at young age. 159 genetically confirmed FD patients without AF (aged 40 ± 14 years, 42.1% male) were included, and risk factors for stroke/TIA events were determined. All patients were followed up over a median period of 60 (quartiles 35-90) months. The pre-defined primary outcomes included new-onset or recurrent stroke/TIA and all-cause death. Prior stroke/TIA (HR 19.97, P < .001), angiokeratoma (HR 4.06, P = .010), elevated creatinine (HR 3.74, P = .011), significant left ventricular hypertrophy (HR 4.07, P = .017), and reduced global systolic strain (GLS, HR 5.19, P = .002) remained as independent risk predictors of new-onset or recurrent stroke/TIA in FD patients without AF. A Fabry-specific score was established based on above defined risk factors, proving somehow superior to the CHA 2 DS 2 -VASc score in predicting new-onset or recurrent stroke/TIA in this cohort (AUC 0.87 vs. 0.75, P = .199). Prior stroke/TIA, angiokeratoma, renal dysfunction, left ventricular hypertrophy, and global systolic dysfunction are independent risk factors for new-onset or recurrent stroke/TIA in FD patients without AF. It is feasible to predict new or recurrent cerebral events with the Fabry-specific score based on the above defined risk factors. Future studies are warranted to test if FD patients with high risk for new-onset or recurrent stroke/TIA, as defined by the Fabry-specific score (≥ 2 points), might benefit from antithrombotic therapy. Clinical trial registration HEAL-FABRY (evaluation of HEArt invoLvement in patients with FABRY disease, NCT03362164).

Varied overground walking-task practice versus body-weight-supported treadmill training in ambulatory adults within one year of stroke: a randomized controlled trial protocol

PubMed Central

2011-01-01

Background Although task-oriented training has been shown to improve walking outcomes after stroke, it is not yet clear whether one task-oriented approach is superior to another. The purpose of this study is to compare the effectiveness of the Motor Learning Walking Program (MLWP), a varied overground walking task program consistent with key motor learning principles, to body-weight-supported treadmill training (BWSTT) in community-dwelling, ambulatory, adults within 1 year of stroke. Methods/Design A parallel, randomized controlled trial with stratification by baseline gait speed will be conducted. Allocation will be controlled by a central randomization service and participants will be allocated to the two active intervention groups (1:1) using a permuted block randomization process. Seventy participants will be assigned to one of two 15-session training programs. In MLWP, one physiotherapist will supervise practice of various overground walking tasks. Instructions, feedback, and guidance will be provided in a manner that facilitates self-evaluation and problem solving. In BWSTT, training will emphasize repetition of the normal gait cycle while supported over a treadmill, assisted by up to three physiotherapists. Outcomes will be assessed by a blinded assessor at baseline, post-intervention and at 2-month follow-up. The primary outcome will be post-intervention comfortable gait speed. Secondary outcomes include fast gait speed, walking endurance, balance self-efficacy, participation in community mobility, health-related quality of life, and goal attainment. Groups will be compared using analysis of covariance with baseline gait speed strata as the single covariate. Intention-to-treat analysis will be used. Discussion In order to direct clinicians, patients, and other health decision-makers, there is a need for a head-to-head comparison of different approaches to active, task-related walking training after stroke. We hypothesize that outcomes will be optimized through the application of a task-related training program that is consistent with key motor learning principles related to practice, guidance and feedback. Trial Registration ClinicalTrials.gov # NCT00561405 PMID:22018267

Effect of screening and lifestyle counselling on incidence of ischaemic heart disease in general population: Inter99 randomised trial.

PubMed

Jørgensen, Torben; Jacobsen, Rikke Kart; Toft, Ulla; Aadahl, Mette; Glümer, Charlotte; Pisinger, Charlotta

2014-06-09

To investigate the effect of systematic screening for risk factors for ischaemic heart disease followed by repeated lifestyle counselling on the 10 year development of ischaemic heart disease at a population level. Randomised controlled community based trial. Suburbs of Copenhagen, Denmark. 59,616 people aged 30-60 years randomised with different age and sex randomisation ratios to an intervention group (n = 11,629) and a control group (n = 47,987). The intervention group was invited for screening, risk assessment, and lifestyle counselling up to four times over a five year period. All participants with an unhealthy lifestyle had individually tailored lifestyle counselling at all visits (at baseline and after one and three years); those at high risk of ischaemic heart disease, according to predefined criteria, were furthermore offered six sessions of group based lifestyle counselling on smoking cessation, diet, and physical activity. After five years all were invited for a final counselling session. Participants were referred to their general practitioner for medical treatment, if relevant. The control group was not invited for screening. The primary outcome measure was incidence of ischaemic heart disease in the intervention group compared with the control group. Secondary outcome measures were stroke, combined events (ischaemic heart disease, stroke, or both), and mortality. 6091 (52.4%) people in the intervention group participated at baseline. Among 5978 people eligible at five year follow-up (59 died and 54 emigrated), 4028 (67.4%) attended. A total of 3163 people died in the 10 year follow-up period. Among 58,308 without a history of ischaemic heart disease at baseline, 2782 developed ischaemic heart disease. Among 58,940 without a history of stroke at baseline, 1726 developed stroke. No significant difference was seen between the intervention and control groups in the primary end point (hazard ratio for ischaemic heart disease 1.03, 95% confidence interval 0.94 to 1.13) or in the secondary endpoints (stroke 0.98, 0.87 to 1.11; combined endpoint 1.01, 0.93 to 1.09; total mortality 1.00, 0.91 to 1.09). A community based, individually tailored intervention programme with screening for risk of ischaemic heart disease and repeated lifestyle intervention over five years had no effect on ischaemic heart disease, stroke, or mortality at the population level after 10 years.Trial registration Clinical trials NCT00289237. © Jørgensen et al 2014.

Efficacy of a Community-Based Physical Activity Program KM2H2 for Stroke and Heart Attack Prevention among Senior Hypertensive Patients: A Cluster Randomized Controlled Phase-II Trial

PubMed Central

Gong, Jie; Chen, Xinguang; Li, Sijian

2015-01-01

Objective To evaluate the efficacy of the program Keep Moving toward Healthy Heart and Healthy Brain (KM2H2) in encouraging physical activities for the prevention of heart attack and stroke among hypertensive patients enrolled in the Community-Based Hypertension Control Program (CBHCP). Design Cluster randomized controlled trial with three waves of longitudinal assessments at baseline, 3 and 6 months post intervention. Setting Community-based and patient-centered self-care for behavioral intervention in urban settings of China. Participants A total of 450 participants diagnosed with hypertension from 12 community health centers in Wuhan, China were recruited, and were randomly assigned by center to receive either KM2H2 plus standard CBHCP care (6 centers and 232 patients) or the standard care only (6 centers and 218 patients). Intervention KM2H2 is a behavioral intervention guided by the Transtheoretical Model, the Model of Personalized Medicine and Social Capital Theory. It consists of six intervention sessions and two booster sessions engineered in a progressive manner. The purpose is to motivate and maintain physical activities for the prevention of heart attack and stroke. Outcome Measures Heart attack and stroke (clinically diagnosed, primary outcome), blood pressure (measured, secondary outcome), and physical activity (self-report, tertiary outcome) were assessed at the individual level during the baseline, 3- and 6-month post-intervention. Results Relative to the standard care, receiving KM2H2 was associated with significant reductions in the incidence of heart attack (3.60% vs. 7.03%, p < .05) and stroke (5.11% vs. 9.90%, p<0.05), and moderate reduction in blood pressure (-3.72mmHg in DBP and -2.92 mmHg in DBP) at 6-month post-intervention; and significant increases in physical activity at 3- (d = 0.53, 95% CI: 0.21, 0.85) and 6-month (d = 0.45, 95% CI: 0.04, 0.85) post-intervention, respectively. Conclusion The program KM2H2 is efficacious to reduce the risk of heart attack and stroke among senior patients who are on anti-hypertensive medication. Findings of this study provide solid data supporting a formal phase-III trial to establish the effectiveness of KM2H2 for use in community settings for prevention. Trial Registration ISRCTN Register ISRCTN12608966 PMID:26426421

Prospective registration trends, reasons for retrospective registration and mechanisms to increase prospective registration compliance: descriptive analysis and survey

PubMed Central

Seidler, Anna Lene; Askie, Lisa M

2018-01-01

Objectives To analyse prospective versus retrospective trial registration trends on the Australian New Zealand Clinical Trials Registry (ANZCTR) and to evaluate the reasons for non-compliance with prospective registration. Design Part 1: Descriptive analysis of trial registration trends from 2006 to 2015. Part 2: Online registrant survey. Participants Part 1: All interventional trials registered on ANZCTR from 2006 to 2015. Part 2: Random sample of those who had retrospectively registered a trial on ANZCTR between 2010 and 2015. Main outcome measures Part 1: Proportion of prospective versus retrospective clinical trial registrations (ie, registration before versus after enrolment of the first participant) on the ANZCTR overall and by various key metrics, such as sponsor, funder, recruitment country and sample size. Part 2: Reasons for non-compliance with prospective registration and perceived usefulness of various proposed mechanisms to improve prospective registration compliance. Results Part 1: Analysis of the complete dataset of 9450 trials revealed that compliance with prospective registration increased from 48% (216 out of 446 trials) in 2006 to 63% (723/1148) in 2012 and has since plateaued at around 64%. Patterns of compliance were relatively consistent across sponsor and funder types (industry vs non-industry), type of intervention (drug vs non-drug) and size of trial (n<100, 100–500, >500). However, primary sponsors from Australia/New Zealand were almost twice as likely to register prospectively (62%; 4613/7452) compared with sponsors from other countries with a WHO Network Registry (35%; 377/1084) or sponsors from countries without a WHO Registry (29%; 230/781). Part 2: The majority (56%; 84/149) of survey respondents cited lack of awareness as a reason for not registering their study prospectively. Seventy-four per cent (111/149) stated that linking registration to ethics approval would facilitate prospective registration. Conclusions Despite some progress, compliance with prospective registration remains suboptimal. Linking registration to ethics approval was the favoured strategy among those sampled for improving compliance. PMID:29496896

Feasibility and Preliminary Efficacy of Visual Cue Training to Improve Adaptability of Walking after Stroke: Multi-Centre, Single-Blind Randomised Control Pilot Trial

PubMed Central

Hollands, Kristen L.; Pelton, Trudy A.; Wimperis, Andrew; Whitham, Diane; Tan, Wei; Jowett, Sue; Sackley, Catherine M.; Wing, Alan M.; Tyson, Sarah F.; Mathias, Jonathan; Hensman, Marianne; van Vliet, Paulette M.

2015-01-01

Objectives Given the importance of vision in the control of walking and evidence indicating varied practice of walking improves mobility outcomes, this study sought to examine the feasibility and preliminary efficacy of varied walking practice in response to visual cues, for the rehabilitation of walking following stroke. Design This 3 arm parallel, multi-centre, assessor blind, randomised control trial was conducted within outpatient neurorehabilitation services Participants Community dwelling stroke survivors with walking speed <0.8m/s, lower limb paresis and no severe visual impairments Intervention Over-ground visual cue training (O-VCT), Treadmill based visual cue training (T-VCT), and Usual care (UC) delivered by physiotherapists twice weekly for 8 weeks. Main outcome measures: Participants were randomised using computer generated random permutated balanced blocks of randomly varying size. Recruitment, retention, adherence, adverse events and mobility and balance were measured before randomisation, post-intervention and at four weeks follow-up. Results Fifty-six participants participated (18 T-VCT, 19 O-VCT, 19 UC). Thirty-four completed treatment and follow-up assessments. Of the participants that completed, adherence was good with 16 treatments provided over (median of) 8.4, 7.5 and 9 weeks for T-VCT, O-VCT and UC respectively. No adverse events were reported. Post-treatment improvements in walking speed, symmetry, balance and functional mobility were seen in all treatment arms. Conclusions Outpatient based treadmill and over-ground walking adaptability practice using visual cues are feasible and may improve mobility and balance. Future studies should continue a carefully phased approach using identified methods to improve retention. Trial Registration Clinicaltrials.gov NCT01600391 PMID:26445137

Trends in Recruitment Rates for Acute Stroke Trials, 1990-2014.

PubMed

Feldman, William B; Kim, Anthony S; Chiong, Winston

2017-03-01

Slow recruitment in acute stroke trials hampers the evaluation of new therapies and delays the adoption of effective therapies into clinical practice. This systematic review evaluates whether recruitment efficiency and rates have increased in acute stroke trials from 1990 to 2014. Acute stroke trials from 2010 to 2014 were identified by a search of PubMed, Medline, the Cochrane Database of Research in Stroke, and the Stroke Trials Registry. These trials were compared to a previously published data set of trials conducted from 1990 to 2004. The median recruitment efficiency of trials from 1990 to 2004 was 0.41 participants/site/month compared with 0.26 participants/site/month from 2010 to 2014 ( P =0.14). The median recruitment rate of trials from 1990 to 2004 was 26.8 participants/month compared with 19.0 participants/month from 2010 to 2014 ( P =0.13). For acute stroke trials, neither recruitment efficiency nor recruitment rates have increased over the past 25 years and, if anything, have declined. © 2017 American Heart Association, Inc.

Refinement of the magnetic resonance diffusion-perfusion mismatch concept for thrombolytic patient selection: insights from the desmoteplase in acute stroke trials.

PubMed

Warach, Steven; Al-Rawi, Yasir; Furlan, Anthony J; Fiebach, Jochen B; Wintermark, Max; Lindstén, Annika; Smyej, Jamal; Bharucha, David B; Pedraza, Salvador; Rowley, Howard A

2012-09-01

The DIAS-2 study was the only large, randomized, intravenous, thrombolytic trial that selected patients based on the presence of ischemic penumbra. However, DIAS-2 did not confirm the positive findings of the smaller DEDAS and DIAS trials, which also used penumbral selection. Therefore, a reevaluation of the penumbra selection strategy is warranted. In post hoc analyses we assessed the relationships of magnetic resonance imaging-measured lesion volumes with clinical measures in DIAS-2, and the relationships of the presence and size of the diffusion-perfusion mismatch with the clinical effect of desmoteplase in DIAS-2 and in pooled data from DIAS, DEDAS, and DIAS-2. In DIAS-2, lesion volumes correlated with National Institutes of Health Stroke Scale (NIHSS) at both baseline and final time points (P<0.0001), and lesion growth was inversely related to good clinical outcome (P=0.004). In the pooled analysis, desmoteplase was associated with 47% clinical response rate (n=143) vs 34% in placebo (n=73; P=0.08). For both the pooled sample and for DIAS-2, increasing the minimum baseline mismatch volume (MMV) for inclusion increased the desmoteplase effect size. The odds ratio for good clinical response between desmoteplase and placebo treatment was 2.83 (95% confidence interval, 1.16-6.94; P=0.023) for MMV >60 mL. Increasing the minimum NIHSS score for inclusion did not affect treatment effect size. Pooled across all desmoteplase trials, desmoteplase appears beneficial in patients with large MMV and ineffective in patients with small MMV. These results support a modified diffusion-perfusion mismatch hypothesis for patient selection in later time-window thrombolytic trials. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique Identifiers: NCT00638781, NCT00638248, NCT00111852.

Development of smartphone application that aids stroke screening and identifying nearby acute stroke care hospitals.

PubMed

Nam, Hyo Suk; Heo, JoonNyung; Kim, Jinkwon; Kim, Young Dae; Song, Tae Jin; Park, Eunjeong; Heo, Ji Hoe

2014-01-01

The benefits of thrombolytic treatment are time-dependent. We developed a smartphone application that aids stroke patient self-screening and hospital selection, and may also decrease hospital arrival time. The application was developed for iPhone and Android smartphones. Map data for the application were adopted from the open map. For hospital registration, a web page (http://stroke119.org) was developed using PHP and MySQL. The Stroke 119 application includes a stroke screening tool and real-time information on nearby hospitals that provide thrombolytic treatment. It also provides information on stroke symptoms, thrombolytic treatment, and prescribed actions when stroke is suspected. The stroke screening tool was adopted from the Cincinnati Prehospital Stroke Scale and is displayed in a cartoon format. If the user taps a cartoon image that represents abnormal findings, a pop-up window shows that the user may be having a stroke, informs the user what to do, and directs the user to call emergency services. Information on nearby hospitals is provided in map and list views, incorporating proximity to the user's location using a Global Positioning System (a built-in function of smartphones). Users can search for a hospital according to specialty and treatment levels. We also developed a web page for hospitals to register in the system. Neurology training hospitals and hospitals that provide acute stroke care in Korea were invited to register. Seventy-seven hospitals had completed registration. This application may be useful for reducing hospital arrival times for thrombolytic candidates.

A multi-centre randomised controlled trial of rehabilitation aimed at improving outdoor mobility for people after stroke: Study protocol for a randomised controlled trial

PubMed Central

2012-01-01

Background Up to 42% of all stroke patients do not get out of the house as much as they would like. This can impede a person’s quality of life. This study is testing the clinical effectiveness and cost effectiveness of a new outdoor mobility rehabilitation intervention by comparing it to usual care. Methods/design This is a multi-centre parallel group individually randomised, controlled trial. At least 506 participants will be recruited through 15 primary and secondary care settings and will be eligible if they are over 18 years of age, have had a stroke and wish to get out of the house more often. Participants are being randomly allocated to either the intervention group or the control group. Intervention group participants receive up to 12 rehabilitation outdoor mobility sessions over up to four months. The main component of the intervention is repeated practice of outdoor mobility with a therapist. Control group participants are receiving the usual intervention for outdoor mobility limitations: verbal advice and provision of leaflets provided over one session. Outcome measures are being collected using postal questionnaires, travel calendars and by independent assessors. The primary outcome measure is the Social Function domain of the SF36v2 quality of life assessment six months after recruitment. The secondary outcome measures include: functional ability, mobility, the number of journeys (monthly travel diaries), satisfaction with outdoor mobility, mood, health-related quality of life, resource use of health and social care. Carer mood information is also being collected. The mean Social Function score of the SF-36v2 will be compared between treatment arms using a multiple membership form of mixed effects multiple regression analysis adjusting for centre (as a fixed effect), age and baseline Social Function score as covariates and therapist as a multiple membership random effect. Regression coefficients and 95% confidence intervals will be presented. Discussion This study protocol describes a pragmatic randomised controlled trial that will hopefully provide robust evidence of the benefit of outdoor mobility interventions after stroke for clinicians working in the community. The results will be available towards the end of 2012. Trial registration ISRCTN58683841 PMID:22721452

Stroke Trials Registry

MedlinePlus

... Trials News About Neurology Image Library Search The Internet Stroke Center Trials Registry Clinical Trials Interventions Conditions ... UT Southwestern Medical Center. Copyright © 1997-2011 - The Internet Stroke Center. All rights reserved. The information contained ...

Cognitive rehabilitation for memory deficits following stroke.

PubMed

Majid, M J; Lincoln, N B; Weyman, N

2000-01-01

Memory problems occur following stroke. Cognitive rehabilitation programmes are provided to retrain memory function or to teach patients strategies to cope despite memory impairment. To determine the effects of cognitive rehabilitation for memory problems following stroke. We searched the Cochrane Stroke Group Trials Register, Medline, EMBASE, CINHAL and CLIN PSYCH databases and reference lists from relevant articles. Date of most recent searches: December 1998. Controlled trials of memory retraining in stroke. Studies with mixed aetiology groups were excluded unless they had more than 75% of stroke patients or separate data were available for the stroke patients. Two reviewers extracted trial data and assessed trial quality. Reviewers contacted investigators for further details of trials. One trial was identified with 12 participants. This showed memory strategy training had no significant effect on memory impairment or subjective memory complaints. There is insufficient evidence to support or refute the effectiveness of cognitive rehabilitation for memory problems after stroke.

Strokes with minor symptoms: an exploratory analysis of the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator trials.

PubMed

Khatri, Pooja; Kleindorfer, Dawn O; Yeatts, Sharon D; Saver, Jeffrey L; Levine, Steven R; Lyden, Patrick D; Moomaw, Charles J; Palesch, Yuko Y; Jauch, Edward C; Broderick, Joseph P

2010-11-01

The pivotal National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator trials excluded patients with ischemic stroke with specific minor presentations or rapidly improving symptoms. The recombinant tissue plasminogen activator product label notes that its use for minor neurological deficit or rapidly improving stroke symptoms has not been evaluated. As a result, patients with low National Institutes of Health Stroke Scale scores are not commonly treated in clinical practice. We sought to further characterize the patients with minor stroke who were included in the National Institute of Neurological Disorders and Stroke trials. Minor strokes were defined as National Institutes of Health Stroke Scale score ≤ 5 at baseline for this retrospective analysis, because this subgroup is most commonly excluded from treatment in clinical practice and trials. Clinical stroke syndromes were defined based on prespecified National Institutes of Health Stroke Scale item score clusters. Clinical outcomes were reviewed generally and within these cluster subgroups. Only 58 cases had National Institutes of Health Stroke Scale scores of 0 to 5 in the National Institute of Neurological Disorders and Stroke trials (42 recombinant tissue plasminogen activator and 16 placebo), and 2971 patients were excluded from the trials due to "rapidly improving" or "minor symptoms" as the primary reason. No patients were enrolled with isolated motor symptoms, isolated facial droop, isolated ataxia, dysarthria, isolated sensory symptoms, or with only symptoms/signs not captured by the National Institutes of Health Stroke Scale score (ie, National Institutes of Health Stroke Scale=0). There were ≤ 3 patients with each of the other isolated deficits enrolled in the trial. The National Institute of Neurological Disorders and Stroke trials excluded a substantial number of strokes with minor presentations, those that were included were small in number, and conclusions about outcomes based on specific syndromes cannot be drawn. Further prospective, systematic study of this subgroup is needed.

Accelerometry Measuring the Outcome of Robot-Supported Upper Limb Training in Chronic Stroke: A Randomized Controlled Trial

PubMed Central

Lemmens, Ryanne J. M.; Timmermans, Annick A. A.; Janssen-Potten, Yvonne J. M.; Pulles, Sanne A. N. T. D.; Geers, Richard P. J.; Bakx, Wilbert G. M.; Smeets, Rob J. E. M.; Seelen, Henk A. M.

2014-01-01

Purpose This study aims to assess the extent to which accelerometers can be used to determine the effect of robot-supported task-oriented arm-hand training, relative to task-oriented arm-hand training alone, on the actual amount of arm-hand use of chronic stroke patients in their home situation. Methods This single-blind randomized controlled trial included 16 chronic stroke patients, randomly allocated using blocked randomization (n = 2) to receive task-oriented robot-supported arm-hand training or task-oriented (unsupported) arm-hand training. Training lasted 8 weeks, 4 times/week, 2×30 min/day using the (T-)TOAT ((Technology-supported)-Task-Oriented-Arm-Training) method. The actual amount of arm-hand use, was assessed at baseline, after 8 weeks training and 6 months after training cessation. Duration of use and intensity of use of the affected arm-hand during unimanual and bimanual activities were calculated. Results Duration and intensity of use of the affected arm-hand did not change significantly during and after training, with or without robot-support (i.e. duration of use of unimanual use of the affected arm-hand: median difference of −0.17% in the robot-group and −0.08% in the control group between baseline and after training cessation; intensity of the affected arm-hand: median difference of 3.95% in the robot-group and 3.32% in the control group between baseline and after training cessation). No significant between-group differences were found. Conclusions Accelerometer data did not show significant changes in actual amount of arm-hand use after task-oriented training, with or without robot-support. Next to the amount of use, discrimination between activities performed and information about quality of use of the affected arm-hand are essential to determine actual arm-hand performance. Trial Registration Controlled-trials.com ISRCTN82787126 PMID:24823925

Auditory training changes temporal lobe connectivity in 'Wernicke's aphasia': a randomised trial.

PubMed

Woodhead, Zoe Vj; Crinion, Jennifer; Teki, Sundeep; Penny, Will; Price, Cathy J; Leff, Alexander P

2017-07-01

Aphasia is one of the most disabling sequelae after stroke, occurring in 25%-40% of stroke survivors. However, there remains a lack of good evidence for the efficacy or mechanisms of speech comprehension rehabilitation. This within-subjects trial tested two concurrent interventions in 20 patients with chronic aphasia with speech comprehension impairment following left hemisphere stroke: (1) phonological training using 'Earobics' software and (2) a pharmacological intervention using donepezil, an acetylcholinesterase inhibitor. Donepezil was tested in a double-blind, placebo-controlled, cross-over design using block randomisation with bias minimisation. The primary outcome measure was speech comprehension score on the comprehensive aphasia test. Magnetoencephalography (MEG) with an established index of auditory perception, the mismatch negativity response, tested whether the therapies altered effective connectivity at the lower (primary) or higher (secondary) level of the auditory network. Phonological training improved speech comprehension abilities and was particularly effective for patients with severe deficits. No major adverse effects of donepezil were observed, but it had an unpredicted negative effect on speech comprehension. The MEG analysis demonstrated that phonological training increased synaptic gain in the left superior temporal gyrus (STG). Patients with more severe speech comprehension impairments also showed strengthening of bidirectional connections between the left and right STG. Phonological training resulted in a small but significant improvement in speech comprehension, whereas donepezil had a negative effect. The connectivity results indicated that training reshaped higher order phonological representations in the left STG and (in more severe patients) induced stronger interhemispheric transfer of information between higher levels of auditory cortex.Clinical trial registrationThis trial was registered with EudraCT (2005-004215-30, https:// eudract .ema.europa.eu/) and ISRCTN (68939136, http://www.isrctn.com/). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Implementing Cough Reflex Testing in a Clinical Pathway for Acute Stroke: A Pragmatic Randomised Controlled Trial.

PubMed

Field, Makaela; Wenke, Rachel; Sabet, Arman; Lawrie, Melissa; Cardell, Elizabeth

2018-05-15

Silent aspiration is common after stroke and can lead to subsequent pneumonia. While standard bedside dysphagia assessments are ineffective at predicting silent aspiration, cough reflex testing (CRT) has shown promise for identifying patients at risk of silent aspiration. We investigated the impact of CRT on patient and service outcomes when embedded into a clinical pathway. 488 acute stoke patients were randomly allocated to receive either CRT or standard care (i.e. bedside assessment). Primary outcomes included confirmed pneumonia within 3 months post stroke and length of acute inpatient stay. Secondary outcomes related to the feasibility of implementing a CRT pathway and clinician and patient satisfaction. There was a non-significant reduction in pneumonia rates by 2.2% points in the CRT group (OR 0.32, 95% CI 0.06-1.62). There was a non-significant difference of 0.7 days (95% CI - 0.29 to 1.71 days) in length of stay between the standard care group and the CRT group. The CRT took on average 3 min longer to complete (p < 0.01) and resulted in a significant 6.7% increase in videofluoroscopic referrals (p = 0.02); however, these results are clinically insignificant. High patient and clinician satisfaction with CRT was found, with clinicians reporting additional knowledge and confidence in decision making for dysphagia management. Post hoc subgroup analyses according to stroke types were conducted and revealed no significant differences in pneumonia rates after adjustment for multiple comparisons. In conclusion, it was possible to implement a CRT pathway with minimal increases in clinician resources. While clinicians perceived CRT as beneficial in clinical decision making, the efficacy of CRT for reducing pneumonia rates in acute stroke remains to be established.Clinical Trial Registration-URL: http://www.anzctr.org.au . Unique identifier: ACTRN12616000724471.

Clinical Effect Size of an Educational Intervention in the Home and Compliance With Mobile Phone-Based Reminders for People Who Suffer From Stroke: Protocol of a Randomized Controlled Trial

PubMed Central

Merchán-Baeza, Jose Antonio

2015-01-01

Background Stroke is the third-leading cause of death and the leading cause of long-term neurological disability in the world. Cognitive, communication, and physical weakness combined with environmental changes frequently cause changes in the roles, routines, and daily occupations of stroke sufferers. Educational intervention combines didactic and interactive intervention, which combines the best choices for teaching new behaviors since it involves the active participation of the patient in learning. Nowadays, there are many types of interventions or means to increase adherence to treatment. Objective The aim of this study is to enable patients who have suffered stroke and been discharged to their homes to improve the performance of the activities of daily living (ADL) in their home environment, based on advice given by the therapist. A secondary aim is that these patients continue the treatment through a reminder app installed on their mobile phones. Methods This study is a clinical randomized controlled trial. The total sample will consist of 80 adults who have suffered a stroke with moderate severity and who have been discharged to their homes in the 3 months prior to recruitment to the study. The following tests and scales will be used to measure the outcome variables: Barthel Index, the Functional Independence Measure, the Mini-Mental State Examination, the Canadian Neurological Scale, the Stroke Impact Scale-16, the Trunk Control Test, the Modified Rankin Scale, the Multidimensional Scale of Perceived Social Support, the Quality of Life Scale for Stroke, the Functional Reach Test, the Romberg Test, the Time Up and Go test, the Timed-Stands Test, a portable dynamometer, and a sociodemographic questionnaire. Descriptive analyses will include mean, standard deviation, and 95% confidence intervals of the values for each variable. The Kolmogov-Smirnov (KS) test and a 2x2 mixed-model analysis of variance (ANOVA) will be used. Intergroup effect sizes will be calculated (Cohen’s d). Results Currently, the study is in the recruitment phase and implementation of the intervention has begun. The authors anticipate that during 2015 the following processes should be completed: recruitment, intervention, and data collection. It is expected that the analysis of all data and the first results should be available in early-to-mid 2016. Conclusions An educational intervention based on therapeutic home advice and a reminder app has been developed by the authors with the intention that patients who have suffered stroke perform the ADL more easily and use their affected limbs more actively in the ADL. The use of reminders via mobile phone is proposed as an innovative tool to increase treatment adherence in this population. Trial Registration ClinicalTrials.gov NCT01980641; https://clinicaltrials.gov/ct2/show/NCT01980641 (Archived by WebCite at http://www.webcitation.org/6WRWFmY6U). PMID:25757808

Immediate effects of acupuncture on biceps brachii muscle function in healthy and post-stroke subjects

PubMed Central

2012-01-01

Background The effects of acupuncture on muscle function in healthy subjects are contradictory and cannot be extrapolated to post-stroke patients. This study evaluated the immediate effects of manual acupuncture on myoelectric activity and isometric force in healthy and post-stroke patients. Methods A randomized clinical trial, with parallel groups, single-blinded study design, was conducted with 32 healthy subjects and 15 post-stroke patients with chronic hemiparesis. Surface electromyography from biceps brachii during maximal isometric voluntary tests was performed before and after 20-min intermittent, and manual stimulation of acupoints Quchi (LI11) or Tianquan (PC2). Pattern differentiation was performed by an automated method based on logistic regression equations. Results Healthy subjects showed a decrease in the root mean-squared (RMS) values after the stimulation of LI11 (pre: 1.392 ± 0.826 V; post: 0.612 ± 0.0.320 V; P = 0.002) and PC2 (pre: 1.494 ± 0.826 V; post: 0.623 ± 0.320 V; P = 0.001). Elbow flexion maximal isometric voluntary contraction (MIVC) was not significantly different after acupuncture stimulation of LI11 (pre: 22.2 ± 10.7 kg; post: 21.7 ± 9.5 kg; P = 0.288) or PC2 (pre: 18.8 ± 4.6 kg; post: 18.7 ± 6.0 kg; P = 0.468). Post-stroke patients did not exhibit any significant decrease in the RMS values after the stimulation of LI11 (pre: 0.627 ± 0.335 V; post: 0.530 ± 0.272 V; P = 0.187) and PC2 (pre: 0.601 ± 0.258 V; post: 0.591 ± 0.326 V; P = 0.398). Also, no significant decrease in the MIVC value was observed after the stimulation of LI11 (pre: 9.6 ± 3.9 kg; post: 9.6 ± 4.7 kg; P = 0.499) or PC2 (pre: 10.7 ± 5.6 kg; post: 10.2 ± 5.3 kg; P = 0.251). Different frequency of patterns was observed among healthy subjects and post-stroke patients groups (χ2 = 9.759; P = 0.021). Conclusion Manual acupuncture provides sufficient neuromuscular stimuli to promote immediate changes in motor unit gross recruitment without repercussion in maximal force output in healthy subjects. Post-stroke patients did not exhibit significant reduction on the myoelectric activity and maximal force output after manual acupuncture and needs further evaluation with a larger sample. Trial registration Brazilian Clinical Trials Registry RBR-5g7xqh. PMID:22417176

Prospective registration trends, reasons for retrospective registration and mechanisms to increase prospective registration compliance: descriptive analysis and survey.

PubMed

Hunter, Kylie Elizabeth; Seidler, Anna Lene; Askie, Lisa M

2018-03-01

To analyse prospective versus retrospective trial registration trends on the Australian New Zealand Clinical Trials Registry (ANZCTR) and to evaluate the reasons for non-compliance with prospective registration. Part 1: Descriptive analysis of trial registration trends from 2006 to 2015. Part 2: Online registrant survey. Part 1: All interventional trials registered on ANZCTR from 2006 to 2015. Part 2: Random sample of those who had retrospectively registered a trial on ANZCTR between 2010 and 2015. Part 1: Proportion of prospective versus retrospective clinical trial registrations (ie, registration before versus after enrolment of the first participant) on the ANZCTR overall and by various key metrics, such as sponsor, funder, recruitment country and sample size. Part 2: Reasons for non-compliance with prospective registration and perceived usefulness of various proposed mechanisms to improve prospective registration compliance. Part 1: Analysis of the complete dataset of 9450 trials revealed that compliance with prospective registration increased from 48% (216 out of 446 trials) in 2006 to 63% (723/1148) in 2012 and has since plateaued at around 64%. Patterns of compliance were relatively consistent across sponsor and funder types (industry vs non-industry), type of intervention (drug vs non-drug) and size of trial (n<100, 100-500, >500). However, primary sponsors from Australia/New Zealand were almost twice as likely to register prospectively (62%; 4613/7452) compared with sponsors from other countries with a WHO Network Registry (35%; 377/1084) or sponsors from countries without a WHO Registry (29%; 230/781). Part 2: The majority (56%; 84/149) of survey respondents cited lack of awareness as a reason for not registering their study prospectively. Seventy-four per cent (111/149) stated that linking registration to ethics approval would facilitate prospective registration. Despite some progress, compliance with prospective registration remains suboptimal. Linking registration to ethics approval was the favoured strategy among those sampled for improving compliance. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Dose-response relationship of robot-assisted stroke motor rehabilitation: the impact of initial motor status.

PubMed

Hsieh, Yu-wei; Wu, Ching-yi; Lin, Keh-chung; Yao, Grace; Wu, Kuen-yuh; Chang, Ya-ju

2012-10-01

The increasing availability of robot-assisted therapy (RT), which provides quantifiable, reproducible, interactive, and intensive practice, holds promise for stroke rehabilitation, but data on its dose-response relation are scanty. This study used 2 different intensities of RT to examine the treatment effects of RT and the effect on outcomes of the severity of initial motor deficits. Fifty-four patients with stroke were randomized to a 4-week intervention of higher-intensity RT, lower-intensity RT, or control treatment. The primary outcome, the Fugl-Meyer Assessment, was administered at baseline, midterm, and posttreatment. Secondary outcomes included the Medical Research Council scale, the Motor Activity Log, and the physical domains of the Stroke Impact Scale. The higher-intensity RT group showed significantly greater improvements on the Fugl-Meyer Assessment than the lower-intensity RT and control treatment groups at midterm (P=0.003 and P=0.02) and at posttreatment (P=0.04 and P=0.02). Within-group gains on the secondary outcomes were significant, but the differences among the 3 groups did not reach significance. Recovery rates of the higher-intensity RT group were higher than those of the lower-intensity RT group, particularly on the Fugl-Meyer Assessment. Scatterplots with curve fitting showed that patients with moderate motor deficits gained more improvements than those with severe or mild deficits after the higher-intensity RT. This study demonstrated the higher treatment intensity provided by RT was associated with better motor outcome for patients with stroke, which may shape further stroke rehabilitation. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00917605.

An economic analysis of robot-assisted therapy for long-term upper-limb impairment after stroke.

PubMed

Wagner, Todd H; Lo, Albert C; Peduzzi, Peter; Bravata, Dawn M; Huang, Grant D; Krebs, Hermano I; Ringer, Robert J; Federman, Daniel G; Richards, Lorie G; Haselkorn, Jodie K; Wittenberg, George F; Volpe, Bruce T; Bever, Christopher T; Duncan, Pamela W; Siroka, Andrew; Guarino, Peter D

2011-09-01

Stroke is a leading cause of disability. Rehabilitation robotics have been developed to aid in recovery after a stroke. This study determined the additional cost of robot-assisted therapy and tested its cost-effectiveness. We estimated the intervention costs and tracked participants' healthcare costs. We collected quality of life using the Stroke Impact Scale and the Health Utilities Index. We analyzed the cost data at 36 weeks postrandomization using multivariate regression models controlling for site, presence of a prior stroke, and Veterans Affairs costs in the year before randomization. A total of 127 participants were randomized to usual care plus robot therapy (n=49), usual care plus intensive comparison therapy (n=50), or usual care alone (n=28). The average cost of delivering robot therapy and intensive comparison therapy was $5152 and $7382, respectively (P<0.001), and both were significantly more expensive than usual care alone (no additional intervention costs). At 36 weeks postrandomization, the total costs were comparable for the 3 groups ($17 831 for robot therapy, $19 746 for intensive comparison therapy, and $19 098 for usual care). Changes in quality of life were modest and not statistically different. The added cost of delivering robot or intensive comparison therapy was recuperated by lower healthcare use costs compared with those in the usual care group. However, uncertainty remains about the cost-effectiveness of robotic-assisted rehabilitation compared with traditional rehabilitation. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00372411.

Leap Motion-based virtual reality training for improving motor functional recovery of upper limbs and neural reorganization in subacute stroke patients.

PubMed

Wang, Zun-Rong; Wang, Ping; Xing, Liang; Mei, Li-Ping; Zhao, Jun; Zhang, Tong

2017-11-01

Virtual reality is nowadays used to facilitate motor recovery in stroke patients. Most virtual reality studies have involved chronic stroke patients; however, brain plasticity remains good in acute and subacute patients. Most virtual reality systems are only applicable to the proximal upper limbs (arms) because of the limitations of their capture systems. Nevertheless, the functional recovery of an affected hand is most difficult in the case of hemiparesis rehabilitation after a stroke. The recently developed Leap Motion controller can track the fine movements of both hands and fingers. Therefore, the present study explored the effects of a Leap Motion-based virtual reality system on subacute stroke. Twenty-six subacute stroke patients were assigned to an experimental group that received virtual reality training along with conventional occupational rehabilitation, and a control group that only received conventional rehabilitation. The Wolf motor function test (WMFT) was used to assess the motor function of the affected upper limb; functional magnetic resonance imaging was used to measure the cortical activation. After four weeks of treatment, the motor functions of the affected upper limbs were significantly improved in all the patients, with the improvement in the experimental group being significantly better than in the control group. The action performance time in the WMFT significantly decreased in the experimental group. Furthermore, the activation intensity and the laterality index of the contralateral primary sensorimotor cortex increased in both the experimental and control groups. These results confirmed that Leap Motion-based virtual reality training was a promising and feasible supplementary rehabilitation intervention, could facilitate the recovery of motor functions in subacute stroke patients. The study has been registered in the Chinese Clinical Trial Registry (registration number: ChiCTR-OCH-12002238).

Leap Motion-based virtual reality training for improving motor functional recovery of upper limbs and neural reorganization in subacute stroke patients

PubMed Central

Wang, Zun-rong; Wang, Ping; Xing, Liang; Mei, Li-ping; Zhao, Jun; Zhang, Tong

2017-01-01

Virtual reality is nowadays used to facilitate motor recovery in stroke patients. Most virtual reality studies have involved chronic stroke patients; however, brain plasticity remains good in acute and subacute patients. Most virtual reality systems are only applicable to the proximal upper limbs (arms) because of the limitations of their capture systems. Nevertheless, the functional recovery of an affected hand is most difficult in the case of hemiparesis rehabilitation after a stroke. The recently developed Leap Motion controller can track the fine movements of both hands and fingers. Therefore, the present study explored the effects of a Leap Motion-based virtual reality system on subacute stroke. Twenty-six subacute stroke patients were assigned to an experimental group that received virtual reality training along with conventional occupational rehabilitation, and a control group that only received conventional rehabilitation. The Wolf motor function test (WMFT) was used to assess the motor function of the affected upper limb; functional magnetic resonance imaging was used to measure the cortical activation. After four weeks of treatment, the motor functions of the affected upper limbs were significantly improved in all the patients, with the improvement in the experimental group being significantly better than in the control group. The action performance time in the WMFT significantly decreased in the experimental group. Furthermore, the activation intensity and the laterality index of the contralateral primary sensorimotor cortex increased in both the experimental and control groups. These results confirmed that Leap Motion-based virtual reality training was a promising and feasible supplementary rehabilitation intervention, could facilitate the recovery of motor functions in subacute stroke patients. The study has been registered in the Chinese Clinical Trial Registry (registration number: ChiCTR-OCH-12002238). PMID:29239328

Stroke subtyping for genetic association studies? A comparison of the CCS and TOAST classifications.

PubMed

Lanfranconi, Silvia; Markus, Hugh S

2013-12-01

A reliable and reproducible classification system of stroke subtype is essential for epidemiological and genetic studies. The Causative Classification of Stroke system is an evidence-based computerized algorithm with excellent inter-rater reliability. It has been suggested that, compared to the Trial of ORG 10172 in Acute Stroke Treatment classification, it increases the proportion of cases with defined subtype that may increase power in genetic association studies. We compared Trial of ORG 10172 in Acute Stroke Treatment and Causative Classification of Stroke system classifications in a large cohort of well-phenotyped stroke patients. Six hundred ninety consecutively recruited patients with first-ever ischemic stroke were classified, using review of clinical data and original imaging, according to the Trial of ORG 10172 in Acute Stroke Treatment and Causative Classification of Stroke system classifications. There was excellent agreement subtype assigned by between Trial of ORG 10172 in Acute Stroke Treatment and Causative Classification of Stroke system (kappa = 0·85). The agreement was excellent for the major individual subtypes: large artery atherosclerosis kappa = 0·888, small-artery occlusion kappa = 0·869, cardiac embolism kappa = 0·89, and undetermined category kappa = 0·884. There was only moderate agreement (kappa = 0·41) for the subjects with at least two competing underlying mechanism. Thirty-five (5·8%) patients classified as undetermined by Trial of ORG 10172 in Acute Stroke Treatment were assigned to a definite subtype by Causative Classification of Stroke system. Thirty-two subjects assigned to a definite subtype by Trial of ORG 10172 in Acute Stroke Treatment were classified as undetermined by Causative Classification of Stroke system. There is excellent agreement between classification using Trial of ORG 10172 in Acute Stroke Treatment and Causative Classification of Stroke systems but no evidence that Causative Classification of Stroke system reduced the proportion of patients classified to undetermined subtypes. The excellent inter-rater reproducibility and web-based semiautomated nature make Causative Classification of Stroke system suitable for multicenter studies, but the benefit of reclassifying cases already classified using the Trial of ORG 10172 in Acute Stroke Treatment system on existing databases is likely to be small. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

The Sleep Apnea cardioVascular Endpoints (SAVE) Trial: Rationale, Ethics, Design, and Progress

PubMed Central

Antic, Nick A.; Heeley, Emma; Anderson, Craig S.; Luo, Yuanming; Wang, Jiguang; Neal, Bruce; Grunstein, Ron; Barbe, Ferran; Lorenzi-Filho, Geraldo; Huang, Shaoguang; Redline, Susan; Zhong, Nanshan; McEvoy, R. Doug

2015-01-01

The Sleep Apnea cardioVascular Endpoints (SAVE) study is an ongoing investigator-initiated and conducted, international, multicenter, open, blinded endpoint, randomized controlled trial that was designed to determine whether treatment of obstructive sleep apnea (OSA) with continuous positive airways pressure (CPAP) can reduce the risk of serious cardiovascular (CV) events in patients with established CV disease (clinical trial registration NCT00738179). The results of this study will have important implications for the provision of health care to patients with sleep apnea around the world. The SAVE study has brought together respiratory, sleep, CV and stroke clinicians-scientists in an interdisciplinary collaboration with industry and government sponsorship to conduct an ambitious clinical trial. Following its launch in Australia and China in late 2008, the recruitment network expanded across 89 sites that included New Zealand, India, Spain, USA, and Brazil for a total of 2,717 patients randomized by December 2013. These patients are being followed until December 2015 so that the average length of follow-up of the cohort will be over 4 y. This article describes the rationale for the SAVE study, considerations given to the design including how various cultural and ethical challenges were addressed, and progress in establishing and maintaining the recruitment network, patient follow-up, and adherence to CPAP and procedures. The assumptions underlying the original trial sample size calculation and why this was revised downward in 2012 are also discussed. Clinical Trials Registration Number: NCT00738179. Australia New Zealand Clinical Trials Registry Number: ACTRN12608000409370. Citation: Antic NA, Heeley E, Anderson CS, Luo Y, Wang J, Neal B, Grunstein R, Barbe F, Lorenzi-Filho G, Huang S, Redline S, Zhong N, McEvoy RD. The sleep apnea cardiovascular endpoints (SAVE) trial: rationale, ethics, design, and progress. SLEEP 2015;38(8):1247–1257. PMID:25669180

Review of the registration of clinical trials in UMIN-CTR from 2 June 2005 to 1 June 2010 - focus on Japan domestic, academic clinical trials

PubMed Central

2013-01-01

Background Established on 1 June 2005, the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) is the largest clinical trial registry in Japan, and joined the World Health Organization (WHO) registry network in October 2008. Our aim was to understand the registration trend and overall characteristics of Japan domestic, academic (non-industry-funded) clinical trials, which constitute the main body of registrations in UMIN-CTR. In addition, we aimed to investigate the accessibility of clinical trials in UMIN-CTR to people worldwide, as well as the accessibility of clinical trials conducted in Japan but registered abroad to Japanese people in the Japanese language. Methods We obtained the data for registrations in UMIN-CTR from the UMIN Center, and extracted Japan domestic, academic clinical trials to analyze their registration trend and overall characteristics. We also investigated how many of the trials registered in UMIN-CTR could be accessed from the International Clinical Trials Registry Platform (ICTRP). Finally, we searched ClinicalTrials.gov for all clinical trials conducted in Japan and investigated how many of them were also registered in Japanese registries. All of the above analyses included clinical trials registered from 2 June 2005 to 1 June 2010. Results During the period examined, the registration trend showed an obvious peak around September 2005 and rapid growth from April 2009. Of the registered trials, 46.4% adopted a single-arm design, 34.5% used an active control, only 10.9% were disclosed before trial commencement, and 90.0% did not publish any results. Overall, 3,063 of 3,064 clinical trials registered in UMIN-CTR could be accessed from ICTRP. Only 8.7% of all clinical trials conducted in Japan and registered in ClinicalTrials.gov were also registered in Japanese registries. Conclusions The International Committee of Medical Journal Editors (ICMJE) announcements about clinical trial registration and the Ethical Guidelines for Clinical Research published by the Japanese government are considered to have promoted clinical trial registration in UMIN-CTR. However, problems associated with trial design, retrospective registration, and publication of trial results need to be addressed in future. Almost all clinical trials registered in UMIN-CTR are accessible to people worldwide through ICTRP. However, many trials conducted in Japan but registered abroad cannot be accessed from Japanese registries in Japanese. PMID:24124926

Endorsement of the CONSORT guidelines, trial registration, and the quality of reporting randomised controlled trials in leading nursing journals: A cross-sectional analysis.

PubMed

Jull, Andrew; Aye, Phyu Sin

2015-06-01

To establish the reporting quality of trials published in leading nursing journals and investigate associations between CONSORT Statement or trial registration endorsment and reporting of design elements. The top 15 nursing journals were searched using Medline for randomised controlled trials published in 2012. Journals were categorised as CONSORT and trial registration promoting based on requirements of submitting authors or the journal's webpage as at January 2014. Data on sequence generation, allocation concealment, follow up, blinding, baseline equivalence and sample size calculation were extracted by one author and independently verified by the second author against source data. Seven journals were CONSORT promoting and three of these journals were also trial registration promoting. 114 citations were identified and 83 were randomised controlled trials. Eighteen trials (21.7%) were registered and those published in trial registration promoting journals were more likely to be registered (RR 2.64 95%CI 1.14-6.09). We assessed 68.7% of trials to be low risk of bias for sequence generation, 20.5% for allocation concealment, 38.6% for blinding, 55.4% for completeness of follow up and 79.5% for baseline equivalence. Trials published in CONSORT promoting journals were more likely to be at low risk of bias for blinding (RR 2.33, 95%CI 1.01-5.34) and completeness of follow up (RR 1.77, 95%CI 1.02-3.10), but journal endorsement of the CONSORT Statement or trial registration otherwise had no significant effect. Trials published in CONSORT and trial registration promoting journals were more likely to have high quality sample size calculations (RR 2.91, 95%CI 1.18-7.19 and RR 1.69, 95%CI 1.08-2.64, respectively). Simple endorsement of the CONSORT Statement and trials registration is insufficient action to encourage improvement of the quality of trial reporting across the most important of trial design elements. Copyright © 2014 Elsevier Ltd. All rights reserved.

Enhancing the development and approval of acute stroke therapies: Stroke Therapy Academic Industry roundtable.

PubMed

Fisher, Marc; Albers, Gregory W; Donnan, Geoffrey A; Furlan, Anthony J; Grotta, James C; Kidwell, Chelsea S; Sacco, Ralph L; Wechsler, Lawrence R

2005-08-01

Previous Stroke Therapy Academic Industry Roundtable (STAIR) meetings focused on preclinical evidence of drug efficacy and enhancing acute stroke trial design and performance. A fourth (STAIR-IV) was held to discuss relevant issues related to acute stroke drug development and regulatory approval. The STAIR-IV meeting had 3 main focus areas. The first topic was novel approaches to statistical design of acute stroke trials and appropriate outcome measures. The second focus was the need for better cooperation among participants in stroke therapy development that may be addressed through a national consortium of stroke trial centers in the United States and elsewhere. Lastly, regulatory issues related to the approval of novel mono and multiple acute stroke therapies were discussed. The development of additional acute stroke therapies represents a large unmet need with many remaining challenges and also opportunities to incorporate novel approaches to clinical trial design that will lead to regulatory approval. The STAIR-IV meeting explored new concepts of trial methodology and data analysis, initiatives for implementing a US clinical trialist consortium, and pertinent regulatory issues to expedite approval of novel therapies.

The combined impact of virtual reality neurorehabilitation and its interfaces on upper extremity functional recovery in patients with chronic stroke.

PubMed

Cameirão, Mónica S; Badia, Sergi Bermúdez i; Duarte, Esther; Frisoli, Antonio; Verschure, Paul F M J

2012-10-01

Although there is strong evidence on the beneficial effects of virtual reality (VR)-based rehabilitation, it is not yet well understood how the different aspects of these systems affect recovery. Consequently, we do not exactly know what features of VR neurorehabilitation systems are decisive in conveying their beneficial effects. To specifically address this issue, we developed 3 different configurations of the same VR-based rehabilitation system, the Rehabilitation Gaming System, using 3 different interface technologies: vision-based tracking, haptics, and a passive exoskeleton. Forty-four patients with chronic stroke were randomly allocated to one of the configurations and used the system for 35 minutes a day for 5 days a week during 4 weeks. Our results revealed significant within-subject improvements at most of the standard clinical evaluation scales for all groups. Specifically we observe that the beneficial effects of VR-based training are modulated by the use/nonuse of compensatory movement strategies and the specific sensorimotor contingencies presented to the user, that is, visual feedback versus combined visual haptic feedback. Our findings suggest that the beneficial effects of VR-based neurorehabilitation systems such as the Rehabilitation Gaming System for the treatment of chronic stroke depend on the specific interface systems used. These results have strong implications for the design of future VR rehabilitation strategies that aim at maximizing functional outcomes and their retention. Clinical Trial Registration- This trial was not registered because it is a small clinical study that evaluates the feasibility of prototype devices.

Nonrigid registration of carotid ultrasound and MR images using a "twisting and bending" model

NASA Astrophysics Data System (ADS)

Nanayakkara, Nuwan D.; Chiu, Bernard; Samani, Abbas; Spence, J. David; Parraga, Grace; Samarabandu, Jagath; Fenster, Aaron

2008-03-01

Atherosclerosis at the carotid bifurcation resulting in cerebral emboli is a major cause of ischemic stroke. Most strokes associated with carotid atherosclerosis can be prevented by lifestyle/dietary changes and pharmacological treatments if identified early by monitoring carotid plaque changes. Plaque composition information from magnetic resonance (MR) carotid images and dynamic characteristics information from 3D ultrasound (US) are necessary for developing and validating US imaging tools to identify vulnerable carotid plaques. Combining these images requires nonrigid registration to correct the non-linear miss-alignments caused by relative twisting and bending in the neck due to different head positions during the two image acquisitions sessions. The high degree of freedom and large number of parameters associated with existing nonrigid image registration methods causes several problems including unnatural plaque morphology alteration, computational complexity, and low reliability. Our approach was to model the normal movement of the neck using a "twisting and bending model" with only six parameters for nonrigid registration. We evaluated our registration technique using intra-subject in-vivo 3D US and 3D MR carotid images acquired on the same day. We calculated the Mean Registration Error (MRE) between the segmented vessel surfaces in the target image and the registered image using a distance-based error metric after applying our "twisting bending model" based nonrigid registration algorithm. We achieved an average registration error of 1.33+/-0.41mm using our nonrigid registration technique. Visual inspection of segmented vessel surfaces also showed a substantial improvement of alignment with our non-rigid registration technique.

Ginkgo biloba extract improved cognitive and neurological functions of acute ischaemic stroke: a randomised controlled trial

PubMed Central

Li, Shanshan; Zhang, Xinjiang; Fang, Qi; Zhou, Junshan; Zhang, Meijuan; Wang, Hui; Chen, Yan; Xu, Biyun; Wu, Yanfeng; Qian, Lai

2017-01-01

Purpose To evaluate the efficacy and safety of Ginkgo biloba extract (GBE) in acute ischaemic stroke and its impact on the recurrence of vascular events. Methods We conducted a multicentre, prospective, randomised, open label, blinded, controlled clinical trial enrollingpatients with an onset of acute stroke within 7 days from five hospitals in China Jiangsu Province. Participants were assigned to the GBE group (450 mg GBE with 100 mg aspirin daily) or the control group (100 mg aspirin daily) for 6 months. The primary outcome was the decline in the Montreal Cognitive Assessment score at 6 months. Secondary outcomes were other neuropsychological tests of cognitive and neurological function, the the incidence of adverse events and vascular events. Results 348 patients were enrolled: 179 in the GBE group and 169 in the control group. With 18 patients lost to follow-up, the dropout rate was 5.17%. Admission data between two groups were similar, but in the GBE group there was a marked slow down in the decline in the Montreal Cognitive Assessment scores (−2.77±0.21 vs −1.99±0.23, P=0.0116 (30 days); −3.34±0.24 vs −2.48±0.26, P=0.0165 (90 days); −4.00±0.26 vs −2.71±0.26, P=0.0004 (180 days)) compared with controls. The National Institutes of Health Stroke Scale scores at 12 and 30 days, the modified Rankin Scale scores for independent rate at 30, 90 and 180 days, and the Barthel Index scores at 30, 90 and 180 days in the GBE group were significantly improved compared with controls. Improvements were also observedin GBE groups for Mini-Metal State Examination scores of 30, 90 and 180 days, Webster’s digit symbol test scores at 30 days and Executive Dysfunction Index scores at 30 and 180 days. No significant differences were seen in the incidence of adverse events or vascular events. Conclusions We conclude that GBE in combination with aspirin treatment alleviated cognitive and neurological deficits after acute ischaemic stroke without increasing the incidence of vascular events. Trial registration number ChiCTR-TRC-12002688. PMID:29507779

Piracetam for Aphasia in Post-stroke Patients: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

PubMed

Zhang, Jie; Wei, Ruili; Chen, Zhongqin; Luo, Benyan

2016-07-01

Aphasia is a common symptom in post-stroke patients. Piracetam is a commonly used nootropic agent that promises various benefits to brain function, including language improvement. We performed a systematic review and meta-analysis to assess whether piracetam facilitates the rehabilitation of language performance in post-stroke patients. Randomized controlled trials (RCTs) of piracetam treatment in post-stroke patients published in any language were included, excluding those involving pre-existing cognitive disorders such as dementia and mood disturbances. We searched several databases including PubMed, EMBASE, Cochrane Central, CINAHL, Web of Science, and PsycINFO for RCTs published up to 31 December 2015. We conducted a meta-analysis using RevMan (version 5.3), with standardized mean differences (SMDs) and fixed-effect models, and used StataSE (version 13) for the detection of publication bias. This study has been submitted to PROSPERO, and its registration number is CRD42016034088. We identified 1180 titles and abstracts, and finally included seven RCTs in this meta-analysis. The number of participants in each study ranged from 19 to 66, summing up to 261 patients overall. The dose of piracetam was consistent while the frequency and time of therapy varied. The assessment of the language at the end of trials showed no significant improvement in overall severity of aphasia [SMD 0.23, 95 % confidence interval (CI) -0.03 to 0.49, P = 0.08], but written language (SMD 0.35, 95 % CI 0.04 to 0.66, P = 0.03) showed pronounced improvement. Subgroup analyses indicated a dissociation of effectiveness between short- and long-term assessment in overall severity (P = 0.008, I (2) = 85.6 %) in terms of tests for subgroup differences, and a mild trend toward dissociation in written subtests (P = 0.30, I (2) = 5.1 %). Funnel plots and Egger's test identified no obvious publication bias in the primary variable. Piracetam plays a limited role in the rehabilitation of overall language impairment and only benefits written language ability at the end of trials. Its effect on overall linguistic level and written language tends to emerge within a short period and declines thereafter.

Music Upper Limb Therapy—Integrated: An Enriched Collaborative Approach for Stroke Rehabilitation

PubMed Central

Raghavan, Preeti; Geller, Daniel; Guerrero, Nina; Aluru, Viswanath; Eimicke, Joseph P.; Teresi, Jeanne A.; Ogedegbe, Gbenga; Palumbo, Anna; Turry, Alan

2016-01-01

Stroke is a leading cause of disability worldwide. It leads to a sudden and overwhelming disruption in one’s physical body, and alters the stroke survivors’ sense of self. Long-term recovery requires that bodily perception, social participation and sense of self are restored; this is challenging to achieve, particularly with a single intervention. However, rhythmic synchronization of movement to external stimuli facilitates sensorimotor coupling for movement recovery, enhances emotional engagement and has positive effects on interpersonal relationships. In this proof-of-concept study, we designed a group music-making intervention, Music Upper Limb Therapy-Integrated (MULT-I), to address the physical, psychological and social domains of rehabilitation simultaneously, and investigated its effects on long-term post-stroke upper limb recovery. The study used a mixed-method pre-post design with 1-year follow up. Thirteen subjects completed the 45-min intervention twice a week for 6 weeks. The primary outcome was reduced upper limb motor impairment on the Fugl-Meyer Scale (FMS). Secondary outcomes included sensory impairment (two-point discrimination test), activity limitation (Modified Rankin Scale, MRS), well-being (WHO well-being index), and participation (Stroke Impact Scale, SIS). Repeated measures analysis of variance (ANOVA) was used to test for differences between pre- and post-intervention, and 1-year follow up scores. Significant improvement was found in upper limb motor impairment, sensory impairment, activity limitation and well-being immediately post-intervention that persisted at 1 year. Activities of daily living and social participation improved only from post-intervention to 1-year follow up. The improvement in upper limb motor impairment was more pronounced in a subset of lower functioning individuals as determined by their pre-intervention wrist range of motion. Qualitatively, subjects reported new feelings of ownership of their impaired limb, more spontaneous movement, and enhanced emotional engagement. The results suggest that the MULT-I intervention may help stroke survivors re-create their sense of self by integrating sensorimotor, emotional and interoceptive information and facilitate long-term recovery across multiple domains of disability, even in the chronic stage post-stroke. Randomized controlled trials are warranted to confirm the efficacy of this approach. Clinical Trial Registration: National Institutes of Health, clinicaltrials.gov, NCT01586221. PMID:27774059

Critical early thrombolytic and endovascular reperfusion therapy for acute ischemic stroke victims: a call for adjunct neuroprotection.

PubMed

Lapchak, Paul A

2015-10-01

Today, there is an enormous amount of excitement in the field of stroke victim care due to the recent success of MR. CLEAN, SWIFT PRIME, ESCAPE, EXTEND-IA, and REVASCAT endovascular trials. Successful intravenous (IV) recombinant tissue plasminogen activator (rt-PA) clinical trials [i.e., National Institute of Neurological Disorders and Stroke (NINDS) rt-PA trial, Third European Cooperative Acute Stroke Study (ECASSIII), and Third International Stroke study (IST-3)] also need to be emphasized. In the recent endovascular and thrombolytic trials, there is statistically significant improvement using both the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Score (mRS) scale, but neither approach promotes complete recovery in patients enrolled within any particular NIHSS or mRS score tier. Absolute improvement (mRS 0-2 at 90 days) with endovascular therapy is 13.5-31 %, whereas thrombolytics alone also significantly improve patient functional independence, but to a lesser degree (NINDS rt-PA trial 13 %). This article has 3 main goals: (1) first to emphasize the utility and cost-effectiveness of rt-PA to treat stroke; (2) second to review the recent endovascular trials with respect to efficacy, safety, and cost-effectiveness as a stroke treatment; and (3) to further consider and evaluate strategies to develop novel neuroprotective drugs. A thesis will be put forth so that future stroke trials and therapy development can optimally promote recovery so that stroke victims can return to "normal" life.

Is Mandatory Prospective Trial Registration Working to Prevent Publication of Unregistered Trials and Selective Outcome Reporting? An Observational Study of Five Psychiatry Journals That Mandate Prospective Clinical Trial Registration.

PubMed

Scott, Amelia; Rucklidge, Julia J; Mulder, Roger T

2015-01-01

To address the bias occurring in the medical literature associated with selective outcome reporting, in 2005, the International Committee of Medical Journal Editors (ICMJE) introduced mandatory trial registration guidelines and member journals required prospective registration of trials prior to patient enrolment as a condition of publication. No research has examined whether these guidelines are impacting psychiatry publications. Our objectives were to determine the extent to which articles published in psychiatry journals adhering to ICMJE guidelines were correctly prospectively registered, whether there was evidence of selective outcome reporting and changes to participant numbers, and whether there was a relationship between registration status and source of funding. Any clinical trial (as defined by ICMJE) published between 1 January 2009 and 31 July 2013 in the top five psychiatry journals adhering to ICMJE guidelines (The American Journal of Psychiatry, Archives of General Psychiatry/JAMA Psychiatry, Biological Psychiatry, Journal of the American Academy of Child and Adolescent Psychiatry, and The Journal of Clinical Psychiatry) and conducted after July 2005 (or 2007 for two journals) was included. For each identified trial, where possible we extracted trial registration information, changes to POMs between publication and registry to assess selective outcome reporting, changes to participant numbers, and funding type. Out of 3305 articles, 181 studies were identified as clinical trials requiring registration: 21 (11.6%) were deemed unregistered, 61 (33.7%) were retrospectively registered, 37 (20.4%) had unclear POMs either in the article or the registry and 2 (1.1%) were registered in an inaccessible trial registry. Only 60 (33.1%) studies were prospectively registered with clearly defined POMs; 17 of these 60 (28.3%) showed evidence of selective outcome reporting and 16 (26.7%) demonstrated a change in participant numbers of 20% or more; only 26 (14.4%) of the 181 the trials were prospectively registered and did not alter their POMs or the time frames at which they were measured. Prospective registration with no changes in POMs occurred more frequently with pharmaceutical funding. Although standards are in place to improve prospective registration and transparency in clinical trials, less than 15% of psychiatry trials were prospectively registered with no changes in POMs. Most trials were either not prospectively registered, changed POMs or the timeframes at some point after registration or changed participant numbers. Authors, journal editors and reviewers need to further efforts to highlight the value of prospective trial registration.

An occupational therapy intervention for residents with stroke related disabilities in UK care homes (OTCH): cluster randomised controlled trial.

PubMed

Sackley, Catherine M; Walker, Marion F; Burton, Christopher R; Watkins, Caroline L; Mant, Jonathan; Roalfe, Andrea K; Wheatley, Keith; Sheehan, Bart; Sharp, Leslie; Stant, Katie E; Fletcher-Smith, Joanna; Steel, Kerry; Wilde, Kate; Irvine, Lisa; Peryer, Guy

2015-02-05

To evaluate the clinical efficacy of an established programme of occupational therapy in maintaining functional activity and reducing further health risks from inactivity in care home residents living with stroke sequelae. Pragmatic, parallel group, cluster randomised controlled trial. 228 care homes (>10 beds each), both with and without the provision of nursing care, local to 11 trial administrative centres across the United Kingdom. 1042 care home residents with a history of stroke or transient ischaemic attack, including those with language and cognitive impairments, not receiving end of life care. 114 homes (n=568 residents, 64% from homes providing nursing care) were allocated to the intervention arm and 114 homes (n=474 residents, 65% from homes providing nursing care) to standard care (control arm). Participating care homes were randomised between May 2010 and March 2012. Targeted three month programme of occupational therapy, delivered by qualified occupational therapists and assistants, involving patient centred goal setting, education of care home staff, and adaptations to the environment. Primary outcome at the participant level: scores on the Barthel index of activities of daily living at three months post-randomisation. Secondary outcome measures at the participant level: Barthel index scores at six and 12 months post-randomisation, and scores on the Rivermead mobility index, geriatric depression scale-15, and EuroQol EQ-5D-3L questionnaire, at all time points. 64% of the participants were women and 93% were white, with a mean age of 82.9 years. Baseline characteristics were similar between groups for all measures, personal characteristics, and diagnostic tests. Overall, 2538 occupational therapy visits were made to 498 participants in the intervention arm (mean 5.1 visits per participant). No adverse events attributable to the intervention were recorded. 162 (11%) died before the primary outcome time point, and 313 (30%) died over the 12 months of the trial. The primary outcome measure did not differ significantly between the treatment arms. The adjusted mean difference in Barthel index score at three months was 0.19 points higher in the intervention arm (95% confidence interval -0.33 to 0.70, P=0.48). Secondary outcome measures also showed no significant differences at all time points. This large phase III study provided no evidence of benefit for the provision of a routine occupational therapy service, including staff training, for care home residents living with stroke related disabilities. The established three month individualised course of occupational therapy targeting stroke related disabilities did not have an impact on measures of functional activity, mobility, mood, or health related quality of life, at all observational time points. Providing and targeting ameliorative care in this clinically complex population requires alternative strategies.Trial registration Current Controlled Trials ISRCTN00757750. © Sackley et al 2015.

An occupational therapy intervention for residents with stroke related disabilities in UK care homes (OTCH): cluster randomised controlled trial

PubMed Central

Sackley, Catherine M; Walker, Marion F; Burton, Christopher R; Watkins, Caroline L; Mant, Jonathan; Roalfe, Andrea K; Wheatley, Keith; Sheehan, Bart; Sharp, Leslie; Stant, Katie E; Fletcher-Smith, Joanna; Steel, Kerry; Wilde, Kate; Irvine, Lisa

2015-01-01

Objective To evaluate the clinical efficacy of an established programme of occupational therapy in maintaining functional activity and reducing further health risks from inactivity in care home residents living with stroke sequelae. Design Pragmatic, parallel group, cluster randomised controlled trial. Setting 228 care homes (>10 beds each), both with and without the provision of nursing care, local to 11 trial administrative centres across the United Kingdom. Participants 1042 care home residents with a history of stroke or transient ischaemic attack, including those with language and cognitive impairments, not receiving end of life care. 114 homes (n=568 residents, 64% from homes providing nursing care) were allocated to the intervention arm and 114 homes (n=474 residents, 65% from homes providing nursing care) to standard care (control arm). Participating care homes were randomised between May 2010 and March 2012. Intervention Targeted three month programme of occupational therapy, delivered by qualified occupational therapists and assistants, involving patient centred goal setting, education of care home staff, and adaptations to the environment. Main outcome measures Primary outcome at the participant level: scores on the Barthel index of activities of daily living at three months post-randomisation. Secondary outcome measures at the participant level: Barthel index scores at six and 12 months post-randomisation, and scores on the Rivermead mobility index, geriatric depression scale-15, and EuroQol EQ-5D-3L questionnaire, at all time points. Results 64% of the participants were women and 93% were white, with a mean age of 82.9 years. Baseline characteristics were similar between groups for all measures, personal characteristics, and diagnostic tests. Overall, 2538 occupational therapy visits were made to 498 participants in the intervention arm (mean 5.1 visits per participant). No adverse events attributable to the intervention were recorded. 162 (11%) died before the primary outcome time point, and 313 (30%) died over the 12 months of the trial. The primary outcome measure did not differ significantly between the treatment arms. The adjusted mean difference in Barthel index score at three months was 0.19 points higher in the intervention arm (95% confidence interval −0.33 to 0.70, P=0.48). Secondary outcome measures also showed no significant differences at all time points. Conclusions This large phase III study provided no evidence of benefit for the provision of a routine occupational therapy service, including staff training, for care home residents living with stroke related disabilities. The established three month individualised course of occupational therapy targeting stroke related disabilities did not have an impact on measures of functional activity, mobility, mood, or health related quality of life, at all observational time points. Providing and targeting ameliorative care in this clinically complex population requires alternative strategies. Trial registration Current Controlled Trials ISRCTN00757750. PMID:25657106

Trial Registration at ClinicalTrials.gov between May and October 2005

PubMed Central

Zarin, Deborah A.; Tse, Tony; Ide, Nicholas C.

2006-01-01

BACKGROUND Clinical trial registration allows interested parties to obtain information about ongoing and completed trials, but there are few data indicating the quality of the information provided during the registration process. We used information in the publicly available ClinicalTrials.gov database to describe patterns of trial registration before and after the implementation by journal editors of a new policy requiring registration as a prerequisite for publication. METHODS We reviewed ClinicalTrials.gov records to determine patterns of completion of the “Intervention Name” and “Primary Outcome Measure” data fields for trials registered on May 20 and October 11, 2005, and for trials registered during the interval between these two dates, inclusively. RESULTS During the interval studied, the number of registrations in ClinicalTrials.gov increased by 73 percent from 13,153 to 22,714. The percentage of interventional trials registered by industry with nonspecific Intervention Name entries (attributable to four drug companies) decreased from 10 percent to 2 percent; all other industry and nonindustry records contained specific entries in this field. Of the 2670 studies registered by industry between the two dates, 76 percent provided information in the Primary Outcome Measure field, although these entries varied markedly in their degree of specificity. In the remaining 24 percent of the records, this field was blank. CONCLUSIONS During the summer of 2005, there were large increases in the number of clinical trial registrations. Overall, the data contained in records were more complete in October than they were in May, but there still is room for substantial improvement. PMID:16382064

An Economic Analysis of Robot-Assisted Therapy for Long-Term Upper-Limb Impairment After Stroke

PubMed Central

Wagner, Todd H.; Lo, Albert C.; Peduzzi, Peter; Bravata, Dawn M.; Huang, Grant D.; Krebs, Hermano I.; Ringer, Robert J.; Federman, Daniel G.; Richards, Lorie G.; Haselkorn, Jodie K.; Wittenberg, George F.; Volpe, Bruce T.; Bever, Christopher T.; Duncan, Pamela W.; Siroka, Andrew; Guarino, Peter D.

2015-01-01

Background and Purpose Stroke is a leading cause of disability. Rehabilitation robotics have been developed to aid in recovery after a stroke. This study determined the additional cost of robot-assisted therapy and tested its cost-effectiveness. Methods We estimated the intervention costs and tracked participants' healthcare costs. We collected quality of life using the Stroke Impact Scale and the Health Utilities Index. We analyzed the cost data at 36 weeks postrandomization using multivariate regression models controlling for site, presence of a prior stroke, and Veterans Affairs costs in the year before randomization. Results A total of 127 participants were randomized to usual care plus robot therapy (n=49), usual care plus intensive comparison therapy (n=50), or usual care alone (n=28). The average cost of delivering robot therapy and intensive comparison therapy was $5152 and $7382, respectively (P<0.001), and both were significantly more expensive than usual care alone (no additional intervention costs). At 36 weeks postrandomization, the total costs were comparable for the 3 groups ($17 831 for robot therapy, $19 746 for intensive comparison therapy, and $19 098 for usual care). Changes in quality of life were modest and not statistically different. Conclusions The added cost of delivering robot or intensive comparison therapy was recuperated by lower healthcare use costs compared with those in the usual care group. However, uncertainty remains about the cost-effectiveness of robotic-assisted rehabilitation compared with traditional rehabilitation. Clinical Trial Registration URL: http://clinicaltrials.gov. Unique identifier: NCT00372411. PMID:21757677

Blood transfusion for preventing primary and secondary stroke in people with sickle cell disease.

PubMed

Wang, Winfred C; Dwan, Kerry

2013-11-14

In sickle cell disease, a common inherited haemoglobin disorder, abnormal haemoglobin distorts red blood cells, causing anaemia, vaso-occlusion and dysfunction in most body organs. Without intervention, stroke affects around 10% of children with sickle cell anaemia (HbSS) and recurrence is likely. Chronic blood transfusion dilutes the sickled red blood cells, reducing the risk of vaso-occlusion and stroke. However, side effects can be severe. To assess risks and benefits of chronic blood transfusion regimens in people with sickle cell disease to prevent first stroke or recurrences. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and conference proceedings.Date of the latest search of the Group's Haemoglobinopathies Trials Register: 28 January 2013. Randomised and quasi-randomised controlled trials comparing blood transfusion as prophylaxis for stroke in people with sickle cell disease to alternative or no treatment. Both authors independently assessed the risk of bias of the included trials and extracted data. Searches identified three eligible randomised trials (n = 342). The first two trials addressed the use of chronic transfusion to prevent primary stroke; the third utilized the drug hydroxycarbamide (hydroxyurea) and phlebotomy to prevent both recurrent (secondary) stroke and iron overload in patients who had already experienced an initial stroke. In the first trial (STOP) a chronic transfusion regimen for maintaining sickle haemoglobin lower than 30% was compared with standard care in 130 children with sickle cell disease judged (through transcranial Doppler ultrasonography) as high-risk for first stroke. During the trial, 11 children in the standard care group suffered a stroke compared to one in the transfusion group, odds ratio 0.08 (95% confidence interval 0.01 to 0.66). This meant the trial was terminated early. The transfusion group had a high complications rate, including iron overload, alloimmunisation, and transfusion reactions. The second trial (STOP II) investigated risk of stroke when transfusion was stopped after at least 30 months in this population. The trial closed early due to a significant difference in risk of stroke between participants who stopped transfusion and those who continued as measured by reoccurrence of abnormal velocities on Doppler examination or the occurrence of overt stroke in the group that stopped transfusion. The third trial (SWiTCH) was a non-inferiority trial comparing transfusion and iron chelation (standard management) with hydroxyurea and phlebotomy (alternative treatment) with the combination endpoint of prevention of stroke recurrence and reduction of iron overload. This trial was stopped early after enrolment and follow up of 133 children because of analysis showing futility in reaching the composite primary endpoint. The stroke rate (seven strokes on hydroxyurea and phlebotomy, none on transfusion and chelation, odds ratio 16.49 (95% confidence interval 0.92 to 294.84)) was within the non-inferiority margin, but the liver iron content was not better in the alternative arm. The STOP trial demonstrated a significantly reduced risk of stroke in participants with abnormal transcranial Doppler ultrasonography velocities receiving regular blood transfusions. The follow-up trial (STOP 2) indicated that individuals may revert to former risk status if transfusion is discontinued. The degree of risk must be balanced against the burden of chronic transfusions. The combination of hydroxyurea and phlebotomy is not as effective as "standard" transfusion and chelation in preventing secondary stroke and iron overload. Ongoing multicentre trials are investigating the use of chronic transfusion to prevent silent infarcts, the use of hydroxyurea as an alternative to transfusion in children with abnormal transcranial Doppler ultrasonography velocities, and the use of hydroxyurea to prevent conversion of transcranial Doppler ultrasonography velocities from conditional (borderline) to abnormal values.

Clinical trial regulation in Argentina: overview and analysis of regulatory framework, use of existing tools, and researchers' perspectives to identify potential barriers.

PubMed

White, Lauren; Ortiz, Zulma; Cuervo, Luis G; Reveiz, Ludovic

2011-11-01

To review and analyze the regulatory framework of clinical trial registration, use of existing tools (publicly accessible national/international registration databases), and users' perspectives to identify possible barriers to registration compliance by sponsors and researchers in Argentina. Internationally registered trials recruiting patients in Argentina were found through clincialtrials.gov and the International Clinical Trial Registration Platform (ICTRP) and compared with publically available clinical trials registered through the National Administration of Drugs, Foods, and Medical Devices (ANMAT). A questionnaire addressing hypothesized attitudinal, knowledge-related, idiomatic, technical, economic, and regulatory barriers that could discourage or impede registration of clinical trials was developed, and semi-structured, in-depth interviews were conducted with a purposively selected sample of researchers (investigators, sponsors, and monitors) in Argentina. A response rate of 74.3% (n = 29) was achieved, and 27 interviews were ultimately used for analysis. Results suggested that the high proportion of foreign-sponsored or multinational trials (64.8% of all protocols approved by ANMAT from 1994-2006) may contribute to a communication gap between locally based investigators and foreign-based administrative officials. A lack of knowledge about available international registration tools and limited awareness of the importance of registration were also identified as limiting factors for local investigators and sponsors. To increase compliance and promote clinical trial registration in Argentina, national health authorities, sponsors, and local investigators could take the following steps: implement a grassroots educational campaign to improve clinical trial regulation, support local investigator-sponsor-initiated clinical trials, and/or encourage local and regional scientific journal compliance with standards from the International Committee of Medical Journal Editors (ICMJE) and/or the World Association of Medical Editors (WAME).

Stress reduction in the secondary prevention of cardiovascular disease: randomized, controlled trial of transcendental meditation and health education in Blacks.

PubMed

Schneider, Robert H; Grim, Clarence E; Rainforth, Maxwell V; Kotchen, Theodore; Nidich, Sanford I; Gaylord-King, Carolyn; Salerno, John W; Kotchen, Jane Morley; Alexander, Charles N

2012-11-01

Blacks have disproportionately high rates of cardiovascular disease. Psychosocial stress may contribute to this disparity. Previous trials on stress reduction with the Transcendental Meditation (TM) program have reported improvements in cardiovascular disease risk factors, surrogate end points, and mortality in blacks and other populations. This was a randomized, controlled trial of 201 black men and women with coronary heart disease who were randomized to the TM program or health education. The primary end point was the composite of all-cause mortality, myocardial infarction, or stroke. Secondary end points included the composite of cardiovascular mortality, revascularizations, and cardiovascular hospitalizations; blood pressure; psychosocial stress factors; and lifestyle behaviors. During an average follow-up of 5.4 years, there was a 48% risk reduction in the primary end point in the TM group (hazard ratio, 0.52; 95% confidence interval, 0.29-0.92; P=0.025). The TM group also showed a 24% risk reduction in the secondary end point (hazard ratio, 0.76; 95% confidence interval, 0.51-0.1.13; P=0.17). There were reductions of 4.9 mmHg in systolic blood pressure (95% confidence interval -8.3 to -1.5 mmHg; P=0.01) and anger expression (P<0.05 for all scales). Adherence was associated with survival. A selected mind-body intervention, the TM program, significantly reduced risk for mortality, myocardial infarction, and stroke in coronary heart disease patients. These changes were associated with lower blood pressure and psychosocial stress factors. Therefore, this practice may be clinically useful in the secondary prevention of cardiovascular disease. Clinical Trial Registration- URL: www.clinicaltrials.gov Unique identifier: NCT01299935.

Quality of Anticoagulation Control in Preventing Adverse Events in Heart Failure Patients in Sinus Rhythm: A Warfarin Aspirin Reduced Cardiac Ejection Fraction Trial (WARCEF) Substudy

PubMed Central

Homma, Shunichi; Thompson, John L.P.; Qian, Min; Ye, Siqin; Di Tullio, Marco R.; Lip, Gregory Y.H.; Mann, Douglas L.; Sacco, Ralph L.; Levin, Bruce; Pullicino, Patrick M.; Freudenberger, Ronald S.; Teerlink, John R.; Graham, Susan; Mohr, J.P.; Labovitz, Arthur J.; Buchsbaum, Richard; Estol, Conrado J.; Lok, Dirk J.; Ponikowski, Piotr; Anker, Stefan D.

2015-01-01

Background The aim of this study is to examine the relationship between time in therapeutic range (TTR) and clinical outcomes in heart failure (HF) patients in sinus rhythm (SR) treated with warfarin. Methods and Results We used data from the Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction Trial (WARCEF) to assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke, intracerebral hemorrhage, or death); with death alone; ischemic stroke alone; major hemorrhage alone; and net clinical benefit (primary outcome and major hemorrhage combined). Multivariable Cox models were used to examine how the event risk changed with TTR and to compare the high TTR, low TTR, and aspirin patients, with TTR being treated as a time-dependent covariate. 2,217 patients were included in the analyses, among whom 1,067 were randomized to warfarin and 1,150 were randomized to aspirin. The median (IQR) follow-up duration was 3.6 (2.0–5.0) years. Mean (±SD) age was 61±11.3 years, with 80% being men. The mean (±SD) TTR was 57% (±28.5%). Increasing TTR was significantly associated with reduction in primary outcome (adjusted p<0.001), death alone (adjusted p=0.001), and improved net clinical benefit (adjusted p<0.001). A similar trend was observed for the other two outcomes but significance was not reached (adjusted p=0.082 for ischemic stroke, adjusted p=0.109 for major hemorrhage). Conclusions In HF patients in SR, increasing TTR is associated with better outcome and improved net clinical benefit. Patients in whom good quality anticoagulation can be achieved may benefit from the use of anticoagulants. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938. PMID:25850425

78 FR 42529 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-16

... Stroke Special Emphasis Panel Stroke Trials Network NCCC SEP. Date: August 15, 2013. Time: 8:00 a.m. to...: National Institute of Neurological Disorders and Stroke Special Emphasis Panel Stroke Trial Network Sites... Related to Neurological Disorders; 93.854, Biological Basis Research in the Neurosciences, National...

Vinpocetine for acute ischaemic stroke.

PubMed

Bereczki, D; Fekete, I

2008-01-23

Vasoactive and neuroprotective drugs such as vinpocetine are used to treat stroke in some countries. To assess the effect of vinpocetine in acute ischaemic stroke. We searched the Cochrane Stroke Group Trials Register (last searched February 2007), MEDLINE (1966 to February 2007) and Scopus (1960 to February 2007). We also searched the Internet Stroke Center Stroke Trials Registry, Google Scholar, the science-specific search engine Scirus and Wanfang Data, the leading information provider in China. We contacted researchers in the field and four pharmaceutical companies that manufacture vinpocetine. Searches were complete to February 2007. Unconfounded randomised trials of vinpocetine compared with placebo, or any other reference treatment, in people with acute ischaemic stroke. We included trials if treatment started no later than 14 days after stroke onset. Two review authors independently applied the inclusion criteria. One review author extracted the data, which was then checked by the second review author. We assessed trial quality. The primary outcome measure was death or dependency. We included two trials, involving a total of 70 participants. Data for 63 participants were reported in the two trials combined. The rate of death or dependency did not differ between the treatment and placebo groups at one and three months. The 95% confidence intervals for the outcome measures were wide and included the possibility of both significant benefit and significant harm. No adverse effects were reported. There is not enough evidence to evaluate the effect of vinpocetine on survival or dependency in patients with acute ischaemic stroke.

A strategic plan to accelerate development of acute stroke treatments.

PubMed

Marler, John R

2012-09-01

In order to reenergize acute stroke research and accelerate the development of new treatments, we need to transform the usual design and conduct of clinical trials to test for small but significant improvements in effectiveness, and treat patients as soon as possible after stroke onset when treatment effects are most detectable. This requires trials that include thousands of acute stroke patients. A plan to make these trials possible is proposed. There are four components: (1) free access to the electronic medical record; (2) a large stroke emergency network and clinical trial coordinating center connected in real time to hundreds of emergency departments; (3) a clinical trial technology development center; and (4) strategic leadership to raise funds, motivate clinicians to participate, and interact with politicians, insurers, legislators, and other national and international organizations working to advance the quality of stroke care. © 2012 New York Academy of Sciences.

Patient-centred communication intervention study to evaluate nurse-patient interactions in complex continuing care

PubMed Central

2012-01-01

Background Communication impairment is a frequent consequence of stroke. Patients who cannot articulate their needs respond with frustration and agitation, resulting in poor optimization of post-stroke functions. A key component of patient-centred care is the ability of staff to communicate in a way that allows them to understand the patient’s needs. We developed a patient-centred communication intervention targeting registered and unregulated nursing staff caring for complex continuing care patients with communication impairments post stroke. Research objectives include 1) examining the effects of the intervention on patients’ quality of life, depression, satisfaction with care, and agitation; and (2) examining the extent to which the intervention improves staff’s attitudes and knowledge in caring for patients with communication impairments. The intervention builds on a previous pilot study. Methods/design A quasi-experimental repeated measures non-equivalent control group design in a complex continuing care facility is being used. Patients with a communication impairment post-stroke admitted to the facility are eligible to participate. All staff nurses are eligible. Baseline data are collected from staff and patients. Follow-up will occur at 1 and 3 months post-intervention. Subject recruitment and data collection from 60 patients and 30 staff will take approximately 36 months. The Patient-Centred Communication Intervention consists of three components: (1) development of an individualized patient communication care plan; (2) a one-day workshop focused on communication and behavioural management strategies for nursing staff; and (3) a staff support system. The intervention takes comprehensive patient assessments into account to inform the development of communication and behavioural strategies specifically tailored to each patient. Discussion The Patient-Centred Communication Intervention will provide staff with strategies to facilitate interactions with patients and to minimize agitation associated with considerable stress. The improvement of these interactions will lead to a reduction of agitation, which has the additional significance of increasing patients’ well-being, quality of life, and satisfaction with care. Trial registration ClinicalTrials.gov Identifier NCT01654029 PMID:23050517

Contralaterally Controlled Functional Electrical Stimulation Improves Hand Dexterity in Chronic Hemiparesis: A Randomized Trial

PubMed Central

Knutson, Jayme S.; Gunzler, Douglas D.; Wilson, Richard D.; Chae, John

2016-01-01

Background and Purpose It is unknown whether one method of neuromuscular stimulation for post-stroke upper limb rehabilitation is more effective than another. Our aim was to compare the effects of contralaterally controlled functional electrical stimulation (CCFES) to cyclic neuromuscular electrical stimulation (cNMES). Methods Stroke patients with chronic (> 6 months) moderate to severe upper extremity hemiparesis (n=80) were randomized to receive 10 sessions/week of CCFES- or cNMES-assisted hand opening exercise at home plus 20 sessions of functional task practice in the lab over 12 weeks. The task practice for the CCFES group was stimulation-assisted. The primary outcome was change in Box and Blocks Test (BBT) score at 6-months post-treatment. Upper extremity Fugl-Meyer (UEFM) and Arm Motor Abilities Test (AMAT) were also measured. Results At 6-months post-treatment, the CCFES group had greater improvement on the BBT, 4.6 (95% CI: 2.2, 7.0), than the cNMES group, 1.8 (95% CI: 0.6, 3.0); between-group difference, 2.8 (95% CI: 0.1, 5.5), p=0.045. No significant between-group difference was found for the UEFM (p=.888) or AMAT (p=.096). Participants who had the largest improvements on BBT were less than two years post-stroke with moderate (i.e., not severe) hand impairment at baseline. Among these, the 6-month post-treatment BBT gains of the CCFES group, 9.6 (95% CI: 5.6, 13.6), were greater than those of the cNMES group, 4.1 (95% CI: 1.7, 6.5); between-group difference, 5.5 (95% CI: 0.8, 10.2), p=0.023. Conclusions CCFES improved hand dexterity more than cNMES in chronic stroke survivors. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00891319. PMID:27608819

Characteristics and Outcomes of Very Elderly Enrolled in a Prehospital Stroke Research Study.

PubMed

Sanossian, Nerses; Apibunyopas, Kathleen C; Liebeskind, David S; Starkman, Sidney; Burgos, Adrian M; Conwit, Robin; Eckstein, Marc; Pratt, Frank; Stratton, Sam; Hamilton, Scott; Saver, Jeffrey L

2016-11-01

Greater numbers of individuals aged ≥80 years enjoy a high quality of life, yet historically stroke trials have excluded this population. We aimed to describe a population of very elderly successfully enrolled into an acute stroke trial and compare their characteristics and outcomes with the younger cohort. We analyzed consecutive patients enrolled <2 hours of symptom onset in a prehospital stroke treatment trial, the FAST-MAG clinical trial (Field Administration of Stroke Therapy-Magnesium). We gathered demographic, treatment, and outcome data for nonelderly (<80 years old), very elderly (≥80 years old), and extreme elderly (≥90 years old). We describe key differences in the population of elderly and the impact of their inclusion on the clinical trial. Of 1700 participants in FAST-MAG, there were 1210 nonelderly, 490 very elderly, and 60 extreme elderly subjects. Very elderly stroke patients successfully enrolled in a research study were more likely to be women, white, and have an ischemic mechanism rather than an intracerebral hemorrhage. Although the very elderly had generally poorer outcomes, 4 in 10 were functionally independent at 90 days. Inclusion of the very elderly population in acute stroke clinical trials would both significantly increase study participation and generalizability of future acute stroke clinical trials. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059332. © 2016 American Heart Association, Inc.

Registration status and outcome reporting of trials published in core headache medicine journals.

PubMed

Rayhill, Melissa L; Sharon, Roni; Burch, Rebecca; Loder, Elizabeth

2015-11-17

To evaluate randomized controlled trial (RCT) registration and outcome reporting compliance in core headache medicine journals. We identified RCTs published in core journals (Headache, Cephalalgia, and the Journal of Headache and Pain) from 2005 through 2014. We searched articles for trial registration numbers, which were verified in the corresponding trial registry. We categorized trial funding sources as industry, academic, government, or mixed. We contacted corresponding authors to assess reasons for nonregistration. We evaluated whether primary outcomes in trial registries matched those in corresponding publications. The journals published 225 RCTs over the study period. Fifty-eight of 225 (26%) reported a trial registration number in the article that could be linked to a corresponding registry entry. Trial registration rates increased over the 9 years of the study. Forty-six of 118 (39%) of industry-funded studies were registered compared with 27% of academic and 0% of government-funded studies. Only 5% of RCTs were prospectively registered, reported primary outcomes identical to those in the trial registry, and did not report unacknowledged post hoc outcomes. The most common reason for nonregistration was lack of awareness. Only about a quarter of the articles published in the core headache medicine journals are compliant with trial registration, but compliance has increased over time. Selective reporting of outcomes remains a problem, and very few trials met all 3 reporting standards assessed in this study. Efforts to improve the quality of trial reporting in the headache literature should continue. © 2015 American Academy of Neurology.

Improving transparency and reproducibility through registration: The status of intervention trials published in clinical psychology journals.

PubMed

Cybulski, Lukasz; Mayo-Wilson, Evan; Grant, Sean

2016-09-01

Prospective registration increases the validity of randomized controlled trials (RCTs). In the United States, registration is a legal requirement for drugs and devices regulated by the Food and Drug Administration (FDA), and many biomedical journals refuse to publish trials that are not registered. Trials in clinical psychology have not been subject to these requirements; it is unknown to what extent they are registered. We searched the 25 highest-impact clinical psychology journals that published at least 1 RCT of a health-related psychological intervention in 2013. For included trials, we evaluated their registration status (prospective, retrospective, not registered) and the completeness of their outcome definitions. We identified 163 articles that reported 165 RCTs; 73 (44%) RCTs were registered, of which only 25 (15%) were registered prospectively. Of registered RCTs, only 42 (58%) indicated their registration status in the publication. Only 2 (1% of all trials) were registered prospectively and defined their primary outcomes completely. For the primary outcome(s), 72 (99%) of all registrations defined the domain, 67 (92%) the time frame, and 48 (66%) the specific measurements. Only 19 (26%) and 5 (7%) defined the specific metric and method of aggregation, respectively, for all primary outcomes. Very few reports of RCTs published in clinical psychology journals were registered prospectively and completely. Clinical psychology journals could improve transparency and reproducibility, as well as reduce bias, by requiring complete prospective trial registration for publication and by including trial registration numbers in all reports of RCTs. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

What is the value of conducting a trial of r-tPA for the treatment of mild stroke patients?

PubMed

Guzauskas, Gregory F; Chen, Er; Lalla, Deepa; Yu, Elaine; Tayama, Darren; Veenstra, David L

2017-02-01

Background The Phase IIIb, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Alteplase in Patients With Mild Stroke: Rapidly Improving Symptoms and Minor Neurologic Deficits (PRISMS) trial will assess r-tPA in ischemic stroke patients who present with mild deficits (i.e. mild stroke). Aims To assess PRISMS's societal value in clarifying the optimal care for patients with mild ischemic stroke. Methods A value of information (VOI) decision model was developed to compare the outcomes of mild stroke patients treated vs. not treated with r-tPA. Model inputs were derived from a subset of Third International Stroke Trial patients, a recent meta-analysis of r-tPA trials, expert opinion, and other published sources. VOI analyses were also used to assess the expected US societal value of the PRISMS trial and the expected value of reducing uncertainty in key trial estimates. Results The expected net societal value of the PRISMS trial was approximately $210 million ($160 m-$260 m), representing a six-fold return on investment. The value of reducing uncertainty in r-tPA efficacy was approximately $150 million ($100 m-$200 m), while reducing uncertainty in r-tPA safety (increased risk for symptomatic intracranial hemorrhage) did not add additional value in comparison. Conclusions Developing a better understanding of the outcomes of r-tPA treatment in patients with mild ischemic stroke will provide tremendous societal value by clarifying current uncertainty around treatment effectiveness. Enrollment in the PRISMS trial for patients presenting with mild ischemic stroke within 0-3 h of symptom onset should be highly encouraged.

Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation.

PubMed

Hart, Robert G; Pearce, Lesly A; Aguilar, Maria I

2007-06-19

Atrial fibrillation is a strong independent risk factor for stroke. To characterize the efficacy and safety of antithrombotic agents for stroke prevention in patients who have atrial fibrillation, adding 13 recent randomized trials to a previous meta-analysis. Randomized trials identified by using the Cochrane Stroke Group search strategy, 1966 to March 2007, unrestricted by language. All published randomized trials with a mean follow-up of 3 months or longer that tested antithrombotic agents in patients who have nonvalvular atrial fibrillation. Two coauthors independently extracted information regarding interventions; participants; and occurrences of ischemic and hemorrhagic stroke, major extracranial bleeding, and death. Twenty-nine trials included 28,044 participants (mean age, 71 years; mean follow-up, 1.5 years). Compared with the control, adjusted-dose warfarin (6 trials, 2900 participants) and antiplatelet agents (8 trials, 4876 participants) reduced stroke by 64% (95% CI, 49% to 74%) and 22% (CI, 6% to 35%), respectively. Adjusted-dose warfarin was substantially more efficacious than antiplatelet therapy (relative risk reduction, 39% [CI, 22% to 52%]) (12 trials, 12 963 participants). Other randomized comparisons were inconclusive. Absolute increases in major extracranial hemorrhage were small (< or =0.3% per year) on the basis of meta-analysis. Methodological features and quality varied substantially and often were incompletely reported. Adjusted-dose warfarin and antiplatelet agents reduce stroke by approximately 60% and by approximately 20%, respectively, in patients who have atrial fibrillation. Warfarin is substantially more efficacious (by approximately 40%) than antiplatelet therapy. Absolute increases in major extracranial hemorrhage associated with antithrombotic therapy in participants from the trials included in this meta-analysis were less than the absolute reductions in stroke. Judicious use of antithrombotic therapy importantly reduces stroke for most patients who have atrial fibrillation.

Stroke: Hope through Research

MedlinePlus

... the Barthel Index. Imaging for the Diagnosis of Acute Stroke Health care professionals also use a variety ... risk population. top Ongoing Clinical Trials Albumin in Acute Ischemic Stroke (ALIAS) Trial Human serum albumin is ...

Apixaban 5 and 2.5 mg twice-daily versus warfarin for stroke prevention in nonvalvular atrial fibrillation patients: Comparative effectiveness and safety evaluated using a propensity-score-matched approach

PubMed Central

Keshishian, Allison; Hamilton, Melissa; Horblyuk, Ruslan; Gupta, Kiran; Luo, Xuemei; Mardekian, Jack; Friend, Keith; Nadkarni, Anagha; Pan, Xianying; Lip, Gregory Y. H.; Deitelzweig, Steve

2018-01-01

Prior real-world studies have shown that apixaban is associated with a reduced risk of stroke/systemic embolism (stroke/SE) and major bleeding versus warfarin. However, few studies evaluated the effectiveness and safety of apixaban according to its dosage, and most studies contained limited numbers of patients prescribed 2.5 mg twice-daily (BID) apixaban. Using pooled data from 4 American claims database sources, baseline characteristics and outcomes for patients prescribed 5 mg BID and 2.5 mg BID apixaban versus warfarin were compared. After 1:1 propensity-score matching, 31,827 5 mg BID apixaban-matched warfarin patients and 6600 2.5 mg BID apixaban-matched warfarin patients were identified. Patients prescribed 2.5 mg BID apixaban were older, had clinically more severe comorbidities, and were more likely to have a history of stroke and bleeding compared with 5 mg BID apixaban patients. Compared with warfarin, 5 mg BID apixaban was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.60–0.81) and major bleeding (HR: 0.59, 95% CI: 0.53–0.66). Compared with warfarin, 2.5 mg BID apixaban was also associated with a lower risk of stroke/SE (HR: 0.63, 95% CI: 0.49–0.81) and major bleeding (HR: 0.59, 95% CI: 0.49–0.71). In this real-world study, both apixaban doses were assessed in 2 patient groups differing in age and clinical characteristics. Each apixaban dose was associated with a lower risk of stroke/SE and major bleeding compared with warfarin in the distinct population for which it is being prescribed in United States clinical practice. Trial registration: Clinicaltrials.Gov Identifier: NCT03087487. PMID:29373602

Predictors of intensive care unit admission and mortality in patients with ischemic stroke: investigating the effects of a pulmonary rehabilitation program.

PubMed

Güngen, Belma Doğan; Tunç, Abdulkadir; Aras, Yeşim Güzey; Gündoğdu, Aslı Aksoy; Güngen, Adil Can; Bal, Serdar

2017-07-11

The aim of this study was to investigate the predictors of intensive care unit (ICU) admission and mortality among stroke patients and the effects of a pulmonary rehabilitation program on stroke patients. This prospective study enrolled 181 acute ischemic stroke patients aged between 40 and 90 years. Demographical characteristics, laboratory tests, diffusion-weighed magnetic resonance imaging (DWI-MRI) time, nutritional status, vascular risk factors, National Institute of Health Stroke Scale (NIHSS) scores and modified Rankin scale (MRS) scores were recorded for all patients. One-hundred patients participated in the pulmonary rehabilitation program, 81 of whom served as a control group. Statistically, one- and three-month mortality was associated with NIHSS and MRS scores at admission and three months (p<0.001; r=0.440, r=0.432, r=0.339 and r=0.410, respectively). One and three months mortality- ICU admission had a statistically significant relationship with parenteral nutrition (p<0.001; r=0.346, r=0.300, respectively; r=0.294 and r=0.294, respectively). Similarly, there was also a statistically significant relationship between pneumonia onset and one- and three-month mortality- ICU admission (p<0.05; r=0.217, r=0.127, r=0.185 and r=0.185, respectively). A regression analysis showed that parenteral nutrition (odds ratio [OR] =13.434, 95% confidence interval [CI] =1.148-157.265, p=0.038) was a significant predictor of ICU admission. The relationship between pulmonary physiotherapy (PPT) and ICU admission- pneumonia onset at the end of three months was statistically significant (p=0.04 and p=0.043, respectively). This study showed that PPT improved the prognosis of ischemic stroke patients. We believe that a pulmonary rehabilitation program, in addition to general stroke rehabilitation programs, can play a critical role in improving survival and functional outcomes. NCT03195907 . Trial registration date: 21.06.2017 'Retrospectively registered'.

Effects of sex difference on clinical features of acute ischemic stroke in Japan.

PubMed

Maeda, Koichiro; Toyoda, Kazunori; Minematsu, Kazuo; Kobayashi, Shotai

2013-10-01

Sex differences in stroke characteristics and outcomes have been inconsistent. The goal of this study was to determine the influence of sex on underlying patient characteristics, stroke subtypes and conditions, and outcomes after ischemic stroke from a nationwide registration study. A total of 33,953 patients with acute ischemic stroke, including 13,323 women, were registered in a multicenter, hospital-based registration study based on a computerized database from 162 Japanese institutes (the Japan Standard Stroke Registry Study) between January 2000 and November 2007. Women were significantly older than men at stroke onset (75.0 ± 11.7 v 69.3 ± 11.4 years; P < .0001). After age adjustment, women more frequently had cardioembolic events (odds ratio [OR] 1.090; 95% confidence interval [95% CI] 1.036-1.146; P = .0009) and other strokes (OR 1.177; 95% CI 1.079-1.284; P = .0003) and were more hypertensive (OR 1.056; 95% CI 1.006-1.108; P = .0267) and more dyslipidemic (OR 1.301; 95% CI 1.234-1.373; P < .0001) than men. After multivariate adjustment, onset-to-arrival time was longer (β = 0.0554; P = .026), the initial National Institutes of Health Stroke Scale score was higher (β = 0.1565; P < .001), and the duration of hospitalization was longer (β = 0.035; P = .010) in women than in men. At hospital discharge, women less commonly had a modified Rankin Scale (mRS) score of 0 to 1 (OR 0.802; 95% CI 0.741-0.868; P < .0001) and more commonly had a mRS score of 4 to 6 (OR 1.410; 95% CI 1.293-1.537; P < .0001) than men. Women developed more severe strokes than men in Japan. After multivariate adjustment for initial severity and other characteristics, acute care hospital stays were longer and stroke outcomes at discharge were worse in women than in men. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Effects of virtual reality for stroke individuals based on the International Classification of Functioning and Health: a systematic review.

PubMed

Palma, Gisele Carla Dos Santos; Freitas, Tatiana Beline; Bonuzzi, Giordano Márcio Gatinho; Soares, Marcos Antonio Arlindo; Leite, Paulo Henrique Wong; Mazzini, Natália Araújo; Almeida, Murilo Ruas Groschitz; Pompeu, José Eduardo; Torriani-Pasin, Camila

2017-05-01

This review determines the effects of virtual reality interventions for stroke subjects based on the International Classification of Functioning, Disability,and Health (ICF) framework. Virtual reality is a promising tool for therapy for stroke rehabilitation, but the effects of virtual reality interventions on post-stroke patients based on the specific ICF domains (Body Structures, Body Functions, Activity, and Participation) have not been investigated. A systematic review was conducted, including trials with adults with a clinical diagnosis of a chronic, subacute, or acute stroke. Eligible trials had to include studies with an intervention protocol and follow-up, with a focus on upper limbs and/or lower limbs and/or balance. The Physiotherapy Evidence Database (PEDro) was used to assess the methodological quality of randomized controlled trials. Each trial was separated according to methodological quality into a high-quality trial (PEDro ≥ 6) and a low-quality trial (PEDro ≤ 6). Only high-quality trials were analyzed specifically based on the outcome of these trials. In total, 54 trials involving 1811 participants were included. Of the papers included and considered high quality, 14 trials evaluated areas of the Body Structures component, 20 trials of the Body Functions domain, 17 trials of the Activity component, and 8 trials of the Participation domain. In relation to ICF Part 2, four trials evaluated areas of the Personal Factors component and one trial evaluated domains of the Environmental Factors component. The effects of virtual reality on stroke rehabilitation based on the ICF framework are positive in Body Function and Body Structure. However, the results in the domains Activity and Participation are inconclusive. More high-quality clinical trials are needed to confirm the effectiveness of virtual reality in the domains of Activity and Participation.

Cortical changes after mental imagery training combined with electromyography-triggered electrical stimulation in patients with chronic stroke.

PubMed

Hong, Il Ki; Choi, Jong Bae; Lee, Jong Ha

2012-09-01

Paresis of the upper extremity after stroke is not effectively solved by existing therapies. We investigated whether mental imagery training combined with electromyogram-triggered electric stimulation improved motor function of the paretic upper extremity in patients with chronic stroke and induced cortical changes. Fourteen subjects with chronic stroke (≥12 months) were randomly allocated to receive mental imagery training combined with electromyogram-triggered electric stimulation (n=7) or generalized functional electric stimulation (n=7) on the forearm extensor muscles of the paretic extremity in 2 20-minute daily sessions 5 days a week for 4 weeks. The upper extremity component of the Fugl-Meyer Motor Assessment, the Motor Activity Log, the modified Barthel Index, and (18)F-fluorodeoxyglucose brain positron emission tomography were measured before and after the intervention. The group receiving mental imagery training combined with electromyogram-triggered electric stimulation exhibited significant improvements in the upper extremity component of the Fugl-Meyer Motor Assessment after intervention (median, 7; interquartile range, 5-8; P<0.05), but the group receiving functional electric stimulation did not (median, 0; interquartile range, 0-3). Differences in score changes between the 2 groups were significant. The mental imagery training combined with electromyogram-triggered electric stimulation group showed significantly increased metabolism in the contralesional supplementary motor, precentral, and postcentral gyri (P(uncorrected)<0.001) after the intervention, but the functional electric stimulation group showed no significant differences. Mental imagery training combined with electromyogram-triggered electric stimulation improved motor function of the paretic extremity in patients with chronic stroke. The intervention increased metabolism in the contralesional motor-sensory cortex. Clinical Trial Registration- URL: https://e-irb.khmccri.or.kr/eirb/receipt/index.html?code=02&status=5. Unique identifier: KHUHMDIRB 1008-02.

Efficacy of antiplatelet therapy in secondary prevention following lacunar stroke: pooled analysis of randomized trials.

PubMed

Kwok, Chun Shing; Shoamanesh, Ashkan; Copley, Hannah Charlotte; Myint, Phyo Kyaw; Loke, Yoon K; Benavente, Oscar R

2015-04-01

Lacunar stroke accounts for ≈25% of ischemic stroke, but optimal antiplatelet regimen to prevent stroke recurrence remains unclear. We aimed to evaluate the efficacy of antiplatelet agents in secondary stroke prevention after a lacunar stroke. We searched MEDLINE, Embase, and the Cochrane library for randomized controlled trials that reported risk of recurrent stroke or death with antiplatelet therapy in patients with lacunar stroke. We used random effects meta-analysis and evaluated heterogeneity with I(2). We included 17 trials with 42,234 participants (mean age 64.4 years, 65% male) and follow up ranging from 4 weeks to 3.5 years. Compared with placebo, any single antiplatelet agent was associated with a significant reduction in recurrence of any stroke (risk ratio [RR] 0.77, 0.62-0.97, 2 studies) and ischemic stroke (RR 0.48, 0.30-0.78, 2 studies), but not for the composite outcome of any stroke, myocardial infarction, or death (RR 0.89, 0.75-1.05, 2 studies). When other antiplatelet agents (ticlodipine, cilostazol, and dipyridamole) were compared with aspirin, there was no consistent reduction in stroke recurrence (RR 0.91, 0.75-1.10, 3 studies). Dual antiplatelet therapy did not confer clear benefit over monotherapy (any stroke RR 0.83, 0.68-1.00, 3 studies; ischemic stroke RR 0.80, 0.62-1.02, 3 studies; composite outcome RR 0.90, 0.80-1.02, 3 studies). Our results suggest that any of the single antiplatelet agents compared with placebo in the included trials is adequate for secondary stroke prevention after lacunar stroke. Dual antiplatelet therapy should not be used for long-term stroke prevention in this stroke subtype. © 2015 American Heart Association, Inc.

Optimizing stroke clinical trial design: estimating the proportion of eligible patients.

PubMed

Taylor, Alexis; Castle, Amanda; Merino, José G; Hsia, Amie; Kidwell, Chelsea S; Warach, Steven

2010-10-01

Clinical trial planning and site selection require an accurate estimate of the number of eligible patients at each site. In this study, we developed a tool to calculate the proportion of patients who would meet a specific trial's age, baseline severity, and time to treatment inclusion criteria. From a sample of 1322 consecutive patients with acute ischemic cerebrovascular syndromes, we developed regression curves relating the proportion of patients within each range of the 3 variables. We used half the patients to develop the model and the other half to validate it by comparing predicted vs actual proportions who met the criteria for 4 current stroke trials. The predicted proportion of patients meeting inclusion criteria ranged from 6% to 28% among the different trials. The proportion of trial-eligible patients predicted from the first half of the data were within 0.4% to 1.4% of the actual proportion of eligible patients. This proportion increased logarithmically with National Institutes of Health Stroke Scale score and time from onset; lowering the baseline limits of the National Institutes of Health Stroke Scale score and extending the treatment window would have the greatest impact on the proportion of patients eligible for a stroke trial. This model helps estimate the proportion of stroke patients eligible for a study based on different upper and lower limits for age, stroke severity, and time to treatment, and it may be a useful tool in clinical trial planning.

Efficacy of homocysteine lowering therapy with folic acid in stroke prevention: a meta-analysis

PubMed Central

Lee, Meng; Hong, Keun-Sik; Chang, Shen-Chih; Saver, Jeffrey L.

2010-01-01

Background and Purpose Although lower serum homocysteine concentration is associated with a reduced risk of stroke in epidemiologic studies, randomized controlled trials (RCTs) have yielded mixed findings regarding the effect of therapeutic homocysteine lowering on stroke prevention. We performed a meta-analysis of RCTs to assess the efficacy of folic acid supplementation in the prevention of stroke. Methods Salient trials were identified by formal literature search. Relative risk (RR) with 95% confidence interval (CI) was used as a measure of the association between folic acid supplementation and risk of stroke, pooling data across trials using a fixed-effects model. Results The search identified 13 RCTs of folic acid therapy to reduce homocysteine, enrolling 39,005 participants, in which stroke was reported as an outcome measure. Across all trials, folic acid supplementation was associated with a trend toward mild benefit that did not reach statistical significance in reducing the risk of stroke (RR 0.93, 95% CI 0.85-1.03; p=0.16). The RR for non-secondary prevention trials was 0.89 (95% CI 0.79-0.99; p=0.03). In stratified analyses, a greater beneficial effect was seen in the trials testing combination therapy of folic acid plus vitamins B6 and B12 (RR 0.83, 0.71-0.97; p=0.02) and in the trials which disproportionately enrolled male patients (men/women > 2, RR 0.84, 0.74-0.94; p=0.003). Conclusions Folic acid supplementation did not demonstrate a major effect in averting stroke. However, potential mild benefits in primary stroke prevention, especially when folate is combined with B vitamins and in male patients, merit further investigation. PMID:20413740

Safety and effectiveness of stem cell therapies in early-phase clinical trials in stroke: a systematic review and meta-analysis.

PubMed

Nagpal, Anjali; Choy, Fong Chan; Howell, Stuart; Hillier, Susan; Chan, Fiona; Hamilton-Bruce, Monica A; Koblar, Simon A

2017-08-30

Stem cells have demonstrated encouraging potential as reparative therapy for patients suffering from post-stroke disability. Reperfusion interventions in the acute phase of stroke have shown significant benefit but are limited by a narrow window of opportunity in which they are beneficial. Thereafter, rehabilitation is the only intervention available. The current review summarises the current evidence for use of stem cell therapies in stroke from early-phase clinical trials. The safety and feasibility of administering different types of stem cell therapies in stroke seem to be reasonably proven. However, the effectiveness needs still to be established through bigger clinical trials with more pragmatic clinical trial designs that address the challenges raised by the heterogeneous nature of stroke per se, as well those due to unique characteristics of stem cells as therapeutic agents.

Three controlled trials of interventions to increase recruitment to a randomized controlled trial of mobile phone based smoking cessation support.

PubMed

Free, Caroline; Hoile, Elizabeth; Robertson, Steven; Knight, Rosemary

2010-06-01

Recruitment is a major challenge for trials but there is little evidence regarding interventions to increase trial recruitment. We report three controlled trials of interventions to increase recruitment to the Txt2stop trial. To evaluate: Trial 1. The impact on registrations of a text message regarding an online registration facility; Trial 2. The impact on randomizations of sending pound5 with a covering letter to those eligible to join the trial; Trial 3. The impact on randomizations of text messages containing quotes from existing participants. Single blind controlled trials with allocation concealment. Trial 1: A text message regarding our new online registration facility; Trial 2: A letter with pound5 enclosed; Trial 3: A series of four text messages containing quotes from participants. The control group in each trial received standard Txt2stop procedures. Trial 1: 3.6% (17/470) of the intervention group and 1.1% (5/467) of the control group registered for the trial, risk difference 2.5% (95% CI 0.6-4.5). 0% (0/ 470) of the intervention group and 0.2% (1/467) of the control group registered successfully online, risk difference -0.2 (95% CI -0.6-0.2); Trial 2: 4.5% (11/246) of the intervention group and 0.4% (1/245) of the control group were randomized into the Txt2stop trial, risk difference 4.0% (95% CI 1.4-6.7); Trial 3: 3.5% (14/405) of the intervention group and 0% (0/406) of the control group were randomized into the Txt2stop trial, risk difference 3.5 (95% CI 1.7-5.2). There were no baseline data available for trial 1. Allocation of participant IDs in trials 2 and 3 were systematic. Sending a text message about an online registration facility increased registrations to Txt2stop, but did not increase online registrations. Sending a pound5 reimbursement for participants' time and sending text messages containing quotes from existing participants increased randomizations into the Txt2stop trial. Clinical Trials 2010; 7: 265-273. http://ctj.sagepub.com.

Prospective registration of clinical trials in India: strategies, achievements & challenges.

PubMed

Tharyan, Prathap

2009-02-01

This paper traces the development of the Clinical Trial Registry-India (CTRI) against the backdrop of the inequities in healthcare and the limitations in the design, conduct, regulation, oversight and reporting of clinical trials in India. It describes the scope and goals of the CTRI, the data elements it seeks and the process of registering clinical trials. It reports progress in trial registration in India and discusses the challenges in ensuring that healthcare decisions are informed by all the evidence. A descriptive survey of developments in clinical trial registration in India from publications in the Indian medical literature supplemented by first hand knowledge of these developments and an evaluation of how well clinical trials registered in the CTRI up to 10 January, 2009 comply with the requirements of the CTRI and the World Health Organization's International Clinical Trial Registry (WHO ICTRP). Considerable inequities exist within the Indian health system. Deficiencies in healthcare provision and uneven regulation of, and access to, affordable healthcare co-exists with a large private health system of uneven quality. India is now a preferred destination for outsourced clinical trials but is plagued by poor ethical oversight of the many trial sites and scant information of their existence. The CTRI's vision of conforming to international requirements for transparency and accountability but also using trial registration as a means of improving trial design, conduct and reporting led to the selection of registry-specific dataset items in addition to those endorsed by the WHO ICTRP. Compliance with these requirements is good for the trials currently registered but these trials represent only a fraction of the trials in progress in India. Prospective trial registration is a reality in India. The challenges facing the CTRI include better engagement with key stakeholders to ensure increased prospective registration of clinical trials and utilization of existing legislative opportunities to complement these efforts. © 2009 Blackwell Publishing Asia Pty Ltd and Chinese Cochrane Center, West China Hospital of Sichuan University.

Window Of Opportunity: Estrogen As A Treatment For Ischemic Stroke✰

PubMed Central

Liu, Ran; Yang, Shao-Hua

2013-01-01

The neuroprotection research in the last 2 decades has witnessed a growing interest in the functions of estrogens as neuroprotectants against neurodegenerative diseases including stroke. The neuroprotective action of estrogens has been well demonstrated in both in vitro and in vivo models of ischemic stroke. However, the major conducted clinical trials so far have raised concern for the protective effect of estrogen replacement therapy in postmenopausal women. The discrepancy could be partly due to the mistranslation between the experimental stroke research and clinical trials. While predominant experimental studies tested the protective action of estrogens on ischemic stroke using acute treatment paradigm, the clinical trials have mainly focused on the effect of estrogen replacement therapy on the primary and secondary stroke prevention which has not been adequately addressed in the experimental stroke study. Although the major conducted clinical trials have indicated that estrogen replacement therapy has an adverse effect and raise concern for long term estrogen replacement therapy for stroke prevention, these are not appropriate for assessing the potential effects of acute estrogen treatment on stroke protection. The well established action of estrogen in the neurovascular unit and its potential interaction with recombinant tissue plasminogen activator (rtPA) makes it a candidate for the combined therapy with rtPA for the acute treatment of ischemic stroke. On the other hand, the “critical period” and newly emerged “biomarkers window” hypotheses have indicated that many clinical relevant factors have been underestimated in the experimental ischemic stroke research. The development and application of ischemic stroke models that replicate the clinical condition is essential for further evaluation of acute estrogen treatment on ischemic stroke which might provide critical information for future clinical trials. PMID:23340160

Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited.

PubMed

Sandercock, Peter; Lindley, Richard; Wardlaw, Joanna; Dennis, Martin; Innes, Karen; Cohen, Geoff; Whiteley, Will; Perry, David; Soosay, Vera; Buchanan, David; Venables, Graham; Czlonkowska, Anna; Kobayashi, Adam; Berge, Eivind; Slot, Karsten Bruins; Murray, Veronica; Peeters, Andre; Hankey, Graeme J; Matz, Karl; Brainin, Michael; Ricci, Stefano; Cantisani, Teresa A; Gubitz, Gordon; Phillips, Stephen J; Antonio, Arauz; Correia, Manuel; Lyrer, Phillippe; Kane, Ingrid; Lundstrom, Erik

2011-11-30

Intravenous recombinant tissue plasminogen activator (rtPA) is approved in Europe for use in patients with acute ischaemic stroke who meet strictly defined criteria. IST-3 sought to improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of rtPA in acute ischaemic stroke, and to determine whether a wider range of patients might benefit. International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rtPA in acute ischaemic stroke. Suitable patients had to be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracranial haemorrhage and stroke mimics. The initial pilot phase was double blind and then, on 01/08/2003, changed to an open design. Recruitment began on 05/05/2000 and closed on 31/07/2011, by which time 3035 patients had been included, only 61 (2%) of whom met the criteria for the 2003 European approval for thrombolysis. 1617 patients were aged over 80 years at trial entry. The analysis plan will be finalised, without reference to the unblinded data, and published before the trial data are unblinded in early 2012. The main trial results will be presented at the European Stroke Conference in Lisbon in May 2012 with the aim to publish simultaneously in a peer-reviewed journal. The trial result will be presented in the context of an updated Cochrane systematic review. We also intend to include the trial data in an individual patient data meta-analysis of all the relevant randomised trials. The data from the trial will: improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of iv rtPA in acute ischaemic stroke; provide: new evidence on the balance of risk and benefit of intravenous rtPA among types of patients who do not clearly meet the terms of the current EU approval; and, provide the first large-scale randomised evidence on effects in patients over 80, an age group which had largely been excluded from previous acute stroke trials. ISRCTN25765518.

Characterizing stroke lesions using digital templates and lesion quantification tools in a web-based imaging informatics system for a large-scale stroke rehabilitation clinical trial

NASA Astrophysics Data System (ADS)

Wang, Ximing; Edwardson, Matthew; Dromerick, Alexander; Winstein, Carolee; Wang, Jing; Liu, Brent

2015-03-01

Previously, we presented an Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE) imaging informatics system that supports a large-scale phase III stroke rehabilitation trial. The ePR system is capable of displaying anonymized patient imaging studies and reports, and the system is accessible to multiple clinical trial sites and users across the United States via the web. However, the prior multicenter stroke rehabilitation trials lack any significant neuroimaging analysis infrastructure. In stroke related clinical trials, identification of the stroke lesion characteristics can be meaningful as recent research shows that lesion characteristics are related to stroke scale and functional recovery after stroke. To facilitate the stroke clinical trials, we hope to gain insight into specific lesion characteristics, such as vascular territory, for patients enrolled into large stroke rehabilitation trials. To enhance the system's capability for data analysis and data reporting, we have integrated new features with the system: a digital brain template display, a lesion quantification tool and a digital case report form. The digital brain templates are compiled from published vascular territory templates at each of 5 angles of incidence. These templates were updated to include territories in the brainstem using a vascular territory atlas and the Medical Image Processing, Analysis and Visualization (MIPAV) tool. The digital templates are displayed for side-by-side comparisons and transparent template overlay onto patients' images in the image viewer. The lesion quantification tool quantifies planimetric lesion area from user-defined contour. The digital case report form stores user input into a database, then displays contents in the interface to allow for reviewing, editing, and new inputs. In sum, the newly integrated system features provide the user with readily-accessible web-based tools to identify the vascular territory involved, estimate lesion area, and store these results in a web-based digital format.

Quality of life after intra-arterial treatment for acute ischemic stroke in the MR CLEAN trial-Update.

PubMed

Schreuders, Jennifer; van den Berg, Lucie A; Fransen, Puck Ss; Berkhemer, Olvert A; Beumer, Debbie; Lingsma, Hester F; van Oostenbrugge, Robert J; van Zwam, Wim H; Majoie, Charles Blm; van der Lugt, Aad; de Kort, Paul Lm; Roos, Yvo Bwem; Dippel, Diederik Wj

2017-10-01

Background Health-related quality of life measured with the EuroQol Group 5-Dimension Self-Report Questionnaire was one of the secondary outcomes in the Multicenter Randomized Clinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN). We reported no statistically significant difference in EuroQol Group 5-Dimension Self-Report Questionnaire score between the intervention and control groups, but deaths were not included. Aims Reanalyze the effect of intra-arterial treatment for large vessel occlusion in acute ischemic stroke patients on health-related quality of life in more detail. We now include patients who died during follow-up. Methods The EuroQol Group 5-Dimension Self-Report Questionnaire questionnaires were obtained 90 days after treatment. We used the Dutch tariff to derive a utility index from the EuroQol Group 5-Dimension Self-Report Questionnaire score. Treatment effect was estimated with the Mann-Whitney U test and linear regression. The effect of treatment on the distribution of EuroQol Group 5-Dimension Self-Report Questionnaire dimension scores was assessed with ordinal logistic regression. Results We obtained EuroQol Group 5-Dimension Self-Report Questionnaire scores from 457 (91.7%) of the 500 patients, including 108 who died before follow-up. Median EuroQol Group 5-Dimension Self-Report Questionnaire score in the intervention group was 0.57, and 0.39 in the control group (p = 0.03). Treatment effect estimated with linear regression was 0.07 (95%CI: -0.001 to 0.143). Treatment specifically affected EuroQol Group 5-Dimension Self-Report Questionnaire dimensions "mobility" (OR: 0.43, 95%CI: 0.29-0.66), "self-care" (OR: 0.60, 95%CI: 0.41-0.89), and "usual activities" (OR: 0.53, 95%CI: 0.36-0.79). Conclusion Treatment had a limited effect on quality of life, as measured with the EuroQol Group 5-Dimension Self-Report Questionnaire. Nevertheless, patients with acute ischemic stroke caused by an intracranial occlusion in the anterior circulation, who had intra-arterial treatment, experience better health-related quality of life than patients without intra-arterial treatment. Trial Registration URL: http://www.isrctn.com/ISRCTN10888758 Unique identifier: ISRCTN10888758.

Transparency of Outcome Reporting and Trial Registration of Randomized Controlled Trials Published in the Journal of Consulting and Clinical Psychology

PubMed Central

Azar, Marleine; Riehm, Kira E.; McKay, Dean; Thombs, Brett D.

2015-01-01

Background Confidence that randomized controlled trial (RCT) results accurately reflect intervention effectiveness depends on proper trial conduct and the accuracy and completeness of published trial reports. The Journal of Consulting and Clinical Psychology (JCCP) is the primary trials journal amongst American Psychological Association (APA) journals. The objectives of this study were to review RCTs recently published in JCCP to evaluate (1) adequacy of primary outcome analysis definitions; (2) registration status; and, (3) among registered trials, adequacy of outcome registrations. Additionally, we compared results from JCCP to findings from a recent study of top psychosomatic and behavioral medicine journals. Methods Eligible RCTs were published in JCCP in 2013–2014. For each RCT, two investigators independently extracted data on (1) adequacy of outcome analysis definitions in the published report, (2) whether the RCT was registered prior to enrolling patients, and (3) adequacy of outcome registration. Results Of 70 RCTs reviewed, 12 (17.1%) adequately defined primary or secondary outcome analyses, whereas 58 (82.3%) had multiple primary outcome analyses without statistical adjustment or undefined outcome analyses. There were 39 (55.7%) registered trials. Only two trials registered prior to patient enrollment with a single primary outcome variable and time point of assessment. However, in one of the two trials, registered and published outcomes were discrepant. No studies were adequately registered as per Standard Protocol Items: Recommendation for Interventional Trials guidelines. Compared to psychosomatic and behavioral medicine journals, the proportion of published trials with adequate outcome analysis declarations was significantly lower in JCCP (17.1% versus 32.9%; p = 0.029). The proportion of registered trials in JCCP (55.7%) was comparable to behavioral medicine journals (52.6%; p = 0.709). Conclusions The quality of published outcome analysis definitions and trial registrations in JCCP is suboptimal. Greater attention to proper trial registration and outcome analysis definition in published reports is needed. PMID:26581079

Transparency of Outcome Reporting and Trial Registration of Randomized Controlled Trials Published in the Journal of Consulting and Clinical Psychology.

PubMed

Azar, Marleine; Riehm, Kira E; McKay, Dean; Thombs, Brett D

2015-01-01

Confidence that randomized controlled trial (RCT) results accurately reflect intervention effectiveness depends on proper trial conduct and the accuracy and completeness of published trial reports. The Journal of Consulting and Clinical Psychology (JCCP) is the primary trials journal amongst American Psychological Association (APA) journals. The objectives of this study were to review RCTs recently published in JCCP to evaluate (1) adequacy of primary outcome analysis definitions; (2) registration status; and, (3) among registered trials, adequacy of outcome registrations. Additionally, we compared results from JCCP to findings from a recent study of top psychosomatic and behavioral medicine journals. Eligible RCTs were published in JCCP in 2013-2014. For each RCT, two investigators independently extracted data on (1) adequacy of outcome analysis definitions in the published report, (2) whether the RCT was registered prior to enrolling patients, and (3) adequacy of outcome registration. Of 70 RCTs reviewed, 12 (17.1%) adequately defined primary or secondary outcome analyses, whereas 58 (82.3%) had multiple primary outcome analyses without statistical adjustment or undefined outcome analyses. There were 39 (55.7%) registered trials. Only two trials registered prior to patient enrollment with a single primary outcome variable and time point of assessment. However, in one of the two trials, registered and published outcomes were discrepant. No studies were adequately registered as per Standard Protocol Items: Recommendation for Interventional Trials guidelines. Compared to psychosomatic and behavioral medicine journals, the proportion of published trials with adequate outcome analysis declarations was significantly lower in JCCP (17.1% versus 32.9%; p = 0.029). The proportion of registered trials in JCCP (55.7%) was comparable to behavioral medicine journals (52.6%; p = 0.709). The quality of published outcome analysis definitions and trial registrations in JCCP is suboptimal. Greater attention to proper trial registration and outcome analysis definition in published reports is needed.

Piracetam for acute ischaemic stroke.

PubMed

Ricci, Stefano; Celani, Maria Grazia; Cantisani, Teresa Anna; Righetti, Enrico

2012-09-12

Piracetam has neuroprotective and antithrombotic effects that may help to reduce death and disability in people with acute stroke. This is an update of a Cochrane Review first published in 1999, and previously updated in 2006 and 2009. To assess the effects of piracetam in acute, presumed ischaemic stroke. We searched the Cochrane Stroke Group Trials Register (last searched 15 May 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), MEDLINE (1966 to May 2011), EMBASE (1980 to May 2011), and ISI Science Citation Index (1981 to May 2011). We also contacted the manufacturer of piracetam to identify further published and unpublished studies. Randomised trials comparing piracetam with control, with at least mortality reported and entry to the trial within three days of stroke onset. Two review authors extracted data and assessed trial quality and this was checked by the other two review authors. We contacted study authors for missing information. We included three trials involving 1002 patients, with one trial contributing 93% of the data. Participants' ages ranged from 40 to 85 years, and both sexes were equally represented. Piracetam was associated with a statistically non-significant increase in death at one month (approximately 31% increase, 95% confidence interval 81% increase to 5% reduction). This trend was no longer apparent in the large trial after correction for imbalance in stroke severity. Limited data showed no difference between the treatment and control groups for functional outcome, dependence or proportion of patients dead or dependent. Adverse effects were not reported. There is some suggestion (but no statistically significant result) of an unfavourable effect of piracetam on early death, but this may have been caused by baseline differences in stroke severity in the trials. There is not enough evidence to assess the effect of piracetam on dependence.

Targeting aspirin in acute disabling ischemic stroke: an individual patient data meta-analysis of three large randomized trials.

PubMed

Thompson, Douglas D; Murray, Gordon D; Candelise, Livia; Chen, Zhengming; Sandercock, Peter A G; Whiteley, William N

2015-10-01

Aspirin is of moderate overall benefit for patients with acute disabling ischemic stroke. It is unclear whether functional outcome could be improved after stroke by targeting aspirin to patients with a high risk of recurrent thrombosis or a low risk of haemorrhage. We aimed to determine whether patients at higher risk of thrombotic events or poor functional outcome, or lower risk of major haemorrhage had a greater absolute risk reduction of poor functional outcome with aspirin than the average patient. We used data on individual ischemic stroke patients from three large trials of aspirin vs. placebo in acute ischemic stroke: the first International Stroke Trial (n = 18,372), the Chinese Acute Stroke Trial (n = 20,172) and the Multicentre Acute Stroke Trial (n = 622). We developed and evaluated clinical prediction models for the following: early thrombotic events (myocardial infarction, ischemic stroke, deep vein thrombosis and pulmonary embolism); early haemorrhagic events (significant intracranial haemorrhage, major extracranial haemorrhage, or haemorrhagic transformation of an infarct); and late poor functional outcome. We calculated the absolute risk reduction of poor functional outcome (death or dependence) at final follow-up in: quartiles of early thrombotic risk; quartiles of early haemorrhagic risk; and deciles of poor functional outcome risk. Ischemic stroke patients who were older, had lower blood pressure, computerized tomography evidence of infarct or more severe deficits due to stroke had increased risk of thrombotic and haemorrhagic events and poor functional outcome. Prediction models built with all baseline variables (including onset to treatment time) discriminated weakly between patients with and without recurrent thrombotic events (area under the receiver operating characteristic curve 0·56, 95% CI:0·53-0·59) and haemorrhagic events (0·57, 0·52-0·64), though well between patients with and without poor functional outcome (0·77, 0·76-0·78) in the International Stroke Trial. We found no evidence that the net benefit of aspirin increased with increasing risk of thrombosis, haemorrhage or poor functional outcome in all three trials. Using simple clinical variables to target aspirin to patients after acute disabling stroke by risk of thrombosis, haemorrhage or poor functional outcome does not lead to greater net clinical benefit. We suggest future risk stratification schemes include new risk factors for thrombosis and intracranial haemorrhage. © 2015 The Authors. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.

Unreported links between trial registrations and published articles were identified using document similarity measures in a cross-sectional analysis of ClinicalTrials.gov.

PubMed

Dunn, Adam G; Coiera, Enrico; Bourgeois, Florence T

2018-03-01

Trial registries can be used to measure reporting biases and support systematic reviews, but 45% of registrations do not provide a link to the article reporting on the trial. We evaluated the use of document similarity methods to identify unreported links between ClinicalTrials.gov and PubMed. We extracted terms and concepts from a data set of 72,469 ClinicalTrials.gov registrations and 276,307 PubMed articles and tested methods for ranking articles across 16,005 reported links and 90 manually identified unreported links. Performance was measured by the median rank of matching articles and the proportion of unreported links that could be found by screening ranked candidate articles in order. The best-performing concept-based representation produced a median rank of 3 (interquartile range [IQR] 1-21) for reported links and 3 (IQR 1-19) for the manually identified unreported links, and term-based representations produced a median rank of 2 (1-20) for reported links and 2 (IQR 1-12) in unreported links. The matching article was ranked first for 40% of registrations, and screening 50 candidate articles per registration identified 86% of the unreported links. Leveraging the growth in the corpus of reported links between ClinicalTrials.gov and PubMed, we found that document similarity methods can assist in the identification of unreported links between trial registrations and corresponding articles. Copyright © 2017 Elsevier Inc. All rights reserved.

Protocol for a prospective collaborative systematic review and meta-analysis of individual patient data from randomized controlled trials of vasoactive drugs in acute stroke: The Blood pressure in Acute Stroke Collaboration, stage-3.

PubMed

Sandset, Else Charlotte; Sanossian, Nerses; Woodhouse, Lisa J; Anderson, Craig; Berge, Eivind; Lees, Kennedy R; Potter, John F; Robinson, Thompson G; Sprigg, Nikola; Wardlaw, Joanna M; Bath, Philip M

2018-01-01

Rationale Despite several large clinical trials assessing blood pressure lowering in acute stroke, equipoise remains particularly for ischemic stroke. The "Blood pressure in Acute Stroke Collaboration" commenced in the mid-1990s focussing on systematic reviews and meta-analysis of blood pressure lowering in acute stroke. From the start, Blood pressure in Acute Stroke Collaboration planned to assess safety and efficacy of blood pressure lowering in acute stroke using individual patient data. Aims To determine the optimal management of blood pressure in patients with acute stroke, including both intracerebral hemorrhage and ischemic stroke. Secondary aims are to assess which clinical and therapeutic factors may alter the optimal management of high blood pressure in patients with acute stroke and to assess the effect of vasoactive treatments on hemodynamic variables. Methods and design Individual patient data from randomized controlled trials of blood pressure management in participants with ischemic stroke and/or intracerebral hemorrhage enrolled during the ultra-acute (pre-hospital), hyper-acute (<6 h), acute (<48 h), and sub-acute (<168 h) phases of stroke. Study outcomes The primary effect variable will be functional outcome defined by the ordinal distribution of the modified Rankin Scale; analyses will also be carried out in pre-specified subgroups to assess the modifying effects of stroke-related and pre-stroke patient characteristics. Key secondary variables will include clinical, hemodynamic and neuroradiological variables; safety variables will comprise death and serious adverse events. Discussion Study questions will be addressed in stages, according to the protocol, before integrating these into a final overreaching analysis. We invite eligible trials to join the collaboration.

Stroke unit care benefits patients with intracerebral hemorrhage: systematic review and meta-analysis.

PubMed

Langhorne, Peter; Fearon, Patricia; Ronning, Ole M; Kaste, Markku; Palomaki, Heikki; Vemmos, Kostos; Kalra, Lalit; Indredavik, Bent; Blomstrand, Christian; Rodgers, Helen; Dennis, Martin S; Al-Shahi Salman, Rustam

2013-11-01

Patients with any type of stroke managed in organized inpatient (stroke unit) care are more likely to survive, return home, and regain independence. However, it is uncertain whether these benefits apply equally to patients with intracerebral hemorrhage and ischemic stroke. We conducted a secondary analysis of a systematic review of controlled clinical trials comparing stroke unit care with general ward care, including only trials published after 1990 that could separately report outcomes for patients with intracerebral hemorrhage and ischemic stroke. We performed random-effects meta-analyses and tested for subgroup interactions by stroke type. We identified 13 trials (3570 patients) of modern stroke unit care that recruited patients with intracerebral hemorrhage and ischemic stroke, of which 8 trials provided data on 2657 patients. Stroke unit care reduced death or dependency (risk ratio [RR], 0.81; 95% confidence interval [CI], 0.471-0.92; P=0.0009; I2=60%) with no difference in benefits for patients with intracerebral hemorrhage (RR, 0.79; 95% CI, 0.61-1.00) than patients with ischemic stroke (RR, 0.82; 95% CI, 0.70-0.97; Pinteraction=0.77). Stroke unit care reduced death (RR, 0.79; 95% CI, 0.64-0.97; P=0.02; I2=49%) to a greater extent for patients with intracerebral hemorrhage (RR, 0.73; 95% CI, 0.54-0.97) than patients with ischemic stroke (RR, 0.82; 95%, CI 0.61-1.09), but this difference was not statistically significant (Pinteraction=0.58). Patients with intracerebral hemorrhage seem to benefit at least as much as patients with ischemic stroke from organized inpatient (stroke unit) care.

Early blood pressure lowering treatment in acute stroke. Ordinal analysis of vascular events in the Scandinavian Candesartan Acute Stroke Trial (SCAST).

PubMed

Jusufovic, Mirza; Sandset, Else Charlotte; Bath, Philip M; Berge, Eivind

2016-08-01

Early blood pressure-lowering treatment appears to be beneficial in patients with acute intracerebral haemorrhage and potentially in ischaemic stroke. We used a new method for analysis of vascular events in the Scandinavian Candesartan Acute Stroke Trial to see if the effect was dependent on the timing of treatment. Scandinavian Candesartan Acute Stroke Trial was a randomized controlled and placebo-controlled trial of candesartan within 30 h of ischaemic or haemorrhagic stroke. Of 2029 patients, 231 (11.4%) had a vascular event (vascular death, nonfatal stroke or nonfatal myocardial infarction) during the first 6 months. The modified Rankin Scale (mRS) score following a vascular event was used to categorize vascular events in order of severity: no event (n = 1798), minor (mRS 0-2, n = 59), moderately severe (mRS 3-4, n = 57) and major event (mRS 5-6, n = 115). We used ordinal logistic regression for analysis and adjusted for predefined prognostic variables. Candesartan had no overall effect on vascular events (adjusted common odds ratio 1.11, 95% confidence interval 0.84-1.47, P = 0.48), and the effects were the same in ischaemic and haemorrhagic stroke. Among the patients treated within 6 h, the adjusted common odds ratio for vascular events was 0.37, 95% confidence interval 0.16-0.84, P = 0.02, and there was no heterogeneity of effect between ischaemic and haemorrhagic strokes. Ordinal analysis of vascular events showed no overall effect of candesartan in the subacute phase of stroke. The effect of treatment given within 6 h of stroke onset appears promising, and will be addressed in ongoing trials. Ordinal analysis of vascular events is feasible and can be used in future trials.

Changing ethnic disparity in ischemic stroke mortality in US children after the STOP trial.

PubMed

Lehman, Laura L; Fullerton, Heather J

2013-08-01

A prior report showed higher stroke mortality in US black children compared with white children (1979-1998), a disparity likely due in part to sickle cell disease, which leads to a high risk of childhood ischemic stroke. We hypothesized that this disparity has diminished since the publication of the Stroke Prevention Trial in Sickle Cell Anemia (STOP trial) in 1998 demonstrating the efficacy of long-term blood transfusions for primary stroke prevention. To evaluate the demographics and secular trends in mortality from ischemic and hemorrhagic stroke (as a primary cause of death) in US children (<20 years) and determine if there has been a decrease in the disparity between white and black children since the publication of the STOP trial in 1998. We used death certificate data from the National Center for Health Statistics, 1988 through 2007. United States. Children who died in 1988 through 2007 in the United States. Publication of the STOP trial. Incidence rate ratios were calculated as the measure of relative risk. Among 1.6 billion person-years of US children (1988-2007), there were 4425 deaths attributed to stroke, yielding an average of 221 deaths per year; 20% were ischemic; 67%, hemorrhagic; and 12%, unspecified. The relative risk of ischemic stroke mortality for black vs white children dropped from 1.74 from 1988 through 1997 to 1.27 from 1998 through 2007. The ethnic disparity in hemorrhagic stroke mortality, however, remained relatively stable between these 2 periods: black vs white relative risk, 1.90 (1988-1997) and 1.97 (1998-2007). The excess risk of death from ischemic, but not hemorrhagic, stroke in US black children has decreased over the past decade. This may be related to the implementation of an effective ischemic stroke prevention strategy for children with sickle cell disease.

Clinical trial registration and reporting: a survey of academic organizations in the United States.

PubMed

Mayo-Wilson, Evan; Heyward, James; Keyes, Anthony; Reynolds, Jesse; White, Sarah; Atri, Nidhi; Alexander, G Caleb; Omar, Audrey; Ford, Daniel E

2018-05-02

Many clinical trials conducted by academic organizations are not published, or are not published completely. Following the US Food and Drug Administration Amendments Act of 2007, "The Final Rule" (compliance date April 18, 2017) and a National Institutes of Health policy clarified and expanded trial registration and results reporting requirements. We sought to identify policies, procedures, and resources to support trial registration and reporting at academic organizations. We conducted an online survey from November 21, 2016 to March 1, 2017, before organizations were expected to comply with The Final Rule. We included active Protocol Registration and Results System (PRS) accounts classified by ClinicalTrials.gov as a "University/Organization" in the USA. PRS administrators manage information on ClinicalTrials.gov. We invited one PRS administrator to complete the survey for each organization account, which was the unit of analysis. Eligible organization accounts (N = 783) included 47,701 records (e.g., studies) in August 2016. Participating organizations (366/783; 47%) included 40,351/47,701 (85%) records. Compared with other organizations, Clinical and Translational Science Award (CTSA) holders, cancer centers, and large organizations were more likely to participate. A minority of accounts have a registration (156/366; 43%) or results reporting policy (129/366; 35%). Of those with policies, 15/156 (11%) and 49/156 (35%) reported that trials must be registered before institutional review board approval is granted or before beginning enrollment, respectively. Few organizations use computer software to monitor compliance (68/366; 19%). One organization had penalized an investigator for non-compliance. Among the 287/366 (78%) accounts reporting that they allocate staff to fulfill ClinicalTrials.gov registration and reporting requirements, the median number of full-time equivalent staff is 0.08 (interquartile range = 0.02-0.25). Because of non-response and social desirability, this could be a "best case" scenario. Before the compliance date for The Final Rule, some academic organizations had policies and resources that facilitate clinical trial registration and reporting. Most organizations appear to be unprepared to meet the new requirements. Organizations could enact the following: adopt policies that require trial registration and reporting, allocate resources (e.g., staff, software) to support registration and reporting, and ensure there are consequences for investigators who do not follow standards for clinical research.

Efficacy of Chinese herbal medicine for stroke modifiable risk factors: a systematic review.

PubMed

Peng, Wenbo; Lauche, Romy; Ferguson, Caleb; Frawley, Jane; Adams, Jon; Sibbritt, David

2017-01-01

The vast majority of stroke burden is attributable to its modifiable risk factors. This paper aimed to systematically summarise the evidence of Chinese herbal medicine (CHM) interventions on stroke modifiable risk factors for stroke prevention. A literature search was conducted via the MEDLINE, CINAHL/EBSCO, SCOPUS, and Cochrane Database from 1996 to 2016. Randomised controlled trials or cross-over studies were included. Risk of bias was assessed according to the Cochrane Risk of Bias tool. A total of 46 trials (6895 participants) were identified regarding the use of CHM interventions in the management of stroke risk factors, including 12 trials for hypertension, 10 trials for diabetes, eight trials for hyperlipidemia, seven trials for impaired glucose tolerance, three trials for obesity, and six trials for combined risk factors. Amongst the included trials with diverse study design, an intervention of CHM as a supplement to biomedicine and/or a lifestyle intervention was found to be more effective in lowering blood pressure, decreasing blood glucose level, helping impaired glucose tolerance reverse to normal, and/or reducing body weight compared to CHM monotherapy. While no trial reported deaths amongst the CHM groups, some papers do report moderate adverse effects associated with CHM use. However, the findings of such beneficial effects of CHM should be interpreted with caution due to the heterogeneous set of complex CHM studied, the various control interventions employed, the use of different participants' inclusion criteria, and low methodological quality across the published studies. The risk of bias of trials identified was largely unclear in the domains of selection bias and detection bias across the included studies. This study showed substantial evidence of varied CHM interventions improving the stroke modifiable risk factors. More rigorous research examining the use of CHM products for sole or multiple major stroke risk factors are warranted.

Quality of registration for clinical trials published in emergency medicine journals.

PubMed

Jones, Christopher W; Platts-Mills, Timothy F

2012-10-01

In 2005, the International Committee of Medical Journal Editors established clinical trial registration as a requirement for articles submitted to member journals, with the goal of improving the transparency of clinical research. The objective of this study is to characterize the registration of clinical trials published in emergency medicine journals. Randomized trials involving human subjects and published between June 1, 2008, and May 31, 2011 in the 5 emergency medicine journals with the highest impact factors were included. We assessed the clarity of registered primary outcomes, timing of registration relative to patient enrollment, and consistency between registered and published outcomes. Of the 123 trials included, registry entries were identified for 57 (46%). Of the 57 registered studies, 45 (79%) were registered after the initiation of subject enrollment, 9 (16%) had registered outcomes that were unclear, and 26 (46%) had discrepancies between registered and published outcomes. Only 5 studies were registered before patient enrollment with a clear primary outcome that was consistent with the published primary outcome. Annals of Emergency Medicine was the only journal in which the majority of trials were registered. Current compliance with clinical trial registration guidelines is poor among trials published in emergency medicine journals. Copyright © 2012. Published by Mosby, Inc.

A cross-laboratory preclinical study on the effectiveness of interleukin-1 receptor antagonist in stroke

PubMed Central

Maysami, Samaneh; Wong, Raymond; Pradillo, Jesus M; Denes, Adam; Dhungana, Hiramani; Malm, Tarja; Koistinaho, Jari; Orset, Cyrille; Rahman, Mahbubur; Rubio, Marina; Schwaninger, Markus; Vivien, Denis; Bath, Philip M; Rothwell, Nancy J

2015-01-01

Stroke represents a global challenge and is a leading cause of permanent disability worldwide. Despite much effort, translation of research findings to clinical benefit has not yet been successful. Failure of neuroprotection trials is considered, in part, due to the low quality of preclinical studies, low level of reproducibility across different laboratories and that stroke co-morbidities have not been fully considered in experimental models. More rigorous testing of new drug candidates in different experimental models of stroke and initiation of preclinical cross-laboratory studies have been suggested as ways to improve translation. However, to our knowledge, no drugs currently in clinical stroke trials have been investigated in preclinical cross-laboratory studies. The cytokine interleukin 1 is a key mediator of neuronal injury, and the naturally occurring interleukin 1 receptor antagonist has been reported as beneficial in experimental studies of stroke. In the present paper, we report on a preclinical cross-laboratory stroke trial designed to investigate the efficacy of interleukin 1 receptor antagonist in different research laboratories across Europe. Our results strongly support the therapeutic potential of interleukin 1 receptor antagonist in experimental stroke and provide further evidence that interleukin 1 receptor antagonist should be evaluated in more extensive clinical stroke trials. PMID:26661169

Exploring recruitment issues in stroke research: a qualitative study of nurse researchers' experiences.

PubMed

Boxall, Leigh; Hemsley, Anthony; White, Nicola

2016-05-01

To explore the practice of experienced stroke nurse researchers to understand the issues they face in recruiting participants. Participant recruitment is one of the greatest challenges in conducting clinical research, with many trials failing due to recruitment problems. Stroke research is a particularly difficult area in which to recruit; however various strategies can improve participation. Analysis revealed three main types of problems for recruiting participants to stroke research: those related to patients, those related to the nurse researcher, and those related to the study itself. Impairments affecting capacity to consent, the acute recruitment time frame of most stroke trials, paternalism by nurse researchers, and low public awareness were especially pertinent. The disabling nature of a stroke, which often includes functional and cognitive impairments, and the acute stage of illness at which patients are appropriate for many trials, make recruiting patients particularly complex and challenging. An awareness of the issues surrounding the recruitment of stroke patients may help researchers in designing and conducting trials. Future work is needed to address the complexities of obtaining informed consent when patient capacity is compromised.

Polypharmacy and effects of apixaban versus warfarin in patients with atrial fibrillation: post hoc analysis of the ARISTOTLE trial

PubMed Central

Brouwer, Marc A; Wojdyla, Daniel M; Thomas, Laine; Lopes, Renato D; Washam, Jeffrey B; Lanas, Fernando; Xavier, Denis; Husted, Steen; Wallentin, Lars; Alexander, John H; Granger, Christopher B; Verheugt, Freek W A

2016-01-01

Objective To determine whether the treatment effect of apixaban versus warfarin differs with increasing numbers of concomitant drugs used by patients with atrial fibrillation. Design Post hoc analysis performed in 2015 of results from ARISTOTLE (apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation)—a multicentre, double blind, double dummy trial that started in 2006 and ended in 2011. Participants 18 201 ARISTOTLE trial participants. Interventions In the ARISTOTLE trial, patients were randomised to either 5 mg apixaban twice daily (n=9120) or warfarin (target international normalised ratio range 2.0-3.0; n=9081). In the post hoc analysis, patients were divided into groups according to the number of concomitant drug treatments used at baseline (0-5, 6-8, ≥9 drugs) with a median follow-up of 1.8 years. Main outcome measures Clinical outcomes and treatment effects of apixaban versus warfarin (adjusted for age, sex, and country). Results Each patient used a median of six drugs (interquartile range 5-9); polypharmacy (≥5 drugs) was seen in 13 932 (76.5%) patients. Greater numbers of concomitant drugs were used in older patients, women, and patients in the United States. The number of comorbidities increased across groups of increasing numbers of drugs (0-5, 6-8, ≥9 drugs), as did the proportions of patients treated with drugs that interact with warfarin or apixaban. Mortality also rose significantly with the number of drug treatments (P<0.001), as did rates of stroke or systemic embolism (1.29, 1.48, and 1.57 per 100 patient years, for 0-5, 6-8, and ≥9 drugs, respectively) and major bleeding (1.91, 2.46, and 3.88 per 100 patient years, respectively). Relative risk reductions in stroke or systemic embolism for apixaban versus warfarin were consistent, regardless of the number of concomitant drugs (Pinteraction=0.82). A smaller reduction in major bleeding was seen with apixaban versus warfarin with increasing numbers of concomitant drugs (Pinteraction=0.017). Patients with interacting (potentiating) drugs for warfarin or apixaban had similar outcomes and consistent treatment effects of apixaban versus warfarin. Conclusions In the ARISTOTLE trial, three quarters of patients had polypharmacy; this subgroup had an increased comorbidity, more interacting drugs, increased mortality, and higher rates of thromboembolic and bleeding complications. In terms of a potential differential response to anticoagulation therapy in patients with atrial fibrillation and polypharmacy, apixaban was more effective than warfarin, and is at least just as safe. Trial registration ARISTOTLE trial, ClinicalTrials.gov NCT00412984. PMID:27306620

Polypharmacy and effects of apixaban versus warfarin in patients with atrial fibrillation: post hoc analysis of the ARISTOTLE trial.

PubMed

Jaspers Focks, Jeroen; Brouwer, Marc A; Wojdyla, Daniel M; Thomas, Laine; Lopes, Renato D; Washam, Jeffrey B; Lanas, Fernando; Xavier, Denis; Husted, Steen; Wallentin, Lars; Alexander, John H; Granger, Christopher B; Verheugt, Freek W A

2016-06-15

 To determine whether the treatment effect of apixaban versus warfarin differs with increasing numbers of concomitant drugs used by patients with atrial fibrillation.  Post hoc analysis performed in 2015 of results from ARISTOTLE (apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation)-a multicentre, double blind, double dummy trial that started in 2006 and ended in 2011.  18 201 ARISTOTLE trial participants.  In the ARISTOTLE trial, patients were randomised to either 5 mg apixaban twice daily (n=9120) or warfarin (target international normalised ratio range 2.0-3.0; n=9081). In the post hoc analysis, patients were divided into groups according to the number of concomitant drug treatments used at baseline (0-5, 6-8, ≥9 drugs) with a median follow-up of 1.8 years.  Clinical outcomes and treatment effects of apixaban versus warfarin (adjusted for age, sex, and country).  Each patient used a median of six drugs (interquartile range 5-9); polypharmacy (≥5 drugs) was seen in 13 932 (76.5%) patients. Greater numbers of concomitant drugs were used in older patients, women, and patients in the United States. The number of comorbidities increased across groups of increasing numbers of drugs (0-5, 6-8, ≥9 drugs), as did the proportions of patients treated with drugs that interact with warfarin or apixaban. Mortality also rose significantly with the number of drug treatments (P<0.001), as did rates of stroke or systemic embolism (1.29, 1.48, and 1.57 per 100 patient years, for 0-5, 6-8, and ≥9 drugs, respectively) and major bleeding (1.91, 2.46, and 3.88 per 100 patient years, respectively). Relative risk reductions in stroke or systemic embolism for apixaban versus warfarin were consistent, regardless of the number of concomitant drugs (Pinteraction=0.82). A smaller reduction in major bleeding was seen with apixaban versus warfarin with increasing numbers of concomitant drugs (Pinteraction=0.017). Patients with interacting (potentiating) drugs for warfarin or apixaban had similar outcomes and consistent treatment effects of apixaban versus warfarin.  In the ARISTOTLE trial, three quarters of patients had polypharmacy; this subgroup had an increased comorbidity, more interacting drugs, increased mortality, and higher rates of thromboembolic and bleeding complications. In terms of a potential differential response to anticoagulation therapy in patients with atrial fibrillation and polypharmacy, apixaban was more effective than warfarin, and is at least just as safe.Trial registration ARISTOTLE trial, ClinicalTrials.gov NCT00412984. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The Women’s Health Initiative Hormone Therapy Trials: Update and Overview of Health Outcomes During the Intervention and Post-Stopping Phases

PubMed Central

Manson, JoAnn E.; Chlebowski, Rowan T.; Stefanick, Marcia L.; Aragaki, Aaron K.; Rossouw, Jacques E.; Prentice, Ross L.; Anderson, Garnet; Howard, Barbara V.; Thomson, Cynthia A.; LaCroix, Andrea Z.; Wactawski-Wende, Jean; Jackson, Rebecca D.; Limacher, Marian; Margolis, Karen L.; Wassertheil-Smoller, Sylvia; Beresford, Shirley A.; Cauley, Jane A.; Eaton, Charles B.; Gass, Margery; Hsia, Judith; Johnson, Karen C.; Kooperberg, Charles; Kuller, Lewis H.; Lewis, Cora E.; Liu, Simin; Martin, Lisa W.; Ockene, Judith K.; O’Sullivan, Mary Jo; Powell, Lynda; Simon, Michael S.; Van Horn, Linda; Vitolins, Mara Z.; Wallace, Robert B.

2014-01-01

IMPORTANCE Menopausal hormone therapy continues in clinical use but questions remain regarding its risks and benefits for chronic disease prevention. OBJECTIVE To provide a comprehensive, integrated overview of findings from the two Women’s Health Initiative (WHI) hormone therapy (HT) trials with extended post-intervention follow up. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS 27,347 postmenopausal women, age 50–79 years, were enrolled at 40 US centers. Interventions were conjugated equine estrogens (CEE, 0.625 mg/day) with medroxyprogesterone acetate (MPA, 2.5 mg/day) for women with an intact uterus (N = 16,608) and CEE alone for women with hysterectomy (N= 10,739), or their placebos. Intervention continued for 5.6 and 7.2 years (median), respectively, with cumulative follow-up of 13 years through September 30, 2010. MAIN OUTCOMES AND MEASURES The primary efficacy and safety outcomes were coronary heart disease (CHD) and invasive breast cancer, respectively. A global index also included stroke, pulmonary embolism, colorectal cancer, endometrial cancer, hip fracture, and deaths. Secondary and quality-of-life outcomes were also assessed. RESULTS During the intervention phase for CEE+MPA, the hazard ratio (HR) for CHD was 1.18 (95% confidence interval [CI] 0.95–1.45) and overall risks outweighed benefits, with increases in invasive breast cancer, stroke, pulmonary embolism, and the global index. Other risks included increased dementia (in women >65 years), gallbladder disease, and urinary incontinence, while benefits included decreased hip fractures, diabetes, and vasomotor symptoms. Post-intervention, most risks and benefits dissipated, although some elevation in breast cancer risk persisted (cumulative hazard ratio [HR] =1.28; 95% confidence interval, 1.11–1.48). During intervention for CEE alone, risks and benefits were more balanced, with a HR for CHD of 0.94 (0.78–1.14), increased stroke and venous thrombosis, decreased hip fractures and diabetes, and over cumulative follow-up, decreased breast cancer (HR=0.79 [0.65–0.97]). Neither regimen affected all-cause mortality. With CEE, younger women (50–59 years) had more favorable results for all-cause mortality, myocardial infarction, and the global index (nominal P values for trend by age <0.05), but not for stroke and venous thrombosis. Absolute risks of adverse events (measured by the global index) per 10,000 women per year on CEE+MPA ranged from 12 excess cases for age 50–59 to 38 for age 70–79 and, for CEE, from 19 fewer cases for age 50–59 to 51 excess cases for age 70–79. Results for quality of life outcomes in both trials were mixed. CONCLUSIONS AND RELEVANCE Menopausal hormone therapy has a complex pattern of risks and benefits. While appropriate for symptom management in some women, its use for chronic disease prevention is not supported by the WHI randomized trials. TRIAL REGISTRATION clinical trials.gov Identifier: NCT00000611 PMID:24084921

Registration practices for observational studies on ClinicalTrials.gov indicated low adherence.

PubMed

Boccia, Stefania; Rothman, Kenneth J; Panic, Nikola; Flacco, Maria Elena; Rosso, Annalisa; Pastorino, Roberta; Manzoli, Lamberto; La Vecchia, Carlo; Villari, Paolo; Boffetta, Paolo; Ricciardi, Walter; Ioannidis, John P A

2016-02-01

The study aims to assess the status of registration of observational studies. We identified studies on cancer research with prospective recruitment of participants that were registered from February 2000 to December 2011 in ClinicalTrials.gov. We recorded the dates of registration and start of recruitment, outcomes, and description of statistical method. We searched for publications corresponding to the registered studies through May 31, 2014. One thousand one hundred nine registered studies were eligible. Primary and secondary outcomes were reported in 809 (73.0%) and 464 (41.8%) of them. The date of registration preceded the month of the study start in 145 (13.8%) and coincided in 205 (19.5%). A total of 151 publications from 120 (10.8%) registered studies were identified. In 2 (33.3%) of the 6 publications where ClinicalTrials.gov reported that the study started recruitment after registration, and in 9 (50.0%) of 18 publications where ClinicalTrials.gov reported the same date for registration and start of recruitment, the articles showed that the study had actually started recruiting before registration. During the period reviewed, few observational studies have been registered. Registration usually occurred after the study started, and prespecification of outcomes and statistical analysis rarely occurred. Copyright © 2016 Elsevier Inc. All rights reserved.

Development of a Mobile Tool That Semiautomatically Screens Patients for Stroke Clinical Trials.

PubMed

Spokoyny, Ilana; Lansberg, Maarten; Thiessen, Rosita; Kemp, Stephanie M; Aksoy, Didem; Lee, YongJae; Mlynash, Michael; Hirsch, Karen G

2016-10-01

Despite several national coordinated research networks, enrollment in many cerebrovascular trials remains challenging. An electronic tool was needed that would improve the efficiency and efficacy of screening for multiple simultaneous acute clinical stroke trials by automating the evaluation of inclusion and exclusion criteria, improving screening procedures and streamlining the communication process between the stroke research coordinators and the stroke clinicians. A multidisciplinary group consisting of physicians, study coordinators, and biostatisticians designed and developed an electronic clinical trial screening tool on a HIPAA (Health Insurance Portability and Accountability Act)-compliant platform. A web-based tool was developed that uses branch logic to determine eligibility for simultaneously enrolling clinical trials and automatically notifies the study coordinator teams about eligible patients. After 12 weeks of use, 225 surveys were completed, and 51 patients were enrolled in acute stroke clinical trials. Compared with the 12 weeks before implementation of the tool, there was an increase in enrollment from 16.5% of patients screened to 23.4% of patients screened (P<0.05). Clinicians and coordinators reported increased satisfaction with the process and improved ease of screening. We created a semiautomated electronic screening tool that uses branch logic to screen patients for stroke clinical trials. The tool has improved efficiency and efficacy of screening, and it could be adapted for use at other sites and in other medical fields. © 2016 American Heart Association, Inc.

Mixed methods feasibility study for a trial of blood pressure telemonitoring for people who have had stroke/transient ischaemic attack (TIA).

PubMed

Hanley, Janet; Fairbrother, Peter; Krishan, Ashma; McCloughan, Lucy; Padfield, Paul; Paterson, Mary; Pinnock, Hilary; Sheikh, Aziz; Sudlow, Cathie; Todd, Allison; McKinstry, Brian

2015-03-25

Good blood pressure (BP) control reduces the risk of recurrence of stroke/transient ischaemic attack (TIA). Although there is strong evidence that BP telemonitoring helps achieve good control, none of the major trials have considered the effectiveness in stroke/TIA survivors. We therefore conducted a feasibility study for a trial of BP telemonitoring for stroke/TIA survivors with uncontrolled BP in primary care. Phase 1 was a pilot trial involving 55 patients stratified by stroke/TIA randomised 3:1 to BP telemonitoring for 6 months or usual care. Phase 2 was a qualitative evaluation and comprised semi-structured interviews with 16 trial participants who received telemonitoring and 3 focus groups with 23 members of stroke support groups and 7 carers. Overall, 125 patients (60 stroke patients, 65 TIA patients) were approached and 55 (44%) patients were randomised including 27 stroke patients and 28 TIA patients. Fifty-two participants (95%) attended the 6-month follow-up appointment, but one declined the second daytime ambulatory blood pressure monitoring (ABPM) measurement resulting in a 93% completion rate for ABPM - the proposed primary outcome measure for a full trial. Adherence to telemonitoring was good; of the 40 participants who were telemonitoring, 38 continued to provide readings throughout the 6 months. There was a mean reduction of 10.1 mmHg in systolic ABPM in the telemonitoring group compared with 3.8 mmHg in the control group, which suggested the potential for a substantial effect from telemonitoring. Our qualitative analysis found that many stroke patients were concerned about their BP and telemonitoring increased their engagement, was easy, convenient and reassuring. A full-scale trial is feasible, likely to recruit well and have good rates of compliance and follow-up. ISRCTN61528726 15/12/2011.

Paracetamol (Acetaminophen) in stroke 2 (PAIS 2): protocol for a randomized, placebo-controlled, double-blind clinical trial to assess the effect of high-dose paracetamol on functional outcome in patients with acute stroke and a body temperature of 36.5 °C or above.

PubMed

de Ridder, Inger R; de Jong, Frank Jan; den Hertog, Heleen M; Lingsma, Hester F; van Gemert, H Maarten A; Schreuder, A H C M L Tobien; Ruitenberg, Annemieke; Maasland, E Lisette; Saxena, Ritu; Oomes, Peter; van Tuijl, Jordie; Koudstaal, Peter J; Kappelle, L Jaap; Algra, Ale; van der Worp, H Bart; Dippel, Diederik W J

2015-04-01

In the first hours after stroke onset, subfebrile temperatures and fever have been associated with poor functional outcome. In the first Paracetamol (Acetaminophen) in Stroke trial, a randomized clinical trial of 1400 patients with acute stroke, patients who were treated with high-dose paracetamol showed more improvement on the modified Rankin Scale at three-months than patients treated with placebo, but this difference was not statistically significant. In the 661 patients with a baseline body temperature of 37.0 °C or above, treatment with paracetamol increased the odds of functional improvement (odds ratio 1.43; 95% confidence interval: 1.02-1.97). This relation was also found in the patients with a body temperature of 36.5 °C or higher (odds ratio 1.31; 95% confidence interval 1.01-1.68). These findings need confirmation. The study aims to assess the effect of high-dose paracetamol in patients with acute stroke and a body temperature of 36.5 °C or above on functional outcome. The Paracetamol (Acetaminophen) In Stroke 2 trial is a multicenter, randomized, double-blind, placebo-controlled clinical trial. We use a power of 85% to detect a significant difference in the scores on the modified Rankin Scale of the paracetamol group compared with the placebo group at a level of significance of 0.05 and assume a treatment effect of 7%. Fifteen-hundred patients with acute ischemic stroke or intracerebral hemorrhage and a body temperature of 36.5 °C or above will be included within 12 h of symptom onset. Patients will be treated with paracetamol in a daily dose of six-grams or matching placebo for three consecutive days. The Paracetamol (Acetaminophen) In Stroke 2 trial has been registered as NTR2365 in The Netherlands Trial Register. The primary outcome will be improvement on the modified Rankin Scale at three-months as analyzed by ordinal logistic regression. If high-dose paracetamol will be proven effective, a simple, safe, and extremely cheap therapy will be available for many patients with acute stroke worldwide. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Evidence-Based Carotid Interventions for Stroke Prevention: State-of-the-art Review

PubMed Central

Morris, Dylan R.; Ayabe, Kengo; Inoue, Takashi; Sakai, Nobuyuki; Bulbulia, Richard; Halliday, Alison

2017-01-01

Carotid artery stenosis is responsible for between 10–20% of all ischaemic strokes. Interventions, such as carotid end-arterectomy and carotid stenting, effectively reduce the risk of stroke in selected individuals. This review describes the history of carotid interventions, and summarises reliable evidence on the safety and efficacy of these interventions gained from large randomised clinical trials. Early trials comparing carotid endarterectomy to medical therapy alone in symptomatic patients, and asymptomatic patients, demonstrated that endarterectomy halved the risk of stroke and perioperative death in these two unique populations. The absolute risk reduction was smaller in the asymptomatic carotid trials, consistent with their lower absolute stroke risk. More recent trials in symptomatic patients, suggest that carotid stenting has similar long term durability to carotid endarterectomy, but possibly has higher procedural hazards dominated by non-disabling strokes. The Asymptomatic Carotid Surgery Trial-2, along with individual patient data meta-analysis of all asymptomatic trials, will provide reliable evidence for the choice of intervention in asymptomatic patients in whom a decision has been made for carotid revascularisation. Given improvements in effective cardiovascular medical therapy, in particular lipid-lowering medications, there is renewed uncertainty as to whether carotid interventions still provide meaningful net reductions in stroke risk in asymptomatic populations. Four large trials in Europe and the US are currently underway, and are expected to report longterm results in the next decade. It is essential that surgeons, interventionalists, and physicians continue to randomise large numbers of patients from around the world to clarify current uncertainty around the management of asymptomatic carotid stenosis. PMID:28260723

Singapore Tele-technology Aided Rehabilitation in Stroke (STARS) trial: protocol of a randomized clinical trial on tele-rehabilitation for stroke patients.

PubMed

Koh, Gerald Choon-Huat; Yen, Shih Cheng; Tay, Arthur; Cheong, Angela; Ng, Yee Sien; De Silva, Deidre Anne; Png, Carolina; Caves, Kevin; Koh, Karen; Kumar, Yogaprakash; Phan, Shi Wen; Tai, Bee Choo; Chen, Cynthia; Chew, Effie; Chao, Zhaojin; Chua, Chun En; Koh, Yen Sin; Hoenig, Helen

2015-09-05

Most acute stroke patients with disabilities do not receive recommended rehabilitation following discharge to the community. Functional and social barriers are common reasons for non-adherence to post-discharge rehabilitation. Home rehabilitation is an alternative to centre-based rehabilitation but is costlier. Tele-rehabilitation is a possible solution, allowing for remote supervision of rehabilitation and eliminating access barriers. The objective of the Singapore Tele-technology Aided Rehabilitation in Stroke (STARS) trial is to determine if a novel tele-rehabilitation intervention for the first three months after stroke admission improves functional recovery compared to usual care. This is a single blind (evaluator blinded), parallel, two-arm randomised controlled trial study design involving 100 recent stroke patients. The inclusion criteria are age ≥40 years, having caregiver support and recent stroke defined as stroke diagnosis within 4 weeks. Consenting participants will be randomized with varying block size of 4 or 6 assuming a 1:1 treatment allocation with the participating centre as the stratification factor. The baseline assessment will be done within 4 weeks of stroke onset, followed by follow-up assessments at 3 and 6 months. The tele-rehabilitation intervention lasts for 3 months and includes exercise 5-days-a-week using an iPad-based system that allows recording of daily exercise with video and sensor data and weekly video-conferencing with tele-therapists after data review. Those allocated to the control group will receive usual care. The primary outcome measure is improvement in life task's social activity participation at three months as measured by the disability component of the Jette Late Life Functional and Disability Instrument (LLFDI). Secondary outcome variables consist of gait speed (Timed 5-Meter Walk Test) and endurance (Two-Minute Walk test), performance of basic activities of daily living (Shah-modified Barthel Index), balance confidence (Activities-Specific Balance Confidence Scale), patient self-reported health-related quality-of-life [Euro-QOL (EQ-5D)], health service utilization (Singapore Stroke Study Health Service Utilization Form) and caregiver reported stress (Zarit Caregiver Burden Inventory). The goal of this trial is to provide evidence on the potential benefit and cost-effectiveness of this novel tele-rehabilitation programme which will guide health care decision-making and potentially improve performance of post-stroke community-based rehabilitation. This trial protocol was registered under ClinicalTrials.gov on 18 July 2013 as study title "The Singapore Tele-technology Aided Rehabilitation in Stroke (STARS) Study" (ID: The STARS Study, ClinicalTrials.gov Identifier: NCT01905917 ).

Haemodilution for acute ischaemic stroke

PubMed Central

Chang, Timothy S; Jensen, Matthew B

2014-01-01

Background Ischaemic stroke interrupts the flow of blood to part of the brain. Haemodilution is thought to improve the flow of blood to the affected areas of the brain and thus reduce infarct size. Objectives To assess the effects of haemodilution in acute ischaemic stroke. Search methods We searched the Cochrane Stroke Group Trials Register (February 2014), the Cochrane Central Register of Controlled Trials (Issue 1, 2014), MEDLINE (January 2008 to October 2013) and EMBASE (January 2008 to October 2013). We also searched trials registers, scanned reference lists and contacted authors. For the previous version of the review, the authors contacted manufacturers and investigators in the field. Selection criteria Randomised trials of haemodilution treatment in people with acute ischaemic stroke. We included only trials in which treatment was started within 72 hours of stroke onset. Data collection and analysis Two review authors assessed trial quality and one review author extracted the data. Main results We included 21 trials involving 4174 participants. Nine trials used a combination of venesection and plasma volume expander. Twelve trials used plasma volume expander alone. The plasma volume expander was plasma alone in one trial, dextran 40 in 12 trials, hydroxyethyl starch (HES) in five trials and albumin in three trials. Two trials tested haemodilution in combination with another therapy. Evaluation was blinded in 14 trials. Five trials probably included some participants with intracerebral haemorrhage. Haemodilution did not significantly reduce deaths within the first four weeks (risk ratio (RR) 1.10; 95% confidence interval (CI) 0.90 to 1.34). Similarly, haemodilution did not influence deaths within three to six months (RR 1.05; 95% CI 0.93 to 1.20), or death and dependency or institutionalisation (RR 0.96; 95% CI 0.85 to 1.07). The results were similar in confounded and unconfounded trials, and in trials of isovolaemic and hypervolaemic haemodilution. No statistically significant benefits were documented for any particular type of haemodiluting agents, but the statistical power to detect effects of HES was weak. Six trials reported venous thromboembolic events. There was a tendency towards reduction in deep venous thrombosis or pulmonary embolism or both at three to six months’ follow-up (RR 0.68; 95% CI 0.37 to 1.24). There was no statistically significant increased risk of serious cardiac events among haemodiluted participants. Authors’ conclusions The overall results of this review showed no clear evidence of benefit of haemodilution therapy for acute ischaemic stroke. These results are compatible with no persuasive beneficial evidence of haemodilution therapy for acute ischaemic stroke. This therapy has not been proven to improve survival or functional outcome. PMID:25159027

Effect of acupuncture on insomnia following stroke: study protocol for a randomized controlled trial.

PubMed

Cao, Yan; Yin, Xuan; Soto-Aguilar, Francisca; Liu, Yiping; Yin, Ping; Wu, Junyi; Zhu, Bochang; Li, Wentao; Lao, Lixing; Xu, Shifen

2016-11-16

The incidence, mortality, and prevalence of stroke are high in China. Stroke is commonly associated with insomnia; both insomnia and stroke have been effectively treated with acupuncture for a long time. The aim of this proposed trial is to assess the therapeutic effect of acupuncture on insomnia following stroke. This proposed study is a single-center, single-blinded (patient-assessor-blinded), parallel-group randomized controlled trial. We will randomly assign 60 participants with insomnia following stroke into two groups in a 1:1 ratio. The intervention group will undergo traditional acupuncture that achieves the De-qi sensation, and the control group will receive sham acupuncture without needle insertion. The same acupoints (DU20, DU24, EX-HN3, EX-HN22, HT7, and SP6) will be used in both groups. Treatments will be given to all participants three times a week for the subsequent 4 weeks. The primary outcome will be the Pittsburgh Sleep Quality Index. The secondary outcomes will be: the Insomnia Severity Index; sleep efficacy, sleep awakenings, and total sleep time recorded via actigraphy; the National Institutes of Health Stroke Scale; the Stroke-Specific Quality of Life score; the Hospital Anxiety and Depression Scale. The use of estazolam will be permitted and regulated under certain conditions. Outcomes will be assessed at baseline, 2 weeks after treatment commencement, 4 weeks after treatment commencement, and at the 8-week follow-up. This proposed study will contribute to expanding knowledge about acupuncture treatment for insomnia following stroke. This will be a high-quality randomized controlled trial with strict methodology and few design deficits. It will investigate the effectiveness of acupuncture as an alternative treatment for insomnia following stroke. Chinese Clinical Trial Registry identifier: ChiCTR-IIC-16008382 . Registered on 28 April 2016.

Details of a prospective protocol for a collaborative meta-analysis of individual participant data from all randomized trials of intravenous rt-PA vs. control: statistical analysis plan for the Stroke Thrombolysis Trialists' Collaborative meta-analysis.

PubMed

2013-06-01

Thrombolysis with intravenous alteplase is both effective and safe when administered to particular types of patient within 4·5 hours of having an ischemic stroke. However, the extent to which effects might vary in different types of patient is uncertain. We describe the protocol for an updated individual patient data meta-analysis of trials of intravenous alteplase, including results from the recently reported third International Stroke Trial, in which a wide range of patients enrolled up to six-hours after stroke onset were randomized to alteplase vs. control. This protocol will specify the primary outcome for efficacy, specified prior to knowledge of the results from the third International Stroke Trial, as the proportion of patients having a 'favorable' stroke outcome, defined by modified Rankin Score 0-1 at final follow-up at three- to six-months. The primary analysis will be to estimate the extent to which the known benefit of alteplase on modified Rankin Score 0-1 diminishes with treatment delay, and the extent to which it is independently modified by age and stroke severity. Key secondary outcomes include effect of alteplase on death within 90 days; analyses of modified Rankin Score using ordinal, rather than dichotomous, methods; and effects of alteplase on symptomatic intracranial hemorrhage, fatal intracranial hemorrhage, symptomatic ischemic brain edema and early edema, effacement and/or midline shift. This collaborative meta-analysis of individual participant data from all randomized trials of intravenous alteplase vs. control will demonstrate how the known benefits of alteplase on ischemic stroke outcome vary across different types of patient. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Pediatric Stroke

MedlinePlus

... Trials News About Neurology Image Library Search The Internet Stroke Center Patients & Families About Stroke Stroke Diagnosis ... UT Southwestern Medical Center. Copyright © 1997-2018 - The Internet Stroke Center. All rights reserved. The information contained ...

The quality of registration of clinical trials.

PubMed

Viergever, Roderik F; Ghersi, Davina

2011-02-24

Lack of transparency in clinical trial conduct, publication bias and selective reporting bias are still important problems in medical research. Through clinical trials registration, it should be possible to take steps towards resolving some of these problems. However, previous evaluations of registered records of clinical trials have shown that registered information is often incomplete and non-meaningful. If these studies are accurate, this negates the possible benefits of registration of clinical trials. A 5% sample of records of clinical trials that were registered between 17 June 2008 and 17 June 2009 was taken from the International Clinical Trials Registry Platform (ICTRP) database and assessed for the presence of contact information, the presence of intervention specifics in drug trials and the quality of primary and secondary outcome reporting. 731 records were included. More than half of the records were registered after recruitment of the first participant. The name of a contact person was available in 94.4% of records from non-industry funded trials and 53.7% of records from industry funded trials. Either an email address or a phone number was present in 76.5% of non-industry funded trial records and in 56.5% of industry funded trial records. Although a drug name or company serial number was almost always provided, other drug intervention specifics were often omitted from registration. Of 3643 reported outcomes, 34.9% were specific measures with a meaningful time frame. Clinical trials registration has the potential to contribute substantially to improving clinical trial transparency and reducing publication bias and selective reporting. These potential benefits are currently undermined by deficiencies in the provision of information in key areas of registered records.

The Quality of Registration of Clinical Trials

PubMed Central

Viergever, Roderik F.; Ghersi, Davina

2011-01-01

Background Lack of transparency in clinical trial conduct, publication bias and selective reporting bias are still important problems in medical research. Through clinical trials registration, it should be possible to take steps towards resolving some of these problems. However, previous evaluations of registered records of clinical trials have shown that registered information is often incomplete and non-meaningful. If these studies are accurate, this negates the possible benefits of registration of clinical trials. Methods and Findings A 5% sample of records of clinical trials that were registered between 17 June 2008 and 17 June 2009 was taken from the International Clinical Trials Registry Platform (ICTRP) database and assessed for the presence of contact information, the presence of intervention specifics in drug trials and the quality of primary and secondary outcome reporting. 731 records were included. More than half of the records were registered after recruitment of the first participant. The name of a contact person was available in 94.4% of records from non-industry funded trials and 53.7% of records from industry funded trials. Either an email address or a phone number was present in 76.5% of non-industry funded trial records and in 56.5% of industry funded trial records. Although a drug name or company serial number was almost always provided, other drug intervention specifics were often omitted from registration. Of 3643 reported outcomes, 34.9% were specific measures with a meaningful time frame. Conclusions Clinical trials registration has the potential to contribute substantially to improving clinical trial transparency and reducing publication bias and selective reporting. These potential benefits are currently undermined by deficiencies in the provision of information in key areas of registered records. PMID:21383991

Issues in recruiting community-dwelling stroke survivors to clinical trials: the AMBULATE trial.

PubMed

Lloyd, Gemma; Dean, Catherine M; Ada, Louise

2010-07-01

Recruitment to clinical trials is often slow and difficult, with a growing body of research examining this issue. However there is very little work related to stroke. The aim of this study was to examine the success and efficiency of recruitment of community-dwelling stroke survivors over the first two years of a clinical trial aiming to improve community ambulation. Recruitment strategies fell into 2 broad categories: (i) advertisement (such as newspaper advertising and media releases), and (ii) referral (via hospital and community physiotherapists, a stroke liaison officer and other researchers). Records were kept of the number of people who were screened, were eligible and were recruited for each strategy. The recruitment target of 60 in the first two years was not met. 111 stroke survivors were screened and 57 were recruited (i.e., a recruitment rate of 51%). The most successful strategy was referral via hospital-based physiotherapists (47% of recruited participants) and the least successful were media release and local newspaper advertising. The referral strategies were all more efficient than any of the advertisement strategies. In general, recruitment was inefficient and costly in terms of human resources. Given that stroke research is underfunded, it is important to find efficient ways of recruiting stroke survivors to clinical trials. An Australian national database similar to other disease-specific data bases (such as the National Cancer Database) is under development. In the interim, recruiting for several clinical trials at once may increase efficiency.

STROKE OUTCOMES AMONG PARTICIPANTS RANDOMIZED TO CHLORTHALIDONE, AMLODIPINE OR LISINOPRIL IN ALLHAT

PubMed Central

Yamal, José-Miguel; Oparil, Suzanne; Davis, Barry R.; Alderman, Michael H.; Calhoun, David A.; Cushman, William C.; Fendley, Herbert F.; Franklin, Stanley S.; Habib, Gabriel B.; Pressel, Sara L.; Probstfield, Jeffrey L.; Sastrasinh, Sithiporn

2014-01-01

Background The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind, practice-based, active-control, comparative effectiveness trial in 33,357 high-risk hypertensive participants. Methods and Results ALLHAT compared cardiovascular disease outcomes in participants initially treated with angiotensin-converting enzyme inhibitor (lisinopril), calcium channel blocker (amlodipine), or thiazide-type diuretic (chlorthalidone). We report stroke outcomes in 1517 participants in-trial and 1596 additional participants during post-trial passive surveillance, for total follow-up of 8–13 years. Stroke rates were higher with lisinopril (6-year rate/100=6.4) than with chlorthalidone (5.8) or amlodipine (5.5) in-trial but not including post-trial (10-year rates/100=13.2 [chlorthalidone], 13.1[amlodipine], and 13.7 [lisinopril]). In- trial differences were driven by race (race-by-lisinopril/chlorthalidone interaction P=0.005, race-by-amlodipine/lisinopril interaction P=0.012) and gender (gender-by-lisinopril/amlodipine interaction P=0.041), separately. No treatment differences overall, or by race or gender, were detected over the 10-year period. No differences appeared among treatment groups in adjusted risk of all-cause mortality including post-trial for participants with nonfatal in-trial strokes. Conclusions Among Blacks and women, lisinopril was less effective in preventing stroke in-trial than either chlorthalidone or amlodipine, even after adjusting for differences in systolic blood pressure. These differences abated by the end of the post-trial period. PMID:25455006

Early mobilization after stroke: an example of an individual patient data meta-analysis of a complex intervention.

PubMed

Craig, Louise E; Bernhardt, Julie; Langhorne, Peter; Wu, Olivia

2010-11-01

Very early mobilization (VEM) is a distinctive characteristic of care in some stroke units; however, evidence of the effectiveness of this approach is limited. To date, only 2 phase II trials have compared VEM with standard care: A Very Early Rehabilitation Trial (AVERT) in Australia and the recently completed Very Early Rehabilitation or Intensive Telemetry after Stroke trial in the United Kingdom. The Very Early Rehabilitation or Intensive Telemetry after Stroke protocol was designed to complement that of AVERT in a number of key areas. The aim of this analysis was to investigate the impact of VEM on independence by pooling data from these 2 comparable trials. Individual data from the 2 trials were pooled. Overall, patients were between 27 and 97 years old, had first or recurring stroke, and were treated within 36 hours after stroke onset. The primary outcome was independence, defined as modified Rankin scale score of 0 to 2 at 3 months. The secondary outcomes included complications of immobility and activities of daily living. Logistic regression was used to assess the effect of VEM on outcome, adjusting for known confounders including age, baseline stroke severity, and premorbid modified Rankin scale score. Findings-All patients in AVERT and Very Early Rehabilitation or Intensive Telemetry after Stroke were included, resulting in 54 patients in the VEM group and 49 patients in the standard care group. The baseline characteristics of VEM patients were largely comparable with standard care patients. Time to first mobilization from symptom onset was significantly shorter among VEM patients (median, 21 hours; interquartile range, 15.8-27.8 hours) compared with standard care patients (median, 31 hours; interquartile range, 23.0-41.2 hours). VEM patients had significantly greater odds of independence compared with standard care patients (adjusted odds ratio, 3.11; 95% confidence interval, 1.03-9.33). Planned collaborations between stroke researchers to conduct trials with common protocols and outcome measures can help advance rehabilitation science. VEM was associated with improved independence at 3 months compared with standard care. However, both trials are limited by small sample sizes. Larger trials (such as AVERT phase III) are still needed in this field.

Increasing upper limb training intensity in chronic stroke using embodied virtual reality: a pilot study.

PubMed

Perez-Marcos, Daniel; Chevalley, Odile; Schmidlin, Thomas; Garipelli, Gangadhar; Serino, Andrea; Vuadens, Philippe; Tadi, Tej; Blanke, Olaf; Millán, José D R

2017-11-17

Technology-mediated neurorehabilitation is suggested to enhance training intensity and therefore functional gains. Here, we used a novel virtual reality (VR) system for task-specific upper extremity training after stroke. The system offers interactive exercises integrating motor priming techniques and embodied visuomotor feedback. In this pilot study, we examined (i) rehabilitation dose and training intensity, (ii) functional improvements, and (iii) safety and tolerance when exposed to intensive VR rehabilitation. Ten outpatient stroke survivors with chronic (>6 months) upper extremity paresis participated in a ten-session VR-based upper limb rehabilitation program (2 sessions/week). All participants completed all sessions of the treatment. In total, they received a median of 403 min of upper limb therapy, with 290 min of effective training. Within that time, participants performed a median of 4713 goal-directed movements. Importantly, training intensity increased progressively across sessions from 13.2 to 17.3 movements per minute. Clinical measures show that despite being in the chronic phase, where recovery potential is thought to be limited, participants showed a median improvement rate of 5.3% in motor function (Fugl-Meyer Assessment for Upper Extremity; FMA-UE) post intervention compared to baseline, and of 15.4% at one-month follow-up. For three of them, this improvement was clinically significant. A significant improvement in shoulder active range of motion (AROM) was also observed at follow-up. Participants reported very low levels of pain, stress and fatigue following each session of training, indicating that the intensive VR intervention was well tolerated. No severe adverse events were reported. All participants expressed their interest in continuing the intervention at the hospital or even at home, suggesting high levels of adherence and motivation for the provided intervention. This pilot study showed how a dedicated VR system could deliver high rehabilitation doses and, importantly, intensive training in chronic stroke survivors. FMA-UE and AROM results suggest that task-specific VR training may be beneficial for further functional recovery both in the chronic stage of stroke. Longitudinal studies with higher doses and sample sizes are required to confirm the therapy effectiveness. This trial was retrospectively registered at ClinicalTrials.gov database (registration number NCT03094650 ) on 14 March 2017.

Effect of Treatment Delay, Stroke Type, and Thrombolysis on the Effect of Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome after Acute Stroke: A Systematic Review and Meta-Analysis of Individual Patient from Randomised Trials.

PubMed

Bath, Philip M; Woodhouse, Lisa; Krishnan, Kailash; Anderson, Craig; Berge, Eivind; Ford, Gary A; Robinson, Thompson G; Saver, Jeffrey L; Sprigg, Nikola; Wardlaw, Joanna M; In Acute Stroke Collaboration Basc, Blood Pressure

2016-01-01

Background. Nitric oxide (NO) donors are a candidate treatment for acute stroke and two trials have suggested that they might improve outcome if administered within 4-6 hours of stroke onset. We assessed the safety and efficacy of NO donors using individual patient data (IPD) from completed trials. Methods. Randomised controlled trials of NO donors in patients with acute or subacute stroke were identified and IPD sought from the trialists. The effect of NO donor versus control on functional outcome was assessed using the modified Rankin scale (mRS) and death, by time to randomisation. Secondary outcomes included measures of disability, mood, and quality of life. Results. Five trials (4,197 participants) were identified, all involving glyceryl trinitrate (GTN). Compared with control, GTN lowered blood pressure by 7.4/3.3 mmHg. At day 90, GTN did not alter any clinical measures. However, in 312 patients randomised within 6 hours of stroke onset, GTN was associated with beneficial shifts in the mRS (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.34-0.78) and reduced death (OR 0.32, 95% CI 0.14-0.78). Conclusions. NO donors do not alter outcome in patients with recent stroke. However, when administered within 6 hours, NO donors might improve outcomes in both ischaemic and haemorrhagic stroke.

Elderly Patients with Dementia-Related Symptoms of Severe Agitation and Aggression: Consensus Statement on Treatment Options, Clinical Trials Methodology, and Policy

PubMed Central

Salzman, C; Jeste, D; Meyer, RE; Cohen-Mansfield, J; Cummings, J; Grossberg, G; Jarvik, L; Kraemer, H; Lebowitz, B; Maslow, K; Pollock, B; Raskind, M; Schultz, S; Wang, P; Zito, JM; Zubenko, GS

2009-01-01

Atypical antipsychotic drugs have been used off-label in clinical practice for treatment of serious dementia-associated agitation and aggression. Following reports of cerebrovascular adverse events associated with the use of atypical antipsychotic in elderly patients with dementia, the FDA issued black box warnings for several atypical antipsychotics, titled “Cerebrovascular Adverse Events, including Stroke, in Elderly Patients with Dementia.” Subsequently, the FDA initiated a meta-analysis of safety data from 17 registration trials across six antipsychotic drugs (five atypical antipsychotics and haloperidol). In 2005, the Agency issued a black box warning regarding increased risk of mortality associated with the use of atypical antipsychotic drugs in this patient population. Geriatric mental health experts participating in a 2006 consensus conference reviewed evidence on the safety and efficacy of antipsychotics, as well as nonpharmacologic approaches, in treating dementia-related symptoms of agitation and aggression. They concluded that, while problems in clinical trials design may have been one of the contributors to the failure to find a signal of drug efficacy, the findings related to drug safety should be taken seriously by clinicians in assessing the potential risks and benefits of treatment in a frail population, and in advising families about treatment. Information provided to patients and family members should be documented in the patient’s chart. Drugs should be used only when non-pharmacologic approaches have failed to adequately control behavioral disruption. Participants also agreed that that there is a need for an FDA-approved medication for the treatment of severe, persistent or recurrent dementia-related symptoms of agitation and aggression (even in the absence of psychosis), that are unresponsive to nonpharmacologic intervention. The authors have outlined methodological enhancements to better evaluate treatment approaches in future registration trials, and they provided an algorithm for improving the treatment of these patients in nursing home and non-nursing home settings. PMID:18494535

Melodic Intonation Therapy in Chronic Aphasia: Evidence from a Pilot Randomized Controlled Trial

PubMed Central

Van Der Meulen, Ineke; Van De Sandt-Koenderman, Mieke W. M. E.; Heijenbrok, Majanka H.; Visch-Brink, Evy; Ribbers, Gerard M.

2016-01-01

Melodic Intonation Therapy (MIT) is a language production therapy for severely non-fluent aphasic patients using melodic intoning and rhythm to restore language. Although many studies have reported its beneficial effects on language production, randomized controlled trials (RCT) examining the efficacy of MIT are rare. In an earlier publication, we presented the results of an RCT on MIT in subacute aphasia and found that MIT was effective on trained and untrained items. Further, we observed a clear trend in improved functional language use after MIT: subacute aphasic patients receiving MIT improved considerably on language tasks measuring connected speech and daily life verbal communication. Here, we present the results of a pilot RCT on MIT in chronic aphasia and compare these to the results observed in subacute aphasia. We used a multicenter waiting-list RCT design. Patients with chronic (>1 year) post-stroke aphasia were randomly allocated to the experimental group (6 weeks MIT) or to the control group (6 weeks no intervention followed by 6 weeks MIT). Assessments were done at baseline (T1), after 6 weeks (T2), and 6 weeks later (T3). Efficacy was evaluated at T2 using univariable linear regression analyses. Outcome measures were chosen to examine several levels of therapy success: improvement on trained items, generalization to untrained items, and generalization to verbal communication. Of 17 included patients, 10 were allocated to the experimental condition and 7 to the control condition. MIT significantly improved repetition of trained items (β = 13.32, p = 0.02). This effect did not remain stable at follow-up assessment. In contrast to earlier studies, we found only a limited and temporary effect of MIT, without generalization to untrained material or to functional communication. The results further suggest that the effect of MIT in chronic aphasia is more restricted than its effect in earlier stages post stroke. This is in line with studies showing larger effects of aphasia therapy in earlier compared to later stages post stroke. The study was designed as an RCT, but was underpowered. The results therefore have to be interpreted cautiously and future larger studies are needed. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NTR 1961. PMID:27847473

Outcomes of Temporary Interruption of Rivaroxaban Compared With Warfarin in Patients With Nonvalvular Atrial Fibrillation

PubMed Central

Sherwood, Matthew W.; Douketis, James D.; Patel, Manesh R.; Piccini, Jonathan P.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Spyropoulos, Alex C.; Hankey, Graeme J.; Singer, Daniel E.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.; Becker, Richard C.

2014-01-01

Background During long-term anticoagulation in atrial fibrillation, temporary interruptions (TIs) of therapy are common, but the relationship between patient outcomes and TIs has not been well studied. We sought to determine reasons for TI, the characteristics of patients undergoing TI, and the relationship between anticoagulant and outcomes among patients with TI. Methods and Results In the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), a randomized, double-blind, double-dummy study of rivaroxaban and warfarin in nonvalvular atrial fibrillation, baseline characteristics, management, and outcomes, including stroke, non–central nervous system systemic embolism, death, myocardial infarction, and bleeding, were reported in participants who experienced TI (3–30 days) for any reason. The at-risk period for outcomes associated with TI was from TI start to 30 days after resumption of study drug. In 14 236 participants who received at least 1 dose of study drug, 4692 (33%) experienced TI. Participants with TI were similar to the overall ROCKET AF population in regard to baseline clinical characteristics. Only 6% (n=483) of TI incidences involved bridging therapy. Stroke/systemic embolism rates during the at-risk period were similar in rivaroxaban-treated and warfarin-treated participants (0.30% versus 0.41% per 30 days; hazard ratio [confidence interval]=0.74 [0.36–1.50]; P=0.40). Risk of major bleeding during the at-risk period was also similar in rivaroxaban-treated and warfarin-treated participants (0.99% versus 0.79% per 30 days; hazard ratio [confidence interval]=1.26 [0.80–2.00]; P=0.32). Conclusions TI of oral anticoagulation is common and is associated with substantial stroke risks and bleeding risks that were similar among patients treated with rivaroxaban or warfarin. Further investigation is needed to determine the optimal management strategy in patients with atrial fibrillation requiring TI of anticoagulation. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00403767. PMID:24552831

Quality of full and final publications reporting acute stroke trials: a systematic review.

PubMed

Bath, F J; Owen, V E; Bath, P M

1998-10-01

Several studies have shown that the quality of reporting of trials throughout medicine is variable and often poor. We report on the quality of the final reports of randomized controlled trials (RCTs) of drug therapies assessed in acute stroke. English-language reports published up to the end of 1996 relating to completed RCTs in acute stroke were identified from electronic searches of the Cochrane Stroke Review Group database of stroke trials and the Cochrane Controlled Trials Register (CD-ROM issue 1, 1997, of the Cochrane Library). Report quality was assessed with the 33 criteria of the CONSORT statement and 53 additional factors relevant to acute stroke or trials in general. Trial quality was also assessed with a 7-point scale. Up to 1996, 114 RCTs were published which involved 20 536 patients (median, 80; range, 16 to 1267 per trial); 39 (35.5%) of these were published in Stroke. The median total report quality was 40/86 (range, 15 to 61) for all criteria and 19/33 (range, 9 to 29) for the CONSORT criteria alone. Although adequate information was given in the introduction and discussion sections of most reports, insufficient details were given on methods, assignment of patients to treatment groups, statistical analyses, the prevalence of risk factors, and assessment of outcomes. Report quality has improved between 1956 and 1996 (Spearman correlation coefficient [rs], 0.575; 95% confidence interval [CI], 0. 439 to 0.685) and was superior in large trials (rs=0.434; 95% CI, 0. 274 to 0.571). Although report quality was related to trial quality (rs=0.675; 95% CI, 0.563 to 0.763), it was not related to journal impact factor (rs=0.170; 95% CI, -0.015 to 0.344). Trials with a positive outcome tended to be less well reported than those with a neutral or negative outcome (rs=-0.192; 95% CI, -0.351 to -0.011). The overall quality of study reports for parallel group RCTs in acute stroke is poor but appears to be improving with time and in parallel with an increase in trial size. Reports often lack detailed information on the methods of randomization, concealment of allocation, and statistical analysis, all factors which can, if undertaken poorly, affect trial results and validity. It is vital that future trials are adequately reported; we believe that authors should follow the CONSORT guidelines and that referees and editors should ensure this happens.

CHHIPS (Controlling Hypertension and Hypotension Immediately Post-Stroke) Pilot Trial: rationale and design.

PubMed

Potter, J; Robinson, T; Ford, G; James, M; Jenkins, D; Mistri, A; Bulpitt, C; Drummond, A; Jagger, C; Knight, J; Markus, H; Beevers, G; Dewey, M; Lees, K; Moore, A; Paul, S

2005-03-01

High and low blood pressure (BP) levels are common following acute stroke, with up to 60% of patients being hypertensive (SBP > 160 mmHg) and nearly 20% having relative hypotension (SBP < or = 140 mmHg), within the first few hours of ictus, both conditions being associated with an adverse prognosis. At present, the optimum management of blood pressure in the immediate post-stroke period is unclear. The primary aim of the Controlling Hypertension and Hypotension Immediately Post-Stroke (CHHIPS) Pilot Trial is to assess whether hypertension and relative hypotension, manipulated therapeutically in the first 24 h following acute stroke, affects short-term outcome measures. The CHHIPS Pilot Trial is a UK based multi-centre, randomized, double-blind, placebo-controlled, titrated dose trial. Acute stroke and medical units in teaching and district general hospitals, in the UK. The CHHIPS Pilot Study aims to recruit 2050 patients, with clinically suspected stroke, confirmed by brain imaging, who have no compelling indication or contraindication for BP manipulation. The primary outcome measure will be the effects of acute pressor therapy (initiated < or = 12 h from stroke onset) or depressor therapy (started < or = 24 h post-ictus) on death and dependency at 14 days post-stroke. Secondary outcome measures will include the influence of therapy on early neurological deterioration, the effectiveness of treatment in manipulating BP levels, the influence of time to treatment and stroke type on response and a cost-effectiveness analysis.

Different systolic blood pressure targets for people with history of stroke or transient ischaemic attack: PAST-BP (Prevention After Stroke—Blood Pressure) randomised controlled trial

PubMed Central

McManus, Richard J; Roalfe, Andrea; Fletcher, Kate; Taylor, Clare J; Martin, Una; Virdee, Satnam; Greenfield, Sheila; Hobbs, F D Richard

2016-01-01

Objective To assess whether using intensive blood pressure targets leads to lower blood pressure in a community population of people with prevalent cerebrovascular disease. Design Open label randomised controlled trial. Setting 99 general practices in England, with participants recruited in 2009-11. Participants People with a history of stroke or transient ischaemic attack whose systolic blood pressure was 125 mm Hg or above. Interventions Intensive systolic blood pressure target (<130 mm Hg or 10 mm Hg reduction from baseline if this was <140 mm Hg) or standard target (<140 mm Hg). Apart from the different target, patients in both arms were actively managed in the same way with regular reviews by the primary care team. Main outcome measure Change in systolic blood pressure between baseline and 12 months. Results 529 patients (mean age 72) were enrolled, 266 to the intensive target arm and 263 to the standard target arm, of whom 379 were included in the primary analysis (182 (68%) intensive arm; 197 (75%) standard arm). 84 patients withdrew from the study during the follow-up period (52 intensive arm; 32 standard arm). Mean systolic blood pressure dropped by 16.1 mm Hg to 127.4 mm Hg in the intensive target arm and by 12.8 mm Hg to 129.4 mm Hg in the standard arm (difference between groups 2.9 (95% confidence interval 0.2 to 5.7) mm Hg; P=0.03). Conclusions Aiming for target below 130 mm Hg rather than 140 mm Hg for systolic blood pressure in people with cerebrovascular disease in primary care led to a small additional reduction in blood pressure. Active management of systolic blood pressure in this population using a <140 mm Hg target led to a clinically important reduction in blood pressure. Trial registration Current Controlled Trials ISRCTN29062286. PMID:26919870

Stroke of Known Cause and Underlying Atrial Fibrillation (STROKE-AF) randomized trial: Design and rationale.

PubMed

Bernstein, Richard A; Kamel, Hooman; Granger, Christopher B; Kowal, Robert C; Ziegler, Paul D; Schwamm, Lee H

2017-08-01

Approximately 20% of ischemic strokes are associated with clinically apparent atrial fibrillation (AF). Regardless of stroke etiology, detection of AF in patients with ischemic strokes often changes antithrombotic treatment from anti-platelet to oral anticoagulation therapy. The role and the optimum duration of cardiac monitoring to detect AF in patients with strokes presumed due to large vessel atherosclerosis or small vessel disease is unknown. This manuscript describes the design and rationale of the STROKE-AF trial. STROKE-AF is a randomized, controlled, open-label, post-market clinical trial. Detection of AF will be evaluated using continuous arrhythmia monitoring with an insertable cardiac monitor (ICM) compared with standard of care follow-up in patients with stroke (within the prior 10 days) that is presumed due to large vessel cervical or intracranial atherosclerosis, or to small vessel disease. Approximately 500 patients will be enrolled at approximately 40 centers in the United States. Patients will be randomized 1:1 to arrhythmia monitoring with an ICM (continuous monitoring arm) or standard of care follow-up (control arm). Subjects will be followed for ≥12 months and up to 3 years. The primary objective is to compare the incidence rate of detected AF through 12 months of follow-up between the two arms. This trial will provide information on the value of ICMs to detect subclinical AF in patients with stroke presumed due to large vessel atherosclerosis or small vessel disease, which will have implications for guiding treatment with oral anticoagulation for secondary stroke prevention. Copyright © 2017 Elsevier Inc. All rights reserved.

How a Stroke Is Diagnosed

MedlinePlus

... Trials News About Neurology Image Library Search The Internet Stroke Center Patients & Families About Stroke Stroke Diagnosis ... UT Southwestern Medical Center. Copyright © 1997-2018 - The Internet Stroke Center. All rights reserved. The information contained ...

Compliance with prospective trial registration guidance remained low in high-impact journals and has implications for primary end point reporting.

PubMed

Dal-Ré, Rafael; Ross, Joseph S; Marušić, Ana

2016-07-01

To examine compliance with International Committee of Medical Journal Editors' (ICMJE) policy on prospective trial registration along with predictors of compliance. Cross-sectional analysis of all articles reporting trial results published in the six highest-impact general medicine journals in January-June 2014 that were registered in a public trial registry. The main outcome measure was compliance with ICMJE policy. The time frame for trial primary end point ascertainment was used to assess whether retrospective registration could have allowed changing of primary end points following an interim analysis. Forty of 144 (28%) articles did not comply with the ICMJE policy. Trials of non-FDA-regulated interventions were less compliant than trials of FDA-regulated interventions (i.e., medicines, medical devices) (42% vs. 21%; P = 0.016). Twenty-nine of these 40 (72%; 20% overall) were registered before any interim analysis of primary end points could have been conducted; 11 (28%; 8% overall) were registered after primary end point ascertainment, such that investigators could have had the opportunity to conduct an interim analysis before trial registration. Twenty-eight percent of trials published in high-impact journals were retrospectively registered including nearly 10% that were registered after primary end point ascertainment could have had taken place. Prospective registration should be prompted and enforced to ensure transparency and accountability in clinical research. Copyright © 2016 Elsevier Inc. All rights reserved.

Acupuncture for acute stroke: study protocol for a multicenter, randomized, controlled trial.

PubMed

Chen, Lifang; Fang, Jianqiao; Ma, Ruijie; Froym, Ronen; Gu, Xudong; Li, Jianhua; Chen, Lina; Xu, Shouyu; Ji, Conghua

2014-06-08

Acupuncture has been widely used as a treatment for stroke in China for more than 3,000 years. However, previous research has not yet shown that acupuncture is effective as a stroke treatment. We report a protocol for a multicenter, randomized, controlled, and outcome assessor-blind trial to evaluate the efficacy and safety of acupuncture on acute ischemic stroke. In a prospective trial involving three hospitals in the Zhejiang Province (China) 250 patients with a recent (less than 1 week previous) episode of ischemic stroke will be included. Patients will be randomized into two groups: an acupuncture group given scalp acupuncture and electroacupuncture, and a control group given no acupuncture. Eighteen treatment sessions will be performed over a three-week period. The primary outcome will be measured by changes in the National Institutes of Health Stroke Scale score at the one, three, and four-week follow-up. Secondary outcome measures will be: 1) the Fugl-Meyer assessment scale for motor function; 2) the mini-mental state examination and Montreal cognitive assessment for cognitive function; 3) the video-fluoroscopic swallowing study for swallowing ability; and 4) the incidence of adverse events. This trial is expected to clarify whether or not acupuncture is effective for acute stroke. It will also show if acupuncture can improve motor, cognitive, or swallowing function. Chinese Clinical Trial Registry ChiCTR-TRC-12001971.

Peer education for secondary stroke prevention in inner-city minorities: design and methods of the prevent recurrence of all inner-city strokes through education randomized controlled trial.

PubMed

Goldfinger, Judith Z; Kronish, Ian M; Fei, Kezhen; Graciani, Albert; Rosenfeld, Peri; Lorig, Kate; Horowitz, Carol R

2012-09-01

The highest risk for stroke is among survivors of strokes or transient ischemic attacks (TIA). However, use of proven-effective cardiovascular medications to control stroke risk is suboptimal, particularly among the Black and Latino populations disproportionately impacted by stroke. A partnership of Harlem and Bronx community representatives, stroke survivors, researchers, clinicians, outreach workers and patient educators used community-based participatory research to conceive and develop the Prevent Recurrence of All Inner-city Strokes through Education (PRAISE) trial. Using data from focus groups with stroke survivors, they tailored a peer-led, community-based chronic disease self-management program to address stroke risk factors. PRAISE will test, in a randomized controlled trial, whether this stroke education intervention improves blood pressure control and a composite outcome of blood pressure control, lipid control, and use of antithrombotic medications. Of the 582 survivors of stroke and TIA enrolled thus far, 81% are Black or Latino and 56% have an annual income less than $15,000. Many (33%) do not have blood pressures in the target range, and most (66%) do not have control of all three major stroke risk factors. Rates of stroke recurrence risk factors remain suboptimal in the high risk, urban, predominantly minority communities studied. With a community-partnered approach, PRAISE has recruited a large number of stroke and TIA survivors to date, and may prove successful in engaging those at highest risk for stroke and reducing disparities in stroke outcomes in inner-city communities. Copyright © 2012 Elsevier Inc. All rights reserved.

Implementing a complex rehabilitation intervention in a stroke trial: a qualitative process evaluation of AVERT.

PubMed

Luker, Julie A; Craig, Louise E; Bennett, Leanne; Ellery, Fiona; Langhorne, Peter; Wu, Olivia; Bernhardt, Julie

2016-05-10

The implementation of multidisciplinary stroke rehabilitation interventions is challenging, even when the intervention is evidence-based. Very little is known about the implementation of complex interventions in rehabilitation clinical trials. The aim of study was to better understand how the implementation of a rehabilitation intervention in a clinical trial within acute stroke units is experienced by the staff involved. This qualitative process evaluation was part of a large Phase III stroke rehabilitation trial (AVERT). A descriptive qualitative approach was used. We purposively sampled 53 allied health and nursing staff from 19 acute stroke units in Australia, New Zealand and Scotland. Semi-structured interviews were conducted by phone, voice-internet, or face to face. Digitally recorded interviews were transcribed and analysed by two researchers using rigorous thematic analysis. Our analysis uncovered ten important themes that provide insight into the challenges of implementing complex new rehabilitation practices within complex care settings, plus factors and strategies that assisted implementation. Themes were grouped into three main categories: staff experience of implementing the trial intervention, barriers to implementation, and overcoming the barriers. Participation in the trial was challenging but had personal rewards and improved teamwork at some sites. Over the years that the trial ran some staff perceived a change in usual care. Barriers to trial implementation at some sites included poor teamwork, inadequate staffing, various organisational barriers, staff attitudes and beliefs, and patient-related barriers. Participants described successful implementation strategies that were built on interdisciplinary teamwork, education and strong leadership to 'get staff on board', and developing different ways of working. The AVERT stroke rehabilitation trial required commitment to deliver an intervention that needed strong collaboration between nurses and physiotherapists and was different to current care models. This qualitative process evaluation contributes unique insights into factors that may be critical to successful trials teams, and as AVERT was a pragmatic trial, success factors to delivering complex intervention in clinical practice. AVERT registered with Australian New Zealand Clinical Trials Registry ACTRN12606000185561 .

What's new in stroke? The top 10 studies of 2009-2011: part II.

PubMed

Hart, Robert G; Oczkowski, Wiesław J

2011-06-01

Five studies published between 2009 and 2011 are reviewed that importantly inform stroke prevention for patients with atrial fibrillation (AF) or with cervical carotid artery stenosis. Two large, phase III randomized trials tested novel oral anticoagulants for stroke prevention in patients with AF: the direct thrombin inhibitor dabigatran 150 mg twice daily was superior to adjusted-dose warfarin (RE-LY trial) and the direct factor Xa inhibitor apixaban was far superior to aspirin in patients deemed unsuitable for warfarin (AVERROES trial). For both novel anticoagulants, major bleeding rates were similar to the comparator treatment. Clopidogrel plus aspirin was more efficacious than aspirin alone for prevention of stroke in patients with AF deemed unsuitable for warfarin, but major bleeding was significantly increased with dual antiplatelet therapy (ACTIVE A trial). Two large randomized trials (CREST, ICSS) provide the best available data on the short-term risks of carotid artery stenting vs. endarterectomy. In both trials, periprocedural stroke was more frequent with stenting than with endarterectomy, but the increased risk was largely confined to patients >70 years old. For younger patients, periprocedural risks were comparable with stenting or endarterectomy, but long-term outcomes are required to assess the relative merits of the two procedures.

Tailored approaches to stroke health education (TASHE): study protocol for a randomized controlled trial.

PubMed

Ravenell, Joseph; Leighton-Herrmann, Ellyn; Abel-Bey, Amparo; DeSorbo, Alexandra; Teresi, Jeanne; Valdez, Lenfis; Gordillo, Madeleine; Gerin, William; Hecht, Michael; Ramirez, Mildred; Noble, James; Cohn, Elizabeth; Jean-Louis, Giardin; Spruill, Tanya; Waddy, Salina; Ogedegbe, Gbenga; Williams, Olajide

2015-04-19

Stroke is a leading cause of adult disability and mortality. Intravenous thrombolysis can minimize disability when patients present to the emergency department for treatment within the 3 - 4½ h of symptom onset. Blacks and Hispanics are more likely to die and suffer disability from stroke than whites, due in part to delayed hospital arrival and ineligibility for intravenous thrombolysis for acute stroke. Low stroke literacy (poor knowledge of stroke symptoms and when to call 911) among Blacks and Hispanics compared to whites may contribute to disparities in acute stroke treatment and outcomes. Improving stroke literacy may be a critical step along the pathway to reducing stroke disparities. The aim of the current study is to test a novel intervention to increase stroke literacy in minority populations in New York City. In a two-arm cluster randomized trial, we will evaluate the effectiveness of two culturally tailored stroke education films - one in English and one in Spanish - on changing behavioral intent to call 911 for suspected stroke, compared to usual care. These films will target knowledge of stroke symptoms, the range of severity of symptoms and the therapeutic benefit of calling 911, as well as address barriers to timely presentation to the hospital. Given the success of previous church-based programs targeting behavior change in minority populations, this trial will be conducted with 250 congregants across 14 churches (125 intervention; 125 control). Our proposed outcomes are (1) recognition of stroke symptoms and (2) behavioral intent to call 911 for suspected stroke, measured using the Stroke Action Test at the 6-month and 1-year follow-up. This is the first randomized trial of a church-placed narrative intervention to improve stroke outcomes in urban Black and Hispanic populations. A film intervention has the potential to make a significant public health impact, as film is a highly scalable and disseminable medium. Since there is at least one church in almost every neighborhood in the USA, churches have the ability and reach to play an important role in the dissemination and translation of stroke prevention programs in minority communities. NCT01909271 ; July 22, 2013.

Acupuncture for stroke rehabilitation.

PubMed

Yang, Ai; Wu, Hong Mei; Tang, Jin-Ling; Xu, Li; Yang, Ming; Liu, Guan J

2016-08-26

Stroke is the second most common cause of death in the world and in China it has now become the main cause of death. It is also a main cause of adult disability and dependency. Acupuncture for stroke has been used in China for hundreds of years and is increasingly practiced in some Western countries. This is an update of the Cochrane review originally published in 2006 . To determine the efficacy and safety of acupuncture therapy in people with subacute and chronic stroke. We intended to test the following hypotheses: 1) acupuncture can reduce the risk of death or dependency in people with subacute and chronic stroke at the end of treatment and at follow-up; 2) acupuncture can improve neurological deficit and quality of life after treatment and at the end of follow-up; 3) acupuncture can reduce the number of people requiring institutional care; and 4) acupuncture is not associated with any intolerable adverse effects. We searched the Cochrane Stroke Group Trials Register (June 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; Cochrane Library 2015, Issue 7), MEDLINE (1966 to July 2015, Ovid), EMBASE (1980 to July 2015, Ovid), CINAHL (1982 to July 2015, EBSCO), and AMED (1985 to July 2015, Ovid). We also searched the following four Chinese medical databases: China Biological Medicine Database (July 2015); Chinese Science and Technique Journals Database (July 2015); China National Infrastructure (July 2015), and Wan Fang database (July 2015). Truly randomised unconfounded clinical trials among people with ischaemic or haemorrhagic stroke, in the subacute or chronic stage, comparing acupuncture involving needling with placebo acupuncture, sham acupuncture, or no acupuncture. Two review authors independently selected trials for inclusion, assessed quality, extracted and cross-checked the data. We included 31 trials with a total of 2257 participants in the subacute or chronic stages of stroke. The methodological quality of most of the included trials was not high. The quality of evidence for the main outcomes was low or very low based on the assessment by the system of Grades of Recommendation, Assessment, Development and Evaluation (GRADE).Two trials compared real acupuncture plus baseline treatment with sham acupuncture plus baseline treatment. There was no evidence of differences in the changes of motor function and quality of life between real acupuncture and sham acupuncture for people with stroke in the convalescent stage.Twenty-nine trials compared acupuncture plus baseline treatment versus baseline treatment alone. Compared with no acupuncture, for people with stroke in the convalescent phase, acupuncture had beneficial effects on the improvement of dependency (activity of daily living) measured by Barthel Index (nine trials, 616 participants; mean difference (MD) 9.19, 95% confidence interval (CI) 4.34 to 14.05; GRADE very low), global neurological deficiency (seven trials, 543 participants; odds ratio (OR) 3.89, 95% CI 1.78 to 8.49; GRADE low), and specific neurological impairments including motor function measured by Fugl-Meyer Assessment (four trials, 245 participants; MD 6.16, 95% CI 4.20 to 8.11; GRADE low), cognitive function measured by the Mini-Mental State Examination (five trials, 278 participants; MD 2.54, 95% CI 0.03 to 5.05; GRADE very low), depression measured by the Hamilton Depression Scale (six trials, 552 participants; MD -2.58, 95% CI -3.28 to -1.87; GRADE very low), swallowing function measured by drinking test (two trials, 200 participants; MD -1.11, 95% CI -2.08 to -0.14; GRADE very low), and pain measured by the Visual Analogue Scale (two trials, 118 participants; MD -2.88, 95% CI -3.68 to -2.09; GRADE low). Sickness caused by acupuncture and intolerance of pain at acupoints were reported in a few participants with stroke in the acupuncture groups. No data on death, the proportion of people requiring institutional care or requiring extensive family support, and all-cause mortality were available in all included trials. From the available evidence, acupuncture may have beneficial effects on improving dependency, global neurological deficiency, and some specific neurological impairments for people with stroke in the convalescent stage, with no obvious serious adverse events. However, most included trials were of inadequate quality and size. There is, therefore, inadequate evidence to draw any conclusions about its routine use. Rigorously designed, randomised, multi-centre, large sample trials of acupuncture for stroke are needed to further assess its effects.

Antiplatelet Agents for the Secondary Prevention of Ischemic Stroke or Transient Ischemic Attack: A Network Meta-Analysis.

PubMed

Wang, Wen; Zhang, Lu; Liu, Weiming; Zhu, Qin; Lan, Qing; Zhao, Jizong

2016-05-01

Stroke can cause high morbidity and mortality, and ischemic stroke (IS) and transient ischemic attack (TIA) patients have a high stroke recurrence rate. Antiplatelet agents are the standard therapy for these patients, but it is often difficult for clinicians to select the best therapy from among the multiple treatment options. We therefore performed a network meta-analysis to estimate the efficacy of antiplatelet agents for secondary prevention of recurrent stroke. We systematically searched 3 databases (PubMed, Embase, and Cochrane) for relevant studies published through August 2015. The primary end points of this meta-analysis were overall stroke, hemorrhagic stroke, and fatal stroke. A total of 30 trials were included in our network meta-analysis and abstracted data. Among the therapies evaluated in the included trials, the estimates for overall stroke and hemorrhagic stroke for cilostazol (Cilo) were significantly better than those for aspirin (odds ratio [OR] = .64, 95% credibility interval [CrI], .45-.91; OR = .23, 95% CrI, .08-.58). The estimate for fatal stroke was highest for Cilo plus aspirin combination therapy, followed by Cilo therapy. The results of our meta-analysis indicate that Cilo significantly improves overall stroke and hemorrhagic stroke in IS or TIA patients and reduces fatal stroke, but with low statistical significance. Our results also show that Cilo was significantly more efficient than other therapies in Asian patients; therefore, future trials should focus on Cilo treatment for secondary prevention of recurrent stroke in non-Asian patients. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Patent Foramen Ovale Closure for Secondary Prevention of Cryptogenic Stroke: Updated Meta-Analysis of Randomized Clinical Trials.

PubMed

Vaduganathan, Muthiah; Qamar, Arman; Gupta, Ankur; Bajaj, Navkaranbir; Golwala, Harsh B; Pandey, Ambarish; Bhatt, Deepak L

2018-05-01

Patent foramen ovale closure represents a potential secondary prevention strategy for cryptogenic stroke, but available trials have varied by size, device studied, and follow-up. We conducted a systematic search of published randomized clinical trials evaluating patent foramen ovale closure versus medical therapy in patients with recent stroke or transient ischemic attack using PubMED, EMBASE, and Cochrane through September 2017. Weighting was by random effects models. Of 480 studies screened, we included 5 randomized clinical trials in the meta-analysis in which 3440 patients were randomized to patent foramen ovale closure (n = 1829) or medical therapy (n = 1611) and followed for an average of 2.0 to 5.9 years. Index stroke/transient ischemic attack occurred within 6 to 9 months of randomization. The primary end point was composite stroke/transient ischemic attack and death (in 3 trials) or stroke alone (in 2 trials). Patent foramen ovale closure reduced the primary end point (0.70 vs 1.48 events per 100 patient-years; risk ratio [RR], 0.52 [0.29-0.91]; I 2  = 55.0%) and stroke/transient ischemic attack (1.04 vs 2.00 events per 100 patient-years; RR, 0.55 [0.37-0.82]; I 2  = 42.2%) with modest heterogeneity compared with medical therapy. Procedural bleeding was not different between study arms (1.8% vs 1.8%; RR, 0.94 [0.49-1.83]; I 2  = 29.2%), but new-onset atrial fibrillation/flutter was increased with patent foramen ovale closure (6.6% vs 0.7%; RR, 4.69 [2.17-10.12]; I 2  = 29.3%). In patients with recent cryptogenic stroke, patent foramen ovale closure reduces recurrent stroke/transient ischemic attack compared with medical therapy, but is associated with a higher risk of new-onset atrial fibrillation/flutter. Copyright © 2018 Elsevier Inc. All rights reserved.

[Clinical trials registry].

PubMed

Ryder, Elena

2004-12-01

Authors and journals are more enthusiastic about the publication of trials with positive results than those negative or inconclusive trials. The International Committee of Medical Journal Editors proposed comprehensive trials registration as a solution to the problem of selective awareness and announces that the ICMJE member journals will adopt a trial-registration policy to promote this goal. They establish as a condition of consideration for publication, registration in a public trials registry. They recommend registries that meet certain criteria as www.clinicaltrials.com. Among those criteria is that the registry must be supported by a non-profit organization. On the other hand, people from Current Controlled Trials Ltd. being a commercial company, but meeting all the other criteria established by the ICMJE, feel that is being put aside. We wonder if clinical trials in our country are being registered in some of these International Registries. If not, would it be time to do so?

Methodology of the Stroke Self-Management Rehabilitation Trial: an international, multisite pilot trial.

PubMed

Jones, Kelly M; Bhattacharjee, Rohit; Krishnamurthi, Rita; Blanton, Sarah; Theadom, Alice; Barker-Collo, Suzanne; Thrift, Amanda; Parmar, Priya; Maujean, Annick; Ranta, Annemarei; Sanya, Emmanuel; Feigin, Valery L

2015-02-01

Stroke is a major cause of long-term adult disability with many survivors living in the community relying on family members for on-going support. However, reports of inadequate understanding of rehabilitation techniques are common. A self-management DVD-based observational learning tool may help improve functional outcomes for survivors of stroke and reduce caregivers' burden. This article describes the methodology of the stroke self-management rehabilitation trial. The overall aim of this pilot trial is to assess the feasibility and preliminary efficacy of a DVD-based intervention for improving functional outcomes of survivors of stroke 2 months postrandomization to inform the design of a full-scale randomized clinical trial. Recruitment of a minimum of 20 survivors of stroke and their informal caregivers (where available) in each of the participating centers will occur across multiple international sites. After baseline assessments, participants will be randomly assigned to an intervention or standard care group. The intervention comprises a structured DVD observation and practice schedule over 8 weeks. All participants will complete follow-up assessments. The outcome measures will include a global shift in the Rankin Scale scores and dichotomized scores, changes in quality of life, general health, depression, and caregiver burden at 2 months postrandomization. A qualitative analysis of the effects of the intervention will also be undertaken. The results of the pilot study will provide knowledge of whether observational learning techniques delivered via DVD can effectively improve recovery after stroke and reduce caregiver burden. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Registration status and methodological reporting of randomized controlled trials in obesity research: A review.

PubMed

Byrne, Jillian L S; Yee, Tamara; O'Connor, Kathleen; Dyson, Michele P; Ball, Geoff D C

2017-04-01

To assess registration and reporting details of randomized controlled trials (RCTs) published from 2011 to 2016 across four obesity journals. All issues from four leading obesity journals were searched systematically for RCTs from January 2011 to June 2016. Data on registration status were extracted from manuscripts, online trial registries, and a trial database; corresponding authors were contacted for registration details, when necessary. The methodological reporting of RCTs was assessed on specific criteria from the Consolidated Standards of Reporting Trials. A total of 223 RCTs were reviewed. Three-quarters (n = 170) were registered publicly; 94 (55.3%) reported registration details in the manuscript, and 82 (48.2%) were registered prospectively. Newer RCTs were more likely to be registered prospectively than older RCTs (2014-2016: 57.3% vs. 2011-2013: 39.2%; c 2  = 5.5, P = 0.02). Assessment on the Consolidated Standards of Reporting Trials demonstrated that less than half of all studies reported data collection dates (n = 108; 48.4%) or included "randomized trial" in the title (n = 89; 39.9%). The methodological reporting of RCTs published in obesity journals is suboptimal, despite current guidelines and policies. To complement existing standards, editorial boards should incorporate mandatory fields within the online manuscript submission process to enhance the quality, transparency, and comprehensiveness of reporting RCTs in obesity journals. © 2017 The Obesity Society.

Left atrial structure and function in atrial fibrillation: ENGAGE AF-TIMI 48

PubMed Central

Gupta, Deepak K.; Shah, Amil M.; Giugliano, Robert P.; Ruff, Christian T.; Antman, Elliott M.; Grip, Laura T.; Deenadayalu, Naveen; Hoffman, Elaine; Patel, Indravadan; Shi, Minggao; Mercuri, Michele; Mitrovic, Veselin; Braunwald, Eugene; Solomon, Scott D.

2014-01-01

Aims The complex relationship between left atrial (LA) structure and function, electrical burden of atrial fibrillation (AF) and stroke risk is not well understood. We aimed to describe LA structure and function in AF. Methods and results Left atrial structure and function was assessed in 971 subjects enrolled in the echocardiographic substudy of ENGAGE AF-TIMI 48. Left atrial size, emptying fraction (LAEF), and contractile function were compared across AF types (paroxysmal, persistent, or permanent) and CHADS2 scores as an estimate of stroke risk. The majority of AF patients (55%) had both LA enlargement and reduced LAEF, with an inverse relationship between LA size and LAEF (R = −0.57, P < 0.001). With an increasing electrical burden of AF and higher CHADS2 scores, LA size increased and LAEF declined. Moreover, 19% of AF subjects had impaired LAEF despite normal LA size, and LA contractile dysfunction was present even among the subset of AF subjects in sinus rhythm at the time of echocardiography. Conclusions In a contemporary AF population, LA structure and function were increasingly abnormal with a greater electrical burden of AF and higher stroke risk estimated by the CHADS2 score. Moreover, LA dysfunction was present despite normal LA size and sinus rhythm, suggesting that the assessment of LA function may add important incremental information in the evaluation of AF patients. Clinical Trial Registration: http://www.clinicaltrials.gov; ID = NCT00781391. PMID:24302269

Improving the development, monitoring and reporting of stroke rehabilitation research: Consensus-based core recommendations from the Stroke Recovery and Rehabilitation Roundtable.

PubMed

Walker, Marion F; Hoffmann, Tammy C; Brady, Marian C; Dean, Catherine M; Eng, Janice J; Farrin, Amanda J; Felix, Cynthia; Forster, Anne; Langhorne, Peter; Lynch, Elizabeth A; Radford, Kathryn A; Sunnerhagen, Katharina S; Watkins, Caroline L

2017-07-01

Recent reviews have demonstrated that the quality of stroke rehabilitation research has continued to improve over the last four decades but despite this progress, there are still many barriers in moving the field forward. Rigorous development, monitoring and complete reporting of interventions in stroke trials are essential in providing rehabilitation evidence that is robust, meaningful and implementable. An international partnership of stroke rehabilitation experts committed to develop consensus-based core recommendations with a remit of addressing the issues identified as limiting stroke rehabilitation research in the areas of developing, monitoring and reporting stroke rehabilitation interventions. Work exploring each of the three areas took place via multiple teleconferences and a two-day meeting in Philadelphia in May 2016. A total of 15 recommendations were made. To validate the need for the recommendations, the group reviewed all stroke rehabilitation trials published in 2015 (n = 182 papers). Our review highlighted that the majority of publications did not clearly describe how interventions were developed or monitored during the trial. In particular, under-reporting of the theoretical rationale for the intervention and the components of the intervention call into question many interventions that have been evaluated for efficacy. More trials were found to have addressed the reporting of interventions recommendations than those related to development or monitoring. Nonetheless, the majority of reporting recommendations were still not adequately described. To progress the field of stroke rehabilitation research and to ensure stroke patients receive optimal evidence-based clinical care, we urge the research community to endorse and adopt our recommendations.

5-Year Outcomes After Left Atrial Appendage Closure: From the PREVAIL and PROTECT AF Trials.

PubMed

Reddy, Vivek Y; Doshi, Shephal K; Kar, Saibal; Gibson, Douglas N; Price, Matthew J; Huber, Kenneth; Horton, Rodney P; Buchbinder, Maurice; Neuzil, Petr; Gordon, Nicole T; Holmes, David R

2017-12-19

The PROTECT AF (WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) trial demonstrated that left atrial appendage closure (LAAC) with the Watchman device (Boston Scientific, St. Paul, Minnesota) was equivalent to warfarin for preventing stroke in atrial fibrillation, but had a high rate of complications. In a second randomized trial, PREVAIL (Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy), the complication rate was low. The warfarin cohort experienced an unexpectedly low ischemic stroke rate, rendering the efficacy endpoints inconclusive. However, these outcomes were based on relatively few patients followed for a relatively short time. The final results of the PREVAIL trial, both alone and as part of a patient-level meta-analysis with the PROTECT AF trial, are reported with patients in both trials followed for 5 years. PREVAIL and PROTECT AF are prospective randomized clinical trials with patients randomized 2:1 to LAAC or warfarin; together, they enrolled 1,114 patients for 4,343 patient-years. Analyses are by intention-to-treat, and rates are events per 100 patient-years. For the PREVAIL trial, the first composite coprimary endpoint of stroke, systemic embolism (SE), or cardiovascular/unexplained death did not achieve noninferiority (posterior probability for noninferiority = 88.4%), whereas the second coprimary endpoint of post-procedure ischemic stroke/SE did achieve noninferiority (posterior probability for noninferiority = 97.5%); the warfarin arm maintained an unusually low ischemic stroke rate (0.73%). In the meta-analysis, the composite endpoint was similar between groups (hazard ratio [HR]: 0.820; p = 0.27), as were all-stroke/SE (HR: 0.961; p = 0.87). The ischemic stroke/SE rate was numerically higher with LAAC, but this difference did not reach statistical significance (HR: 1.71; p = 0.080). However, differences in hemorrhagic stroke, disabling/fatal stroke, cardiovascular/unexplained death, all-cause death, and post-procedure bleeding favored LAAC (HR: 0.20; p = 0.0022; HR: 0.45; p = 0.03; HR: 0.59; p = 0.027; HR: 0.73; p = 0.035; HR: 0.48; p = 0.0003, respectively). These 5-year outcomes of the PREVAIL trial, combined with the 5-year outcomes of the PROTECT AF trial, demonstrate that LAAC with Watchman provides stroke prevention in nonvalvular atrial fibrillation comparable to warfarin, with additional reductions in major bleeding, particularly hemorrhagic stroke, and mortality. (WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation; NCT00129545; and Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy; NCT01182441). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Do emergency medicine journals promote trial registration and adherence to reporting guidelines? A survey of "Instructions for Authors".

PubMed

Sims, Matthew T; Henning, Nolan M; Wayant, C Cole; Vassar, Matt

2016-11-24

The aim of this study was to evaluate the current state of two publication practices, reporting guidelines requirements and clinical trial registration requirements, by analyzing the "Instructions for Authors" of emergency medicine journals. We performed a web-based data abstraction from the "Instructions for Authors" of the 27 Emergency Medicine journals catalogued in the Expanded Science Citation Index of the 2014 Journal Citation Reports and Google Scholar Metrics h5-index to identify whether each journal required, recommended, or made no mention of the following reporting guidelines: EQUATOR Network, ICMJE, ARRIVE, CARE, CONSORT, STARD, TRIPOD, CHEERS, MOOSE, STROBE, COREQ, SRQR, SQUIRE, PRISMA-P, SPIRIT, PRISMA, and QUOROM. We also extracted whether journals required or recommended trial registration. Authors were blinded to one another's ratings until completion of the data validation. Cross-tabulations and descriptive statistics were calculated using IBM SPSS 22. Of the 27 emergency medicine journals, 11 (11/27, 40.7%) did not mention a single guideline within their "Instructions for Authors," while the remaining 16 (16/27, 59.3%) mentioned one or more guidelines. The QUOROM statement and SRQR were not mentioned by any journals whereas the ICMJE guidelines (18/27, 66.7%) and CONSORT statement (15/27, 55.6%) were mentioned most often. Of the 27 emergency medicine journals, 15 (15/27, 55.6%) did not mention trial or review registration, while the remaining 12 (12/27, 44.4%) at least mentioned one of the two. Trial registration through ClinicalTrials.gov was mentioned by seven (7/27, 25.9%) journals while the WHO registry was mentioned by four (4/27, 14.8%). Twelve (12/27, 44.4%) journals mentioned trial registration through any registry platform. The aim of this study was to evaluate the current state of two publication practices, reporting guidelines requirements and clinical trial registration requirements, by analyzing the "Instructions for Authors" of emergency medicine journals. In this study, there was not a single reporting guideline mentioned in more than half of the journals. This undermines efforts of other journals to improve the completeness and transparency of research reporting. Reporting guidelines are infrequently required or recommended by emergency medicine journals. Furthermore, few require clinical trial registration. These two mechanisms may limit bias and should be considered for adoption by journal editors in emergency medicine. UMIN000022486.

Patent Foramen Ovale Closure in the Setting of Cryptogenic Stroke: A Meta-Analysis of Five Randomized Trials.

PubMed

Garg, Lohit; Haleem, Affan; Varade, Shweta; Sivakumar, Keithan; Shah, Mahek; Patel, Brijesh; Agarwal, Manyoo; Agrawal, Sahil; Leary, Megan; Kluck, Bryan

2018-05-24

The clinical benefit of patent foramen ovale (PFO) closure after cryptogenic stroke has been a topic of debate for decades. Recently, 3 randomized controlled trials of PFO closure in patients with cryptogenic stroke demonstrated a significantly reduced risk of recurrent stroke compared with standard medical therapy alone. This meta-analysis was performed to clarify the efficacy of PFO closure for future stroke prevention in this population. A systematic literature search was undertaken. Published pooled data from 5 large randomized clinical trials (CLOSE, RESPECT, Gore REDUCE, CLOSURE I, and PC) were combined and then subsequently analyzed. Enrolled patients with cryptogenic stroke were assigned to receive standard medical care or to undergo endovascular PFO closure, with a primary outcome of reduction in stroke recurrence rate. Secondary outcomes included rates of transient ischemic attack (TIA), composite outcome of stroke, TIA, and death from all causes, and rates of atrial fibrillation events. We analyzed data for 3412 patients. Transcatheter PFO closure resulted in a statistically significant reduced rate of recurrent stroke, compared with medication alone. Patients undergoing closure were 58% less likely to have another stroke. The number needed to treat with PFO closure to reduce recurrent stroke for 1 patient was 40. Endovascular PFO closure was associated with a reduced risk of recurrent stroke in patients with a prior cryptogenic cerebral infarct. Although the absolute stroke reduction was small, these findings are clinically significant, given the young age of this patient population and the patients' lifetime risk of recurrent stroke. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Safety of percutaneous left atrial appendage closure: results from the Watchman Left Atrial Appendage System for Embolic Protection in Patients with AF (PROTECT AF) clinical trial and the Continued Access Registry.

PubMed

Reddy, Vivek Y; Holmes, David; Doshi, Shephal K; Neuzil, Petr; Kar, Saibal

2011-02-01

The Watchman Left Atrial Appendage System for Embolic Protection in Patients With AF (PROTECT AF) randomized trial compared left atrial appendage closure against warfarin in atrial fibrillation (AF) patients with CHADS₂ ≥1. Although the study met the primary efficacy end point of being noninferior to warfarin therapy for the prevention of stroke/systemic embolism/cardiovascular death, there was a significantly higher risk of complications, predominantly pericardial effusion and procedural stroke related to air embolism. Here, we report the influence of experience on the safety of percutaneous left atrial appendage closure. The study cohort for this analysis included patients in the PROTECT AF trial who underwent attempted device left atrial appendage closure (n=542 patients) and those from a subsequent nonrandomized registry of patients undergoing Watchman implantation (Continued Access Protocol [CAP] Registry; n=460 patients). The safety end point included bleeding- and procedure-related events (pericardial effusion, stroke, device embolization). There was a significant decline in the rate of procedure- or device-related safety events within 7 days of the procedure across the 2 studies, with 7.7% and 3.7% of patients, respectively, experiencing events (P=0.007), and between the first and second halves of PROTECT AF and CAP, with 10.0%, 5.5%, and 3.7% of patients, respectively, experiencing events (P=0.006). The rate of serious pericardial effusion within 7 days of implantation, which had made up >50% of the safety events in PROTECT AF, was lower in the CAP Registry (5.0% versus 2.2%, respectively; P=0.019). There was a similar experience-related improvement in procedure-related stroke (0.9% versus 0%, respectively; P=0.039). Finally, the functional impact of these safety events, as defined by significant disability or death, was statistically superior in the Watchman group compared with the warfarin group in PROTECT AF. This remained true whether significance was defined as a change in the modified Rankin score of ≥1, ≥2, or ≥3 (1.8 versus 4.3 events per 100 patient-years; relative risk, 0.43; 95% confidence interval, 0.24 to 0.82; 1.5 versus 3.7 events per 100 patient-years; relative risk, 0.41; 95% confidence interval, 0.22 to 0.82; and 1.4 versus 3.3 events per 100 patient-years; relative risk, 0.43; 95% confidence interval, 0.22 to 0.88, respectively). As with all interventional procedures, there is a significant improvement in the safety of Watchman left atrial appendage closure with increased operator experience. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00129545.

Subarachnoid Hemorrhage

MedlinePlus

... Trials News About Neurology Image Library Search The Internet Stroke Center Patients & Families About Stroke Stroke Diagnosis ... UT Southwestern Medical Center. Copyright © 1997-2018 - The Internet Stroke Center. All rights reserved. The information contained ...

Intracerebral Hemorrhage

MedlinePlus

... Trials News About Neurology Image Library Search The Internet Stroke Center Patients & Families About Stroke Stroke Diagnosis ... UT Southwestern Medical Center. Copyright © 1997-2018 - The Internet Stroke Center. All rights reserved. The information contained ...

Blood Pressure Control and Risk of Stroke or Systemic Embolism in Patients With Atrial Fibrillation: Results From the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial.

PubMed

Rao, Meena P; Halvorsen, Sigrun; Wojdyla, Daniel; Thomas, Laine; Alexander, John H; Hylek, Elaine M; Hanna, Michael; Bahit, M Cecilia; Lopes, Renato D; De Caterina, Raffaele; Erol, Cetin; Goto, Shinya; Lanas, Fernando; Lewis, Basil S; Husted, Steen; Gersh, Bernard J; Wallentin, Lars; Granger, Christopher B

2015-12-01

Patients with atrial fibrillation (AF) and hypertension are at high risk for stroke. Previous studies have shown elevated risk of stroke in patients with AF who have a history of hypertension (regardless of blood pressure [BP] control) and in patients with elevated BP. We assessed the association of hypertension and BP control on clinical outcomes. In ARISTOTLE (n=18 201), BP was evaluated as history of hypertension requiring treatment and elevated BP (systolic ≥140 and/or diastolic ≥90 mm Hg) at study entry and any point during the trial. Hazard ratios (HRs) were derived from Cox proportional hazards models including BP as a time-dependent covariate. A total of 15 916 (87.5%) patients had a history of hypertension requiring treatment. In patients with elevated BP measurement at any point during the trial, the rate of stroke or systemic embolism was significantly higher (HR, 1.53; 95% confidence interval [CI], 1.25-1.86), as was hemorrhagic stroke (HR 1.85; 95% CI, 1.26-2.72) and ischemic stroke (HR, 1.50; 95% CI, 1.18-1.90). Rates of major bleeding were lower in patients with a history of hypertension (HR, 0.80; 95% CI, 0.66-0.98) and nonsignificantly lower in patients with elevated BP at study entry (HR, 0.89; 95% CI, 0.77-1.03). The benefit of apixaban versus warfarin on preventing stroke or systemic embolism was consistent among patients with and without a history of hypertension (P interaction=0.27), BP control at baseline (P interaction=0.43), and BP control during the trial (P interaction=0.97). High BP measurement at any point during the trial was independently associated with a substantially higher risk of stroke or systemic embolism. These results strongly support efforts to treat elevated BP as an important strategy to optimally lower risk of stroke in patients with AF. URL: https://ClinicalTrials.gov/. Unique identifier: NCT00412984. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Powered robotic exoskeletons in post-stroke rehabilitation of gait: a scoping review.

PubMed

Louie, Dennis R; Eng, Janice J

2016-06-08

Powered robotic exoskeletons are a potential intervention for gait rehabilitation in stroke to enable repetitive walking practice to maximize neural recovery. As this is a relatively new technology for stroke, a scoping review can help guide current research and propose recommendations for advancing the research development. The aim of this scoping review was to map the current literature surrounding the use of robotic exoskeletons for gait rehabilitation in adults post-stroke. Five databases (Pubmed, OVID MEDLINE, CINAHL, Embase, Cochrane Central Register of Clinical Trials) were searched for articles from inception to October 2015. Reference lists of included articles were reviewed to identify additional studies. Articles were included if they utilized a robotic exoskeleton as a gait training intervention for adult stroke survivors and reported walking outcome measures. Of 441 records identified, 11 studies, all published within the last five years, involving 216 participants met the inclusion criteria. The study designs ranged from pre-post clinical studies (n = 7) to controlled trials (n = 4); five of the studies utilized a robotic exoskeleton device unilaterally, while six used a bilateral design. Participants ranged from sub-acute (<7 weeks) to chronic (>6 months) stroke. Training periods ranged from single-session to 8-week interventions. Main walking outcome measures were gait speed, Timed Up and Go, 6-min Walk Test, and the Functional Ambulation Category. Meaningful improvement with exoskeleton-based gait training was more apparent in sub-acute stroke compared to chronic stroke. Two of the four controlled trials showed no greater improvement in any walking outcomes compared to a control group in chronic stroke. In conclusion, clinical trials demonstrate that powered robotic exoskeletons can be used safely as a gait training intervention for stroke. Preliminary findings suggest that exoskeletal gait training is equivalent to traditional therapy for chronic stroke patients, while sub-acute patients may experience added benefit from exoskeletal gait training. Efforts should be invested in designing rigorous, appropriately powered controlled trials before powered exoskeletons can be translated into a clinical tool for gait rehabilitation post-stroke.

Feasibility study of the effects of art as a creative engagement intervention during stroke rehabilitation on improvement of psychosocial outcomes: study protocol for a single blind randomized controlled trial: the ACES study.

PubMed

Morris, Jacqui H; Kelly, Chris; Toma, Madalina; Kroll, Thilo; Joice, Sara; Mead, Gillian; Donnan, Peter; Williams, Brian

2014-09-28

Benefits of art participation after stroke are becoming increasingly recognized. Qualitative studies suggest that participation in visual arts creative engagement interventions (CEIs) during rehabilitation after stroke may improve mood, self-esteem, hope and some aspects of physical recovery. This study examines the feasibility of undertaking a randomized controlled trial of a CEI delivered by artists within in-patient stroke rehabilitation to test effectiveness. This trial is a two arm, single-blind, randomized controlled feasibility trial within in-patient stroke rehabilitation. We will recruit 80 patients receiving stroke rehabilitation in two stroke units in a health board area of Scotland (40 patients in each arm). Intervention arm participants will receive a visual-arts based CEI facilitated by experienced artists. Artists will follow an intervention protocol with specific components that enable participants to set, achieve and review artistic goals. Participants will receive up to eight intervention sessions, four within a group and four one-to-one with the artist. Control group participants will receive usual care only.Data collection will occur at baseline, post-intervention and three-month follow-up. Stroke-related health status is the primary outcome; mood, self-esteem, self-efficacy, perceived recovery control and hope are secondary outcomes. Semi-structured interviews will be conducted with purposively selected patients, artists and healthcare staff to elicit views and experiences of the intervention and feasibility and acceptability of trial processes. Recruitment rates, retention rates and patient preference for art participation will also be collected. Data will indicate, with confidence intervals, the proportion of patients choosing or refusing participation in the CEI and will allow calculation of recruitment rates for a future definitive trial. Summary data will indicate potential variability, magnitude and direction of difference between groups. Findings will inform sample size calculations for a definitive trial. Thematic analysis of qualitative data will be managed using the Framework Approach. Framework is an analytical approach for qualitative data, commonly used in policy and medical research. If shown to demonstrate effects, this intervention has the potential to address aspects of stroke recovery previously. Not routinely addressed in rehabilitation. Registered with Clinical Trials.Gov: NCT02085226 on 6th March 2014.

Rationale and design of the EPISTEME trial: efficacy of post-stroke intensive rosuvastatin treatment for aortogenic embolic stroke.

PubMed

Ueno, Yuji; Yamashiro, Kazuo; Tanaka, Yasutaka; Watanabe, Masao; Shimada, Yoshiaki; Kuroki, Takuma; Miyamoto, Nobukazu; Daimon, Masao; Tanaka, Ryota; Miyauchi, Katsumi; Daida, Hiroyuki; Hattori, Nobutaka; Urabe, Takao

2014-02-01

Large atheromatous aortic plaques (AAPs) are associated with stroke recurrence. Rosuvastatin is a potent lipid-lowering agent and suppresses carotid and coronary artery atherosclerosis. It is unclear whether rosuvastatin has anti-atherogenic effects against AAPs in stroke patients. We designed a clinical trial in stroke patients to analyze changes in AAPs after rosuvastatin treatment using repeated transesophageal echocardiography (TEE). This trial is a prospective randomized open label study. Inclusion criteria were patients were ischemic stroke with hypercholesterolemia and AAPs ≥ 4 mm in thickness. The patients are randomly assigned to either a group treated with 5 mg/day rosuvastatin or a control group. Primary endpoint is the changes in volume and composition of AAPs after 6 months using transesophageal echocardiography (TEE). Biochemical findings are analyzed. By using repeated TEE and binary image analysis, we will be able to compare the dynamic changes in plaque composition of AAPs before and after therapy in the two groups. The EPISTEME trial will provide information on the changes in plaque volume and composition achieved by improvement of lipid profiles with rosuvastatin therapy in stroke patients with aortic atherosclerosis. The results of the study may provide evidence for a therapeutic strategy for aortogenic brain embolism. This study is registered with UMIN-CTR (UMIN000010548).

THrombolysis for Acute Wake-up and unclear-onset Strokes with alteplase at 0·6 mg/kg (THAWS) Trial

PubMed Central

Koga, Masatoshi; Toyoda, Kazunori; Kimura, Kazumi; Yamamoto, Haruko; Sasaki, Makoto; Hamasaki, Toshimitsu; Kitazono, Takanari; Aoki, Junya; Seki, Kenta; Homma, Kazunari; Sato, Shoichiro; Minematsu, Kazuo

2014-01-01

Rationale Because of lack of information regarding timing of stroke, patients who suffer stroke during sleep are generally ineligible for intravenous thrombolysis, although many of these patients could potentially recover with this treatment. Magnetic resonance image findings with positive diffusion-weighted imaging and no marked parenchymal hyperintensity on fluid-attenuated inversion recovery (negative pattern) can identify acute ischemic stroke patients within 4·5 h from symptom onset. Aims The THrombolysis for Acute Wake-up and unclear-onset Strokes with alteplase at 0·6 mg/kg trial aims to determine the efficacy and safety of intravenous thrombolysis with alteplase at 0·6 mg/kg body weight, the approved dose for Japanese stroke patients, using magnetic resonance image-based selection in ischemic stroke patients with unclear time of symptom onset, and compare findings with standard treatment. Design This is an investigator-initiated, multicenter, prospective, randomized, open-treatment, blinded-end-point clinical trial. The design is similar to the Efficacy and Safety of MRI-based Thrombolysis in Wake-up Stroke trial. Patients with unclear-onset time of stroke symptoms beyond 4·5 h and within 12 h after the time of the last-known-well period and within 4·5 h after symptom recognition, who showed a negative fluid-attenuated inversion recovery pattern, are randomized to either intravenous thrombolysis or standard treatment. Study outcomes The primary efficacy end-point is modified Rankin Scale 0–1 at 90 days. The safety outcome measures are symptomatic intracranial hemorrhage at 22–36 h, and major bleeding and mortality at 90 days. Discussion This trial may help determine if low-dose alteplase at 0·6 mg/kg should be recommended as a routine clinical strategy for ischemic stroke patients with unclear-onset time. PMID:25088843

Stroke management in northern Lombardy: organization of an emergency-urgency network and development of a connection between prehospital and in-hospital settings.

PubMed

Vidale, Simone; Verrengia, Elena; Gerardi, Francesca; Arnaboldi, Marco; Bezzi, Giacomo; Bono, Giorgio; Guidotti, Mario; Grampa, Giampiero; Perrone, Patrizia; Zarcone, Davide; Zoli, Alberto; Beghi, Ettore; Agostoni, Elio; Porazzi, Daniele; Landriscina, Mario

2012-08-01

Stroke is the leading cause of disability in adulthood, and the principal aim of care in cerebrovascular disease is the reduction of this negative outcome and mortality. Several studies demonstrated the efficacy of thrombolytic therapy in ischemic stroke, but up to 80% of cases could not be treated because the diagnostic workup exceeds the time limit. In this article, we described the design of a study conducted in the northern Lombardy, within the district of Sondrio, Lecco, Como, and Varese. The awaited results of this study are reduction of avoidable delay, organization of an operative stroke emergency network, and identification of highly specialized structures. The study schedules education and data registration with implementation and training of acute stroke management algorithms. The use of standardized protocols during prehospital and in-hospital phase can optimize acute stroke pathways. The results of this study could contribute to the assessment of an effective and homogeneous health system to manage acute stroke. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

Is blood pressure reduction a valid surrogate endpoint for stroke prevention? an analysis incorporating a systematic review of randomised controlled trials, a by-trial weighted errors-in-variables regression, the surrogate threshold effect (STE) and the biomarker-surrogacy (BioSurrogate) evaluation schema (BSES)

PubMed Central

2012-01-01

Background Blood pressure is considered to be a leading example of a valid surrogate endpoint. The aims of this study were to (i) formally evaluate systolic and diastolic blood pressure reduction as a surrogate endpoint for stroke prevention and (ii) determine what blood pressure reduction would predict a stroke benefit. Methods We identified randomised trials of at least six months duration comparing any pharmacologic anti-hypertensive treatment to placebo or no treatment, and reporting baseline blood pressure, on-trial blood pressure, and fatal and non-fatal stroke. Trials with fewer than five strokes in at least one arm were excluded. Errors-in-variables weighted least squares regression modelled the reduction in stroke as a function of systolic blood pressure reduction and diastolic blood pressure reduction respectively. The lower 95% prediction band was used to determine the minimum systolic blood pressure and diastolic blood pressure difference, the surrogate threshold effect (STE), below which there would be no predicted stroke benefit. The STE was used to generate the surrogate threshold effect proportion (STEP), a surrogacy metric, which with the R-squared trial-level association was used to evaluate blood pressure as a surrogate endpoint for stroke using the Biomarker-Surrogacy Evaluation Schema (BSES3). Results In 18 qualifying trials representing all pharmacologic drug classes of antihypertensives, assuming a reliability coefficient of 0.9, the surrogate threshold effect for a stroke benefit was 7.1 mmHg for systolic blood pressure and 2.4 mmHg for diastolic blood pressure. The trial-level association was 0.41 and 0.64 and the STEP was 66% and 78% for systolic and diastolic blood pressure respectively. The STE and STEP were more robust to measurement error in the independent variable than R-squared trial-level associations. Using the BSES3, assuming a reliability coefficient of 0.9, systolic blood pressure was a B + grade and diastolic blood pressure was an A grade surrogate endpoint for stroke prevention. In comparison, using the same stroke data sets, no STEs could be estimated for cardiovascular (CV) mortality or all-cause mortality reduction, although the STE for CV mortality approached 25 mmHg for systolic blood pressure. Conclusions In this report we provide the first surrogate threshold effect (STE) values for systolic and diastolic blood pressure. We suggest the STEs have face and content validity, evidenced by the inclusivity of trial populations, subject populations and pharmacologic intervention populations in their calculation. We propose that the STE and STEP metrics offer another method of evaluating the evidence supporting surrogate endpoints. We demonstrate how surrogacy evaluations are strengthened if formally evaluated within specific-context evaluation frameworks using the Biomarker- Surrogate Evaluation Schema (BSES3), and we discuss the implications of our evaluation of blood pressure on other biomarkers and patient-reported instruments in relation to surrogacy metrics and trial design. PMID:22409774

Evolution of upper limb kinematics four years after subacute robot-assisted rehabilitation in stroke patients.

PubMed

Pila, Ophélie; Duret, Christophe; Gracies, Jean-Michel; Francisco, Gerard E; Bayle, Nicolas; Hutin, Émilie

2018-04-25

To assess functional status and robot-based kinematic measures four years after subacute robot-assisted rehabilitation in hemiparesis. Twenty-two patients with stroke-induced hemiparesis underwent a ≥3-month upper limb combined program of robot-assisted and occupational therapy from two months post-stroke, and received community-based therapy after discharge. Four years later, 19 (86%) participated in this follow-up study. Assessments 2, 5 and 54 months post-stroke included Fugl-Meyer (FM), Modified Frenchay Scale (MFS, at Month 54) and robot-based kinematic measures of targeting tasks in three directions, north, paretic and non-paretic: distance covered, velocity, accuracy (root mean square (RMS) error from straight line) and smoothness (number of velocity peaks; upward changes in accuracy and smoothness represent worsening). Analysis was stratified by FM score at two months: ≥17 (Group 1) or <17 (Group 2). Correlation between impairment (FM) and function (MFS) was explored at 54 months. FM scores were stable from 5 to 54 months (+1[-2;4], median [1st; 3rd quartiles], ns). Kinematic changes (three directions pooled) were: distance -1[-17;2]% (ns); velocity, -8[-32;28]% (ns); accuracy, +6[-13;98]% (ns); smoothness, +44[-6;126]% (p < 0.05). Group 2 showed decline vs. Group 1 (p < 0.001) in FM (Group 1, +3[1;5], p < 0.01; Group 2, -7[-11;-1], ns) and accuracy (Group 1, -3[-27;38]%, ns; Group 2, +29[17;140]%, p < 0.001). At 54 months, FM and MFS were highly correlated (Pearson's rho = 0.89; p < 0.001). While impairment appeared stable four years after robot-assisted upper limb training during subacute post-stroke phase, movement kinematics deteriorated despite community-based therapy, especially in more severely impaired patients. EudraCT 2016-005121-36. Registration: 2016-12-20. Date of enrolment of the first participant to the trial: 2009-11-24.

Aspirin for acute stroke of unknown etiology in resource-limited settings: a decision analysis.

PubMed

Berkowitz, Aaron L; Westover, M Brandon; Bianchi, Matt T; Chou, Sherry H-Y

2014-08-26

To analyze the potential impact of aspirin on outcome at hospital discharge after acute stroke in resource-limited settings without access to neuroimaging to distinguish ischemic stroke from intracerebral hemorrhage (ICH). A decision analysis was conducted to evaluate aspirin use in all patients with acute stroke of unknown type for the duration of initial hospitalization. Data were obtained from the International Stroke Trial and Chinese Acute Stroke Trial. Predicted in-hospital mortality and stroke recurrence risk were determined across the worldwide reported range of the proportion of strokes caused by ICH. Sensitivity analyses were performed on aspirin-associated relative risks in patients with ICH. At the highest reported proportion of strokes due to ICH from a large epidemiologic study (34% in sub-Saharan Africa), aspirin initiation after acute stroke of undetermined etiology is predicted to reduce in-hospital mortality (from 85/1,000 without treatment to 81/1,000 with treatment), in-hospital stroke recurrence (58/1,000 to 50/1,000), and combined risk of in-hospital mortality or stroke recurrence (127/1,000 to 114/1,000). Benefits of aspirin therapy remained in sensitivity analyses across a range of plausible parameter estimates for relative risks associated with aspirin initiation after ICH. Aspirin treatment for the period of initial hospitalization after acute stroke of undetermined etiology is predicted to decrease acute stroke-related mortality and in-hospital stroke recurrence even at the highest reported proportion of acute strokes due to ICH. In the absence of clinical trials to test this approach empirically, clinical decisions require patient-specific evaluation of risks and benefits of aspirin in this context. © 2014 American Academy of Neurology.

Presentation and outcomes of "wake-up strokes" in a large randomized stroke trial: analysis of data from the International Stroke Trial.

PubMed

Moradiya, Yogesh; Janjua, Nazli

2013-11-01

Recent studies comparing the outcomes of wake-up stroke (WUS) and stroke while awake (SWA) patients reveal better outcomes among SWA patients, attributable in part to their higher rates of thrombolysis. Patients with WUS are largely excluded from therapy. Earlier analyses, conducted before the approval of alteplase for acute stroke, show the true divergence of natural histories between these 2 groups. We analyzed 17,398 patients with ischemic stroke from the International Stroke Trial and compared both presentations and outcomes between the WUS and SWA groups. Severity was assessed by level of consciousness, Oxfordshire Community Stroke Project (OCSP) stroke classification, number of neurologic deficits, and predicted probability of dependency or death. Outcomes were assessed at day 14 and at 6 months. Outcome assessments were controlled for potential confounders. WUS represented 29.6% of all ischemic strokes. More severe OSCP stroke type (total anterior circulation syndrome) was less common in WUS. Although more patients with WUS were alert at presentation with a lower predicted probability of dependency, the 14-day mortality rates and rates of poor outcome at 6 months were similar between the 2 groups. WUS patients comprise one quarter to one third of ischemic stroke patients. Despite their more benign presentations, they deteriorate to outcome rates similar to SWA. Although they are typically excluded from time-dependent acute interventions, patients with WUS may benefit from acute intervention to prevent this worsening natural history. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

The Quality of Registration of Clinical Trials: Still a Problem

PubMed Central

Viergever, Roderik F.; Karam, Ghassan; Reis, Andreas; Ghersi, Davina

2014-01-01

Introduction The benefits of clinical trials registration include improved transparency on clinical trials for healthcare workers and patients, increased accountability of trialists, the potential to address publication bias and selective reporting, and possibilities for research collaboration and prioritization. However, poor quality of information in registered records of trials has been found to undermine these benefits in the past. Trialists' increasing experience with trial registration and recent developments in registration systems may have positively affected data quality. This study was conducted to investigate whether the quality of registration has improved. Methods We repeated a study from 2009, using the same methods and the same research team. A random sample of 400 records of clinical trials that were registered between 01/01/2012 and 01/01/2013 was taken from the International Clinical Trials Registry Platform (ICTRP) and assessed for the quality of information on 1) contact details, 2) interventions and 3) primary outcomes. Results were compared to the equivalent assessments from our previous study. Results There was a small and not statistically significant increase from 81.0% to 85.5% in the percentage of records that provided a name of a contact person. There was a significant increase from 68.7% to 74.9% in the number of records that provided either an email address or a telephone number. There was a significant increase from 44.2% to 51.9% in the number of intervention arms that were complete in registering intervention specifics. There was a significant increase from 38.2% to 57.6% in the number of primary outcomes that were specific measures with a meaningful timeframe. Approximately half of all trials continued to be retrospectively registered. Discussion There have been small but significant improvements in the quality of registration since 2009. Important problems with quality remain and continue to constitute an impediment to the meaningful utilization of registered trial information. PMID:24427293

Economic Evaluation Plan (EEP) for A Very Early Rehabilitation Trial (AVERT): An international trial to compare the costs and cost-effectiveness of commencing out of bed standing and walking training (very early mobilization) within 24 h of stroke onset with usual stroke unit care.

PubMed

Sheppard, Lauren; Dewey, Helen; Bernhardt, Julie; Collier, Janice M; Ellery, Fiona; Churilov, Leonid; Tay-Teo, Kiu; Wu, Olivia; Moodie, Marj

2016-06-01

A key objective of A Very Early Rehabilitation Trial is to determine if the intervention, very early mobilisation following stroke, is cost-effective. Resource use data were collected to enable an economic evaluation to be undertaken and a plan for the main economic analyses was written prior to the completion of follow up data collection. To report methods used to collect resource use data, pre-specify the main economic evaluation analyses and report other intended exploratory analyses of resource use data. Recruitment to the trial has been completed. A total of 2,104 participants from 56 stroke units across three geographic regions participated in the trial. Resource use data were collected prospectively alongside the trial using standardised tools. The primary economic evaluation method is a cost-effectiveness analysis to compare resource use over 12 months with health outcomes of the intervention measured against a usual care comparator. A cost-utility analysis is also intended. The primary outcome in the cost-effectiveness analysis will be favourable outcome (modified Rankin Scale score 0-2) at 12 months. Cost-utility analysis will use health-related quality of life, reported as quality-adjusted life years gained over a 12 month period, as measured by the modified Rankin Scale and the Assessment of Quality of Life. Outcomes of the economic evaluation analysis will inform the cost-effectiveness of very early mobilisation following stroke when compared to usual care. The exploratory analysis will report patterns of resource use in the first year following stroke. © 2016 World Stroke Organization.

Occupational therapy for patients with problems in personal activities of daily living after stroke: systematic review of randomised trials

PubMed Central

Drummond, Avril; Leonardi-Bee, Jo; Gladman, J R F; Donkervoort, Mireille; Edmans, Judi; Gilbertson, Louise; Jongbloed, Lyn; Logan, Pip; Sackley, Catherine; Walker, Marion; Langhorne, Peter

2007-01-01

Objective To determine whether occupational therapy focused specifically on personal activities of daily living improves recovery for patients after stroke. Design Systematic review and meta-analysis. Data sources The Cochrane stroke group trials register, the Cochrane central register of controlled trials, Medline, Embase, CINAHL, PsycLIT, AMED, Wilson Social Sciences Abstracts, Science Citation Index, Social Science Citation, Arts and Humanities Citation Index, Dissertations Abstracts register, Occupational Therapy Research Index, scanning reference lists, personal communication with authors, and hand searching. Review methods Trials were included if they evaluated the effect of occupational therapy focused on practice of personal activities of daily living or where performance in such activities was the target of the occupational therapy intervention in a stroke population. Original data were sought from trialists. Two reviewers independently reviewed each trial for methodological quality. Disagreements were resolved by consensus. Results Nine randomised controlled trials including 1258 participants met the inclusion criteria. Occupational therapy delivered to patients after stroke and targeted towards personal activities of daily living increased performance scores (standardised mean difference 0.18, 95% confidence interval 0.04 to 0.32, P=0.01) and reduced the risk of poor outcome (death, deterioration or dependency in personal activities of daily living) (odds ratio 0.67, 95% confidence interval 0.51 to 0.87, P=0.003). For every 100 people who received occupational therapy focused on personal activities of daily living, 11 (95% confidence interval 7 to 30) would be spared a poor outcome. Conclusions Occupational therapy focused on improving personal activities of daily living after stroke can improve performance and reduce the risk of deterioration in these abilities. Focused occupational therapy should be available to everyone who has had a stroke. PMID:17901469

Costs and cost-effectiveness of carotid stenting versus endarterectomy for patients at standard surgical risk: results from the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST).

PubMed

Vilain, Katherine R; Magnuson, Elizabeth A; Li, Haiyan; Clark, Wayne M; Begg, Richard J; Sam, Albert D; Sternbergh, W Charles; Weaver, Fred A; Gray, William A; Voeks, Jenifer H; Brott, Thomas G; Cohen, David J

2012-09-01

The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) demonstrated similar rates of the primary composite end point between carotid artery stenting (CAS) and carotid endarterectomy (CEA), although the risk of stroke was higher with CAS, and the risk of myocardial infarction was higher with CEA. Given the large number of patients who are candidates for these procedures, an understanding of their relative cost and cost-effectiveness may have important implications for health care policy and treatment guidelines. We performed a formal economic evaluation alongside the CREST trial. Costs were estimated from all trial participants over the first year of follow-up using a combination of resource use data and hospital billing data. Patient-level health use scores were obtained using data from the SF-36. We then used a Markov disease-simulation model calibrated to the CREST results to project 10-year costs and quality-adjusted life expectancy for the 2 treatment groups. Although initial procedural costs were $1025/patient higher with CAS, postprocedure costs and physician costs were lower such that total costs for the index hospitalization were similar for the CAS and CEA groups ($15 055 versus $14 816; mean difference, $239/patient; 95% CI for difference, -$297 to $775). Neither follow-up costs after discharge nor total 1-year costs differed significantly. For the CREST population, model-based projections over a 10-year time horizon demonstrated that CAS would result in a mean incremental cost of $524/patient and a reduction in quality-adjusted life expectancy of 0.008 years compared with CEA. Probabilistic sensitivity analysis demonstrated that CEA was economically attractive at an incremental cost-effectiveness threshold of $50 000/quality-adjusted life-year gained in 54% of samples, whereas CAS was economically attractive in 46%. Despite slightly lower in-trial costs and lower rates of stroke with CEA compared with CAS, projected 10-year outcomes from this controlled clinical trial demonstrate only trivial differences in overall healthcare costs and quality-adjusted life expectancy between the 2 strategies. If the CREST results can be replicated in clinical practice, these findings suggest that factors other than cost-effectiveness should be considered when deciding between treatment options for carotid artery stenosis in patients at standard risk for surgical complications. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique Identifier: NCT00004732.

The FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke: statistical and health economic analysis plan for the trials and for the individual patient data meta-analysis.

PubMed

Graham, Catriona; Lewis, Steff; Forbes, John; Mead, Gillian; Hackett, Maree L; Hankey, Graeme J; Gommans, John; Nguyen, Huy Thang; Lundström, Erik; Isaksson, Eva; Näsman, Per; Rudberg, Ann-Sofie; Dennis, Martin

2017-12-28

Small trials have suggested that fluoxetine may improve neurological recovery from stroke. FOCUS, AFFINITY and EFFECTS are a family of investigator-led, multicentre, parallel group, randomised, placebo-controlled trials which aim to determine whether the routine administration of fluoxetine (20 mg daily) for six months after an acute stroke improves patients' functional outcome. The core protocol for the three trials has been published (Mead et al., Trials 20:369, 2015). The trials include patients aged 18 years and older with a clinical diagnosis of stroke and persisting focal neurological deficits at randomisation 2-15 days after stroke onset. Patients are randomised centrally via each trials' web-based randomisation system using a common minimisation algorithm. Patients are allocated fluoxetine 20 mg once daily or matching placebo capsules for six months. The primary outcome measure is the modified Rankin scale (mRS) at six months. Secondary outcomes include: living circumstances; the Stroke Impact Scale; EuroQol (EQ5D-5 L); the vitality subscale of the 36-Item Short Form Health Survey (SF36); diagnosis of depression; adherence to medication; serious adverse events including death and recurrent stroke; and resource use at six and 12 months and the mRS at 12 months. Minor variations have been tailored to the national setting in the UK (FOCUS), Australia, New Zealand and Vietnam (AFFINITY) and Sweden (EFFECTS). Each trial is run and funded independently and will report its own results. A prospectively planned individual patient data meta-analysis of all three trials will provide the most precise estimate of the overall effect and establish whether any effects differ between trials or subgroups. This statistical analysis plan describes the core analyses for all three trials and that for the individual patient data meta-analysis. Recruitment and follow-up in the FOCUS trial is expected to be completed by the end of 2018. AFFINITY and EFFECTS are likely to complete follow-up in 2020. FOCUS: ISRCTN , ISRCTN83290762 . Registered on 23 May 2012. EudraCT, 2011-005616-29. Registered on 3 February 2012. Australian New Zealand Clinical Trials Registry, ACTRN12611000774921 . Registered on 22 July 2011. ISRCTN , ISRCTN13020412 . Registered on 19 December 2014. Clinicaltrials.gov, NCT02683213 . Registered on 2 February 2016. EudraCT, 2011-006130-16 . Registered on 8 August 2014.

Comparative effectiveness of home blood pressure telemonitoring (HBPTM) plus nurse case management versus HBPTM alone among Black and Hispanic stroke survivors: study protocol for a randomized controlled trial.

PubMed

Spruill, Tanya M; Williams, Olajide; Teresi, Jeanne A; Lehrer, Susan; Pezzin, Liliana; Waddy, Salina P; Lazar, Ronald M; Williams, Stephen K; Jean-Louis, Girardin; Ravenell, Joseph; Penesetti, Sunil; Favate, Albert; Flores, Judith; Henry, Katherine A; Kleiman, Anne; Levine, Steven R; Sinert, Richard; Smith, Teresa Y; Stern, Michelle; Valsamis, Helen; Ogedegbe, Gbenga

2015-03-15

Black and Hispanic stroke survivors experience higher rates of recurrent stroke than whites. This disparity is partly explained by disproportionately higher rates of uncontrolled hypertension in these populations. Home blood pressure telemonitoring (HBPTM) and nurse case management (NCM) have proven efficacy in addressing the multilevel barriers to blood pressure (BP) control and reducing BP. However, the effectiveness of these interventions has not been evaluated in stroke patients. This study is designed to evaluate the comparative effectiveness, cost-effectiveness and sustainability of these two telehealth interventions in reducing BP and recurrent stroke among high-risk Black and Hispanic stroke survivors with uncontrolled hypertension. A total of 450 Black and Hispanic patients with recent nondisabling stroke and uncontrolled hypertension are randomly assigned to one of two 12-month interventions: 1) HBPTM with wireless feedback to primary care providers or 2) HBPTM plus individualized, culturally-tailored, telephone-based NCM. Patients are recruited from stroke centers and primary care practices within the Health and Hospital Corporations (HHC) Network in New York City. Study visits occur at baseline, 6, 12 and 24 months. The primary outcomes are within-patient change in systolic BP at 12 months, and the rate of stroke recurrence at 24 months. The secondary outcome is the comparative cost-effectiveness of the interventions at 12 and 24 months; and exploratory outcomes include changes in stroke risk factors, health behaviors and treatment intensification. Recruitment for the stroke telemonitoring hypertension trial is currently ongoing. The combination of two established and effective interventions along with the utilization of health information technology supports the sustainability of the HBPTM + NCM intervention and feasibility of its widespread implementation. Results of this trial will provide strong empirical evidence to inform clinical guidelines for management of stroke in minority stroke survivors with uncontrolled hypertension. If effective among Black and Hispanic stroke survivors, these interventions have the potential to substantially mitigate racial and ethnic disparities in stroke recurrence. ClinicalTrials.gov NCT02011685 . Registered 10 December 2013.

A Very Early Rehabilitation Trial after stroke (AVERT): a Phase III, multicentre, randomised controlled trial.

PubMed

Langhorne, Peter; Wu, Olivia; Rodgers, Helen; Ashburn, Ann; Bernhardt, Julie

2017-09-01

Mobilising patients early after stroke [early mobilisation (EM)] is thought to contribute to the beneficial effects of stroke unit care but it is poorly defined and lacks direct evidence of benefit. We assessed the effectiveness of frequent higher dose very early mobilisation (VEM) after stroke. We conducted a parallel-group, single-blind, prospective randomised controlled trial with blinded end-point assessment using a web-based computer-generated stratified randomisation. The trial took place in 56 acute stroke units in five countries. We included adult patients with a first or recurrent stroke who met physiological inclusion criteria. Patients received either usual stroke unit care (UC) or UC plus VEM commencing within 24 hours of stroke. The primary outcome was good recovery [modified Rankin scale (mRS) score of 0-2] 3 months after stroke. Secondary outcomes at 3 months were the mRS, time to achieve walking 50 m, serious adverse events, quality of life (QoL) and costs at 12 months. Tertiary outcomes included a dose-response analysis. Patients, outcome assessors and investigators involved in the trial were blinded to treatment allocation. We recruited 2104 (UK, n  = 610; Australasia, n  = 1494) patients: 1054 allocated to VEM and 1050 to UC. Intervention protocol targets were achieved. Compared with UC, VEM patients mobilised 4.8 hours [95% confidence interval (CI) 4.1 to 5.7 hours; p  < 0.0001] earlier, with an additional three (95% CI 3.0 to 3.5; p  < 0.0001) mobilisation sessions per day. Fewer patients in the VEM group ( n  = 480, 46%) had a favourable outcome than in the UC group ( n  = 525, 50%) (adjusted odds ratio 0.73, 95% CI 0.59 to 0.90; p  = 0.004). Results were consistent between Australasian and UK settings. There were no statistically significant differences in secondary outcomes at 3 months and QoL at 12 months. Dose-response analysis found a consistent pattern of an improved odds of efficacy and safety outcomes in association with increased daily frequency of out-of-bed sessions but a reduced odds with an increased amount of mobilisation (minutes per day). UC clinicians started mobilisation earlier each year altering the context of the trial. Other potential confounding factors included staff patient interaction. Patients in the VEM group were mobilised earlier and with a higher dose of therapy than those in the UC group, which was already early. This VEM protocol was associated with reduced odds of favourable outcome at 3 months cautioning against very early high-dose mobilisation. At 12 months, health-related QoL was similar regardless of group. Shorter, more frequent mobilisation early after stroke may be associated with a more favourable outcome. These results informed a new trial proposal [A Very Early Rehabilitation Trial - DOSE (AVERT-DOSE)] aiming to determine the optimal frequency and dose of EM. The trial is registered with the Australian New Zealand Clinical Trials Registry number ACTRN12606000185561, Current Controlled Trials ISRCTN98129255 and ISRCTN98129255. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 21, No. 54. See the NIHR Journals Library website for further project information. Funding was also received from the National Health and Medical Research Council Australia, Singapore Health, Chest Heart and Stroke Scotland, Northern Ireland Chest Heart and Stroke, and the Stroke Association. In addition, National Health and Medical Research Council fellowship funding was provided to Julie Bernhardt (1058635), who also received fellowship funding from the Australia Research Council (0991086) and the National Heart Foundation (G04M1571). The Florey Institute of Neuroscience and Mental Health, which hosted the trial, acknowledges the support received from the Victorian Government via the Operational Infrastructure Support Scheme.

Long-Term Effect of Participation in an Early Exercise and Education Program on Clinical Outcomes and Cost Implications, in Patients with TIA and Minor, Non-Disabling Stroke.

PubMed

Faulkner, James; Stoner, Lee; Lanford, Jeremy; Jolliffe, Evan; Mitchelmore, Andrew; Lambrick, Danielle

2017-06-01

Participation in exercise and education programs following transient ischemic attack (TIA) or minor stroke may decrease cardiovascular disease risk. The purpose of this study was to assess the long-term effect (3.5 years) of an exercise and education program administered soon after TIA or minor stroke diagnosis on clinical outcome measures (stroke classification and number, patient deaths, hospital/emergency department admission) and cost implications obtained from standard hospital records. Hospital records were screened for 60 adults (male, n = 31; 71 ± 10 years), diagnosed with TIA or non-disabling stroke, who had previously been randomised and completed either an 8-week exercise and education program, or usual care control. Follow-up clinical outcomes and cost implications were obtained 3.5 ± 0.3 years post-exercise. Participants randomised to the exercise and education program had significantly fewer recurrent stroke/TIAs (n = 3 vs. n = 13, Cohen's d = 0.79) than the control group (P ≤ 0.003). Similar finding were reported for patient deaths (n = 0 vs. n = 4, d = 0.53), and hospital admissions (n = 48 vs. n = 102, d = 0.54), although these findings were only approaching statistical significance. The relative risk (mean; 95%CI) of death, stroke/TIAs and hospital admissions were 0.11 (0.01 to 1.98), 0.23 (0.07 to 0.72) and 0.79 (0.57 to 1.09), respectively. Hospital admission costs were significantly lower for the exercise group ($9041 ± 15,080 NZD [~$6000 ± 10,000 USD]) than the control group ($21,750 ± 22,973 NZD [~$14,000 ± 15,000 USD]) during the follow-up period (P < 0.05, d = 0.69). The present study demonstrates the long-term patient benefit and economic importance of providing secondary prevention, exercise and education programs for patients with TIA and minor stroke. URL: http://www.anzctr.org.au/ ; Trial Registration Number: ACTRN12611000630910.

A task-specific interactive game-based virtual reality rehabilitation system for patients with stroke: a usability test and two clinical experiments.

PubMed

Shin, Joon-Ho; Ryu, Hokyoung; Jang, Seong Ho

2014-03-06

Virtual reality (VR) is not commonly used in clinical rehabilitation, and commercial VR gaming systems may have mixed effects in patients with stroke. Therefore, we developed RehabMaster™, a task-specific interactive game-based VR system for post-stroke rehabilitation of the upper extremities, and assessed its usability and clinical efficacy. A participatory design and usability tests were carried out for development of RehabMaster with representative user groups. Two clinical trials were then performed. The first was an observational study in which seven patients with chronic stroke received 30 minutes of RehabMaster intervention per day for two weeks. The second was a randomised controlled trial of 16 patients with acute or subacute stroke who received 10 sessions of conventional occupational therapy only (OT-only group) or conventional occupational therapy plus 20 minutes of RehabMaster intervention (RehabMaster + OT group). The Fugl-Meyer Assessment score (FMA), modified Barthel Index (MBI), adverse effects, and drop-out rate were recorded. The requirements of a VR system for stroke rehabilitation were established and incorporated into RehabMaster. The reported advantages from the usability tests were improved attention, the immersive flow experience, and individualised intervention. The first clinical trial showed that the RehabMaster intervention improved the FMA (P = .03) and MBI (P = .04) across evaluation times. The second trial revealed that the addition of RehabMaster intervention tended to enhance the improvement in the FMA (P = .07) but did not affect the improvement in the MBI. One patient with chronic stroke left the trial, and no adverse effects were reported. The RehabMaster is a feasible and safe VR system for enhancing upper extremity function in patients with stroke.

A task-specific interactive game-based virtual reality rehabilitation system for patients with stroke: a usability test and two clinical experiments

PubMed Central

2014-01-01

Background Virtual reality (VR) is not commonly used in clinical rehabilitation, and commercial VR gaming systems may have mixed effects in patients with stroke. Therefore, we developed RehabMaster™, a task-specific interactive game-based VR system for post-stroke rehabilitation of the upper extremities, and assessed its usability and clinical efficacy. Methods A participatory design and usability tests were carried out for development of RehabMaster with representative user groups. Two clinical trials were then performed. The first was an observational study in which seven patients with chronic stroke received 30 minutes of RehabMaster intervention per day for two weeks. The second was a randomised controlled trial of 16 patients with acute or subacute stroke who received 10 sessions of conventional occupational therapy only (OT-only group) or conventional occupational therapy plus 20 minutes of RehabMaster intervention (RehabMaster + OT group). The Fugl-Meyer Assessment score (FMA), modified Barthel Index (MBI), adverse effects, and drop-out rate were recorded. Results The requirements of a VR system for stroke rehabilitation were established and incorporated into RehabMaster. The reported advantages from the usability tests were improved attention, the immersive flow experience, and individualised intervention. The first clinical trial showed that the RehabMaster intervention improved the FMA (P = .03) and MBI (P = .04) across evaluation times. The second trial revealed that the addition of RehabMaster intervention tended to enhance the improvement in the FMA (P = .07) but did not affect the improvement in the MBI. One patient with chronic stroke left the trial, and no adverse effects were reported. Conclusions The RehabMaster is a feasible and safe VR system for enhancing upper extremity function in patients with stroke. PMID:24597650

Characterization of Patients with Embolic Strokes of Undetermined Source in the NAVIGATE ESUS Randomized Trial.

PubMed

Kasner, Scott E; Lavados, Pablo; Sharma, Mukul; Wang, Yongjun; Wang, Yilong; Dávalos, Antoni; Shamalov, Nikolay; Cunha, Luis; Lindgren, Arne; Mikulik, Robert; Arauz, Antonio; Lang, Wilfried; Czlonkowska, Anna; Eckstein, Jens; Gagliardi, Rubens; Amarenco, Pierre; Ameriso, Sebastián F; Tatlisumak, Turgut; Veltkamp, Roland; Hankey, Graeme J; Toni, Danilo S; Bereczki, Daniel; Uchiyama, Shinichiro; Ntaios, George; Yoon, Byung-Woo; Brouns, Raf; DeVries Basson, M M; Endres, Matthias; Muir, Keith; Bornstein, Natan; Ozturk, Serefnur; O'Donnell, Martin; Mundl, Hardi; Pater, Calin; Weitz, Jeffrey; Peacock, W Frank; Swaminathan, Balakumar; Kirsch, Bodo; Berkowitz, Scott D; Peters, Gary; Pare, Guillaume; Themeles, Ellison; Shoamanesh, Ashkan; Connolly, Stuart J; Hart, Robert G

2018-06-01

The New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs. ASA to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) trial is a randomized phase-III trial comparing rivaroxaban versus aspirin in patients with recent ESUS. We aimed to describe the baseline characteristics of this large ESUS cohort to explore relationships among key subgroups. We enrolled 7213 patients at 459 sites in 31 countries. Prespecified subgroups for primary safety and efficacy analyses included age, sex, race, global region, stroke or transient ischemic attack prior to qualifying event, time to randomization, hypertension, and diabetes mellitus. Mean age was 66.9 ± 9.8 years; 24% were under 60 years. Older patients had more hypertension, coronary disease, and cancer. Strokes in older subjects were more frequently cortical and accompanied by radiographic evidence of prior infarction. Women comprised 38% of participants and were older than men. Patients from East Asia were oldest whereas those from Latin America were youngest. Patients in the Americas more frequently were on aspirin prior to the qualifying stroke. Acute cortical infarction was more common in the United States, Canada, and Western Europe, whereas prior radiographic infarctions were most common in East Asia. Approximately forty-five percent of subjects were enrolled within 30 days of the qualifying stroke, with earliest enrollments in Asia and Eastern Europe. NAVIGATE-ESUS is the largest randomized trial comparing antithrombotic strategies for secondary stroke prevention in patients with ESUS. The study population encompasses a broad array of patients across multiple continents and these subgroups provide ample opportunities for future research. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Multiattribute selection of acute stroke imaging software platform for Extending the Time for Thrombolysis in Emergency Neurological Deficits (EXTEND) clinical trial.

PubMed

Churilov, Leonid; Liu, Daniel; Ma, Henry; Christensen, Soren; Nagakane, Yoshinari; Campbell, Bruce; Parsons, Mark W; Levi, Christopher R; Davis, Stephen M; Donnan, Geoffrey A

2013-04-01

The appropriateness of a software platform for rapid MRI assessment of the amount of salvageable brain tissue after stroke is critical for both the validity of the Extending the Time for Thrombolysis in Emergency Neurological Deficits (EXTEND) Clinical Trial of stroke thrombolysis beyond 4.5 hours and for stroke patient care outcomes. The objective of this research is to develop and implement a methodology for selecting the acute stroke imaging software platform most appropriate for the setting of a multi-centre clinical trial. A multi-disciplinary decision making panel formulated the set of preferentially independent evaluation attributes. Alternative Multi-Attribute Value Measurement methods were used to identify the best imaging software platform followed by sensitivity analysis to ensure the validity and robustness of the proposed solution. Four alternative imaging software platforms were identified. RApid processing of PerfusIon and Diffusion (RAPID) software was selected as the most appropriate for the needs of the EXTEND trial. A theoretically grounded generic multi-attribute selection methodology for imaging software was developed and implemented. The developed methodology assured both a high quality decision outcome and a rational and transparent decision process. This development contributes to stroke literature in the area of comprehensive evaluation of MRI clinical software. At the time of evaluation, RAPID software presented the most appropriate imaging software platform for use in the EXTEND clinical trial. The proposed multi-attribute imaging software evaluation methodology is based on sound theoretical foundations of multiple criteria decision analysis and can be successfully used for choosing the most appropriate imaging software while ensuring both robust decision process and outcomes. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

Beyond Stroke Prevention in Atrial Fibrillation: Exploring Further Unmet Needs with Rivaroxaban.

PubMed

Gibson, C M; Hankey, G J; Nafee, T; Welsh, R C

2018-03-22

With improved life expectancy and the aging population, the global burden of atrial fibrillation (AF) continues to increase, and with AF comes an estimated fivefold increased risk of ischaemic stroke. Prophylactic anticoagulant therapy is more effective in reducing the risk of ischaemic stroke in AF patients than acetylsalicylic acid or dual-antiplatelet therapy combining ASA with clopidogrel. Non-vitamin K antagonist oral anticoagulants are the standard of care for stroke prevention in patients with non-valvular AF. The optimal anticoagulant strategy to prevent thromboembolism in AF patients who are undergoing percutaneous coronary intervention and stenting, those who have undergone successful transcatheter aortic valve replacement and those with embolic stroke of undetermined source are areas of ongoing research. This article provides an update on three randomized controlled trials of rivaroxaban, a direct, oral factor Xa inhibitor, that are complete or are ongoing, in these unmet areas of stroke prevention: oPen-label, randomized, controlled, multicentre study explorIng twO treatmeNt stratEgiEs of Rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment strategy in patients with Atrial Fibrillation who undergo Percutaneous Coronary Intervention (PIONEER AF-PCI) trial; the New Approach riVaroxaban Inhibition of factor Xa in a Global trial vs Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS) trial and the Global study comparing a rivAroxaban-based antithrombotic strategy to an antipLatelet-based strategy after transcatheter aortIc vaLve rEplacement to Optimize clinical outcomes (GALILEO) trial. The data from these studies are anticipated to help address continuing challenges for a range of patients at risk of stroke. Schattauer.

Combined Cognitive-Strategy and Task-Specific Training Affects Cognition and Upper-Extremity Function in Subacute Stroke: An Exploratory Randomized Controlled Trial

PubMed Central

Polatajko, Helene; Baum, Carolyn; Rios, Jorge; Cirone, Dianne; Doherty, Meghan; McEwen, Sara

2016-01-01

The purpose of this study was to estimate the effect of Cognitive Orientation to Daily Occupational Performance (CO–OP) compared with usual occupational therapy on upper-extremity movement, cognitive flexibility, and stroke impact in people less than 3 mo after stroke. An exploratory, single-blind randomized controlled trial was conducted with people referred to outpatient occupational therapy services at two rehabilitation centers. Arm movement was measured with the Action Research Arm Test, cognitive flexibility with the Delis–Kaplan Executive Function System Trail Making subtest, and stroke impact with subscales of the Stroke Impact Scale. A total of 35 participants were randomized, and 26 completed the intervention. CO–OP demonstrated measurable effects over usual care on all measures. These data provide early support for the use of CO–OP to improve performance and remediate cognitive and arm movement impairments after stroke over usual care; however, future study is warranted to confirm the effects observed in this trial. PMID:26943113

Impact of registration on clinical trials on infection risk in pediatric acute myeloid leukemia.

PubMed

Dix, David; Aplenc, Richard; Bowes, Lynette; Cellot, Sonia; Ethier, Marie-Chantal; Feusner, Jim; Gillmeister, Biljana; Johnston, Donna L; Lewis, Victor; Michon, Bruno; Mitchell, David; Portwine, Carol; Price, Victoria; Silva, Mariana; Stobart, Kent; Yanofsky, Rochelle; Zelcer, Shayna; Beyene, Joseph; Sung, Lillian

2016-04-01

Little is known about the impact of enrollment on therapeutic clinical trials on adverse event rates. Primary objective was to describe the impact of clinical trial registration on sterile site microbiologically documented infection for children with newly diagnosed acute myeloid leukemia (AML). We conducted a multicenter cohort study that included children aged ≤18 years with de novo AML. Primary outcome was microbiologically documented sterile site infection. Infection rates were compared between those registered and not registered on clinical trials. Five hundred seventy-four children with AML were included of which 198 (34.5%) were registered on a therapeutic clinical trial. Overall, 400 (69.7%) had at least one sterile site microbiologically documented infection. In multiple regression, registration on clinical trials was independently associated with a higher risk of microbiologically documented sterile site infection [adjusted odds ratio (OR) 1.24, 95% confidence interval (CI) 1.01-1.53; p = 0.040] and viridans group streptococcal infection (OR 1.46, 95% CI 1.08-1.98; p = 0.015). Registration on trials was not associated with Gram-negative or invasive fungal infections. Children with newly diagnosed AML enrolled on clinical trials have a higher risk of microbiologically documented sterile site infection. This information may impact on supportive care practices in pediatric AML. © 2015 UICC.

Effect of Right Insular Involvement on Death and Functional Outcome After Acute Ischemic Stroke in the IST-3 Trial (Third International Stroke Trial).

PubMed

Sposato, Luciano A; Cohen, Geoffrey; Wardlaw, Joanna M; Sandercock, Peter; Lindley, Richard I; Hachinski, Vladimir

2016-12-01

In patients with acute ischemic stroke, whether involvement of the insular cortex influences outcome is controversial. Much of the apparent adverse outcome may relate to such strokes usually being severe. We examined the influence of right and left insular involvement on stroke outcomes among patients from the IST-3 study (Third International Stroke Trial) who had visible ischemic stroke on neuroimaging. We used multiple logistic regression to compare outcomes of left versus right insular and noninsular strokes across strata of stroke severity, on death, proportion dead or dependent, and level of disability (ordinalized Oxford Handicap Score) at 6 months, with adjustment for the effects of age, lesion size, and presence of atrial fibrillation. Of 3035 patients recruited, 2099 had visible ischemic strokes limited to a single hemisphere on computed tomography/magnetic resonance scans. Of these, 566 and 714 had infarction of right and left insula. Six months after randomization, right insular involvement was associated with increased odds of death when compared with noninsular strokes on the left side (adjusted odds ratio, 1.83; 95% confidence interval, 1.33-2.52), whereas the adjusted odds ratio comparing mortality after insular versus noninsular strokes on the left side was not significant. Among mild/moderate strokes, outcomes for right insular involvement were worse than for left insular, but among more severe strokes, the difference in outcomes was less substantial. We found an association between right insular involvement and higher odds of death and worse functional outcome. The difference between right- and left-sided insular lesions on outcomes seemed to be most evident for mild/moderate strokes. URL: http://www.isrctn.com. Unique identifier: ISRCTN25765518. © 2016 American Heart Association, Inc.

Heart rate as a predictor of stroke in high-risk, hypertensive patients with previous stroke or transient ischemic attack.

PubMed

Sandset, Else Charlotte; Berge, Eivind; Kjeldsen, Sverre E; Julius, Stevo; Holzhauer, Björn; Krarup, Lars-Henrik; Hua, Tsushung A

2014-01-01

Risk factors for first stroke are well established, but less is known about risk factors for recurrent stroke. In the present analysis, we aimed to assess the effect of heart rate and other possible predictors of stroke in a hypertensive population with previous stroke or transient ischemic attack (TIA). The Valsartan Antihypertensive Long-Term Use Evaluation trial was a multicentre, double-masked, randomized controlled, parallel group trial comparing the effects of an angiotensin receptor blocker (valsartan) and a calcium channel blocker (amlodipine) in patients with hypertension and high cardiovascular risk. We used Cox proportional hazard models to investigate the effect of baseline variables on the risk of stroke. Quadratic terms of the continuous variables were entered in the models to test for linearity. Of 15,245 patients included in the trial, 3014 had a previous stroke or TIA at baseline and were included in the present analysis. Stroke recurrence occurred in 239 patients (7.9%) during a median of 4.5 years of follow-up. Resting heart rate (per 10 beats per minute; hazard ratio [HR], 2.78; 95% confidence interval [CI], 1.18-6.58) and diabetes mellitus at baseline (HR, 1.47; 95% CI, 1.03-2.10) were significantly associated with an increased risk of stroke recurrence in the multivariable analysis. In high-risk, hypertensive patients with previous stroke or TIA, resting heart rate was the strongest predictor of recurrent stroke. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Apixaban for stroke prevention in atrial fibrillation: a review of the clinical trial evidence.

PubMed

Yates, Scott W

2011-10-01

The objective of this review is to summarize data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) and Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) trials of apixaban for stroke prevention in patients with atrial fibrillation (AF). The ARISTOTLE trial compared apixaban with warfarin in 18 201 patients with AF and ≥ 1 additional risk factor for stroke. The AVERROES trial compared apixaban with aspirin in 5599 patients with AF who were at increased risk of stroke and for whom vitamin K antagonists were unsuitable. In ARISTOTLE, apixaban reduced the risk of stroke or systemic embolism by 21% compared with warfarin (1.27% vs 1.60% per year; hazard ratio, 0.79; 95% confidence interval, 0.66-0.95). The reduction was significant and demonstrated the superiority of apixaban over warfarin for the primary outcome of preventing stroke or systemic embolism (P = 0.01 for superiority). Apixaban also reduced all-cause mortality by 11% (P = 0.047) and major bleeding by 31% (P < 0.001) compared with warfarin. The benefits of apixaban observed in ARISTOTLE are further supported by the results from AVERROES, which demonstrated a 55% reduction in the risk of stroke or systemic embolism compared with aspirin. Risk of major bleeding was not significantly different between apixaban and aspirin. Subgroup analyses in both trials demonstrated that the effects of apixaban are highly consistent across various patient subpopulations. Discontinuation of study medication was significantly lower with apixaban than with either warfarin in ARISTOTLE or aspirin in AVERROES. Apixaban is the first new oral anticoagulant that has been shown to be superior to warfarin in reducing stroke or systemic embolism, all-cause mortality, and major bleeding in patients with AF. Moreover, in patients with AF who are considered unsuitable for warfarin therapy, apixaban was more effective than aspirin for stroke prevention and had a similar rate of major bleeding.

Does the use of Nintendo Wii Sports™ improve arm function and is it acceptable to patients after stroke? Publication of the Protocol of the Trial of Wii™ in Stroke - TWIST.

PubMed

Adie, Katja; Schofield, Christine; Berrow, Margie; Wingham, Jennifer; Freeman, Janet; Humfryes, John; Pritchard, Colin

2014-01-01

Many stroke patients experience loss of arm function requiring rehabilitation, which is expensive, repetitive, and does not always translate into "real life." Nintendo Wii Sports™ (Wii™) may offer task-specific training that is repetitive and motivating. The Trial of Wii™ in Stroke (TWIST) is designed to investigate feasibility, efficacy, and acceptability using Wii™ to improve affected arm function for patients after stroke. This is a randomized controlled trial (RCT), incorporating a qualitative study and health economics analysis that compares playing Wii™ versus arm exercises in patients receiving standard rehabilitation in a home setting within 6 months of stroke with a motor deficit of less than 5 on the MRC (Medical Research Council) scale (arm). In this study, we expect to randomize 240 participants. Primary outcome is change in affected arm function at 6 weeks follow-up in intervention and control group using the Action Research Arm Test. Secondary outcomes include occupational performance using the Canadian Occupational Performance Measure, quality of life using the Stroke Impact Scale, cost effectiveness analysis, and a qualitative study investigating factors that influence use of Wii™ for patients and carers. TWIST is the first UK RCT assessing the feasibility, cost effectiveness, and acceptability of Wii™ in stroke rehabilitation. The trial has been registered with ISRCTN 06807619 and UK CRN 11030. Results of the study will be published after completion of study in August 2014.

Sex Differences in Stroke Therapies

PubMed Central

Sohrabji, Farida; Park, Min Jung; Mahnke, Amanda H

2016-01-01

Stroke is the 5th leading cause of death and acquired disability in aged populations. Women are disproportionally affected by stroke, having a higher incidence and worse outcomes than men. Numerous preclinical studies have discovered novel therapies for the treatment of stroke, but almost all of these were found to be unsuccessful in clinical trials. Despite known sex differences in occurrence and severity of stroke, few therapeutics, both preclinically and clinically, take into account possible sex differences in treatment. Reanalysis of data from the only currently FDA-approved stroke therapy, tPA, has shown to not only improve stroke outcomes for both sexes, but to also show sexual dimorphism by more robust improvement in stroke outcome in females. Experimental evidence supports the inclusion of sex as a variable in the study of a number of novel stroke drugs and therapies, including preclinical studies of anti-inflammatory drugs (minocycline), stimulators of cell survival (IGF-1), and inhibitors of cell death pathways (pharmacological inhibition of PARP-1, NO production, and caspase activation), as well as in current clinical trials of stem cell therapy and cortical stimulation. Overall, study design and analyses in clinical trials, as well as in preclinical studies, must include both sexes equally, consider possible sex differences in the analyses, and report the differences/similarities in more systemized/structured way to translate promising therapies to both sexes and increase stroke recovery. PMID:27870437

A systematic review and meta-analysis of acute stroke unit care: What’s beyond the statistical significance?

PubMed Central

2013-01-01

Background The benefits of stroke unit care in terms of reducing death, dependency and institutional care were demonstrated in a 2009 Cochrane review carried out by the Stroke Unit Trialists’ Collaboration. Methods As requested by the Belgian health authorities, a systematic review and meta-analysis of the effect of acute stroke units was performed. Clinical trials mentioned in the original Cochrane review were included. In addition, an electronic database search on Medline, Embase, the Cochrane Central Register of Controlled Trials, and Physiotherapy Evidence Database (PEDro) was conducted to identify trials published since 2006. Trials investigating acute stroke units compared to alternative care were eligible for inclusion. Study quality was appraised according to the criteria recommended by Scottish Intercollegiate Guidelines Network (SIGN) and the GRADE system. In the meta-analysis, dichotomous outcomes were estimated by calculating odds ratios (OR) and continuous outcomes were estimated by calculating standardized mean differences. The weight of a study was calculated based on inverse variance. Results Evidence from eight trials comparing acute stroke unit and conventional care (general medical ward) were retained for the main synthesis and analysis. The findings from this study were broadly in line with the original Cochrane review: acute stroke units can improve survival and independency, as well as reduce the chance of hospitalization and the length of inpatient stay. The improvement with stroke unit care on mortality was less conclusive and only reached borderline level of significance (OR 0.84, 95% CI 0.70 to 1.00, P = 0.05). This improvement became statistically non-significant (OR 0.87, 95% CI 0.74 to 1.03, P = 0.12) when data from two unpublished trials (Goteborg-Ostra and Svendborg) were added to the analysis. After further also adding two additional trials (Beijing, Stockholm) with very short observation periods (until discharge), the difference between acute stroke units and general medical wards on death remained statistically non-significant (OR 0.86, 95% CI 0.74 to 1.01, P = 0.06). Furthermore, based on figures reported by the clinical trials included in this study, a slightly higher proportion of patients became dependent after receiving care in stroke units than those treated in general medical wards – although the difference was not statistically significant. This result could have an impact on the future demand for healthcare services for individuals that survive a stroke but became dependent on their care-givers. Conclusions These findings demonstrate that a well-conducted meta-analysis can produce results that can be of value to policymakers but the choice of inclusion/exclusion criteria and outcomes in this context needs careful consideration. The financing of interventions such as stroke units that increase independency and reduce inpatient stays are worthwhile in a context of an ageing population with increasing care needs. One limitation of this study was the selection of trials published in only four languages: English, French, Dutch and German. This choice was pragmatic in the context of this study, where the objective was to support health authorities in their decision processes. PMID:24164771

Reporting of Positive Results in Randomized Controlled Trials of Mindfulness-Based Mental Health Interventions.

PubMed

Coronado-Montoya, Stephanie; Levis, Alexander W; Kwakkenbos, Linda; Steele, Russell J; Turner, Erick H; Thombs, Brett D

2016-01-01

A large proportion of mindfulness-based therapy trials report statistically significant results, even in the context of very low statistical power. The objective of the present study was to characterize the reporting of "positive" results in randomized controlled trials of mindfulness-based therapy. We also assessed mindfulness-based therapy trial registrations for indications of possible reporting bias and reviewed recent systematic reviews and meta-analyses to determine whether reporting biases were identified. CINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS databases were searched for randomized controlled trials of mindfulness-based therapy. The number of positive trials was described and compared to the number that might be expected if mindfulness-based therapy were similarly effective compared to individual therapy for depression. Trial registries were searched for mindfulness-based therapy registrations. CINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS were also searched for mindfulness-based therapy systematic reviews and meta-analyses. 108 (87%) of 124 published trials reported ≥1 positive outcome in the abstract, and 109 (88%) concluded that mindfulness-based therapy was effective, 1.6 times greater than the expected number of positive trials based on effect size d = 0.55 (expected number positive trials = 65.7). Of 21 trial registrations, 13 (62%) remained unpublished 30 months post-trial completion. No trial registrations adequately specified a single primary outcome measure with time of assessment. None of 36 systematic reviews and meta-analyses concluded that effect estimates were overestimated due to reporting biases. The proportion of mindfulness-based therapy trials with statistically significant results may overstate what would occur in practice.

The Sleep Apnea cardioVascular Endpoints (SAVE) Trial: Rationale, Ethics, Design, and Progress.

PubMed

Antic, Nick A; Heeley, Emma; Anderson, Craig S; Luo, Yuanming; Wang, Jiguang; Neal, Bruce; Grunstein, Ron; Barbe, Ferran; Lorenzi-Filho, Geraldo; Huang, Shaoguang; Redline, Susan; Zhong, Nanshan; McEvoy, R Doug

2015-08-01

The Sleep Apnea cardioVascular Endpoints (SAVE) study is an ongoing investigator-initiated and conducted, international, multicenter, open, blinded endpoint, randomized controlled trial that was designed to determine whether treatment of obstructive sleep apnea (OSA) with continuous positive airways pressure (CPAP) can reduce the risk of serious cardiovascular (CV) events in patients with established CV disease (clinical trial registration NCT00738179). The results of this study will have important implications for the provision of health care to patients with sleep apnea around the world. The SAVE study has brought together respiratory, sleep, CV and stroke clinicians-scientists in an interdisciplinary collaboration with industry and government sponsorship to conduct an ambitious clinical trial. Following its launch in Australia and China in late 2008, the recruitment network expanded across 89 sites that included New Zealand, India, Spain, USA, and Brazil for a total of 2,717 patients randomized by December 2013. These patients are being followed until December 2015 so that the average length of follow-up of the cohort will be over 4 y. This article describes the rationale for the SAVE study, considerations given to the design including how various cultural and ethical challenges were addressed, and progress in establishing and maintaining the recruitment network, patient follow-up, and adherence to CPAP and procedures. The assumptions underlying the original trial sample size calculation and why this was revised downward in 2012 are also discussed. NCT00738179. ACTRN12608000409370. © 2015 Associated Professional Sleep Societies, LLC.

An open-label study to assess safety, tolerability, and effectiveness of dextromethorphan/quinidine for pseudobulbar affect in dementia: PRISM II results.

PubMed

Doody, Rachelle S; D'Amico, Stephen; Cutler, Andrew J; Davis, Charles S; Shin, Paul; Ledon, Fred; Yonan, Charles; Siffert, João

2016-12-01

Dextromethorphan (DM)/quinidine (Q) is an approved treatment for pseudobulbar affect (PBA) based on trials in amyotrophic lateral sclerosis or multiple sclerosis. PRISM II evaluated DM/Q effectiveness and tolerability for PBA secondary to dementia, stroke, or traumatic brain injury; dementia cohort results are reported. This was an open-label, multicenter, 90 day trial; patients received DM/Q 20/10 mg twice daily. Primary outcome was change in Center for Neurologic Study-Lability Scale (CNS-LS) score. Secondary outcomes included PBA episode count and Clinical and Patient/Caregiver Global Impression of Change scores with respect to PBA (CGI-C/PGI-C). 134 patients were treated. CNS-LS improved by a mean (SD) of 7.2 (6.0) points at Day 90/Endpoint (P<.001) vs. baseline. PBA episodes were reduced 67.7% (P<.001) vs. baseline; global measures showed 77.5% CGI-C and 76.5% PGI-C "much"/"very much" improved. Adverse events included headache (7.5%), urinary tract infection (4.5%), and diarrhea (3.7%); few patients dropped out for adverse events (10.4%). DM/Q significantly reduced PBA symptoms in patients with dementia; reported adverse events were consistent with the known safety profile of DM/Q. Trial Registration clinicaltrials.gov identifier: NCT01799941.

Point-of-care cluster randomized trial in stroke secondary prevention using electronic health records.

PubMed

Dregan, Alex; van Staa, Tjeerd P; McDermott, Lisa; McCann, Gerard; Ashworth, Mark; Charlton, Judith; Wolfe, Charles D A; Rudd, Anthony; Yardley, Lucy; Gulliford, Martin C; Trial Steering Committee

2014-07-01

The aim of this study was to evaluate whether the remote introduction of electronic decision support tools into family practices improves risk factor control after first stroke. This study also aimed to develop methods to implement cluster randomized trials in stroke using electronic health records. Family practices were recruited from the UK Clinical Practice Research Datalink and allocated to intervention and control trial arms by minimization. Remotely installed, electronic decision support tools promoted intensified secondary prevention for 12 months with last measure of systolic blood pressure as the primary outcome. Outcome data from electronic health records were analyzed using marginal models. There were 106 Clinical Practice Research Datalink family practices allocated (intervention, 53; control, 53), with 11 391 (control, 5516; intervention, 5875) participants with acute stroke ever diagnosed. Participants at trial practices had similar characteristics as 47,887 patients with stroke at nontrial practices. During the intervention period, blood pressure values were recorded in the electronic health records for 90% and cholesterol values for 84% of participants. After intervention, the latest mean systolic blood pressure was 131.7 (SD, 16.8) mm Hg in the control trial arm and 131.4 (16.7) mm Hg in the intervention trial arm, and adjusted mean difference was -0.56 mm Hg (95% confidence interval, -1.38 to 0.26; P=0.183). The financial cost of the trial was approximately US $22 per participant, or US $2400 per family practice allocated. Large pragmatic intervention studies may be implemented at low cost by using electronic health records. The intervention used in this trial was not found to be effective, and further research is needed to develop more effective intervention strategies. http://www.controlled-trials.com. Current Controlled Trials identifier: ISRCTN35701810. © 2014 American Heart Association, Inc.

Serious adverse events and compensation in registration trials: a review of data from a Japanese university hospital

PubMed Central

2014-01-01

Background Clinical trials leading to regulatory approval, or registration trials, play a central role in the development of drugs and medical devices. The contribution of support staff, such as the clinical research coordinator (CRC) and administrative officers, in registration trials is now widely recognized. Attending to serious adverse events is an important duty of the CRC and investigators alike, and managing these complications and compensation constitutes a key responsibility. We retrospectively examined the frequency of serious adverse events and compensation events reported from 2007 through 2011 at Tokushima University Hospital, an academic hospital in rural Japan. We present herein the results of our analysis. Results Over the five-year period, 284 subjects participating in 106 registration trials experienced a total of 43 serious adverse events, and eight compensation events were documented. Among the serious adverse events, 35 (81.4%) were considered not related to the investigational drug, and 17 (39.5%) resulted in withdrawal of the study drug. Patients with malignant diseases experienced serious adverse events significantly more frequently compared to those with non-malignant diseases (28.3% versus 8.2%, respectively; P < 0.01). Conclusions The CRC should be vigilant for serious adverse events in oncology clinical trials due to the generally higher frequency of these complications in subjects with malignancy. However, on an individual basis, the CRC may be seldom involved in the process for compensating serious adverse events. Therefore, the CRC’s ability to share such experiences may serve as an opportunity for educating clinical trial support staff at the study site as well as those at other sites. However, further study is warranted to determine the role of the clinical trial support staff in optimizing methods for managing adverse events requiring compensation in registration trials. PMID:24742228

Efficacy of Intensive Control of Glucose in Stroke Prevention: A Meta-Analysis of Data from 59197 Participants in 9 Randomized Controlled Trials

PubMed Central

Zhang, Chi; Zhou, Yu-Hao; Xu, Chun-Li; Chi, Feng-Ling; Ju, Hai-Ning

2013-01-01

Background The efficacy of treatments that lower glucose in reducing the risk of incident stroke remains unclear. We therefore did a systematic review and meta-analysis to evaluate the efficacy of intensive control of glucose in the prevention of stroke. Methodology/Principal Findings We systematically searched Medline, EmBase, and the Cochrane Library for trials published between 1950 and June, 2012. We included randomized controlled trials that reported on the effects of intensive control of glucose on incident stroke compared with standard care. Summary estimates of relative risk (RR) reductions were calculated with a random effects model, and the analysis was further stratified by factors that could affect the treatment effects. Of 649 identified studies, we included nine relevant trials, which provided data for 59197 patients and 2037 events of stroke. Overall, intensive control of glucose as compared to standard care had no effect on incident stroke (RR, 0.96; 95%CI 0.88–1.06; P = 0.445). In the stratified analyses, a beneficial effect was seen in those trials when body mass index (BMI) more than 30 (RR, 0.86; 95%CI: 0.75–0.99; P = 0.041). No other significant differences were detected between the effect of intensive control of glucose and standard care when based on other subset factors. Conclusions/Significance Our study indicated intensive control of glucose can effectively reduce the risk of incident stroke when patients with BMI more than 30. PMID:23372729

Cupping for stroke rehabilitation: a systematic review.

PubMed

Lee, Myeong Soo; Choi, Tae-Young; Shin, Byung-Cheul; Han, Chang-ho; Ernst, Edzard

2010-07-15

Cupping is often used for stroke rehabilitation in Asian countries. Currently, no systematic review of this topic is available. The aim of this systematic review is to summarize and critically evaluate the evidence for and against the effectiveness of cupping for stroke rehabilitation. Thirteen databases were searched from their inception through March of 2010 without language restrictions. Prospective clinical trials were included if cupping was tested as the sole treatment or as an adjunct to other conventional treatments for stroke rehabilitation. We found 43 potentially relevant articles, of which 5 studies including 3 randomized clinical trials (RCTs) and 2 uncontrolled observational studies (UOSs) met our inclusion criteria. Cupping was compared with acupuncture, electro-acupuncture and warm needling. Some superior effects of cupping were found in two of the RCTs when compared to acupuncture in hemiplegic shoulder pain and high upper-limb myodynamia after stroke. The other RCT failed to show favorable effects of cupping when compared to acupuncture and warm needling in patients with hemiplegic hand edema. The two UOSs reported favorable effects of cupping on aphasia and intractable hiccup after stroke. There are not enough trials to provide evidence for the effectiveness of cupping for stroke rehabilitation because most of the included trials compared the effects with unproven evidence and were not informative. Future RCTs seem warranted but must overcome the methodological shortcomings of the existing evidence. Copyright 2010 Elsevier B.V. All rights reserved.

Motivational interviewing for improving recovery after stroke.

PubMed

Cheng, Daobin; Qu, Zhanli; Huang, Jianyi; Xiao, Yousheng; Luo, Hongye; Wang, Jin

2015-06-03

Psychological problems are common complications following stroke that can cause stroke survivors to lack the motivation to take part in activities of daily living. Motivational interviewing provides a specific way for enhancing intrinsic motivation, which may help to improve activities of daily living for stroke survivors. To investigate the effect of motivational interviewing for improving activities of daily living after stroke. We searched the Cochrane Stroke Group's Trials Register (November 2014), the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 1), MEDLINE (1948 to March 2015), EMBASE (1980 to March 2015), CINAHL (1982 to March 2015), AMED (1985 to March 2015), PsycINFO (1806 to March 2015), PsycBITE (March 2015) and four Chinese databases. In an effort to identify further published, unpublished and ongoing trials, we searched ongoing trials registers and conference proceedings, checked reference lists, and contacted authors of relevant studies. Randomised controlled trials (RCTs) comparing motivational interviewing with no intervention, sham motivational interviewing or other psychological therapy for people with stroke were eligible. Two review authors independently selected studies for inclusion, extracted eligible data and assessed risk of bias. Outcome measures included activities of daily living, mood and death. One study involving a total of 411 participants, which compared motivational interviewing with usual care, met our inclusion criteria. The results of this review did not show significant differences between groups receiving motivational interviewing or usual stroke care for participants who were not dependent on others for activities of daily living, nor on the death rate after three-month and 12-month follow-up, but participants receiving motivational interviewing were more likely to have a normal mood than those who received usual care at three-months and 12-months follow-up. There is insufficient evidence to support the use of motivational interviewing for improving activities of daily living after stroke. Further well designed RCTs are needed.

Qualitative investigation of the perceptions and experiences of nursing and allied health professionals involved in the implementation of an enriched environment in an Australian acute stroke unit

PubMed Central

Brauer, Sandra G; Fitzhenry, Sarah; Grimley, Rohan S; Hayward, Kathryn S

2017-01-01

Objective An enriched environment embedded in an acute stroke unit can increase activity levels of patients who had stroke, with changes sustained 6 months post-implementation. The objective of this study was to understand perceptions and experiences of nursing and allied health professionals involved in implementing an enriched environment in an acute stroke unit. Design A descriptive qualitative approach. Setting An acute stroke unit in a regional Australian hospital. Participants We purposively recruited three allied health and seven nursing professionals involved in the delivery of the enriched environment. Face-to-face, semistructured interviews were conducted 8 weeks post-completion of the enriched environment study. One independent researcher completed all interviews. Voice-recorded interviews were transcribed verbatim and analysed by three researchers using a thematic approach to identify main themes. Results Three themes were identified. First, staff perceived that ‘the road to recovery had started’ for patients. An enriched environment was described to shift the focus to recovery in the acute setting, which was experienced through increased patient activity, greater psychological well-being and empowering patients and families. Second, ‘it takes a team’ to successfully create an enriched environment. Integral to building the team were positive interdisciplinary team dynamics and education. The impact of the enriched environment on workload was diversely experienced by staff. Third, ‘keeping it going’ was perceived to be challenging. Staff reflected that changing work routines was difficult. Contextual factors such as a supportive physical environment and variety in individual enrichment opportunities were indicated to enhance implementation. Key to sustaining change was consistency in staff and use of change management strategies. Conclusion Investigating staff perceptions and experiences of an enrichment model in an acute stroke unit highlighted the need for effective teamwork. To facilitate staff in their new work practice, careful selection of change management strategies are critical to support clinical translation of an enriched environment. Trial registration number ANZCTN12614000679684; Results. PMID:29273658

Evaluation of a web based informatics system with data mining tools for predicting outcomes with quantitative imaging features in stroke rehabilitation clinical trials

NASA Astrophysics Data System (ADS)

Wang, Ximing; Kim, Bokkyu; Park, Ji Hoon; Wang, Erik; Forsyth, Sydney; Lim, Cody; Ravi, Ragini; Karibyan, Sarkis; Sanchez, Alexander; Liu, Brent

2017-03-01

Quantitative imaging biomarkers are used widely in clinical trials for tracking and evaluation of medical interventions. Previously, we have presented a web based informatics system utilizing quantitative imaging features for predicting outcomes in stroke rehabilitation clinical trials. The system integrates imaging features extraction tools and a web-based statistical analysis tool. The tools include a generalized linear mixed model(GLMM) that can investigate potential significance and correlation based on features extracted from clinical data and quantitative biomarkers. The imaging features extraction tools allow the user to collect imaging features and the GLMM module allows the user to select clinical data and imaging features such as stroke lesion characteristics from the database as regressors and regressands. This paper discusses the application scenario and evaluation results of the system in a stroke rehabilitation clinical trial. The system was utilized to manage clinical data and extract imaging biomarkers including stroke lesion volume, location and ventricle/brain ratio. The GLMM module was validated and the efficiency of data analysis was also evaluated.

Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial.

PubMed

Easton, J Donald; Lopes, Renato D; Bahit, M Cecilia; Wojdyla, Daniel M; Granger, Christopher B; Wallentin, Lars; Alings, Marco; Goto, Shinya; Lewis, Basil S; Rosenqvist, Mårten; Hanna, Michael; Mohan, Puneet; Alexander, John H; Diener, Hans-Christoph

2012-06-01

In the ARISTOTLE trial, the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation (AF). Patients with AF and previous stroke or transient ischaemic attack (TIA) have a high risk of stroke. We therefore aimed to assess the efficacy and safety of apixaban compared with warfarin in prespecified subgroups of patients with and without previous stroke or TIA. Between Dec 19, 2006, and April 2, 2010, patients were enrolled in the ARISTOTLE trial at 1034 clinical sites in 39 countries. 18,201 patients with AF or atrial flutter were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalised ratio 2·0-3·0). The median duration of follow-up was 1·8 years (IQR 1·4-2·3). The primary efficacy outcome was stroke or systemic embolism, analysed by intention to treat. The primary safety outcome was major bleeding in the on-treatment population. All participants, investigators, and sponsors were masked to treatment assignments. In this subgroup analysis, we estimated event rates and used Cox models to compare outcomes in patients with and without previous stroke or TIA. The ARISTOTLE trial is registered with ClinicalTrials.gov, number NTC00412984. Of the trial population, 3436 (19%) had a previous stroke or TIA. In the subgroup of patients with previous stroke or TIA, the rate of stroke or systemic embolism was 2·46 per 100 patient-years of follow-up in the apixaban group and 3·24 in the warfarin group (hazard ratio [HR] 0·76, 95% CI 0·56 to 1·03); in the subgroup of patients without previous stroke or TIA, the rate of stroke or systemic embolism was 1·01 per 100 patient-years of follow-up with apixaban and 1·23 with warfarin (HR 0·82, 95% CI 0·65 to 1·03; p for interaction=0·71). The absolute reduction in the rate of stroke and systemic embolism with apixaban versus warfarin was 0·77 per 100 patient-years of follow-up (95% CI -0·08 to 1·63) in patients with and 0·22 (-0·03 to 0·47) in those without previous stroke or TIA. The difference in major bleeding with apixaban compared with warfarin was 1·07 per 100 patient-years (95% CI 0·09-2·04) in patients with and 0·93 (0·54-1·32) in those without previous stroke or TIA. The effects of apixaban versus warfarin were consistent in patients with AF with and without previous stroke or TIA. Owing to the higher risk of these outcomes in patients with previous stroke or TIA, the absolute benefits of apixaban might be greater in this population. Bristol-Myers Squibb and Pfizer. Copyright © 2012 Elsevier Ltd. All rights reserved.

A noninferiority confirmatory trial of prasugrel versus clopidogrel in Japanese patients with non-cardioembolic stroke: rationale and study design for a randomized controlled trial - PRASTRO-I trial.

PubMed

Nagao, Takehiko; Toyoda, Kazunori; Kitagawa, Kazuo; Kitazono, Takanari; Yamagami, Hiroshi; Uchiyama, Shinichiro; Tanahashi, Norio; Matsumoto, Masayasu; Minematsu, Kazuo; Nagata, Izumi; Nishikawa, Masakatsu; Nanto, Shinsuke; Abe, Kenji; Ikeda, Yasuo; Ogawa, Akira

2018-04-01

This comparison of PRAsugrel and clopidogrel in Japanese patients with ischemic STROke (PRASTRO)-I trial investigates the noninferiority of prasugrel to clopidogrel sulfate in the prevention of recurrence of primary events (ischemic stroke, myocardial infarction, and death from other vascular causes), and the long-term safety of prasugrel in Japanese patients with non-cardioembolic stroke. This was an active-controlled, randomized, double-blind, double-dummy, parallel-group study conducted between July 2011 and March 2016 at multiple centers around Japan. Patients had to meet eligibility criteria before receiving 3.75 mg prasugrel or 75 mg clopidogrel orally once daily for a period of 96-104 weeks. A total of 3747 patients were included in this trial; 1598 in the 3.75 mg prasugrel group and 1551 in the 75 mg clopidogrel group completed the study. During the study period, 287 (15.2%) patients in the prasugrel group and 311 (16.7%) in the clopidogrel group discontinued treatment. Baseline characteristics, safety, and efficacy results are forthcoming and will be published separately. This article presents the study design and rationale for a trial investigating the noninferiority of prasugrel to clopidogrel sulfate with regards to the inhibitory effect on primary events in patients with non-cardioembolic stroke.

Rethinking the continuum of stroke rehabilitation.

PubMed

Teasell, Robert W; Murie Fernandez, Manuel; McIntyre, Amanda; Mehta, Swati

2014-04-01

Suffering a stroke can be a devastating and life-changing event. Although there is a large evidence base for stroke rehabilitation in the acute and subacute stages, it has been long accepted that patients with stroke reach a plateau in their rehabilitation recovery relatively early. We have recently published the results of a systematic review designed to identify all randomized controlled trials (RCTs) where a rehabilitation intervention was initiated more than 6 months after the onset of the stroke. Of the trials identified, 339 RCTs met inclusion criteria, demonstrating an evidence base for stroke rehabilitation in the chronic phase as well. This seems at odds with the assumption that further recovery is unlikely and the subsequent lack of resources devoted to chronic stroke rehabilitation and management. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

The effect of antihypertensive treatment on the incidence of stroke and cognitive decline in the elderly: a meta-analysis.

PubMed

Parsons, Christine; Murad, Mohammad Hassan; Andersen, Stuart; Mookadam, Farouk; Labonte, Helene

2016-03-01

To evaluate the effectiveness of antihypertensives in reducing neurocognitive outcomes in elderly patients. We conducted a systematic literature search of randomized trials in which hypertensive patients with a mean age ≥65 years received antihypertensive or control treatment. Outcomes were stroke, transient ischemic attack, cognitive decline and dementia. We included 14 trials for meta-analysis. Compared to placebo, antihypertensive treatment reduced the risk of stroke (RR: 0.67 [95% CI: 0.57-0.79]). Reduced risk was significant for transient ischemic attack, fatal stroke, nonfatal stroke and total stroke. There were insufficient data to compare individual agents. Antihypertensive treatment is associated with a significant reduction in stroke in elderly individuals. Reductions in dementia and cognitive decline were not significant; however, there was short follow-up. Comparative effectiveness evidence is limited.

Evaluating an extended rehabilitation service for stroke patients (EXTRAS): study protocol for a randomised controlled trial.

PubMed

Rodgers, Helen; Shaw, Lisa; Cant, Robin; Drummond, Avril; Ford, Gary A; Forster, Anne; Hills, Katie; Howel, Denise; Laverty, Anne-Marie; McKevitt, Christopher; McMeekin, Peter; Price, Christopher

2015-05-05

Development of longer term stroke rehabilitation services is limited by lack of evidence of effectiveness for specific interventions and service models. We describe the protocol for a multicentre randomised controlled trial which is evaluating an extended stroke rehabilitation service. The extended service commences when routine 'organised stroke care' (stroke unit and early supported discharge (ESD)) ends. This study is a multicentre randomised controlled trial with health economic and process evaluations. It is set within NHS stroke services which provide ESD. Participants are adults who have experienced a new stroke (and carer if appropriate), discharged from hospital under the care of an ESD team. The intervention group receives an extended stroke rehabilitation service provided for 18 months following completion of ESD. The extended rehabilitation service involves regular contact with a senior ESD team member who leads and coordinates further rehabilitation. Contact is usually by telephone. The control group receives usual stroke care post-ESD. Usual care may involve referral of patients to a range of rehabilitation services upon completion of ESD in accordance with local clinical practice. Randomisation is via a central independent web-based service. The primary outcome is extended activities of daily living (Nottingham Extended Activities of Daily Living Scale) at 24 months post-randomisation. Secondary outcomes (at 12 and 24 months post-randomisation) are health status, quality of life, mood and experience of services for patients, and quality of life, experience of services and carer stress for carers. Resource use and adverse events are also collected. Outcomes are undertaken by a blinded assessor. Implementation and delivery of the extended stroke rehabilitation service will also be described. Semi-structured interviews will be conducted with a subsample of participants and staff to gain insight into perceptions and experiences of rehabilitation services delivered or received. Allowing for 25% attrition, 510 participants are needed to provide 90% power to detect a difference in mean Nottingham Extended Activities of Daily Living Scale score of 6 with a 5% significance level. The provision of longer term support for stroke survivors is currently limited. The results from this trial will inform future stroke service planning and configuration. This trial was registered with ISRCTN (identifier: ISRCTN45203373 ) on 9 August 2012.

Association of Osteopontin, Neopterin, and Myeloperoxidase With Stroke Risk in Patients With Prior Stroke or Transient Ischemic Attacks: Results of an Analysis of 13 Biomarkers From the Stroke Prevention by Aggressive Reduction in Cholesterol Levels Trial.

PubMed

Ganz, Peter; Amarenco, Pierre; Goldstein, Larry B; Sillesen, Henrik; Bao, Weihang; Preston, Gregory M; Welch, K Michael A

2017-12-01

Established risk factors do not fully identify patients at risk for recurrent stroke. The SPARCL trial (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) evaluated the effect of atorvastatin on stroke risk in patients with a recent stroke or transient ischemic attack and no known coronary heart disease. This analysis explored the relationships between 13 plasma biomarkers assessed at trial enrollment and the occurrence of outcome strokes. We conducted a case-cohort study of 2176 participants; 562 had outcome strokes and 1614 were selected randomly from those without outcome strokes. Time to stroke was evaluated by Cox proportional hazards models. There was no association between time to stroke and lipoprotein-associated phospholipase A 2 , monocyte chemoattractant protein-1, resistin, matrix metalloproteinase-9, N-terminal fragment of pro-B-type natriuretic peptide, soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1, or soluble CD40 ligand. In adjusted analyses, osteopontin (hazard ratio per SD change, 1.362; P <0.0001), neopterin (hazard ratio, 1.137; P =0.0107), myeloperoxidase (hazard ratio, 1.177; P =0.0022), and adiponectin (hazard ratio, 1.207; P =0.0013) were independently associated with outcome strokes. After adjustment for the Stroke Prognostic Instrument-II and treatment, osteopontin, neopterin, and myeloperoxidase remained independently associated with outcome strokes. The addition of these 3 biomarkers to Stroke Prognostic Instrument-II increased the area under the receiver operating characteristic curve by 0.023 ( P =0.015) and yielded a continuous net reclassification improvement (29.1%; P <0.0001) and an integrated discrimination improvement (42.3%; P <0.0001). Osteopontin, neopterin, and myeloperoxidase were independently associated with the risk of recurrent stroke and improved risk classification when added to a clinical risk algorithm. URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00147602. © 2017 American Heart Association, Inc.

Enhancing the Alignment of the Preclinical and Clinical Stroke Recovery Research Pipeline: Consensus-Based Core Recommendations From the Stroke Recovery and Rehabilitation Roundtable Translational Working Group.

PubMed

Corbett, Dale; Carmichael, S Thomas; Murphy, Timothy H; Jones, Theresa A; Schwab, Martin E; Jolkkonen, Jukka; Clarkson, Andrew N; Dancause, Numa; Weiloch, Tadeusz; Johansen-Berg, Heidi; Nilsson, Michael; McCullough, Louise D; Joy, Mary T

2017-08-01

Stroke recovery research involves distinct biological and clinical targets compared to the study of acute stroke. Guidelines are proposed for the pre-clinical modeling of stroke recovery and for the alignment of pre-clinical studies to clinical trials in stroke recovery.

Thrombus Aspiration in ThrOmbus containing culpRiT lesions in Non-ST-Elevation Myocardial Infarction (TATORT-NSTEMI): study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Current guidelines recommend thrombus aspiration in patients with ST-elevation myocardial infarction (STEMI); however, there are insufficient data to unequivocally support thrombectomy in patients with non-STEMI (NSTEMI). Methods/Design The TATORT-NSTEMI (Thrombus Aspiration in ThrOmbus containing culpRiT lesions in Non-ST-Elevation Myocardial Infarction) trial is a prospective, controlled, multicenter, randomized, open-label trial enrolling 460 patients. The hypothesis is that, against a background of early revascularization, adjunctive thrombectomy leads to less microvascular obstruction (MO) compared with conventional percutaneous coronary intervention (PCI) alone, as assessed by cardiac magnetic resonance imaging (CMR) in patients with NSTEMI. Patients will be randomized in a 1:1 fashion to one of the two treatment arms. The primary endpoint is the extent of late MO assessed by CMR. Secondary endpoints include early MO, infarct size, and myocardial salvage assessed by CMR as well as enzymatic infarct size and angiographic parameters, such as thrombolysis in myocardial infarction flow post-PCI and myocardial blush grade. Furthermore, clinical endpoints including death, myocardial re-infarction, target vessel revascularization, and new congestive heart failure will be recorded at 6 and 12 months. Safety will be assessed by the incidence of bleeding and stroke. Summary The TATORT-NSTEMI trial has been designed to test the hypothesis that thrombectomy will improve myocardial perfusion in patients with NSTEMI and relevant thrombus burden in the culprit vessel reperfused by early PCI. Trial registration The trial is registered under http://www.clinicaltrials.gov: NCT01612312. PMID:23782681

Hematology journals do not sufficiently adhere to reporting guidelines: a systematic review.

PubMed

Wayant, C; Smith, C; Sims, M; Vassar, M

2017-04-01

Essentials Reporting guidelines and trial/review registration aim to limit bias in research. We systematically reviewed hematology journals to examine the use of these policies. Forty-eight percent of journals made no use of these policies. Improving the use of reporting guidelines will improve research for all stakeholders. Background Reporting guidelines and trial/review registration policies have been instituted in order to minimize bias and improve research practices. Objective The objective of this study was to investigate the policies of hematology journals concerning reporting guideline adoption and trial/review registration. Methods We performed a web-based data abstraction from the Instructions for Authors of 67 hematology journals catalogued in the Expanded Science Citation Index of the 2014 Journal Citation Reports to identify whether each journal required, recommended or made no mention of the following reporting guidelines: EQUATOR, ICMJE, CONSORT, MOOSE, QUOROM, PRISMA, STARD, STROBE, ARRIVE and CARE. We also extracted whether journals required or recommended trial or systematic review registration. We e-mailed editors three times to determine which types of studies their journal accepts. Results Forty-eight per cent (32/67) of hematology journals do not adhere to any reporting guidelines. For responding journals, the QUOROM statement, MOOSE, CARE and PROSPERO were the least often mentioned, whereas the ICMJE guidelines, CONSORT statement and general trial registration were most often mentioned. Discussion Reporting guidelines are infrequently required or recommended by hematology journals. Furthermore, few require clinical trial or systematic review database registration. A higher rate of adherence to reporting guidelines can prevent bias from entering the literature. Participation from all stakeholders, including authors and journal editors, to improve reporting guideline and policy practices is required. © 2017 International Society on Thrombosis and Haemostasis.

Influence of handrim wheelchair propulsion training in adolescent wheelchair users, a pilot study.

PubMed

Dysterheft, Jennifer L; Rice, Ian M; Rice, Laura A

2015-01-01

Ten full-time adolescent wheelchair users (ages 13-18) completed a total of three propulsion trials on carpet and tile surfaces, at a self-selected velocity, and on a concrete surface, at a controlled velocity. All trials were performed in their personal wheelchair with force and moment sensing wheels attached bilaterally. The first two trials on each surface were used as pre-intervention control trials. The third trial was performed after receiving training on proper propulsion technique. Peak resultant force, contact angle, stroke frequency, and velocity were recorded during all trials for primary analysis. Carpet and tile trials resulted in significant increases in contact angle and peak total force with decreased stroke frequency after training. During the velocity controlled trials on concrete, significant increases in contact angle occurred, as well as decreases in stroke frequency after training. Overall, the use of a training video and verbal feedback may help to improve short-term propulsion technique in adolescent wheelchair users and decrease the risk of developing upper limb pain and injury.

Systematic Review and Meta-Analysis of Randomized Controlled Trials of Xingnaojing Treatment for Stroke

PubMed Central

Wang, Weihao; Xing, Zhihua

2014-01-01

Objective. Xingnaojing injection (XNJ) is a well-known traditional Chinese patent medicine (TCPM) for stroke. The aim of this study is to assess the efficacy of XNJ for stroke including ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). Methods. An extensive search was performed within using eight databases up to November 2013. Randomized controlled trials (RCTs) on XNJ for treatment of stroke were collected. Study selection, data extraction, quality assessment, and meta-analysis were conducted according to the Cochrane standards, and RevMan5.0 was used for meta-analysis. Results. This review included 13 RCTs and a total of 1,514 subjects. The overall methodological quality was poor. The meta-analysis showed that XNJ combined with conventional treatment was more effective for total efficacy, neurological deficit improvement, and reduction of TNF-α levels compared with those of conventional treatment alone. Three trials reported adverse events, of these one trial reported mild impairment of kidney and liver function, whereas the other two studies failed to report specific adverse events. Conclusion. Despite the limitations of this review, we suggest that XNJ in combination with conventional medicines might be beneficial for the treatment of stroke. Currently there are various methodological problems in the studies. Therefore, high-quality, large-scale RCTs are urgently needed. PMID:24707306

Warfarin for prevention of thromboembolism in atrial fibrillation: comparison of patient characteristics and outcomes of the "Real-World" Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry to the RE-LY, ROCKET-AF, and ARISTOTLE trials.

PubMed

Hughey, Andrew B; Gu, Xiaokui; Haymart, Brian; Kline-Rogers, Eva; Almany, Steve; Kozlowski, Jay; Besley, Dennis; Krol, Gregory D; Ahsan, Syed; Kaatz, Scott; Froehlich, James B; Barnes, Geoffrey D

2018-06-14

Randomized controlled trials (RCTs) examining warfarin use for stroke prevention in atrial fibrillation (AF) may not accurately reflect real-world populations. We aimed to determine the representativeness of the RCT populations to real-world patients and to describe differences in the characteristics of trial populations from trial eligible patients in a real-world setting. We hypothesized that a significant fraction of real-world patients would not qualify for the RE-LY, ROCKET-AF, and ARISTOTLE trials and that real-world patients qualifying for the studies may have more strokes and bleeding events. We compared the inclusion and exclusion criteria, patient characteristics, and clinical outcomes from RE-LY, ROCKET-AF, and ARISTOTLE against data from the Michigan Anticoagulation Quality Improvement Initiative (MAQI 2 ), a regional network of six community- and academic-based anticoagulation clinics. Of the 1446 non-valvular AF patients in the MAQI 2 registry taking warfarin, approximately 40-60% would meet the selection criteria used in RE-LY (788, 54.5%), ROCKET-AF (566, 39.1%), and ARISTOTLE (866, 59.9%). The most common reasons for exclusion from one or more trial were anemia (15.1%), other concurrent medications (11.2%), and chronic kidney disease (9.4%). Trial-eligible MAQI 2 patients were older, more frequently female, with a higher rate of paroxysmal AF, and lower rates of congestive heart failure, previous stroke, and previous myocardial infarction than the trial populations. MAQI 2 patients eligible for each trial had a lower rate of stroke and similar rate of major bleeding than was observed in the trials. A sizable proportion of real-world AF patients managed in anticoagulation clinics would not have been eligible for the RE-LY, ROCKET-AF, and ARISOTLE trials. The expected stroke risk reduction and bleeding risk among real-world AF patients on warfarin may not be congruent with published clinical trial data.

Effect of methylphenidate and/or levodopa coupled with physiotherapy on functional and motor recovery after stroke--a randomized, double-blind, placebo-controlled trial.

PubMed

Lokk, J; Salman Roghani, R; Delbari, A

2011-04-01

Amphetamine-like drugs are reported to enhance motor recovery and activities of daily living (ADL) in stroke rehabilitation, but results from trials with humans are inconclusive. This study is aimed at investigating whether levodopa (LD) and/or methylphenidate (MPH) in combination with physiotherapy could improve functional motor recovery and ADL in patients with stroke. A randomized, double-blind, placebo-controlled trial with ischemic stroke patients randomly allocated to one of four treatment groups of either MPH, LD or MPH+LD or placebo combined with physiotherapy was performed. Motor function, ADL, and stroke severity were assessed by Fugl-Meyer (FM), Barthel index (BI), and National Institute of Health Stroke Scale (NIHSS) at baseline, 15, 90, and 180 days respectively. All participants showed recovery of motor function and ADL during treatment and at 6-month follow-up. There were slightly but significant differences in BI and NIHSS compared to placebo at the 6-month follow-up. Ischemic chronic stroke patients having MPH and/or LD in combination with physiotherapy showed a slight ADL and stroke severity improvement over time. Future studies should address the issue of the optimal therapeutic window and dosage of medications to identify those patients who would benefit most. © 2010 John Wiley & Sons A/S.

Rehabilitation therapy services for stroke patients living at home: systematic review of randomised trials.

PubMed

Legg, L; Langhorne, P

2004-01-31

Stroke-unit care can be valuable for stroke patients in hospital, but effectiveness of outpatient care is less certain. We aimed to assess the effects of therapy-based rehabilitation services targeted at stroke patients resident in the community within 1 year of stroke onset or discharge from hospital. We did a systematic review of randomised trials of outpatient services, including physiotherapy, occupational therapy, and multidisciplinary teams. We used Cochrane collaboration methodology. We identified a heterogeneous group of 14 trials (1617 patients). Therapy-based rehabilitation services for stroke patients living at home reduced the odds of deteriorating in personal activities of daily living (odds ratio 0.72 [95% CI 0.57-0.92], p=0.009) and increased ability of patients to do personal activities of daily living (standardised mean difference 0.14 [95% CI 0.02-0.25], p=0.02). For every 100 stroke patients resident in the community receiving therapy-based rehabilitation services, seven (95% CI 2-11) would not deteriorate. Therapy-based rehabilitation services targeted at selected patients resident in the community after stroke improve ability to undertake personal activities of daily living and reduce risk of deterioration in ability. These findings should be considered in future service planning.

National trends in incidence rates of hospitalization for stroke in children with sickle cell disease.

PubMed

McCavit, Timothy L; Xuan, Lei; Zhang, Song; Flores, Glenn; Quinn, Charles T

2013-05-01

The success of primary stroke prevention for children with sickle cell disease (SCD) throughout the United States is unknown. Therefore, we aimed to generate national incidence rates of hospitalization for stroke in children with sickle cell disease (SCD) before and after publication of the Stroke Prevention Trial in Sickle Cell Anemia (STOP trial) in 1998. We performed a retrospective trend analysis of the 1993-2009 Nationwide Inpatient Sample and Kids' Inpatient Databases. Hospitalizations for SCD patients 0-18 years old with stroke were identified by ICD-9CM code. The primary outcome, the trend in annual incidence rate of hospitalization for stroke in children with SCD, was analyzed by linear regression. Incidence rates of hospitalization for stroke before and after 1998 were compared by the Wilcoxon rank-sum test. From 1993 to 2009, 2,024 hospitalizations were identified for stroke. Using the mean annual incidence rate of hospitalization for stroke from 1993 to 1998 as the baseline, the rate decreased from 1993 to 2009 (point estimate = -0.022/100 patient years [95% CI, -0.039, -0.005], P = 0.027). The mean annual incidence rate of hospitalization stroke decreased by 45% from 0.51 per 100 patient years in 1993-1998 to 0.28 per 100 patient years in 1999-2009 (P = 0.008). Total hospital days and charges attributed to stroke also decreased by 45% and 24%, respectively. After publication of the STOP trial and hydroxyurea licensure in 1998, the incidence of hospitalization for stroke in children with SCD decreased across the United States, suggesting that primary stroke prevention has been effective nationwide, but opportunity for improvement remains. Copyright © 2012 Wiley Periodicals, Inc.

National Trends in Incidence Rates of Hospitalization for Stroke in Children With Sickle Cell Disease

PubMed Central

McCavit, Timothy L.; Xuan, Lei; Zhang, Song; Flores, Glenn; Quinn, Charles T.

2014-01-01

Background The success of primary stroke prevention for children with sickle cell disease (SCD) throughout the United States is unknown. Therefore, we aimed to generate national incidence rates of hospitalization for stroke in children with sickle cell disease (SCD) before and after publication of the Stroke Prevention Trial in Sickle Cell Anemia (STOP trial) in 1998. Procedure We performed a retrospective trend analysis of the 1993–2009 Nationwide Inpatient Sample and Kids’ Inpatient Databases. Hospitalizations for SCD patients 0–18 years old with stroke were identified by ICD-9CM code. The primary outcome, the trend in annual incidence rate of hospitalization for stroke in children with SCD, was analyzed by linear regression. Incidence rates of hospitalization for stroke before and after 1998 were compared by the Wilcoxon rank-sum test. Results From 1993 to 2009, 2,024 hospitalizations were identified for stroke. Using the mean annual incidence rate of hospitalization for stroke from 1993 to 1998 as the baseline, the rate decreased from 1993 to 2009 (point estimate = −0.022/100 patient years [95% CI, −0.039, −0.005], P = 0.027). The mean annual incidence rate of hospitalization stroke decreased by 45% from 0.51 per 100 patient years in 1993–1998 to 0.28 per 100 patient years in 1999–2009 (P = 0.008). Total hospital days and charges attributed to stroke also decreased by 45% and 24%, respectively. Conclusions After publication of the STOP trial and hydroxyurea licensure in 1998, the incidence of hospitalization for stroke in children with SCD decreased across the United States, suggesting that primary stroke prevention has been effective nationwide, but opportunity for improvement remains. PMID:23151905

Twelve-Month Clinical and Quality-of-Life Outcomes in the Interventional Management of Stroke III Trial.

PubMed

Palesch, Yuko Y; Yeatts, Sharon D; Tomsick, Thomas A; Foster, Lydia D; Demchuk, Andrew M; Khatri, Pooja; Hill, Michael D; Jauch, Edward C; Jovin, Tudor G; Yan, Bernard; von Kummer, Rüdiger; Molina, Carlos A; Goyal, Mayank; Schonewille, Wouter J; Mazighi, Mikael; Engelter, Stefan T; Anderson, Craig; Spilker, Judith; Carrozzella, Janice; Ryckborst, Karla J; Janis, L Scott; Simpson, Annie; Simpson, Kit N; Broderick, Joseph P

2015-05-01

Randomized trials have indicated a benefit for endovascular therapy in appropriately selected stroke patients at 3 months, but data regarding outcomes at 12 months are currently lacking. We compared functional and quality-of-life outcomes at 12 months overall and by stroke severity in stroke patients treated with intravenous tissue-type plasminogen activator followed by endovascular treatment as compared with intravenous tissue-type plasminogen activator alone in the Interventional Management of Stroke III Trial. The key outcome measures were a modified Rankin Scale score ≤2 (functional independence) and the Euro-QoL EQ-5D, a health-related quality-of-life measure. 656 subjects with moderate-to-severe stroke (National Institutes of Health Stroke Scale ≥8) were enrolled at 58 centers in the United States (41 sites), Canada (7), Australia (4), and Europe (6). There was an interaction between treatment group and stroke severity in the repeated measures analysis of modified Rankin Scale ≤2 outcome (P=0.039). In the 204 participants with severe stroke (National Institutes of Health Stroke Scale ≥20), a greater proportion of the endovascular group had a modified Rankin Scale ≤2 (32.5%) at 12 months as compared with the intravenous tissue-type plasminogen activator group (18.6%, P=0.037); no difference was seen for the 452 participants with moderately severe strokes (55.6% versus 57.7%). In participants with severe stroke, the endovascular group had 35.2 (95% confidence interval: 2.1, 73.3) more quality-adjusted-days over 12 months as compared with intravenous tissue-type plasminogen activator alone. Endovascular therapy improves functional outcome and health-related quality-of-life at 12 months after severe ischemic stroke. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359424. © 2015 American Heart Association, Inc.

Early High-dosage Atorvastatin Treatment Improved Serum Immune-inflammatory Markers and Functional Outcome in Acute Ischemic Strokes Classified as Large Artery Atherosclerotic Stroke: A Randomized Trial.

PubMed

Tuttolomondo, Antonino; Di Raimondo, Domenico; Pecoraro, Rosaria; Maida, Carlo; Arnao, Valentina; Della Corte, Vittoriano; Simonetta, Irene; Corpora, Francesca; Di Bona, Danilo; Maugeri, Rosario; Iacopino, Domenico Gerardo; Pinto, Antonio

2016-03-01

Statins have beneficial effects on cerebral circulation and brain parenchyma during ischemic stroke and reperfusion. The primary hypothesis of this randomized parallel trial was that treatment with 80 mg/day of atorvastatin administered early at admission after acute atherosclerotic ischemic stroke could reduce serum levels of markers of immune-inflammatory activation of the acute phase and that this immune-inflammatory modulation could have a possible effect on prognosis of ischemic stroke evaluated by some outcome indicators. We enrolled 42 patients with acute ischemic stroke classified as large arteries atherosclerosis stroke (LAAS) randomly assigned in a randomized parallel trial to the following groups: Group A, 22 patients treated with atorvastatin 80 mg (once-daily) from admission day until discharge; Group B, 20 patients not treated with atorvastatin 80 mg until discharge, and after discharge, treatment with atorvastatin has been started. At 72 hours and at 7 days after acute ischemic stroke, subjects of group A showed significantly lower plasma levels of tumor necrosis factor-α, interleukin (IL)-6, vascular cell adhesion molecule-1, whereas no significant difference with regard to plasma levels of IL-10, E-Selectin, and P-Selectin was observed between the 2 groups. At 72 hours and 7 days after admission, stroke patients treated with atorvastatin 80 mg in comparison with stroke subjects not treated with atorvastatin showed a significantly lower mean National Institutes of Health Stroke Scale and modified Rankin scores. Our findings provide the first evidence that atorvastatin acutely administered immediately after an atherosclerotic ischemic stroke exerts a lowering effect on immune-inflammatory activation of the acute phase of stroke and that its early use is associated to a better functional and prognostic profile.

Stop Stroke: development of an innovative intervention to improve risk factor management after stroke.

PubMed

Redfern, Judith; Rudd, Anthony D; Wolfe, Charles D A; McKevitt, Christopher

2008-08-01

Stroke survivors are at high risk of stroke recurrence yet current strategies to reduce recurrence risk are sub-optimal. The UK Medical Research Council (MRC) have proposed a framework for developing and evaluating complex interventions, such as community management of stroke secondary prevention. The Framework outlines a five-phased approach from theory through to implementation of effective interventions. This paper reports Phases I-III of the development of a novel intervention to improve risk factor management after stroke. The pre-clinical/theoretical phase entailed reviewing the literature and undertaking quantitative and qualitative studies to identify current practices and barriers to secondary prevention. In Phase I (modelling), findings were used to design an intervention with the potential to overcome barriers to effective stroke secondary prevention management. The feasibility of delivering the intervention and its acceptability were tested in the Phase II exploratory trial involving 25 stroke survivors and their general practitioners. This led to the development of the definitive risk factor management intervention. This comprises multiple components and involves using an on-going population stroke register to target patients, carers and health care professionals with tailored secondary prevention advice. Clinical, socio-demographic and service use data collected by the stroke register are transformed to provide an individualised secondary prevention package for patients, carers and health care professionals at three time points: within 10 weeks, 3 and 6 months post-stroke. The intervention is currently being evaluated in a randomised controlled trial. Further research is needed to test generalisability to other aspects of stroke management and for other chronic diseases. The MRC Framework for complex interventions provides a structured approach to guide the development of novel interventions in public health. Implications for practice in stroke secondary prevention will emerge when the results of our randomised controlled trial are published.

The synergistic effect of acupuncture and computer-based cognitive training on post-stroke cognitive dysfunction: a study protocol for a randomized controlled trial of 2 × 2 factorial design.

PubMed

Yang, Shanli; Ye, Haicheng; Huang, Jia; Tao, Jing; Jiang, Cai; Lin, Zhicheng; Zheng, Guohua; Chen, Lidian

2014-08-07

Stroke is one of the most common causes of cognitive impairment. Up to 75% of stroke survivors may be considered to have cognitive impairment, which severely limit individual autonomy for successful reintegration into family, work and social life. The clinical efficacy of acupuncture with Baihui (DU20) and Shenting (DU24) in stroke and post-stroke cognitive impairment has been previously demonstrated. Computer-assisted cognitive training is part of conventional cognitive rehabilitation and has also shown to be effective in improvement of cognitive function of affected patients. However, the cognitive impairment after stroke is so complexity that one single treatment cannot resolve effectively. Besides, the effects of acupuncture and RehaCom cognitive training have not been systematically compared, nor has the possibility of a synergistic effect of combination of the two therapeutic modalities been evaluated. Our primary aim of this trial is to evaluate the synergistic effect of acupuncture and RehaCom cognitive training on cognitive dysfunction after stroke. A randomized controlled trial of 2 × 2 factorial design will be conducted in the Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine. A total of 240 patients with cognitive dysfunction after stroke who meet the eligibility criteria will be recruited and randomized into RehaCom training group, acupuncture group, a combination of both or control group in a 1:1:1:1 ratio. All patients will receive conventional treatment. The interventions will last for 12 weeks (30 min per day, Monday to Friday every week). Evaluations will be conducted by blinded assessors at baseline and again at 4, 8 and 12 weeks. Outcome measurements include mini-mental state examination (MMSE), Montreal cognitive assessments (MoCA), functional independence measure scale (FIM) and adverse events. The results of this trial are expected to clarify the synergistic effect of acupuncture and RehaCom cognitive training on cognitive dysfunction after stroke. Furthermore, to confirm whether combined or alone of acupuncture and RehaCom cognitive training, is more effective than conventional treatment in the management of post-stroke cognitive dysfunction. Chinese Clinical Trial Registry: ChiCTR-TRC-13003704.

Smoking cessation and outcome after ischemic stroke or TIA.

PubMed

Epstein, Katherine A; Viscoli, Catherine M; Spence, J David; Young, Lawrence H; Inzucchi, Silvio E; Gorman, Mark; Gerstenhaber, Brett; Guarino, Peter D; Dixit, Anand; Furie, Karen L; Kernan, Walter N

2017-10-17

To assess whether smoking cessation after an ischemic stroke or TIA improves outcomes compared to continued smoking. We conducted a prospective observational cohort study of 3,876 nondiabetic men and women enrolled in the Insulin Resistance Intervention After Stroke (IRIS) trial who were randomized to pioglitazone or placebo within 180 days of a qualifying stroke or TIA and followed up for a median of 4.8 years. A tobacco use history was obtained at baseline and updated during annual interviews. The primary outcome, which was not prespecified in the IRIS protocol, was recurrent stroke, myocardial infarction (MI), or death. Cox regression models were used to assess the differences in stroke, MI, and death after 4.8 years, with correction for adjustment variables prespecified in the IRIS trial: age, sex, stroke (vs TIA) as index event, history of stroke, history of hypertension, history of coronary artery disease, and systolic and diastolic blood pressures. At the time of their index event, 1,072 (28%) patients were current smokers. By the time of randomization, 450 (42%) patients had quit smoking. Among quitters, the 5-year risk of stroke, MI, or death was 15.7% compared to 22.6% for patients who continued to smoke (adjusted hazard ratio 0.66, 95% confidence interval 0.48-0.90). Cessation of cigarette smoking after an ischemic stroke or TIA was associated with significant health benefits over 4.8 years in the IRIS trial cohort. © 2017 American Academy of Neurology.

Sex differences in stroke therapies.

PubMed

Sohrabji, Farida; Park, Min Jung; Mahnke, Amanda H

2017-01-02

Stroke is the fifth leading cause of death and acquired disability in aged populations. Women are disproportionally affected by stroke, having a higher incidence and worse outcomes than men. Numerous preclinical studies have discovered novel therapies for the treatment of stroke, but almost all of these have been shown to be unsuccessful in clinical trials. Despite known sex differences in occurrence and severity of stroke, few preclinical or clinical therapeutics take into account possible sex differences in treatment. Reanalysis of data from studies of tissue plasminogen activator (tPA), the only currently FDA-approved stroke therapy, has shown that tPA improves stroke outcomes for both sexes and also shows sexual dimorphism by more robust improvement in stroke outcome in females. Experimental evidence supports the inclusion of sex as a variable in the study of a number of novel stroke drugs and therapies, including preclinical studies of anti-inflammatory drugs (minocycline), stimulators of cell survival (insulin-like growth factor-1), and inhibitors of cell death pathways (pharmacological inhibition of poly[ADP-ribose] polymerase-1, nitric oxide production, and caspase activation) as well as in current clinical trials of stem cell therapy and cortical stimulation. Overall, study design and analysis in clinical trials as well as in preclinical studies must include both sexes equally, consider possible sex differences in the analyses, and report the differences/similarities in more systematic/structured ways to allow promising therapies for both sexes and increase stroke recovery. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Modulation of walking speed by changing optic flow in persons with stroke

PubMed Central

Lamontagne, Anouk; Fung, Joyce; McFadyen, Bradford J; Faubert, Jocelyn

2007-01-01

Background Walking speed, which is often reduced after stroke, can be influenced by the perception of optic flow (OF) speed. The present study aims to: 1) compare the modulation of walking speed in response to OF speed changes between persons with stroke and healthy controls and 2) investigate whether virtual environments (VE) manipulating OF speed can be used to promote volitional changes in walking speed post stroke. Methods Twelve persons with stroke and 12 healthy individuals walked on a self-paced treadmill while viewing a virtual corridor in a helmet-mounted display. Two experiments were carried out on the same day. In experiment 1, the speed of an expanding OF was varied sinusoidally at 0.017 Hz (sine duration = 60 s), from 0 to 2 times the subject's comfortable walking speed, for a total duration of 5 minutes. In experiment 2, subjects were exposed to expanding OFs at discrete speeds that ranged from 0.25 to 2 times their comfortable speed. Each test trial was paired with a control trial performed at comfortable speed with matching OF. For each of the test trials, subjects were instructed to walk the distance within the same time as during the immediately preceding control trial. VEs were controlled by the CAREN-2 system (Motek). Instantaneous changes in gait speed (experiment 1) and the ratio of speed changes in the test trial over the control trial (experiment 2) were contrasted between the two groups of subjects. Results When OF speed was changing continuously (experiment 1), an out-of-phase modulation was observed in the gait speed of healthy subjects, such that slower OFs induced faster walking speeds, and vice versa. Persons with stroke displayed weaker (p < 0.05, T-test) correlation coefficients between gait speed and OF speed, due to less pronounced changes and an altered phasing of gait speed modulation. When OF speed was manipulated discretely (experiment 2), a negative linear relationship was generally observed between the test-control ratio of gait speed and OF speed in healthy and stroke individuals. The slope of this relationship was similar between the stroke and healthy groups (p > 0.05, T-test). Conclusion Stroke affects the modulation of gait speed in response to changes in the perception of movement through different OF speeds. Nevertheless, the preservation of even a modest modulation enabled the persons with stroke to increase walking speed when presented with slower OFs. Manipulation of OF speed using virtual reality technology could be implemented in a gait rehabilitation intervention to promote faster walking speeds after stroke. PMID:17594501

Effect of a Task-Oriented Rehabilitation Program on Upper Extremity Recovery Following Motor Stroke

PubMed Central

Winstein, Carolee J.; Wolf, Steven L.; Dromerick, Alexander W.; Lane, Christianne J.; Nelsen, Monica A.; Lewthwaite, Rebecca; Cen, Steven Yong; Azen, Stanley P.

2016-01-01

IMPORTANCE Clinical trials suggest that higher doses of task-oriented training are superior to current clinical practice for patients with stroke with upper extremity motor deficits. OBJECTIVE To compare the efficacy of a structured, task-oriented motor training program vs usual and customary occupational therapy (UCC) during stroke rehabilitation. DESIGN, SETTING, AND PARTICIPANTS Phase 3, pragmatic, single-blind randomized trial among 361 participants with moderate motor impairment recruited from 7 US hospitals over 44 months, treated in the outpatient setting from June 2009 to March 2014. INTERVENTIONS Structured, task-oriented upper extremity training (Accelerated Skill Acquisition Program[ASAP]; n = 119); dose-equivalent occupational therapy (DEUCC; n = 120); or monitoring-only occupational therapy (UCC; n = 122). The DEUCC group was prescribed 30 one-hour sessions over 10 weeks; the UCC group was only monitored, without specification of dose. MAIN OUTCOMES AND MEASURES The primary outcome was 12-month change in log-transformed Wolf Motor Function Test time score (WMFT, consisting of a mean of 15 timed arm movements and hand dexterity tasks). Secondary outcomes were change in WMFT time score (minimal clinically important difference [MCID] = 19 seconds) and proportion of patients improving ≥25 points on the Stroke Impact Scale (SIS) hand function score (MCID = 17.8 points). RESULTS Among the 361 randomized patients (mean age, 60.7 years; 56% men; 42% African American; mean time since stroke onset, 46 days), 304 (84%) completed the 12-month primary outcome assessment; in intention-to-treat analysis, mean group change scores (log WMFT, baseline to 12 months) were, for the ASAP group, 2.2 to 1.4 (difference, 0.82); DEUCC group, 2.0 to 1.2 (difference, 0.84); and UCC group, 2.1 to 1.4 (difference, 0.75), with no significant between-group differences (ASAP vs DEUCC:0.14; 95% CI, −0.05 to 0.33; P = .16; ASAP vs UCC: −0.01; 95% CI, −0.22 to 0.21; P = .94; and DEUCC vs UCC: −0.14; 95% CI, −0.32 to 0.05; P = .15). Secondary outcomes for the ASAP group were WMFT change score, −8.8 seconds, and improved SIS, 73%; DEUCC group, WMFT, −8.1 seconds, and SIS, 72%; and UCC group, WMFT, −7.2 seconds, and SIS, 69%, with no significant pairwise between-group differences (ASAP vs DEUCC: WMFT, 1.8 seconds; 95% CI, −0.8 to 4.5 seconds; P = .18; improved SIS, 1%; 95% CI, −12% to 13%; P = .54; ASAP vs UCC: WMFT, −0.6 seconds, 95% CI, −3.8 to 2.6 seconds; P = .72; improved SIS, 4%; 95% CI, −9% to 16%; P = .48; and DEUCC vs UCC: WMFT, −2.1 seconds; 95% CI, −4.5 to 0.3 seconds; P = .08; improved SIS, 3%; 95% CI, −9% to 15%; P = .22). A total of 168 serious adverse events occurred in 109 participants, resulting in 8 patients withdrawing from the study. CONCLUSIONS AND RELEVANCE Among patients with motor stroke and primarily moderate upper extremity impairment, use of a structured, task-oriented rehabilitation program did not significantly improve motor function or recovery beyond either an equivalent or a lower dose of UCC upper extremity rehabilitation. These findings do not support superiority of this program among patients with motor stroke and primarily moderate upper extremity impairment. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00871715 PMID:26864411

Promoting deceased organ and tissue donation registration in family physician waiting rooms (RegisterNow-1 trial): study protocol for a pragmatic, stepped-wedge, cluster randomized controlled registry.

PubMed

Li, Alvin H; Garg, Amit X; Prakash, Versha; Grimshaw, Jeremy M; Taljaard, Monica; Mitchell, Joanna; Matti, Danny; Linklater, Stefanie; Naylor, Kyla L; Dixon, Stephanie; Faulds, Cathy; Bevan, Rachel; Getchell, Leah; Knoll, Greg; Kim, S Joseph; Sontrop, Jessica; Bjerre, Lise M; Tong, Allison; Presseau, Justin

2017-12-21

There is a worldwide shortage of organs available for transplant, leading to preventable mortality associated with end-stage organ disease. While most citizens in many countries with an intent-to-donate "opt-in" system support organ donation, registration rates remain low. In Canada, most Canadians support organ donation but less than 25% in most provinces have registered their desire to donate their organs when they die. The family physician office is a promising yet underused setting in which to promote organ donor registration and address known barriers and enablers to registering for deceased organ and tissue donation. We developed a protocol to evaluate an intervention to promote registration for organ and tissue donation in family physician waiting rooms. This protocol describes a planned, stepped-wedge, cluster randomized registry trial in six family physician offices in Ontario, Canada to evaluate the effectiveness of reception staff providing patients with a pamphlet that addresses barriers and enablers to registration including a description of how to register for organ donation. An Internet-enabled tablet will also be provided in waiting rooms so that interested patients can register while waiting for their appointments. Family physicians and reception staff will be provided with training and/or materials to support any conversations about organ donation with their patients. Following a 2-week control period, the six offices will cross sequentially into the intervention arm in randomized sequence at 2-week intervals until all offices deliver the intervention. The primary outcome will be the proportion of patients visiting the office who are registered organ donors 7 days following their office visit. We will evaluate this outcome using routinely collected registry data from provincial administrative databases. A post-trial qualitative evaluation process will assess the experiences of reception staff and family physicians with the intervention and the stepped-wedge trial design. Promoting registration for organ donation in family physician offices is a potentially useful strategy for increasing registration for organ donation. Increased registration may ultimately help to increase the number of organs available for transplant. The results of this trial will provide important preliminary data on the effectiveness of using family physician offices to promote registration for organ donation. ClinicalTrials.gov, ID: NCT03213171 . Registered on 11 July 2017.

Early Rehabilitation After Stroke: a Narrative Review

PubMed Central

Moudgal, Rohitha; Lang, Kathryn; Hyacinth, Hyacinth I.; Awosika, Oluwole O.; Kissela, Brett M.; Feng, Wuwei

2018-01-01

Purpose of Review Despite current rehabilitative strategies, stroke remains a leading cause of disability in the USA. There is a window of enhanced neuroplasticity early after stroke, during which the brain’s dynamic response to injury is heightened and rehabilitation might be particularly effective. This review summarizes the evidence of the existence of this plastic window, and the evidence regarding safety and efficacy of early rehabilitative strategies for several stroke domain-specific deficits. Recent Findings Overall, trials of rehabilitation in the first 2 weeks after stroke are scarce. In the realm of very early mobilization, one large and one small trial found potential harm from mobilizing patients within the first 24 h after stroke, and only one small trial found benefit in doing so. For the upper extremity, constraint-induced movement therapy appears to have benefit when started within 2 weeks of stroke. Evidence for non-invasive brain stimulation in the acute period remains scant and inconclusive. For aphasia, the evidence is mixed, but intensive early therapy might be of benefit for patients with severe aphasia. Mirror therapy begun early after stroke shows promise for the alleviation of neglect. Novel approaches to treating dysphagia early after stroke appear promising, but the high rate of spontaneous improvement makes their benefit difficult to gauge. Summary The optimal time to begin rehabilitation after a stroke remains unsettled, though the evidence is mounting that for at least some deficits, initiation of rehabilitative strategies within the first 2 weeks of stroke is beneficial. Commencing intensive therapy in the first 24 h may be harmful. PMID:29116473

Early Rehabilitation After Stroke: a Narrative Review.

PubMed

Coleman, Elisheva R; Moudgal, Rohitha; Lang, Kathryn; Hyacinth, Hyacinth I; Awosika, Oluwole O; Kissela, Brett M; Feng, Wuwei

2017-11-07

Despite current rehabilitative strategies, stroke remains a leading cause of disability in the USA. There is a window of enhanced neuroplasticity early after stroke, during which the brain's dynamic response to injury is heightened and rehabilitation might be particularly effective. This review summarizes the evidence of the existence of this plastic window, and the evidence regarding safety and efficacy of early rehabilitative strategies for several stroke domain-specific deficits. Overall, trials of rehabilitation in the first 2 weeks after stroke are scarce. In the realm of very early mobilization, one large and one small trial found potential harm from mobilizing patients within the first 24 h after stroke, and only one small trial found benefit in doing so. For the upper extremity, constraint-induced movement therapy appears to have benefit when started within 2 weeks of stroke. Evidence for non-invasive brain stimulation in the acute period remains scant and inconclusive. For aphasia, the evidence is mixed, but intensive early therapy might be of benefit for patients with severe aphasia. Mirror therapy begun early after stroke shows promise for the alleviation of neglect. Novel approaches to treating dysphagia early after stroke appear promising, but the high rate of spontaneous improvement makes their benefit difficult to gauge. The optimal time to begin rehabilitation after a stroke remains unsettled, though the evidence is mounting that for at least some deficits, initiation of rehabilitative strategies within the first 2 weeks of stroke is beneficial. Commencing intensive therapy in the first 24 h may be harmful.

Using Artificial Intelligence to Reduce the Risk of Nonadherence in Patients on Anticoagulation Therapy

PubMed Central

Labovitz, Daniel L.; Shafner, Laura; Gil, Morayma Reyes; Virmani, Deepti; Hanina, Adam

2017-01-01

Background and Purpose This study evaluated the use of an artificial intelligence (AI) platform on mobile devices in measuring and increasing medication adherence in stroke patients on anticoagulation therapy. The introduction of direct oral anticoagulants (DOACs), while reducing the need for monitoring, have also placed pressure on patients to self-manage. Suboptimal adherence goes undetected as routine laboratory tests are not reliable indicators of adherence, placing patients at increased risk of stroke and bleeding. Methods A randomized, parallel-group, 12-week study was conducted in adults (n = 28) with recently diagnosed ischemic stroke receiving any anticoagulation. Patients were randomized to daily monitoring by the AI Platform (intervention) or to no daily monitoring (control). The AI application visually identified the patient, the medication and confirmed ingestion. Adherence was measured by pill counts and plasma sampling in both groups. Results For all patients (n = 28), mean (standard deviation [SD]) age was 57 (13.2) years and 53.6% were female. Mean (SD) cumulative adherence based on the AI Platform was 90.5% (7.5%). Plasma drug concentration levels indicated that adherence was 100% (15 of 15) and 50% (6 of 12) in the intervention and control groups, respectively. Conclusions Patients, some with little experience using a smartphone, successfully used the technology and demonstrated a 50% improvement in adherence based on plasma drug concentration levels. For patients receiving DOACs, absolute improvement increased to 67%. Real-time monitoring has the potential to increase adherence and change behavior, particularly in patients on DOAC therapy. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT02599259. PMID:28386037

Randomized Controlled Trial of Early Versus Delayed Statin Therapy in Patients With Acute Ischemic Stroke: ASSORT Trial (Administration of Statin on Acute Ischemic Stroke Patient).

PubMed

Yoshimura, Shinichi; Uchida, Kazutaka; Daimon, Takashi; Takashima, Ryuzo; Kimura, Kazuhiro; Morimoto, Takeshi

2017-11-01

Several studies suggested that statins during hospitalization were associated with better disability outcomes in patients with acute ischemic stroke, but only 1 small randomized trial is available. We conducted a multicenter, open-label, randomized controlled trial in patients with acute ischemic strokes in 11 hospitals in Japan. Patients with acute ischemic stroke and dyslipidemia randomly received statins within 24 hours after admission in the early group or on the seventh day in the delayed group, in a 1:1 ratio. Statins were administered for 12 weeks. The primary outcome was patient disability assessed by modified Rankin Scale at 90 days. A total of 257 patients were randomized and analyzed (early 131, delayed 126). At 90 days, modified Rankin Scale score distribution did not differ between groups ( P =0.68), and the adjusted common odds ratio of the early statin group was 0.84 (95% confidence interval, 0.53-1.3; P =0.46) compared with the delayed statin group. There were 3 deaths at 90 days (2 in the early group, 1 in the delayed group) because of malignancy. Ischemic stroke recurred in 9 patients (6.9%) in the early group and 5 patients (4.0%) in the delayed group. The safety profile was similar between groups. Our randomized trial involving patients with acute ischemic stroke and dyslipidemia did not show any superiority of early statin therapy within 24 hours of admission compared with delayed statin therapy 7 days after admission to alleviate the degree of disability at 90 days after onset. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02549846. © 2017 American Heart Association, Inc.

Cluster Randomized Controlled Trial

PubMed Central

Young, John; Chapman, Katie; Nixon, Jane; Patel, Anita; Holloway, Ivana; Mellish, Kirste; Anwar, Shamaila; Breen, Rachel; Knapp, Martin; Murray, Jenni; Farrin, Amanda

2015-01-01

Background and Purpose— We developed a new postdischarge system of care comprising a structured assessment covering longer-term problems experienced by patients with stroke and their carers, linked to evidence-based treatment algorithms and reference guides (the longer-term stroke care system of care) to address the poor longer-term recovery experienced by many patients with stroke. Methods— A pragmatic, multicentre, cluster randomized controlled trial of this system of care. Eligible patients referred to community-based Stroke Care Coordinators were randomized to receive the new system of care or usual practice. The primary outcome was improved patient psychological well-being (General Health Questionnaire-12) at 6 months; secondary outcomes included functional outcomes for patients, carer outcomes, and cost-effectiveness. Follow-up was through self-completed postal questionnaires at 6 and 12 months. Results— Thirty-two stroke services were randomized (29 participated); 800 patients (399 control; 401 intervention) and 208 carers (100 control; 108 intervention) were recruited. In intention to treat analysis, the adjusted difference in patient General Health Questionnaire-12 mean scores at 6 months was −0.6 points (95% confidence interval, −1.8 to 0.7; P=0.394) indicating no evidence of statistically significant difference between the groups. Costs of Stroke Care Coordinator inputs, total health and social care costs, and quality-adjusted life year gains at 6 months, 12 months, and over the year were similar between the groups. Conclusions— This robust trial demonstrated no benefit in clinical or cost-effectiveness outcomes associated with the new system of care compared with usual Stroke Care Coordinator practice. Clinical Trial Registration— URL: http://www.controlled-trials.com. Unique identifier: ISRCTN 67932305. PMID:26152298

Patent foramen ovale closure and medical treatments for secondary stroke prevention: a systematic review of observational and randomized evidence.

PubMed

Kitsios, Georgios D; Dahabreh, Issa J; Abu Dabrh, Abd Moain; Thaler, David E; Kent, David M

2012-02-01

Patients discovered to have a patent foramen ovale in the setting of a cryptogenic stroke may be treated with percutaneous closure, antiplatelet therapy, or anticoagulants. A recent randomized trial (CLOSURE I) did not detect any benefit of closure over medical treatment alone; the optimal medical therapy is also unknown. We synthesized the available evidence on secondary stroke prevention in patients with patent foramen ovale and cryptogenic stroke. A MEDLINE search was performed for finding longitudinal studies investigating medical treatment or closure, meta-analysis of incidence rates (IR), and IR ratios of recurrent cerebrovascular events. Fifty-two single-arm studies and 7 comparative nonrandomized studies and the CLOSURE I trial were reviewed. The summary IR of recurrent stroke was 0.36 events (95% confidence interval [CI], 0.24-0.56) per 100 person-years with closure versus 2.53 events (95% CI, 1.91-3.35) per 100 person-years with medical therapy. In comparative observational studies, closure was superior to medical therapy (IR ratio=0.19; 95% CI, 0.07-0.54). The IR for the closure arm of the CLOSURE I trial was higher than the summary estimate from observational studies; there was no significant benefit of closure over medical treatment (P=0.002 comparing efficacy estimates between observational studies and the trial). Observational and randomized data (9 studies) comparing medical therapies were consistent and suggested that anticoagulants are superior to antiplatelets for preventing stroke recurrence (IR ratio=0.42; 95% CI, 0.18-0.98). Although further randomized trial data are needed to precisely determine the effects of closure on stroke recurrence, the results of CLOSURE I challenge the credibility of a substantial body of observational evidence strongly favoring mechanical closure over medical therapy.

Clinical trial transparency: a reassessment of industry compliance with clinical trial registration and reporting requirements in the United States

PubMed Central

Lassman, Scott M; Shopshear, Olivia M; Jazic, Ina; Ulrich, Jocelyn; Francer, Jeffrey

2017-01-01

Objective To evaluate the accuracy of a 2015 cross-sectional analysis published in the BMJ Open which reported that pharmaceutical industry compliance with clinical trial registration and results reporting requirements under US law was suboptimal and varied widely among companies. Design We performed a reassessment of the data reported in Miller et al to evaluate whether statutory compliance analyses and conclusions were valid. Data sources Information from the Dryad Digital Repository, ClinicalTrials.gov, Drugs@FDA and direct communications with sponsors. Main outcome measures Compliance with the clinical trial registration and results reporting requirements under the Food and Drug Administration Amendments Act (FDAAA). Results Industry compliance with FDAAA disclosure requirements was notably higher than reported by Miller et al. Among trials subject to FDAAA, Miller et al reported that, per drug, a median of 67% (middle 50% range: 0%–100%) of trials fully complied with registration and results reporting requirements. On reanalysis of the data, we found that a median of 100% (middle 50% range: 93%–100%) of clinical trials for a particular drug fully complied with the law. When looking at overall compliance at the trial level, our reassessment yields 94% timely registration and 90% timely results reporting among the 49 eligible trials, and an overall FDAAA compliance rate of 86%. Conclusions The claim by Miller et al that industry compliance is below legal standards is based on an analysis that relies on an incomplete dataset and an interpretation of FDAAA that requires disclosure of study results for drugs that have not yet been approved for any indication. On reanalysis using a different interpretation of FDAAA that focuses on whether results were disclosed within 30 days of drug approval, we found that industry compliance with US statutory disclosure requirements for the 15 reviewed drugs was consistently high. PMID:28942418

Reflections on 50 Years of Neuroscience Nursing: The Growth of Stroke Nursing.

PubMed

Jackson, Nancy; Haxton, Elaine; Morrison, Kathy; Markey, Erin; Andreoli, Linda J; Maloney, Theresa; Omelchenko, Nataliya; Aroose, Amanda; Stevens, Lynn B

2018-05-10

Over the past 50 years, the Journal of Neuroscience Nursing (JNN) has grown from a neurosurgical focus to the broader neuroscience focus alongside the professional nursing organization that it supports. Stroke care in JNN focused on the surgical treatment and nursing care for cranial treatment of conditions such as cerebral aneurysm, carotid disease, arteriovenous malformation, and artery bypass procedures. As medical science has grown and new medications and treatment modalities have been successfully trialed, JNN has brought to its readership this information about recombinant tissue plasminogen activator, endovascular trials, and new assessment tools such as the National Institute of Health Stroke Scale. JNN is on the forefront of publishing nursing research in the areas of stroke caregiver needs and community education for rapid treatment of stroke and stroke risk reduction. The journal has been timely and informative in keeping neuroscience nurses on the forefront of the changing world of stroke nursing.

Causes and Severity of Ischemic Stroke in Patients with Symptomatic Intracranial Arterial Stenosis

PubMed Central

Famakin, Bolanle M; Chimowitz, Marc I; Lynn, Michael J; Stern, Barney J; George, Mary G.

2009-01-01

Background and purpose There are limited data on the causes and severity of subsequent stroke in patients presenting initially with TIA or stroke attributed to intracranial arterial stenosis. Methods We evaluated the location, type (lacunar vs. non-lacunar), cause, and severity of stroke in patients who had an ischemic stroke endpoint in the Warfarin Aspirin Symptomatic Intracranial Disease (WASID) trial. Results Of the 569 patients enrolled in the WASID trial, 106 patients (18.6%) had an ischemic stroke during a mean follow-up of 1.8 years. Stroke occurred in the territory of the symptomatic artery in 77 (73%) of 106 patients. Among the 77 strokes in the territory, 70 (91%) were non-lacunar and 34 (44%) were disabling. Stroke out of the territory of the symptomatic artery occurred in 29 (27%) of 106 patients. Among these 29 strokes, 24 (83%) were non-lacunar, 14 (48%) were due to previously asymptomatic intracranial stenosis, and 9 (31%) were disabling. Conclusions Most subsequent strokes in patients with symptomatic intracranial artery stenosis are in the same territory and non-lacunar, and nearly half of the strokes in the territory are disabling. The most commonly identified cause of stroke out of the territory was a previously asymptomatic intracranial stenosis. Penetrating artery disease was responsible for a low number of strokes. PMID:19407228

Critical periods after stroke study: translating animal stroke recovery experiments into a clinical trial

PubMed Central

Dromerick, Alexander W.; Edwardson, Matthew A.; Edwards, Dorothy F.; Giannetti, Margot L.; Barth, Jessica; Brady, Kathaleen P.; Chan, Evan; Tan, Ming T.; Tamboli, Irfan; Chia, Ruth; Orquiza, Michael; Padilla, Robert M.; Cheema, Amrita K.; Mapstone, Mark E.; Fiandaca, Massimo S.; Federoff, Howard J.; Newport, Elissa L.

2015-01-01

Introduction: Seven hundred ninety-five thousand Americans will have a stroke this year, and half will have a chronic hemiparesis. Substantial animal literature suggests that the mammalian brain has much potential to recover from acute injury using mechanisms of neuroplasticity, and that these mechanisms can be accessed using training paradigms and neurotransmitter manipulation. However, most of these findings have not been tested or confirmed in the rehabilitation setting, in large part because of the challenges in translating a conceptually straightforward laboratory experiment into a meaningful and rigorous clinical trial in humans. Through presentation of methods for a Phase II trial, we discuss these issues and describe our approach. Methods: In rodents there is compelling evidence for timing effects in rehabilitation; motor training delivered at certain times after stroke may be more effective than the same training delivered earlier or later, suggesting that there is a critical or sensitive period for strongest rehabilitation training effects. If analogous critical/sensitive periods can be identified after human stroke, then existing clinical resources can be better utilized to promote recovery. The Critical Periods after Stroke Study (CPASS) is a phase II randomized, controlled trial designed to explore whether such a sensitive period exists. We will randomize 64 persons to receive an additional 20 h of upper extremity therapy either immediately upon rehab admission, 2–3 months after stroke onset, 6 months after onset, or to an observation-only control group. The primary outcome measure will be the Action Research Arm Test (ARAT) at 1 year. Blood will be drawn at up to 3 time points for later biomarker studies. Conclusion: CPASS is an example of the translation of rodent motor recovery experiments into the clinical setting; data obtained from this single site randomized controlled trial will be used to finalize the design of a Phase III trial. PMID:25972803

The effects of mental practice in neurological rehabilitation; a systematic review and meta-analysis

PubMed Central

Braun, Susy; Kleynen, Melanie; van Heel, Tessa; Kruithof, Nena; Wade, Derick; Beurskens, Anna

2013-01-01

Objective: To investigate the beneficial and adverse effects of a mental practice intervention on activities, cognition, and emotion in patients after stroke, patients with Parkinson's disease or multiple sclerosis. Methods: Electronic databases PubMed/Medline, PEDro, Science Direct, Cochrane Library, PsycINFO, Rehadat, Embase, and Picarta were searched until June 2012. Fourteen randomized controlled trials in stroke and two randomized controlled trials in Parkinson's disease were included, representing 491 patients (421 with stroke). No randomized controlled trials in multiple sclerosis were identified. The methodologic quality of the included trials was assessed with the Amsterdam-Maastricht-Consensus-List (AMCL). Information on study characteristics and outcomes was summarized and evidence for effects described. Data from individual studies in stroke with same outcome measures were pooled. Results: The included 16 randomized controlled trials were heterogeneous and methodologic quality varied. Ten trials reported significant effects in favor of mental practice in patients with stroke (n = 9) and Parkinson's disease (n = 1). In six studies mental practice had similar effects as therapy as usual (n = 5 in stroke and n = 1 in Parkinson's disease). Of six performed meta-analyses with identical measures in stroke studies only two showed significant effects of mental practice: short-term improvement of arm-hand-ability (ARAT: SMD 0.62; 95% CI: 0.05 to 1.19) and improvement of performance of activities (NRS: SMD 0.9; 95% CI: 0.04 to 1.77). Five studies found effects on cognition (e.g., effects on attention, plan actions in unfamiliar surroundings) and four reported observed side-effects, both positive (e.g., might increase motivation and arousal and reduce depression) and negative (e.g., diminished concentration, irritation). Conclusions: Mental practice might have positive effects on performance of activities in patients with neurological diseases, but this review reports less positive results than earlier published ones. Strengths and limitations of past studies are pointed out. Methodologic recommendations for future studies are given. PMID:23935572

Clopidogrel With Aspirin in Acute Minor Stroke or Transient Ischemic Attack (CHANCE) Trial: One-Year Outcomes.

PubMed

Wang, Yilong; Pan, Yuesong; Zhao, Xingquan; Li, Hao; Wang, David; Johnston, S Claiborne; Liu, Liping; Meng, Xia; Wang, Anxin; Wang, Chunxue; Wang, Yongjun

2015-07-07

The Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial showed that the combined treatment of clopidogrel and aspirin decreases the 90-day risk of stroke without increasing hemorrhage in comparison with aspirin alone, but provided insufficient data to establish whether the benefit persisted over a longer period of time beyond the trial termination. We report the 1-year follow-up outcomes of this trial. The trial was a randomized, double-blind, placebo-controlled trial conducted at 114 centers in China. We randomly assigned 5170 patients within 24 hours after onset of minor stroke or high-risk transient ischemic attack to clopidogrel-aspirin therapy (loading dose of 300 mg of clopidogrel on day 1, followed by 75 mg of clopidogrel per day for 90 days, plus 75 mg of aspirin per day for the first 21 days) or to the aspirin-alone group (75 mg/d for 90 days). The primary outcome was stroke event (ischemic or hemorrhagic) during 1-year follow-up. Differences in outcomes between groups were assessed by using the Cox proportional hazards model. Stroke occurred in 275 (10.6%) patients in the clopidogrel-aspirin group, in comparison with 362 (14.0%) patients in the aspirin group (hazard ratio, 0.78; 95% confidence interval, 0.65-0.93; P=0.006). Moderate or severe hemorrhage occurred in 7 (0.3%) patients in the clopidogrel-aspirin group and in 9 (0.4%) patients in the aspirin group (P=0.44). The early benefit of clopidogrel-aspirin treatment in reducing the risk of subsequent stroke persisted for the duration of 1-year of follow-up. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589. © 2015 American Heart Association, Inc.

Direct comparative effectiveness and safety between non-vitamin K antagonist oral anticoagulants for stroke prevention in nonvalvular atrial fibrillation: a systematic review and meta-analysis of observational studies.

PubMed

Li, Guowei; Lip, Gregory Y H; Holbrook, Anne; Chang, Yaping; Larsen, Torben B; Sun, Xin; Tang, Jie; Mbuagbaw, Lawrence; Witt, Daniel M; Crowther, Mark; Thabane, Lehana; Levine, Mitchell A H

2018-06-08

The non-vitamin K antagonist oral anticoagulants (NOACs) have been increasingly prescribed in clinical practice for stroke prevention in patients with nonvalvular atrial fibrillation (AF). Direct comparisons between NOACs in trials are lacking, leaving an important clinical decision-making gap. We aimed to perform a systematic review and meta-analysis to summarize the evidence of observational studies for direct comparative effectiveness and safety amongst NOACs in patients with AF. Conference proceedings and electronic databases including MEDLINE, CINAHL, EMBASE and PUBMED were systematically searched. We included observational studies directly comparing individual NOACs in patients with nonvalvular AF who were aged ≥ 18 years for stroke prevention. Primary outcome included effectiveness outcome (stroke or systemic embolism) and safety outcome (major bleeding). Data were extracted in duplicated by two reviewers independently. A random-effects meta-analysis was conducted to synthesize the data from included observational studies. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to rate the overall quality of evidence for each outcome. Fifteen studies were included for qualitative synthesis, twelve studies for meta-analyses. It was found that rivaroxaban and dabigatran were similar with regard to risk of stroke or systemic embolism (Hazard ratio [HR] = 1.00, 95% CI 0.91-1.10; evidence quality: low), but rivaroxaban was associated with higher risk of major bleeding (HR = 1.39, 95% CI 1.28-1.50; evidence quality: moderate). Compared with apixaban, a significantly higher risk of major bleeding was observed with rivaroxaban (HR = 1.71, 95% CI 1.51-1.94; evidence quality: low). Apixaban was associated with lower risk of major bleeding, in comparison with dabigatran (HR = 0.80, 95% CI 0.68-0.95; evidence quality: low). No differences in risk of stroke or systemic embolism was observed between rivaroxaban versus apixaban, and apixaban versus dabigatran. In this study, apixaban was found to have the most favorable safety profile amongst the three NOACs. No significant difference was observed in risk of stroke or systemic embolism between the NOACs. Such findings may provide some decision-making support for physicians regarding their choices amongst NOACs in patients with AF.Registration PROSPERO (identifier: CRD42016052908).

Twelve-month Clinical and Quality-of-Life Outcomes in the Interventional Management of Stroke III Trial

PubMed Central

Palesch, Yuko Y.; Yeatts, Sharon D.; Tomsick, Thomas A; Foster, Lydia D.; Demchuk, Andrew M.; Khatri, Pooja; Hill, Michael D.; Jauch, Edward C.; Jovin, Tudor G.; Yan, Bernard; von Kummer, Rüdiger; Molina, Carlos A.; Goyal, Mayank; Schonewille, Wouter J.; Mazighi, Mikael; Engelter, Stefan T.; Anderson, Craig; Spilker, Judith; Carrozzella, Janice; Ryckborst, Karla J.; Janis, L. Scott; Simpson, Annie; Simpson, Kit N.; Broderick, Joseph P.

2015-01-01

Background and Purpose Randomized trials have indicated a benefit for endovascular therapy in appropriately selected stroke patients at 3 months but data regarding outcomes at 12 months are currently lacking. Methods We compared functional and quality of life outcomes at 12 months overall and by stroke severity in stroke patients treated with intravenous (IV) tissue plasminogen activator (t-PA) followed by endovascular treatment as compared to IV t-PA alone in the Interventional Management of Stroke (IMS) III Trial. The key outcome measures were a modified Rankin Scale (mRS) score ≤ 2 (functional independence) and the Euro-QoL EQ-5D, a health-related quality-of-life measure (HRQoL). Results 656 subjects with moderate to severe stroke (National Institutes of Health Stroke Scale ≥ 8) were enrolled at 58 centers in the United States (41 sites), Canada (7), Australia (4), and Europe (6). There was an interaction between treatment group and stroke severity in the repeated measures analysis of mRS ≤ 2 outcome (p=0.039). In the 204 participants with severe stroke (NIHSS ≥ 20), a greater proportion of the endovascular group had a mRS ≤ 2 (32.5%) at 12 months as compared to the IV t-PA group (18.6%, p=0.037); no difference was seen for the 452 participants with moderately-severe strokes (55.6% vs. 57.7%). In participants with severe stroke, the endovascular group had 35.2 (95% CI: 2.1, 73.3) more quality-adjusted-days over 12 months as compared to IV t-PA alone. Conclusions Endovascular therapy improves functional outcome and HRQoL at 12 months after severe ischemic stroke. PMID:25858239

Dipyridamole for preventing recurrent ischemic stroke and other vascular events: a meta-analysis of individual patient data from randomized controlled trials.

PubMed

Leonardi-Bee, Jo; Bath, Philip M W; Bousser, Marie-Germaine; Davalos, Antoni; Diener, Hans-Christoph; Guiraud-Chaumeil, Bernard; Sivenius, Juhani; Yatsu, Frank; Dewey, Michael E

2005-01-01

Results from randomized controlled trials of dipyridamole, given with or without aspirin, for secondary prevention after ischemic stroke or transient ischemic attack (TIA) have given conflicting results. We performed a meta-analysis using individual patient data from relevant randomized controlled trials. Randomized controlled trials involving dipyridamole in patients with previous ischemic stroke or TIA were sought from searches of the Cochrane Library, other electronic databases, references lists, earlier reviews, and contact with the manufacturer of dipyridamole. Individual patient data were merged from 5 of 7 relevant trials involving 11 459 patients. Results were adjusted for age, gender, qualifying event, and history of previous hypertension. Recurrent stroke was reduced by dipyridamole as compared with control (OR, 0.82; 95% CI, 0.68 to 1.00), and by combined aspirin and dipyridamole versus aspirin alone (OR, 0.78; 95% CI, 0.65 to 0.93), dipyridamole alone (OR, 0.74; 95% CI, 0.60 to 0.90), or control (OR, 0.61; 95% CI, 0.51 to 0.71). The point estimates obtained for the comparisons of aspirin and dipyridamole versus control (OR, 0.63; significant) or versus aspirin (OR, 0.88; nonsignificant) were similar if the data from the largest trial, ESPS II (which provided 57% of data), were excluded. Similar findings were observed for nonfatal stroke. The combination of aspirin and dipyridamole also significantly reduced the composite outcome of nonfatal stroke, nonfatal myocardial infarction, and vascular death as compared with aspirin alone (OR, 0.84; 95% CI, 0.72 to 0.97), dipyridamole alone (OR, 0.76; 95% CI, 0.64 to 0.90), or control (OR, 0.66; 95% CI, 0.57 to 0.75). Vascular death was not altered in any group. Dipyridamole, given alone or with aspirin, reduces stroke recurrence in patients with previous ischemic cerebrovascular disease. The combination of aspirin and dipyridamole also reduces the composite of nonfatal stroke, nonfatal myocardial infarction, and vascular death as compared with aspirin alone.

Power of an Adaptive Trial Design for Endovascular Stroke Studies: Simulations Using IMS (Interventional Management of Stroke) III Data.

PubMed

Lansberg, Maarten G; Bhat, Ninad S; Yeatts, Sharon D; Palesch, Yuko Y; Broderick, Joseph P; Albers, Gregory W; Lai, Tze L; Lavori, Philip W

2016-12-01

Adaptive trial designs that allow enrichment of the study population through subgroup selection can increase the chance of a positive trial when there is a differential treatment effect among patient subgroups. The goal of this study is to illustrate the potential benefit of adaptive subgroup selection in endovascular stroke studies. We simulated the performance of a trial design with adaptive subgroup selection and compared it with that of a traditional design. Outcome data were based on 90-day modified Rankin Scale scores, observed in IMS III (Interventional Management of Stroke III), among patients with a vessel occlusion on baseline computed tomographic angiography (n=382). Patients were categorized based on 2 methods: (1) according to location of the arterial occlusive lesion and onset-to-randomization time and (2) according to onset-to-randomization time alone. The power to demonstrate a treatment benefit was based on 10 000 trial simulations for each design. The treatment effect was relatively homogeneous across categories when patients were categorized based on arterial occlusive lesion and time. Consequently, the adaptive design had similar power (47%) compared with the fixed trial design (45%). There was a differential treatment effect when patients were categorized based on time alone, resulting in greater power with the adaptive design (82%) than with the fixed design (57%). These simulations, based on real-world patient data, indicate that adaptive subgroup selection has merit in endovascular stroke trials as it substantially increases power when the treatment effect differs among subgroups in a predicted pattern. © 2016 American Heart Association, Inc.

Effect of Continuous Positive Airway Pressure on Stroke Rehabilitation: A Pilot Randomized Sham-Controlled Trial

PubMed Central

Khot, Sandeep P.; Davis, Arielle P.; Crane, Deborah A.; Tanzi, Patricia M.; Li Lue, Denise; Claflin, Edward S.; Becker, Kyra J.; Longstreth, W.T.; Watson, Nathaniel F.; Billings, Martha E.

2016-01-01

Study Objectives: Obstructive sleep apnea (OSA) predicts poor functional outcome after stroke and increases the risk for recurrent stroke. Less is known about continuous positive airway pressure (CPAP) treatment on stroke recovery. Methods: In a pilot randomized, double-blind, sham-controlled trial, adult stroke rehabilitation patients were assigned to auto-titrating or sham CPAP without diagnostic testing for OSA. Change in Functional Independence Measure (FIM), a measure of disability, was assessed between rehabilitation admission and discharge. Results: Over 18 months, 40 patients were enrolled and 10 withdrew from the study: 7 from active and 3 from sham CPAP (p > 0.10). For the remaining 30 patients, median duration of CPAP use was 14 days. Average CPAP use was 3.7 h/night, with at least 4 h nightly use among 15 patients. Adherence was not influenced by treatment assignment or stroke severity. In intention-to-treat analyses (n = 40), the median change in FIM favored active CPAP over sham but did not reach statistical significance (34 versus 26, p = 0.25), except for the cognitive component (6 versus 2.5, p = 0.04). The on-treatment analyses (n = 30) yielded similar results (total FIM: 32 versus 26, p = 0.11; cognitive FIM: 6 versus 2, p = 0.06). Conclusions: A sham-controlled CPAP trial among stroke rehabilitation patients was feasible in terms of recruitment, treatment without diagnostic testing and adequate blinding—though was limited by study retention and CPAP adherence. Despite these limitations, a trend towards a benefit of CPAP on recovery was evident. Tolerance and adherence must be improved before the full benefits of CPAP on recovery can be assessed in larger trials. Citation: Khot SP, Davis AP, Crane DA, Tanzi PM, Li Lue D, Claflin ES, Becker KJ, Longstreth WT, Watson NF, Billings ME. Effect of continuous positive airway pressure on stroke rehabilitation: a pilot randomized sham-controlled trial. J Clin Sleep Med 2016;12(7):1019–1026. PMID:27092703

Synergistic effect of acupuncture and mirror therapy on post-stroke upper limb dysfunction: a study protocol for a randomized controlled trial.

PubMed

Xu, Ying; Lin, Shufang; Jiang, Cai; Ye, Xiaoqian; Tao, Jing; Wilfried, Schupp; Wong, Alex W K; Chen, Lidian; Yang, Shanli

2018-05-31

Upper limb dysfunction is common after stroke, posing an important challenge for post-stroke rehabilitation. The clinical efficacy of acupuncture for the recovery of post-stroke upper limb function has been previously demonstrated. Mirror therapy (MT) has also been found to be effective. However, the effects of acupuncture and MT have not been systematically compared. This trial aims to elucidate the synergistic effects of acupuncture and MT on upper limb dysfunction after stroke. A 2 × 2 factorial randomized controlled trial will be conducted at the rehabilitation hospitals affiliated with Fujian University of Traditional Chinese Medicine. A total of 136 eligible subjects will be randomly divided into acupuncture treatment (AT), MT, combined treatment, and control groups in a 1:1:1:1 ratio. All subjects will receive conventional treatment. The interventions will be performed 5 days per week for 4 weeks. AT, MT, and combined treatment will be performed for 30 min per day (combined treatment: AT 15 min + MT 15 min). The primary outcomes in this study will be the mean change in scores on both the FMA and WMFT from baseline to 4 weeks intervention and at 12 weeks follow-up between the two groups and within groups. The secondary outcomes are the mean change in the scores on the Visual Analogue Scale, Stroke Impact Scale, and modified Barthel index. Medical abstraction of adverse events will be assessed at each visit. The results of this trial will demonstrate the synergistic effect of acupuncture and MT on upper limb motor dysfunction after stroke. In addition, whether AT and MT, either combined or alone, are more effective than the conventional treatment in the management of post-stroke upper limb dysfunction will also be determined. Chinese Clinical Trial Registry: ChiCTR-IOR-17011118 . Registered on April 11, 2017. Version number: 01.2016.09.1.

Design and rationale of the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE) Trial.

PubMed

Kidwell, Chelsea S; Jahan, Reza; Alger, Jeffry R; Schaewe, Timothy J; Guzy, Judy; Starkman, Sidney; Elashoff, Robert; Gornbein, Jeffrey; Nenov, Val; Saver, Jeffrey L

2014-01-01

Multimodal imaging has the potential to identify acute ischaemic stroke patients most likely to benefit from late recanalization therapies. The general aim of the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy Trial is to investigate whether multimodal imaging can identify patients who will benefit substantially from mechanical embolectomy for the treatment of acute ischaemic stroke up to eight-hours from symptom onset. Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy is a randomized, controlled, blinded-outcome clinical trial. Acute ischaemic stroke patients with large vessel intracranial internal carotid artery or middle cerebral artery M1 or M2 occlusion enrolled within eight-hours of symptom onset are eligible. The study sample size is 120 patients. Patients are randomized to endovascular embolectomy employing the Merci Retriever (Concentric Medical, Mountain View, CA) or the Penumbra System (Penumbra, Alameda, CA) vs. standard medical care, with randomization stratified by penumbral pattern. The primary aim of the trial is to test the hypothesis that the presence of substantial ischaemic penumbral tissue visualized on multimodal imaging (magnetic resonance imaging or computed tomography) predicts patients most likely to respond to mechanical embolectomy for treatment of acute ischaemic stroke due to a large vessel, intracranial occlusion up to eight-hours from symptom onset. This hypothesis will be tested by analysing whether pretreatment imaging pattern has a significant interaction with treatment as a determinant of functional outcome based on the distribution of scores on the modified Rankin Scale measure of global disability assessed 90 days post-stroke. Nested hypotheses test for (1) treatment efficacy in patients with a penumbral pattern pretreatment, and (2) absence of treatment benefit (equivalency) in patients without a penumbral pattern pretreatment. An additional aim will only be tested if the primary hypothesis of an interaction is negative: that patients treated with mechanical embolectomy have improved functional outcome vs. standard medical management. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

Non-invasive versus invasive management in patients with prior coronary artery bypass surgery with a non-ST segment elevation acute coronary syndrome: study design of the pilot randomised controlled trial and registry (CABG-ACS)

PubMed Central

Lee, Matthew M Y; Petrie, Mark C; Rocchiccioli, Paul; Simpson, Joanne; Jackson, Colette; Brown, Ammani; Corcoran, David; Mangion, Kenneth; McEntegart, Margaret; Shaukat, Aadil; Rae, Alan; Hood, Stuart; Peat, Eileen; Findlay, Iain; Murphy, Clare; Cormack, Alistair; Bukov, Nikolay; Balachandran, Kanarath; Papworth, Richard; Ford, Ian; Briggs, Andrew; Berry, Colin

2016-01-01

Introduction There is an evidence gap about how to best treat patients with prior coronary artery bypass grafts (CABGs) presenting with non-ST segment elevation acute coronary syndromes (NSTE-ACS) because historically, these patients were excluded from pivotal randomised trials. We aim to undertake a pilot trial of routine non-invasive management versus routine invasive management in patients with NSTE-ACS with prior CABG and optimal medical therapy during routine clinical care. Our trial is a proof-of-concept study for feasibility, safety, potential efficacy and health economic modelling. We hypothesise that a routine invasive approach in patients with NSTE-ACS with prior CABG is not superior to a non-invasive approach with optimal medical therapy. Methods and analysis 60 patients will be enrolled in a randomised clinical trial in 4 hospitals. A screening log will be prospectively completed. Patients not randomised due to lack of eligibility criteria and/or patient or physician preference and who give consent will be included in a registry. We will gather information about screening, enrolment, eligibility, randomisation, patient characteristics and adverse events (including post-discharge). The primary efficacy outcome is the composite of all-cause mortality, rehospitalisation for refractory ischaemia/angina, myocardial infarction and hospitalisation for heart failure. The primary safety outcome is the composite of bleeding, stroke, procedure-related myocardial infarction and worsening renal function. Health status will be assessed using EuroQol 5 Dimensions (EQ-5D) assessed at baseline and 6 monthly intervals, for at least 18 months. Trial registration number NCT01895751 (ClinicalTrials.gov). PMID:27110377

Trends and Disparities in Stroke Mortality by Region for American Indians and Alaska Natives

PubMed Central

Ayala, Carma; Valderrama, Amy L.; Veazie, Mark A.

2014-01-01

Objectives. We evaluated trends and disparities in stroke death rates for American Indians and Alaska Natives (AI/ANs) and White people by Indian Health Service region. Methods. We identified stroke deaths among AI/AN persons and Whites (adults aged 35 years or older) using National Vital Statistics System data for 1990 to 2009. We used linkages with Indian Health Service patient registration data to adjust for misclassification of race for AI/AN persons. Analyses excluded Hispanics and focused on Contract Health Service Delivery Area (CHSDA) counties. Results. Stroke death rates among AI/AN individuals were higher than among Whites for both men and women in CHSDA counties and were highest in the youngest age groups. Rates and AI/AN:White rate ratios varied by region, with the highest in Alaska and the lowest in the Southwest. Stroke death rates among AI/AN persons decreased in all regions beginning in 2001. Conclusions. Although stroke death rates among AI/AN populations have decreased over time, rates are still higher for AI/AN persons than for Whites. Interventions that address reducing stroke risk factors, increasing awareness of stroke symptoms, and increasing access to specialty care for stroke may be more successful at reducing disparities in stroke death rates. PMID:24754653

Heparin in acute ischemic stroke revisited.

PubMed

Chamorro, A

2008-10-01

The evidence gathered in clinical trials of low molecular weight heparins (LMWHs) or with unfractionated heparin (UH) given subcutaneously at low or medium doses to patients with acute stroke cannot be extrapolated to the insufficiently tested effects of intravenous, weight-adjusted UH. Recent small studies have provided encouraging results but are potentially confounded and deserve confirmation in larger randomized controlled trials. In accordance with the current understanding of the biology of acute ischemic stroke and the pharmacology of UH, the new randomized controlled trials on heparin should give appropriate credit to the importance of a short therapeutic window, adequate dose adjustment of the drug, intravenous administration, and close monitoring of biological effects. UH is an orphan drug and only an academic driven trial would be able to face such an enterprise. Meanwhile, recommendations against the value of "early" anticoagulation with full dose of weight adjusted UH in the setting of acute ischemic stroke are not based on direct evidence but on extrapolations.

Recommendations for Management of Patients with Carotid Stenosis

PubMed Central

Lovrencic-Huzjan, Arijana; Rundek, Tatjana; Katsnelson, Michael

2012-01-01

Stroke is a one of the leading causes of morbidity and mortality in the world. Carotid atherosclerosis is recognized as an important factor in stroke pathophysiology and represents a key target in stroke prevention; multiple treatment modalities have been developed to battle this disease. Multiple randomized trials have shown the efficacy of carotid endarterectomy in secondary stroke prevention. Carotid stenting, a newer treatment option, presents a less invasive alternative to the surgical intervention on carotid arteries. Advances in medical therapy have also enabled further risk reduction in the overall incidence of stroke. Despite numerous trials and decades of clinical research, the optimal management of symptomatic and asymptomatic carotid disease remains controversial. We will attempt to highlight some of the pivotal trials already completed, discuss the current controversies and complexities in the treatment decision-making, and postulate on what likely lies ahead. This paper will highlight the complexities of decision-making optimal treatment recommendations for patients with symptomatic and asymptomatic carotid stenosis. PMID:22645702

Association of the FDA Amendment Act with trial registration, publication, and outcome reporting.

PubMed

Phillips, Adam T; Desai, Nihar R; Krumholz, Harlan M; Zou, Constance X; Miller, Jennifer E; Ross, Joseph S

2017-07-18

Selective clinical trial publication and outcome reporting has the potential to bias the medical literature. The 2007 Food and Drug Administration (FDA) Amendment Act (FDAAA) mandated clinical trial registration and outcome reporting on ClinicalTrials.gov, a publicly accessible trial registry. Using publicly available data from ClinicalTrials.gov, FDA documents, and PubMed, we determined registration, publication, and reporting of findings for all efficacy trials supporting FDA approval of new drugs for cardiovascular disease and diabetes between 2005 and 2014, before and after the FDAAA. For published trials, we compared the published interpretation of the findings (positive, equivocal, or negative) with the FDA reviewer's interpretation. Between 2005 and 2014, the FDA approved 30 drugs for 32 indications of cardiovascular disease (n = 17) and diabetes (n = 15) on the basis of 183 trials (median per indication 5.7 (IQR, 3-8)). Compared with pre FDAAA, post-FDAAA studies were more likely to be registered (78 of 78 (100%) vs 73 of 105 (70%); p < 0.001), to be published (76 of 78 (97%) vs 93 of 105 (89%); p = 0.03), and to present findings concordant with the FDA reviewer's interpretation (74 of 76 (97%) vs 78 of 93 (84%); p = 0.004). Pre FDAAA, the FDA reviewer interpreted 80 (76%) trials as positive and 91 (98%) were published as positive. Post FDAAA, the FDA reviewer interpreted 71 (91%) trials as positive and 71 (93%) were published as positive. FDAAA was associated with increased registration, publication, and FDA-concordant outcome reporting for trials supporting FDA approval of new drugs for cardiovascular disease and diabetes.

Robot Assisted Training for the Upper Limb after Stroke (RATULS): study protocol for a randomised controlled trial.

PubMed

Rodgers, Helen; Shaw, Lisa; Bosomworth, Helen; Aird, Lydia; Alvarado, Natasha; Andole, Sreeman; Cohen, David L; Dawson, Jesse; Eyre, Janet; Finch, Tracy; Ford, Gary A; Hislop, Jennifer; Hogg, Steven; Howel, Denise; Hughes, Niall; Krebs, Hermano Igo; Price, Christopher; Rochester, Lynn; Stamp, Elaine; Ternent, Laura; Turner, Duncan; Vale, Luke; Warburton, Elizabeth; van Wijck, Frederike; Wilkes, Scott

2017-07-20

Loss of arm function is a common and distressing consequence of stroke. We describe the protocol for a pragmatic, multicentre randomised controlled trial to determine whether robot-assisted training improves upper limb function following stroke. Study design: a pragmatic, three-arm, multicentre randomised controlled trial, economic analysis and process evaluation. NHS stroke services. adults with acute or chronic first-ever stroke (1 week to 5 years post stroke) causing moderate to severe upper limb functional limitation. Randomisation groups: 1. Robot-assisted training using the InMotion robotic gym system for 45 min, three times/week for 12 weeks 2. Enhanced upper limb therapy for 45 min, three times/week for 12 weeks 3. Usual NHS care in accordance with local clinical practice Randomisation: individual participant randomisation stratified by centre, time since stroke, and severity of upper limb impairment. upper limb function measured by the Action Research Arm Test (ARAT) at 3 months post randomisation. upper limb impairment (Fugl-Meyer Test), activities of daily living (Barthel ADL Index), quality of life (Stroke Impact Scale, EQ-5D-5L), resource use, cost per quality-adjusted life year and adverse events, at 3 and 6 months. Blinding: outcomes are undertaken by blinded assessors. Economic analysis: micro-costing and economic evaluation of interventions compared to usual NHS care. A within-trial analysis, with an economic model will be used to extrapolate longer-term costs and outcomes. Process evaluation: semi-structured interviews with participants and professionals to seek their views and experiences of the rehabilitation that they have received or provided, and factors affecting the implementation of the trial. allowing for 10% attrition, 720 participants provide 80% power to detect a 15% difference in successful outcome between each of the treatment pairs. Successful outcome definition: baseline ARAT 0-7 must improve by 3 or more points; baseline ARAT 8-13 improve by 4 or more points; baseline ARAT 14-19 improve by 5 or more points; baseline ARAT 20-39 improve by 6 or more points. The results from this trial will determine whether robot-assisted training improves upper limb function post stroke. ISRCTN, identifier: ISRCTN69371850 . Registered 4 October 2013.

China Angioplasty and Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS): A new, prospective, multicenter, randomized controlled trial in China

PubMed Central

Gao, Peng; Zhao, Zhenwei; Wang, Daming; Wu, Jian; Cai, Yiling; Li, Tianxiao; Wu, Wei; Shi, Huaizhang; He, Weiwen; Zhu, Fengshui; Ling, Feng

2015-01-01

Background Patients with symptomatic stenosis of intradural arteries are at high risk for subsequent stroke. Since the SAMMPRIS trial, stenting is no longer recommended as primary treatment; however, the results of this trial, its inclusion criteria and its center selection received significant criticism and did not appear to reflect our experience regarding natural history nor treatment complications rate. As intracranial atherosclerosis (ICAS) is the most common cause for stroke in Asian countries, we are hereby proposing a refined prospective, randomized, multicenter study in an Asian population with strictly defined patient and participating center inclusion criteria. Methods The China Angioplasty and Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS) trial is an ongoing, government-funded, prospective, multicenter, randomized trial. It recruits patients with recent TIA or stroke caused by 70%–99% stenosis of a major intracranial artery. Patients with previous stroke related to perforator ischemia will not be included. Only high-volume centers with a proven track record will enroll patients as determined by a lead-in phase. Patients will be randomized (1:1) to best medical therapy alone or medical therapy plus stenting. Primary endpoints are any stroke or death within 30 days after enrollment or after any revascularization procedure of the qualifying lesion during follow-up, or stroke in the territory of the symptomatic intracranial artery beyond 30 days. The CASSISS trial will be conducted in eight sites in China with core imaging lab review at a North American site and aims to have a sample size of 380 participants (stenting, 190; medical therapy, 190). Recruitment is expected to be finished by December 2016. Patients will be followed for at least three years. The trial is scheduled to complete in 2019. Conclusion In the proposed trial, certain shortcomings of SAMMPRIS including patient and participating center selection will be addressed. The present manuscript outlines the rationale and design of the study. We estimate that this trial will allow for a critical reappraisal of the role of intracranial stenting for selected patients in high-volume centers. PMID:25934656

Statins for stroke prevention: disappointment and hope.

PubMed

Amarenco, Pierre; Tonkin, Andrew M

2004-06-15

The occurrence of stroke increases with age, particularly affecting the older elderly, a population also at higher risk for coronary heart disease (CHD). Epidemiological and observational studies have not shown a clear association between cholesterol levels and all causes of stroke. Nonetheless, large, long-term statin trials in patients with established CHD or at high risk for CHD have shown that statins decrease stroke incidence in these populations. Combined data from 9 trials including 70,070 patients indicated relative and absolute risk reductions for stroke of 21% and 0.9%, respectively, with statins. The number of strokes prevented per 1000 patients treated for 5 years in patients with CHD is 9 for statins, compared with 17.3 for antiplatelet agents. Statins have not yet been shown to reduce stroke risk in the typical general population without known CHD, nor have they been shown to prevent recurrent stroke in patients with prior stroke. Potential reasons for the effects of statins on stroke and the non-cholesterol-lowering mechanisms that may be involved are discussed. Treatment strategies based on global cardiovascular risk may be most effective. Additional studies in patients representative of the typical stroke population are needed.

Lacunar Infarcts, Depression, and Anxiety Symptoms One Year after Stroke.

PubMed

Arba, Francesco; Ali, Myzoon; Quinn, Terence J; Hankey, Graeme J; Lees, Kennedy R; Inzitari, Domenico

2016-04-01

Mood disorders are frequent after stroke and are associated with poorer quality of life. Previous studies have reported conflicting results as to stroke subtype in the incidence of poststroke mood disorders. We explored the relationship between subcortical ischemic stroke subtype (lacunar) and presence of such symptoms at 1 year after stroke. Anonymized data were accessed from the Virtual International Stroke Trials Archive. Stroke subtypes were classified according to the Trial of Org 10172 in Acute Stroke Treatment classification. Depression and anxiety symptoms were assessed using Hospital Anxiety and Depression Scale. We investigated independent predictors of depression and anxiety symptoms using a logistic regression model. Data were available for 2160 patients. Almost one fifth of the patients developed both anxiety and depression at 1-year follow-up. After adjusting for confounders, the lacunar subtype was least associated with both anxiety (odds ratio [OR] = .61; 95% confidence interval [CI] = .46-.80) and depression symptoms (OR = .71; CI = .55-.93) versus other stroke subtypes. Lacunar strokes have a weaker association with presence of anxiety and depression symptoms compared with other subtypes. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

L-Arginine Affects Aerobic Capacity and Muscle Metabolism in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes) Syndrome

PubMed Central

Rodan, Lance H.; Wells, Greg D.; Banks, Laura; Thompson, Sara; Schneiderman, Jane E.; Tein, Ingrid

2015-01-01

Objective To study the effects of L-arginine (L-Arg) on total body aerobic capacity and muscle metabolism as assessed by 31Phosphorus Magnetic Resonance Spectroscopy (31P-MRS) in patients with MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes) syndrome. Methods We performed a case control study in 3 MELAS siblings (m.3243A>G tRNAleu(UUR) in MTTL1 gene) with different % blood mutant mtDNA to evaluate total body maximal aerobic capacity (VO2peak) using graded cycle ergometry and muscle metabolism using 31P-MRS. We then ran a clinical trial pilot study in MELAS sibs to assess response of these parameters to single dose and a 6-week steady-state trial of oral L-Arginine. Results At baseline (no L-Arg), MELAS had lower serum Arg (p = 0.001). On 31P-MRS muscle at rest, MELAS subjects had increased phosphocreatine (PCr) (p = 0.05), decreased ATP (p = 0.018), and decreased intracellular Mg2+ (p = 0.0002) when compared to matched controls. With L-arginine therapy, the following trends were noted in MELAS siblings on cycle ergometry: (1) increase in mean % maximum work at anaerobic threshold (AT) (2) increase in % maximum heart rate at AT (3) small increase in VO2peak. On 31P-MRS the following mean trends were noted: (1) A blunted decrease in pH after exercise (less acidosis) (2) increase in Pi/PCr ratio (ADP) suggesting increased work capacity (3) a faster half time of PCr recovery (marker of mitochondrial activity) following 5 minutes of moderate intensity exercise (4) increase in torque. Significance These results suggest an improvement in aerobic capacity and muscle metabolism in MELAS subjects in response to supplementation with L-Arg. Intramyocellular hypomagnesemia is a novel finding that warrants further study. Classification of Evidence Class III evidence that L-arginine improves aerobic capacity and muscle metabolism in MELAS subjects. Trial Registration ClinicalTrials.gov NCT01603446. PMID:25993630

Hyperglycaemia, Insulin Therapy and Critical Penumbral Regions for Prognosis in Acute Stroke: Further Insights from the INSULINFARCT Trial

PubMed Central

Rosso, Charlotte; Pires, Christine; Corvol, Jean-Christophe; Baronnet, Flore; Crozier, Sophie; Leger, Anne; Deltour, Sandrine; Valabregue, Romain; Amor-Sahli, Mélika; Lehéricy, Stéphane; Dormont, Didier; Samson, Yves

2015-01-01

Background Recently, the concept of ‘clinically relevant penumbra’ was defined as an area saved by arterial recanalization and correlated with stroke outcome. This clinically relevant penumbra was located in the subcortical structures, especially the periventricular white matter. Our aims were to confirm this hypothesis, to investigate the impact of admission hyperglycemia and of insulin treatment on the severity of ischemic damages in this area and to study the respective contributions of infarct volume and ischemic damage severity of the clinically relevant penumbra on 3-month outcome. Methods We included 99 patients from the INSULINFARCT trial. Voxel-Based Analysis was carried on the Apparent Diffusion Coefficient (ADC) maps obtained at day one to localize the regions, which were more damaged in patients i) with poor clinical outcomes at three months and ii) without arterial recanalization. We determined the intersection of the detected areas, which represents the clinically relevant penumbra and investigated whether hyperglycemic status and insulin regimen affected the severity of ischemic damages in this area. We performed logistic regression to examine the contribution of infarct volume or early ADC decrease in this strategic area on 3-month outcome. Findings Lower ADC values were found in the corona radiata in patients with poor prognosis (p< 0.0001) and in those without arterial recanalization (p< 0.0001). The tracking analysis showed that lesions in this area interrupted many important pathways. ADC values in this area were lower in hyperglycemic than in normoglycemic patients (average decrease of 41.6 ± 20.8 x10−6mm2/s) and unaffected by the insulin regimen (p: 0.10). ADC values in the clinically relevant penumbra, but not infarct volumes, were significant predictors of 3-month outcome. Conclusion These results confirm that the deep hemispheric white matter is part of the clinically relevant penumbra and show that hyperglycaemia exacerbates the apparition of irreversible ischemic damage within 24 hours in this area. However, early intensive insulin therapy fails to protect this area from infarction. Trial Registration ClinicalTrials.gov NCT00472381 PMID:25793765

Cluster Randomized Controlled Trial: Clinical and Cost-Effectiveness of a System of Longer-Term Stroke Care.

PubMed

Forster, Anne; Young, John; Chapman, Katie; Nixon, Jane; Patel, Anita; Holloway, Ivana; Mellish, Kirste; Anwar, Shamaila; Breen, Rachel; Knapp, Martin; Murray, Jenni; Farrin, Amanda

2015-08-01

We developed a new postdischarge system of care comprising a structured assessment covering longer-term problems experienced by patients with stroke and their carers, linked to evidence-based treatment algorithms and reference guides (the longer-term stroke care system of care) to address the poor longer-term recovery experienced by many patients with stroke. A pragmatic, multicentre, cluster randomized controlled trial of this system of care. Eligible patients referred to community-based Stroke Care Coordinators were randomized to receive the new system of care or usual practice. The primary outcome was improved patient psychological well-being (General Health Questionnaire-12) at 6 months; secondary outcomes included functional outcomes for patients, carer outcomes, and cost-effectiveness. Follow-up was through self-completed postal questionnaires at 6 and 12 months. Thirty-two stroke services were randomized (29 participated); 800 patients (399 control; 401 intervention) and 208 carers (100 control; 108 intervention) were recruited. In intention to treat analysis, the adjusted difference in patient General Health Questionnaire-12 mean scores at 6 months was -0.6 points (95% confidence interval, -1.8 to 0.7; P=0.394) indicating no evidence of statistically significant difference between the groups. Costs of Stroke Care Coordinator inputs, total health and social care costs, and quality-adjusted life year gains at 6 months, 12 months, and over the year were similar between the groups. This robust trial demonstrated no benefit in clinical or cost-effectiveness outcomes associated with the new system of care compared with usual Stroke Care Coordinator practice. URL: http://www.controlled-trials.com. Unique identifier: ISRCTN 67932305. © 2015 Bradford Teaching Hospitals NHS Foundation Trust.

Design of the stenting and aggressive medical management for preventing recurrent stroke in intracranial stenosis trial.

PubMed

Chimowitz, Marc I; Lynn, Michael J; Turan, Tanya N; Fiorella, David; Lane, Bethany F; Janis, Scott; Derdeyn, Colin P

2011-01-01

Patients with recent transient ischemic attack (TIA) or stroke caused by 70% to 99% stenosis of a major intracranial artery are at high risk of recurrent stroke on usual medical management, suggesting the need for alternative therapies for this disease. The Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis trial is an ongoing, randomized, multicenter, 2-arm trial that will determine whether intracranial angioplasty and stenting adds benefit to aggressive medical management alone for preventing the primary endpoint (any stroke or death within 30 days after enrollment or after any revascularization procedure of the qualifying lesion during follow-up, or stroke in the territory of the symptomatic intracranial artery beyond 30 days) during a mean follow-up of 2 years in patients with recent TIA or stroke caused by 70% to 99% stenosis of a major intracranial artery. Aggressive medical management in both arms consists of aspirin 325 mg per day, clopidogrel 75 mg per day for 90 days after enrollment, intensive risk factor management primarily targeting systolic blood pressure <140 mm Hg (<130 mm Hg in diabetics) and low density cholesterol <70 mg/dL, and a lifestyle modification program. The sample size required to detect a 35% reduction in the rate of the primary endpoint from angioplasty and stenting based on the log-rank test with an alpha of 0.05, 80% power, and adjusting for a 2% loss to follow-up and 5% crossover from the medical to the stenting arm is 382 patients per group. Enrollment began in November 2008 and 451 patients have been enrolled as of March 31, 2011. This is the first randomized stroke prevention trial to compare angioplasty and stenting with medical therapy in patients with intracranial arterial stenosis and to incorporate intensive management of multiple risk factors and a lifestyle modification program in the study design. Hopefully, the results of the trial will lead to more effective therapy for this high-risk disease. Copyright © 2011 National Stroke Association. All rights reserved.

Multicenter Randomized Trial of Robot-Assisted Rehabilitation for Chronic Stroke: Methods and Entry Characteristics for VA ROBOTICS

PubMed Central

Lo, Albert C.; Guarino, Peter; Krebs, Hermano I.; Volpe, Bruce T.; Bever, Christopher T.; Duncan, Pamela W.; Ringer, Robert J.; Wagner, Todd H.; Richards, Lorie G.; Bravata, Dawn M.; Haselkorn, Jodie K.; Wittenberg, George F.; Federman, Daniel G.; Corn, Barbara H.; Maffucci, Alysia D.; Peduzzi, Peter

2017-01-01

Background Chronic upper extremity impairment due to stroke has significant medical, psychosocial, and financial consequences, but few studies have examined the effectiveness of rehabilitation therapy during the chronic stroke period. Objective To test the safety and efficacy of the MIT-Manus robotic device for chronic upper extremity impairment following stroke. Methods The VA Cooperative Studies Program initiated a multicenter, randomized, controlled trial in November 2006 (VA ROBOTICS). Participants with upper extremity impairment ≥6 months poststroke were randomized to robot-assisted therapy (RT), intensive comparison therapy (ICT), or usual care (UC). RT and ICT consisted of three 1-hour treatment sessions per week for 12 weeks. The primary outcome was change in the Fugl-Meyer Assessment upper extremity motor function score at 12 weeks relative to baseline. Secondary outcomes included the Wolf Motor Function Test and the Stroke Impact Scale. Results A total of 127 participants were randomized: 49 to RT, 50 to ICT, and 28 to UC. The majority of participants were male (96%), with a mean age of 65 years. The primary stroke type was ischemic (85%), and 58% of strokes occurred in the anterior circulation. Twenty percent of the participants reported a stroke in addition to their index stroke. The average time from the index stroke to enrollment was 56 months (range, 6 months to 24 years). The mean Fugl-Meyer score at entry was 18.9. Conclusions VA ROBOTICS demonstrates the feasibility of conducting multicenter clinical trials to rigorously test new rehabilitative devices before their introduction to clinical practice. The results are expected in early 2010. PMID:19541917

Physiotherapy treatment approaches for the recovery of postural control and lower limb function following stroke: a systematic review.

PubMed

Pollock, Alex; Baer, Gillian; Langhorne, Peter; Pomeroy, Valerie

2007-05-01

To determine whether there is a difference in global dependency and functional independence in patients with stroke associated with different approaches to physiotherapy treatment. We searched the Cochrane Stroke Group Trials Register (last searched May 2005), Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 2, 2005), MEDLINE (1966 to May 2005), EMBASE (1980 to May 2005) and CINAHL (1982 to May 2005). We contacted experts and researchers with an interest in stroke rehabilitation. Inclusion criteria were: (a) randomized or quasi-randomized controlled trials; (b) adults with a clinical diagnosis of stroke; (c) physiotherapy treatment approaches aimed at promoting postural control and lower limb function; (d) measures of disability, motor impairment or participation. Two independent reviewers categorized identified trials according to the inclusion/exclusion criteria, documented the methodological quality and extracted the data. Twenty trials (1087 patients) were included in the review. Comparisons included: neurophysiological approach versus other approach; motor learning approach versus other approach; mixed approach versus other approach for the outcomes of global dependency and functional independence. A mixed approach was significantly more effective than no treatment control at improving functional independence (standardized mean difference (SMD) 0.94, 95% confidence interval (CI) 0.08 to 1.80). There were no significant differences found for any other comparisons. Physiotherapy intervention, using a 'mix' of components from different 'approaches' is more effective than no treatment control in attaining functional independence following stroke. There is insufficient evidence to conclude that any one physiotherapy 'approach' is more effective in promoting recovery of disability than any other approach.

Feasibility and Efficacy of the Nintendo Wii Gaming System to Improve Balance Performance Post-Stroke: Protocol of a Phase II Randomized Controlled Trial in an Inpatient Rehabilitation Setting.

PubMed

Bower, Kelly J; Clark, Ross A; McGinley, Jennifer L; Martin, Clarissa L; Miller, Kimberly J

2013-04-01

Balance deficits following stroke are common and debilitating. Commercially available gaming systems, such as the Nintendo(®) (Kyoto, Japan) Wii™, have been widely adopted clinically; however, there is limited evidence supporting their feasibility and efficacy for improving balance performance following stroke. The aim of this trial is to investigate the clinical feasibility and efficacy of using the Nintendo Wii gaming system as an adjunct to standard care to improve balance performance following stroke in an inpatient rehabilitation setting. Thirty participants undergoing inpatient stroke rehabilitation will be recruited into this Phase II, single-blind, randomized controlled trial. Participants will be allocated into a Balance or Upper Limb Group, and both groups will perform activities using the Nintendo Wii in addition to their standard care. Participants will attend three 45-minute sessions per week, for a minimum of 2 and a maximum of 4 weeks. The main focus of the study is to investigate the feasibility of the intervention protocol. This will be evaluated through recruitment, retention, adherence, acceptability, and safety. The Step Test and Functional Reach Test will be the primary efficacy outcomes. Secondary outcomes will include force platform, mobility, and upper limb measures. Assessments will occur at baseline, 2 weeks, and 4 weeks after study entry. To the authors' knowledge, this will be the largest randomized clinical trial to investigate the feasibility and efficacy of the Nintendo Wii gaming system for improving balance performance in a stroke population. The results will inform the design of a Phase III multicenter trial.

The web of clinical trial registration obligations: have foreign clinical trials been caught?

PubMed

Hathaway, Carolyne R; Manthei, John R; Haas, J Ben; Meltzer, Elizabeth D

2009-01-01

The web of overlapping requirements, standards, recommendations and policies governing the conduct of clinical trials highlights the intense scrutiny of the ethical, data quality and public access issues raised by human trials that are conducted to demonstrate the safety and efficacy of medical products marketed in the United States. One relatively recent development is the requirement that sponsors register and make public information about their clinical trials and clinical trial results. These clinical trial registration requirements illustrate the interests of patients, providers and researchers in increased visibility, transparency and accessibility of clinical trials and the data they generate. These requirements, however, pose regulatory, logistical and practical hurdles for companies sponsoring clinical trials of drugs and medical devices.

Telestroke 10 years later--'telestroke 2.0'.

PubMed

Switzer, Jeffrey A; Levine, Steven R; Hess, David C

2009-01-01

The lack of physicians with specialty stroke training represents a significant challenge to the future of stroke. This deficit limits both quality stroke care and clinical research initiatives. The use of telemedicine for stroke ('telestroke') has been an attempt to overcome this shortage and extend stroke expertise to locations which lack coverage. However, the initial telestroke systems required a point-to-point connection for transmission and only provided videoconferencing which limited their generalizability and usefulness. 'Telestroke 2.0' is the authors' vision of an integrative web-based telestroke system combining high-quality audiovideo transmission, the ability of consults and teleradiology to be carried out from any desktop or laptop computer with web-access, decision and technical support, creation of billable physician documentation and electronic medical record connectivity. These features will facilitate the development of statewide and regional telestroke call networks with an opportunity for physician supply companies to fill in coverage gaps. In addition, telestroke 2.0 may improve acute stroke research by increasing trial efficiency via the addition of non-academic recruitment sites, enhancing trial validity by centralizing neurologic examinations via recorded encounters, and generalizing clinical trial results to community hospital settings. Greater diffusion and long-term sustainability of telestroke systems will be dependent upon improvements in patient and hospital reimbursement for acute stroke and telestroke care. Copyright 2009 S. Karger AG, Basel.

Home-based neurologic music therapy for arm hemiparesis following stroke: results from a pilot, feasibility randomized controlled trial.

PubMed

Street, Alexander J; Magee, Wendy L; Bateman, Andrew; Parker, Michael; Odell-Miller, Helen; Fachner, Jorg

2018-01-01

To assess the feasibility of a randomized controlled trial to evaluate music therapy as a home-based intervention for arm hemiparesis in stroke. A pilot feasibility randomized controlled trial, with cross-over design. Randomization by statistician using computer-generated, random numbers concealed in opaque envelopes. Participants' homes across Cambridgeshire, UK. Eleven people with stroke and arm hemiparesis, 3-60 months post stroke, following discharge from community rehabilitation. Each participant engaged in therapeutic instrumental music performance in 12 individual clinical contacts, twice weekly for six weeks. Feasibility was estimated by recruitment from three community stroke teams over a 12-month period, attrition rates, completion of treatment and successful data collection. Structured interviews were conducted pre and post intervention to establish participant tolerance and preference. Action Research Arm Test and Nine-hole Peg Test data were collected at weeks 1, 6, 9, 15 and 18, pre and post intervention by a blinded assessor. A total of 11 of 14 invited participants were recruited (intervention n = 6, waitlist n = 5). In total, 10 completed treatment and data collection. It cannot be concluded whether a larger trial would be feasible due to unavailable data regarding a number of eligible patients screened. Adherence to treatment, retention and interview responses might suggest that the intervention was motivating for participants. ClinicalTrials.gov identifier NCT 02310438.

Influence of Handrim Wheelchair Propulsion Training in Adolescent Wheelchair Users, A Pilot Study

PubMed Central

Dysterheft, Jennifer L.; Rice, Ian M.; Rice, Laura A.

2015-01-01

Ten full-time adolescent wheelchair users (ages 13–18) completed a total of three propulsion trials on carpet and tile surfaces, at a self-selected velocity, and on a concrete surface, at a controlled velocity. All trials were performed in their personal wheelchair with force and moment sensing wheels attached bilaterally. The first two trials on each surface were used as pre-intervention control trials. The third trial was performed after receiving training on proper propulsion technique. Peak resultant force, contact angle, stroke frequency, and velocity were recorded during all trials for primary analysis. Carpet and tile trials resulted in significant increases in contact angle and peak total force with decreased stroke frequency after training. During the velocity controlled trials on concrete, significant increases in contact angle occurred, as well as decreases in stroke frequency after training. Overall, the use of a training video and verbal feedback may help to improve short-term propulsion technique in adolescent wheelchair users and decrease the risk of developing upper limb pain and injury. PMID:26042217

Alternative strategies for stroke care: a prospective randomised controlled trial.

PubMed

Kalra, L; Evans, A; Perez, I; Knapp, M; Donaldson, N; Swift, C G

2000-09-09

Organised specialist care for stroke improves outcome, but the merits of different methods of organisation are in doubt. This study compares the efficacy of stroke unit with stroke team or domiciliary care. A single-blind, randomised, controlled trial was undertaken in 457 acute-stroke patients (average age 76 years, 48% women) randomly assigned to stroke unit, general wards with stroke team support, or domiciliary stroke care, within 72 h of stroke onset. Outcome was assessed at 3, 6, and 12 months. The primary outcome measure was death or institutionalisation at 12 months. Analyses were by intention to treat. 152 patients were allocated to the stroke unit, 152 to stroke team, and 153 to domiciliary stroke care. 51 (34%) patients in the domiciliary group were admitted to hospital after randomisation. Mortality or institutionalisation at 1 year were lower in patients on a stroke unit than for those receiving care from a stroke team (21/152 [14%] vs 45/149 [30%]; p<0.001) or domiciliary care (21/152 [14%] vs 34/144 [24%]; p=0.03), mainly as a result of reduction in mortality. The proportion of patients alive without severe disability at 1 year was also significantly higher on the stroke unit compared with stroke team (129/152 [85%] vs 99/149 [66%]; p<0.001) or domiciliary care (129/152 [85%] vs 102/144 [71%]; p=0.002). These differences were present at 3 and 6 months after stroke. Stroke units are more effective than a specialist stroke team or specialist domiciliary care in reducing mortality, institutionalisation, and dependence after stroke.

76 FR 28054 - National Institute of Neurological Disorders and Stroke; Notice of Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-13

... Neurological Disorders and Stroke; Notice of Meetings Pursuant to section 10(d) of the Federal Advisory... Neurological Disorders and Stroke Council. The meetings will be open to the public as indicated below, with... Committee: National Advisory Neurological Disorders and Stroke Council, Clinical Trials Subcommittee. Date...

75 FR 52010 - National Institute of Neurological Disorders and Stroke; Notice of Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-24

... Neurological Disorders and Stroke; Notice of Meetings Pursuant to section 10(d) of the Federal Advisory... Neurological Disorders and Stroke Council. The meeting will be open to the public as indicated below, with... Committee: National Advisory Neurological Disorders and Stroke Council; Clinical Trials Subcommittee. Date...

75 FR 22607 - National Institute of Neurological Disorders and Stroke; Notice of Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-29

... Neurological Disorders and Stroke; Notice of Meetings Pursuant to section 10(d) of the Federal Advisory... Neurological Disorders and Stroke Council. The meetings will be open to the public as indicated below, with... Committee: National Advisory Neurological Disorders and Stroke Council, Clinical Trials Subcommittee. Date...

76 FR 2129 - National Institute of Neurological Disorders And Stroke; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-12

... Neurological Disorders And Stroke; Notice of Meeting Pursuant to section 10(d) of the Federal Advisory... Neurological Disorders and Stroke Council. The meeting will be open to the public as indicated below, with... Committee: National Advisory Neurological Disorders and Stroke Council Clinical Trials Subcommittee. Date...

Electroacupuncture for poststroke spasticity (EAPSS): protocol for a randomised controlled trial

PubMed Central

Cai, Yiyi; Ouyang, Wenwei; Li, Jianmin; Nong, Wenheng; Zhang, Anthony Lin

2018-01-01

Introduction Spasticity is a common complication of stroke. Current therapies for poststroke spasticity (PSS) have been reported to be associated with high costs, lack of long-term benefit and unwanted adverse events (AEs). Electroacupuncture (EA) has been used for PSS, however, its efficacy and safety is yet to be confirmed by high-quality clinical studies. This study is designed to evaluate the add-on effects and safety profile of EA when used in combination with usual care (UC). Methods and analysis This study is a parallel group randomised controlled trial. A total of 136 participants will be included and randomly assigned to either the treatment group (EA plus UC) or the control group (UC alone). Prior to the main trial, a pilot study involving 30 participants will be conducted to assess the feasibility of the trial protocol. EA will be administered by registered acupuncturists for 20min to 30 min, three times per week for 4 weeks. The primary outcome measure (Modified Ashworth Scale) and secondary outcome measures (Fugl-Meyer Assessment and Barthel Index) will be evaluated at baseline, the end of treatment (week 4) and the end of follow-up (week 8). AEs will be monitored, recorded and reported, and their causality will be explored. Ethics and dissemination Ethics approval was obtained from the ethics committees of Guangdong Provincial Hospital of Chinese Medicine and RMIT University in December 2016. The results will be disseminated in a peer-reviewed journal, and PhD theses and might be presented at international conferences. Trial registration number ChiCTR-IOR-16010283; Pre-results. PMID:29487073

Prevalence of Imaging Biomarkers to Guide the Planning of Acute Stroke Reperfusion Trials.

PubMed

Jiang, Bin; Ball, Robyn L; Michel, Patrik; Jovin, Tudor; Desai, Manisha; Eskandari, Ashraf; Naqvi, Zack; Wintermark, Max

2017-06-01

Imaging biomarkers are increasingly used as selection criteria for stroke clinical trials. The goal of our study was to determine the prevalence of commonly studied imaging biomarkers in different time windows after acute ischemic stroke onset to better facilitate the design of stroke clinical trials using such biomarkers for patient selection. This retrospective study included 612 patients admitted with a clinical suspicion of acute ischemic stroke with symptom onset no more than 24 hours before completing baseline imaging. Patients with subacute/chronic/remote infarcts and hemorrhage were excluded from this study. Imaging biomarkers were extracted from baseline imaging, which included a noncontrast head computed tomography (CT), perfusion CT, and CT angiography. The prevalence of dichotomized versions of each of the imaging biomarkers in several time windows (time since symptom onset) was assessed and statistically modeled to assess time dependence (not lack thereof). We created tables showing the prevalence of the imaging biomarkers pertaining to the core, the penumbra and the arterial occlusion for different time windows. All continuous imaging features vary over time. The dichotomized imaging features that vary significantly over time include: noncontrast head computed tomography Alberta Stroke Program Early CT (ASPECT) score and dense artery sign, perfusion CT infarct volume, and CT angiography collateral score and visible clot. The dichotomized imaging features that did not vary significantly over time include the thresholded perfusion CT penumbra volumes. As part of the feasibility analysis in stroke clinical trials, this analysis and the resulting tables can help investigators determine sample size and the number needed to screen. © 2017 American Heart Association, Inc.

Baduanjin Exercise for Stroke Rehabilitation: A Systematic Review with Meta-Analysis of Randomized Controlled Trials

PubMed Central

Wang, Chaoyi; Chen, Xiaoan; Wang, Huiru

2018-01-01

Objective: The purpose of this review was to objectively evaluate the effects of Baduanjin exercise on rehabilitative outcomes in stroke patients. Methods: Both Chinese and English electronic databases were searched for potentially relevant trials. Two review authors independently screened eligible trials against the inclusion criteria, extracted data, and assessed the methodological quality by using the revised PEDro scale. Meta-analysis was only performed for balance function. Results: In total, there were eight randomized controlled trials selected in this systematic review. The aggregated result of four trials has shown a significant benefit in favor of Baduanjin on balance function (Hedges’ g = 2.39, 95% CI 2.14 to 2.65, p < 0.001, I2 = 61.54). Additionally, Baduanjin exercise effectively improved sensorimotor function of lower extremities and ability of daily activities as well as reduced depressive level, leading to improved quality of life. Conclusion: Baduanjin exercise as an adjunctive and safe method may be conducive to help stroke patients achieve the best possible short-term outcome and should be integrated with mainstream rehabilitation programs. More rigorous randomized controlled trials with long-term intervention periods among a large sample size of stroke patients are needed to draw a firm conclusion regarding the rehabilitative effects for this population. PMID:29584623

Effects of aspirin on risk and severity of early recurrent stroke after transient ischaemic attack and ischaemic stroke: time-course analysis of randomised trials.

PubMed

Rothwell, Peter M; Algra, Ale; Chen, Zhengming; Diener, Hans-Christoph; Norrving, Bo; Mehta, Ziyah

2016-07-23

Aspirin is recommended for secondary prevention after transient ischaemic attack (TIA) or ischaemic stroke on the basis of trials showing a 13% reduction in long-term risk of recurrent stroke. However, the risk of major stroke is very high for only the first few days after TIA and minor ischaemic stroke, and observational studies show substantially greater benefits of early medical treatment in the acute phase than do longer-term trials. We hypothesised that the short-term benefits of early aspirin have been underestimated. Pooling the individual patient data from all randomised trials of aspirin versus control in secondary prevention after TIA or ischaemic stroke, we studied the effects of aspirin on the risk and severity of recurrent stroke, stratified by the following time periods: less than 6 weeks, 6-12 weeks, and more than 12 weeks after randomisation. We compared the severity of early recurrent strokes between treatment groups with shift analysis of modified Rankin Scale (mRS) score. To understand possible mechanisms of action, we also studied the time course of the interaction between effects of aspirin and dipyridamole in secondary prevention of stroke. In a further analysis we pooled data from trials of aspirin versus control in which patients were randomised less than 48 h after major acute stroke, stratified by severity of baseline neurological deficit, to establish the very early time course of the effect of aspirin on risk of recurrent ischaemic stroke and how this differs by severity at baseline. We pooled data for 15,778 participants from 12 trials of aspirin versus control in secondary prevention. Aspirin reduced the 6 week risk of recurrent ischaemic stroke by about 60% (84 of 8452 participants in the aspirin group had an ischaemic stroke vs 175 of 7326; hazard ratio [HR] 0·42, 95% CI 0·32-0·55, p<0·0001) and disabling or fatal ischaemic stroke by about 70% (36 of 8452 vs 110 of 7326; 0·29, 0·20-0·42, p<0·0001), with greatest benefit noted in patients presenting with TIA or minor stroke (at 0-2 weeks, two of 6691 participants in the aspirin group with TIA or minor stroke had a disabling or fatal ischaemic stroke vs 23 of 5726 in the control group, HR 0·07, 95% CI 0·02-0·31, p=0·0004; at 0-6 weeks, 14 vs 60 participants, 0·19, 0·11-0·34, p<0·0001). The effect of aspirin on early recurrent ischaemic stroke was due partly to a substantial reduction in severity (mRS shift analysis odds ratio [OR] 0·42, 0·26-0·70, p=0·0007). These effects were independent of dose, patient characteristics, or aetiology of TIA or stroke. Some further reduction in risk of ischaemic stroke accrued for aspirin only versus control from 6-12 weeks, but there was no benefit after 12 weeks (stroke risk OR 0·97, 0·84-1·12, p=0·67; severity mRS shift OR 1·00, 0·77-1·29, p=0·97). By contrast, dipyridamole plus aspirin versus aspirin alone had no effect on risk or severity of recurrent ischaemic stroke within 12 weeks (OR 0·90, 95% CI 0·65-1·25, p=0·53; mRS shift OR 0·90, 0·37-1·72, p=0·99), but dipyridamole did reduce risk thereafter (0·76, 0·63-0·92, p=0·005), particularly of disabling or fatal ischaemic stroke (0·64, 0·49-0·84, p=0·0010). We pooled data for 40,531 participants from three trials of aspirin versus control in major acute stroke. The reduction in risk of recurrent ischaemic stroke at 14 days was most evident in patients with less severe baseline deficits, and was substantial by the second day after starting treatment (2-3 day HR 0·37, 95% CI 0·25-0·57, p<0·0001). Our findings confirm that medical treatment substantially reduces the risk of early recurrent stroke after TIA and minor stroke and identify aspirin as the key intervention. The considerable early benefit from aspirin warrants public education about self-administration after possible TIA. The previously unrecognised effect of aspirin on severity of early recurrent stroke, the diminishing benefit with longer-term use, and the contrasting time course of effects of dipyridamole have implications for understanding mechanisms of action. Wellcome Trust, the National Institute of Health Research (NIHR) Biomedical Research Centre, Oxford. Copyright © 2016 Rothwell et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

[Effect of RAAS inhibition on stroke prevention].

PubMed

Tanahashi, Norio

2012-09-01

Recently, molecular and experimental studies revealed that the brain possesses its own renin-angiotensin-aldosterone system(RAAS) and the brain angiotensin(Ang) II plays an important role on stroke protection, mediating its effects through stimulation of AT2 and possibly the AT4 receptors. Moreover, the novel ACE2/Ang-(1-7)/Mas receptor axis was found to counterbalance the vasoconstrictive actions of the ACE/Ang II/AT1 receptor. Recent clinical trials indicate that blockade of RAAS has a potential role in stroke prevention, but was not conclusive. More carefully designed large clinical trial are needed to verify blood pressure-independent stroke prevention effect by RAAS inhibition.

Effect of aerobic training on inter-arm coordination in highly trained swimmers.

PubMed

Schnitzler, Christophe; Seifert, Ludovic; Chollet, Didier; Toussaint, Huub

2014-02-01

The effect of three months of aerobic training on spatio-temporal and coordination parameters was examined during a swim trial at maximal aerobic speed. Nine male swimmers swam a 400-m front crawl at maximal speed twice: in trial 1, after summer break, and trial 2, after three months of aerobic training. Video analysis determined the stroke (swimming speed, stroke length, and stroke rate) and coordination (Index of Coordination and propulsive phase duration) parameters for every 50-m segment. All swimmers significantly increased their swimming speed after training. For all swimmers except one, stroke length increased and stroke rate remained constant, whereas the Index of Coordination and the propulsive phase duration decreased (p<.05). This study suggests that aerobic training developed a greater force impulse in the swimmers during the propulsive phases, which allowed them to take advantage of longer non-propulsive phases. In this case, catch-up coordination, if associated with greater stroke length, can be an efficient coordination mode that reflects optimal drag/propulsion adaptation. This finding thus provides new insight into swimmers' adaptations to the middle-distance event. Copyright © 2013 Elsevier B.V. All rights reserved.

Combined Electrical Stimulation and Exercise for Swallow Rehabilitation Post-Stroke: A Pilot Randomized Control Trial

ERIC Educational Resources Information Center

Sproson, Lise; Pownall, Sue; Enderby, Pam; Freeman, Jenny

2018-01-01

Background: Dysphagia is common after stroke, affecting up to 50% of patients initially. It can lead to post-stroke pneumonia, which causes 30% of stroke-related deaths, a longer hospital stay and poorer health outcomes. Dysphagia care post-stroke generally focuses on the management of symptoms, via modified oral intake textures and adapted…

Stroke: advances in medical therapy and acute stroke intervention.

PubMed

Barrett, Kevin M; Lal, Brajesh K; Meschia, James F

2015-10-01

Evidence-based therapeutic options for stroke continue to emerge based on results from well-designed clinical studies. Ischemic stroke far exceeds hemorrhagic stroke in terms of prevalence and incidence, both in the USA and worldwide. The public health effect of reducing death and disability related to ischemic stroke justifies the resources that have been invested in identifying safe and effective treatments. The emergence of novel oral anticoagulants for ischemic stroke prevention in atrial fibrillation has introduced complexity to clinical decision making for patients with this common cardiac arrhythmia. Some accepted ischemic stroke preventative strategies, such as carotid revascularization for asymptomatic carotid stenosis, require reassessment, given advances in risk factor management, antithrombotic therapy, and surgical techniques. Intra-arterial therapy, particularly with stent retrievers after intravenous tissue plasminogen activator, has recently been demonstrated to improve functional outcomes and will require investment in system-based care models to ensure that effective treatments are received by patients in a timely fashion. The purpose of this review is to describe recent advances in medical and surgical approaches to ischemic stroke prevention and acute treatment. Results from recently published clinical trials will be highlighted along with ongoing clinical trials addressing key questions in ischemic stroke management and prevention where equipoise remains.

Stroke event rates in anticoagulated patients with paroxysmal atrial fibrillation.

PubMed

Lip, G Y H; Frison, L; Grind, M

2008-07-01

To test the hypothesis that stroke and systemic embolic events (SEE) in the stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) III and V trials are different between paroxysmal and persistent atrial fibrillation (AF). Data analysis from two cohorts of patients enrolled in the prospective SPORTIF III and V clinical trials (n = 7329); 836 subjects (11.4%) with paroxysmal AF [mean age 70.1 years (SD = 9.5)] were compared with 6493 subjects with persistent AF for this ancillary study. The annual event rates for stroke/SEE are 1.73% for persistent AF and 0.93% for paroxysmal AF. In a multivariate analysis, after adjusting for stroke risk factors, gender and aspirin usage, the differences remained statistically significant with a higher hazard ratio (HR) for stroke/SEE in persistent AF [vs. paroxysmal AF, HR 1.87, 95% confidence interval (CI) 1.04-3.36; P = 0.037]. In 'high risk' patients (with >or=2 stroke risk factors) annual event rates for stroke/SEE were 2.08% for persistent AF and 1.27% for paroxysmal AF (adjusted HR = 1.68, 95% CI 0.91-3.1, P = 0.098). Elderly patients had annual event rates for stroke/SEE of 2.38% for persistent AF and 1.13% for paroxysmal AF (adjusted HR = 2.27, 95% CI 0.92-5.59, P = 0.075). Vitamin K antagonist (VKA)-naive paroxysmal AF patients had a 1.89%/year stroke/SEE rate, compared with 0.61% for previous VKA takers (HR = 0.33, 95% CI 0.11-1.01, P = 0.052). In this large clinical trial cohort of anticoagulated AF patients, those with paroxysmal AF had stroke rates which were lower than for patients with persistent AF, although both groups had broadly similar stroke risk factors. Subjects with paroxysmal AF at 'high risk' had stroke/SEE rates that were not significantly different to persistent AF subjects.

Secondary stroke prevention with ximelagatran versus warfarin in patients with atrial fibrillation: pooled analysis of SPORTIF III and V clinical trials.

PubMed

Akins, Paul T; Feldman, Harvey A; Zoble, Robert G; Newman, David; Spitzer, Stefan G; Diener, Hans-Christoph; Albers, Gregory W

2007-03-01

Patients with nonvalvular atrial fibrillation and prior stroke or transient ischemic attack (TIA) are at high risk for recurrent stroke. We investigated whether ximelagatran was noninferior to warfarin in patients with prior stroke or TIA. We analyzed pooled data from the SPORTIF III and V trials in patients with prior stroke/TIA. The primary outcome was the composite annual rate of both ischemic and hemorrhagic strokes and systemic embolic events. Secondary analyses considered ischemic and hemorrhagic strokes separately, bleeding, and nonrandomized, concomitant therapy with aspirin < or =100 mg/d. Patients from SPORTIF III (n=3407) and SPORTIF V (n=3922) trials were categorized by prior stroke/TIA (21%) versus no prior stroke/TIA (79%) and by treatment group (ximelagatran vs warfarin). The primary event rate in patients with prior stroke/TIA was 2.83%/y with ximelagatran and 3.27%/y with warfarin (absolute difference, -0.44%; 95% CI, -1.88 to1.01; P=0.625). In those without prior stroke/TIA, the primary event rate was 1.31%/y with ximelagatran and 1.26%/y with warfarin (P=NS). Ischemic strokes outnumbered cerebral hemorrhages with both warfarin (31 of 36) and ximelagatran (30 of 32) treatment (difference between treatments was not significant). Combining aspirin with either anticoagulant was associated with higher rates of major bleeding (1.5%/y with warfarin and 4.95%/y with warfarin plus aspirin, P=0.004; 2.35%/y with ximelagatran and 5.09%/y with ximelagatran plus aspirin, P=0.046) but not lower rates of primary events. Ximelagatran was at least as effective as well-controlled warfarin for the secondary prevention of stroke. The nonrandomized, concomitant treatment with aspirin and anticoagulation was associated with increased bleeding without evidence of a reduction in primary outcome events.

The effect of whole body vibration on balance, gait performance and mobility in people with stroke: a systematic review and meta-analysis.

PubMed

Yang, Xiaotian; Wang, Pu; Liu, Chuan; He, Chengqi; Reinhardt, Jan D

2015-07-01

To examine the effect of whole body vibration on balance, gait performance and mobility among people with stroke. A systematic review was conducted by two independent reviewers who completed the article search and selection. We included randomized controlled trials published in English examining effects of whole body vibration on balance, gait, mobility, muscle strength and muscle tone in adults with a clinical diagnosis of stroke. Articles were excluded if they were research studies on people with other primary diagnosis, abstracts published in the conferences or books. The Cochrane risk of bias tool was used to assess the methodological quality of the selected studies. Sources included Cochrane Central Register of Controlled Trials, Pubmed, MEDLINE, CINAHL, EMBASE, PEDro, PsycINFO, Science Citation Index, ClinicalTrials.gov, Current Controlled Trials, Stroke Trials Registry, and reference lists of all relevant articles. Eight randomized controlled trials (nine articles) involving 271 participants were included in this meta-analysis. No significant improvement was found regarding Berg balance scale (SMD=-0.08, 95%CI=-1.35 to 1.19, P=0.91), mobility (SMD=0.45, 95%CI=-0.46 to 1.37, P=0.33), maximal isometric contracion of knee extension strength (SMD=0.23, 95%CI=-0.27 to 0.74, P=0.36), and maximal isometric contracion of knee extension strength (SMD=0.09, 95%CI=-0.38 to 0.56, P=0.71). There was no evidence for effects of whole body vibration on balance in people with stroke. Effects of whole body vibration on mobility and gait performance remain inconclusive. More large and high-quality trials are required. © The Author(s) 2014.

Effects of Electrical Stimulation in Spastic Muscles After Stroke: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PubMed

Stein, Cinara; Fritsch, Carolina Gassen; Robinson, Caroline; Sbruzzi, Graciele; Plentz, Rodrigo Della Méa

2015-08-01

Neuromuscular electric stimulation (NMES) has been used to reduce spasticity and improve range of motion in patients with stroke. However, contradictory results have been reported by clinical trials. A systematic review of randomized clinical trials was conducted to assess the effect of treatment with NMES with or without association to another therapy on spastic muscles after stroke compared with placebo or another intervention. We searched the following electronic databases (from inception to February 2015): Medline (PubMed), EMBASE, Cochrane Central Register of Controlled Trials and Physiotherapy Evidence Database (PEDro). Two independent reviewers assessed the eligibility of studies based on predefined inclusion criteria (application of electric stimulation on the lower or upper extremities, regardless of NMES dosage, and comparison with a control group which was not exposed to electric stimulation), excluding studies with <3 days of intervention. The primary outcome extracted was spasticity, assessed by the Modified Ashworth Scale, and the secondary outcome extracted was range of motion, assessed by Goniometer. Of the total of 5066 titles, 29 randomized clinical trials were included with 940 subjects. NMES provided reductions in spasticity (-0.30 [95% confidence interval, -0.58 to -0.03], n=14 randomized clinical trials) and increase in range of motion when compared with control group (2.87 [95% confidence interval, 1.18-4.56], n=13 randomized clinical trials) after stroke. NMES combined with other intervention modalities can be considered as a treatment option that provides improvements in spasticity and range of motion in patients after stroke. URL: http://www.crd.york.ac.uk/PROSPERO. Unique identifier: CRD42014008946. © 2015 American Heart Association, Inc.

Blood transfusion for preventing primary and secondary stroke in people with sickle cell disease.

PubMed

Estcourt, Lise J; Fortin, Patricia M; Hopewell, Sally; Trivella, Marialena; Wang, Winfred C

2017-01-17

Sickle cell disease is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. Sickle cell disease can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Stroke affects around 10% of children with sickle cell anaemia (HbSS). Chronic blood transfusions may reduce the risk of vaso-occlusion and stroke by diluting the proportion of sickled cells in the circulation.This is an update of a Cochrane Review first published in 2002, and last updated in 2013. To assess risks and benefits of chronic blood transfusion regimens in people with sickle cell disease for primary and secondary stroke prevention (excluding silent cerebral infarcts). We searched for relevant trials in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to 04 April 2016.We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register: 25 April 2016. Randomised controlled trials comparing red blood cell transfusions as prophylaxis for stroke in people with sickle cell disease to alternative or standard treatment. There were no restrictions by outcomes examined, language or publication status. Two authors independently assessed trial eligibility and the risk of bias and extracted data. We included five trials (660 participants) published between 1998 and 2016. Four of these trials were terminated early. The vast majority of participants had the haemoglobin (Hb)SS form of sickle cell disease.Three trials compared regular red cell transfusions to standard care in primary prevention of stroke: two in children with no previous long-term transfusions; and one in children and adolescents on long-term transfusion.Two trials compared the drug hydroxyurea (hydroxycarbamide) and phlebotomy to long-term transfusions and iron chelation therapy: one in primary prevention (children); and one in secondary prevention (children and adolescents).The quality of the evidence was very low to moderate across different outcomes according to GRADE methodology. This was due to the trials being at a high risk of bias due to lack of blinding, indirectness and imprecise outcome estimates. Red cell transfusions versus standard care Children with no previous long-term transfusionsLong-term transfusions probably reduce the incidence of clinical stroke in children with a higher risk of stroke (abnormal transcranial doppler velocities or previous history of silent cerebral infarct), risk ratio 0.12 (95% confidence interval 0.03 to 0.49) (two trials, 326 participants), moderate quality evidence.Long-term transfusions may: reduce the incidence of other sickle cell disease-related complications (acute chest syndrome, risk ratio 0.24 (95% confidence interval 0.12 to 0.48)) (two trials, 326 participants); increase quality of life (difference estimate -0.54, 95% confidence interval -0.92 to -0.17) (one trial, 166 participants); but make little or no difference to IQ scores (least square mean: 1.7, standard error 95% confidence interval -1.1 to 4.4) (one trial, 166 participants), low quality evidence.We are very uncertain whether long-term transfusions: reduce the risk of transient ischaemic attacks, Peto odds ratio 0.13 (95% confidence interval 0.01 to 2.11) (two trials, 323 participants); have any effect on all-cause mortality, no deaths reported (two trials, 326 participants); or increase the risk of alloimmunisation, risk ratio 3.16 (95% confidence interval 0.18 to 57.17) (one trial, 121 participants), very low quality evidence. Children and adolescents with previous long-term transfusions (one trial, 79 participants)We are very uncertain whether continuing long-term transfusions reduces the incidence of: stroke, risk ratio 0.22 (95% confidence interval 0.01 to 4.35); or all-cause mortality, Peto odds ratio 8.00 (95% confidence interval 0.16 to 404.12), very low quality evidence.Several review outcomes were only reported in one trial arm (sickle cell disease-related complications, alloimmunisation, transient ischaemic attacks).The trial did not report neurological impairment, or quality of life. Hydroxyurea and phlebotomy versus red cell transfusions and chelationNeither trial reported on neurological impairment, alloimmunisation, or quality of life. Primary prevention, children (one trial, 121 participants)Switching to hydroxyurea and phlebotomy may have little or no effect on liver iron concentrations, mean difference -1.80 mg Fe/g dry-weight liver (95% confidence interval -5.16 to 1.56), low quality evidence.We are very uncertain whether switching to hydroxyurea and phlebotomy has any effect on: risk of stroke (no strokes); all-cause mortality (no deaths); transient ischaemic attacks, risk ratio 1.02 (95% confidence interval 0.21 to 4.84); or other sickle cell disease-related complications (acute chest syndrome, risk ratio 2.03 (95% confidence interval 0.39 to 10.69)), very low quality evidence. Secondary prevention, children and adolescents (one trial, 133 participants)Switching to hydroxyurea and phlebotomy may: increase the risk of sickle cell disease-related serious adverse events, risk ratio 3.10 (95% confidence interval 1.42 to 6.75); but have little or no effect on median liver iron concentrations (hydroxyurea, 17.3 mg Fe/g dry-weight liver (interquartile range 10.0 to 30.6)); transfusion 17.3 mg Fe/g dry-weight liver (interquartile range 8.8 to 30.7), low quality evidence.We are very uncertain whether switching to hydroxyurea and phlebotomy: increases the risk of stroke, risk ratio 14.78 (95% confidence interval 0.86 to 253.66); or has any effect on all-cause mortality, Peto odds ratio 0.98 (95% confidence interval 0.06 to 15.92); or transient ischaemic attacks, risk ratio 0.66 (95% confidence interval 0.25 to 1.74), very low quality evidence. There is no evidence for managing adults, or children who do not have HbSS sickle cell disease.In children who are at higher risk of stroke and have not had previous long-term transfusions, there is moderate quality evidence that long-term red cell transfusions reduce the risk of stroke, and low quality evidence they also reduce the risk of other sickle cell disease-related complications.In primary and secondary prevention of stroke there is low quality evidence that switching to hydroxyurea with phlebotomy has little or no effect on the liver iron concentration.In secondary prevention of stroke there is low-quality evidence that switching to hydroxyurea with phlebotomy increases the risk of sickle cell disease-related events.All other evidence in this review is of very low quality.

Blood transfusion for preventing primary and secondary stroke in people with sickle cell disease

PubMed Central

Estcourt, Lise J; Fortin, Patricia M; Hopewell, Sally; Trivella, Marialena; Wang, Winfred C

2017-01-01

Background Sickle cell disease is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. Sickle cell disease can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Stroke affects around 10% of children with sickle cell anaemia (HbSS). Chronic blood transfusions may reduce the risk of vaso-occlusion and stroke by diluting the proportion of sickled cells in the circulation. This is an update of a Cochrane Review first published in 2002, and last updated in 2013. Objectives To assess risks and benefits of chronic blood transfusion regimens in people with sickle cell disease for primary and secondary stroke prevention (excluding silent cerebral infarcts). Search methods We searched for relevant trials in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to 04 April 2016. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register: 25 April 2016. Selection criteria Randomised controlled trials comparing red blood cell transfusions as prophylaxis for stroke in people with sickle cell disease to alternative or standard treatment. There were no restrictions by outcomes examined, language or publication status. Data collection and analysis Two authors independently assessed trial eligibility and the risk of bias and extracted data. Main results We included five trials (660 participants) published between 1998 and 2016. Four of these trials were terminated early. The vast majority of participants had the haemoglobin (Hb)SS form of sickle cell disease. Three trials compared regular red cell transfusions to standard care in primary prevention of stroke: two in children with no previous long-term transfusions; and one in children and adolescents on long-term transfusion. Two trials compared the drug hydroxyurea (hydroxycarbamide) and phlebotomy to long-term transfusions and iron chelation therapy: one in primary prevention (children); and one in secondary prevention (children and adolescents). The quality of the evidence was very low to moderate across different outcomes according to GRADE methodology. This was due to the trials being at a high risk of bias due to lack of blinding, indirectness and imprecise outcome estimates. Red cell transfusions versus standard care Children with no previous long-term transfusions Long-term transfusions probably reduce the incidence of clinical stroke in children with a higher risk of stroke (abnormal transcranial doppler velocities or previous history of silent cerebral infarct), risk ratio 0.12 (95% confidence interval 0.03 to 0.49) (two trials, 326 participants), moderate quality evidence. Long-term transfusions may: reduce the incidence of other sickle cell disease-related complications (acute chest syndrome, risk ratio 0.24 (95% confidence interval 0.12 to 0.48)) (two trials, 326 participants); increase quality of life (difference estimate -0.54, 95% confidence interval -0.92 to -0.17) (one trial, 166 participants); but make little or no difference to IQ scores (least square mean: 1.7, standard error 95% confidence interval -1.1 to 4.4) (one trial, 166 participants), low quality evidence. We are very uncertain whether long-term transfusions: reduce the risk of transient ischaemic attacks, Peto odds ratio 0.13 (95% confidence interval 0.01 to 2.11) (two trials, 323 participants); have any effect on all-cause mortality, no deaths reported (two trials, 326 participants); or increase the risk of alloimmunisation, risk ratio 3.16 (95% confidence interval 0.18 to 57.17) (one trial, 121 participants), very low quality evidence. Children and adolescents with previous long-term transfusions (one trial, 79 participants) We are very uncertain whether continuing long-term transfusions reduces the incidence of: stroke, risk ratio 0.22 (95% confidence interval 0.01 to 4.35); or all-cause mortality, Peto odds ratio 8.00 (95% confidence interval 0.16 to 404.12), very low quality evidence. Several review outcomes were only reported in one trial arm (sickle cell disease-related complications, alloimmunisation, transient ischaemic attacks). The trial did not report neurological impairment, or quality of life. Hydroxyurea and phlebotomy versus red cell transfusions and chelation Neither trial reported on neurological impairment, alloimmunisation, or quality of life. Primary prevention, children (one trial, 121 participants) Switching to hydroxyurea and phlebotomy may have little or no effect on liver iron concentrations, mean difference -1.80 mg Fe/g dry-weight liver (95% confidence interval -5.16 to 1.56), low quality evidence. We are very uncertain whether switching to hydroxyurea and phlebotomy has any effect on: risk of stroke (no strokes); all-cause mortality (no deaths); transient ischaemic attacks, risk ratio 1.02 (95% confidence interval 0.21 to 4.84); or other sickle cell disease-related complications (acute chest syndrome, risk ratio 2.03 (95% confidence interval 0.39 to 10.69)), very low quality evidence. Secondary prevention, children and adolescents (one trial, 133 participants) Switching to hydroxyurea and phlebotomy may: increase the risk of sickle cell disease-related serious adverse events, risk ratio 3.10 (95% confidence interval 1.42 to 6.75); but have little or no effect on median liver iron concentrations (hydroxyurea, 17.3 mg Fe/g dry-weight liver (interquartile range 10.0 to 30.6)); transfusion 17.3 mg Fe/g dry-weight liver (interquartile range 8.8 to 30.7), low quality evidence. We are very uncertain whether switching to hydroxyurea and phlebotomy: increases the risk of stroke, risk ratio 14.78 (95% confidence interval 0.86 to 253.66); or has any effect on all-cause mortality, Peto odds ratio 0.98 (95% confidence interval 0.06 to 15.92); or transient ischaemic attacks, risk ratio 0.66 (95% confidence interval 0.25 to 1.74), very low quality evidence. Authors’ conclusions There is no evidence for managing adults, or children who do not have HbSS sickle cell disease. In children who are at higher risk of stroke and have not had previous long-term transfusions, there is moderate quality evidence that long-term red cell transfusions reduce the risk of stroke, and low quality evidence they also reduce the risk of other sickle cell disease-related complications. In primary and secondary prevention of stroke there is low quality evidence that switching to hydroxyurea with phlebotomy has little or no effect on the liver iron concentration. In secondary prevention of stroke there is low-quality evidence that switching to hydroxyurea with phlebotomy increases the risk of sickle cell disease-related events. All other evidence in this review is of very low quality. PMID:24226646

Translating knowledge for action against stroke--using 5-minute videos for stroke survivors and caregivers to improve post-stroke outcomes: study protocol for a randomized controlled trial (Movies4Stroke).

PubMed

Kamal, Ayeesha Kamran; Khoja, Adeel; Usmani, Bushra; Muqeet, Abdul; Zaidi, Fabiha; Ahmed, Masood; Shakeel, Saadia; Soomro, Nabila; Gowani, Ambreen; Asad, Nargis; Ahmed, Asma; Sayani, Saleem; Azam, Iqbal; Saleem, Sarah

2016-01-27

Two thirds of the global mortality of stroke is borne by low and middle income countries (LMICs). Pakistan is the world's sixth most populous country with a stroke-vulnerable population and is without a single dedicated chronic care center. In order to provide evidence for a viable solution responsive to this health care gap, and leveraging the existing >70% mobile phone density, we thought it rational to test the effectiveness of a mobile phone-based video intervention of short 5-minute movies to educate and support stroke survivors and their primary caregivers. Movies4Stroke will be a randomized control, outcome assessor blinded, parallel group, single center superiority trial. Participants with an acute stroke, medically stable, with mild to moderate disability and having a stable primary caregiver will be included. After obtaining informed consent the stroke survivor-caregiver dyad will be randomized. Intervention participants will have the movie program software installed in their phone, desktop, or Android device which will allow them to receive, view and repeat 5-minute videos on stroke-related topics at admission, discharge and first and third months after enrollment. The control arm will receive standard of care at an internationally accredited center with defined protocols. The primary outcome measure is medication adherence as ascertained by a locally validated Morisky Medication Adherence Scale and control of major risk factors such as blood pressure, blood sugar and blood cholesterol at 12 months post discharge. Secondary outcome measures are post-stroke complications and mortality, caregiver knowledge and change in functional outcomes after acute stroke at 1, 3, 6, 9 and 12 months. Movies4Stroke is designed to enroll 300 participant dyads after inflating 10% to incorporate attrition and non-compliance and has been powered at 95% to detect a 15% difference between intervention and usual care arm. Analysis will be done by the intention-to-treat principle. Movies4Stroke is a randomized trial testing an application aimed at supporting caregivers and stroke survivors in a LMIC with no rehabilitation or chronic support systems. NCT02202330 (28 January 2015).

Exploratory Network Meta Regression Analysis of Stroke Prevention in Atrial Fibrillation Fails to Identify Any Interactions with Treatment Effect.

PubMed

Batson, Sarah; Sutton, Alex; Abrams, Keith

2016-01-01

Patients with atrial fibrillation are at a greater risk of stroke and therefore the main goal for treatment of patients with atrial fibrillation is to prevent stroke from occurring. There are a number of different stroke prevention treatments available to include warfarin and novel oral anticoagulants. Previous network meta-analyses of novel oral anticoagulants for stroke prevention in atrial fibrillation acknowledge the limitation of heterogeneity across the included trials but have not explored the impact of potentially important treatment modifying covariates. To explore potentially important treatment modifying covariates using network meta-regression analyses for stroke prevention in atrial fibrillation. We performed a network meta-analysis for the outcome of ischaemic stroke and conducted an exploratory regression analysis considering potentially important treatment modifying covariates. These covariates included the proportion of patients with a previous stroke, proportion of males, mean age, the duration of study follow-up and the patients underlying risk of ischaemic stroke. None of the covariates explored impacted relative treatment effects relative to placebo. Notably, the exploration of 'study follow-up' as a covariate supported the assumption that difference in trial durations is unimportant in this indication despite the variation across trials in the network. This study is limited by the quantity of data available. Further investigation is warranted, and, as justifying further trials may be difficult, it would be desirable to obtain individual patient level data (IPD) to facilitate an effort to relate treatment effects to IPD covariates in order to investigate heterogeneity. Observational data could also be examined to establish if there are potential trends elsewhere. The approach and methods presented have potentially wide applications within any indication as to highlight the potential benefit of extending decision problems to include additional comparators outside of those of primary interest to allow for the exploration of heterogeneity.

Review of the randomized clinical stroke rehabilitation trials in 2009

PubMed Central

Rabadi, Meheroz H.

2011-01-01

Summary Background Recent review of the available evidence on interventions for motor recovery after stroke, showed that improvements in recovery of arm function were seen for constraint-induced movement therapy, electromyographic biofeedback, mental practice with motor imagery, and robotics. Similar improvement in transfer ability or balance were seen with repetitive task training, biofeedback, and training with a moving platform. Walking speed was improved by physical fitness training, high-intensity physiotherapy and repetitive task training. However, most of these trials were small and had design limitations. Material/Methods In this article, randomized control trials (RCT’s) published in 2009 of rehabilitation therapies for acute (≤2 weeks), sub-acute (2 to 12 weeks) and chronic (≥12 weeks) stroke was reviewed. A Medline search was performed to identify all RCT’s in stroke rehabilitation in the year 2009. The search strategy that was used for PubMed is presented in the Appendix 1. The objective was to examine the effectiveness of these treatment modalities in stroke rehabilitation. Results This generated 35 RCT’s under 5 categories which were found and analyzed. The methodological quality was assessed by using the PEDro scale for external and internal validity. Conclusions These trials were primarily efficacy studies. Most of these studies enrolled small numbers of patient which precluded their clinical applicability (limited external validity). However, the constraint induced movement therapy (CIT), regularly used in chronic stroke patients did not improve affected arm-hand function when used in acute stroke patients at ≤4 weeks. Intensive CIT did not lead to motor improvement in arm-hand function. Robotic arm treatment helped decrease motor impairment and improved function in chronic stroke patients only. Therapist provided exercise programs (when self-administered by patients during their off-therapy time in a rehabilitation setting) did improve arm-hand function. Tai Chi exercises helped improve balance and weight bearing. Exercise programs for community dwelling stroke patient helped maintain and even improve their functional state. PMID:21278702

Review of the randomized clinical stroke rehabilitation trials in 2009.

PubMed

Rabadi, Meheroz H

2011-02-01

Recent review of the available evidence on interventions for motor recovery after stroke, showed that improvements in recovery of arm function were seen for constraint-induced movement therapy, electromyographic biofeedback, mental practice with motor imagery, and robotics. Similar improvement in transfer ability or balance were seen with repetitive task training, biofeedback, and training with a moving platform. Walking speed was improved by physical fitness training, high-intensity physiotherapy and repetitive task training. However, most of these trials were small and had design limitations. In this article, randomized control trials (RCT's) published in 2009 of rehabilitation therapies for acute (≤ 2 weeks), sub-acute (2 to 12 weeks) and chronic (≥ 12 weeks) stroke was reviewed. A Medline search was performed to identify all RCT's in stroke rehabilitation in the year 2009. The search strategy that was used for PubMed is presented in the Appendix 1. The objective was to examine the effectiveness of these treatment modalities in stroke rehabilitation. This generated 35 RCT's under 5 categories which were found and analyzed. The methodological quality was assessed by using the PEDro scale for external and internal validity. These trials were primarily efficacy studies. Most of these studies enrolled small numbers of patient which precluded their clinical applicability (limited external validity). However, the constraint induced movement therapy (CIT), regularly used in chronic stroke patients did not improve affected arm-hand function when used in acute stroke patients at ≤ 4 weeks. Intensive CIT did not lead to motor improvement in arm-hand function. Robotic arm treatment helped decrease motor impairment and improved function in chronic stroke patients only. Therapist provided exercise programs (when self-administered by patients during their off-therapy time in a rehabilitation setting) did improve arm-hand function. Tai Chi exercises helped improve balance and weight bearing. Exercise programs for community dwelling stroke patient helped maintain and even improve their functional state.

78 FR 72683 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-03

... Disorders and Stroke, Special Emphasis Panel, Stroke Trials Network-NDMC. Date: December 18, 2013. Time: 9... Program Nos. 93.853, Clinical Research Related to Neurological Disorders; 93.854, Biological Basis...

Role of inflammation and its mediators in acute ischemic stroke

PubMed Central

Jin, Rong; Liu, Lin; Zhang, Shihao; Nanda, Anil; Li, Guohong

2013-01-01

Inflammation plays an important role in the pathogenesis of ischemic stroke and other forms of ischemic brain injury. Increasing evidence suggests that inflammatory response is a double-edged sword, as it not only exacerbates secondary brain injury in the acute stage of stroke but also beneficially contributes to brain recovery after stroke. In this article, we provide an overview on the role of inflammation and its mediators in acute ischemic stroke. We discuss various pro-inflammatory and anti-inflammatory responses in different phases after ischemic stroke and the possible reasons for their failures in clinical trials. Undoubtedly, there is still much to be done in order to translate promising pre-clinical findings into clinical practice. A better understanding of the dynamic balance between pro- and anti-inflammatory responses and identifying the discrepancies between pre-clinical studies and clinical trials may serve as a basis for designing effective therapies. PMID:24006091

Prediction of motor recovery after stroke: advances in biomarkers.

PubMed

Stinear, Cathy M

2017-10-01

Stroke remains a leading cause of adult disability, and the recovery of motor function after stroke is crucial for the patient to regain independence. However, making accurate predictions of a patient's motor recovery and outcome is difficult when based on clinical assessment alone. Clinical assessment of motor impairment within a few days of stroke can help to predict subsequent recovery, while neurophysiological and neuroimaging biomarkers of corticomotor structure and function can help to predict both motor recovery and motor outcome after stroke. The combination of biomarkers can provide clinically useful information when planning the personalised rehabilitation of a patient. These biomarkers can also be used for patient selection and stratification in trials investigating rehabilitation interventions that are initiated early after stroke. Ongoing multicentre trials that incorporate motor biomarkers could help to bring their use into routine clinical practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cost-Effectiveness of Solitaire Stent Retriever Thrombectomy for Acute Ischemic Stroke: Results From the SWIFT-PRIME Trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke).

PubMed

Shireman, Theresa I; Wang, Kaijun; Saver, Jeffrey L; Goyal, Mayank; Bonafé, Alain; Diener, Hans-Christoph; Levy, Elad I; Pereira, Vitor M; Albers, Gregory W; Cognard, Christophe; Hacke, Werner; Jansen, Olav; Jovin, Tudor G; Mattle, Heinrich P; Nogueira, Raul G; Siddiqui, Adnan H; Yavagal, Dileep R; Devlin, Thomas G; Lopes, Demetrius K; Reddy, Vivek K; du Mesnil de Rochemont, Richard; Jahan, Reza; Vilain, Katherine A; House, John; Lee, Jin-Moo; Cohen, David J

2017-02-01

Clinical trials have demonstrated improved 90-day outcomes for patients with acute ischemic stroke treated with stent retriever thrombectomy plus tissue-type plasminogen activator (SST+tPA) compared with tPA. Previous studies suggested that this strategy may be cost-effective, but models were derived from pooled data and older assumptions. In this prospective economic substudy conducted alongside the SWIFT-PRIME trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), in-trial costs were measured for patients using detailed medical resource utilization and hospital billing data. Utility weights were assessed at 30 and 90 days using the EuroQol-5 dimension questionnaire. Post-trial costs and life-expectancy were estimated for each surviving patient using a model based on trial data and inputs derived from a contemporary cohort of ischemic stroke survivors. Index hospitalization costs were $17 183 per patient higher for SST+tPA than for tPA ($45 761 versus $28 578; P<0.001), driven by initial procedure costs. Between discharge and 90 days, costs were $4904 per patient lower for SST+tPA than for tPA ($11 270 versus $16 174; P=0.014); total 90-day costs remained higher with SST+tPA ($57 031 versus $44 752; P<0.001). Higher utility values for SST+tPA led to higher in-trial quality-adjusted life years (0.131 versus 0.105; P=0.005). In lifetime projections, SST+tPA was associated with substantial gains in quality-adjusted life years (6.79 versus 5.05), cost savings of $23 203 per patient and was economically dominant when compared with tPA in 90% of bootstrap replicates. Among patients with acute ischemic stroke enrolled in the SWIFT-PRIME trial, SST increased initial treatment costs, but was projected to improve quality-adjusted life-expectancy and reduce healthcare costs over a lifetime horizon compared with tPA. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461. © 2016 American Heart Association, Inc.

Methods to improve patient recruitment and retention in stroke trials.

PubMed

Berge, Eivind; Stapf, Christian; Al-Shahi Salman, Rustam; Ford, Gary A; Sandercock, Peter; van der Worp, H Bart; Petersson, Jesper; Dippel, Diederik Wj; Krieger, Derk W; Lees, Kennedy R

2016-08-01

The success of randomized-controlled stroke trials is dependent on the recruitment and retention of a sufficient number of patients, but fewer than half of all trials meet their target number of patients. We performed a search and review of the literature, and conducted a survey and workshop among 56 European stroke trialists, to identify barriers, suggest methods to improve recruitment and retention, and make a priority list of interventions that merit further evaluation. The survey and workshop identified a number of barriers to patient recruitment and retention, from patients' incapacity to consent, to handicaps that prevent patients from participation in trial-specific follow-up. Methods to improve recruitment and retention may include simple interventions with individual participants, funding of research networks, and reimbursement of new treatments by health services only when delivered within clinical trials. The literature review revealed that few methods have been formally evaluated. The top five priorities for evaluation identified in the workshop were as follows: short and illustrated patient information leaflets, nonwritten consent, reimbursement for new interventions only within a study, and monetary incentives to institutions taking part in research (for recruitment); and involvement of patient groups, remote and central follow-up, use of mobile devices, and reminders to patients about their consent to participate (for retention). Many interventions have been used with the aim of improving recruitment and retention of patients in stroke studies, but only a minority has been evaluated. We have identified methods that could be tested, and propose that such evaluations may be nested within on-going clinical trials. © 2016 World Stroke Organization.

Measurement properties of self-report physical activity assessment tools in stroke: a protocol for a systematic review

PubMed Central

Martins, Júlia Caetano; Aguiar, Larissa Tavares; Nadeau, Sylvie; Scianni, Aline Alvim; Teixeira-Salmela, Luci Fuscaldi; Faria, Christina Danielli Coelho de Morais

2017-01-01

Introduction Self-report physical activity assessment tools are commonly used for the evaluation of physical activity levels in individuals with stroke. A great variety of these tools have been developed and widely used in recent years, which justify the need to examine their measurement properties and clinical utility. Therefore, the main objectives of this systematic review are to examine the measurement properties and clinical utility of self-report measures of physical activity and discuss the strengths and limitations of the identified tools. Methods and analysis A systematic review of studies that investigated the measurement properties and/or clinical utility of self-report physical activity assessment tools in stroke will be conducted. Electronic searches will be performed in five databases: Medical Literature Analysis and Retrieval System Online (MEDLINE) (PubMed), Excerpta Medica Database (EMBASE), Physiotherapy Evidence Database (PEDro), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) and Scientific Electronic Library Online (SciELO), followed by hand searches of the reference lists of the included studies. Two independent reviewers will screen all retrieve titles, abstracts, and full texts, according to the inclusion criteria and will also extract the data. A third reviewer will be referred to solve any disagreement. A descriptive summary of the included studies will contain the design, participants, as well as the characteristics, measurement properties, and clinical utility of the self-report tools. The methodological quality of the studies will be evaluated using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist and the clinical utility of the identified tools will be assessed considering predefined criteria. This systematic review will follow the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. Discussion This systematic review will provide an extensive review of the measurement properties and clinical utility of self-report physical activity assessment tools used in individuals with stroke, which would benefit clinicians and researchers. Trial registration number PROSPERO CRD42016037146. PMID:28193848

A post hoc analysis of saxagliptin efficacy and safety in patients with type 2 diabetes stratified by UKPDS 10-year cardiovascular risk score.

PubMed

Bonora, E; Bryzinski, B; Hirshberg, B; Cook, W

2016-05-01

To assess the efficacy and safety of saxagliptin 2.5 and 5 mg/d in patients with type 2 diabetes mellitus (T2DM) and high risk of coronary heart disease (CHD) or stroke as estimated by the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. Post hoc analysis of data pooled from 5 previously reported phase 3, randomized, placebo-controlled, 24-week studies was conducted. Patients were stratified into subgroups by UKPDS 10-year CHD and/or stroke risk ≥20% and CHD and stroke risk <20%. End points were adjusted mean change from baseline in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), 120-min postprandial glucose (PPG), and body weight and the proportion of patients achieving HbA1c <7% and ≤8% at week 24. Pooled safety data were analyzed for adverse events (AEs) and hypoglycemia. Both doses of saxagliptin reduced HbA1c, FPG, and PPG to a greater extent than placebo regardless of UKPDS risk score. The proportions of patients achieving HbA1c <7% and ≤8% were greater with saxagliptin than placebo and consistent across risk score groups. AE profile and hypoglycemia incidence were similar for saxagliptin and placebo across UKPDS risk score groups. Saxagliptin was well tolerated and improved glycemic control in patients with T2DM regardless of their CHD and stroke UKPDS risk score. Clinical trial registration numbers: Clinicaltrials.gov NCT00121641, NCT00316082, NCT00121667, NCT00313313, and NCT00295633. Copyright © 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Fluid responsiveness predicted by transcutaneous partial pressure of oxygen in patients with circulatory failure: a prospective study.

PubMed

Xu, Jingyuan; Peng, Xiao; Pan, Chun; Cai, Shixia; Zhang, Xiwen; Xue, Ming; Yang, Yi; Qiu, Haibo

2017-12-01

Significant effort has been devoted to defining parameters for predicting fluid responsiveness. Our goal was to study the feasibility of predicting fluid responsiveness by transcutaneous partial pressure of oxygen (PtcO 2 ) in the critically ill patients. This was a single-center prospective study conducted in the intensive care unit of a tertiary care teaching hospital. Shock patients who presented with at least one clinical sign of inadequate tissue perfusion, defined as systolic blood pressure <90 mmHg or a decrease >40 mmHg in previously hypertensive patients or the need for vasopressive drugs; urine output <0.5 ml/kg/h for 2 h; tachycardia; lactate >4 mmol/l, for less than 24 h in the absence of a contraindication for fluids were eligible to participate in the study. PtcO 2 was continuously recorded before and during a passive leg raising (PLR) test, and then before and after a 250 ml rapid saline infusion in 10 min. Fluid responsiveness is defined as a change in the stroke volume ≥10% after 250 ml of volume infusion. Thirty-four patients were included, and 14 responded to volume expansion. In the responders, the mean arterial pressure, central venous pressure, cardiac output, stroke volume and PtcO 2 increased significantly, while the heart rate decreased significantly by both PLR and volume expansion. Changes in the stroke volume induced either by PLR or volume expansion were significantly greater in responders than in non-responders. The correlation between the changes in PtcO 2 and stroke volume induced by volume expansion was significant. Volume expansion induced an increase in the PtcO 2 of 14% and PLR induced an increase in PtcO 2 of 13% predicted fluid responsiveness. This study suggested the changes in PtcO 2 induced by volume expansion and a PLR test predicted fluid responsiveness in critically ill patients. Trial registration NCT02083757.

Systematic review of mirror therapy compared with conventional rehabilitation in upper extremity function in stroke survivors.

PubMed

Pérez-Cruzado, David; Merchán-Baeza, Jose Antonio; González-Sánchez, Manuel; Cuesta-Vargas, Antonio I

2017-04-01

Stroke is a leading cause of disability in developed countries. One of the most widespread techniques in clinical practice is mirror therapy (MT). To determine the effectiveness of MT over other methods of intervention in the recovery of upper limb function in people who have had a stroke. A systematic review was conducted. The search string was established based on the last systematic review about MT that dated from 2009: "upper extremity" OR "upper limb "AND "mirror therapy" AND stroke. For this search Pubmed, Scopus and SciELO databases were used. Fifteen studies were included in the systematic review. Recovery of the upper limb, upper limb function and gross manual dexterity were frequently measured in these studies. In the primary variables in promoting recovery, MT alone showed better results in acute and chronic stroke patients in upper limb functioning than either conventional rehabilitation (CR) or CR plus MT. PROSPERO registration number: CRD42015026869. © 2016 Occupational Therapy Australia.

Stroke rehabilitation evidence and comorbidity: a systematic scoping review of randomized controlled trials.

PubMed

Nelson, Michelle L A; McKellar, Kaileah A; Yi, Juliana; Kelloway, Linda; Munce, Sarah; Cott, Cheryl; Hall, Ruth; Fortin, Martin; Teasell, Robert; Lyons, Renee

2017-07-01

Most strokes occur in the context of other medical diagnoses. Currently, stroke rehabilitation evidence reviews have not synthesized or presented evidence with a focus on comorbidities and correspondingly may not align with current patient population. The purpose of this review was to determine the extent and nature of randomized controlled trial stroke rehabilitation evidence that included patients with multimorbidity. A systematic scoping review was conducted. Electronic databases were searched using a combination of terms related to "stroke" and "rehabilitation." Selection criteria captured inpatient rehabilitation studies. Methods were modified to account for the amount of literature, classified by study design, and randomized controlled trials (RCTs) were abstracted. The database search yielded 10771 unique articles. Screening resulted in 428 included RCTs. Three studies explicitly included patients with a comorbid condition. Fifteen percent of articles did not specify additional conditions that were excluded. Impaired cognition was the most commonly excluded condition. Approximately 37% of articles excluded patients who had experienced a previous stroke. Twenty-four percent excluded patients one or more Charlson Index condition, and 83% excluded patients with at least one other medical condition. This review represents a first attempt to map literature on stroke rehabilitation related to co/multimorbidity and identify gaps in existing research. Existing evidence on stroke rehabilitation often excluded individuals with comorbidities. This is problematic as the evidence that is used to generate clinical guidelines may not match the patient typically seen in practice. The use of alternate research methods are therefore needed for studying the care of individuals with stroke and multimorbidity.

A randomized controlled trial on rehabilitation through caregiver-delivered nurse-organized service programs for disabled stroke patients in rural china (the RECOVER trial): design and rationale.

PubMed

Yan, Lijing L; Chen, Shu; Zhou, Bo; Zhang, Jing; Xie, Bin; Luo, Rong; Wang, Ninghua; Lindley, Richard; Zhang, Yuhong; Zhao, Yi; Li, Xian; Liu, Xiao; Peoples, Nicholas; Bettger, Janet Prvu; Anderson, Craig; Lamb, Sarah E; Wu, Yangfeng; Shi, Jingpu

2016-10-01

Stroke is the leading cause of death and disability in rural China. For stroke patients residing in resource-limited rural areas, secondary prevention and rehabilitation are largely unavailable, and where present, are far below evidence-based standards. This study aims to develop and implement a simplified stroke rehabilitation program that utilizes nurses and family caregivers for service delivery, and evaluate its feasibility and effectiveness in rural China. This 2-year randomized controlled trial is being conducted in 2-3 county hospitals located in northwest, northeast, and southwest China. Eligible and consenting stroke inpatients (200 in total) have been recruited and randomized into either a control or intervention group. Nurses in the county hospital are trained by rehabilitation specialists and in turn train the family caregivers in the intervention group. They also provide telephone follow-up care three times post discharge. The recruitment, baseline, intervention, follow-up care, and evaluation are guided by the RECOVER mobile phone app specifically designed for this study. The primary outcome is patients' Barthel Index (activities of daily living: mobility, self-care, and toileting) at 6 months. Process and economic evaluation will also be conducted. The results of our study will generate initial high-quality evidence to improve stroke care in resource-scarce settings. If proven effective, this innovative care delivery model has the potential to improve the health and function of stroke patients, relieve caregiver burden, guide policy-making, and advance translational research in the field of stroke care. © 2016 World Stroke Organization.

Nursing home care educational intervention for family caregivers of older adults post stroke (SHARE): study protocol for a randomised trial.

PubMed

Day, Carolina Baltar; Bierhals, Carla Cristiane Becker Kottwitz; Santos, Naiana Oliveira Dos; Mocellin, Duane; Predebon, Mariane Lurdes; Dal Pizzol, Fernanda Laís Fengler; Paskulin, Lisiane Manganelli Girardi

2018-02-09

Family caregivers of aged stroke survivors face challenging difficulties such as the lack of support and the knowledge and skills to practice home care. These aspects negatively influence the caregivers' burden and quality of life, the use of health services, and hospital readmissions of the stroke survivor. The aim of this research is to describe an educational intervention focused on family caregivers of stroke survivors for the development of home care in the south of Brazil. A randomized clinical trial with 48 family caregivers of stroke survivors will be recruited and divided into two groups: 24 in the intervention group and 24 in the control group. The intervention will consist of the systematic follow-up by nurses who will perform three home visits over a period of 1 month. The control group will not receive the visits and will have the usual care guidelines of the health services. Primary outcomes: burden and quality of life of the caregiver. functional capacity and readmissions of the stroke survivors; the use of health services of the stroke survivors and their family caregivers. Outcomes will be measured 2 months after discharge. The project was approved in April 2016. This research offers information for conducting educational intervention with family caregivers of stroke survivors, presenting knowledge so that nurses can structure and plan the actions aimed at the education of the family caregiver. It is expected that the educational intervention will contribute to reducing caregiver burden and improving their quality of life, as well as avoiding readmissions and inadequate use of health services by stroke survivors. ClinicalTrials.gov, ID: NCT02807012 . Registered on 3 June 2016. Name: Nursing Home Care Intervention Post Stroke (SHARE).

Atrial fibrillation detected by continuous electrocardiographic monitoring using implantable loop recorder to prevent stroke in individuals at risk (the LOOP study): Rationale and design of a large randomized controlled trial.

PubMed

Diederichsen, Søren Zöga; Haugan, Ketil Jørgen; Køber, Lars; Højberg, Søren; Brandes, Axel; Kronborg, Christian; Graff, Claus; Holst, Anders Gaarsdal; Nielsen, Jonas Bille; Krieger, Derk; Svendsen, Jesper Hastrup

2017-05-01

Atrial fibrillation (AF) increases the rate of stroke 5-fold, and AF-related strokes have a poorer prognosis compared with non-AF-related strokes. Atrial fibrillation and stroke constitute an intensifying challenge, and health care organizations are calling for awareness on the topic. Previous studies have demonstrated that AF is often asymptomatic and consequently undiagnosed. The implantable loop recorder (ILR) allows for continuous, long-term electrocardiographic monitoring with daily transmission of arrhythmia information, potentially leading to improvement in AF detection and stroke prevention. The LOOP study is an investigator-initiated, randomized controlled trial with 6,000 participants randomized 3:1 to a control group or to receive an ILR with continuous electrocardiographic monitoring. Participants are identified from Danish registries and are eligible for inclusion if 70years or older and previously diagnosed as having at least one of the following conditions: hypertension, diabetes mellitus, heart failure, or previous stroke. Exclusion criteria include history of AF and current oral anticoagulation treatment. When an AF episode lasting ≥6minutes is detected, oral anticoagulation will be initiated according to guidelines. Expected follow-up is 4years. The primary end point is time to stroke or systemic embolism, whereas secondary end points include time to AF diagnosis and death. The LOOP study will evaluate health benefits and cost-effectiveness of ILR as a screening tool for AF to prevent stroke in patients at risk. Secondary objectives include identification of risk factors for the development of AF and characterization of arrhythmias in the population. The trial holds the potential to influence the future of stroke prevention. Copyright © 2017 Elsevier Inc. All rights reserved.

75 FR 2149 - National Institute of Neurological Disorders and Stroke; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-14

... Neurological Disorders and Stroke; Notice of Meeting Pursuant to section 10(d) of the Federal Advisory... Neurological Disorders and Stroke Council. The meeting will be open to the public as indicated below, with... Disorders and Stroke Council, Clinical Trials Subcommittee. Date: February 3-4, 2010. [[Page 2150

[Mobile stroke unit for prehospital stroke treatment].

PubMed

Walter, S; Grunwald, I Q; Fassbender, K

2016-01-01

The management of acute stroke patients suffers from several major problems in the daily clinical routine. In order to achieve optimal treatment a complex diagnostic work-up and rapid initiation of therapy are necessary; however, most patients arrive at hospital too late for any type of acute stroke treatment, although all forms of treatment are highly time-dependent according to the generally accepted "time is brain" concept. Recently, two randomized clinical trials demonstrated the feasibility of prehospital stroke diagnostic work-up and treatment. This was accomplished by use of a specialized ambulance, equipped with computed tomography for multimodal imaging and a point-of-care laboratory system. In both trials the results demonstrated a clear superiority of the prehospital treatment group with a significant reduction of treatment times, significantly increased number of patients treated within the first 60 min after symptom onset and an optimized triage to the correct target hospital. Currently, mobile stroke units are in operation in various countries and should lead to an improvement in stroke treatment; nevertheless, intensive research is still needed to analyze the best framework settings for prehospital stroke management.

Changes to registration elements and results in a cohort of Clinicaltrials.gov trials were not reflected in published articles.

PubMed

Pranić, Shelly; Marušić, Ana

2016-02-01

To assess effectiveness of legislative initiatives to stimulate public registration of trial results, we assessed adherence to protocol and results reporting, changes to registry, and publication data for randomized controlled trials (RCTs) after introduction of Food and Drug Administration Amendment Act (FDAAA). Observational study of a cohort of ClinicalTrials.gov registered FDAAA-covered RCTs found through ClinicalTrials.gov between 2009 and 2012 and data from corresponding publications. WHO Minimum Data Set items were abstracted by one author and verified by the other author. Among 81 eligible trials, most were industry-funded, with a drug intervention in parallel assignment. Secondary outcomes at the initial and last registration were omitted for 17% and 19.7% of RCTs, respectively. RCT registration changes mostly involved scientific title (18.8%). Inclusion criteria omission was most common (88%) in publications. Inferential statistical methods for primary and secondary outcomes matched between registry and publication for 53.4% and 28.6% of RCTs, respectively. Serious and other adverse events (AEs) that were absent for 23.8% and 4.8% of RCTs, respectively, were published as nonoccurring. Discrepancies remain relatively high between registered and published outcomes, particularly regarding registered omissions in publications and concomitant reporting, nature of statistical method used, and reporting of AEs. This seriously undermines transparency of clinical trials and needs immediate attention of all stakeholders in health research. Copyright © 2016 Elsevier Inc. All rights reserved.

ClinicalTrials.gov registration can supplement information in abstracts for systematic reviews: a comparison study.

PubMed

Scherer, Roberta W; Huynh, Lynn; Ervin, Ann-Margret; Taylor, Jakeisha; Dickersin, Kay

2013-06-18

The inclusion of randomized controlled trials (RCTs) reported in conference abstracts in systematic reviews is controversial, partly because study design information and risk of bias is often not fully reported in the abstract. The Association for Research in Vision and Ophthalmology (ARVO) requires trial registration of abstracts submitted for their annual conference as of 2007. Our goal was to assess the feasibility of obtaining study design information critical to systematic reviews, but not typically included in conference abstracts, from the trial registration record. We reviewed all conference abstracts presented at the ARVO meetings from 2007 through 2009, and identified 496 RCTs; 154 had a single matching registration record in ClinicalTrials.gov. Two individuals independently extracted information from the abstract and the ClinicalTrials.gov record, including study design, sample size, inclusion criteria, masking, interventions, outcomes, funder, and investigator name and contact information. Discrepancies were resolved by consensus. We assessed the frequencies of reporting variables appearing in the abstract and the trial register and assessed agreement of information reported in both sources. We found a substantial amount of study design information in the ClinicalTrials.gov record that was unavailable in the corresponding conference abstract, including eligibility criteria associated with gender (83%; 128/154); masking or blinding of study participants (53%, 82/154), persons administering treatment (30%, 46/154), and persons measuring the outcomes (40%, 61/154)); and number of study centers (58%; 90/154). Only 34% (52/154) of abstracts explicitly described a primary outcome, but a primary outcome was included in the "Primary Outcome" field in the ClinicalTrials.gov record for 82% (126/154) of studies. One or more study interventions were reported in each abstract, but agreed exactly with those reported in ClinicalTrials.gov only slightly more than half the time (88/154, 56%). We found no contact information for study investigators in the abstract, but this information was available in less than one quarter of ClinicalTrial.gov records (17%; 26/154). RCT design information not reported in conference abstracts is often available in the corresponding ClinicalTrials.gov registration record. Sometimes there is conflicting information reported in the two sources and further contact with the trial investigators may still be required.

ClinicalTrials.gov registration can supplement information in abstracts for systematic reviews: a comparison study

PubMed Central

2013-01-01

Background The inclusion of randomized controlled trials (RCTs) reported in conference abstracts in systematic reviews is controversial, partly because study design information and risk of bias is often not fully reported in the abstract. The Association for Research in Vision and Ophthalmology (ARVO) requires trial registration of abstracts submitted for their annual conference as of 2007. Our goal was to assess the feasibility of obtaining study design information critical to systematic reviews, but not typically included in conference abstracts, from the trial registration record. Methods We reviewed all conference abstracts presented at the ARVO meetings from 2007 through 2009, and identified 496 RCTs; 154 had a single matching registration record in ClinicalTrials.gov. Two individuals independently extracted information from the abstract and the ClinicalTrials.gov record, including study design, sample size, inclusion criteria, masking, interventions, outcomes, funder, and investigator name and contact information. Discrepancies were resolved by consensus. We assessed the frequencies of reporting variables appearing in the abstract and the trial register and assessed agreement of information reported in both sources. Results We found a substantial amount of study design information in the ClinicalTrials.gov record that was unavailable in the corresponding conference abstract, including eligibility criteria associated with gender (83%; 128/154); masking or blinding of study participants (53%, 82/154), persons administering treatment (30%, 46/154), and persons measuring the outcomes (40%, 61/154)); and number of study centers (58%; 90/154). Only 34% (52/154) of abstracts explicitly described a primary outcome, but a primary outcome was included in the “Primary Outcome” field in the ClinicalTrials.gov record for 82% (126/154) of studies. One or more study interventions were reported in each abstract, but agreed exactly with those reported in ClinicalTrials.gov only slightly more than half the time (88/154, 56%). We found no contact information for study investigators in the abstract, but this information was available in less than one quarter of ClinicalTrial.gov records (17%; 26/154). Conclusion RCT design information not reported in conference abstracts is often available in the corresponding ClinicalTrials.gov registration record. Sometimes there is conflicting information reported in the two sources and further contact with the trial investigators may still be required. PMID:23773868

Transcranial laser therapy in acute stroke treatment: results of neurothera effectiveness and safety trial 3, a phase III clinical end point device trial.

PubMed

Hacke, Werner; Schellinger, Peter D; Albers, Gregory W; Bornstein, Natan M; Dahlof, Bjorn L; Fulton, Rachael; Kasner, Scott E; Shuaib, Ashfaq; Richieri, Steven P; Dilly, Stephen G; Zivin, Justin; Lees, Kennedy R

2014-11-01

On the basis of phase II trials, we considered that transcranial laser therapy could have neuroprotective effects in patients with acute ischemic stroke. We studied transcranial laser therapy in a double-blind, sham-controlled randomized clinical trial intended to enroll 1000 patients with acute ischemic stroke treated ≤24 hours after stroke onset and who did not undergo thrombolytic therapy. The primary efficacy measure was the 90-day functional outcome as assessed by the modified Rankin Scale, with hierarchical Bayesian analysis incorporating relevant previous data. Interim analyses were planned after 300 and 600 patients included. The study was terminated on recommendation by the Data Monitoring Committee after a futility analysis of 566 completed patients found no difference in the primary end point (transcranial laser therapy 140/282 [49.6%] versus sham 140/284 [49.3%] for good functional outcome; modified Rankin Scale, 0-2). The results remained stable after inclusion of all 630 randomized patients (adjusted odds ratio, 1.024; 95% confidence interval, 0.705-1.488). Once the results of the interim futility analysis became available, all study support was immediately withdrawn by the capital firms behind PhotoThera, and the company was dissolved. Proper termination of the trial was difficult but was finally achieved through special efforts by former employees of PhotoThera, the CRO Parexel and members of the steering and the safety committees. We conclude that transcranial laser therapy does not have a measurable neuroprotective effect in patients with acute ischemic stroke when applied within 24 hours after stroke onset. http://www.clinicaltrials.gov. Unique identifier: NCT01120301. © 2014 American Heart Association, Inc.

ICARUSS, the Integrated Care for the Reduction of Secondary Stroke trial: rationale and design of a randomized controlled trial of a multimodal intervention to prevent recurrent stroke in patients with a recent cerebrovascular event, ACTRN = 12611000264987.

PubMed

Joubert, J; Davis, S M; Hankey, G J; Levi, C; Olver, J; Gonzales, G; Donnan, G A

2015-07-01

The majority of strokes, both ischaemic and haemorrhagic, are attributable to a relatively small number of risk factors which are readily manageable in primary care setting. Implementation of best-practice recommendations for risk factor management is calculated to reduce stroke recurrence by around 80%. However, risk factor management in stroke survivors has generally been poor at primary care level. A model of care that supports long-term effective risk factor management is needed. To determine whether the model of Integrated Care for the Reduction of Recurrent Stroke (ICARUSS) will, through promotion of implementation of best-practice recommendations for risk factor management reduce the combined incidence of stroke, myocardial infarction and vascular death in patients with recent stroke or transient ischaemic attack (TIA) of the brain or eye. A prospective, Australian, multicentre, randomized controlled trial. Academic stroke units in Melbourne, Perth and the John Hunter Hospital, New South Wales. 1000 stroke survivors recruited as from March 2007 with a recent (<3 months) stroke (ischaemic or haemorrhagic) or a TIA (brain or eye). Randomization and data collection are performed by means of a central computer generated telephone system (IVRS). Exposure to the ICARUSS model of integrated care or usual care. The composite of stroke, MI or death from any vascular cause, whichever occurs first. Risk factor management in the community, depression, quality of life, disability and dementia. With 1000 patients followed up for a median of one-year, with a recurrence rate of 7-10% per year in patients exposed to usual care, the study will have at least 80% power to detect a significant reduction in primary end-points The ICARUSS study aims to recruit and follow up patients between 2007 and 2013 and demonstrate the effectiveness of exposure to the ICARUSS model in stroke survivors to reduce recurrent stroke or vascular events and promote the implementation of best practice risk factor management at primary care level. © 2015 World Stroke Organization.

Development and validation of a patient-reported outcome measure for stroke patients.

PubMed

Luo, Yanhong; Yang, Jie; Zhang, Yanbo

2015-05-08

Family support and patient satisfaction with treatment are crucial for aiding in the recovery from stroke. However, current validated stroke-specific questionnaires may not adequately capture the impact of these two variables on patients undergoing clinical trials of new drugs. Therefore, the aim of this study was to develop and evaluate a new stroke patient-reported outcome measure (Stroke-PROM) instrument for capturing more comprehensive effects of stroke on patients participating in clinical trials of new drugs. A conceptual framework and a pool of items for the preliminary Stroke-PROM were generated by consulting the relevant literature and other questionnaires created in China and other countries, and interviewing 20 patients and 4 experts to ensure that all germane parameters were included. During the first item-selection phase, classical test theory and item response theory were applied to an initial scale completed by 133 patients with stroke. During the item-revaluation phase, classical test theory and item response theory were used again, this time with 475 patients with stroke and 104 healthy participants. During the scale assessment phase, confirmatory factor analysis was applied to the final scale of the Stroke-PROM using the same study population as in the second item-selection phase. Reliability, validity, responsiveness and feasibility of the final scale were tested. The final scale of Stroke-PROM contained 46 items describing four domains (physiology, psychology, society and treatment). These four domains were subdivided into 10 subdomains. Cronbach's α coefficients for the four domains ranged from 0.861 to 0.908. Confirmatory factor analysis supported the validity of the final scale, and the model fit index satisfied the criterion. Differences in the Stroke-PROM mean scores were significant between patients with stroke and healthy participants in nine subdomains (P < 0.001), indicating that the scale showed good responsiveness. The Stroke-PROM is a patient-reported outcome multidimensional questionnaire developed especially for clinical trials of new drugs and is focused on issues of family support and patient satisfaction with treatment. Extensive data analyses supported the validity, reliability and responsiveness of the Stroke-PROM.

Renal dysfunction as a predictor of stroke and systemic embolism in patients with nonvalvular atrial fibrillation: validation of the R(2)CHADS(2) index in the ROCKET AF (Rivaroxaban Once-daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) and ATRIA (AnTicoagulation and Risk factors In Atrial fibrillation) study cohorts.

PubMed

Piccini, Jonathan P; Stevens, Susanna R; Chang, YuChiao; Singer, Daniel E; Lokhnygina, Yuliya; Go, Alan S; Patel, Manesh R; Mahaffey, Kenneth W; Halperin, Jonathan L; Breithardt, Günter; Hankey, Graeme J; Hacke, Werner; Becker, Richard C; Nessel, Christopher C; Fox, Keith A A; Califf, Robert M

2013-01-15

We sought to define the factors associated with the occurrence of stroke and systemic embolism in a large, international atrial fibrillation (AF) trial. In ROCKET AF (Rivaroxaban Once-daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation), 14 264 patients with nonvalvular AF and creatinine clearance ≥30 mL/min were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards modeling was used to identify factors at randomization independently associated with the occurrence of stroke or non-central nervous system embolism based on intention-to-treat analysis. A risk score was developed in ROCKET AF and validated in ATRIA (AnTicoagulation and Risk factors In Atrial fibrillation), an independent AF patient cohort. Over a median follow-up of 1.94 years, 575 patients (4.0%) experienced primary end-point events. Reduced creatinine clearance was a strong, independent predictor of stroke and systemic embolism, second only to prior stroke or transient ischemic attack. Additional factors associated with stroke and systemic embolism included elevated diastolic blood pressure and heart rate, as well as vascular disease of the heart and limbs (C-index 0.635). A model that included creatinine clearance (R(2)CHADS(2)) improved net reclassification index by 6.2% compared with CHA(2)DS(2)VASc (C statistic=0.578) and by 8.2% compared with CHADS(2) (C statistic=0.575). The inclusion of creatinine clearance <60 mL/min and prior stroke or transient ischemic attack in a model with no other covariates led to a C statistic of 0.590.Validation of R(2)CHADS(2) in an external, separate population improved net reclassification index by 17.4% (95% confidence interval, 12.1%-22.5%) relative to CHADS(2). In patients with nonvalvular AF at moderate to high risk of stroke, impaired renal function is a potent predictor of stroke and systemic embolism. Stroke risk stratification in patients with AF should include renal function. URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00403767.

Gait training assisted by multi-channel functional electrical stimulation early after stroke: study protocol for a randomized controlled trial.

PubMed

van Bloemendaal, Maijke; Bus, Sicco A; de Boer, Charlotte E; Nollet, Frans; Geurts, Alexander C H; Beelen, Anita

2016-10-01

Many stroke survivors suffer from paresis of lower limb muscles, resulting in compensatory gait patterns characterised by asymmetries in spatial and temporal parameters and reduced walking capacity. Functional electrical stimulation has been used to improve walking capacity, but evidence is mostly limited to the orthotic effects of peroneal functional electrical stimulation in the chronic phase after stroke. The aim of this study is to investigate the therapeutic effects of up to 10 weeks of multi-channel functional electrical stimulation (MFES)-assisted gait training on the restoration of spatiotemporal gait symmetry and walking capacity in subacute stroke patients. In a proof-of-principle study with a randomised controlled design, 40 adult patients with walking deficits who are admitted for inpatient rehabilitation within 31 days since the onset of stroke are randomised to either MFES-assisted gait training or conventional gait training. Gait training is delivered in 30-minute sessions each workday for up to 10 weeks. The step length symmetry ratio is the primary outcome. Blinded assessors conduct outcome assessments at baseline, every 2 weeks during the intervention period, immediately post intervention and at 3-month follow-up. This study aims to provide preliminary evidence for the feasibility and effectiveness of MFES-assisted gait rehabilitation early after stroke. Results will inform the design of a larger multi-centre trial. This trial is registered at the Netherlands Trial Register (number NTR4762 , registered 28 August 2014).

Granulocyte-Colony Stimulating Factor (G-CSF) for stroke: an individual patient data meta-analysis.

PubMed

England, Timothy J; Sprigg, Nikola; Alasheev, Andrey M; Belkin, Andrey A; Kumar, Amit; Prasad, Kameshwar; Bath, Philip M

2016-11-15

Granulocyte colony stimulating factor (G-CSF) may enhance recovery from stroke through neuroprotective mechanisms if administered early, or neurorepair if given later. Several small trials suggest administration is safe but effects on efficacy are unclear. We searched for randomised controlled trials (RCT) assessing G-CSF in patients with hyperacute, acute, subacute or chronic stroke, and asked Investigators to share individual patient data on baseline characteristics, stroke severity and type, end-of-trial modified Rankin Scale (mRS), Barthel Index, haematological parameters, serious adverse events and death. Multiple variable analyses were adjusted for age, sex, baseline severity and time-to-treatment. Individual patient data were obtained for 6 of 10 RCTs comprising 196 stroke patients (116 G-CSF, 80 placebo), mean age 67.1 (SD 12.9), 92% ischaemic, median NIHSS 10 (IQR 5-15), randomised 11 days (interquartile range IQR 4-238) post ictus; data from three commercial trials were not shared. G-CSF did not improve mRS (ordinal regression), odds ratio OR 1.12 (95% confidence interval 0.64 to 1.96, p = 0.62). There were more patients with a serious adverse event in the G-CSF group (29.6% versus 7.5%, p = 0.07) with no significant difference in all-cause mortality (G-CSF 11.2%, placebo 7.6%, p = 0.4). Overall, G-CSF did not improve stroke outcome in this individual patient data meta-analysis.

Interventions for preventing silent cerebral infarcts in people with sickle cell disease

PubMed Central

Estcourt, Lise J; Fortin, Patricia M; Hopewell, Sally; Trivella, Marialena; Doree, Carolyn; Abboud, Miguel R

2017-01-01

Background Sickle cell disease (SCD) is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Silent cerebral infarcts are the commonest neurological complication in children and probably adults with SCD. Silent cerebral infarcts also affect academic performance, increase cognitive deficits and may lower intelligence quotient. Objectives To assess the effectiveness of interventions to reduce or prevent silent cerebral infarcts in people with SCD. Search methods We searched for relevant trials in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to 19 September 2016. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register: 06 October 2016. Selection criteria Randomised controlled trials comparing interventions to prevent silent cerebral infarcts in people with SCD. There were no restrictions by outcomes examined, language or publication status. Data collection and analysis We used standard Cochrane methodological procedures. Main results We included five trials (660 children or adolescents) published between 1998 and 2016. Four of the five trials were terminated early. The vast majority of participants had the haemoglobin (Hb)SS form of SCD. One trial focused on preventing silent cerebral infarcts or stroke; three trials were for primary stroke prevention and one trial dealt with secondary stroke prevention. Three trials compared the use of regular long-term red blood cell transfusions to standard care. Two of these trials included children with no previous long-term transfusions: one in children with normal transcranial doppler (TCD) velocities; and one in children with abnormal TCD velocities. The third trial included children and adolescents on long-term transfusion. Two trials compared the drug hydroxyurea and phlebotomy to long-term transfusions and iron chelation therapy: one in primary prevention (children), and one in secondary prevention (children and adolescents). The quality of the evidence was moderate to very low across different outcomes according to GRADE methodology. This was due to trials being at high risk of bias because they were unblinded; indirectness (available evidence was only for children with HbSS); and imprecise outcome estimates. Long-term red blood cell transfusions versus standard care Children with no previous long-term transfusions and higher risk of stroke (abnormal TCD velocities or previous history of silent cerebral infarcts) Long-term red blood cell transfusions may reduce the incidence of silent cerebral infarcts in children with abnormal TCD velocities, risk ratio (RR) 0.11 (95% confidence interval (CI) 0.02 to 0.86) (one trial, 124 participants, low-quality evidence); but make little or no difference to the incidence of silent cerebral infarcts in children with previous silent cerebral infarcts on magnetic resonance imaging and normal or conditional TCDs, RR 0.70 (95% CI 0.23 to 2.13) (one trial, 196 participants, low-quality evidence). No deaths were reported in either trial. Long-term red blood cell transfusions may reduce the incidence of: acute chest syndrome, RR 0.24 (95% CI 0.12 to 0.49) (two trials, 326 participants, low-quality evidence); and painful crisis, RR 0.63 (95% CI 0.42 to 0.95) (two trials, 326 participants, low-quality evidence); and probably reduces the incidence of clinical stroke, RR 0.12 (95% CI 0.03 to 0.49) (two trials, 326 participants, moderate-quality evidence). Long-term red blood cell transfusions may improve quality of life in children with previous silent cerebral infarcts (difference estimate -0.54; 95% confidence interval -0.92 to -0.17; one trial; 166 participants), but may have no effect on cognitive function (least squares means: 1.7, 95% CI -1.1 to 4.4) (one trial, 166 participants, low-quality evidence). Transfusions continued versus transfusions halted: children and adolescents with normalised TCD velocities (79 participants; one trial) Continuing red blood cell transfusions may reduce the incidence of silent cerebral infarcts, RR 0.29 (95% CI 0.09 to 0.97 (low-quality evidence). We are very uncertain whether continuing red blood cell transfusions has any effect on all-cause mortality, Peto odds ratio (OR) 8.00 (95% CI 0.16 to 404.12); or clinical stroke, RR 0.22 (95% CI 0.01 to 4.35) (very low-quality evidence). The trial did not report: comparative numbers for SCD-related adverse events; quality of life; or cognitive function. Hydroxyurea and phlebotomy versus transfusions and chelation Primary prevention, children (121 participants; one trial) We are very uncertain whether switching to hydroxyurea and phlebotomy has any effect on: silent cerebral infarcts (no infarcts); all-cause mortality (no deaths); risk of stroke (no strokes); or SCD-related complications, RR 1.52 (95% CI 0.58 to 4.02) (very low-quality evidence). Secondary prevention, children and adolescents with a history of stroke (133 participants; one trial) We are very uncertain whether switching to hydroxyurea and phlebotomy has any effect on: silent cerebral infarcts, Peto OR 7.28 (95% CI 0.14 to 366.91); all-cause mortality, Peto OR 1.02 (95% CI 0.06 to 16.41); or clinical stroke, RR 14.78 (95% CI 0.86 to 253.66) (very low-quality evidence). Switching to hydroxyurea and phlebotomy may increase the risk of SCD-related complications, RR 3.10 (95% CI 1.42 to 6.75) (low-quality evidence). Neither trial reported on quality of life or cognitive function. Authors’ conclusions We identified no trials for preventing silent cerebral infarcts in adults, or in children who do not have HbSS SCD. Long-term red blood cell transfusions may reduce the incidence of silent cerebral infarcts in children with abnormal TCD velocities, but may have little or no effect on children with normal TCD velocities. In children who are at higher risk of stroke and have not had previous long-term transfusions, long-term red blood cell transfusions probably reduce the risk of stroke, and other SCD-related complications (acute chest syndrome and painful crises). In children and adolescents at high risk of stroke whose TCD velocities have normalised, continuing red blood cell transfusions may reduce the risk of silent cerebral infarcts. No treatment duration threshold has been established for stopping transfusions. Switching to hydroxyurea with phlebotomy may increase the risk of silent cerebral infarcts and SCD-related serious adverse events in secondary stroke prevention. All other evidence in this review is of very low-quality. PMID:28500860

Citicoline for Acute Ischemic Stroke: A Systematic Review and Formal Meta-analysis of Randomized, Double-Blind, and Placebo-Controlled Trials.

PubMed

Secades, Julio J; Alvarez-Sabín, José; Castillo, José; Díez-Tejedor, Exuperio; Martínez-Vila, Eduardo; Ríos, José; Oudovenko, Natalia

2016-08-01

Citicoline is a drug approved for the treatment of acute ischemic stroke. Although evidence of its efficacy has been reported, recently published results of a large placebo-controlled clinical trial did not show differences. This study aims to assess whether starting citicoline treatment within 14 days after stroke onset improves the outcome in patients with acute ischemic stroke, as compared with placebo. A systematic search was performed to identify all published, unconfounded, randomized, double-blind, and placebo-controlled clinical trials of citicoline in acute ischemic stroke. Ten randomized clinical trials met our inclusion criteria. The administration of citicoline was associated with a significant higher rate of independence, independently of the method of evaluation used (odds ratio [OR] 1.56, 95% confidence interval [CI] = 1.12-2.16 under random effects; OR 1.20, 95% CI = 1.06-1.36 under fixed effects). After studying the cumulative meta-analysis, and with the results obtained with the subgroup of patients who were not treated with recombinant tissue plasminogen activator (rtPA) (OR 1.63, 95% CI = 1.18-2.24 under random effects; OR 1.42, 95% CI = 1.22-1.66 under fixed effects), our hypothesis of dilution of the effect of citicoline was confirmed. When we analyzed the effect of citicoline in patients who were not treated with rtPA and were receiving the highest dose of citicoline started in the first 24 hours after onset, based on more recent trials, there was no heterogeneity, and the size of the effect has an OR of 1.27 (95% CI = 1.05-1.53). This systematic review supports some benefits of citicoline in the treatment of acute ischemic stroke. But, on top of the best treatment available (rtPA), citicoline offers a limited benefit. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Physiotherapy treatment approaches for the recovery of postural control and lower limb function following stroke.

PubMed

Pollock, A; Baer, G; Pomeroy, V; Langhorne, P

2007-01-24

There are a number of different approaches to physiotherapy treatment following stroke that, broadly speaking, are based on neurophysiological, motor learning and orthopaedic principles. Some physiotherapists base their treatment on a single approach, while others use a mixture of components from a number of different approaches. To determine if there is a difference in the recovery of postural control and lower limb function in patients with stroke if physiotherapy treatment is based on orthopaedic or neurophysiological or motor learning principles, or on a mixture of these treatment principles. We searched the Cochrane Stroke Group Trials Register (last searched May 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2005), MEDLINE (1966 to May 2005), EMBASE (1980 to May 2005) and CINAHL (1982 to May 2005). We contacted experts and researchers with an interest in stroke rehabilitation. Randomised or quasi-randomised controlled trials of physiotherapy treatment approaches aimed at promoting the recovery of postural control and lower limb function in adult participants with a clinical diagnosis of stroke. Outcomes included measures of disability, motor impairment or participation. Two review authors independently categorised the identified trials according to the inclusion and exclusion criteria, documented their methodological quality, and extracted the data. Twenty-one trials were included in the review, five of which were included in two comparisons. Eight trials compared a neurophysiological approach with another approach; eight compared a motor learning approach with another approach; and eight compared a mixed approach with another approach. A mixed approach was significantly more effective than no treatment or placebo control for improving functional independence (standardised mean difference (SMD) 0.94, 95% confidence intervals (CI) 0.08 to 1.80). There was no significant evidence that any single approach had a better outcome than any other single approach or no treatment control. There is evidence that physiotherapy intervention, using a mix of components from different approaches, is significantly more effective than no treatment or placebo control in the recovery of functional independence following stroke. There is insufficient evidence to conclude that any one physiotherapy approach is more effective in promoting recovery of lower limb function or postural control following stroke than any other approach. We recommend that future research should concentrate on investigating the effectiveness of clearly described individual techniques and task-specific treatments, regardless of their historical or philsophical origin.

Efficacy and safety of very early mobilisation within 24 h of stroke onset (AVERT): a randomised controlled trial.

PubMed

2015-07-04

Early mobilisation after stroke is thought to contribute to the effects of stroke-unit care; however, the intervention is poorly defined and not underpinned by strong evidence. We aimed to compare the effectiveness of frequent, higher dose, very early mobilisation with usual care after stroke. We did this parallel-group, single-blind, randomised controlled trial at 56 acute stroke units in five countries. Patients (aged ≥18 years) with ischaemic or haemorrhagic stroke, first or recurrent, who met physiological criteria were randomly assigned (1:1), via a web-based computer generated block randomisation procedure (block size of six), to receive usual stroke-unit care alone or very early mobilisation in addition to usual care. Treatment with recombinant tissue plasminogen activator was allowed. Randomisation was stratified by study site and stroke severity. Patients, outcome assessors, and investigators involved in trial and data management were masked to treatment allocation. The primary outcome was a favourable outcome 3 months after stroke, defined as a modified Rankin Scale score of 0-2. We did analysis on an intention-to-treat basis. The trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12606000185561. Between July 18, 2006, and Oct 16, 2014, we randomly assigned 2104 patients to receive either very early mobilisation (n=1054) or usual care (n=1050); 2083 (99%) patients were included in the 3 month follow-up assessment. 965 (92%) patients were mobilised within 24 h in the very early mobilisation group compared with 623 (59%) patients in the usual care group. Fewer patients in the very early mobilisation group had a favourable outcome than those in the usual care group (n=480 [46%] vs n=525 [50%]; adjusted odds ratio [OR] 0·73, 95% CI 0·59-0·90; p=0·004). 88 (8%) patients died in the very early mobilisation group compared with 72 (7%) patients in the usual care group (OR 1·34, 95% CI 0·93-1·93, p=0·113). 201 (19%) patients in the very early mobilisation group and 208 (20%) of those in the usual care group had a non-fatal serious adverse event, with no reduction in immobility-related complications with very early mobilisation. First mobilisation took place within 24 h for most patients in this trial. The higher dose, very early mobilisation protocol was associated with a reduction in the odds of a favourable outcome at 3 months. Early mobilisation after stroke is recommended in many clinical practice guidelines worldwide, and our findings should affect clinical practice by refining present guidelines; however, clinical recommendations should be informed by future analyses of dose-response associations. National Health and Medical Research Council, Singapore Health, Chest Heart and Stroke Scotland, Northern Ireland Chest Heart and Stroke, UK Stroke Association, National Institute of Health Research. Copyright © 2015 Bernhardt et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by Elsevier Ltd.. All rights reserved.

Closure versus medical therapy for preventing recurrent stroke in patients with patent foramen ovale and a history of cryptogenic stroke or transient ischemic attack.

PubMed

Li, Jie; Liu, Junfeng; Liu, Ming; Zhang, Shihong; Hao, Zilong; Zhang, Jing; Zhang, Canfei

2015-09-08

The optimal therapy for preventing recurrent stroke in people with cryptogenic stroke and patent foramen ovale (PFO) has not been defined. The choice between medical therapy (antithrombotic treatment with antiplatelet agents or anticoagulants) and transcatheter device closure has been the subject of intense debate over the past several years. Despite the lack of scientific evidence, a substantial number of people undergo transcatheter device closure (TDC) for secondary stroke prevention. To: 1) compare the safety and efficacy of TDC with best medical therapy alone for preventing recurrent stroke (fatal or non-fatal) or transient ischemic attacks (TIAs) in people with PFO and a history of cryptogenic stroke or TIA; 2) identify specific subgroups of people most likely to benefit from closure for secondary prevention; and 3) assess the cost-effectiveness of this strategy, if possible. We searched the Cochrane Stroke Group Trials Register (July 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2014), MEDLINE (1950 to July 2014) and EMBASE (1980 to July 2014). In an effort to identify unpublished and ongoing trials we searched seven trials registers and checked reference lists. We included randomized controlled trials (RCTs), irrespective of blinding, publication status, and language, comparing the safety and efficacy of device closure with medical therapy for preventing recurrent stroke or TIA in people with PFO and a history of cryptogenic stroke or TIA. Two review authors independently selected trials for inclusion, assessed quality and risk of bias, and extracted data. The primary outcome measures of this analysis were the composite endpoint of ischemic stroke or TIA events as well as recurrent fatal or non-fatal ischemic stroke. Secondary endpoints included all-cause mortality, serious adverse events (atrial fibrillation, myocardial infarction, bleeding) and procedural success and effective closure. We used the Mantel-Haenszel method to obtain pooled risk ratios (RRs) using the random-effects model regardless of the level of heterogeneity. We pooled data for the primary outcome measure with the generic inverse variance method using the random-effects model, yielding risk estimates as pooled hazard ratio (HR), which accounts for time-to-event outcomes. We included three RCTs involving a total of 2303 participants: 1150 participants were randomized to receive TDC and 1153 participants were randomized to receive medical therapy. Overall, the risk of bias was regarded as high. The mean follow-up period of all three included trials was less than five years. Baseline characteristics (age, sex, and vascular risk factors) were similar across trials. Intention-to-treat analyses did not show a statistically significant risk reduction in the composite endpoint of recurrent stroke or TIA in the TDC group when compared with medical therapy (RR 0.73, 95% CI 0.45 to 1.17). A time-to-event analysis combining the results of two RCTs also failed to show a significant risk reduction with TDC (HR 0.69, 95% CI 0.43 to 1.13). When assessing stroke prevention alone, TDC still did not show a statistically significant benefit (RR 0.61, 95% CI 0.29 to 1.27) (HR 0.55, 95% CI 0.26 to 1.18). In a sensitivity analysis including the two studies using the Amplatzer PFO occluder, TDC showed a possible protective effect on recurrent stroke compared with medical therapy (HR 0.38, 95% CI 0.14 to 1.02); however, it did not reach statistical significance. Safety analysis found that the overall risks for all-cause mortality and adverse events were similar in both the TDC and medical therapy groups. However, TDC increased the risk of new-onset atrial fibrillation (RR 3.50, 95% CI 1.47 to 8.35) and may be associated with the type of device used. The combined data from recent RCTs have shown no statistically significant differences between TDC and medical therapy in the prevention of recurrent ischemic stroke. TDC closure was associated with an increased risk of atrial fibrillation but not with serious adverse events.

Baseline characteristics, analysis plan and report on feasibility for the Prevention Of Decline in Cognition After Stroke Trial (PODCAST).

PubMed

Scutt, Polly; Blackburn, Dan; Krishnan, Kailash; Ballard, Clive; Burns, Alistair; Ford, Gary A; Mant, Jonathan; Passmore, Peter; Pocock, Stuart; Reckless, John; Sprigg, Nikola; Stewart, Rob; Wardlaw, Joanna M; Bath, Philip M

2015-11-07

A common complication after stroke is development of cognitive impairment and dementia. However, effective strategies for reducing the risk of developing these problems remain undefined. Potential strategies include intensive lowering of blood pressure (BP) and/or lipids. This paper summarises the baseline characteristics, statistical analysis plan and feasibility of a randomised control trial of blood pressure and lipid lowering in patients post-stroke with the primary objective of reducing cognitive impairment and dementia. The Prevention Of Decline in Cognition After Stroke Trial (PODCAST) was a multi-centre prospective randomised open-label blinded-endpoint controlled partial-factorial internal pilot trial running in secondary and primary care. Participants without dementia were enrolled 3-7 months post ischaemic stroke or spontaneous intracerebral haemorrhage, and randomised to intensive versus guideline BP lowering (target systolic BP <125 mmHg versus <140 mmHg); patients with ischaemic stroke were also randomised to intensive or guideline lipid lowering (target LDL cholesterol <1.4 mmol/L versus <3 mmol/L). The primary outcome was the Addenbrooke's Cognitive Examination-Revised; a key secondary outcome was to assess feasibility of performing a large trial of one or both interventions. Data are number (%) or mean (standard deviation). The trial was planned to last for 8 years with follow-up between 1 and 8 years. The plan for reporting the main results is included as Additional file 2. 83 patients (of a planned 600) were recruited from 19 UK sites between 7 October 2010 and 31 January 2014. Delays, due to difficulties in the provision of excess treatment costs and to complexity of follow-up, led to few centres taking part and a much lower recruitment rate than planned. Patient characteristics at baseline were: age 74 (SD 7) years, male 64 (77 %), index stroke ischaemic 77 (93 %), stroke onset to randomisation 4.5 [SD 1.3] months, Addenbrooke's Cognitive Examination-Revised 86 (of 100, SD 8), Montreal Cognitive Assessment 24 (of 30, SD 3), BP 147/82 (SD 19/11) mmHg, total cholesterol 4.0 (SD 0.8) mmol/L and LDL cholesterol 2.0 (SD 0.7) mmol/L, modified Rankin Scale 1.1 (SD 0.8). Limited recruitment suggests that a large trial is not feasible using the current protocol. The effects of the interventions on BP, lipids, and cognition will be reported in the main publication. ISRCTN85562386 registered on 23 September 2009.

Stroke treatment academic industry roundtable: research priorities in the assessment of neurothrombectomy devices.

PubMed

Saver, Jeffrey L; Jovin, Tudor G; Smith, Wade S; Albers, Gregory W; Baron, Jean-Claude; Boltze, Johannes; Broderick, Joseph P; Davis, Lisa A; Demchuk, Andrew M; DeSena, Salvatore; Fiehler, Jens; Gorelick, Philip B; Hacke, Werner; Holt, Bill; Jahan, Reza; Jing, Hui; Khatri, Pooja; Kidwell, Chelsea S; Lees, Kennedy R; Lev, Michael H; Liebeskind, David S; Luby, Marie; Lyden, Patrick; Megerian, J Thomas; Mocco, J; Muir, Keith W; Rowley, Howard A; Ruedy, Richard M; Savitz, Sean I; Sipelis, Vitas J; Shimp, Samuel K; Wechsler, Lawrence R; Wintermark, Max; Wu, Ona; Yavagal, Dileep R; Yoo, Albert J

2013-12-01

The goal of the Stroke Treatment Academic Industry Roundtable (STAIR) meetings is to advance the development of stroke therapies. At STAIR VIII, consensus recommendations were developed for clinical trial strategies to demonstrate the benefit of endovascular reperfusion therapies for acute ischemic stroke. Prospects for success with forthcoming endovascular trials are robust, because new neurothrombectomy devices have superior reperfusion efficacy compared with earlier-generation interventions. Specific recommendations are provided for trial designs in 3 populations: (1) patients undergoing intravenous fibrinolysis, (2) early patients ineligible for or having failed intravenous fibrinolysis, and (3) wake-up and other late-presenting patients. Among intravenous fibrinolysis-eligible patients, key principles are that CT or MRI confirmation of target arterial occlusions should precede randomization; endovascular intervention should be pursued with the greatest rapidity possible; and combined intravenous and neurothrombectomy therapy is more promising than neurothrombectomy alone. Among patients ineligible for or having failed intravenous fibrinolysis, scientific equipoise was affirmed and the need to randomize all eligible patients emphasized. Vessel imaging to confirm occlusion is mandatory, and infarct core and penumbral imaging is desirable in later time windows. Additional STAIR VIII recommendations include approaches to test multiple devices in a single trial, utility weighting of disability end points, and adaptive designs to delineate time and tissue injury thresholds at which benefits from intervention no longer accrue. Endovascular research priorities in acute ischemic stroke are to perform trials testing new, highly effective neuro thrombectomy devices rapidly deployed in patients confirmed to have target vessel occlusions.

The effect of a therapeutic regimen of Traditional Chinese Medicine rehabilitation for post-stroke cognitive impairment: study protocol for a randomized controlled trial.

PubMed

Huang, Jia; Lin, Zhengkun; Wang, Qin; Liu, Feiwen; Liu, Jiao; Fang, Yunhua; Chen, Shanjia; Zhou, Xiaoxuan; Hong, Wenjun; Wu, Jinsong; Madrigal-Mora, Natalia; Zheng, Guohua; Yang, Shanli; Tao, Jing; Chen, Lidian

2015-06-16

Post-stroke cognitive impairment (PSCI) lessens quality of life, restricts the rehabilitation of stroke, and increases the social and economic burden stroke imposes on patients and their families. Therefore effective treatment is of paramount importance. However, the treatment of PSCI is very limited. The primary aim of this protocol is to propose a lower cost and more effective therapy, and to confirm the long-term effectiveness of a therapeutic regimen of Traditional Chinese Medicine (TCM) rehabilitation for PSCI. A prospective, multicenter, large sample, randomized controlled trial will be conducted. A total of 416 eligible patients will be recruited from seven inpatient and outpatient stroke rehabilitation units and randomly allocated into a therapeutic regimen of TCM rehabilitation group or cognitive training (CT) control group. The intervention period of both groups will last 12 weeks (30 minutes per day, five days per week). Primary and secondary outcomes will be measured at baseline, 12 weeks (at the end of the intervention), and 36 weeks (after the 24-week follow-up period). This protocol presents an objective design of a multicenter, large sample, randomized controlled trial that aims to put forward a lower cost and more effective therapy, and confirm the long-term effectiveness of a therapeutic regimen of TCM rehabilitation for PSCI through subjective and objective assessments, as well as highlight its economic advantages. This trial was registered with the Chinese Clinical Trial Registry (identifier: ChiCTR-TRC-14004872 ) on 23 June 2014.

Promoting psychosocial well-being following stroke: study protocol for a randomized, controlled trial.

PubMed

Kirkevold, Marit; Kildal Bragstad, Line; Bronken, Berit A; Kvigne, Kari; Martinsen, Randi; Gabrielsen Hjelle, Ellen; Kitzmüller, Gabriele; Mangset, Margrete; Angel, Sanne; Aadal, Lena; Eriksen, Siren; Wyller, Torgeir B; Sveen, Unni

2018-04-03

Stroke is a major public health threat globally. Psychosocial well-being may be affected following stroke. Depressive symptoms, anxiety, general psychological distress and social isolation are prevalent. Approximately one third report depressive symptoms and 20% report anxiety during the first months or years after the stroke. Psychosocial difficulties may impact significantly on long-term functioning and quality of life, reduce the effects of rehabilitation services and lead to higher mortality rates. The aim of the study is to evaluate the effect of a previously developed and feasibility tested dialogue-based psychosocial intervention aimed at promoting psychosocial well-being and coping following stroke among stroke survivors with and without aphasia. The study will be conducted as a multicenter, randomized, single blind controlled trial with one intervention and one control arm. It will include a total of 330 stroke survivors randomly allocated into either an intervention group (dialogue-based intervention to promote psychosocial well-being) or a control group (usual care). Participants in the intervention group will receive eight individual sessions of supported dialogues in their homes during the first six months following an acute stroke. The primary outcome measure will be psychosocial well-being measured by the General Health Questionnaire (GHQ). Secondary outcome measures will be quality of life (SAQoL), sense of coherence (SOC), and depression (Yale). Process evaluation will be conducted in a longitudinal mixed methods study by individual qualitative interviews with 15-20 participants in the intervention and control groups, focus group interviews with the intervention personnel and data collectors, and a comprehensive analysis of implementation fidelity. The intervention described in this study protocol is based on thorough development and feasibility work, guided by the UK medical research council framework for developing and testing complex interventions. It combines classical effectiveness evaluation with a thorough process evaluation. The results from this study may inform the development of further trials aimed at promoting psychosocial well-being following stroke as well as inform the psychosocial follow up of stroke patients living at home. NCT02338869 ; registered 10/04/2014 (On-going trial).

A randomized controlled trial of very early rehabilitation in speech after stroke.

PubMed

Godecke, Erin; Armstrong, Elizabeth A; Rai, Tapan; Middleton, Sandy; Ciccone, Natalie; Whitworth, Anne; Rose, Miranda; Holland, Audrey; Ellery, Fiona; Hankey, Graeme J; Cadilhac, Dominique A; Bernhardt, Julie

2016-07-01

The efficacy of rehabilitation therapy for aphasia caused by stroke is uncertain. The Very Early Rehabilitation of Speech (VERSE) trial aims to determine if intensive prescribed aphasia therapy (VERSE) is more effective and cost saving than non-prescribed, intensive (usual care-plus) and non-intensive usual care (UC) therapy when started within 15 days of stroke onset and continued daily over four weeks. We hypothesize that aphasia therapy when started very early after stroke and delivered daily could enhance recovery of communication compared with UC. A total of 246 participants (82 per arm) will provide 80% power to detect a 4.4% improvement on aphasia quotient between VERSE and UC plus at a significance level of α = 0.05. Acute-care hospitals and accompanying rehabilitation services throughout Australia, 2014-2017. Three-arm, prospective, randomized, parallel group, open-label, blinded endpoint assessment (PROBE) trial. Acute stroke in previous 14 days and aphasia diagnosed by aphasia quotient (AQ) of the Western Aphasia Battery (WAB). Computer-generated blocked randomization procedure stratified by aphasia severity according to Western Aphasia Battery, to one of three arms. All participants receive UC-usual ward-based aphasia therapy. Arm 1: UC-no additional therapy; Arm 2: UC-plus usual ward-based therapy; Arm 3: VERSE therapy-a prescribed and structured aphasia therapy program. Arms 2 and 3 receive a total of 20 additional sessions (45-60 min, provided daily) of aphasia therapy. The additional intervention must be provided before day 50 post stroke. The aphasia quotient of Western Aphasia Battery at 12 weeks post stroke. Secondary outcomes include discourse measures, the Stroke and Aphasia Quality of Life Scale-39 and the Aphasia Depression Rating Scale at 12 and 26 weeks. Incremental cost-effectiveness ratios at 26 weeks will be reported. This trial is designed to test whether the intensive and prescribed VERSE intervention is effective in promoting maximum recovery and preventing costly health complications in a vulnerable population of survivors of stroke. It will also provide novel, prospective, aphasia specific cost-effectiveness data to guide future policy development for this population. © 2016 World Stroke Organization.

Intensive versus Guideline Blood Pressure and Lipid Lowering in Patients with Previous Stroke: Main Results from the Pilot 'Prevention of Decline in Cognition after Stroke Trial' (PODCAST) Randomised Controlled Trial.

PubMed

Bath, Philip M; Scutt, Polly; Blackburn, Daniel J; Ankolekar, Sandeep; Krishnan, Kailash; Ballard, Clive; Burns, Alistair; Mant, Jonathan; Passmore, Peter; Pocock, Stuart; Reckless, John; Sprigg, Nikola; Stewart, Rob; Wardlaw, Joanna M; Ford, Gary A

2017-01-01

Stroke is associated with the development of cognitive impairment and dementia. We assessed the effect of intensive blood pressure (BP) and/or lipid lowering on cognitive outcomes in patients with recent stroke in a pilot trial. In a multicentre, partial-factorial trial, patients with recent stroke, absence of dementia, and systolic BP (SBP) 125-170 mmHg were assigned randomly to at least 6 months of intensive (target SBP <125 mmHg) or guideline (target SBP <140 mmHg) BP lowering. The subset of patients with ischaemic stroke and total cholesterol 3.0-8.0 mmol/l were also assigned randomly to intensive (target LDL-cholesterol <1.3 mmol/l) or guideline (target LDL-c <3.0 mmol/l) lipid lowering. The primary outcome was the Addenbrooke's Cognitive Examination-Revised (ACE-R). We enrolled 83 patients, mean age 74.0 (6.8) years, and median 4.5 months after stroke. The median follow-up was 24 months (range 1-48). Mean BP was significantly reduced with intensive compared to guideline treatment (difference -10·6/-5·5 mmHg; p<0·01), as was total/LDL-cholesterol with intensive lipid lowering compared to guideline (difference -0·54/-0·44 mmol/l; p<0·01). The ACE-R score during treatment did not differ for either treatment comparison; mean difference for BP lowering -3.6 (95% CI -9.7 to 2.4), and lipid lowering 4.4 (95% CI -2.1 to 10.9). However, intensive lipid lowering therapy was significantly associated with improved scores for ACE-R at 6 months, trail making A, modified Rankin Scale and Euro-Qol Visual Analogue Scale. There was no difference in rates of dementia or serious adverse events for either comparison. In patients with recent stroke and normal cognition, intensive BP and lipid lowering were feasible and safe, but did not alter cognition over two years. The association between intensive lipid lowering and improved scores for some secondary outcomes suggests further trials are warranted. ISRCTN ISRCTN85562386.

The effects of a rhythm and music-based therapy program and therapeutic riding in late recovery phase following stroke: a study protocol for a three-armed randomized controlled trial.

PubMed

Bunketorp Käll, Lina; Lundgren-Nilsson, Åsa; Blomstrand, Christian; Pekna, Marcela; Pekny, Milos; Nilsson, Michael

2012-11-21

Stroke represents one of the most costly and long-term disabling conditions in adulthood worldwide and there is a need to determine the effectiveness of rehabilitation programs in the late phase after stroke. Limited scientific support exists for training incorporating rhythm and music as well as therapeutic riding and well-designed trials to determine the effectiveness of these treatment modalities are warranted. A single blinded three-armed randomized controlled trial is described with the aim to evaluate whether it is possible to improve the overall health status and functioning of individuals in the late phase of stroke (1-5 years after stroke) through a rhythm and music-based therapy program or therapeutic riding. About 120 individuals will be consecutively and randomly allocated to one of three groups: (T1) rhythm and music-based therapy program; (T2) therapeutic riding; or (T3) control group receiving the T1 training program a year later. Evaluation is conducted prior to and after the 12-week long intervention as well as three and six months later. The evaluation comprises a comprehensive functional and cognitive assessment (both qualitative and quantitative), and questionnaires. Based on the International classification of functioning, disability, and health (ICF), the outcome measures are classified into six comprehensive domains, with participation as the primary outcome measure assessed by the Stroke Impact Scale (SIS, version 2.0.). The secondary outcome measures are grouped within the following domains: body function, activity, environmental factors and personal factors. Life satisfaction and health related quality of life constitute an additional domain. A total of 84 participants were randomised and have completed the intervention. Recruitment proceeds and follow-up is on-going, trial results are expected in early 2014. This study will ascertain whether any of the two intervention programs can improve overall health status and functioning in the late phase of stroke. A positive outcome would increase the scientific basis for the use of such interventions in the late phase after stroke. Clinical Trials.gov Identifier: NCT01372059.

[Effectiveness of special stroke units in treatment of acute stroke].

PubMed

Nikolaus, T; Jamour, M

2000-04-01

In Germany the implementation of specialized wards for the care of stroke patients is proposed. However, which type of organized inpatient stroke unit care is most effective and which group of patients will benefit most remains unclear. Based on the analyses of the Stroke Unit Trialists' Collaboration this paper reports results of randomized and quasi-randomized trials that compared organized inpatient (stroke unit) care with contemporary conventional care. The primary analyses examined death, dependency and institutionalization. Secondary outcome measures included patient quality of life, patient and carer satisfaction and length of stay in hospital and/or institution. The analysis of twenty trails with 3864 patients showed a reduction in the rate of deaths in the stroke unit group as compared with the control group (OR 0.83, 95% CI 0.71-0.97). The odds of death or institutionalized care were lower (OR 0.76, 95% CI 0.65-0.90) as were death or dependency (OR 0.75, 95% CI 0.65-0.87). The results were independent of patient age, sex, stroke severity, and type of stroke unit organization. Organized care in stroke units resulted in benefits for stroke patients with regard to survival, independence, and probability of living at home. However, these results refer exclusively to Anglo-American and Scandinavian trials. German stroke unit services are organized in a different way. No data about the effectiveness of the German model is yet available.

An intervention to support stroke survivors and their carers in the longer term (LoTS2Care): study protocol for a cluster randomised controlled feasibility trial.

PubMed

Forster, Anne; Hartley, Suzanne; Barnard, Lorna; Ozer, Seline; Hardicre, Natasha; Crocker, Tom; Fletcher, Marie; Moreau, Lauren; Atkinson, Ross; Hulme, Claire; Holloway, Ivana; Schmitt, Laetitia; House, Allan; Hewison, Jenny; Richardson, Gillian; Farrin, Amanda

2018-06-11

Despite the evidence that many stroke survivors report longer term unmet needs, the provision of longer term care is limited. To address this, we are conducting a programme of research to develop an evidence-based and replicable longer term care strategy. The developed complex intervention (named New Start), which includes needs identification, exploration of social networks and components of problem solving and self-management, was designed to improve quality of life by addressing unmet needs and increasing participation. A multicentre, cluster randomised controlled feasibility trial designed to inform the design of a possible future definitive cluster randomised controlled trial (cRCT) and explore the potential clinical and cost-effectiveness of New Start. Ten stroke services across the UK will be randomised on a 1:1 basis either to implement New Start or continue with usual care only. New Start will be delivered by trained facilitators and will be offered to all stroke survivors within the services allocated to the intervention arm. Stroke survivors will be eligible for the trial if they are 4-6 months post-stroke and residing in the community. Carers (if available) will also be invited to take part. Invitation to participate will be initiated by post and outcome measures will be collected via postal questionnaires at 3, 6 and 9 months after recruitment. Outcome data relating to perceived health and disability, wellbeing and quality of life as well as unmet needs will be collected. A 'study within a trial' (SWAT) is planned to determine the most acceptable format in which to provide the postal questionnaires. Details of health and social care service usage will also be collected to inform the economic evaluation. The feasibility of recruiting services and stroke survivors to the trial and of collecting postal outcomes will be assessed and the potential for effectiveness will be investigated. An embedded process evaluation (reported separately) will assess implementation fidelity and explore and clarify causal assumptions regarding implementation. This feasibility trial with embedded process evaluation will allow us to gather important and detailed data regarding methodological and implementation issues to inform the design of a possible future definitive cRCT of this complex intervention. ISRCTN38920246 . Registered 22 June 2016.

Patent Foramen Ovale, Ischemic Stroke and Migraine: Systematic Review and Stratified Meta-Analysis of Association Studies

PubMed Central

Davis, Daniel; Gregson, John; Willeit, Peter; Stephan, Blossom; Al-Shahi Salman, Rustam; Brayne, Carol

2012-01-01

Background Observational data have reported associations between patent foramen ovale (PFO), cryptogenic stroke and migraine. However, randomized trials of PFO closure do not demonstrate a clear benefit either because the underlying association is weaker than previously suggested or because the trials were underpowered. In order to resolve the apparent discrepancy between observational data and randomized trials, we investigated associations between (1) migraine and ischemic stroke, (2) PFO and ischemic stroke, and (3) PFO and migraine. Methods Eligibility criteria were consistent; including all studies with specifically defined exposures and outcomes unrestricted by language. We focused on studies at lowest risk of bias by stratifying analyses based on methodological design and quantified associations using fixed-effects meta-analysis models. Results We included 37 studies of 7,686 identified. Compared to reports in the literature as a whole, studies with population-based comparators showed weaker associations between migraine with aura and cryptogenic ischemic stroke in younger women (OR 1.4; 95% CI 0.9–2.0; 1 study), PFO and ischemic stroke (HR 1.6; 95 CI 1.0–2.5; 2 studies; OR 1.3; 95% CI 0.9–1.9; 3 studies), or PFO and migraine (OR 1.0; 95% CI 0.6–1.6; 1 study). It was not possible to look for interactions or effect modifiers. These results are limited by sources of bias within individual studies. Conclusions The overall pairwise associations between PFO, cryptogenic ischemic stroke and migraine do not strongly suggest a causal role for PFO. Ongoing randomized trials of PFO closure may need larger numbers of participants to detect an overall beneficial effect. PMID:23075508

Patent foramen ovale, ischemic stroke and migraine: systematic review and stratified meta-analysis of association studies.

PubMed

Davis, Daniel; Gregson, John; Willeit, Peter; Stephan, Blossom; Al-Shahi Salman, Rustam; Brayne, Carol

2013-01-01

Observational data have reported associations between patent foramen ovale (PFO), cryptogenic stroke and migraine. However, randomized trials of PFO closure do not demonstrate a clear benefit either because the underlying association is weaker than previously suggested or because the trials were underpowered. In order to resolve the apparent discrepancy between observational data and randomized trials, we investigated associations between (1) migraine and ischemic stroke, (2) PFO and ischemic stroke, and (3) PFO and migraine. Eligibility criteria were consistent; including all studies with specifically defined exposures and outcomes unrestricted by language. We focused on studies at lowest risk of bias by stratifying analyses based on methodological design and quantified associations using fixed-effects meta-analysis models. We included 37 studies of 7,686 identified. Compared to reports in the literature as a whole, studies with population-based comparators showed weaker associations between migraine with aura and cryptogenic ischemic stroke in younger women (OR 1.4; 95% CI 0.9-2.0; 1 study), PFO and ischemic stroke (HR 1.6; 95 CI 1.0-2.5; 2 studies; OR 1.3; 95% CI 0.9-1.9; 3 studies), or PFO and migraine (OR 1.0; 95% CI 0.6-1.6; 1 study). It was not possible to look for interactions or effect modifiers. These results are limited by sources of bias within individual studies. The overall pairwise associations between PFO, cryptogenic ischemic stroke and migraine do not strongly suggest a causal role for PFO. Ongoing randomized trials of PFO closure may need larger numbers of participants to detect an overall beneficial effect. Copyright © 2012 S. Karger AG, Basel.

Rehab-let: touchscreen tablet for self-training impaired dexterity post stroke: study protocol for a pilot randomized controlled trial.

PubMed

Rand, Debbie; Zeilig, Gabi; Kizony, Rachel

2015-06-18

Impaired dexterity of the weaker upper extremity is common post stroke and it is recommended that these individuals practice many repetitions of movement to regain function. However, stroke rehabilitation methods do not achieve the required intensity to be effective. Touchscreen tablet technology may be used as a motivating tool for self-training impaired dexterity of the weaker upper extremity post stroke. Rehab-let is a self-training protocol utilizing game apps on a touchscreen for practicing movement of the weaker upper extremity. We will conduct a pilot randomized controlled trial to assess Rehab-let compared to traditional self-training to improve dexterity of the weaker hand, and to increase self-training time and satisfaction in individuals with subacute stroke. Forty individuals with stroke undergoing subacute rehabilitation will be randomly allocated to Rehab-let or a traditional self-training program using therapeutic aids such as balls, blocks and pegs. All participants will be requested to perform self-training for 60 minutes a day, 5 times a week for 4 weeks. Dexterity assessed by The Nine Hole Peg Test is the main outcome measure. Assessments will be administered pre and post the self-training intervention by assessors blind to the group allocation. The outcomes of this study will inform the design of a fully powered randomized controlled trial to evaluate the effectiveness of Rehab-let. If found to be effective, Rehab-let can be used during subacute rehabilitation to increase treatment intensity and improve dexterity. Potentially, Rehab-let can also be used after discharge and might be ideal for individuals with mild stroke who are often not referred to formal rehabilitation. Current Controlled Trials NCT02136433 registered on 17 September 2014.

RECAST (Remote Ischemic Conditioning After Stroke Trial): A Pilot Randomized Placebo Controlled Phase II Trial in Acute Ischemic Stroke.

PubMed

England, Timothy J; Hedstrom, Amanda; O'Sullivan, Saoirse; Donnelly, Richard; Barrett, David A; Sarmad, Sarir; Sprigg, Nikola; Bath, Philip M

2017-05-01

Repeated episodes of limb ischemia and reperfusion (remote ischemic conditioning [RIC]) may improve outcome after acute stroke. We performed a pilot blinded placebo-controlled trial in patients with acute ischemic stroke, randomized 1:1 to receive 4 cycles of RIC within 24 hours of ictus. The primary outcome was tolerability and feasibility. Secondary outcomes included safety, clinical efficacy (day 90), putative biomarkers (pre- and post-intervention, day 4), and exploratory hemodynamic measures. Twenty-six patients (13 RIC and 13 sham) were recruited 15.8 hours (SD 6.2) post-onset, age 76.2 years (SD 10.5), blood pressure 159/83 mm Hg (SD 25/11), and National Institutes of Health Stroke Scale (NIHSS) score 5 (interquartile range, 3.75-9.25). RIC was well tolerated with 49 out of 52 cycles completed in full. Three patients experienced vascular events in the sham group: 2 ischemic strokes and 2 myocardial infarcts versus none in the RIC group ( P =0.076, log-rank test). Compared with sham, there was a significant decrease in day 90 NIHSS score in the RIC group, median NIHSS score 1 (interquartile range, 0.5-5) versus 3 (interquartile range, 2-9.5; P =0.04); RIC augmented plasma HSP27 (heat shock protein 27; P <0.05, repeated 2-way ANOVA) and phosphorylated HSP27 ( P <0.001) but not plasma S100-β, matrix metalloproteinase-9, endocannabinoids, or arterial compliance. RIC after acute stroke is well tolerated and appears safe and feasible. RIC may improve neurological outcome, and protective mechanisms may be mediated through HSP27. A larger trial is warranted. URL: http://www.isrctn.com. Unique identifier: ISRCTN86672015. © 2017 American Heart Association, Inc.

A Neuromuscular Electrical Stimulation (NMES) and robot hybrid system for multi-joint coordinated upper limb rehabilitation after stroke.

PubMed

Rong, Wei; Li, Waiming; Pang, Mankit; Hu, Junyan; Wei, Xijun; Yang, Bibo; Wai, Honwah; Zheng, Xiaoxiang; Hu, Xiaoling

2017-04-26

It is a challenge to reduce the muscular discoordination in the paretic upper limb after stroke in the traditional rehabilitation programs. In this study, a neuromuscular electrical stimulation (NMES) and robot hybrid system was developed for multi-joint coordinated upper limb physical training. The system could assist the elbow, wrist and fingers to conduct arm reaching out, hand opening/grasping and arm withdrawing by tracking an indicative moving cursor on the screen of a computer, with the support from the joint motors and electrical stimulations on target muscles, under the voluntary intention control by electromyography (EMG). Subjects with chronic stroke (n = 11) were recruited for the investigation on the assistive capability of the NMES-robot and the evaluation of the rehabilitation effectiveness through a 20-session device assisted upper limb training. In the evaluation, the movement accuracy measured by the root mean squared error (RMSE) during the tracking was significantly improved with the support from both the robot and NMES, in comparison with those without the assistance from the system (P < 0.05). The intra-joint and inter-joint muscular co-contractions measured by EMG were significantly released when the NMES was applied to the agonist muscles in the different phases of the limb motion (P < 0.05). After the physical training, significant improvements (P < 0.05) were captured by the clinical scores, i.e., Modified Ashworth Score (MAS, the elbow and the wrist), Fugl-Meyer Assessment (FMA), Action Research Arm Test (ARAT), and Wolf Motor Function Test (WMFT). The EMG-driven NMES-robotic system could improve the muscular coordination at the elbow, wrist and fingers. ClinicalTrials.gov. NCT02117089 ; date of registration: April 10, 2014.

Multi-system verification of registrations for image-guided radiotherapy in clinical trials.

PubMed

Cui, Yunfeng; Galvin, James M; Straube, William L; Bosch, Walter R; Purdy, James A; Li, X Allen; Xiao, Ying

2011-09-01

To provide quantitative information on the image registration differences from multiple systems for image-guided radiotherapy (IGRT) credentialing and margin reduction in clinical trials. Images and IGRT shift results from three different treatment systems (Tomotherapy Hi-Art, Elekta Synergy, Varian Trilogy) have been sent from various institutions to the Image-Guided Therapy QA Center (ITC) for evaluation for the Radiation Therapy Oncology Group (RTOG) trials. Nine patient datasets (five head-and-neck and four prostate) were included in the comparison, with each patient having 1-4 daily individual IGRT studies. In all cases, daily shifts were re-calculated by re-registration of the planning CT with the daily IGRT data using three independent software systems (MIMvista, FocalSim, VelocityAI). Automatic fusion was used in all calculations. The results were compared with those submitted from institutions. Similar regions of interest (ROIs) and same initial positions were used in registrations for inter-system comparison. Different slice spacings for CBCT sampling and different ROIs for registration were used in some cases to observe the variation of registration due to these factors. For the 54 comparisons with head-and-neck datasets, the absolute values of differences of the registration results between different systems were 2.6±2.1 mm (mean±SD; range 0.1-8.6 mm, left-right [LR]), 1.7±1.3 mm (0.0-4.9 mm, superior-inferior [SI]), and 1.8±1.1 mm (0.1-4.0 mm, anterior-posterior [AP]). For the 66 comparisons in prostate cases, the differences were 1.1±1.0 mm (0.0-4.6 mm, LR), 2.1±1.7 mm (0.0-6.6 mm, SI), and 2.0±1.8 mm (0.1-6.9 mm, AP). The differences caused by the slice spacing variation were relatively small, and the different ROI selections in FocalSim and MIMvista also had limited impact. The extent of differences was reported when different systems were used for image registration. Careful examination and quality assurance of the image registration process are crucial before considering margin reduction using IGRT in clinical trials. Copyright © 2011 Elsevier Inc. All rights reserved.

Interventions in the management of serum lipids for preventing stroke recurrence.

PubMed

Manktelow, B; Gillies, C; Potter, J F

2002-01-01

A close association between serum lipid levels and the incidence of coronary heart disease (CHD) has been well proven in middle aged and older persons, up to the age of 70-75 years. Individual studies have shown interventions to reduce total and low density lipoprotein (LDL) cholesterol levels, especially with 3-hydroxy-3-methylglutaryl coenzyme a (HMG-CoA) reductase inhibitors (statins), to be of benefit in reducing CHD and stroke events in those with a history of coronary heart disease. However, the relation of serum cholesterol and cholesterol sub-fractions with cerebrovascular disease is less clear. It is unclear whether lipid levels in the post-stroke period are a predictor of recurrence and whether treatment to alter levels can prevent recurrence of either stroke or cardiovascular events. To investigate the effect of altering serum lipids in the prevention of cardiovascular disease and stroke recurrence in subjects with a history of stroke. The Cochrane Group Trials Register was searched up to 8 May 2001 along with MEDLINE (from 1966), EMBASE (from 1980) and the Cochrane Controlled Trials Register. All pharmaceutical firms known to produce a lipid lowering agent were also contacted and asked to provide information on publications or unpublished work relevant to this review. This review included unconfounded randomised trials of subjects aged 18 years and over with a history of stroke or Transient Ischaemic Attack (TIA). The data were extracted independently by the three reviewers. MetaView 4.1 was used for all statistical analyses. Five studies involving 1700 patients were included in the review. The active intervention in two of the studies was Clofibrate, Pravastatin in another two and Conjugated Oestrogen in the fifth. Fixed effects analysis showed no evidence of a difference in stroke recurrence between the treatment and placebo groups for those with a previous history of stroke or TIA (odds ratio 0.96, 95% confidence interval 0.71 to 1.30). In addition there was also no evidence, based on two studies, that intervention reduced the odds of all cause mortality (odds ratio 0.87, 95% confidence interval 0.55 to 1.39) nor, from one study, that there was any effect on subsequent vascular events (odds ratio 1.27, 95% confidence interval 0.84 to 1.89). These trials do not provide evidence for a benefit, or harm, from interventions to alter serum lipid levels in patients with a history solely of cerebrovascular disease. Their use, therefore, cannot yet be recommended routinely in this patient group, but ischaemic stroke patients with a history of myocardial infarction should receive statin therapy along the lines of the previous recommendations for those patients with a history of myocardial ischaemia. There are currently three ongoing trials which will recruit approximately 30,000 patients, including those with a history of stroke, and the results of these trials may have a significant effect on these conclusions.

Adding value to clinical trial registries: insights from Australian Cancer Trials Online, a website for consumers.

PubMed

Dear, Rachel; Barratt, Alexandra; Askie, Lisa; McGeechan, Kevin; Arora, Sheena; Crossing, Sally; Currow, David; Tattersall, Martin

2011-02-01

Clinical trials registries are now operating in the USA, Europe, Australia, China, and India and more are planned. Trial registries could be an excellent source of information about clinical trials for patients and others affected by cancer as well as health care professionals, but may be difficult for patients to navigate and use. An opportunity arose in Australia to develop a consumer friendly cancer clinical trials website (Australian Cancer Trials Online (ACTO), www.australiancancertrials.gov.au) using an automated data feed from two large clinical trial registries. In this article, we describe aspects of this new website, and explore ways in which such a website may add value to clinical trial data which are already collected and held by trial registries. The development of ACTO was completed by a Web company working in close association with staff at the Australian New Zealand Clinical Trials Registry (ANZCTR), and with consumer representatives. Data for the website were sourced directly and only from clinical trial registries, thus avoiding the creation of an additional trials database. It receives an automated, daily data feed of newly registered cancer clinical trials from both the ANZCTR and Clinical Trials.gov. The development of ACTO exemplifies the advantage of a local clinical trial registry working with consumers to provide accessible information about cancer clinical trials to meet consumers' information needs. We found that the inclusion of a lay summary added substantial value for consumers, and recommend that consideration be given to adding a lay summary to the mandatory data items collected by all trial registries. Furthermore, improved navigation, decision support tools, and consistency in data collection between clinical trial registries will also enable consumer websites to provide additional value for users. Clinical trial registration is not compulsory in Australia. If the additional cancer items (including a lay summary) are not provided by registrants of cancer trials on ANZCTR, this can compromise the quality and usefulness of the data for the end-user, in this case consumers, as they may encounter gaps in the data. Expanding the World Health Organization Trial Registration Data Set to include this additional information, particularly the lay summary, would be valuable. A well-coordinated system of clinical trial registration is critical to the success of efforts to provide better access for all to inform about clinical trials.

Effect of timing and method of enteral tube feeding for dysphagic stroke patients (FOOD): a multicentre randomised controlled trial.

PubMed

Dennis, M S; Lewis, S C; Warlow, C

Undernutrition is common in patients admitted with stroke. We aimed to establish whether the timing and route of enteral tube feeding after stroke affected patients' outcomes at 6 months. The FOOD trials consist of three pragmatic multicentre randomised controlled trials, two of which included dysphagic stroke patients. In one trial, patients enrolled within 7 days of admission were randomly allocated to early enteral tube feeding or no tube feeding for more than 7 days (early versus avoid). In the other, patients were allocated percutaneous endoscopic gastrostomy (PEG) or nasogastric feeding. The primary outcome was death or poor outcome at 6 months. Analysis was by intention to treat. Between Nov 1, 1996, and July 31, 2003, 859 patients were enrolled by 83 hospitals in 15 countries into the early versus avoid trial. Early tube feeding was associated with an absolute reduction in risk of death of 5.8% (95% CI -0.8 to 12.5, p=0.09) and a reduction in death or poor outcome of 1.2% (-4.2 to 6.6, p=0.7). In the PEG versus nasogastric tube trial, 321 patients were enrolled by 47 hospitals in 11 countries. PEG feeding was associated with an absolute increase in risk of death of 1.0% (-10.0 to 11.9, p=0.9) and an increased risk of death or poor outcome of 7.8% (0.0 to 15.5, p=0.05). Early tube feeding might reduce case fatality, but at the expense of increasing the proportion surviving with poor outcome. Our data do not support a policy of early initiation of PEG feeding in dysphagic stroke patients.

Noninvasive Ventilatory Correction in Patients With Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

PubMed

Tsivgoulis, Georgios; Alexandrov, Andrei V; Katsanos, Aristeidis H; Barlinn, Kristian; Mikulik, Robert; Lambadiari, Vaia; Bonakis, Anastasios; Alexandrov, Anne W

2017-08-01

Even though current guidelines suggest that noninvasive ventilatory correction (NIVC) could be considered for acute ischemic stroke patients with obstructive sleep apnea, available evidence is conflicting, with no adequately powered randomized clinical trial being available to date. We conducted a systematic review and meta-analysis of all available literature data evaluating the effect of NIVC on neurological improvement (based on decrease in National Institutes of Health Stroke Scale score), vascular events (recurrent stroke, transient ischemic attack, myocardial infarction and unstable angina), and mortality during the follow-up period. We identified 4 randomized clinical trials and 1 prospectively matched observational cohort, comprising a total of 389 patients (59.8% males, mean age: 64.4 years). The risk of both performance and detection bias was considered high in most of the included randomized clinical trials because of the lack of blinding in participants, personnel and/or outcome assessors. The mean decrease in National Institutes of Health Stroke Scale scores during the first (≤30) days of acute ischemic stroke was found to be greater in NIVC-treated patients in comparison to controls (standardized mean difference, 0.38; 95% confidence interval, 0.11-0.66; P =0.007). However, no significant differences were detected between NIVC-treated acute ischemic stroke patients and controls on both the risk of vascular events (risk ratio, 0.53; 95% confidence interval, 0.25-1.14; P =0.11) and mortality (risk ratio, 0.71; 95% confidence interval, 0.37-1.36; P =0.30). No evidence of heterogeneity ( I 2 =0%; P for Cochran Q>0.50) or publication bias were detected in all analyses. NIVC seems to be associated with greater short-term neurological improvement in acute ischemic stroke patients with obstructive sleep apnea. This finding deserves further investigation within the settings of an adequately powered, sham-control, randomized clinical trial. © 2017 American Heart Association, Inc.

Does touch massage facilitate recovery after stroke? A study protocol of a randomized controlled trial.

PubMed

Lämås, Kristina; Häger, Charlotte; Lindgren, Lenita; Wester, Per; Brulin, Christine

2016-02-04

Despite high quality stroke care, decreased sensorimotor function, anxiety and pain often remain one year after stroke which can lead to impaired health and dependence, as well as higher healthcare costs. Touch massage (TM) has been proven to decrease anxiety and pain, and improve quality of health in other conditions of reduced health, where reduced anxiety seems to be the most pronounced benefit. Thus there are reasons to believe that TM may also reduce anxiety and pain, and improve quality of life after stroke. Further, several studies indicate that somatosensory stimulation can increase sensorimotor function, and it seems feasible to believe that TM could increase independence after stroke. In this study we will evaluate effects of TM after stroke compared to sham treatment. This is a prospective randomized open-labelled control trial with blinded evaluation (PROBE-design). Fifty patients with stroke admitted to stroke units will be randomized (1:1) to either a TM intervention or a non-active transcutaneous electrical nerve stimulation (non-TENS) control group. Ten sessions of 30 min treatments (TM or control) will be administered during two weeks. Assessment of status according to the International Classification of Functioning, Disability and Health (ICF), including body function, activity, and participation. Assessment of body function will include anxiety, pain, and stress response (heart rate variability and salivary cortisol), where anxiety is the primary outcome. Activity will be assessed by means of sensorimotor function and disability, and participation by means of health-related quality of life. Assessments will be made at baseline, after one week of treatment, after two weeks of treatment, and finally a follow-up after two months. The trial has been approved by the Regional Ethical Review Board. TM seems to decrease anxiety and pain, increase health-related quality of life, and improve sensorimotor functions after stroke, but the field is largely unexplored. Considering the documented pleasant effects of massage in general, absence of reported adverse effects, and potential effects in relation to stroke, it is essential to evaluate effects of TM during the sub-acute phase after stroke. The results of this project will hopefully provide important knowledge for evidence-based care. ClinicalTrials.gov: NTC01883947.

Time to brain imaging in acute stroke is improving: secondary analysis of the INSTINCT trial.

PubMed

Sauser, Kori; Burke, James F; Levine, Deborah A; Scott, Phillip A; Meurer, William J

2014-01-01

Patients with acute ischemic stroke benefit from rapid evaluation and treatment, and timely brain imaging is a necessary component. We determined the effect of a targeted behavioral intervention on door-to-imaging time (DIT) among patients with ischemic stroke treated with tissue-type plasminogen activator. Second, we examined the variation in DIT accounted for by patient-level and hospital-level factors. The Increasing Stroke Treatment through Interventional behavioral Change Tactics (INSTINCT) trial was a cluster-randomized, controlled trial involving 24 Michigan hospitals. The intervention aimed to increase tissue-type plasminogen activator utilization. Detailed chart abstractions collected data for 557 patients with ischemic stroke. We used a series of hierarchical linear mixed-effects models to evaluate the effect of the intervention on DIT (difference-in-differences analysis) and used patient-level and hospital-level explanatory variables to decompose variation in DIT. DIT improved over time, without a difference between intervention and control hospitals (intervention: 23.7-19.3 minutes, control: 28.9-19.2 minutes; P=0.56). Adjusted DIT was faster in patients who arrived by ambulance (7.2 minutes; 95% confidence interval, 4.1-10.2), had severe strokes (1.0 minute per +5-point National Institutes of Health Stroke Scale; 95% confidence interval, 0.1-2.0), and presented in the postintervention period (4.9 minutes; 95% confidence interval, 2.3-7.4). After accounting for these factors, 13.8% of variation in DIT was attributable to hospital. Neither hospital stroke volume nor stroke center status was associated with DIT. Performance on DIT improved similarly in intervention and control hospitals, suggesting that nonintervention factors explain the improvement. Hospital-level factors explain a modest proportion of variation in DIT, but further research is needed to identify the hospital-level factors responsible.

Long-term outcome of endovascular treatment versus medical care for carotid artery stenosis in patients not suitable for surgery and randomised in the Carotid and Vertebral Artery Transluminal Angioplasty study (CAVATAS).

PubMed

Ederle, Jörg; Featherstone, Roland L; Brown, Martin M

2009-01-01

Optimal treatment of carotid stenosis in patients not suitable for surgery is unclear. The Carotid and Vertebral Artery Transluminal Angioplasty study contained a trial comparing medical and endovascular treatment in patients not suitable for surgery. Forty patients were randomised to medical or endovascular treatment in equal numbers, and patients were followed up for up to 10 years. The primary outcome measure was defined as stroke or death during follow-up, analysed by intention-to-treat. Secondary analyses included disabling stroke, death, any stroke, any stroke or transient ischemic attack (TIA), all during follow-up. Baseline characteristics were similar. The risk of stroke, retinal infarction or death within 30 days of endovascular treatment was 5% (95% CI: 0.1-24.9%). By the study end, >50% of patients had suffered a recurrent TIA, stroke or died. One third of events were non-stroke deaths. Overall, there was no significant difference between medical and endovascular treatment in the primary outcome rate of stroke or death after randomisation (hazard ratio: 0.98, 95% CI: 0.39-2.48) or the rate of any stroke or TIA (hazard ratio: 1.43, 95% CI: 0.54-3.75). We failed to show superiority of endovascular treatment above medical care alone for carotid stenosis in a very small group of patients not suitable for surgical treatment. However, the trial randomised only 40 patients, and was therefore severely underpowered to detect clinically relevant treatment differences. Ongoing trials of carotid stenting will need to demonstrate improved safety and efficacy before endovascular treatment should enter routine practice. (c) 2009 S. Karger AG, Basel.

Endovascular Therapy Is Effective and Safe for Patients With Severe Ischemic Stroke: Pooled Analysis of Interventional Management of Stroke III and Multicenter Randomized Clinical Trial of Endovascular Therapy for Acute Ischemic Stroke in the Netherlands Data.

PubMed

Broderick, Joseph P; Berkhemer, Olvert A; Palesch, Yuko Y; Dippel, Diederik W J; Foster, Lydia D; Roos, Yvo B W E M; van der Lugt, Aad; Tomsick, Thomas A; Majoie, Charles B L M; van Zwam, Wim H; Demchuk, Andrew M; van Oostenbrugge, Robert J; Khatri, Pooja; Lingsma, Hester F; Hill, Michael D; Roozenbeek, Bob; Jauch, Edward C; Jovin, Tudor G; Yan, Bernard; von Kummer, Rüdiger; Molina, Carlos A; Goyal, Mayank; Schonewille, Wouter J; Mazighi, Mikael; Engelter, Stefan T; Anderson, Craig S; Spilker, Judith; Carrozzella, Janice; Ryckborst, Karla J; Janis, L Scott; Simpson, Kit N

2015-12-01

We assessed the effect of endovascular treatment in acute ischemic stroke patients with severe neurological deficit (National Institutes of Health Stroke Scale score, ≥20) after a prespecified analysis plan. The pooled analysis of the Interventional Management of Stroke III (IMS III) and Multicenter Randomized Clinical Trial of Endovascular Therapy for Acute Ischemic Stroke in the Netherlands (MR CLEAN) trials included participants with an National Institutes of Health Stroke Scale score of ≥20 before intravenous tissue-type plasminogen activator (tPA) treatment (IMS III) or randomization (MR CLEAN) who were treated with intravenous tPA ≤3 hours of stroke onset. Our hypothesis was that participants with severe stroke randomized to endovascular therapy after intravenous tPA would have improved 90-day outcome (distribution of modified Rankin Scale scores), when compared with those who received intravenous tPA alone. Among 342 participants in the pooled analysis (194 from IMS III and 148 from MR CLEAN), an ordinal logistic regression model showed that the endovascular group had superior 90-day outcome compared with the intravenous tPA group (adjusted odds ratio, 1.78; 95% confidence interval, 1.20-2.66). In the logistic regression model of the dichotomous outcome (modified Rankin Scale score, 0-2, or functional independence), the endovascular group had superior outcomes (adjusted odds ratio, 1.97; 95% confidence interval, 1.09-3.56). Functional independence (modified Rankin Scale score, ≤2) at 90 days was 25% in the endovascular group when compared with 14% in the intravenous tPA group. Endovascular therapy after intravenous tPA within 3 hours of symptom onset improves functional outcome at 90 days after severe ischemic stroke. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359424 (IMS III) and ISRCTN10888758 (MR CLEAN). © 2015 American Heart Association, Inc.

Stroke With Unknown Time of Symptom Onset: Baseline Clinical and Magnetic Resonance Imaging Data of the First Thousand Patients in WAKE-UP (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke: A Randomized, Doubleblind, Placebo-Controlled Trial).

PubMed

Thomalla, Götz; Boutitie, Florent; Fiebach, Jochen B; Simonsen, Claus Z; Nighoghossian, Norbert; Pedraza, Salvador; Lemmens, Robin; Roy, Pascal; Muir, Keith W; Ebinger, Martin; Ford, Ian; Cheng, Bastian; Galinovic, Ivana; Cho, Tae-Hee; Puig, Josep; Thijs, Vincent; Endres, Matthias; Fiehler, Jens; Gerloff, Christian

2017-03-01

We describe clinical and magnetic resonance imaging (MRI) characteristics of stroke patients with unknown time of symptom onset potentially eligible for thrombolysis from a large prospective cohort. We analyzed baseline data from WAKE-UP (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke: A Randomized, Doubleblind, Placebo-Controlled Trial), an investigator-initiated, randomized, placebo-controlled trial of MRI-based thrombolysis in stroke patients with unknown time of symptom onset. MRI judgment included assessment of the mismatch between visibility of the acute ischemic lesion on diffusion-weighted imaging and fluid-attenuated inversion recovery. Of 1005 patients included, diffusion-weighted imaging and fluid-attenuated inversion recovery mismatch was present in 479 patients (48.0%). Patients with daytime-unwitnessed stroke (n=138, 13.7%) had a shorter delay between symptom recognition and hospital arrival (1.5 versus 1.8 hours; P =0.002), a higher National Institutes of Stroke Scale score on admission (8 versus 6; P <0.001), and more often aphasia (72.5% versus 34.0%; P <0.001) when compared with stroke patients waking up from nighttime sleep. Frequency of diffusion-weighted imaging and fluid-attenuated inversion recovery mismatch was comparable between both groups (43.7% versus 48.7%; P =0.30). Almost half of the patients with unknown time of symptom onset stroke otherwise eligible for thrombolysis had MRI findings making them likely to be within a time window for safe and effective thrombolysis. Patients with daytime onset unwitnessed stroke differ from wake-up stroke patients with regards to clinical characteristics but are comparable in terms of MRI characteristics of lesion age. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01525290. URL: https://www.clinicaltrialsregister.eu. Unique identifier: 2011-005906-32. © 2017 American Heart Association, Inc.

Association of MTHFR C677T Genotype With Ischemic Stroke Is Confined to Cerebral Small Vessel Disease Subtype

PubMed Central

Traylor, Matthew; Adib-Samii, Poneh; Thijs, Vincent; Sudlow, Cathie; Rothwell, Peter M.; Boncoraglio, Giorgio; Dichgans, Martin; Meschia, James; Maguire, Jane; Levi, Christopher; Rost, Natalia S.; Rosand, Jonathan; Hassan, Ahamad; Bevan, Steve; Markus, Hugh S.

2016-01-01

Background and Purpose— Elevated plasma homocysteine levels are associated with stroke. However, this might be a reflection of bias or confounding because trials have failed to demonstrate an effect from homocysteine lowering in stroke patients, although a possible benefit has been suggested in lacunar stroke. Genetic studies could potentially overcome these issues because genetic variants are inherited randomly and are fixed at conception. Therefore, we tested the homocysteine levels–associated genetic variant MTHFR C677T for association with magnetic resonance imaging–confirmed lacunar stroke and compared this with associations with large artery and cardioembolic stroke subtypes. Methods— We included 1359 magnetic resonance imaging–confirmed lacunar stroke cases, 1824 large artery stroke cases, 1970 cardioembolic stroke cases, and 14 448 controls, all of European ancestry. Furthermore, we studied 3670 ischemic stroke patients in whom white matter hyperintensities volume was measured. We tested MTHFR C677T for association with stroke subtypes and white matter hyperintensities volume. Because of the established association of homocysteine with hypertension, we additionally stratified for hypertension status. Results— MTHFR C677T was associated with lacunar stroke (P=0.0003) and white matter hyperintensity volume (P=0.04), but not with the other stroke subtypes. Stratifying the lacunar stroke cases for hypertension status confirmed this association in hypertensive individuals (P=0.0002), but not in normotensive individuals (P=0.30). Conclusions— MTHFR C677T was associated with magnetic resonance imaging–confirmed lacunar stroke, but not large artery or cardioembolic stroke. The association may act through increased susceptibility to, or interaction with, high blood pressure. This heterogeneity of association might explain the lack of effect of lowering homocysteine in secondary prevention trials which included all strokes. PMID:26839351

Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) Trial: rationale and design

PubMed Central

Johnston, S. Claiborne; Easton, J. Donald; Farrant, Mary; Barsan, William; Battenhouse, Holly; Conwit, Robin; Dillon, Catherine; Elm, Jordan; Lindblad, Anne; Morgenstern, Lewis; Poisson, Sharon N.; Palesch, Yuko

2015-01-01

Background Ischemic stroke and other vascular outcomes occur in 10–20% of patients in the 3 months following a TIA or minor ischemic stroke, and many are disabling. The highest risk period for these outcomes is the early hours and days immediately following the ischemic event. Aspirin is the most common antithrombotic treatment used for these patients. Aim The aim of POINT is to determine whether clopidogrel plus aspirin taken <12 hours after TIA or minor ischemic stroke symptom onset is more effective in preventing major ischemic vascular events at 90 days in the high-risk, and acceptably safe, compared to aspirin alone. Design POINT is a prospective, randomized, double-blind, multicenter trial in patients with TIA or minor ischemic stroke. Subjects are randomized to clopidogrel (600 mg loading dose followed by 75 mg/day) or matching placebo, and all will receive open-label aspirin 50–325 mg/day, with a dose of 162 mg daily for 5 days followed by 81 mg daily strongly recommended. Study Outcomes The primary efficacy outcome is the composite of new ischemic vascular events: ischemic stroke, myocardial infarction or ischemic vascular death, by 90 days. The primary safety outcome is major hemorrhage, which includes symptomatic intracranial hemorrhage. Discussion Aspirin is the most common antithrombotic given to patients with a stroke or TIA as it reduces the risk subsequent of stroke. This trial expects to determine whether more aggressive antithrombotic therapy with clopidogrel plus aspirin, initiated acutely, is more effective than aspirin alone. PMID:23879752

Effect of hand paddles and parachute on backstroke coordination and stroke parameters.

PubMed

Telles, Thiago; Barroso, Renato; Figueiredo, Pedro; Salgueiro, Diego Fortes de Souza; Vilas-Boas, João Paulo; Junior, Orival Andries

2017-05-01

Hand paddles and parachutes have been used in order to overload swimmers, and consequently increase the propulsive force generation in swimming. However, their use may affect not only kinematical parameters (average speed, stroke length and stroke rate), but also time gaps between propulsive phases, assessed through the index of coordination (IdC). The objective of this study was to assess the effects of hand paddles and parachute use, isolated or combined, on kinematical parameters and coordination. Eleven swimmers (backstroke 50-m time: 29.16 ± 1.43 s) performed four 15-m trials in a randomised order at maximal intensity: (1) without implements (FREE), (2) with hand paddles (HPD), (3) with parachute (PCH) and (4) with hand paddles plus parachute (HPD+PCH). All trials were video-recorded (60 Hz) in order to assess average speed, stroke rate, stroke length, five stroke phases and index of coordination. When average swimming speed was compared to FREE, it was lower in PCH and HPD+PCH, and higher in HPD. Stroke rate decreased in all overloaded trials compared to FREE. The use of hand paddles and parachute increased and decreased stroke length, respectively. In addition, propulsive phase duration was increased when hand paddles were used, and time gaps shifted towards zero (no time gap), especially when hand paddles were combined with parachute. It is conceivable that the combined use of hand paddles and parachute, once allowing overloading both propulsive and resistive forces, provides a specific stimulus to improve muscle strength and propulsive continuity.

ERic Acute StrokE Recanalization: A study using predictive analytics to assess a new device for mechanical thrombectomy.

PubMed

Siemonsen, Susanne; Forkert, Nils D; Bernhardt, Martina; Thomalla, Götz; Bendszus, Martin; Fiehler, Jens

2017-08-01

Aim and hypothesis Using a new study design, we investigate whether next-generation mechanical thrombectomy devices improve clinical outcomes in ischemic stroke patients. We hypothesize that this new methodology is superior to intravenous tissue plasminogen activator therapy alone. Methods and design ERic Acute StrokE Recanalization is an investigator-initiated prospective single-arm, multicenter, controlled, open label study to compare the safety and effectiveness of a new recanalization device and distal access catheter in acute ischemic stroke patients with symptoms attributable to acute ischemic stroke and vessel occlusion of the internal cerebral artery or middle cerebral artery. Study outcome The primary effectiveness endpoint is the volume of saved tissue. Volume of saved tissue is defined as difference of the actual infarct volume and the brain volume that is predicted to develop infarction by using an optimized high-level machine learning model that is trained on data from a historical cohort treated with IV tissue plasminogen activator. Sample size estimates Based on own preliminary data, 45 patients fulfilling all inclusion criteria need to complete the study to show an efficacy >38% with a power of 80% and a one-sided alpha error risk of 0.05 (based on a one sample t-test). Discussion ERic Acute StrokE Recanalization is the first prospective study in interventional stroke therapy to use predictive analytics as primary and secondary endpoint. Such trial design cannot replace randomized controlled trials with clinical endpoints. However, ERic Acute StrokE Recanalization could serve as an exemplary trial design for evaluating nonpivotal neurovascular interventions.

Comparison of Registered and Reported Outcomes in Randomized Clinical Trials Published in Anesthesiology Journals.

PubMed

Jones, Philip M; Chow, Jeffrey T Y; Arango, Miguel F; Fridfinnson, Jason A; Gai, Nan; Lam, Kevin; Turkstra, Timothy P

2017-10-01

Randomized clinical trials (RCTs) provide high-quality evidence for clinical decision-making. Trial registration is one of the many tools used to improve the reporting of RCTs by reducing publication bias and selective outcome reporting bias. The purpose of our study is to examine whether RCTs published in the top 6 general anesthesiology journals were adequately registered and whether the reported primary and secondary outcomes corresponded to the originally registered outcomes. Following a prespecified protocol, an electronic database was used to systematically screen and extract data from RCTs published in the top 6 general anesthesiology journals by impact factor (Anaesthesia, Anesthesia & Analgesia, Anesthesiology, British Journal of Anaesthesia, Canadian Journal of Anesthesia, and European Journal of Anaesthesiology) during the years 2007, 2010, 2013, and 2015. A manual search of each journal's Table of Contents was performed (in duplicate) to identify eligible RCTs. An adequately registered trial was defined as being registered in a publicly available trials registry before the first patient being enrolled with an unambiguously defined primary outcome. For adequately registered trials, the outcomes registered in the trial registry were compared with the outcomes reported in the article, with outcome discrepancies documented and analyzed by the type of discrepancy. During the 4 years studied, there were 860 RCTs identified, with 102 RCTs determined to be adequately registered (12%). The proportion of adequately registered trials increased over time, with 38% of RCTs being adequately registered in 2015. The most common reason in 2015 for inadequate registration was registering the RCT after the first patient had already been enrolled. Among adequately registered trials, 92% had at least 1 primary or secondary outcome discrepancy. In 2015, 42% of RCTs had at least 1 primary outcome discrepancy, while 90% of RCTs had at least 1 secondary outcome discrepancy. Despite trial registration being an accepted best practice, RCTs published in anesthesiology journals have a high rate of inadequate registration. While mandating trial registration has increased the proportion of adequately registered trials over time, there is still an unacceptably high proportion of inadequately registered RCTs. Among adequately registered trials, there are high rates of discrepancies between registered and reported outcomes, suggesting a need to compare a published RCT with its trial registry entry to be able to fully assess the quality of the study. If clinicians base their decisions on evidence distorted by primary outcome switching, patient care could be negatively affected.

Novel Oral Anticoagulants in Atrial Fibrillation: Update on Apixaban

PubMed Central

Mezue, Kenechukwu; Obiagwu, Chukwudi; John, Jinu; Sharma, Abhishek; Yang, Felix; Shani, Jacob

2017-01-01

Almost 800,000 new or recurrent strokes occur every year. Atrial fibrillation, the most common cardiac arrhythmia, is a major risk factor for stroke, accounting for 15-20% of ischemic strokes. Apixaban is a direct inhibitor of Factor Xa that was approved in December 2012 by the US Food and Drug Administration (FDA) for the prevention of stroke in patients with non-valvular atrial fibrillation. It is part of a family of novel oral anticoagulants (NOACs) which has advantage over warfarin of less dosing variability, rapid onset of action and no INR monitoring required. Apixaban showed superiority to warfarin in both primary efficacy and primary safety outcomes by simultaneously showing both significantly lower rates of strokes and systemic embolism and a reduced risk of major clinical bleeding in clinical trials. Warfarin remains the anticoagulant of choice for patients with prosthetic heart valves and significant mitral stenosis. There are currently no head-to-head studies that directly compare the different NOACs with one another, but it is expected that there will be more trials in the future that will explore this comparison. Dabigatran is the only NOAC with an FDA approved reversal agent. However, a reversal agent for apixaban is being developed and was successful in recent clinical trials. This review summarizes the clinical trial data on apixaban for atrial fibrillation, compares apixaban to other NOACs and discusses apixaban use in clinical practice. PMID:27450450

77 FR 37421 - National Institute of Neurological Disorders and Stroke; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-21

... Neurological Disorders and Stroke; Notice of Closed Meetings Pursuant to section 10(d) of the Federal Advisory... Disorders and Stroke Special Emphasis Panel, NINDS Center for Clinical Trial Resources. Date: July 10, 2012... Stroke Special Emphasis Panel, PD Biomarker Review. Date: July 18, 2012. Time: 8:00 a.m. to 6:00 p.m...

Stroke Treatment Academic Industry Roundtable Recommendations for Individual Data Pooling Analyses in Stroke.

PubMed

Lees, Kennedy R; Khatri, Pooja

2016-08-01

Pooled analysis of individual patient data from stroke trials can deliver more precise estimates of treatment effect, enhance power to examine prespecified subgroups, and facilitate exploration of treatment-modifying influences. Analysis plans should be declared, and preferably published, before trial results are known. For pooling trials that used diverse analytic approaches, an ordinal analysis is favored, with justification for considering deaths and severe disability jointly. Because trial pooling is an incremental process, analyses should follow a sequential approach, with statistical adjustment for iterations. Updated analyses should be published when revised conclusions have a clinical implication. However, caution is recommended in declaring pooled findings that may prejudice ongoing trials, unless clinical implications are compelling. All contributing trial teams should contribute to leadership, data verification, and authorship of pooled analyses. Development work is needed to enable reliable inferences to be drawn about individual drug or device effects that contribute to a pooled analysis, versus a class effect, if the treatment strategy combines ≥2 such drugs or devices. Despite the practical challenges, pooled analyses are powerful and essential tools in interpreting clinical trial findings and advancing clinical care. © 2016 American Heart Association, Inc.

Economic Analysis of Apixaban Therapy for Patients With Atrial Fibrillation From a US Perspective

PubMed Central

Sheng, Shubin; Lopes, Renato D.; Anstrom, Kevin J.; Stafford, Judith A.; Davidson-Ray, Linda; Al-Khatib, Sana M.; Ansell, Jack; Dorian, Paul; Husted, Steen; McMurray, John J. V.; Steg, P. Gabriel; Alexander, John H.; Wallentin, Lars; Granger, Christopher B.; Mark, Daniel B.

2017-01-01

Importance The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial reported that apixaban therapy was superior to warfarin therapy in preventing stroke and all-cause death while causing significantly fewer major bleeds. To establish the value proposition of substituting apixiban therapy for warfarin therapy in patients with atrial fibrillation, we performed a cost-effectiveness analysis using patient-level data from the ARISTOTLE trial. Objective To assess the cost and cost-effectiveness of apixaban therapy compared with warfarin therapy in patients with atrial fibrillation from the perspective of the US health care system. Design, Setting, and Participants This economic analysis uses patient-level resource use and clinical data collected in the ARISTOTLE trial, a multinational randomized clinical trial that observed 18 201 patients (3417 US patients) for a median of 1.8 years between 2006 and 2011. Interventions Apixaban therapy vs warfarin therapy. Main Outcomes and Measures Within-trial resource use and cost were compared between treatments, using externally derived US cost weights. Life expectancies for US patients were estimated according to their baseline risk and treatment using time-based and age-based survival models developed using the overall ARISTOTLE population. Quality-of-life adjustment factors were obtained from external sources. Cost-effectiveness (incremental cost per quality-adjusted life-year gained) was evaluated from a US perspective, and extensive sensitivity analyses were performed. Results Of the 3417 US patients enrolled in ARISTOTLE, the mean (SD) age was 71 (10) years; 2329 (68.2%) were male and 3264 (95.5%) were white. After 2 years of anticoagulation therapy, health care costs (excluding the study drug) of patients treated with apixaban therapy and warfarin therapy were not statistically different (difference, −$60; 95% CI, −$2728 to $2608). Life expectancy, modeled from ARISTOTLE outcomes, was significantly longer with apixaban therapy vs warfarin therapy (7.94 vs 7.54 quality-adjusted life years). The incremental cost, including cost of anticoagulant and monitoring, of achieving these benefits was within accepted US norms ($53 925 per quality-adjusted life year, with 98% likelihood of meeting a $100 000 willingness-to-pay threshold). Results were generally consistent when model assumptions were varied, with lifetime cost-effectiveness most affected by the price of apixaban and the time horizon. Conclusions and Relevance Apixaban therapy for ARISTOTLE-eligible patients with atrial fibrillation provides clinical benefits at an incremental cost that represents reasonable value for money judged using US benchmarks for cost-effectiveness. Trial Registration clinicaltrials.gov Identifier: NCT00412984 PMID:28355434

Adopting new technologies in stroke rehabilitation: the influence of the US health care system.

PubMed

Stein, J

2009-06-01

Stroke rehabilitation is entering a new era of technological innovation, including the development of robotic aids for therapy, peripheral electrical stimulation devices, and brain stimulation systems. These technologies have the potential to significantly improve the efficiency and efficacy of stroke rehabilitation. The United States health care system creates both opportunities for new technologies to be created and adopted, as well as important barriers. Inadequate support of clinical trials of the efficacy of new non-invasive devices is a particular concern for practitioners seeking to determine if new devices are clinically useful. Government support of clinical trials of efficacy, coupled with reform of FDA approval processes for novel therapies, is needed to create an evidence-based approach to improving stroke rehabilitation.

Twelve month follow-up on a randomised controlled trial of relaxation training for post-stroke anxiety.

PubMed

Golding, Katherine; Fife-Schaw, Chris; Kneebone, Ian

2017-09-01

To follow up participants in a randomised controlled trial of relaxation training for anxiety after stroke at 12 months. Twelve month follow-up to a randomised controlled trial, in which the control group also received treatment. Community. Fifteen of twenty one original participants with post-stroke anxiety participated in a one year follow-up study. A self-help autogenic relaxation CD listened to five times a week for one month, immediately in the intervention group and after three months in the control group. Hospital Anxiety and Depression Scale-Anxiety subscale and the Telephone Interview of Cognitive Status for inclusion. Hospital Anxiety and Depression Scale-Anxiety subscale for outcome. All measures were administered by phone. Anxiety ratings reduced significantly between pre and post-intervention, and between pre-intervention and one year follow-up ( χ 2 (2) = 22.29, p < 0.001). Reductions in anxiety in stroke survivors who received a self-help autogenic relaxation CD appear to be maintained after one year.

Trial participants' experiences of early enhanced speech and language therapy after stroke compared with employed visitor support: a qualitative study nested within a randomized controlled trial.

PubMed

Young, Alys; Gomersall, Timothy; Bowen, Audrey

2013-02-01

To explore trial participants' experiences of the process and outcomes of early, enhanced speech and language therapy after stroke with support from an employed visitor. Qualitative study nested within a randomized controlled trial. Twney-two people who, after stroke, had a diagnosis of aphasia (12), dysarthria (5) or both (5) and who participated in the ACT NoW study. Eight English NHS usual care settings. Individual interviews. Thematic content analysis assisted by a bespoke data transformation protocol for incorporating non-verbal and semantically ambiguous data. Participants highly regarded regular and sustained contact with someone outside of immediate family/friends who engaged them in deliberate activities/communication in the early months after stroke. Participants identified differences in the process of intervention between speech and language therapists and employed visitors. But no major discriminations were made between the impact or value of this contact according to whether provided by a speech and language therapist or employed visitor. Participant-defined criteria for effectiveness of contact included: impact on mood and confidence, self-recognition of progress and the meeting of individual needs. As in the randomized controlled trial, participants reported no evidence of added benefit of early communication therapy beyond that from attention control. The findings do not imply that regular contact with any non-professional can have beneficial effects for someone with aphasia or dysarthria in the early weeks following a stroke. The study points to specific conditions that would have to be met for contact to have a positive effect.

Does the use of Nintendo Wii SportsTM improve arm function? Trial of WiiTM in Stroke: a randomized controlled trial and economics analysis.

PubMed

Adie, Katja; Schofield, Christine; Berrow, Margie; Wingham, Jennifer; Humfryes, John; Pritchard, Colin; James, Martin; Allison, Rhoda

2017-02-01

The Trial of Wii™ in Stroke investigated the efficacy of using the Nintendo Wii Sports™ (Wii TM ) to improve affected arm function after stroke. Multicentre, pragmatic, parallel group, randomized controlled trial. Home-based rehabilitation. A total of 240 participants aged 24-90 years with arm weakness following a stroke within the previous six months. Participants were randomly assigned to exercise daily for six weeks using the Wii TM or arm exercises at home. Primary outcome was change in the affected arm function at six weeks follow-up using the Action Research Arm Test. Secondary outcomes included occupational performance, quality of life, arm function at six months and a cost effectiveness analysis. The study was completed by 209 participants (87.1%). There was no significant difference in the primary outcome of affected arm function at six weeks follow-up (mean difference -1.7, 95% CI -3.9 to 0.5, p = 0.12) and no significant difference in secondary outcomes, including occupational performance, quality of life or arm function at six months, between the two groups. No serious adverse events related to the study treatment were reported. The cost effectiveness analysis showed that the Wii TM was more expensive than arm exercises £1106 (SD 1656) vs. £730 (SD 829) (probability 0.866). The trial showed that the Wii TM was not superior to arm exercises in home-based rehabilitation for stroke survivors with arm weakness. The Wii TM was well tolerated but more expensive than arm exercises.

PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2): Results of a Randomized, Double-Blind Placebo-Controlled Clinical Trial.

PubMed

de Ridder, Inger R; den Hertog, Heleen M; van Gemert, H Maarten A; Schreuder, A H C M L Tobien; Ruitenberg, Annemieke; Maasland, E Lisette; Saxena, Ritu; van Tuijl, Jordie H; Jansen, Ben P W; Van den Berg-Vos, Renske M; Vermeij, Frederique; Koudstaal, Peter J; Kappelle, L Jaap; Algra, Ale; van der Worp, H Bart; Dippel, Diederik W J

2017-04-01

Subfebrile body temperature and fever in the first days after stroke are strongly associated with unfavorable outcome. A subgroup analysis of a previous trial suggested that early treatment with paracetamol may improve functional outcome in patients with acute stroke and a body temperature of ≥36.5°C. In the present trial, we aimed to confirm this finding. PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2) was a multicenter, randomized, double-blind, placebo-controlled clinical trial. We aimed to include 1500 patients with acute ischemic stroke or intracerebral hemorrhage within 12 hours of symptom onset. Patients were treated with paracetamol in a daily dose of 6 g or matching placebo for 3 consecutive days. The primary outcome was functional outcome at 3 months, assessed with the modified Rankin Scale and analyzed with multivariable ordinal logistic regression. Because of slow recruitment and lack of funding, the study was stopped prematurely. Between December 2011 and October 2015, we included 256 patients, of whom 136 (53%) were allocated to paracetamol. In this small sample, paracetamol had no effect on functional outcome (adjusted common odds ratio, 1.15; 95% confidence interval, 0.74-1.79). There was no difference in the number of serious adverse events (paracetamol n=35 [26%] versus placebo n=28 [24%]). Treatment with high-dose paracetamol seemed to be safe. The effect of high-dose paracetamol on functional outcome remains uncertain. Therefore, a large trial of early treatment with high-dose paracetamol is still needed. URL: http://www.trialregister.nl. Unique identifier: NTR2365. © 2017 American Heart Association, Inc.

Neuroprotection as initial therapy in acute stroke. Third Report of an Ad Hoc Consensus Group Meeting. The European Ad Hoc Consensus Group.

PubMed

1998-01-01

Although a considerable body of scientific data is now available on neuroprotection in acute ischaemic stroke, this field is not yet established in clinical practice. At its third meeting, the European Ad Hoc Consensus Group considered the potential for neuroprotection in acute stroke and the practical problems attendant on the existence of a very limited therapeutic window before irreversible brain damage occurs, and came to the following conclusions. NEUROPROTECTANTS IN CLINICAL DEVELOPMENT: Convincing clinical evidence for an efficacious neuroprotective treatment in acute stroke is still required. Caution should be exercised in interpreting and extrapolating experimental results to stroke patients, who are a very heterogeneous group. The limitations of the time windows and the outcome measures chosen in trials of acute stroke therapy have an important influence on the results. The overall distribution of functional outcomes provides more statistical information than the proportion above a threshold outcome value. Neurological outcome should also be assessed. Neuroprotectants should not be tested clinically in phase II or phase III trials in a time window that exceeds those determined in experimental studies. The harmful effects of a drug in humans may override its neuroprotective potential determined in animals. Agents that act at several different levels in the ischaemic cascade may be more effective than those with a single mechanism of action. CURRENT IN-HOSPITAL MANAGEMENT OF ACUTE STROKE: The four major physiological variables that must be monitored and managed are blood pressure, arterial blood gas levels, body temperature, and glycaemia. The effects of controlling these physiological variables have not been studied in prospective trials, though they may all contribute to the outcome of acute ischaemic stroke and affect the duration of the therapeutic window. Optimal physiological parameters are inherently neuroprotective. Trials of new agents for the treatment of acute stroke should aim to maintain these physiological variables as close to normal as possible, and certainly within strictly defined limits. THE PLACE OF NEUROPROTECTANTS IN ACUTE STROKE MANAGEMENT: Stroke patients are a very heterogeneous group with respect to stroke mechanisms and severity, general condition, age and co-morbidities. At the present time, the only firm guideline than can be proposed for patient selection is the need for early admission to enable neuroprotectant and/or thrombolytic treatment to be started as soon as possible within the therapeutic window. The severity of potential side-effects will largely determine who should assess a patient with suspected stroke and initiate treatment. There is little information on which to base the duration of neuroprotectant therapy, and more experimental data are needed. Even if prehospital treatment proves to be feasible, it should not replace comprehensive stroke management in a specialist hospital unit. Clinical trials of neuroprotectants should only be performed in stroke units. The combined approach of restoring blood flow and providing neuroprotection may be the most productive in human stroke, but current clinical trial design will have to change in order to test combination therapy. Important side-effects are those that interfere with any possible benefit or increase mortality. PHARMACO-ECONOMIC ASPECTS OF NEUROPROTECTANTS: The early increase in hospital cost associated with neuroprotectant therapy may be balanced by the shorter length of hospital stay and lesser degree of disability of the surviving patients. The overall direct financial cost is highly dependent on the number of patients eligible for neuroprotectant therapy, which is itself dependent on the length of the therapeutic window and the severity of potential side-effects. A treatment that achieves a good functional outcome is the most cost-effective approach.

Endovascular vs medical management of acute ischemic stroke

PubMed Central

Ding, Dale; Starke, Robert M.; Mehndiratta, Prachi; Crowley, R. Webster; Liu, Kenneth C.; Southerland, Andrew M.; Worrall, Bradford B.

2015-01-01

Objective: To compare the outcomes between endovascular and medical management of acute ischemic stroke in recent randomized controlled trials (RCT). Methods: A systematic literature review was performed, and multicenter, prospective RCTs published from January 1, 2013, to May 1, 2015, directly comparing endovascular therapy to medical management for patients with acute ischemic stroke were included. Meta-analyses of modified Rankin Scale (mRS) and mortality at 90 days and symptomatic intracranial hemorrhage (sICH) for endovascular therapy and medical management were performed. Results: Eight multicenter, prospective RCTs (Interventional Management of Stroke [IMS] III, Local Versus Systemic Thrombolysis for Acute Ischemic Stroke [SYNTHESIS] Expansion, Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy [MR RESCUE], Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands [MR CLEAN], Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness [ESCAPE], Extending the Time for Thrombolysis in Emergency Neurological Deficits–Intra-Arterial [EXTEND-IA], Solitaire With the Intention For Thrombectomy as Primary Endovascular Treatment [SWIFT PRIME], and Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours [REVASCAT]) comprising 2,423 patients were included. Meta-analysis of pooled data demonstrated functional independence (mRS 0–2) at 90 days in favor of endovascular therapy (odds ratio [OR] = 1.71; p = 0.005). Subgroup analysis of the 6 trials with large vessel occlusion (LVO) criteria also demonstrated functional independence at 90 days in favor of endovascular therapy (OR = 2.23; p < 0.00001). Subgroup analysis of the 5 trials that primarily utilized stent retriever devices (≥70%) in the intervention arm demonstrated functional independence at 90 days in favor of endovascular therapy (OR = 2.39; p < 0.00001). No difference was found for mortality at 90 days and sICH between endovascular therapy and medical management in all analyses and subgroup analyses. Conclusions: This meta-analysis provides strong evidence that endovascular intervention combined with medical management, including IV tissue plasminogen activator for eligible patients, improves the outcomes of appropriately selected patients with acute ischemic stroke in the setting of LVO. PMID:26537058

Stroke mortality variations in South-East Asia: empirical evidence from the field.

PubMed

Hoy, Damian G; Rao, Chalapati; Hoa, Nguyen Phuong; Suhardi, S; Lwin, Aye Moe Moe

2013-10-01

Stroke is a leading cause of death in Asia; however, many estimates of stroke mortality are based on epidemiological models rather than empirical data. Since 2005, initiatives have been undertaken in a number of Asian countries to strengthen and analyse vital registration data. This has increased the availability of empirical data on stroke mortality. The aim of this paper is to present estimates of stroke mortality for Indonesia, Myanmar, Viet Nam, Thailand, and Malaysia, which have been derived using these empirical data. Age-specific stroke mortality rates were calculated in each of the five countries, and adjusted for data completeness or misclassification where feasible. All data were age-standardized and the resulting rates were compared with World Health Organization estimates, which are largely based on epidemiological models. Using empirical data, stroke ranked as the leading cause of death in all countries except Malaysia, where it ranked as the second leading cause. Age-standardized rates for males ranged from 94 per 100,000 in Thailand, to over 300 per 100,000 in Indonesia. In all countries, rates were higher for males than for females, and those compiled from empirical data were generally higher than modelled estimates published by World Health Organization. This study highlights the extent of stroke mortality in selected Asian countries, and provides important baseline information to investigate the aetiology of stroke in Asia and design appropriate public health strategies to address the rapidly growing burden from stroke. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

Effects of statins on stroke prevention in patients with and without coronary heart disease: a meta-analysis of randomized controlled trials.

PubMed

Briel, Matthias; Studer, Marco; Glass, Tracy R; Bucher, Heiner C

2004-10-15

To assess if lipid-lowering interventions (statins, fibrates, resins, n-3 fatty acids, diet) prevent nonfatal and fatal strokes in patients with and without coronary heart disease. We systematically searched the literature up to August 2002 to retrieve all randomized controlled trials of lipid-lowering interventions that reported nonfatal and fatal stroke and mortality data. The search yielded 65 trials with 200,607 patients for a meta-analysis to determine whether treatment effects differed between types of lipid-lowering interventions and between patient samples with and without coronary heart disease. The risk ratio for nonfatal and fatal stroke for statins as compared with control interventions was 0.82 (95% confidence interval [CI]: 0.76 to 0.90). The corresponding risk ratios for statins as compared with control were 0.75 (95% CI: 0.65 to 0.87) for patients with coronary heart disease and 0.77 (95% CI: 0.62 to 0.95) for those without coronary heart disease. The confidence intervals of risk ratios for nonfatal and fatal stroke associated with fibrates, resins, n-3 fatty acids, and diet all included 1, as did the confidence intervals for these interventions in patients with and without coronary heart disease. Weighted meta-regression analysis suggested a stronger association of stroke reduction with statin treatment than with the extent of cholesterol reduction. This meta-analysis suggests that statins reduce the incidence of stroke in patients with and without coronary heart disease.

Digoxin for atrial fibrillation and atrial flutter: A systematic review with meta-analysis and trial sequential analysis of randomised clinical trials

PubMed Central

Gluud, Christian; Jakobsen, Janus C.

2018-01-01

Background During recent years, systematic reviews of observational studies have compared digoxin to no digoxin in patients with atrial fibrillation or atrial flutter, and the results of these reviews suggested that digoxin seems to increase the risk of all-cause mortality regardless of concomitant heart failure. Our objective was to assess the benefits and harms of digoxin for atrial fibrillation and atrial flutter based on randomized clinical trials. Methods We searched CENTRAL, MEDLINE, Embase, LILACS, SCI-Expanded, BIOSIS for eligible trials comparing digoxin versus placebo, no intervention, or other medical interventions in patients with atrial fibrillation or atrial flutter in October 2016. Our primary outcomes were all-cause mortality, serious adverse events, and quality of life. Our secondary outcomes were heart failure, stroke, heart rate control, and conversion to sinus rhythm. We performed both random-effects and fixed-effect meta-analyses and chose the more conservative result as our primary result. We used Trial Sequential Analysis (TSA) to control for random errors. We used GRADE to assess the quality of the body of evidence. Results 28 trials (n = 2223 participants) were included. All were at high risk of bias and reported only short-term follow-up. When digoxin was compared with all control interventions in one analysis, we found no evidence of a difference on all-cause mortality (risk ratio (RR), 0.82; TSA-adjusted confidence interval (CI), 0.02 to 31.2; I2 = 0%); serious adverse events (RR, 1.65; TSA-adjusted CI, 0.24 to 11.5; I2 = 0%); quality of life; heart failure (RR, 1.05; TSA-adjusted CI, 0.00 to 1141.8; I2 = 51%); and stroke (RR, 2.27; TSA-adjusted CI, 0.00 to 7887.3; I2 = 17%). Our analyses on acute heart rate control (within 6 hours of treatment onset) showed firm evidence of digoxin being superior compared with placebo (mean difference (MD), -12.0 beats per minute (bpm); TSA-adjusted CI, -17.2 to -6.76; I2 = 0%) and inferior compared with beta blockers (MD, 20.7 bpm; TSA-adjusted CI, 14.2 to 27.2; I2 = 0%). Meta-analyses on acute heart rate control showed that digoxin was inferior compared with both calcium antagonists (MD, 21.0 bpm; TSA-adjusted CI, -30.3 to 72.3) and with amiodarone (MD, 14.7 bpm; TSA-adjusted CI, -0.58 to 30.0; I2 = 42%), but in both comparisons TSAs showed that we lacked information. Meta-analysis on acute conversion to sinus rhythm showed that digoxin compared with amiodarone reduced the probability of converting atrial fibrillation to sinus rhythm, but TSA showed that we lacked information (RR, 0.54; TSA-adjusted CI, 0.13 to 2.21; I2 = 0%). Conclusions The clinical effects of digoxin on all-cause mortality, serious adverse events, quality of life, heart failure, and stroke are unclear based on current evidence. Digoxin seems to be superior compared with placebo in reducing the heart rate, but inferior compared with beta blockers. The long-term effect of digoxin is unclear, as no trials reported long-term follow-up. More trials at low risk of bias and low risk of random errors assessing the clinical effects of digoxin are needed. Systematic review registration PROSPERO CRD42016052935 PMID:29518134

A Cluster-Randomized Controlled Trial of a Simplified Multifaceted Management Program for Individuals at High Cardiovascular Risk (SimCard Trial) in Rural Tibet, China and Haryana, India

PubMed Central

Tian, Maoyi; Ajay, Vamadevan S.; Dunzhu, Danzeng; Hameed, Safraj S.; Li, Xian; Liu, Zhong; Li, Cong; Chen, Hao; Cho, KaWing; Li, Ruilai; Zhao, Xingshan; Jindal, Devraj; Rawal, Ishita; Ali, Mohammed K.; Peterson, Eric D.; Ji, Jiachao; Amarchand, Ritvik; Krishnan, Anand; Tandon, Nikhil; Xu, Li-Qun; Wu, Yangfeng; Prabhakaran, Dorairaj; Yan, Lijing L.

2015-01-01

Background In rural areas in China and India, cardiovascular disease burden is high but economic and healthcare resources are limited. This study aims to develop and evaluate a simplified cardiovascular management program (SimCard) delivered by community health workers (CHWs) with the aid of a smartphone-based electronic decision support system. Methods and Results The SimCard study was a yearlong cluster-randomized controlled trial conducted in 47 villages (27 in China and 20 in India). 2,086 ‘high cardiovascular risk’ individuals (aged 40 years or older with self-reported history of coronary heart disease, stroke, diabetes, and/or measured systolic blood pressure ≥160 mmHg) were recruited. Participants in the intervention villages were managed by CHWs through an Android-powered “app” on a monthly basis focusing on two medication use and two lifestyle modifications. Compared with the control group, the intervention group had a 25.5% (P<0.001) higher net increase in the primary outcome of the proportion of patient-reported anti-hypertensive medication use pre-and-post intervention. There were also significant differences in certain secondary outcomes: aspirin use (net difference 17.1%, P<0.001) and systolic blood pressure (−2.7 mmHg, P=0.04). However, no significant changes were observed in the lifestyle factors. The intervention was culturally tailored and country-specific results revealed important differences between the regions. Conclusions The results indicate that the simplified cardiovascular management program improved quality of primary care and clinical outcomes in resource-poor settings in China and India. Larger trials in more places are needed to ascertain potential impacts on mortality and morbidity outcomes. Clinical Trial Registration Information clinicaltrials.gov. Identifier: NCT01503814. PMID:26187183

Treadmill training with partial body weight support after stroke.

PubMed

Hesse, Stefan; Werner, Cordula; von Frankenberg, Sophie; Bardeleben, Anita

2003-02-01

Treadmill therapy with partial BWS is a promising new approach to improve gait ability after stroke. This task-specific approach enables nonambulatory patients the repetitive practice of complex gait cycles instead of single-limb gait-preparatory maneuvers. Patients walk more symmetrically with less spasticity and better cardiovascular efficiency on the treadmill than with floor walking. Several controlled, clinical studies have shown the potential of treadmill training as a therapeutic intervention for nonambulatory patients with chronic stroke-related hemiplegia. Furthermore, controlled trials in acute stroke survivors have shown that treadmill training is as effective as other physiotherapy approaches that stress the repetitive practice of gait. Controlled multicenter trials comparing locomotor training with conventional therapy will be forthcoming. An electromechanical gait trainer that relieves the strenuous effort of the therapists and provides control of the trunk in a phase-dependent manner is a new technical alternative for gait training in severely impaired stroke patients.

A review of apixaban for stroke prevention in atrial fibrillation: insights from ARISTOTLE.

PubMed

Hess, Connie N; Al-Khatib, Sana M; Granger, Christopher B; Lopes, Renato

2013-09-01

Atrial fibrillation (AF) is associated with significant mortality and morbidity, and stroke represents the most-feared complication. Consequently, AF treatment has focused on thromboprophylaxis, with warfarin as the mainstay of therapy. However, concerns over ease of use and safety have limited its use. Three novel oral anticoagulants have been approved for use in stroke prevention in AF based on randomized data: 1) dabigatran, studied in Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY); 2) rivaroxaban, studied in Rivaroxaban Once-daily, Oral, Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF); and 3) apixaban, studied in Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE). In this review, we focus on apixaban and discuss subgroup analyses that have been performed in the three trials comparing novel oral anticoagulants with warfarin. We conclude with recommendations regarding further investigations.

Reducing depressive or anxiety symptoms in post-stroke patients: Pilot trial of a constructive integrative psychosocial intervention

PubMed Central

Fang, Yihong; Mpofu, Elias; Athanasou, James

2017-01-01

Background: About 30% of stroke survivors clinically have depressive symptoms at some point following stroke and anxiety prevalence is around 20-25%. Objective: The purpose of this brief report is to evaluate a pilot trial of a constructive integrative psychosocial intervention (CIPI) over standard care in post-stroke depression or anxiety. Methods: Patients were randomly assigned to either CIPI (n = 23) or standard care (n = 19). Patients were assessed using the Hospital Anxiety and Depression Scale at the 1st, 3rd, and 6th months to monitor changes of mood. Results: A Wilcoxon signed-rank test indicated that compared to admission baseline, patients with the intervention had significantly normal post-stroke depression symptom levels at the 1st, 3rd, and 6th months (P < 0.005). Conclusion: CIPI appears to be of incremental value in treating depression as well as anxiety in subacute care. PMID:29085269

Cost-effectiveness of anticoagulation in nonrheumatic atrial fibrillation in the primary prevention of ischemic stroke.

PubMed

Lightowlers, S; McGuire, A

1998-09-01

A number of clinical trials have shown the value of anticoagulating patients with nonrheumatic atrial fibrillation to prevent ischemic stroke. The purpose of this study was to assess the cost-effectiveness of anticoagulation in nonrheumatic atrial fibrillation with particular reference to the very elderly (aged >75 years) who have a higher incidence of bleeding events while undergoing anticoagulation. We calculated the incremental costs per life-year gained for 4 base cases using efficacy data from the Boston Area Anticoagulation Trial for Atrial Fibrillation, the meta-analysis of the 5 nonrheumatic atrial fibrillation trials, cost data from a district general hospital, and review of the literature. The cost per life-year gained free from stroke over 10 years ranged from -pound sterling 400.45 (ie, a resource saving achieved for each life-year gained free from stroke) to pound sterling 13,221.29. The results were most sensitive to alteration in the frequency of anticoagulation monitoring. For medical and economic reasons, anticoagulation treatment in the prevention of ischemic stroke is justified. Although older patients are more at risk of adverse events, anticoagulation is more cost-effective in this group.

Psychosocial Outcomes in StrokE: the POISE observational stroke study protocol

PubMed Central

Hackett, Maree L; Glozier, Nick; Jan, Stephen; Lindley, Richard

2009-01-01

Background Each year, approximately 12,000 Australians of working age survive a stroke. As a group, younger stroke survivors have less physical impairment and lower mortality after stroke compared with older survivors; however, the psychosocial and economic consequences are potentially substantial. Most of these younger stroke survivors have responsibility for generating an income or providing family care and indicate that their primary objective is to return to work. However, effective vocational rehabilitation strategies to increase the proportion of younger stroke survivors able to return to work, and information on the key target areas for those strategies, are currently lacking. Methods/Design This multi-centre, three year cohort study will recruit a representative sample of younger (< 65 years) stroke survivors to determine the modifiable predictors of subsequent return to work. Participants will be recruited from the New South Wales Stroke Services (SSNSW) network, the only well established and cohesively operating and managed, network of acute stroke units in Australia. It is based within the Greater Metropolitan area of Sydney including Wollongong and Newcastle, and extends to rural areas including Wagga Wagga. The study registration number is ACTRN12608000459325. Discussion The study is designed to identify targets for rehabilitation-, social- and medical-intervention strategies that promote and maintain healthy ageing in people with cardiovascular and mental health conditions, two of the seven Australian national health priority areas. This will rectify the paucity of information internationally around optimal clinical practice and social policy in this area. PMID:19519918

Cost-Effectiveness of Solitaire Stent Retriever Thrombectomy for Acute Ischemic Stroke

PubMed Central

Shireman, Theresa I.; Wang, Kaijun; Saver, Jeffrey L.; Goyal, Mayank; Bonafé, Alain; Diener, Hans-Christoph; Levy, Elad I.; Pereira, Vitor M.; Albers, Gregory W.; Cognard, Christophe; Hacke, Werner; Jansen, Olav; Jovin, Tudor G.; Mattle, Heinrich P.; Nogueira, Raul G.; Siddiqui, Adnan H.; Yavagal, Dileep R.; Devlin, Thomas G.; Lopes, Demetrius K.; Reddy, Vivek K.; de Rochemont, Richard du Mesnil; Jahan, Reza; Vilain, Katherine A.; House, John; Lee, Jin-Moo; Cohen, David J.

2017-01-01

Background and Purpose Clinical trials have demonstrated improved 90-day outcomes for patients with acute ischemic stroke treated with stent retriever thrombectomy plus tissue-type plasminogen activator (SST+tPA) compared with tPA. Previous studies suggested that this strategy may be cost-effective, but models were derived from pooled data and older assumptions. Methods In this prospective economic substudy conducted alongside the SWIFT-PRIME trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), in-trial costs were measured for patients using detailed medical resource utilization and hospital billing data. Utility weights were assessed at 30 and 90 days using the EuroQol-5 dimension questionnaire. Post-trial costs and life-expectancy were estimated for each surviving patient using a model based on trial data and inputs derived from a contemporary cohort of ischemic stroke survivors. Results Index hospitalization costs were $17 183 per patient higher for SST+tPA than for tPA ($45 761 versus $28 578; P<0.001), driven by initial procedure costs. Between discharge and 90 days, costs were $4904 per patient lower for SST+tPA than for tPA ($11 270 versus $16 174; P=0.014); total 90-day costs remained higher with SST+tPA ($57 031 versus $44 752; P<0.001). Higher utility values for SST+tPA led to higher in-trial quality-adjusted life years (0.131 versus 0.105; P=0.005). In lifetime projections, SST+tPA was associated with substantial gains in quality-adjusted life years (6.79 versus 5.05), cost savings of $23 203 per patient and was economically dominant when compared with tPA in 90% of bootstrap replicates. Conclusions Among patients with acute ischemic stroke enrolled in the SWIFT-PRIME trial, SST increased initial treatment costs, but was projected to improve quality-adjusted life-expectancy and reduce healthcare costs over a lifetime horizon compared with tPA. PMID:28028150

37 CFR 7.41 - Renewal of international registration and extension of protection.

Code of Federal Regulations, 2013 CFR

2013-07-01

... registration may be issued to 2.171 Not domiciled in U.S. 3.61 Right to take action when assignment is recorded... Trial and Appeal Board 2.145(d) Waiver of right to proceed by civil action in ex parte case 2.145(c)(2... Trial and Appeal Board) Ex parte matter disclosed but not tried in inter partes case 2.131 Express...

B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial.

PubMed

2010-09-01

Epidemiological studies suggest that raised plasma concentrations of total homocysteine might be a risk factor for major vascular events. Whether lowering total homocysteine with B vitamins prevents major vascular events in patients with previous stroke or transient ischaemic attack is unknown. We aimed to assess whether the addition of once-daily supplements of B vitamins to usual medical care would lower total homocysteine and reduce the combined incidence of non-fatal stroke, non-fatal myocardial infarction, and death attributable to vascular causes in patients with recent stroke or transient ischaemic attack of the brain or eye. In this randomised, double-blind, parallel, placebo-controlled trial, we assigned patients with recent stroke or transient ischaemic attack (within the past 7 months) from 123 medical centres in 20 countries to receive one tablet daily of placebo or B vitamins (2 mg folic acid, 25 mg vitamin B6, and 0.5 mg vitamin B12). Patients were randomly allocated by means of a central 24-h telephone service or an interactive website, and allocation was by use of random permuted blocks stratified by hospital. Participants, clinicians, carers, and investigators who assessed outcomes were masked to the assigned intervention. The primary endpoint was the composite of stroke, myocardial infarction, or vascular death. All patients randomly allocated to a group were included in the analysis of the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT00097669, and Current Controlled Trials, ISRCTN74743444. Between Nov 19, 1998, and Dec 31, 2008, 8164 patients were randomly assigned to receive B vitamins (n=4089) or placebo (n=4075). Patients were followed up for a median duration of 3.4 years (IQR 2.0-5.5). 616 (15%) patients assigned to B vitamins and 678 (17%) assigned to placebo reached the primary endpoint (risk ratio [RR] 0.91, 95% CI 0.82 to 1.00, p=0.05; absolute risk reduction 1.56%, -0.01 to 3.16). There were no unexpected serious adverse reactions and no significant differences in common adverse effects between the treatment groups. Daily administration of folic acid, vitamin B6, and vitamin B12 to patients with recent stroke or transient ischaemic attack was safe but did not seem to be more effective than placebo in reducing the incidence of major vascular events. These results do not support the use of B vitamins to prevent recurrent stroke. The results of ongoing trials and an individual patient data meta-analysis will add statistical power and precision to present estimates of the effect of B vitamins. Australia National Health and Medical Research Council, UK Medical Research Council, Singapore Biomedical Research Council, Singapore National Medical Research Council, Australia National Heart Foundation, Royal Perth Hospital Medical Research Foundation, and Health Department of Western Australia. Copyright 2010 Elsevier Ltd. All rights reserved.

Nonvitamin-K-antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and previous stroke or transient ischemic attack: An updated systematic review and meta-analysis of randomized controlled trials.

PubMed

Ntaios, George; Papavasileiou, Vasileios; Diener, Hans-Chris; Makaritsis, Konstantinos; Michel, Patrik

2017-08-01

Background In a previous systematic review and meta-analysis, we assessed the efficacy and safety of nonvitamin-K antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and stroke or transient ischemic attack. Since then, new information became available. Aim The aim of the present work was to update the results of the previous systematic review and meta-analysis. Methods We searched PubMed until 24 August 2016 for randomized controlled trials using the following search items: "atrial fibrillation" and "anticoagulation" and "warfarin" and "previous stroke or transient ischemic attack." Eligible studies had to be phase III trials in patients with atrial fibrillation comparing warfarin with nonvitamin-K antagonist oral anticoagulants currently on the market or with the intention to be brought to the market in North America or Europe. The outcomes assessed in the efficacy analysis included stroke or systemic embolism, stroke, ischemic or unknown stroke, disabling or fatal stroke, hemorrhagic stroke, cardiovascular death, death from any cause, and myocardial infarction. The outcomes assessed in the safety analysis included major bleeding, intracranial bleeding, and major gastrointestinal bleeding. We performed fixed effects analyses on intention-to-treat basis. Results Among 183 potentially eligible articles, four were included in the meta-analysis. In 20,500 patients, compared to warfarin, nonvitamin-K antagonist oral anticoagulants were associated with a significant reduction of stroke/systemic embolism (relative risk reduction: 13.7%, absolute risk reduction: 0.78%, number needed to treat to prevent one event: 127), hemorrhagic stroke (relative risk reduction: 50.0%, absolute risk reduction: 0.63%, number needed to treat: 157), any stroke (relative risk reduction: 13.1%, absolute risk reduction: 0.7%, number needed to treat: 142), and intracranial hemorrhage (relative risk reduction: 46.1%, absolute risk reduction: 0.88%, number needed to treat: 113) over 1.8-2.8 years. Conclusions This updated meta-analysis in 20,500 atrial fibrillation patients with previous stroke or transient ischemic attack shows that compared to warfarin non-vitamin-K antagonist oral anticoagulants are associated with a significant reduction of stroke, stroke or systemic embolism, hemorrhagic stroke, and intracranial bleeding.

Oxfordshire community stroke project clinical stroke syndrome and appearances of tissue and vascular lesions on pretreatment ct in hyperacute ischemic stroke among the first 510 patients in the Third International Stroke Trial (IST-3).

PubMed

Kobayashi, Adam; Wardlaw, Joanna M; Lindley, Richard I; Lewis, Steff C; Sandercock, Peter A G; Czlonkowska, Anna

2009-03-01

The Oxfordshire Community Stroke Project (OCSP) clinical stroke syndrome classification correlates well with the stroke lesion in established ischemic stroke, but there are few data in patients with hyperacute stroke. We wished to assess whether the OCSP correlated with the site and size of the ischemic lesion and location of cerebral vessel lesion on computed tomography (CT) in hyperacute stroke. Prospective study of ischemic stroke patients presenting within 6 hours of onset in the Third International Stroke Trial (IST-3), a randomized, controlled trial of rt-PA. OCSP syndrome was assigned by a computer-based algorithm. The CT assessment was made by a neuroradiologist blinded to clinical details. We assessed baseline data and CT findings for the first 510 patients; early tissue ischemic changes were present in 329/510 (65%) total anterior circulation syndrome (TACS) - 79%; partial anterior circulation syndrome (PACS) - 57%, lacunar syndrome (LACS) - 40%; posterior circulation syndrome (POCS) - 33%. The site and size of ischemic change on CT was compatible with the clinical syndrome in 79%, 37%, 2%, and 14%, respectively. Assuming that all patients with a normal CT scan will develop an incompatible lesion these numbers reflected the "worst possible scenario." For the "best possible scenario" we presumed that those with a normal CT will develop concordant ischemic change and the proportions were 100%, 80%, 62% and 81%, respectively. The hyperattenuated artery sign was seen in 206/510 (40%); (TACS 54%; PACS 35%, LACS 5%, and POCS 19%). Within 6 hours of stroke, in patients with a nonlacunar syndrome, the OCSP syndrome correlated well with the pattern of ischemic change on CT. For clinicians who wish to restrict the use of thrombolytic therapy to large-artery ischemic stroke, concordance of clinical and CT appearances may give greater confidence in making therapeutic decisions in hyperacute stroke. In centers where immediate access to MR is limited, use of the classification may help focus use of MR on patients with suspected LACS and POCS. The utility of the classification may further increase if IST-3 establishes that the OCSP syndrome significantly modifies response to thrombolytic therapy.

Prevention of Stroke with Ticagrelor in Patients with Prior Myocardial Infarction: Insights from PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54).

PubMed

Bonaca, Marc P; Goto, Shinya; Bhatt, Deepak L; Steg, P Gabriel; Storey, Robert F; Cohen, Marc; Goodrich, Erica; Mauri, Laura; Ophuis, Ton Oude; Ruda, Mikhail; Špinar, Jindřich; Seung, Ki-Bae; Hu, Dayi; Dalby, Anthony J; Jensen, Eva; Held, Peter; Morrow, David A; Braunwald, Eugene; Sabatine, Marc S

2016-09-20

In the PEGASUS-TIMI 54 trial (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54), ticagrelor reduced the risk of major adverse cardiovascular events when added to low-dose aspirin in stable patients with prior myocardial infarction, resulting in the approval of ticagrelor 60 mg twice daily for long-term secondary prevention. We investigated the incidence of stroke, outcomes after stroke, and the efficacy of ticagrelor focusing on the approved 60 mg twice daily dose for reducing stroke in this population. Patients were followed for a median of 33 months. Stroke events were adjudicated by a central committee. Data from similar trials were combined using meta-analysis. Of 14 112 patients randomly assigned to placebo or ticagrelor 60 mg, 213 experienced a stroke; 85% of these strokes were ischemic. A total of 18% of strokes were fatal and another 15% led to either moderate or severe disability at 30 days. Ticagrelor significantly reduced the risk of stroke (hazard ratio, 0.75; 95% confidence interval, 0.57-0.98; P=0.034), driven by a reduction in ischemic stroke (hazard ratio, 0.76; 95% confidence interval, 0.56-1.02). Hemorrhagic stroke occurred in 9 patients on placebo and 8 patients on ticagrelor. A meta-analysis across 4 placebo-controlled trials of more intensive antiplatelet therapy in 44 816 patients with coronary disease confirmed a marked reduction in ischemic stroke (hazard ratio, 0.66; 95% confidence interval, 0.54-0.81; P=0.0001). High-risk patients with prior myocardial infarction are at risk for stroke, approximately one-third of which are fatal or lead to moderate-to-severe disability. The addition of ticagrelor 60 mg twice daily significantly reduced this risk without an excess of hemorrhagic stroke but with more major bleeding. In high-risk patients with coronary disease, more intensive antiplatelet therapy should be considered not only to reduce the risk of coronary events, but also of stroke. URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01225562. © 2016 American Heart Association, Inc.

Cerebrovascular accidents in elderly people treated with antipsychotic drugs: a systematic review.

PubMed

Sacchetti, Emilio; Turrina, Cesare; Valsecchi, Paolo

2010-04-01

After 2002, an association between stroke and antipsychotic use was reported in clinical trials and large database studies. This review considers previous quantitative reviews, newly published clinical trials, and recent observational cohort and case-control studies, and focuses on the clinical significance of the risk for stroke, the difference between typical and atypical antipsychotics, the possible at-risk patient profile and the timing of stroke after exposure. A search of MEDLINE covering the period from 1966 to June 2009 was carried out using selected keywords. Inclusion criteria were (i) quantitative reviews on stroke and antipsychotics; (ii) double-blind, placebo-controlled clinical trials involving patients with dementia treated with antipsychotics; and (iii) observational database cohort studies and observational case-control studies investigating the association between stroke and antipsychotics. Clinical trials were excluded if they were single-blind or if patients were affected by dementia and/or other neurological illnesses. Four reviews with aggregate data, 2 meta-analyses, 13 randomized, double-blind, controlled trials, 7 observational cohort studies and 4 observational case-control studies were selected and analysed. The incidence of cerebrovascular accidents (CVAs) was found to be very low in aggregate reviews and meta-analyses (2-4%). When the number collected was sufficiently high, or different drug treatments were grouped together, the higher rate in subjects exposed to antipsychotics was statistically significant. Inspection of other randomized controlled clinical trials, not included in aggregate reviews and meta-analyses, reported similar rates of CVAs. The majority of observational cohort studies compared typical and atypical antipsychotics and no significant class differences were found. A comparison with non-users was carried out in some cohort studies. In case-control studies, the probability of CVAs in users compared with non-users was in the range of 1.3- to 2-fold greater. Preliminary data also indicate that the highest risk of stroke is related to the first weeks of treatment, and a risk profile for stroke is emerging, such as older age, cognitive impairment and vascular illness. Different pathophysiological pathways may be involved, ranging from the facilitation of thrombosis, pre-existing cardiovascular factors, sedation and a common diathesis for stroke of dementia, schizophrenia and affective illness. Before prescribing an antipsychotic, clinicians should weigh all the risk factors for a given patient and consider not only the indications as provided by the regulatory agencies, but also the overall effectiveness of typical and atypical antipsychotics.

Stroke liaison workers for stroke patients and carers: an individual patient data meta-analysis.

PubMed

Ellis, Graham; Mant, Jonathan; Langhorne, Peter; Dennis, Martin; Winner, Simon

2010-05-12

Many patients experience depression, social isolation and anxiety post stroke. These are associated with a poorer outcome. Ameliorating these problems may improve patient wellbeing. To evaluate the impact of a healthcare worker or volunteer whose multi-dimensional roles have been grouped under the title 'stroke liaison worker'. We searched the Cochrane Stroke Group Trials Register (searched February 2009), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2009), MEDLINE (1966 to 2009), EMBASE (1980 to 2009) and four other databases. We performed a cited reference search, searched conference proceedings and trials registers, checked reference lists and contacted authors and trial investigators. Randomised controlled trials investigating the impact of a stroke liaison worker versus usual care. We invited trialists to participate in a review of individual patient data. Primary outcomes for patients were subjective health status and extended activities of daily living. Primary outcomes for carers were subjective health status including measures of carer strain. We included 16 trials involving 4759 participants. Analysis did not show a significant overall difference for subjective health status (standardised mean difference (SMD) -0.03, 95% confidence interval (CI) -0.11 to 0.04, P = 0.34) or extended activities of daily living (SMD 0.04, 95% CI -0.03 to 0.11, P = 0.22). There was no overall significant effect for the outcome of carer subjective health status (SMD 0.04, 95% CI -0.05 to 0.14, P = 0.37). Patients with mild to moderate disability (Barthel 15 to 19) had a significant reduction in dependence (odds ratio (OR) 0.62, 95% CI 0.44 to 0.87, P = 0.006). This would equate to 10 fewer dependent patients (95% CI 17 fewer to 4 fewer) for every 100 patients seen by the stroke liaison worker. Similar results were seen for the outcome of death or dependence for the subgroup with Barthel 15 to 19 (OR 0.55, 95% CI 0.38 to 0.81, P = 0.002). This risk difference equates to 11 fewer dead or dependent patients (95% CI 17 fewer to 4 fewer) for every 100 patients seen by the stroke liaison worker. There is no evidence for the effectiveness of this multifaceted intervention in improving outcomes for all groups of patients or carers. Patients with mild to moderate disability benefit from a reduction in death and disability. Patients and carers do report improved satisfaction with some aspects of service provision.

Thrombolysis for acute ischaemic stroke with alteplase in an Asian population: results of the multicenter, multinational Safe Implementation of Thrombolysis in Stroke-Non-European Union World (SITS-NEW).

PubMed

Rha, Joung-Ho; Shrivastava, Vasantha Padma; Wang, Yongjun; Lee, Kim En; Ahmed, Niaz; Bluhmki, Erich; Hermansson, Karin; Wahlgren, Nils

2014-10-01

Safe Implementation of Thrombolysis in Stroke-Non-European Union World was a multinational, prospective, open, monitored, observational study of intravenous alteplase as thrombolytic therapy in clinical practice. Safe Implementation of Thrombolysis in Stroke-Non-European Union World was required to assess the safety of alteplase in an Asian population by comparison with results from the European Safe Implementation of Thrombolysis in Stroke-Monitoring Study and pooled results from randomized controlled trials. To evaluate the efficacy and safety of intravenous alteplase (0·9 mg/kg) as thrombolytic therapy within three-hours of onset of acute ischaemic stroke in an Asian population. The 591 patients included were treated at 48 centers in four countries (South Korea, China, India, and Singapore) between 2006 and 2008. Primary outcomes were symptomatic (deterioration in National Institutes of Health Stroke Scale score ≥4 or death within the first 24 h) intracerebral haemorrhage type 2 22-36 h after the thrombolysis and mortality at three-month follow-up. The secondary outcome was functional independence (modified Rankin Scale score 0-2) at three-months. Results were compared with those from Safe Implementation of Thrombolysis in Stroke-Monitoring Study (n = 6483) and pooled results of patients (n = 415) who received intravenous alteplase (0·9 mg/kg) zero- to three-hours from onset of stroke symptoms in four randomized controlled trials (National Institute of Neurological Disorders and Stroke A and B, Altephase Thrombolysis for Acute Noninterventional Therapy in Ischaemic Stroke, and European Cooperative Acute Stroke Study II). Results are presented as Safe Implementation of Thrombolysis in Stroke-Non-European Union World vs. Safe Implementation of Thrombolysis in Stroke-Monitoring Study vs. pooled randomized controlled trials. Median age was 64 vs. 68 vs. 70 years, National Institutes of Health Stroke Scale score at baseline was 12 vs. 12 vs. 13, time from stroke onset to treatment was 130 vs. 140 vs. 135 mins, and females were 36·4% vs. 39·8% vs. 41·2%. Main outcomes (proportion of patients and 95% confidence intervals) were symptomatic intracerebral haemorrhage: 1·9% (1·1-3·3) vs. 1·7% (1·4-2·0) vs. 3·1% (1·8-5·3); mortality: 10·2% (8·0-12·9) vs. 11·3% (10·5-12·1) vs. 16·4% (13·1-20·3); and functional independence: 62·5% (58·5-66·4) vs. 54·8% (53·5-56·0) vs. 50·1% (45·3-54·9) at three-months. Adjusted odds ratio (95% confidence intervals) between Safe Implementation of Thrombolysis in Stroke-Non-European Union World and Safe Implementation of Thrombolysis in Stroke-Monitoring Study, and between Safe Implementation of Thrombolysis in Stroke-Non-European Union World and the pooled trials were 1·83 (0·89-3·77; P = 0·1156) and 0·63 (0·19-2·07; P = 0·4470) for symptomatic intracerebral haemorrhage, 0·90 (0·64-1·25; P = 0·5092) and 0·93 (0·52-1·64; P = 0·7915) for mortality at three-months, and 1·57 (1·25-1·96; P < 0·0001) and 1·35 (0·91-2·00; P = 0·1325) for functional independence. These data demonstrate the safety and efficacy of the standard dose of intravenous alteplase (0·9 mg/kg) in an Asian population, as previously observed in the European population studied in Safe Implementation of Thrombolysis in Stroke-Monitoring Study and the populations in pooled randomized controlled trials, when used in routine clinical practice within three-hours of stroke onset. The findings should encourage wider use of thrombolytic therapy in Asian countries for suitable patients treated in stroke centers. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

Greater Cincinnati/Northern Kentucky Stroke Study: volume of first-ever ischemic stroke among blacks in a population-based study.

PubMed

Kissela, B; Broderick, J; Woo, D; Kothari, R; Miller, R; Khoury, J; Brott, T; Pancioli, A; Jauch, E; Gebel, J; Shukla, R; Alwell, K; Tomsick, T

2001-06-01

The volume of ischemic stroke on CT scans has been studied in a standardized fashion in acute stroke therapy trials with median volumes between 10.5 to 55 cm(3). The volume of first-ever ischemic stroke in the population is not known. The first phase of the population-based Greater Cincinnati/Northern Kentucky Stroke Study identified all ischemic strokes occurring in blacks in the greater Cincinnati region between January and June of 1993. The patients in this phase of the study who had a first-ever ischemic clinical stroke were identified, and the volume of ischemic stroke was measured. There were 257 verified clinical cases of ischemic stroke, of which 181 had a first-ever ischemic infarct. Imaging was available for 150 of these patients, and 79 had an infarct on the CT or MRI study that was definitely or possibly related to the clinical symptoms. For these patients, volumetric measurements were performed by means of the modified ellipsoid method. The median volume of first-ever ischemic stroke for the 79 patients was 2.5 cm(3) (interquartile range, 0.5 to 8.8 cm(3)). There was a significant relation between location of lesion and infarct size (P<0.001) and between volume and mechanism of stroke (P=0.001). The volume of first-ever ischemic stroke among blacks in our population-based study is smaller than has been previously reported in acute stroke therapy trials. The large proportion of small, mild strokes in blacks may be an important reason for the low percentage of patients who meet the inclusion criteria for tissue plasminogen activator. Further study is necessary to see if these results are generalizable to a multiracial population.

Predictors of stroke recurrence in patients with recent lacunar stroke and response to interventions according to risk status: secondary prevention of small subcortical strokes trial.

PubMed

Hart, Robert G; Pearce, Lesly A; Bakheet, Majid F; Benavente, Oscar R; Conwit, Robin A; McClure, Leslie A; Talbert, Robert L; Anderson, David C

2014-04-01

Among participants in the Secondary Prevention of Small Subcortical Strokes randomized trial, we sought to identify patients with high versus low rates of recurrent ischemic stroke and to assess effects of aggressive blood pressure control and dual antiplatelet therapy according to risk status. Multivariable analyses of 3020 participants with recent magnetic resonance imaging-defined lacunar strokes followed for a mean of 3.7 years with 243 recurrent ischemic strokes. Prior symptomatic lacunar stroke or transient ischemic attack (TIA) (hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.6, 2.9), diabetes (HR 2.0, 95% CI 1.5, 2.5), black race (HR 1.7, 95% CI 1.3, 2.3), and male sex (HR 1.5, 95% CI 1.1, 1.9) were each independently predictive of recurrent ischemic stroke. Recurrent ischemic stroke occurred at a rate of 4.3% per year (95% CI 3.4, 5.5) in patients with prior symptomatic lacunar stroke or TIA (15% of the cohort), 3.1% per year (95% CI 2.6, 3.9) in those with more than 1 of the other 3 risk factors (27% of the cohort), and 1.3% per year (95% CI 1.0, 1.7) in those with 0-1 risk factors (58% of the cohort). There were no significant interactions between treatment effects and stroke risk status. In this large, carefully followed cohort of patients with recent lacunar stroke and aggressive blood pressure management, prior symptomatic lacunar ischemia, diabetes, black race, and male sex independently predicted ischemic stroke recurrence. The effects of blood pressure targets and dual antiplatelet therapy were similar across the spectrum of independent risk factors and recurrence risk. Copyright © 2014 National Stroke Association. All rights reserved.

Post-stroke dysphagia: A review and design considerations for future trials.

PubMed

Cohen, David L; Roffe, Christine; Beavan, Jessica; Blackett, Brenda; Fairfield, Carol A; Hamdy, Shaheen; Havard, Di; McFarlane, Mary; McLauglin, Carolee; Randall, Mark; Robson, Katie; Scutt, Polly; Smith, Craig; Smithard, David; Sprigg, Nikola; Warusevitane, Anushka; Watkins, Caroline; Woodhouse, Lisa; Bath, Philip M

2016-06-01

Post-stroke dysphagia (a difficulty in swallowing after a stroke) is a common and expensive complication of acute stroke and is associated with increased mortality, morbidity, and institutionalization due in part to aspiration, pneumonia, and malnutrition. Although most patients recover swallowing spontaneously, a significant minority still have dysphagia at six months. Although multiple advances have been made in the hyperacute treatment of stroke and secondary prevention, the management of dysphagia post-stroke remains a neglected area of research, and its optimal management, including diagnosis, investigation and treatment, have still to be defined. © 2016 World Stroke Organization.

Blood pressure as a therapeutic target in stroke.

PubMed

Armario, Pedro; de la Sierra, Alejandro

2009-01-01

Stroke, as a clinical manifestation of the cardiovascular diseases, is one of the leading causes of death and disability in both developed and developing countries. Hypertension is by far, the most important risk factor for stroke. Epidemiological data indicate that the risk of stroke increases with both systolic and diastolic blood pressure elevation, from levels of 115/75 mmHg. It is also evident that most adults worldwide have values above these limits, thus emphasizing the importance of blood pressure as a risk factor for stroke. Clinical trials of antihypertensive treatment, both in studies that have compared active drugs against placebo or in those comparing different types of drugs have clearly demonstrated a protective effect of blood pressure reduction in the prevention of stroke. The degree of protection is directly related to blood pressure reduction and, the lower the level, the better the prognosis. Although data on secondary stroke prevention are scarcer, studies also seem to indicate that lowering blood pressure with antihypertensive treatment protects against stroke recurrence. At the present moment there is still uncertainty on 2 different aspects regarding the relationship between antihypertensive treatment and stroke. First, the blood pressure management during acute stroke has not adequately investigated in clinical trials. Second, the possibility of a protective role of specific types of antihypertensive drugs beyond blood pressure reduction is a matter of debate. Independently of these unresolved issues, prevention of hypertension development by lifestyle changes and adequate treatment and control to the hypertensive population will be a very effective measure in reducing stroke incidence, stroke recurrence, and stroke mortality.

Antihypertensive treatment and stroke prevention: are angiotensin receptor blockers superior to other antihypertensive agents?

PubMed

Armario, Pedro; de la Sierra, Alejandro

2009-06-01

Stroke remains a common vascular event with high mortality and morbidity. After heart disease, stroke is the second leading cause of death worldwide in adult persons. Silent or subclinical stroke is likely to occur with even greater frequency than clinical stroke and increases the risk of subsequent cerebrovascular events. Hypertension is by far the single most important controllable risk factor for stroke. The relationship between blood pressure (BP) and stroke mortality is strong, linear, and continuous in subjects with levels of BP higher than 115/75 mm Hg. Blood pressure reduction by antihypertensive treatment is clearly efficacious in the prevention of stroke (both primary and secondary). Although meta-analyses suggest that BP reduction, per se, is the most important determinant for stroke risk reduction, the question is if specific classes of antihypertensive drugs offer special protection against stroke is still controversial. Some studies have suggested that angiotensin receptors blockers (ARBs) appear to offer additional protection against stroke. This has been hypothesized in studies in hypertensives, such as LIFE and SCOPE, and especially in the only comparative trial focused on secondary stroke prevention. In the MOSES trial, the comparison of eprosartan versus nitrendipine in patients with a previous stroke resulted, despite a similar BP reduction, in a significant reduction in the primary composite endpoint of total mortality plus cardiovascular and cerebrovascular events, including recurrent events. These results may suggest a blood pressure-independent effect of ARBs, which can be mediated through several mechanisms, including their ability to counteract other markers of target organ damage, but also through a direct neuroprotective effect.

Risk of recurrent stroke in patients with silent brain infarction in the PRoFESS Imaging Substudy

PubMed Central

Weber, Ralph; Weimar, Christian; Wanke, Isabel; Möller-Hartmann, Claudia; Gizewski, Elke R.; Blatchford, Jon; Hermansson, Karin; Demchuk, Andrew M.; Forsting, Michael; Sacco, Ralph L.; Saver, Jeffrey L.; Warach, Steven; Diener, Hans Christoph; Diehl, Anke

2012-01-01

Background and Purpose Silent brain infarctions are associated with an increased risk of stroke in healthy individuals. Risk of recurrent stroke in patients with both symptomatic and silent brain infarction (SBI) has only been investigated in patients with cardioembolic stroke in the European Atrial Fibrillation Trial. We assessed whether patients with recent non-cardioembolic stroke and SBI detected on MRI are at increased risk for recurrent stroke, other cardiovascular events, and mortality. Methods The prevalence of SBI detected on MRI was assessed in 1014 patients enrolled in the imaging substudy of the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. The primary outcome was first recurrence of stroke in patients with both symptomatic stroke and SBI in comparison with age and sex matched stroke patients without SBI. Secondary outcomes were a combined vascular endpoint, other vascular events and mortality. The two groups were compared using conditional logistic regression. Results Silent brain infarction was detected in 207 (20.4%) patients of the 1014 patients. Twenty-seven (13.0%) patients with SBI and 19 (9.2%) without SBI had a recurrent stroke (odds ratio 1.42, 95% confidence interval 0.79 to 2.56; p=0.24) during a mean follow-op of 2.5 years. Similarly, there was no statistically significant difference for all secondary outcome parameters between patients with SBI and matched patients without SBI. Conclusion The presence of SBI in patients with recent mild non-cardioembolic ischemic stroke could not be shown to be an independent risk factor for recurrent stroke, other vascular events, or a higher mortality. PMID:22267825

Adopting a Patient-Centered Approach to Primary Outcome Analysis of Acute Stroke Trials by Use of a Utility-Weighted Modified Rankin Scale

PubMed Central

Chaisinanunkul, Napasri; Adeoye, Opeolu; Lewis, Roger J.; Grotta, James C.; Broderick, Joseph; Jovin, Tudor G.; Nogueira, Raul G.; Elm, Jordan; Graves, Todd; Berry, Scott; Lees, Kennedy R.; Barreto, Andrew D.; Saver, Jeffrey L.

2015-01-01

Background and Purpose Although the modified Rankin Scale (mRS) is the most commonly employed primary endpoint in acute stroke trials, its power is limited when analyzed in dichotomized fashion and its indication of effect size challenging to interpret when analyzed ordinally. Weighting the seven Rankin levels by utilities may improve scale interpretability while preserving statistical power. Methods A utility weighted mRS (UW-mRS) was derived by averaging values from time-tradeoff (patient centered) and person-tradeoff (clinician centered) studies. The UW-mRS, standard ordinal mRS, and dichotomized mRS were applied to 11 trials or meta-analyses of acute stroke treatments, including lytic, endovascular reperfusion, blood pressure moderation, and hemicraniectomy interventions. Results Utility values were: mRS 0–1.0; mRS 1 - 0.91; mRS 2 - 0.76; mRS 3 - 0.65; mRS 4 - 0.33; mRS 5 & 6 - 0. For trials with unidirectional treatment effects, the UW-mRS paralleled the ordinal mRS and outperformed dichotomous mRS analyses. Both the UW-mRS and the ordinal mRS were statistically significant in six of eight unidirectional effect trials, while dichotomous analyses were statistically significant in two to four of eight. In bidirectional effect trials, both the UW-mRS and ordinal tests captured the divergent treatment effects by showing neutral results whereas some dichotomized analyses showed positive results. Mean utility differences in trials with statistically significant positive results ranged from 0.026 to 0.249. Conclusion A utility-weighted mRS performs similarly to the standard ordinal mRS in detecting treatment effects in actual stroke trials and ensures the quantitative outcome is a valid reflection of patient-centered benefits. PMID:26138130

Primary care interventions and current service innovations in modifying long-term outcomes after stroke: a protocol for a scoping review

PubMed Central

Pindus, Dominika M; Lim, Lisa; Rundell, A Viona; Hobbs, Victoria; Aziz, Noorazah Abd; Mullis, Ricky; Mant, Jonathan

2016-01-01

Introduction Interventions delivered by primary and/or community care have the potential to reach the majority of stroke survivors and carers and offer ongoing support. However, an integrative account emerging from the reviews of interventions addressing specific long-term outcomes after stroke is lacking. The aims of the proposed scoping review are to provide an overview of: (1) primary care and community healthcare interventions by generalist healthcare professionals to stroke survivors and/or their informal carers to address long-term outcomes after stroke, (2) the scope and characteristics of interventions which were successful in addressing long-term outcomes, and (3) developments in current clinical practice. Methods and analysis Studies that focused on adult community dwelling stroke survivors and informal carers were included. Academic electronic databases will be searched to identify reviews of randomised controlled trials (RCTs) and controlled trials, trials from the past 5 years; reviews of observational studies. Practice exemplars from grey literature will be identified through advanced Google search. Reports, guidelines and other documents of major health organisations, clinical professional bodies, and stroke charities in the UK and internationally will be included. Two reviewers will independently screen titles, abstracts and full texts for inclusion of published literature. One reviewer will screen search results from the grey literature and identify relevant documents for inclusion. Data synthesis will include analysis of the number, type of studies, year and country of publication, a summary of intervention components/service or practice, outcomes addressed, main results (an indicator of effectiveness) and a description of included interventions. Ethics and dissemination The review will help identify components of care and care pathways for primary care services for stroke. By comparing the results with stroke survivors' and carers' needs identified in the literature, the review will highlight potential gaps in research and practice relevant to long-term care after stroke. PMID:27798023

Blood pressure and stroke: an overview of published reviews.

PubMed

Lawes, Carlene M M; Bennett, Derrick A; Feigin, Valery L; Rodgers, Anthony

2004-04-01

The last few years have seen a considerable increase in the amount of information available concerning blood pressure (BP) and stroke associations. This article provides an overview of published reviews of the effects on stroke seen in trials of BP-lowering drugs and compares these with the results available from cohort studies. We present a review of major overviews of prospective cohort studies and an updated meta-analysis of >40 randomized controlled trials of BP lowering, which included >188 000 participants and approximately 6800 stroke events. Cohort studies now indicate that in the Asia Pacific region as well as in North America and Western Europe, each 10 mm Hg lower systolic BP is associated with a decrease in risk of stroke of approximately one third in subjects aged 60 to 79 years. The association is continuous down to levels of at least 115/75 mm Hg and is consistent across sexes, regions, and stroke subtypes and for fatal and nonfatal events. The proportional association is age dependent but is still strong and positive in those aged 80 years. Data from randomized controlled trials, in which mean age at event was approximately 70 years, indicate that a 10 mm Hg reduction in systolic BP is associated with a reduction in risk of stroke of approximately one third. Per mm Hg systolic BP reduction, the relative benefits for stroke appear similar between agents, by baseline BP levels, and whether or not individuals have a past history of cardiovascular disease. There is, however, evidence of greater benefit with a larger BP reduction. The epidemiologically expected benefits of BP lowering for stroke risk reduction are broadly consistent across a range of different population subgroups. There are greater benefits from larger BP reductions, and initiating and maintaining BP reduction for stroke prevention is a more important issue than choice of initial agent.

Acupuncture lowering blood pressure for secondary prevention of stroke: a study protocol for a multicenter randomized controlled trial.

PubMed

Du, Yu-Zheng; Gao, Xin-Xin; Wang, Cheng-Ting; Zheng, Hai-Zhen; Lei, Yun; Wu, Meng-Han; Shi, Xue-Min; Ban, Hai-Peng; Gu, Wen-Long; Meng, Xiang-Gang; Wei, Mao-Ti; Hu, Chun-Xiao

2017-09-15

Stroke is the prime cause of morbidity and mortality in the general population, and hypertension will increase the recurrence and mortality of stroke. We report a protocol of a pragmatic randomized controlled trial (RCT) using blood pressure (BP)-lowering acupuncture add-on treatment to treat patients with hypertension and stroke. This is a large-scale, multicenter, subject-, assessor- and analyst-blinded, pragmatic RCT. A total of 480 patients with hypertension and ischemic stroke will be randomly assigned to two groups: an experimental group and a control group. The experimental group will receive "HuoXueSanFeng" acupuncture combined with one antihypertensive medication in addition to routine ischemic stroke treatment. The control group will only receive one antihypertensive medication and basic treatments for ischemic stroke. HuoXueSanFeng acupuncture will be given for six sessions weekly for the first 6 weeks and three times weekly for the next 6 weeks. A 9-month follow-up will, thereafter, be conducted. Antihypertensive medication will be adjusted based on BP levels. The primary outcome will be the recurrence of stroke. The secondary outcomes including 24-h ambulatory BP, the TCM syndrome score, the Short Form 36-item Health Survey (SF-36), the National Institute of Health Stroke Scale (NIHSS), as well as the Barthel Index (BI) scale will be assessed at baseline, 6 weeks and 12 weeks post initiating treatments; cardiac ultrasound, carotid artery ultrasound, transcranial Doppler, and lower extremity ultrasound will be evaluated at baseline and 12 weeks after treatment. The safety of acupuncture will also be assessed. We aim to determine the clinical effects of controlling BP for secondary prevention of stroke with acupuncture add-on treatment. ClinicalTrials.gov, ID: NCT02967484 . Registered on 13 February 2017; last updated on 27 June 2017.

Impact of General Practitioner Transient Ischemic Attack Training on 90-Day Stroke Outcomes: Secondary Analysis of a Cluster Randomized Controlled Trial.

PubMed

Ranta, Annemarei; Dovey, Susan; Gommans, John; Tilyard, Murray; Weatherall, Mark

2018-07-01

Many patients with transient ischemic attack (TIA) receive initial assessments by general practitioners (GPs) who may lack TIA management experience. In a randomized controlled trial (RCT), we showed that electronic decision support for GPs improves patient outcomes and guideline adherence. Some stroke services prefer to improve referrer expertise through TIA/stroke education sessions instead of promoting TIA decision aids or triaging tools. This is a secondary analysis of whether a GP education session influenced TIA management and outcomes. Post hoc analysis of a multicenter, single blind, parallel group, cluster RCT comparing TIA/stroke electronic decision support guided GP management with usual care to assess whether a pretrial TIA/stroke education session also affected RCT outcomes. Of 181 participating GPs, 79 (43.7%) attended an education session and 140 of 291 (48.1%) trial patients were managed by these GPs. There were fewer 90-day stroke events and 90-day vascular events or deaths in patients treated by GPs who attended education; 2 of 140 (1.4%) and 10 of 140 (7.1%) respectively, compared with those who did not; 5 of 151 (3.3%), and 14 of 151 (9.3%), respectively. Logistic regression for association between 90-day stroke and 90-day vascular events or death and education, however, was nonsignificant (odds ratio [OR] .42 (.08 to 2.22), P = .29 and .59 (95% confidence interval [CI] .27 to 1.29), P = .18 respectively. Guideline adherence was not improved by the education session: OR .84 (95% CI .49 to 1.45), P = .54. In the described setting, a GP TIA/stroke education session did not significantly enhance guideline adherence or reduce 90-day stroke or vascular events following TIA. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Blood-pressure targets in patients with recent lacunar stroke: the SPS3 randomised trial.

PubMed

Benavente, O R; Coffey, C S; Conwit, R; Hart, R G; McClure, L A; Pearce, L A; Pergola, P E; Szychowski, J M

2013-08-10

Lowering of blood pressure prevents stroke but optimum target levels to prevent recurrent stroke are unknown. We investigated the effects of different blood-pressure targets on the rate of recurrent stroke in patients with recent lacunar stroke. In this randomised open-label trial, eligible patients lived in North America, Latin America, and Spain and had recent, MRI-defined symptomatic lacunar infarctions. Patients were recruited between March, 2003, and April, 2011, and randomly assigned, according to a two-by-two multifactorial design, to a systolic-blood-pressure target of 130-149 mm Hg or less than 130 mm Hg. The primary endpoint was reduction in all stroke (including ischaemic strokes and intracranial haemorrhages). Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT 00059306. 3020 enrolled patients, 1519 in the higher-target group and 1501 in the lower-target group, were followed up for a mean of 3·7 (SD 2·0) years. Mean age was 63 (SD 11) years. After 1 year, mean systolic blood pressure was 138 mm Hg (95% CI 137-139) in the higher-target group and 127 mm Hg (95% CI 126-128) in the lower-target group. Non-significant rate reductions were seen for all stroke (hazard ratio 0·81, 95% CI 0·64-1·03, p=0·08), disabling or fatal stroke (0·81, 0·53-1·23, p=0·32), and the composite outcome of myocardial infarction or vascular death (0·84, 0·68-1·04, p=0·32) with the lower target. The rate of intracerebral haemorrhage was reduced significantly (0·37, 0·15-0·95, p=0·03). Treatment-related serious adverse events were infrequent. Although the reduction in stroke was not significant, our results support that in patients with recent lacunar stroke, the use of a systolic-blood-pressure target of less than 130 mm Hg is likely to be beneficial. National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS). Copyright © 2013 Elsevier Ltd. All rights reserved.

Participant Recruitment and Engagement in Automated eHealth Trial Registration: Challenges and Opportunities for Recruiting Women Who Experience Violence

PubMed Central

McLean, Christine; Rohan, Maheswaran; Sisk, Rose; Dobbs, Terry; Nada-Raja, Shyamala; Wilson, Denise; Vandal, Alain C

2016-01-01

Background Automated eHealth Web-based research trials offer people an accessible, confidential opportunity to engage in research that matters to them. eHealth trials may be particularly useful for sensitive issues when seeking health care may be accompanied by shame and mistrust. Yet little is known about people’s early engagement with eHealth trials, from recruitment to preintervention autoregistration processes. A recent randomized controlled trial that tested the effectiveness of an eHealth safety decision aid for New Zealand women in the general population who experienced intimate partner violence (isafe) provided the opportunity to examine recruitment and preintervention participant engagement with a fully automated Web-based registration process. The trial aimed to recruit 340 women within 24 months. Objective The objective of our study was to examine participant preintervention engagement and recruitment efficiency for the isafe trial, and to analyze dropout through the registration pathway, from recruitment to eligibility screening and consent, to completion of baseline measures. Methods In this case study, data collection sources included the trial recruitment log, Google Analytics reports, registration and program metadata, and costs. Analysis included a qualitative narrative of the recruitment experience and descriptive statistics of preintervention participant engagement and dropout rates. A Koyck model investigated the relationship between Web-based online marketing website advertisements (ads) and participant accrual. Results The isafe trial was launched on September 17, 2012. Placement of ads in an online classified advertising platform increased the average number of recruited participants per month from 2 to 25. Over the 23-month recruitment period, the registration website recorded 4176 unique visitors. Among 1003 women meeting eligibility criteria, 51.55% (517) consented to participate; among the 501 women who enrolled (consented, validated, and randomized), 412 (82.2%) were accrued (completed baseline assessments). The majority (n=52, 58%) of the 89 women who dropped out between enrollment and accrual never logged in to the allocated isafe website. Of every 4 accrued women, 3 (314/412, 76.2%) identified the classified ad as their referral source, followed by friends and family (52/412, 12.6%). Women recruited through a friend or relative were more likely to self-identify as indigenous Māori and live in the highest-deprivation areas. Ads increased the accrual rate by a factor of 74 (95% CI 49–112). Conclusions Print advertisements, website links, and networking were costly and inefficient methods for recruiting participants to a Web-based eHealth trial. Researchers are advised to limit their recruitment efforts to Web-based online marketplace and classified advertising platforms, as in the isafe case, or to social media. Online classified advertising in “Jobs–Other–volunteers” successfully recruited a diverse sample of women experiencing intimate partner violence. Preintervention recruitment data provide critical information to inform future research and critical analysis of Web-based eHealth trials. ClinicalTrial Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12612000708853; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612000708853 (Archived by WebCite at http://www.webcitation/6lMGuVXdK) PMID:27780796

Performance of stroke risk scores in older people with atrial fibrillation not taking warfarin: comparative cohort study from BAFTA trial.

PubMed

Hobbs, F D R; Roalfe, A K; Lip, G Y H; Fletcher, K; Fitzmaurice, D A; Mant, J

2011-06-23

To compare the predictive power of the main existing and recently proposed schemes for stratification of risk of stroke in older patients with atrial fibrillation. Comparative cohort study of eight risk stratification scores. Trial of thromboprophylaxis in stroke, the Birmingham Atrial Fibrillation in the Aged (BAFTA) trial. 665 patients aged 75 or over with atrial fibrillation based in the community who were randomised to the BAFTA trial and were not taking warfarin throughout or for part of the study period. Events rates of stroke and thromboembolism. 54 (8%) patients had an ischaemic stroke, four (0.6%) had a systemic embolism, and 13 (2%) had a transient ischaemic attack. The distribution of patients classified into the three risk categories (low, moderate, high) was similar across three of the risk stratification scores (revised CHADS(2), NICE, ACC/AHA/ESC), with most patients categorised as high risk (65-69%, n = 460-457) and the remaining classified as moderate risk. The original CHADS(2) (Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes, previous Stroke) score identified the lowest number as high risk (27%, n = 180). The incremental risk scores of CHADS(2), Rietbrock modified CHADS(2), and CHA(2)DS(2)-VASc (CHA(2)DS(2)-Vascular disease, Age 65-74 years, Sex) failed to show an increase in risk at the upper range of scores. The predictive accuracy was similar across the tested schemes with C statistic ranging from 0.55 (original CHADS(2)) to 0.62 (Rietbrock modified CHADS(2)), with all except the original CHADS(2) predicting better than chance. Bootstrapped paired comparisons provided no evidence of significant differences between the discriminatory ability of the schemes. Based on this single trial population, current risk stratification schemes in older people with atrial fibrillation have only limited ability to predict the risk of stroke. Given the systematic undertreatment of older people with anticoagulation, and the relative safety of warfarin versus aspirin in those aged over 70, there could be a pragmatic rationale for classifying all patients over 75 as "high risk" until better tools are available.

Constraint-induced aphasia therapy in post-stroke aphasia rehabilitation: A systematic review and meta-analysis of randomized controlled trials

PubMed Central

Bao, Yong; Xie, Qing; Xu, Yang; Zhang, Junmei

2017-01-01

Background Constraint-induced aphasia therapy (CIAT) has been widely used in post-stroke aphasia rehabilitation. An increasing number of clinical controlled trials have investigated the efficacy of the CIAT for the post-stroke aphasia. Purpose To systematically review the randomized controlled trials (RCTs) concerning the effect of the CIAT in post-stroke patients with aphasia, and to identify the useful components of CIAT in post-stroke aphasia rehabilitation. Methods A computerized database search was performed through five databases (Pubmed, EMbase, Medline, ScienceDirect and Cochrane library). Cochrane handbook domains were used to evaluate the methodological quality of the included RCTs. Results Eight RCTs qualified in the inclusion criteria. Inconsistent results were found in comparing the CIAT with conventional therapies without any component from the CIAT based on the results of three RCTs. Five RCTs showed that the CIAT performed equally well as other intensive aphasia therapies, in terms of improving language performance. One RCT showed that therapies embedded with social interaction were likely to enhance the efficacy of the CIAT. Conclusion CIAT may be useful for improving chronic post-stroke aphasia, however, limited evidence to support its superiority to other aphasia therapies. Massed practice is likely to be a useful component of CIAT, while the role of “constraint” is needed to be further explored. CIAT embedded with social interaction may gain more benefits. PMID:28846724

Stroke Caused by Atherosclerosis of the Major Intracranial Arteries

PubMed Central

Banerjee, Chirantan; Chimowitz, Marc I.

2017-01-01

Our goal in this review is to discuss the pathophysiology, diagnosis and treatment of stroke caused by atherosclerosis of the major intracranial arteries. References for the review were identified by searching PubMed for related studies published from 1955 to June 2016 using search terms “intracranial stenosis” and “intracranial atherosclerosis”. Reference sections of published randomized clinical trials and previously published reviews were searched for additional references. Intracranial atherosclerotic disease (ICAD) is a highly prevalent cause of stroke that is associated with a high risk of recurrent stroke. It is more prevalent among blacks, Hispanics and Asians compared with whites. Diabetes, hypertension, metabolic syndrome, smoking, hyperlipidemia and a sedentary lifestyle are the major modifiable risk factors associated with ICAD. Randomized clinical trials comparing aggressive management (dual antiplatelet treatment for 90 days followed by aspirin monotherapy and intensive management of vascular risk factors) with intracranial stenting plus aggressive medical management have shown medical management alone to be safer and more effective for preventing stroke. As such, aggressive medical management has become the standard of care for symptomatic patients with ICAD. Nevertheless, there are subgroups of patients who are still at high risk of stroke despite being treated with aggressive medical management. Future research should aim to establish clinical, serologic, and imaging biomarkers to identify high-risk patients, and clinical trials evaluating novel therapies should be focused on these patients. PMID:28154100

Constraint-induced aphasia therapy in post-stroke aphasia rehabilitation: A systematic review and meta-analysis of randomized controlled trials.

PubMed

Zhang, Jiaqi; Yu, Jiadan; Bao, Yong; Xie, Qing; Xu, Yang; Zhang, Junmei; Wang, Pu

2017-01-01

Constraint-induced aphasia therapy (CIAT) has been widely used in post-stroke aphasia rehabilitation. An increasing number of clinical controlled trials have investigated the efficacy of the CIAT for the post-stroke aphasia. To systematically review the randomized controlled trials (RCTs) concerning the effect of the CIAT in post-stroke patients with aphasia, and to identify the useful components of CIAT in post-stroke aphasia rehabilitation. A computerized database search was performed through five databases (Pubmed, EMbase, Medline, ScienceDirect and Cochrane library). Cochrane handbook domains were used to evaluate the methodological quality of the included RCTs. Eight RCTs qualified in the inclusion criteria. Inconsistent results were found in comparing the CIAT with conventional therapies without any component from the CIAT based on the results of three RCTs. Five RCTs showed that the CIAT performed equally well as other intensive aphasia therapies, in terms of improving language performance. One RCT showed that therapies embedded with social interaction were likely to enhance the efficacy of the CIAT. CIAT may be useful for improving chronic post-stroke aphasia, however, limited evidence to support its superiority to other aphasia therapies. Massed practice is likely to be a useful component of CIAT, while the role of "constraint" is needed to be further explored. CIAT embedded with social interaction may gain more benefits.

Effects of acupuncture and computer-assisted cognitive training for post-stroke attention deficits: study protocol for a randomized controlled trial.

PubMed

Huang, Jia; McCaskey, Michael A; Yang, Shanli; Ye, Haicheng; Tao, Jing; Jiang, Cai; Schuster-Amft, Corina; Balzer, Christian; Ettlin, Thierry; Schupp, Wilfried; Kulke, Hartwig; Chen, Lidian

2015-12-02

A majority of stroke survivors present with cognitive impairments. Attention disturbance, which leads to impaired concentration and overall reduced cognitive functions, is strongly associated with stroke. The clinical efficacy of acupuncture with Baihui (GV20) and Shenting (GV24) as well as computer-assisted cognitive training in stroke and post-stroke cognitive impairment have both been demonstrated in previous studies. To date, no systematic comparison of these exists and the potential beneficial effects of a combined application are yet to be examined. The main objective of this pilot study is to evaluate the effects of computer-assisted cognitive training compared to acupuncture on the outcomes of attention assessments. The second objective is to test the effects of a combined cognitive intervention that incorporates computer-assisted cognitive training and acupuncture (ACoTrain). An international multicentre, single-blinded, randomised controlled pilot trial will be conducted. In a 1:1:1 ratio, 60 inpatients with post-stroke cognitive dysfunction will be randomly allocated into either the acupuncture group, the computer-assisted cognitive training group, or the ACoTrain group in addition to their individual rehabilitation programme. The intervention period of this pilot trial will last 4 weeks (30 minutes per day, 5 days per week, Monday to Friday). The primary outcome is the test battery for attentional performance. The secondary outcomes include the Trail Making Test, Test des Deux Barrages, National Institute of Health Stroke Scale, and Modified Barthel Index for assessment of daily life competence, and the EuroQol Questionnaire for health-related quality of life. This trial mainly focuses on evaluating the effects of computer-assisted cognitive training compared to acupuncture on the outcomes of attention assessments. The results of this pilot trial are expected to provide new insights on how Eastern and Western medicine can complement one another and improve the treatment of cognitive impairments in early stroke rehabilitation. Including patients with different cultural backgrounds allows a more generalisable interpretation of the results but also poses risks of performance bias. Using standardised and well-described assessments, validated for each region, is pivotal to allow pooling of the data. Clinical Trails.gov ID: NCT02324959 (8 December 2014).

Methodological issues in negative symptom trials.

PubMed

Marder, Stephen R; Daniel, David G; Alphs, Larry; Awad, A George; Keefe, Richard S E

2011-03-01

Individuals from academia, the pharmaceutical industry, and the US Food and Drug Administration used a workshop format to discuss important methodological issues in the design of trials of pharmacological agents for improving negative symptoms in schizophrenia. The issues addressed included the need for a coprimary functional measure for registration trials; the characteristics of individuals who should enter negative symptom trials; the optimal duration for a proof-of-concept or registration trial; the optimal design of a study of a broad-spectrum agent that treats both positive and negative symptoms or a co-medication that is added to an antipsychotic; the relative strengths and weaknesses of available instruments for measuring negative symptoms; the definition of clinically meaningful improvement for these trials; and whether drugs can be approved for a subdomain of negative symptoms.

Methodological Issues in Negative Symptom Trials

PubMed Central

Marder, Stephen R.; Daniel, David G.; Alphs, Larry; Awad, A. George; Keefe, Richard S. E.

2011-01-01

Individuals from academia, the pharmaceutical industry, and the US Food and Drug Administration used a workshop format to discuss important methodological issues in the design of trials of pharmacological agents for improving negative symptoms in schizophrenia. The issues addressed included the need for a coprimary functional measure for registration trials; the characteristics of individuals who should enter negative symptom trials; the optimal duration for a proof-of-concept or registration trial; the optimal design of a study of a broad-spectrum agent that treats both positive and negative symptoms or a co-medication that is added to an antipsychotic; the relative strengths and weaknesses of available instruments for measuring negative symptoms; the definition of clinically meaningful improvement for these trials; and whether drugs can be approved for a subdomain of negative symptoms. PMID:21270473

Implementation of Remote 3-Dimensional Image Guided Radiation Therapy Quality Assurance for Radiation Therapy Oncology Group Clinical Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cui Yunfeng; Galvin, James M.; Radiation Therapy Oncology Group, American College of Radiology, Philadelphia, Pennsylvania

2013-01-01

Purpose: To report the process and initial experience of remote credentialing of three-dimensional (3D) image guided radiation therapy (IGRT) as part of the quality assurance (QA) of submitted data for Radiation Therapy Oncology Group (RTOG) clinical trials; and to identify major issues resulting from this process and analyze the review results on patient positioning shifts. Methods and Materials: Image guided radiation therapy datasets including in-room positioning CT scans and daily shifts applied were submitted through the Image Guided Therapy QA Center from institutions for the IGRT credentialing process, as required by various RTOG trials. A centralized virtual environment is establishedmore » at the RTOG Core Laboratory, containing analysis tools and database infrastructure for remote review by the Physics Principal Investigators of each protocol. The appropriateness of IGRT technique and volumetric image registration accuracy were evaluated. Registration accuracy was verified by repeat registration with a third-party registration software system. With the accumulated review results, registration differences between those obtained by the Physics Principal Investigators and from the institutions were analyzed for different imaging sites, shift directions, and imaging modalities. Results: The remote review process was successfully carried out for 87 3D cases (out of 137 total cases, including 2-dimensional and 3D) during 2010. Frequent errors in submitted IGRT data and challenges in the review of image registration for some special cases were identified. Workarounds for these issues were developed. The average differences of registration results between reviewers and institutions ranged between 2 mm and 3 mm. Large discrepancies in the superior-inferior direction were found for megavoltage CT cases, owing to low spatial resolution in this direction for most megavoltage CT cases. Conclusion: This first experience indicated that remote review for 3D IGRT as part of QA for RTOG clinical trials is feasible and effective. The magnitude of registration discrepancy between institution and reviewer was presented, and the major issues were investigated to further improve this remote evaluation process.« less

Variations in Kinematics during Clinical Gait Analysis in Stroke Patients

PubMed Central

Boudarham, Julien; Roche, Nicolas; Pradon, Didier; Bonnyaud, Céline; Bensmail, Djamel; Zory, Raphael

2013-01-01

In addition to changes in spatio-temporal and kinematic parameters, patients with stroke exhibit fear of falling as well as fatigability during gait. These changes could compromise interpretation of data from gait analysis. The aim of this study was to determine if the gait of hemiplegic patients changes significantly over successive gait trials. Forty two stroke patients and twenty healthy subjects performed 9 gait trials during a gait analysis session. The mean and variability of spatio-temporal and kinematic joint parameters were analyzed during 3 groups of consecutive gait trials (1–3, 4–6 and 7–9). Principal component analysis was used to reduce the number of variables from the joint kinematic waveforms and to identify the parts of the gait cycle which changed during the gait analysis session. The results showed that i) spontaneous gait velocity and the other spatio-temporal parameters significantly increased, and ii) gait variability decreased, over the last 6 gait trials compared to the first 3, for hemiplegic patients but not healthy subjects. Principal component analysis revealed changes in the sagittal waveforms of the hip, knee and ankle for hemiplegic patients after the first 3 gait trials. These results suggest that at the beginning of the gait analysis session, stroke patients exhibited phase of adaptation,characterized by a “cautious gait” but no fatigue was observed. PMID:23799100

Study design for the fostering eating after stroke with transcranial direct current stimulation trial: a randomized controlled intervention for improving Dysphagia after acute ischemic stroke.

PubMed

Marchina, Sarah; Schlaug, Gottfried; Kumar, Sandeep

2015-03-01

Dysphagia is a major stroke complication but lacks effective therapy that can promote recovery. Noninvasive brain stimulation with and without peripheral sensorimotor activities may be an attractive treatment option for swallowing recovery but has not been systematically investigated in the stroke population. This article describes the study design of the first prospective, single-center, double-blinded trial of anodal versus sham transcranial direct current stimulation (tDCS) used in combination with swallowing exercises in patients with dysphagia from an acute ischemic stroke. The aim of this study is to gather safety data on cumulative sessions of tDCS in acute-subacute phases of stroke, obtain information about effects of this intervention on important physiologic and clinically relevant swallowing parameters, and examine possible dose effects. Ninety-nine consecutive patients with dysphagia from an acute unilateral hemispheric infarction with a Penetration and Aspiration Scale (PAS) score of 4 or more and without other confounding reasons for dysphagia will be enrolled at a single tertiary care center. Subjects will be randomized to either a high or low dose tDCS or a sham group and will undergo 10 sessions over 5 consecutive days concomitantly with effortful swallowing maneuvers. The main efficacy measures are a change in the PAS score before and after treatment; the main safety measures are mortality, seizures, neurologic, motor, and swallowing deterioration. The knowledge gained from this study will help plan a larger confirmatory trial for treating stroke-related dysphagia and advance our understanding of important covariates influencing swallowing recovery and response to the proposed intervention. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Patent foramen ovale closure versus medical therapy after cryptogenic stroke: An updated meta-analysis of all randomized clinical trials.

PubMed

Kheiri, Babikir; Abdalla, Ahmed; Osman, Mohammed; Ahmed, Sahar; Hassan, Mustafa; Bachuwa, Ghassan

2018-03-07

Cryptogenic strokes can be attributed to paradoxical emboli through patent foramen ovale (PFO). However, the effectiveness of PFO closure in preventing recurrent stroke is uncertain and the results of previous randomized clinical trials (RCTs) have been inconclusive. Hence, this study provides an updated meta-analysis of all RCTs comparing PFO closure with medical therapy for secondary prevention of cryptogenic stroke. All RCTs were identified by a comprehensive literature search of PubMed, Embase, the Cochrane Collaboration Central Register of Controlled Trials, Scopus, and Clinicaltrials.gov. The primary outcome was recurrent ischemic stroke and secondary outcomes were transient ischemic attack (TIA), all-cause mortality, new-onset atrial fibrillation (AF), serious adverse events, and major bleeding. 5 RCTs with 3440 participants were included in the present study (1829 patients underwent PFO closure and 1611 were treated medically). Pooled analysis showed a statistically significant reduction in the rate of recurrent stroke with PFO closure in comparison to medical therapy (OR 0.41; 95% CI 0.19-0.90; p = 0.03). However, there were no statistically significant reductions of recurrent TIAs (OR 0.77; 95% CI 0.51-1.14; p = 0.19) or all-cause mortality (OR 0.76; 95% CI 0.35-1.65; p = 0.48). The risk of developing new-onset AF was increased significantly with PFO closure (OR 4.74; 95% CI 2.33-9.61; p < 0.0001), but no significant differences in terms of serious adverse events or major bleeding between both groups. Patent foramen ovale closure in adults with recent cryptogenic stroke was associated with a lower rate of recurrent strokes in comparison with medical therapy alone.

Safety of intravenous alteplase within 4.5 hours for patients awakening with stroke symptoms.

PubMed

Urrutia, Victor C; Faigle, Roland; Zeiler, Steven R; Marsh, Elisabeth B; Bahouth, Mona; Cerdan Trevino, Mario; Dearborn, Jennifer; Leigh, Richard; Rice, Susan; Lane, Karen; Saheed, Mustapha; Hill, Peter; Llinas, Rafael H

2018-01-01

Up to 25% of acute stroke patients first note symptoms upon awakening. We hypothesized that patients awaking with stroke symptoms may be safely treated with intravenous alteplase (IV tPA) using non-contrast head CT (NCHCT), if they meet all other standard criteria. The SAfety of Intravenous thromboLytics in stroke ON awakening (SAIL ON) was a prospective, open-label, single treatment arm, pilot safety trial of standard dose IV tPA in patients who presented with stroke symptoms within 0-4.5 hours of awakening. From January 30, 2013, to September 1, 2015, twenty consecutive wakeup stroke patients selected by NCHCT were enrolled. The primary outcome was symptomatic intracerebral hemorrhage (sICH) in the first 36 hours. Secondary outcomes included NIH stroke scale (NIHSS) at 24 hours; and modified Rankin Score (mRS), NIHSS, and Barthel index at 90 days. The average age was 65 years (range 47-83); 40% were women; 50% were African American. The average NIHSS was 6 (range 4-11). The average time from wake-up to IV tPA was 205 minutes (range 114-270). The average time from last known well to IV tPA was 580 minutes (range 353-876). The median mRS at 90 days was 1 (range 0-5). No patients had sICH; two of 20 (10%) had asymptomatic ICH on routine post IV tPA brain imaging. Administration of IV tPA was feasible and may be safe in wakeup stroke patients presenting within 4.5 hours from awakening, screened with NCHCT. An adequately powered randomized clinical trial is needed. ClinicalTrials.gov NCT01643902.

Effects of clopidogrel and aspirin in combination versus aspirin alone on platelet activation and major receptor expression in patients after recent ischemic stroke: for the Plavix Use for Treatment of Stroke (PLUTO-Stroke) trial.

PubMed

Serebruany, Victor L; Malinin, Alex I; Ziai, Wendy; Pokov, Alex N; Bhatt, Deepak L; Alberts, Mark J; Hanley, Dan F

2005-10-01

Clopidogrel is widely used in patients after recent ischemic stroke; however, its ability to yield additional antiplatelet protection on top of aspirin has never been explored in a controlled study. To determine whether clopidogrel with aspirin (C+ASA) will produce more potent platelet inhibition than aspirin alone (ASA) in patients after ischemic stroke, we conducted the Plavix Use for Treatment of Stroke trial. Seventy patients after ischemic stroke were randomly assigned to C+ASA or ASA groups. Platelet studies included aggregometry; cartridge-based analyzers; expression of PECAM-1, P-selectin, GP IIb/IIIa (antigen and activity), vitronectin receptor, and formation of platelet-leukocyte microparticles by flow cytometry. Platelet tests were performed at baseline and after 30 days after randomization. There were no deaths, hospitalizations, or serious adverse events. There were no differences in the baseline platelet characteristics between C+ASA and ASA groups, or significant changes in platelet parameters in the ASA group, except diminished collagen-induced aggregation (P=0.001). In contrast, therapy with C+ASA resulted in a significant inhibition of platelet activity assessed by ADP- (P=0.00001) and collagen-induced (P=0.02) aggregation; closure time prolongation (P=0.03), and reduction of platelet activation units with Ultegra (P=0.00001); expression of PECAM-1 (P=0.01), and GP IIb/IIIa activity with PAC-1 (P=0.02) when compared with ASA group. Therapy with C+ASA also resulted in the reduced formation of platelet-leukocyte microparticles (P=0.02). Treatment with C+ASA for 1 month provides significantly greater inhibition of platelet activity than ASA alone in patients after recent ischemic stroke in the frame of the small randomized trial.

Primary prevention of stroke and cardiovascular disease in the community (PREVENTS): Methodology of a health wellness coaching intervention to reduce stroke and cardiovascular disease risk, a randomized clinical trial.

PubMed

Mahon, Susan; Krishnamurthi, Rita; Vandal, Alain; Witt, Emma; Barker-Collo, Suzanne; Parmar, Priya; Theadom, Alice; Barber, Alan; Arroll, Bruce; Rush, Elaine; Elder, Hinemoa; Dyer, Jesse; Feigin, Valery

2018-02-01

Rationale Stroke is a major cause of death and disability worldwide, yet 80% of strokes can be prevented through modifications of risk factors and lifestyle and by medication. While management strategies for primary stroke prevention in high cardiovascular disease risk individuals are well established, they are underutilized and existing practice of primary stroke prevention are inadequate. Behavioral interventions are emerging as highly promising strategies to improve cardiovascular disease risk factor management. Health Wellness Coaching is an innovative, patient-focused and cost-effective, multidimensional psychological intervention designed to motivate participants to adhere to recommended medication and lifestyle changes and has been shown to improve health and enhance well-being. Aims and/or hypothesis To determine the effectiveness of Health Wellness Coaching for primary stroke prevention in an ethnically diverse sample including Māori, Pacific Island, New Zealand European and Asian participants. Design A parallel, prospective, randomized, open-treatment, single-blinded end-point trial. Participants include 320 adults with absolute five-year cardiovascular disease risk ≥ 10%, calculated using the PREDICT web-based clinical tool. Randomization will be to Health Wellness Coaching or usual care groups. Participants randomized to Health Wellness Coaching will receive 15 coaching sessions over nine months. Study outcomes A substantial relative risk reduction of five-year cardiovascular disease risk at nine months post-randomization, which is defined as 10% relative risk reduction among those at moderate five-year cardiovascular disease risk (10-15%) and 25% among those at high risk (>15%). Discussion This clinical trial will determine whether Health Wellness Coaching is an effective intervention for reducing modifiable risk factors, and hence decrease the risk of stroke and cardiovascular disease.

Rivaroxaban for stroke prevention in East Asian patients from the ROCKET AF trial.

PubMed

Wong, Ka Sing Lawrence; Hu, Dai Yi; Oomman, Abraham; Tan, Ru-San; Patel, Manesh R; Singer, Daniel E; Breithardt, Günter; Mahaffey, Kenneth W; Becker, Richard C; Califf, Robert; Fox, Keith A A; Berkowitz, Scott D; Hacke, Werner; Hankey, Graeme J

2014-06-01

In Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial, rivaroxaban was noninferior to dose-adjusted warfarin in preventing stroke or systemic embolism among patients with nonvalvular atrial fibrillation at moderate to high stroke risk. Because of differences in patient demographics, epidemiology, and stroke risk management in East Asia, outcomes and relative effects of rivaroxaban versus warfarin were assessed to determine consistency among East Asians versus other ROCKET AF participants. Baseline demographics and interaction of treatment effects of rivaroxaban and warfarin among patients within East Asia and outside were assessed. A total of 932 (6.5%) ROCKET AF participants resided in East Asia. At baseline, East Asians had lower weight, creatinine clearance, and prior vitamin K antagonist use; higher prevalence of prior stroke; and less congestive heart failure and prior myocardial infarction than other participants. Despite higher absolute event rates for efficacy and safety outcomes in East Asians, the relative efficacy of rivaroxaban (20 mg once daily; 15 mg once daily for creatinine clearance of 30-49 mL/min) versus warfarin with respect to the primary efficacy end point (stroke/systemic embolism) was consistent among East Asians and non-East Asians (interaction P=0.666). Relative event rates for the major or nonmajor clinically relevant bleeding in patients treated with rivaroxaban and warfarin were consistent among East Asians and non-East Asians (interaction P=0.867). Observed relative efficacy and safety of rivaroxaban versus warfarin were similar among patients within and outside East Asia. Rivaroxaban, 20 mg once daily, is an alternative to warfarin for stroke prevention in East Asians with nonvalvular atrial fibrillation. © 2014 American Heart Association, Inc.

Warm-needle moxibustion for spasticity after stroke: A systematic review of randomized controlled trials.

PubMed

Yang, Liu; Tan, Jing-Yu; Ma, Haili; Zhao, Hongjia; Lai, Jinghui; Chen, Jin-Xiu; Suen, Lorna K P

2018-03-22

Spasticity is a common post-stroke complication, and it results in substantial deterioration in the quality of life of patients. Although potential positive effects of warm-needle moxibustion on spasticity after stroke have been observed, evidence on its definitive effect remains uncertain. This study aimed to summarize clinical evidence pertaining to therapeutic effects and safety of warm-needle moxibustion for treating spasticity after stroke. Randomized controlled trials were reviewed systematically on the basis of the Cochrane Handbook for Systematic Reviews of Interventions. The report follows the PRISMA statement. Ten electronic databases (PubMed, CENTRAL, EMBASE, AMED, CINAHL, Web of Science, CBM, CNKI, WanFang, and VIP) were explored, and articles were retrieved manually from two Chinese journals (The Journal of Traditional Chinese Medicine and Zhong Guo Zhen Jiu) through retrospective search. Randomized controlled trials with warm-needle moxibustion as treatment intervention for patients with limb spasm after stroke were included in this review. The risk of bias assessment tool was utilized in accordance with Cochrane Handbook 5.1.0. All included studies reported spasm effect as primary outcome. Effect size was estimated using relative risk, standardized mean difference, or mean difference with a corresponding 95% confidence interval. Review Manager 5.3 was utilized for meta-analysis. Twelve randomized controlled trials with certain methodological flaws and risk of bias were included, and they involved a total of 878 participants. Warm-needle moxibustion was found to be superior to electroacupuncture or acupuncture in reducing spasm and in promoting motor function and daily living activities. Pooled results for spasm effect and motor function were significant when warm-needle moxibustion was compared with electroacupuncture or acupuncture. A comparison of daily living activities indicated significant differences between warm-needle moxibustion and electroacupuncture. However, no difference was observed between warm-needle moxibustion and acupuncture. Warm-needle moxibustion may be a promising intervention to reduce limb spasm as well as improve motor function and daily living activities for stroke patients with spasticity. However, evidence was not conclusive. Rigorously designed randomized controlled trials with sample sizes larger than that in the included trials should be conducted for verification. Copyright © 2018 Elsevier Ltd. All rights reserved.

Predictors of stroke recurrence in patients with recent lacunar stroke and response to interventions according to risk status: Secondary Prevention of Small Subcortical Strokes (SPS3) trial

PubMed Central

Hart, Robert G.; Pearce, Lesly A.; Bakheet, Majid F.; Benavente, Oscar; Conwit, Robin A.; McClure, Leslie A.; Talbert, Robert L.; Anderson, David C.

2013-01-01

Background Among participants in the Secondary Prevention of Small Subcortical Strokes randomized trial, we sought to identify patients with high vs. low rates of recurrent ischemic stroke and to assess effects of aggressive blood pressure control and dual antiplatelet therapy according to risk status. Methods Multivariable analyses of 3020 participants with recent MRI-defined lacunar strokes followed for a mean of 3.7 years with 243 recurrent ischemic strokes. Results: Prior symptomatic lacunar stroke or TIA (HR 2.2, 95%CI 1.6,2.9), diabetes (HR 2.0, 95%CI 1.5,2.5), Black race (HR 1.7, 95%CI 1.3,2.3) and male sex (HR 1.5, 95%CI 1.1,1.9) were each independently predictive of recurrent ischemic stroke. Recurrent ischemic stroke occurred at a rate of 4.3%/yr (95% CI 3.3, 5.5) in patients with prior symptomatic lacunar stroke or TIA (15% of the cohort), 3.1%/yr (95%CI 2.6, 3.9) in those with >1 of the other 3 risk factors (27% of the cohort), and 1.3%/yr (95%CI 1.0,1.7) in those with 0 to 1 risk factors (58% of the cohort). There were no significant interactions between treatment effects and stroke risk status. Conclusions In this large, carefully followed cohort of patients with recent lacunar stroke and aggressive blood pressure management, prior symptomatic lacunar ischemia, diabetes, Black race and male sex independently predicted ischemic stroke recurrence. The effects of blood pressure targets and dual antiplatelet therapy were similar across the spectrum of independent risk factors and recurrence risk. PMID:23800503

Risk of recurrent stroke in patients with silent brain infarction in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) imaging substudy.

PubMed

Weber, Ralph; Weimar, Christian; Wanke, Isabel; Möller-Hartmann, Claudia; Gizewski, Elke R; Blatchford, Jon; Hermansson, Karin; Demchuk, Andrew M; Forsting, Michael; Sacco, Ralph L; Saver, Jeffrey L; Warach, Steven; Diener, Hans Christoph; Diehl, Anke

2012-02-01

Silent brain infarctions are associated with an increased risk of stroke in healthy individuals. Risk of recurrent stroke in patients with both symptomatic and silent brain infarction (SBI) has only been investigated in patients with cardioembolic stroke in the European Atrial Fibrillation Trial. We assessed whether patients with recent noncardioembolic stroke and SBI detected on MRI are at increased risk for recurrent stroke, other cardiovascular events, and mortality. The prevalence of SBI detected on MRI was assessed in 1014 patients enrolled in the imaging substudy of the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. The primary outcome was first recurrence of stroke in patients with both symptomatic stroke and SBI in comparison with age- and sex-matched patients with stroke without SBI. Secondary outcomes were a combined vascular end point, other vascular events, and mortality. The 2 groups were compared using conditional logistic regression. Silent brain infarction was detected in 207 (20.4%) of the 1014 patients. Twenty-seven (13.0%) patients with SBI and 19 (9.2%) without SBI had a recurrent stroke (OR, 1.42; 95% CI, 0.79-2.56; P=0.24) during a mean follow-up of 2.5 years. Similarly, there was no statistically significant difference for all secondary outcome parameters between patients with SBI and matched patients without SBI. The presence of SBI in patients with recent mild noncardioembolic ischemic stroke could not be shown to be an independent risk factor for recurrent stroke, other vascular events, or a higher mortality rate. URL: http://clinicaltrials.gov. Unique identifier: NCT00153062.

Quality of life after lacunar stroke: the Secondary Prevention of Small Subcortical Strokes study.

PubMed

Dhamoon, Mandip S; McClure, Leslie A; White, Carole L; Lau, Helena; Benavente, Oscar; Elkind, Mitchell S V

2014-01-01

We sought to describe the course and predictors of quality of life (QOL) after lacunar stroke. We hypothesized that there is a decline in QOL after recovery from lacunar stroke. The Secondary Prevention of Small Subcortical Strokes is a clinical trial in lacunar stroke patients with annual assessments of QOL with the stroke-specific QOL score. The overall score was used and analyzed as a continuous variable (range 0-5). We fit linear mixed models to assess the trend in QOL over time, assuming linearity of time, and adjusted for demographics, medical risk factors, cognitive factors, and functional status in univariable and multivariable models. Among 2870 participants, mean age was 63.4 years (SD 10.7), 63% were men, 51% White, 32% Hispanic, 36% had college education, 36% had diabetes, 89% had hypertension, and 10% had prior stroke. Mean poststroke Barthel Index (BI) score was 95.4 (assessed on average 6 months after stroke). In the final multivariable model, there was an average increase in QOL of .6% per year, and factors associated with decline in QOL over time included age (-.0003 per year, P < .0001), any college education (-.0013 per year, .01), prior stroke (-.004 per year, P < .0001), and BI (-.0002 per year, P < .0001). In this clinical trial of lacunar stroke patients, there was a slight annual increase in QOL overall, and age, level of education, and prior stroke were associated with changes in QOL over time. Multiple strokes may cause decline in QOL over time in the absence of recurrent events. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Pharmacy Students' Knowledge and Attitude toward Registration Trials and Clinical Research: A Survey in a Japanese University Hospital.

PubMed

Ise, Natsuko; Takechi, Kenshi; Miyamoto, Toshiko; Ishizawa, Keisuke; Yanagawa, Hiroaki

2017-12-11

Clinical research plays a fundamental role in establishing new treatments. Clinical research coordinators are considered essential in clinical research, and medical professionals such as pharmacists often take on this role. Pharmacy students can be considered future candidates for this task. We used questionnaires to survey the knowledge of and attitudes toward registration trials and clinical research of pharmacy students at Tokushima University Hospital. All pharmacy students (103) to whom questionnaires were sent responded. Almost all respondents were aware of registration trials and clinical research. More than 90% were aware of the existence of clinical research coordinators, and about half (48.6%) understood their role. In clinical research terminology, most respondents were aware of informed consent and related issues, but fewer than 20% were aware of more practical things. In total, 29.1% and 40.8% of the respondents were willing to carry out and coordinate research. These findings suggest that pharmacy students have basic knowledge of clinical research and that many students are willing to carry out and coordinate clinical research. More practical exposure to clinical research may help to strengthen their future contribution. Further studies may help to determine how to provide education on registration trials and clinical research to pharmacy students.

Transparency of outcome reporting and trial registration of randomized controlled trials in top psychosomatic and behavioral health journals: A systematic review.

PubMed

Milette, Katherine; Roseman, Michelle; Thombs, Brett D

2011-03-01

The most reliable evidence for evaluating healthcare interventions comes from well-designed and conducted randomized controlled trials (RCTs). The extent to which published RCTs reflect the efficacy of interventions, however, depends on the completeness and accuracy of published results. The Consolidated Standards of Reporting Trials statement, initially developed in 1996, provides guidelines intended to improve the transparency of published RCT reports. A policy of the International Committee of Medical Journal Editors, initiated in 2005, requires clinical trials published in member journals to be registered in publicly accessible registries prior to patient enrollment. The objective of this study was to assess the clarity of outcome reporting, proportion of registered trials, and adequacy of outcome registration in RCTs published in top behavioral health journals. Eligible studies were primary or secondary reports of RCTs published in Annals of Behavioral Medicine, Health Psychology, Journal of Psychosomatic Research, and Psychosomatic Medicine from January 2008 to September 2009. Data were extracted for each study on adequacy of outcome reporting and registration. Of 63 articles reviewed, only 25 (39.7%) had adequately declared primary or secondary outcomes, whereas 38 (60.3%) had multiple primary outcomes or did not define outcomes. Only 13 studies (20.6%) were registered. Only 1 study registered sufficiently precise outcome information to compare with published outcomes, and registered and published outcomes were discrepant in that study. Greater attention to outcome reporting and trial registration by researchers, peer reviewers, and journal editors will increase the likelihood that effective behavioral health interventions are readily identified and made available to patients. Copyright © 2011 Elsevier Inc. All rights reserved.

Do Chinese Researchers Conduct Ethical Research and Use Ethics Committee Review in Clinical Trials of Anti-Dementia Drugs? An Analysis of Biomedical Publications Originating from China.

PubMed

Zeng, Lingfeng; Liang, Weixiong; Pan, Jianke; Cao, Ye; Liu, Jun; Wang, Qi; Wang, Lu; Zou, Yuanping; Wang, Kezhu; Kong, Lingshuo; Xie, Hui; Xu, Weihua; Li, Weirong; Zhao, Wei; Mi, Suiqing; Chen, Yunbo; Cheng, Shuyi; Li, Xiaoyan; Cao, Qian; Zeng, Xing; Wang, Ningsheng

2016-03-25

Medical research using human participants must conform to the basic ethical principles found in the Declaration of Helsinki (DoH) of the World Medical Association. The purpose of this review was to assess whether journals in China have improved in regard to the fulfillment of ethical disclosure procedures for clinical trials of anti-dementia drugs. Four medical databases were searched for articles reporting clinical trials of oral anti-dementia drugs published in China in 2003, 2009, and 2014. The frequencies of reporting of informed consent from participants (ICP), approval of a regional ethical committee (REC), reference to DoH, and study registration were estimated respectively. Statistical analyses were conducted with SPSS v21 software. Among those randomized controlled trials published in 2003, 2009, and 2014, disclosure of REC approval was present for 2.67%, 1.15%, and 6.84%; statements of ICP were included in 9.33%, 7.76%, and 17.34%; reference to DoH was found for 4.00%, 1.44%, and 7.45%; and study registration reporting was included in 2.67%, 2.59%, and 9.28%, respectively. Improvements to reporting rates between 2009 and 2014 were seen, with more than twice as many trials reporting REC approval, ICP, reference to DoH, and study registration compared with 2009. Compared with 2003 and 2009, reporting rates for REC approval, ICP, reference to DoH, and study registration for clinical trials of anti-dementia drugs were enhanced in 2014 in the major medical journals of China. However, biomedical publications without definite statements of ethical considerations remain common, and this continues to be seen in Chinese journals. It is imperative that measures are taken to reinforce the ethical protection in clinical trials in China.

Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials.

PubMed

Ruff, Christian T; Giugliano, Robert P; Braunwald, Eugene; Hoffman, Elaine B; Deenadayalu, Naveen; Ezekowitz, Michael D; Camm, A John; Weitz, Jeffrey I; Lewis, Basil S; Parkhomenko, Alexander; Yamashita, Takeshi; Antman, Elliott M

2014-03-15

Four new oral anticoagulants compare favourably with warfarin for stroke prevention in patients with atrial fibrillation; however, the balance between efficacy and safety in subgroups needs better definition. We aimed to assess the relative benefit of new oral anticoagulants in key subgroups, and the effects on important secondary outcomes. We searched Medline from Jan 1, 2009, to Nov 19, 2013, limiting searches to phase 3, randomised trials of patients with atrial fibrillation who were randomised to receive new oral anticoagulants or warfarin, and trials in which both efficacy and safety outcomes were reported. We did a prespecified meta-analysis of all 71,683 participants included in the RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48 trials. The main outcomes were stroke and systemic embolic events, ischaemic stroke, haemorrhagic stroke, all-cause mortality, myocardial infarction, major bleeding, intracranial haemorrhage, and gastrointestinal bleeding. We calculated relative risks (RRs) and 95% CIs for each outcome. We did subgroup analyses to assess whether differences in patient and trial characteristics affected outcomes. We used a random-effects model to compare pooled outcomes and tested for heterogeneity. 42,411 participants received a new oral anticoagulant and 29,272 participants received warfarin. New oral anticoagulants significantly reduced stroke or systemic embolic events by 19% compared with warfarin (RR 0·81, 95% CI 0·73-0·91; p<0·0001), mainly driven by a reduction in haemorrhagic stroke (0·49, 0·38-0·64; p<0·0001). New oral anticoagulants also significantly reduced all-cause mortality (0·90, 0·85-0·95; p=0·0003) and intracranial haemorrhage (0·48, 0·39-0·59; p<0·0001), but increased gastrointestinal bleeding (1·25, 1·01-1·55; p=0·04). We noted no heterogeneity for stroke or systemic embolic events in important subgroups, but there was a greater relative reduction in major bleeding with new oral anticoagulants when the centre-based time in therapeutic range was less than 66% than when it was 66% or more (0·69, 0·59-0·81 vs 0·93, 0·76-1·13; p for interaction 0·022). Low-dose new oral anticoagulant regimens showed similar overall reductions in stroke or systemic embolic events to warfarin (1·03, 0·84-1·27; p=0·74), and a more favourable bleeding profile (0·65, 0·43-1·00; p=0·05), but significantly more ischaemic strokes (1·28, 1·02-1·60; p=0·045). This meta-analysis is the first to include data for all four new oral anticoagulants studied in the pivotal phase 3 clinical trials for stroke prevention or systemic embolic events in patients with atrial fibrillation. New oral anticoagulants had a favourable risk-benefit profile, with significant reductions in stroke, intracranial haemorrhage, and mortality, and with similar major bleeding as for warfarin, but increased gastrointestinal bleeding. The relative efficacy and safety of new oral anticoagulants was consistent across a wide range of patients. Our findings offer clinicians a more comprehensive picture of the new oral anticoagulants as a therapeutic option to reduce the risk of stroke in this patient population. None. Copyright © 2014 Elsevier Ltd. All rights reserved.

Characteristic adverse events and their incidence among patients participating in acute ischemic stroke trials.

PubMed

Hesse, Kerrick; Fulton, Rachael L; Abdul-Rahim, Azmil H; Lees, Kennedy R

2014-09-01

Adverse events (AE) in trial populations present a major burden to researchers and patients, yet most events are unrelated to investigational treatment. We aimed to develop a coherent list of expected AEs, whose incidence can be predicted by patient characteristics that will inform future trials and perhaps general poststroke care. We analyzed raw AE data from patients participating in acute ischemic stroke trials. We identified events that occurred with a lower 99% confidence bound greater than nil. Among these, we applied receiver operating characteristic principles to select the fewest types of events that together represented the greatest number of reports. Using ordinal logistic regression, we modeled the incidence of these events as a function of patient age, sex, baseline National Institutes of Health Stroke Scale, and multimorbidity status, defining P<0.05 as statistically significant. We analyzed 5775 placebo-treated patients, reporting 21 217 AEs. Among 756 types of AEs, 132 accounted for 82.7%, of which 80% began within 10 days after stroke. Right hemisphere (odds ratio [OR], 1.67), increasing baseline National Institutes of Health Stroke Scale (OR, 1.11), multimorbidity status (OR, 1.09 per disease), patient age (OR, 1.01 per year), height (OR, 1.01 per centimeter), diastolic blood pressure (OR, 0.99 per mm Hg), and smoking (OR, 0.82) were independently associated with developing more AEs but together explained only 13% of the variation. A list of 132 expected AEs after acute ischemic stroke may be used to simplify interpretation and reporting of complications. AEs can be modestly predicted by patient characteristics, facilitating stratification of patients by risk for poststroke complications. © 2014 American Heart Association, Inc.

Carotid artery stenting in high surgical risk patients using the FiberNet embolic protection system: the EPIC trial results.

PubMed

Myla, Subbarao; Bacharach, J Michael; Ansel, Gary M; Dippel, Eric J; McCormick, Daniel J; Popma, Jeffrey J

2010-05-01

The multicenter EPIC (FiberNet Embolic Protection System in Carotid Artery Stenting Trial) single-arm trial evaluated the 30-day outcomes of a new design concept for embolic protection during carotid artery stenting (CAS). Embolic protection filters available for use during CAS include fixed and over-the-wire systems that rely on embolic material capture within a "basket" structure. The FiberNet Embolic Protection System (EPS), which features a very low crossing profile, consists of a three-dimensional fiber-based filter distally mounted on a 0.014 inch guidewire with integrated aspiration during filter retrieval. The trial enrolled 237 patients from 26 centers. Demographics, clinical and lesion characteristics, as well as adverse events through a 30-day follow-up were recorded. The mean age of the patients was 74 years, 64% were male and 20% had symptomatic carotid artery disease. The combined major adverse event (MAE) rate at 30 days for all death, stroke, and myocardial infarction was 3.0%. There were three major strokes (two ischemic and one hemorrhagic) and two minor strokes (both ischemic) for a 2.1% 30-day stroke rate. The procedural technical success rate was 97.5% and macroscopic evidence of debris was reported in 90.9% of the procedures. The FiberNet EPS, used with commercially available stents, produced low stroke rates following CAS in high surgical risk patients presenting with carotid artery disease. The unique filter design including aspiration during retrieval may have contributed to the low 30-day stroke rate reported during CAS in patients considered at high risk for complications following carotid endarterectomy (CEA). Copyright 2010 Wiley-Liss, Inc.

Brain-computer interfaces for post-stroke motor rehabilitation: a meta-analysis.

PubMed

Cervera, María A; Soekadar, Surjo R; Ushiba, Junichi; Millán, José Del R; Liu, Meigen; Birbaumer, Niels; Garipelli, Gangadhar

2018-05-01

Brain-computer interfaces (BCIs) can provide sensory feedback of ongoing brain oscillations, enabling stroke survivors to modulate their sensorimotor rhythms purposefully. A number of recent clinical studies indicate that repeated use of such BCIs might trigger neurological recovery and hence improvement in motor function. Here, we provide a first meta-analysis evaluating the clinical effectiveness of BCI-based post-stroke motor rehabilitation. Trials were identified using MEDLINE, CENTRAL, PEDro and by inspection of references in several review articles. We selected randomized controlled trials that used BCIs for post-stroke motor rehabilitation and provided motor impairment scores before and after the intervention. A random-effects inverse variance method was used to calculate the summary effect size. We initially identified 524 articles and, after removing duplicates, we screened titles and abstracts of 473 articles. We found 26 articles corresponding to BCI clinical trials, of these, there were nine studies that involved a total of 235 post-stroke survivors that fulfilled the inclusion criterion (randomized controlled trials that examined motor performance as an outcome measure) for the meta-analysis. Motor improvements, mostly quantified by the upper limb Fugl-Meyer Assessment (FMA-UE), exceeded the minimal clinically important difference (MCID=5.25) in six BCI studies, while such improvement was reached only in three control groups. Overall, the BCI training was associated with a standardized mean difference of 0.79 (95% CI: 0.37 to 1.20) in FMA-UE compared to control conditions, which is in the range of medium to large summary effect size. In addition, several studies indicated BCI-induced functional and structural neuroplasticity at a subclinical level. This suggests that BCI technology could be an effective intervention for post-stroke upper limb rehabilitation. However, more studies with larger sample size are required to increase the reliability of these results.

Dexamphetamine improves upper extremity outcome during rehabilitation after stroke: a pilot randomized controlled trial.

PubMed

Schuster, Corina; Maunz, Gerd; Lutz, Karin; Kischka, Udo; Sturzenegger, Rolf; Ettlin, Thierry

2011-10-01

For early inpatient stroke rehabilitation, the effectiveness of amphetamine combined with physiotherapy varies across studies. To investigate whether the recovery of activities of daily living (ADL, primary outcome) and motor function (secondary outcome) can be improved by dexamphetamine added to physiotherapy. In a double-blind, placebo-controlled trial, 16 patients, from 918 who were screened, were randomized to the experimental group (EG, dexamphetamine + physiotherapy) or control group (CG, placebo + physiotherapy). Both groups received multidisciplinary inpatient rehabilitation. Dexamphetamine (10 mg oral) or placebo was administered 2 days per week before physiotherapy. ADL and motor function were measured using the Chedoke-McMaster Stroke Assessment (CMSA) twice during baseline, every week during the 5-week treatment period, and at follow-up 1 week, 6 months, and 12 months after intervention. The majority of ineligible patients had too little paresis, were on anticoagulants, or had a stroke >60 days prior to entry. Participants (EG, n = 7, age 70.3 ± 10 years, 5 women, 37.9 ± 9 days after stroke; CG, n = 9, age 65.2 ± 17 years, 3 women, 40.3 ± 9 days after stroke) did not differ at baseline except for the leg subscale. Analysis of variance from baseline to 1 week follow-up revealed significant improvements in favor of EG for subscales ADL (P = .023) and arm function (P = .020) at end of treatment. No adverse events were detected. In this small trial that was based on prior positive trials, significant gains in ADL and arm function suggest that the dose and timing of dexamphetamine can augment physiotherapy. Effect size calculation suggests inclusion of at least 25 patients per group in future studies.

Transition of patients from blinded study drug to open-label anticoagulation: the ENGAGE AF-TIMI 48 trial.

PubMed

Ruff, Christian T; Giugliano, Robert P; Braunwald, Eugene; Mercuri, Michele; Curt, Valentin; Betcher, Joshua; Grip, Laura; Cange, Abby L; Crompton, Andrea E; Murphy, Sabina A; Deenadayalu, Naveen; Antman, Elliott M

2014-08-12

At the end of 2 previous trials, an excess of stroke and bleeding was observed in patients with AF randomized to a new oral anticoagulant (NOAC) who transitioned to a vitamin K antagonist (VKA). The ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) trial compared once-daily edoxaban to warfarin for stroke prevention in patients with AF. An end-of-trial transition plan was developed to minimize the risks of stroke due to inadequate anticoagulation and bleeding from excessive anticoagulation during this critical period. All patients on the blinded study drug at the trial's conclusion were included in this analysis. In pre-specified analyses, stroke, bleeding, and death that occurred through 30 days after the end-of-trial visit were stratified by randomized treatment allocation and open-label anticoagulant selected post-trial. Of the 13,642 patients taking the blinded study drug at the end of the trial, 9,304 (68.2%) were transitioned to open-label VKA and 4,258 patients (31.2%) to an NOAC. There were 21 strokes evenly distributed across the 3 randomized treatment arms: warfarin 7 (1.90%/year), edoxaban high dose 7 (1.89%/year), edoxaban low dose 7 (1.85%/year). Major bleeding was also similar across the 3 treatment arms: warfarin 11 (2.98%/year), edoxaban high dose 10 (2.69%/year), edoxaban low dose 18 (4.76%/year). In patients transitioned to VKA, 85% of patients had at least 1 INR ≥ 2 by day 14 after the transition and 99% by day 30. The ENGAGE AF-TIMI 48 transition plan protected patients from an excess of thrombotic and bleeding events and should be helpful in clinical practice when patients are transitioned between oral anticoagulants. (Global Study to Assess the Safety and Effectiveness of Edoxaban [DU-176b] vs Standard Practice of Dosing With Warfarin in Patients With Atrial Fibrillation [EngageAFTIMI48]; NCT00781391). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

CPAP as treatment of sleep apnea after stroke: A meta-analysis of randomized trials.

PubMed

Brill, Anne-Kathrin; Horvath, Thomas; Seiler, Andrea; Camilo, Millene; Haynes, Alan G; Ott, Sebastian R; Egger, Matthias; Bassetti, Claudio L

2018-04-03

To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) examining the effectiveness of continuous positive airway pressure (CPAP) in stroke patients with sleep disordered breathing (SDB). In a systematic literature search of electronic databases (MEDLINE, Embase, and the Cochrane Library) from 1980 to November 2016, we identified RCTs that assessed CPAP compared to standard care or sham CPAP in adult patients with stroke or TIA with SDB. Mean CPAP use, odds ratios (ORs), and standardized mean differences (SMDs) were calculated. The prespecified outcomes were adherence to CPAP, neurologic improvement, adverse events, new vascular events, and death. Ten RCTs (564 participants) with CPAP as intervention were included. Two studies compared CPAP with sham CPAP; 8 compared CPAP with usual care. Mean CPAP use across the trials was 4.53 hours per night (95% confidence interval [CI] 3.97-5.08). The OR of dropping out with CPAP was 1.83 (95% CI 1.05-3.21, p = 0.033). The combined analysis of the neurofunctional scales (NIH Stroke Scale and Canadian Neurological Scale) showed an overall neurofunctional improvement with CPAP (SMD 0.5406, 95% CI 0.0263-1.0548) but with a considerable heterogeneity ( I 2 = 78.9%, p = 0.0394) across the studies. Long-term survival was improved with CPAP in 1 trial. CPAP use after stroke is acceptable once the treatment is tolerated. The data indicate that CPAP might be beneficial for neurologic recovery, which justifies larger RCTs. © 2018 American Academy of Neurology.

Participant Recruitment and Engagement in Automated eHealth Trial Registration: Challenges and Opportunities for Recruiting Women Who Experience Violence.

PubMed

Koziol-McLain, Jane; McLean, Christine; Rohan, Maheswaran; Sisk, Rose; Dobbs, Terry; Nada-Raja, Shyamala; Wilson, Denise; Vandal, Alain C

2016-10-25

Automated eHealth Web-based research trials offer people an accessible, confidential opportunity to engage in research that matters to them. eHealth trials may be particularly useful for sensitive issues when seeking health care may be accompanied by shame and mistrust. Yet little is known about people's early engagement with eHealth trials, from recruitment to preintervention autoregistration processes. A recent randomized controlled trial that tested the effectiveness of an eHealth safety decision aid for New Zealand women in the general population who experienced intimate partner violence (isafe) provided the opportunity to examine recruitment and preintervention participant engagement with a fully automated Web-based registration process. The trial aimed to recruit 340 women within 24 months. The objective of our study was to examine participant preintervention engagement and recruitment efficiency for the isafe trial, and to analyze dropout through the registration pathway, from recruitment to eligibility screening and consent, to completion of baseline measures. In this case study, data collection sources included the trial recruitment log, Google Analytics reports, registration and program metadata, and costs. Analysis included a qualitative narrative of the recruitment experience and descriptive statistics of preintervention participant engagement and dropout rates. A Koyck model investigated the relationship between Web-based online marketing website advertisements (ads) and participant accrual. The isafe trial was launched on September 17, 2012. Placement of ads in an online classified advertising platform increased the average number of recruited participants per month from 2 to 25. Over the 23-month recruitment period, the registration website recorded 4176 unique visitors. Among 1003 women meeting eligibility criteria, 51.55% (517) consented to participate; among the 501 women who enrolled (consented, validated, and randomized), 412 (82.2%) were accrued (completed baseline assessments). The majority (n=52, 58%) of the 89 women who dropped out between enrollment and accrual never logged in to the allocated isafe website. Of every 4 accrued women, 3 (314/412, 76.2%) identified the classified ad as their referral source, followed by friends and family (52/412, 12.6%). Women recruited through a friend or relative were more likely to self-identify as indigenous Māori and live in the highest-deprivation areas. Ads increased the accrual rate by a factor of 74 (95% CI 49-112). Print advertisements, website links, and networking were costly and inefficient methods for recruiting participants to a Web-based eHealth trial. Researchers are advised to limit their recruitment efforts to Web-based online marketplace and classified advertising platforms, as in the isafe case, or to social media. Online classified advertising in "Jobs-Other-volunteers" successfully recruited a diverse sample of women experiencing intimate partner violence. Preintervention recruitment data provide critical information to inform future research and critical analysis of Web-based eHealth trials. Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12612000708853; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612000708853 (Archived by WebCite at http://www.webcitation/6lMGuVXdK).

Regional variation in acute stroke care organisation.

PubMed

Muñoz Venturelli, Paula; Robinson, Thompson; Lavados, Pablo M; Olavarría, Verónica V; Arima, Hisatomi; Billot, Laurent; Hackett, Maree L; Lim, Joyce Y; Middleton, Sandy; Pontes-Neto, Octavio; Peng, Bin; Cui, Liying; Song, Lily; Mead, Gillian; Watkins, Caroline; Lin, Ruey-Tay; Lee, Tsong-Hai; Pandian, Jeyaraj; de Silva, H Asita; Anderson, Craig S

2016-12-15

Few studies have assessed regional variation in the organisation of stroke services, particularly health care resourcing, presence of protocols and discharge planning. Our aim was to compare stroke care organisation within middle- (MIC) and high-income country (HIC) hospitals participating in the Head Position in Stroke Trial (HeadPoST). HeadPoST is an on-going international multicenter crossover cluster-randomized trial of 'sitting-up' versus 'lying-flat' head positioning in acute stroke. As part of the start-up phase, one stroke care organisation questionnaire was completed at each hospital. The World Bank gross national income per capita criteria were used for classification. 94 hospitals from 9 countries completed the questionnaire, 51 corresponding to MIC and 43 to HIC. Most participating hospitals had a dedicated stroke care unit/ward, with access to diagnostic services and expert stroke physicians, and offering intravenous thrombolysis. There was no difference for the presence of a dedicated multidisciplinary stroke team, although greater access to a broad spectrum of rehabilitation therapists in HIC compared to MIC hospitals was observed. Significantly more patients arrived within a 4-h window of symptoms onset in HIC hospitals (41 vs. 13%; P<0.001), and a significantly higher proportion of acute ischemic stroke patients received intravenous thrombolysis (10 vs. 5%; P=0.002) compared to MIC hospitals. Although all hospitals provided advanced care for people with stroke, differences were found in stroke care organisation and treatment. Future multilevel analyses aims to determine the influence of specific organisational factors on patient outcomes. Copyright © 2016 Elsevier B.V. All rights reserved.

Microbubble signal and trial of org in acute stroke treatment (TOAST) classification in ischemic stroke.

PubMed

Lee, Chan-Hyuk; Kang, Hyun Goo; Lee, Ji Sung; Ryu, Han Uk; Jeong, Seul-Ki

2018-07-15

Right-to-left shunt (RLS) through a patent foramen ovale (PFO) is likely associated with ischemic stroke. Many studies have attempted to demonstrate the association between RLS and ischemic stroke. However, information on the association between the degree of RLS and the subtypes of ischemic stroke categorized by the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification is lacking. This was a retrospective study involving 508 patients with ischemic stroke who underwent a transcranial Doppler (TCD) microbubble test between 2013 and 2015. The degree of RLS was divided into 4 grades according to the microbubble signal (MBS) as follows: no MBS, grade 1; MBS < 20, grade 2; MBS > 20, grade 3; curtain sign, grade 4. The degree of RLS and the type of ischemic stroke as classified by TOAST were analyzed and compared with other clinical information and laboratory findings. The higher RLS grade was associated with the cardioembolism (CE) and stroke of undetermined etiology (SUE), and the microbubble signals were inversely related with small vessel disease (SVD). An MBS higher than grade 3 showed a 2.95-fold higher association with SUE than large artery atherosclerosis (LAA), while grade 4 MBS revealed an approximately 8-fold higher association with SUE than LAA. RLS identified by the TCD microbubble test was significantly and independently associated with cryptogenic ischemic stroke (negative evaluation). Subsequent studies are needed to determine the biologic relationship between RLS and ischemic stroke, particularly the cryptogenic subtype of ischemic stroke. Copyright © 2018 Elsevier B.V. All rights reserved.

Barriers and enablers to implementing clinical treatment protocols for fever, hyperglycaemia, and swallowing dysfunction in the Quality in Acute Stroke Care (QASC) Project--a mixed methods study.

PubMed

Dale, Simeon; Levi, Christopher; Ward, Jeanette; Grimshaw, Jeremy M; Jammali-Blasi, Asmara; D'Este, Catherine; Griffiths, Rhonda; Quinn, Clare; Evans, Malcolm; Cadilhac, Dominique; Cheung, N Wah; Middleton, Sandy

2015-02-01

The Quality in Acute Stroke Care (QASC) trial evaluated systematic implementation of clinical treatment protocols to manage fever, sugar, and swallow (FeSS protocols) in acute stroke care. This cluster-randomised controlled trial was conducted in 19 stroke units in Australia. To describe perceived barriers and enablers preimplementation to the introduction of the FeSS protocols and, postimplementation, to determine which of these barriers eventuated as actual barriers. Preimplementation: Workshops were held at the intervention stroke units (n = 10). The first workshop involved senior clinicians who identified perceived barriers and enablers to implementation of the protocols, the second workshop involved bedside clinicians. Postimplementation, an online survey with stroke champions from intervention sites was conducted. A total of 111 clinicians attended the preimplementation workshops, identifying 22 barriers covering four main themes: (a) need for new policies, (b) limited workforce (capacity), (c) lack of equipment, and (d) education and logistics of training staff. Preimplementation enablers identified were: support by clinical champions, medical staff, nursing management and allied health staff; easy adaptation of current protocols, care-plans, and local policies; and presence of specialist stroke unit staff. Postimplementation, only five of the 22 barriers identified preimplementation were reported as actual barriers to adoption of the FeSS protocols, namely, no previous use of insulin infusions; hyperglycaemic protocols could not be commenced without written orders; medical staff reluctance to use the ASSIST swallowing screening tool; poor level of engagement of medical staff; and doctors' unawareness of the trial. The process of identifying barriers and enablers preimplementation allowed staff to take ownership and to address barriers and plan for change. As only five of the 22 barriers identified preimplementation were reported to be actual barriers at completion of the trial, this suggests that barriers are often overcome whilst some are only ever perceived rather than actual barriers. © 2015 Sigma Theta Tau International.

Stroke prevention in atrial fibrillation: pooled analysis of SPORTIF III and V trials.

PubMed

Albers, Gregory W

2004-12-01

This article will review 2 clinical trials that recently compared the safety and efficacy of the oral direct thrombin inhibitor ximelagatran (fixed dose, 36 mg twice daily) with warfarin (adjusted dose, target international normalized ratio [INR] 2.0-3.0) in patients with nonvalvular atrial fibrillation and at least 1 risk factor for stroke. These noninferiority trials involved 7329 patients and a mean exposure to study drug of 18.5 months. The Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) III (open-label, N = 3407) and V trials (double-blind, N = 3922) were designed for pooled analysis, and the data showed the efficacy of ximelagatran therapy was comparable (noninferior) with extremely well-controlled warfarin therapy in preventing stroke and systemic embolic events; the primary event rates were 1.65% per year and 1.62% per year in the warfarin and ximelagatran groups, respectively (P = .941). In patients with a history of stroke or transient ischemic attack (about 20% of the SPORTIF population), the event rates were 3.27% per year and 2.83% per year in the warfarin and ximelagatran groups, respectively (P = .625). The distribution of stroke subtypes was similar in the 2 treatment groups. Intracranial hemorrhage occurred at a rate of 0.20% per year with warfarin and 0.11% per year with ximelagatran. Combined rates of minor and major bleeding were significantly lower with ximelagatran than with warfarin (32% per year vs 39% per year; P < .0001). The myocardial infarction rates were the same in the pooled database (no difference between agents). The aspirin data will be the subject of two substudy papers. Oral ximelagatran administered without coagulation monitoring or dose adjustment was as effective as well-controlled, adjusted-dose warfarin for prevention of stroke and systemic embolic events and was associated with significantly less total bleeding. This oral direct thrombin inhibitor is a potentially promising treatment option for the prevention of thromboembolism.

Art participation for psychosocial wellbeing during stroke rehabilitation: a feasibility randomised controlled trial.

PubMed

Morris, Jacqui H; Kelly, Chris; Joice, Sara; Kroll, Thilo; Mead, Gillian; Donnan, Peter; Toma, Madalina; Williams, Brian

2017-08-30

To examine the feasibility of undertaking a pragmatic single-blind randomised controlled trial (RCT) of a visual arts participation programme to evaluate effects on survivor wellbeing within stroke rehabilitation. Stroke survivors receiving in-patient rehabilitation were randomised to receive eight art participation sessions (n = 41) or usual care (n = 40). Recruitment, retention, preference for art participation and change in selected outcomes were evaluated at end of intervention outcome assessment and three-month follow-up. Of 315 potentially eligible participants 81 (29%) were recruited. 88% (n = 71) completed outcome and 77% (n = 62) follow-up assessments. Of eight intervention group non-completers, six had no preference for art participation. Outcome completion varied between 97% and 77%. Running groups was difficult because of randomisation timing. Effectiveness cannot be determined from this feasibility study but effects sizes suggested art participation may benefit emotional wellbeing, measured on the positive and negative affect schedule, and self-efficacy for Art (d = 0.24-0.42). Undertaking a RCT of art participation within stroke rehabilitation was feasible. Art participation may enhance self-efficacy and positively influence emotional wellbeing. These should be outcomes in a future definitive trial. A cluster RCT would ensure art groups could be reliably convened. Fewer measures, and better retention strategies are required. Implications for Rehabilitation This feasibility randomised controlled trial (RCT) showed that recruiting and retaining stroke survivors in an RCT of a visual arts participation intervention within stroke rehabilitation was feasible. Preference to participate in art activities may influence recruitment and drop-out rates, and should be addressed and evaluated fully. Art participation as part of rehabilitation may improve some aspects of post-stroke wellbeing, including positive affect and self-efficacy for art. A future definitive cluster RCT would facilitate full evaluation of the value art participation can add to rehabilitation.

Transcatheter closure of patent foramen ovale for secondary prevention of ischemic stroke: Quantitative synthesis of pooled randomized trial data.

PubMed

Hakeem, Abdul; Cilingiroglu, Mehmet; Katramados, Angelos; Boudoulas, Konstantinos Dean; Iliescu, Cezar; Gundogdu, Betul; Marmagkiolis, Konstantinos

2018-01-14

To evaluate the safety and efficacy of percutaneous device closure of patent foramen ovale (PFO) for secondary prevention of ischemic stroke BACKGROUND: Stroke remains the leading cause of serious long-term disability in the United States. The effectiveness of a percutaneous PFO closure in the prevention of recurrent cryptogenic strokes has not been established. We performed a literature search using PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Google Scholar, and Internet-based sources from January 2003 to September 2017. Randomized controlled trails (RCTs) comparing percutaneous PFO closure to medical therapy alone. Five RCTs (CLOSURE I, PC Trial, REDUCE, RESPECT, and CLOSE) with 1,829 patients in the device group and 1,611 patients in the medical group met inclusion criteria. The cumulative incidence of recurrent stroke was 2.02% in the PFO closure arm and 4.4% in the medical therapy group (RR 0.42, 95%CI 0.20, 0.91; P = 0.03). There was no difference in the incidence of death [0.7% vs. 0.9%; RR 0.76 (95% CI 0.35, 1.64), P = 0.49] or adverse events during the follow-up period [24.6% vs. 23.7% (RR 1.03; 95% CI 0.91, 1.16), P = 0.65] between the closure and medical therapy groups. Incidence of atrial fibrillation was significantly higher in closure group compared to medical therapy [4% vs. 0.6% (RR 4.73; 95% CI 2.09, 10.70), P = 0.0002]. The comparative effectiveness of PFO closure (compared to medical therapy) was significantly more pronounced in those younger than 45 years, males, larger shunts and disc design platforms (P < 0.05). Based on the results of this analysis of randomized trial data, percutaneous PFO closure appears to be a safe and effective therapeutic option for the secondary prevention of ischemic stroke in patients with PFO and cryptogenic stroke. © 2018 Wiley Periodicals, Inc.

Effects of action observation therapy and mirror therapy after stroke on rehabilitation outcomes and neural mechanisms by MEG: study protocol for a randomized controlled trial.

PubMed

Shih, Tsai-Yu; Wu, Ching-Yi; Lin, Keh-Chung; Cheng, Chia-Hsiung; Hsieh, Yu-Wei; Chen, Chia-Ling; Lai, Chih-Jou; Chen, Chih-Chi

2017-10-04

Loss of upper-extremity motor function is one of the most debilitating deficits following stroke. Two promising treatment approaches, action observation therapy (AOT) and mirror therapy (MT), aim to enhance motor learning and promote neural reorganization in patients through different afferent inputs and patterns of visual feedback. Both approaches involve different patterns of motor observation, imitation, and execution but share some similar neural bases of the mirror neuron system. AOT and MT used in stroke rehabilitation may confer differential benefits and neural activities that remain to be determined. This clinical trial aims to investigate and compare treatment effects and neural activity changes of AOT and MT with those of the control intervention in patients with subacute stroke. An estimated total of 90 patients with subacute stroke will be recruited for this study. All participants will be randomly assigned to receive AOT, MT, or control intervention for a 3-week training period (15 sessions). Outcome measurements will be taken at baseline, immediately after treatment, and at the 3-month follow-up. For the magnetoencephalography (MEG) study, we anticipate that we will recruit 12 to 15 patients per group. The primary outcome will be the Fugl-Meyer Assessment score. Secondary outcomes will include the modified Rankin Scale, the Box and Block Test, the ABILHAND questionnaire, the Questionnaire Upon Mental Imagery, the Functional Independence Measure, activity monitors, the Stroke Impact Scale version 3.0, and MEG signals. This clinical trial will provide scientific evidence of treatment effects on motor, functional outcomes, and neural activity mechanisms after AOT and MT in patients with subacute stroke. Further application and use of AOT and MT may include telerehabilitation or home-based rehabilitation through web-based or video teaching. ClinicalTrials.gov, ID: NCT02871700 . Registered on 1 August 2016.

Alternative Calculations of Individual Patient Time in Therapeutic Range While Taking Warfarin: Results From the ROCKET AF Trial

PubMed Central

Singer, Daniel E.; Hellkamp, Anne S.; Yuan, Zhong; Lokhnygina, Yuliya; Patel, Manesh R.; Piccini, Jonathan P.; Hankey, Graeme J.; Breithardt, Günter; Halperin, Jonathan L.; Becker, Richard C.; Hacke, Werner; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.

2015-01-01

Background In the ROCKET AF (Rivaroxaban–Once‐daily, oral, direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial, marked regional differences in control of warfarin anticoagulation, measured as the average individual patient time in the therapeutic range (iTTR) of the international normalized ratio (INR), were associated with longer inter‐INR test intervals. The standard Rosendaal approach can produce biased low estimates of TTR after an appropriate dose change if the follow‐up INR test interval is prolonged. We explored the effect of alternative calculations of TTR that more immediately account for dose changes on regional differences in mean iTTR in the ROCKET AF trial. Methods and Results We used an INR imputation method that accounts for dose change. We compared group mean iTTR values between our dose change–based method with the standard Rosendaal method and determined that the differences between approaches depended on the balance of dose changes that produced in‐range INRs (“corrections”) versus INRs that were out of range in the opposite direction (“overshoots”). In ROCKET AF, the overall mean iTTR of 55.2% (Rosendaal) increased up to 3.1% by using the dose change–based approach, depending on assumptions. However, large inter‐regional differences in anticoagulation control persisted. Conclusions TTR, the standard measure of control of warfarin anticoagulation, depends on imputing daily INR values for the vast majority of follow‐up days. Our TTR calculation method may better reflect the impact of warfarin dose changes than the Rosendaal approach. In the ROCKET AF trial, this dose change–based approach led to a modest increase in overall mean iTTR but did not materially affect the large inter‐regional differences previously reported. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00403767. PMID:25736441

A pragmatic approach to sonothrombolysis in acute ischaemic stroke: the Norwegian randomised controlled sonothrombolysis in acute stroke study (NOR-SASS).

PubMed

Nacu, Aliona; Kvistad, Christopher E; Logallo, Nicola; Naess, Halvor; Waje-Andreassen, Ulrike; Aamodt, Anne Hege; Solhoff, Ragnar; Lund, Christian; Tobro, Håkon; Rønning, Ole Morten; Salvesen, Rolf; Idicula, Titto T; Thomassen, Lars

2015-07-11

Ultrasound accelerates thrombolysis with tPA (sonothrombolysis). Ultrasound in the absence of tPA also accelerates clot break-up (sonolysis). Adding intravenous gaseous microbubbles may potentiate the effect of ultrasound in both sonothrombolysis and sonolysis. The Norwegian Sonothrombolysis in Acute Stroke Study aims in a pragmatic approach to assess the effect and safety of contrast enhanced ultrasound treatment in unselected acute ischaemic stroke patients. Acute ischaemic stroke patients ≥ 18 years, with or without visible arterial occlusion on computed tomography angiography (CTA) and treatable ≤ 4(½) hours after symptom onset, are included in NOR-SASS. NOR-SASS is superimposed on a separate trial randomising patients with acute ischemic stroke to either tenecteplase or alteplase (The Norwegian Tenecteplase Stroke Trial NOR-TEST). The NOR-SASS trial has two arms: 1) the thrombolysis-arms (NOR-SASS A and B) includes patients given intravenous thrombolysis (tenecteplase or alteplase), and 2) the no-thrombolysis-arm (NOR-SASS C) includes patients with contraindications to thrombolysis. First step randomisation of NOR-SASS A is embedded in NOR-TEST as a 1:1 randomisation to either tenecteplase or alteplase. Second step NOR-SASS randomisation is 1:1 to either contrast enhanced sonothrombolysis (CEST) or sham CEST. Randomisation in NOR-SASS B (routine alteplase group) is 1:1 to either CEST or sham CEST. Randomisation of NOR-SASS C is 1:1 to either contrast enhanced sonolysis (CES) or sham CES. Ultrasound is given for one hour using a 2-MHz pulsed-wave diagnostic ultrasound probe. Microbubble contrast (SonoVue®) is given as a continuous infusion for ~30 min. Recanalisation is assessed at 60 min after start of CEST/CES. Magnetic resonance imaging and angiography is performed after 24 h of stroke onset. Primary study endpoints are 1) major neurological improvement measured with NIHSS score at 24 h and 2) favourable functional outcome defined as mRS 0-1 at 90 days. NOR-SASS is the first randomised controlled trial designed to test the superiority of contrast enhanced ultrasound treatment given ≤ 4(½) hours after stroke onset in an unselected acute ischaemic stroke population eligible or not eligible for intravenous thrombolysis, with or without a defined arterial occlusion on CTA. If a positive effect and safety can be proven, contrast enhanced ultrasound treatment will be an option for all acute ischaemic stroke patients. EudraCT No 201200032341; www.clinicaltrials.gov NCT01949961.

Reducing Trunk Compensation in Stroke Survivors: A Randomized Crossover Trial Comparing Visual and Force Feedback Modalities.

PubMed

Valdés, Bulmaro Adolfo; Schneider, Andrea Nicole; Van der Loos, H F Machiel

2017-10-01

To investigate whether the compensatory trunk movements of stroke survivors observed during reaching tasks can be decreased by force and visual feedback, and to examine whether one of these feedback modalities is more efficacious than the other in reducing this compensatory tendency. Randomized crossover trial. University research laboratory. Community-dwelling older adults (N=15; 5 women; mean age, 64±11y) with hemiplegia from nontraumatic hemorrhagic or ischemic stroke (>3mo poststroke), recruited from stroke recovery groups, the research group's website, and the community. In a single session, participants received augmented feedback about their trunk compensation during a bimanual reaching task. Visual feedback (60 trials) was delivered through a computer monitor, and force feedback (60 trials) was delivered through 2 robotic devices. Primary outcome measure included change in anterior trunk displacement measured by motion tracking camera. Secondary outcomes included trunk rotation, index of curvature (measure of straightness of hands' path toward target), root mean square error of hands' movement (differences between hand position on every iteration of the program), completion time for each trial, and posttest questionnaire to evaluate users' experience and system's usability. Both visual (-45.6% [45.8 SD] change from baseline, P=.004) and force (-41.1% [46.1 SD], P=.004) feedback were effective in reducing trunk compensation. Scores on secondary outcome measures did not improve with either feedback modality. Neither feedback condition was superior. Visual and force feedback show promise as 2 modalities that could be used to decrease trunk compensation in stroke survivors during reaching tasks. It remains to be established which one of these 2 feedback modalities is more efficacious than the other as a cue to reduce compensatory trunk movement. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Predictors of stroke in patients with impaired glucose tolerance: results from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research trial.

PubMed

Preiss, David; Giles, Thomas D; Thomas, Laine E; Sun, Jie-Lena; Haffner, Steven M; Holman, Rury R; Standl, Eberhard; Mazzone, Theodore; Rutten, Guy E; Tognoni, Gianni; Chiang, Fu-Tien; McMurray, John J V; Califf, Robert M

2013-09-01

Risk factors for stroke are well-established in general populations but sparsely studied in individuals with impaired glucose tolerance. We identified predictors of stroke among participants with impaired glucose tolerance in the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. Cox proportional-hazard regression models were constructed using baseline variables, including the 2 medications studied, valsartan and nateglinide. Among 9306 participants, 237 experienced a stroke over 6.4 years. Predictors of stroke included classical risk factors such as existing cerebrovascular and coronary heart disease, higher pulse pressure, higher low-density lipoprotein cholesterol, older age, and atrial fibrillation. Other factors, including previous venous thromboembolism, higher waist circumference, lower estimated glomerular filtration rate, lower heart rate, and lower body mass index, provided additional important predictive information, yielding a C-index of 0.72. Glycemic measures were not predictive of stroke. Variables associated with stroke were similar in participants with no prior history of cerebrovascular disease at baseline. The most powerful predictors of stroke in patients with impaired glucose tolerance included a combination of established risk factors and novel variables, such as previous venous thromboembolism and elevated waist circumference, allowing moderately effective identification of high-risk individuals.

The effect of arm support combined with rehabilitation games on upper-extremity function in subacute stroke: a randomized controlled trial.

PubMed

Prange, Gerdienke B; Kottink, Anke I R; Buurke, Jaap H; Eckhardt, Martine M E M; van Keulen-Rouweler, Bianca J; Ribbers, Gerard M; Rietman, Johan S

2015-02-01

Use of rehabilitation technology, such as (electro)mechanical devices or robotics, could partly relieve the increasing strain on stroke rehabilitation caused by an increasing prevalence of stroke. Arm support (AS) training showed improvement of unsupported arm function in chronic stroke. To examine the effect of weight-supported arm training combined with computerized exercises on arm function and capacity, compared with dose-matched conventional reach training in subacute stroke patients. In a single-blind, multicenter, randomized controlled trial, 70 subacute stroke patients received 6 weeks of training with either an AS device combined with computerized exercises or dose-matched conventional training (CON). Arm function was evaluated pretraining and posttraining by Fugl-Meyer assessment (FM), maximal reach distance, Stroke Upper Limb Capacity Scale (SULCS), and arm pain via Visual Analogue Scale, in addition to perceived motivation by Intrinsic Motivation Inventory posttraining. FM and SULCS scores and reach distance improved significantly within both groups. These improvements and experienced pain did not differ between groups. The AS group reported higher interest/enjoyment during training than the CON group. AS training with computerized exercises is as effective as conventional therapy dedicated to the arm to improve arm function and activity in subacute stroke rehabilitation, when applied at the same dose. © The Author(s) 2014.