Granulocyte Colony Stimulating Factor and Physiotherapy after Stroke: Results of a Feasibility Randomised Controlled Trial: Stem Cell Trial of Recovery EnhanceMent after Stroke-3 (STEMS-3 ISRCTN16714730)

Background: Granulocyte-colony stimulating factor (G-CSF) mobilises endogenous haematopoietic stem cells and enhances recovery in experimental stroke. Recovery may also be dependent on an enriched environment and physical activity. G-CSF may have the potential to enhance recovery when used in combination with physiotherapy, in patients with disability late after stroke. Methods: A pilot 2 x 2 factorial randomised (1:1) placebo-controlled trial of G-CSF (double-blind), and/or a 6 week course of physiotherapy, in 60 participants with disability (mRS >1), at least 3 months after stroke. Primary outcome was feasibility, acceptability and tolerability. Secondary outcomes included death, dependency, motor function and quality of life measured 90 and 365 days after enrolment. Results: Recruitment to the trial was feasible and acceptable; of 118 screened patients, 92 were eligible and 32 declined to participate. 60 patients were recruited between November 2011 and July 2013. All participants received some allocated treatment. Although 29 out of 30 participants received all 5 G-CSF/placebo injections, only 7 of 30 participants received all 18 therapy sessions. G-CSF was well tolerated but associated with a tendency to more adverse events than placebo (16 vs 10 patients, p=0.12) and serious adverse events (SAE) (9 vs 3, p=0.10). On average, patients received 14 (out of 18 planned) therapy sessions, interquartile range [12, 17]. Only a minority (23%) of participants completed all physiotherapy sessions, a large proportion of sessions (114 of 540, 21%) were cancelled due to patient (94, 17%) and therapist factors (20, 4%). No significant differences in functional outcomes were detected in either the G-CSF or physiotherapy group at day 90 or 365. Conclusions – Delivery of G-CSF is feasible in chronic stroke. However, the study failed to demonstrate feasibility for delivering additional physiotherapy sessions late after stroke. Future work should occur earlier after stroke, alongside on-going clinical rehabilitation

Findings from an opt-in eye examination service in English special schools. Is vision screening effective for this population?

Our objective was to present the findings of an opt-in, school-based eye care service for children attending 11 special schools in England and use these findings to determine whether a vision screening programme would be appropriate for this population. Data from eye examinations provided to 949 pupils (mean age 10.7 years) was analysed to determine the prevalence and aetiology of visual deficiencies and reported eye care history. For 46.2% (n = 438) of pupils, a visual deficiency was recorded. 12.5% of all the children seen (n = 119) had a visual deficiency that was previously undiagnosed. Referral for a medical opinion was made for 3.1% (n = 29) of pupils seen by the service. Spectacle correction was needed for 31.5% (n = 299) of pupils; for 12.9% (122) these were prescribed for the first time. 3.7% (n = 11) of parents/carers of pupils needing spectacles chose not to use the spectacle dispensing service offered in school. Eye care history was available for 847 pupils (89.3%). Of the pupils for whom an eye care history was available, 44% (n = 373) reported no history of any previous eye care and10.7% (n = 91) reported a history of attending a community optical practice/opticians. Only one pupil from the school entry 4–5 age group (0.6% of age group n = 156) would have passed vision screening using current Public Health England screening guidelines. Children with a diagnosis of autism were significantly less likely to be able to provide a reliable measurement of visual acuity. This study supports previously published evidence of a very high prevalence of visual problems in children with the most complex needs and a significant unmet need in this group. It demonstrates routine school entry vision screening using current Public Health England guidelines is not appropriate for this group of children and very low uptake of community primary eye care services

Continuing or temporarily stopping prestroke antihypertensive medication in acute stroke: an individual patient data meta-analysis

Over 50% of patients are already taking blood pressure–lowering therapy on hospital admission for acute stroke. An individual patient data meta-analysis from randomized controlled trials was undertaken to determine the effect of continuation versus temporarily stopping preexisting antihypertensive medication in acute stroke. Key databases were searched for trials against the following inclusion criteria: randomized design; stroke onset ≤48 hours; investigating the effect of continuation versus stopping prestroke antihypertensive medication; and follow-up of ≥2 weeks. Two randomized controlled trials were identified and included in this meta-analysis of individual patient data from 2860 patients with ≤48 hours of acute stroke. Risk of bias in each study was low. In adjusted logistic regression and multiple regression analyses (using random effects), we found no significant association between continuation of prestroke antihypertensive therapy (versus stopping) and risk of death or dependency at final follow-up: odds ratio 0.96 (95% confidence interval, 0.80–1.14). No significant associations were found between continuation (versus stopping) of therapy and secondary outcomes at final follow-up. Analyses for death and dependency in prespecified subgroups revealed no significant associations with continuation versus temporarily stopping therapy, with the exception of patients randomized ≤12 hours, in whom a difference favoring stopping treatment met statistical significance. We found no significant benefit with continuation of antihypertensive treatment in the acute stroke period. Therefore, there is no urgency to administer preexisting antihypertensive therapy in the first few hours or days after stroke, unless indicated for other comorbid conditions

Data sharing: experience of accessing individual patient data from completed randomised controlled trials in vascular and cognitive medicine

ObjectivesMeta-analysis based on individual patient data (IPD) from randomised trials is superior to using published summary data since it facilitates subgroup and multiple variable analyses. Guidelines and funders expect that researchers share IPD for bona fide analyses, but in practice, this is done variably. Here we report the experience of obtaining IPD for two collaborative analysis studies.SettingTwo linked studies required IPD from published randomised trials. The leading researchers for eligible trials were approached and asked to share IPD including trial characteristics, patient demographics, baseline clinical data and outcome measures. ParticipantsParticipants in eligible randomised controlled trials included patients with or at risk of cognitive decline/vascular events.Primary and secondary outcome measuresNumbers (%) of trials where the leading researcher responded favourably/negatively or did not respond. If negative, reasons behind the response were collected. If positive, methods used to share IPD were recorded.ResultsAcross the two studies, 391 completed trials were identified. Email addresses for researchers were found for 313 (80%) of the trials. 148 (47%) researchers did not respond despite being sent multiple emails. Following contact, positive initial responses were received from 92 researchers, resulting in IPD being shared for 78 trials. 87 (28%) researchers declined to share data; justifications were recorded. The median time from first request to accessing data in one study was 241 [IQR 383.3] days. IPD sources included: direct from researcher, via academic trial funders repository and a website requiring remote analysis of commercial data. Where data were shared, a variety of methods were used to transfer data.ConclusionSharing of IPD from trials is desirable and a requirement of many funding bodies. However, accessing IPD faces multiple challenges including refusals to share, delays in access to data, and having to perform analyses on a remote website