Amanda G. Thrift

Inactive and Alone Physical Activity Within the First 14 Days of Acute Stroke Unit Care

Background and Purpose— One way that stroke units may improve outcome is by reducing complications of immobility through early mobilization; however, this intervention needs testing. The purpose of this study was to determine the physical activity patterns of stroke patients managed within acute stroke units as a first step in developing an early mobilization protocol. Methods— We recruited 64 patients within 14 days after stroke from 5 metropolitan stroke units and observed them for 2 consecutive days at 10-minute intervals between the hours of 8 am and 5 pm. At each observation, we ascertained physical activity, location, and other person(s) present. Therapists recorded therapy details. Results— The 58 patients who completed the study had a mean age of 71.3 years. Stroke severity ranged from mild (National Institutes of Health Stroke Scale score, 1) to severe (score, 27), and mean time after stroke at observation was 5.6 days (range, 0 to 13 days). Only 9 patients were restricted to bed. During the therapeutic day, patients spent >50% resting in bed, 28% sitting out of bed, and only 13% engaged in activities with the potential to prevent complications and improve recovery of mobility. Patients were alone >60% of the time. Conclusions— This is the first multicenter study of physical activity early after stroke. We believe the next step is to conduct a randomized controlled trial to evaluate the effect of increased levels of physical activity early after stroke compared with current standards of care.

Quality of Life After Stroke The North East Melbourne Stroke Incidence Study (NEMESIS)

Background and Purpose— Health-related quality of life (HRQoL) data are scarce from unselected populations. The aims were to assess HRQoL at 2 years poststroke, to identify determinants of HRQoL in stroke survivors, and to identify predictors at stroke onset of subsequent HRQoL. Methods— All first-ever cases of stroke in a population of 306 631 over a 1-year period were assessed. Stroke severity, comorbidity, and demographic information were recorded. Two-year poststroke HRQoL was assessed using the Assessment of Quality of Life (AQoL) instrument (deceased patients score=0). Handicap, disability, physical impairment, depression, anxiety, living arrangements, and recurrent stroke at 2 years were documented. If necessary, proxy assessments were obtained, except for mood. Linear regression analyses were performed to identify factors independently associated with HRQoL. Results— Of 266 incident cases alive at 2 years, 225 (85%) were assessed. The mean AQoL utility score for all survivors was 0.47 (95% CI, 0.42 to 0.52). Almost 25% of survivors had a score of ≤0.1. The independent determinants of HRQoL in survivors were handicap, physical impairment, anxiety and depression, disability, institutionalization, dementia, and age. The factors present at stroke onset that independently predicted HRQoL at 2 years poststroke were age, female sex, initial NIHSS score, neglect, and low socioeconomic status. Conclusions— A substantial proportion of stroke survivors have very poor HRQoL. Interventions targeting handicap and mood have the potential to improve HRQoL independently of physical impairment and disability.

Incidence of the Major Stroke Subtypes Initial Findings From the North East Melbourne Stroke Incidence Study (NEMESIS)

Background and Purpose— Population-based stroke incidence studies are the only accurate way to determine the number of strokes that occur in a given society. Because the major stroke subtypes have different patterns of incidence and outcome, information on the natural history of stroke subtypes is essential. The purpose of the present study was to determine the incidence and case-fatality rate of the major stroke subtypes in a geographically defined region of Melbourne, Australia. Methods— All suspected strokes that occurred among 133 816 residents of suburbs north and east of Melbourne, Australia, during a 12-month period of 1996 and 1997 were identified and assessed. Multiple overlapping sources were used to ascertain cases, and standard criteria for stroke and case-fatality were used. Stroke subtypes were defined by CT, MRI, and autopsy. Results— Three hundred eighty-one strokes occurred among 353 persons during the study period, with 276 (72%) being first-ever-in-a-lifetime strokes. Of these, 72.5% (95% CI 67.2% to 77.7%) were cerebral infarction, 14.5% (95% CI 10.3% to 18.6%) were intracerebral hemorrhage, 4.3% (95% CI 1.9% to 6.8%) were subarachnoid hemorrhage, and 8.7% (95% CI 5.4% to 12.0%) were stroke of undetermined type. The 28-day case-fatality rate was 12% (95% CI 7% to 16%) for cerebral infarction, 45% (95% CI 30% to 60%) for intracerebral hemorrhage, 50% (95% CI 22% to 78%) for subarachnoid hemorrhage, and 38% (95% CI 18% to 57%) for stroke of undetermined type. Conclusions— The overall distribution of stroke subtypes and 28-day case-fatality rates are not significantly different from those of most European countries or the United States. There may, however, be some differences in the incidence of subtypes within Australia.

A very early rehabilitation trial for stroke (AVERT) phase II safety and feasibility

Background and Purpose— Very early rehabilitation, with an emphasis on mobilization, may contribute to improved outcomes after stroke. We hypothesized that a very early rehabilitation protocol would be safe and feasible. Methods— We performed a randomized, controlled trial with blinded outcome assessment. Patients at <24 hours after stroke were recruited from 2 Melbourne metropolitan stroke units. Patients were randomly assigned to receive standard care (SC) or SC plus very early mobilization (VEM) until discharge or 14 days (whichever was sooner). The primary safety outcome was the number of deaths at 3 months. The primary feasibility outcome was a higher “dose” of mobilization achieved in VEM. Secondary safety outcomes included adverse events (including falls and early neurologic deterioration), compliance with physiologic monitoring criteria, and patient fatigue after interventions. Secondary feasibility outcomes included “contamination” of standard care. Results— Overall, 18% of patients screened were suitable for recruitment. Seventy-one patients were recruited and randomized, with 2 dropouts by 12 months. The majority experienced ischemic strokes (87%). The group mean±SD age was 74.7±12.5 years, and 58% (n=41) had a National Institutes of Health Stroke Scale score >7. There was no significant difference in the number of deaths between groups (SC, 3 of 33; VEM, 8 of 38; P=0.20). Almost all deaths occurred in patients with severe stroke. Secondary safety outcomes were similar between groups. The intervention protocol was successfully delivered, achieving VEM dose targets (double SC, P=0.003) and faster time to first mobilization (P<0.001). Conclusions— VEM of patients within 24 hours of acute stroke appears safe and feasible. Intervention efficacy and cost-effectiveness are currently being tested in a large randomized, controlled trial.

Efficacy and safety of very early mobilisation within 24 h of stroke onset (AVERT): a randomised controlled trial.

BACKGROUND 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. METHODS 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. FINDINGS 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. INTERPRETATION 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. FUNDING 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.

Stroke Incidence on the East Coast of Australia: The North East Melbourne Stroke Incidence Study (NEMESIS)

Background and Purpose Community-based stroke incidence studies are the most accurate way of explaining mortality trends and developing public health policy. The purpose of this study was to determine the incidence of stroke in a geographically defined region of Melbourne, Australia. Methods All suspected strokes occurring in a population of 133 816 residents in suburbs north and east of Melbourne, Australia, during a 12-month period of 1996 and 1997 were found and assessed. Multiple overlapping sources were used to ascertain cases, and standard definitions and criteria for stroke and case fatality were used. Results A total of 381 strokes occurred among 353 people during the study period, 276 (72%) of which were first-ever-in-a-lifetime strokes. The crude annual incidence rate (first-ever strokes) was 206 (95% CI, 182 to 231) per 100 000 per year overall, 195 (95% CI, 161 to 229) for males, and 217 (95% CI, 182 to 252) for females. The corresponding rates adjusted to the “world” population were 100 (95% CI, 80 to 119) overall, 113 (95% CI, 92 to 134) for males, and 89 (95% CI, 70 to 107) for females. The 28-day case fatality rate for first-ever strokes was 20% (95% CI, 16% to 25%). Conclusions The incidence rate of stroke in our population-based study is similar to that of many European studies but is significantly higher than that observed on the west coast of Australia.

Very Early Mobilization After Stroke Fast-Tracks Return to Walking Further Results From the Phase II AVERT Randomized Controlled Trial

Background and Purpose— Regaining functional independence is an important goal for people who have experienced stroke. We hypothesized that introducing earlier and more intensive out-of-bed activity after stroke would reduce time to unassisted walking and improve independence in activities of daily living. Methods— A Very Early Rehabilitation Trial (AVERT) was a phase II randomized controlled trial. Patients with confirmed stroke (infarct or hemorrhage) admitted <24 hours after stroke and who met physiological safety criteria were eligible. Patients randomized to the very early and intensive mobilization group were mobilized within 24 hours of stroke and at regular intervals thereafter. Control patients received standard stroke unit care. The primary outcome for this analysis was the number of days required to return to walking 50 m unassisted. Secondary outcomes were the Barthel Index and Rivermead Motor Assessment at 3 and 12 months after stroke. Results— Seventy-one stroke patients with a mean age of 74.7 years were recruited from 2 hospitals. Adjusted Cox regression indicated that very early and intensive mobilization group patients returned to walking significantly faster than did standard stroke unit care controls (P=0.032; median 3.5 vs 7.0 days). Multivariable regression revealed that exposure to very early and intensive mobilization was independently associated with good functional outcome on the Barthel Index at 3 months (P=0.008) and on the Rivermead Motor Assessment at 3 (P=0.050) and 12 (P=0.024) months. Conclusions— Earlier and more intensive mobilization after stroke may fast-track return to unassisted walking and improve functional recovery. Clinical Trial Registration— This trial was not registered because enrollment began before July 2005.

Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990-2015

Importance Elevated systolic blood (SBP) pressure is a leading global health risk. Quantifying the levels of SBP is important to guide prevention policies and interventions. Objective To estimate the association between SBP of at least 110 to 115 mm Hg and SBP of 140 mm Hg or higher and the burden of different causes of death and disability by age and sex for 195 countries and territories, 1990-2015. Design A comparative risk assessment of health loss related to SBP. Estimated distribution of SBP was based on 844 studies from 154 countries (published 1980-2015) of 8.69 million participants. Spatiotemporal Gaussian process regression was used to generate estimates of mean SBP and adjusted variance for each age, sex, country, and year. Diseases with sufficient evidence for a causal relationship with high SBP (eg, ischemic heart disease, ischemic stroke, and hemorrhagic stroke) were included in the primary analysis. Main Outcomes and Measures Mean SBP level, cause-specific deaths, and health burden related to SBP (≥110-115 mm Hg and also ≥140 mm Hg) by age, sex, country, and year. Results Between 1990-2015, the rate of SBP of at least 110 to 115 mm Hg increased from 73 119 (95% uncertainty interval [UI], 67 949-78 241) to 81 373 (95% UI, 76 814-85 770) per 100 000, and SBP of 140 mm Hg or higher increased from 17 307 (95% UI, 17 117-17 492) to 20 526 (95% UI, 20 283-20 746) per 100 000. The estimated annual death rate per 100 000 associated with SBP of at least 110 to 115 mm Hg increased from 135.6 (95% UI, 122.4-148.1) to 145.2 (95% UI 130.3-159.9) and the rate for SBP of 140 mm Hg or higher increased from 97.9 (95% UI, 87.5-108.1) to 106.3 (95% UI, 94.6-118.1). Loss of disability-adjusted life-years (DALYs) associated with SBP of at least 110 to 115 mm Hg increased from 148 million (95% UI, 134-162 million) to 211 million (95% UI, 193-231 million), and for SBP of 140 mm Hg or higher, the loss increased from 5.2 million (95% UI, 4.6-5.7 million) to 7.8 million (95% UI, 7.0-8.7 million). The largest numbers of SBP-related deaths were caused by ischemic heart disease (4.9 million [95% UI, 4.0-5.7 million]; 54.5%), hemorrhagic stroke (2.0 million [95% UI, 1.6-2.3 million]; 58.3%), and ischemic stroke (1.5 million [95% UI, 1.2-1.8 million]; 50.0%). In 2015, China, India, Russia, Indonesia, and the United States accounted for more than half of the global DALYs related to SBP of at least 110 to 115 mm Hg. Conclusions and Relevance In international surveys, although there is uncertainty in some estimates, the rate of elevated SBP (≥110-115 and ≥140 mm Hg) increased substantially between 1990 and 2015, and DALYs and deaths associated with elevated SBP also increased. Projections based on this sample suggest that in 2015, an estimated 3.5 billion adults had SBP of at least 110 to 115 mm Hg and 874 million adults had SBP of 140 mm Hg or higher.

Informal Care for Stroke Survivors: Results From the North East Melbourne Stroke Incidence Study (NEMESIS)

Background and Purpose— Informal caregivers play an important role in the lives of stroke patients, but the cost of providing this care has not been estimated. The purpose of this study was to determine the nature and amount of informal care provided to stroke patients and to estimate the economic cost of that care. Methods— The primary caregivers of stroke patients registered in the North East Melbourne Stroke Incidence Study (NEMESIS) were interviewed at 3, 6, and 12 months after stroke, and the nature and amount of informal care provided were documented. The opportunity and replacement costs of informal care for all first-ever-in-a-lifetime strokes (excluding subarachnoid hemorrhages) that occurred in 1997 in Australia were estimated. Results— Among 3-month stroke survivors, 74% required assistance with activities of daily living and received informal care from family or friends. Two thirds of primary caregivers were women, and most primary caregivers (>90%) provided care during family or leisure time. Total first-year caregiver time costs for all first-ever-in-a-lifetime strokes were estimated to be A

Three Important Subgroups of Hypertensive Persons at Greater Risk of Intracerebral Hemorrhage

21.7 million (opportunity cost approach) or A