Very early versus delayed mobilisation after stroke.

BACKGROUND: Very early mobilisation (VEM) is performed in some stroke units and recommended in some acute stroke clinical guidelines. However, it is unclear whether very early mobilisation independently improves outcome after stroke. OBJECTIVES: To determine whether very early mobilisation (started as soon as possible, and no later than 48 hours after onset of symptoms) in people with acute stroke improves recovery (primarily the proportion of independent survivors) compared with usual care. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched 31 July 2017). We also systematically searched 19 electronic databases including; CENTRAL; 2017, Issue 7 in the Cochrane Library (searched July 2017), MEDLINE Ovid (1950 to August 2017), Embase Ovid (1980 to August 2017), CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to August 2017) , PsycINFO Ovid (1806 to August 2017), AMED Ovid (Allied and Complementary Medicine Database), SPORTDiscus EBSCO (1830 to August 2017). We searched relevant ongoing trials and research registers (searched December 2016), the Chinese medical database, Wanfangdata (searched to November 2016), and reference lists, and contacted researchers in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) of people with acute stroke, comparing an intervention group that started out-of-bed mobilisation within 48 hours of stroke, and aimed to reduce time-to-first mobilisation, with or without an increase in the amount or frequency (or both) of mobilisation activities, with usual care, where time-to-first mobilisation was commenced later. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, extracted data, assessed risk of bias, and applied the GRADE approach to assess the quality of the evidence. The primary outcome was death or poor outcome (dependency or institutionalisation) at the end of scheduled follow-up. Secondary outcomes included death, dependency, institutionalisation, activities of daily living (ADL), extended ADL, quality of life, walking ability, complications (e.g. deep vein thrombosis), patient mood, and length of hospital stay. We also analysed outcomes at three-month follow-up. MAIN RESULTS: We included nine RCTs with 2958 participants; one trial provided most of the information (2104 participants). The median (range) delay to starting mobilisation after stroke onset was 18.5 (13.1 to 43) hours in the VEM group and 33.3 (22.5 to 71.5) hours in the usual care group. The median difference within trials was 12.7 (4 to 45.6) hours. Other differences in intervention varied between trials; in five trials, the VEM group were also reported to have received more time in therapy, or more mobilisation activity.Primary outcome data were available for 2542 of 2618 (97.1%) participants randomized and followed up for a median of three months. VEM probably led to similar or slightly more deaths and participants who had a poor outcome, compared with delayed mobilisation (51% versus 49%; odds ratio (OR) 1.08, 95% confidence interval (CI) 0.92 to 1.26; P = 0.36; 8 trials; moderate-quality evidence). Death occurred in 7% of participants who received delayed mobilisation, and 8.5% of participants who received VEM (OR 1.27, 95% CI 0.95 to 1.70; P = 0.11; 8 trials, 2570 participants; moderate-quality evidence), and the effects on experiencing any complication were unclear (OR 0.88; 95% CI 0.73 to 1.06; P = 0.18; 7 trials, 2778 participants; low-quality evidence). Analysis using outcomes collected only at three-month follow-up did not alter the conclusions.The mean ADL score (measured at end of follow-up, with the 20-point Barthel Index) was higher in those who received VEM compared with the usual care group (mean difference (MD) 1.94, 95% CI 0.75 to 3.13, P = 0.001; 8 trials, 9 comparisons, 2630/2904 participants (90.6%); low-quality evidence), but there was substantial heterogeneity (93%). Effect sizes were smaller for outcomes collected at three-month follow-up, rather than later.The mean length of stay was shorter in those who received VEM compared with the usual care group (MD -1.44, 95% CI -2.28 to -0.60, P = 0.0008; 8 trials, 2532/2618 participants (96.7%); low-quality evidence). Confidence in the answer was limited by the variable definitions of length of stay. The other secondary outcome analyses (institutionalisation, extended activities of daily living, quality of life, walking ability, patient mood) were limited by lack of data.Sensitivity analyses by trial quality: none of the outcome conclusions were altered if we restricted analyses to trials with the lowest risk of bias (based on method of randomization, allocation concealment, completeness of follow-up, and blinding of final assessment), or information about the amount of mobilisation.Sensitivity analysis by intervention characteristics: analyses restricted to trials where the mean VEM time-to-first mobilisation was less than 24 hours, showed an odds of death of 1.35 (95% CI 0.99 to 1.83; P = 0.06; I² = 25%; 5 trials). Analyses restricted to the trials that clearly reported a more prolonged out-of-bed activity showed a similar primary outcome (OR 1.14; 0.96 to 1.35; P = 0.13; I² = 28%; 5 trials), and odds of death (OR 1.27; 0.93 to 1.73; P = 0.13; I² = 0%; 4 trials) to the main analysis.Exploratory network meta-analysis (NMA): we were unable to analyze by the amount of therapy, but low-quality evidence indicated that time-to-first mobilisation at around 24 hours was associated with the lowest odds of death or poor outcome, compared with earlier or later mobilisation. AUTHORS' CONCLUSIONS: VEM, which usually involved first mobilisation within 24 hours of stroke onset, did not increase the number of people who survived or made a good recovery after their stroke. VEM may have reduced the length of stay in hospital by about one day, but this was based on low-quality evidence. Based on the potential hazards reported in the single largest RCT, the sensitivity analysis of trials commencing mobilisation within 24 hours, and the NMA, there was concern that VEM commencing within 24 hours may carry an increased risk, at least in some people with stroke. Given the uncertainty around these effect estimates, more detailed research is still required.

Very early versus delayed mobilisation after stroke.

BACKGROUND: Very early mobilisation is performed in some stroke units and recommended in acute stroke clinical guidelines. It is unclear whether very early mobilisation independently improves outcome after stroke. OBJECTIVES: To determine the benefits and harms of very early mobilisation (commenced within 48 hours of stroke) compared with conventional care. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched April 2008). In addition, we searched 25 databases including the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2007), MEDLINE (1950 to August 2007), EMBASE (1980 to September 2007), CINAHL (1982 to December 2006), and AMED (1985 to January 2007). We also searched relevant ongoing trials and research registers (searched January 2007) and the Chinese medical database Wanfangdata (searched March 2007), handsearched journals, searched reference lists and contacted researchers in the field. SELECTION CRITERIA: Unconfounded RCTs of acute stroke patients, comparing an intervention group that started out of bed mobilisation within 48 hours of stroke and aimed to reduce time to first mobilisation and/or increase the amount or frequency (or both) of mobilisation, with conventional care. DATA COLLECTION AND ANALYSIS: One review author eliminated obviously irrelevant records; two review authors independently applied selection criteria to remaining studies. The primary outcome was death or poor outcome (dependency or institutionalisation) at the end of scheduled follow up. Secondary outcomes included mortality, dependency, institutionalisation, activities of daily living (ADLs), quality of life, time to walking, adverse events (e.g. deep vein thrombosis) and patient mood. MAIN RESULTS: One study, involving 71 participants, was included. In this study the experimental group had earlier and more frequent mobilisation than the control group (median 18.1 hours post stroke for experimental group versus 30.8 hours control; 167 minutes of mobilisation (interquartile range (IQR) 62 to 305) during admission for experimental group versus 69 (IQR 31 to 115) minutes control). Fewer patients who received early and frequent mobilisation were dead or disabled at three months, but this was not statistically significant and the confidence intervals were wide (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.25 to 1.79, P = 0.42). No significant difference on any secondary outcomes of interest were found. AUTHORS' CONCLUSIONS: We found insufficient evidence to support or refute the efficacy of routine very early mobilisation after stroke, compared with conventional care. More research is required to determine the benefits and harms of very early mobilisation after stroke.

Spinal cord detethering procedures in children: a 5 year retrospective cohort study of the early post-operative course.

Tethered spinal cord can cause neurological, orthopaedic and sphincteric problems in children and detethering surgery may prevent or reverse these problems. This 5 year retrospective cohort study aimed to review our experience of detethering surgery at The Children's Hospital at Westmead, Sydney, Australia, particularly examining the early post-operative complications of this procedure. Between 2007 and 2012, 61 children underwent 63 detethering procedures. The median age at detethering surgery was 1.4 years old (interquartile range: 0.7-5.6 years). Fifty-five children (90.1%) had lumbosacral procedures, 31 (50.8%) were asymptomatic from tethering, 11 (18.0%) had motor or gait disturbance, 11 (18.0%) sphincteric disturbance, eight (13.1%) lower limb orthopaedic deformities, eight (13.1%) scoliosis, six (9.8%) back or leg pain and two (3.3%) sensory disturbance. The most common tethering pathologies were spinal lipomas in 32 children (52.5%), filum abnormalities in 23 (37.7%), dorsal sinus tracts in eight (13.1%) and diastematomyelia in seven (11.5%). Twenty-six children (42.6%) had either a syrinx or central canal dilatation preoperatively. The most common complications were wound infection and cerebrospinal fluid leak. Six children (9.8%) required reoperation for wound issues and two patients (3.3%) required subsequent reoperation for cord retethering during the study period. There were no deaths and no new neurological deficits. Of the children with the above preoperative deficits, 26.7% were documented to have improvement or resolution of their symptoms post-operatively. The highest rate of improvement occurred in children with motor or gait disturbance (36.4%) or sphincteric disturbance (27.3%).

A novel literature-based approach to identify genetic and molecular predictors of survival in glioblastoma multiforme: Analysis of 14,678 patients using systematic review and meta-analytical tools.

Glioblastoma multiforme (GBM) has a poor prognosis despite maximal multimodal therapy. Biomarkers of relevance to prognosis which may also identify treatment targets are needed. A few hundred genetic and molecular predictors have been implicated in the literature, however with the exception of IDH1 and O6-MGMT, there is uncertainty regarding their true prognostic relevance. This study analyses reported genetic and molecular predictors of prognosis in GBM. For each, its relationship with univariate overall survival in adults with GBM is described. A systematic search of MEDLINE (1998-July 2010) was performed. Eligible papers studied the effect of any genetic or molecular marker on univariate overall survival in adult patients with histologically diagnosed GBM. Primary outcomes were median survival difference in months and univariate hazard ratios. Analyses included converting 126 Kaplan-Meier curves and 27 raw data sets into primary outcomes. Seventy-four random effects meta-analyses were performed on 39 unique genetic or molecular factors. Objective criteria were designed to classify factors into the categories of clearly prognostic, weakly prognostic, non-prognostic and promising. Included were 304 publications and 174 studies involving 14,678 unique patients from 33 countries. We identified 422 reported genetic and molecular predictors, of which 52 had ⩾2 studies. IDH1 mutation and O6-MGMT were classified as clearly prognostic, validating the methodology. High Ki-67/MIB-1 and loss of heterozygosity of chromosome 10/10q were classified as weakly prognostic. Four factors were classified as non-prognostic and 13 factors were classified as promising and worthy of additional investigation. Funnel plot analysis did not identify any evidence of publication bias. This study demonstrates a novel literature and meta-analytical based approach to maximise the value that can be derived from the plethora of literature reports of molecular and genetic factors in GBM. Caution is advised in over-interpreting the results due to study limitations. Further research to develop this methodology and improvements in study reporting are suggested.

Stroke rehabilitation in China: a systematic review and meta-analysis.

BACKGROUND: Stroke rehabilitation is regarded as an essential component of organized care, therefore withholding treatment is considered unethical in Western trials. Poststroke rehabilitation is not standard in China, and trials with no treatment controls have been possible. We believed aggregation of these data represented a unique opportunity to examine the 'effect size' of this intervention. AIM: The aim of this study was to systematically review randomized controlled trials that compare rehabilitation to standard care after stroke in China. METHODS: We searched 24 databases including Wanfangdata (China), MEDLINE, EMBASE, CENTRAL, Cochrane Stroke Group Register, and Cochrane Central Register of Controlled trials. The primary outcome of interest was activities of daily living (Barthel Index), and the secondary outcome was disability (Fugl-Meyer Score). Random-effect meta-analysis was performed. RESULTS: Thirty-seven randomized controlled trials consisting of 5916 patients met inclusion criteria. Mean age reported in each study range from 47.2 to 72.5 years, 52.6% were male and 23.8% had a haemorrhagic stroke. Rehabilitation interventions varied between studies, but all included additional exercise therapy. Control patients had no formal rehabilitation. Patients who received rehabilitation showed marked improvements in Barthel Index (standardized mean difference: 1.04, 95% confidence interval: 0.88-1.21, P < 0.001, I(2) = 85.9%) and Fugl-Meyer Score (standardized mean difference: 1.10, 95% confidence interval: 0.82-1.38, P < 0.001, I(2) = 94.3%) compared with controls. However, reporting quality was low, and time to start of rehabilitation was often unclear. CONCLUSION: These data provide some evidence that rehabilitation poststroke is more effective than no rehabilitation, improving activities of daily living and reducing disability. Although results are limited by low reporting quality and study heterogeneity, conducting research in countries in which rehabilitation is not standard care provides an opportunity to advance our understanding and should be encouraged.

Cadaveric dissection identifying the left superior anastomotic vein of Trolard communicating indirectly with the superior sagittal sinus via a lateral lacuna.

A cadaveric dissection of the calvarium of a 90 year old woman demonstrated a left superior anastomotic vein of Trolard communicating indirectly with the superior sagittal sinus via a left lateral lacunae. This is an anatomical variant contrary to the textbook description of a direct communication between the vein of Trolard and the superior sagittal sinus. A literature search failed to identify a previous description of this variation. Possible clinical implications of this finding will be discussed.

Acute hyperglycaemia and mortality in patients with transient ischaemic attack.

Acute hyperglycaemia is associated with poorer outcome in stroke, however limited evidence is available regarding its association with transient ischaemic attack (TIA). This study aimed to determine the association between acute hyperglycaemia and mortality in 194 patients with TIA. Mortality data were obtained from a state-wide death registry. No significant association was identified with either multivariate Cox regression (p=0.65) or Kaplan-Meier analysis (p=0.85). Because of the low death rate, a larger sample is required to reliably exclude an association. Univariate analysis identified significantly associated variables, including TIA clinical prediction scores (e.g. ABCD and ABCD2). Multivariate analysis identified age, atrial fibrillation and duration 1 hour as independent significant predictors of mortality.