A pilot randomized controlled trial to evaluate the benefit of the cardiac rehabilitation paradigm for the non-acute ischaemic stroke population. Hyperbaric oxygen therapy in acute ischemic stroke: results of the Hyperbaric Oxygen in Acute Ischemic Stroke Trial Pilot Study. AXIS: a trial of intravenous granulocyte colony-stimulating factor in acute ischemic stroke. Modified constraint-induced therapy in chronic stroke: results of a single-blinded randomized controlled trial. Admitting acute ischemic stroke patients to a stroke care monitoring unit versus a conventional stroke unit: a randomized pilot study. A cluster-randomized trial to improve stroke care in hospitals. Granulocyte colony-stimulating factor for acute ischemic stroke: a randomized controlled trial. Erythropoietin therapy for acute stroke is both safe and beneficial. The development of a stroke clinical pathway: an experience in a medium-sized community hospital.
To evaluate risk factor reduction and health-related quality of life following a 10-week cardiac rehabilitation programme in non-acute ischaemic stroke subjects.
                Single-blinded randomized control trial.
                Outpatient rehabilitation.
                Forty-eight community-dwelling ischaemic stroke patients (38 independently mobile, 9 requiring assistance, 1 non-ambulatory) were randomly assigned to intervention or control groups by concealed allocation.
                The trial consisted of a 10-week schedule with measures taken at weeks 1 and 10. Both groups continued usual care (excluding aerobic exercise); intervention subjects attended 16 cycle ergometry sessions of aerobic-training intensity and two stress-management classes.
                Cardiac risk score (CRS); VO(2) (mL O(2)/kg per minute) and Borg Rate of Perceived Exertion (RPE) assessed during a standardized ergometry test; Hospital Anxiety and Depression Scale (HADS); Frenchay Activity Index; Fasting Lipid Profiles and Resting Blood Pressure.
                Group comparison with independent t-tests showed significantly greater improvement at follow-up by intervention subjects than controls in VO(2) (intervention 10.6 +/-1.6 to 12.0 +/- 2.2, control 11.1 +/-1.8 to 11.1 +/-1.9 t=4.734, P<0.001) and CRS (intervention 13.4 +/-10.1 to 12.4 +/-10.5, control 9.4 +/-6.7 to 15.0 +/-6.1 t=-2.537, P<0.05). RPE rating decreased in intervention subjects (13.4 +/-12.2 to 12.4 +/-2.0) and increased in controls (13.8 +/-1.8 to 14.4 +/-1.6); Mann-Whitney U (U = 173.5, P<0.05). Within-group comparison showed significant decrease in the HADS depression subscale in the intervention group alone (5.1 +/-3.4 to 3.0 +/-2.8) (Wilcoxon signed ranks test Z=-3.278, P<0.001).
                Preliminary findings suggest non-acute ischaemic stroke patients can improve their cardiovascular fitness and reduce their CRS with a cardiac rehabilitation programme. The intervention was associated with improvement in self-reported depression. Hyperbaric oxygen therapy (HBO) has promise as a treatment for acute stroke. This study was conducted to evaluate the efficacy, safety, and feasibility of using HBO in acute ischemic stroke.
                We conducted a randomized, prospective, double-blind, sham-controlled pilot study of 33 patients presenting with acute ischemic stroke who did not receive thrombolytics over a 24-month period. Patients were randomized to treatment for 60 minutes in a monoplace hyperbaric chamber pressurized with 100% O2 to 2.5-atm absolute (ATA) in the HBO group or 1.14 ATA in the sham group. Primary outcomes measured included percentage of patients with improvement at 24 hours (National Institutes of Health Stroke Scale [NIHSS]) and 90 days (NIHSS, Barthel Index, modified Rankin Scale, Glasgow Outcome Scale). Secondary measurements included complications of treatment and mortality at 90 days.
                Baseline demographics were similar in both groups. There were no differences between the groups at 24 hours (P=0.44). At 3 months, however, a larger percentage of the sham patients had a good outcome defined by their stroke scores compared with the HBO group (NIHSS, 80% versus 31.3%; P=0.04; Barthel Index, 81.8% versus 50%; P=0.12; modified Rankin Scale, 81.8% versus 31.3%; P=0.02; Glasgow Outcome Scale, 90.9% versus 37.5%; P=0.01) with loss of statistical significance in a intent-to-treat analysis.
                Although our HBO protocol appears feasible and safe, it does not appear to be beneficial and may be harmful in patients with acute ischemic stroke. Granulocyte colony-stimulating factor (G-CSF) is a promising stroke drug candidate. The present phase IIa study assessed safety and tolerability over a broad dose range of G-CSF doses in acute ischemic stroke patients and explored outcome data.
                Four intravenous dose regimens (total cumulative doses of 30-180 μg/kg over the course of 3 days) of G-CSF were tested in 44 patients in a national, multicenter, randomized, placebo-controlled dose escalation study (NCT00132470; www.clinicaltrial.gov). Main inclusion criteria were a 12-hour time window after stroke onset, infarct localization to the middle cerebral artery territory, a baseline National Institutes of Health Stroke Scale range of 4 to 22, and presence of diffusion-weighted imaging/perfusion-weighted imaging mismatch.
                Concerning the primary safety end points, we observed no increase of thromboembolic events in the active treatment groups, and no increase in related serious adverse events. G-CSF led to expected increases in neutrophils and monocytes that resolved rapidly after end of treatment. We observed a clinically insignificant drug-related decrease of platelets. As expected from the low number of patients, we did not observe significant differences in clinical outcome in treatment vs. placebo. In exploratory analyses, we observed an interesting dose-dependent beneficial effect of treatment in patients with DWI lesions > 14-17 cm³.
                We conclude that G-CSF was well-tolerated even at high dosages in patients with acute ischemic stroke, and that a substantial increase in leukocytes appears not problematic in stroke patients. In addition, exploratory analyses suggest treatment effects in patients with larger baseline diffusion-weighted imaging lesions. The obtained data provide the basis for a second trial aimed to demonstrate safety and efficacy of G-CSF on clinical end points. This single-blinded randomized controlled trial compared the efficacy of a reimbursable, outpatient, modified constraint-induced therapy (mCIT) protocol (half-hour therapy sessions occurring 3 days per week in which subjects used the more affected arm combined with less affected arm restriction 5 days per week for 5 hours; both of these regimens were administered during a 10-week period) with that of a time-matched exercise program for the more affected arm or a no-treatment control regimen.
                Thirty-five subjects with chronic stroke participated in the study.
                The Action Research Arm Test (ARAT), Fugl-Meyer Assessment of Motor Recovery After Stroke (FM), and Motor Activity Log (MAL) were administered to the subjects.
                After intervention, significant differences were observed on the ARAT and MAL Amount of Use and Quality of Movement scales, all in favor of the mCIT group.
                The data affirm previous findings suggesting that this reimbursable, outpatient protocol increases more affected arm use and function. Magnitude of changes was consistent with those reported in more intense protocols, such as constraint-induced therapy. Pathophysiological considerations and observational studies indicate that elevated body temperature, hypoxia, hypotension, and cardiac arrhythmias in the acute phase of ischemic stroke may aggravate brain damage and worsen outcome.
                Both units were organized with the same standard care and multidisciplinary approach to nursing and rehabilitation. A blinded observer assessed functional outcome at 3 months with the modified Rankin scale (mRS) and Barthel Index (BI). End points were (1) poor outcome, defined as either mRS > or =4 or BI <60 or the need for institutional care and (2) mortality.
                Fifty-four patients meeting the inclusion criteria were randomized. The groups were well matched for baseline characteristics, stroke subtype, stroke severity, vascular risk factors, and prognostic factors. Poor outcome was seen in 7 (25.9%) patients in the SCMU group and in 13 (48.1%) in the SU group (P=0.16). Mortality was lower in the SCMU group than in the SU group (1 [3.7%] vs 7 [25.9%]; odds ratio, 0.11 [95% CI, 0.02 to 0.96], P=0.05).
                This pilot study suggests that admission of acute stroke patients to an SCMU may reduce mortality and poor outcome. A larger trial is required to confirm these findings. We evaluated the effect of performance feedback on acute ischemic stroke care quality in Minnesota hospitals.
                A cluster-randomized controlled trial design with hospital as the unit of randomization was used. Care quality was defined as adherence to 10 performance measures grouped into acute, in-hospital, and discharge care. Following preintervention data collection, all hospitals received a report on baseline care quality. Additionally, in experimental hospitals, clinical opinion leaders delivered customized feedback to care providers and study personnel worked with hospital administrators to implement changes targeting identified barriers to stroke care. Multilevel models examined experimental vs control, preintervention and postintervention performance changes and secular trends in performance.
                Nineteen hospitals were randomized with a total of 1,211 acute ischemic stroke cases preintervention and 1,094 cases postintervention. Secular trends were significant with improvement in both experimental and control hospitals for acute (odds ratio = 2.7, p = 0.007) and in-hospital (odds ratio = 1.5, p < 0.0001) care but not discharge care. There was no significant intervention effect for acute, in-hospital, or discharge care.
                There was no definite intervention effect: both experimental and control hospitals showed significant secular trends with performance improvement. Our results illustrate the potential fallacy of using historical controls for evaluating quality improvement interventions.
                This study provides Class II evidence that informing hospital leaders of compliance with ischemic stroke quality indicators followed by a structured quality improvement intervention did not significantly improve compliance more than informing hospital leaders of compliance with stroke quality indicators without a quality improvement intervention. Because granulocyte colony-stimulating factor (G-CSF) has anti-inflammatory and neuroprotective properties and is known to mobilize stem cells, it may be useful in the treatment of acute ischemic stroke. We sought to examine the feasibility, safety and efficacy of using G-CSF to treat acute stroke.
                We conducted a randomized, blinded controlled trial involving 10 patients with acute cerebral infarction (middle cerebral artery territory as documented by the admission MRI) who presented within 7 days of onset and whose scores on the National Institutes of Health Stroke Scale (NIHSS) were between 9 and 20. Patients were assigned to either G-CSF therapy or usual care. The G-CSF group (n = 7) received subcutaneous G-CSF injections (15 microg/kg per day) for 5 days. The primary outcome was percentage changes between baseline and 12-month follow-up in mean group scores on 4 clinical scales: the NIHSS, European Stroke Scale (ESS), ESS Motor Subscale (EMS) and Barthel Index (BI). We also assessed neurologic functioning using PET to measure cerebral uptake of fluorodeoxyglucose in the cortical areas surrounding the ischemic core.
                All of the patients completed the 5-day course of treatment, and none were lost to follow-up. No severe adverse effects were seen in patients receiving G-CSF. There was greater improvement in neurologic functioning between baseline and 12-month follow-up in the G-CSF group than in the control group (NIHSS: 59% change in the mean G-CSF group score v. 36% in the mean control group score, ESS: 33% v. 20%, EMS: 106% v. 58%, BI: 120% v. 60%). Although at 12 months there was no difference between the 2 groups in cerebral uptake of fluorodeoxyglucose in the ischemic core, uptake in the area surrounding the core was significantly improved in the G-CSF group compared with the control group. There was positive correlation between metabolic activity and EMS score following simple linear correlation analysis.
                Our preliminary evidence suggests that using G-CSF as therapy for acute stroke is safe and feasible and leads to improved neurologic outcomes. Erythropoietin (EPO) and its receptor play a major role in embryonic brain, are weakly expressed in normal postnatal/adult brain and up-regulated upon metabolic stress. EPO protects neurons from hypoxic/ ischemic injury. The objective of this trial is to study the safety and efficacy of recombinant human EPO (rhEPO) for treatment of ischemic stroke in man.
                The trial consisted of a safety part and an efficacy part. In the safety study, 13 patients received rhEPO intravenously (3.3 X 10(4) IU/50 ml/30 min) once daily for the first 3 days after stroke. In the double-blind randomized proof-of-concept trial, 40 patients received either rhEPO or saline. Inclusion criteria were age <80 years, ischemic stroke within the middle cerebral artery territory confirmed by diffusion-weighted MRI, symptom onset <8 hr before drug administration, and deficits on stroke scales. The study endpoints were functional outcome at day 30 (Barthel Index, modified Rankin scale), NIH and Scandinavian stroke scales, evolution of infarct size (sequential MRI evaluation using diffusion-weighted [DWI] and fluid-attenuated inversion recovery sequences [FLAIR]) and the damage marker S100ss.
                No safety concerns were identified. Cerebrospinal fluid EPO increased to 60-100 times that of nontreated patients, proving that intravenously administered rhEPO reaches the brain. In the efficacy trial, patients received rhEPO within 5 hr of onset of symptoms (median, range 2:40-7:55). Admission neurologic scores and serum S100beta concentrations were strong predictors ofoutcome. Analysis of covariance controlled for these two variables indicated that rhEPO treatment was associated with an improvement in follow-up and outcome scales. A strong trend for reduction in infarct size in rhEPO patients as compared to controls was observed by MRI.
                Intravenous high-dose rhEPO is well tolerated in acute ischemic stroke and associated with an improvement in clinical outcome at 1 month. A larger scale clinical trial is warranted. Patients with acute ischemic strokes were studied in a medium-sized community hospital in Mississippi. Studies were done before and after implementation of the stroke clinical care pathway with emphasis on the following clinical indicators: 1) performance of a brain CT scan, 2) the search for the etiology of the stroke, 3) whether the patient was treated emergently for hypertension, 4) the use of measures to prevent deep-vein thrombosis, and 5) prophylactic drug treatment against recurrent stroke after hospital discharge. Following application of the clinical pathway, there was a significant improvement in all the clinical indicators that were felt to require further attention and none had a setback. The length of hospital stay was decreased, and there was no significant increase in the hospital costs in the post-pathway study despite an increase in the number of diagnostic and therapeutic procedures performed. When applied properly, clinical pathways can effectively mobilize hospital resources, maximize quality of care, and at the same time minimize costs.
We did not find good evidence to show that HBOT improves clinical outcomes when applied during the acute presentation of ischaemic stroke. While evidence from the six RCTs is insufficient to provide clear guidelines for practice, the possibility of clinical benefit has not been excluded. Further research is required to better define the role of HBOT in this condition.