ORCID Profile
0000-0002-6105-1720
Current Organisations
The George Institute For Global Health China
,
UNSW Sydney
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Publisher: SAGE Publications
Date: 21-06-2019
Abstract: Controversy persists over the benefits of low-dose versus standard-dose intravenous alteplase for the treatment of acute ischemic stroke. We sought to determine in idual patient factors that contribute to the risk–benefit balance of low-dose alteplase treatment. Observational study using data from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), an international, randomized, open-label, blinded-endpoint trial that assessed low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) intravenous alteplase in acute ischemic stroke patients. Logistic regression models were used to estimate the benefit of good functional outcome (scores 0 or 1 on the modified Rankin scale at 90 days) and risk (symptomatic intracerebral hemorrhage), under both regimens for in idual patients. The net advantage for low-dose, relative to standard-dose, alteplase was calculated by iding excess benefit by excess risk according to a combination of patient characteristics. The algorithms were externally validated in a nationwide acute stroke registry database in South Korea. Patients with an estimated net advantage from low-dose alteplase, compared with without, were younger (mean age of 66 vs. 75 years), had lower systolic blood pressure (148 vs. 160 mm Hg), lower National Institute of Health Stroke Scale score (median of 8 vs. 16), and no atrial fibrillation (10.3% vs. 97.4%), diabetes mellitus (19.2% vs. 22.4%), or premorbid symptoms (defined by modified Rankin scale = 1) (16.3% vs. 37.8%). Use of low-dose alteplase may be preferable in acute ischemic stroke patients with a combination of favorable characteristics, including younger age, lower systolic blood pressure, mild neurological impairment, and no atrial fibrillation, diabetes mellitus, or premorbid symptoms.
Publisher: BMJ
Date: 28-09-2020
Abstract: The COVID-19 pandemic and physical distancing guidelines have compelled stroke practices worldwide to reshape their delivery of care significantly. We aimed to illustrate how the stroke services were interrupted during the pandemic in China. A 61-item questionnaire designed on Wenjuanxing Form was completed by doctors or nurses who were involved in treating patients with stroke from 1 February to 31 March 2020. A total of 415 respondents completed the online survey after informed consent was obtained. Of the respondents, 37.8%, 35.2% and 27.0% were from mild, moderate and severe epidemic areas, respectively. Overall, the proportion of severe impact (reduction %) on the admission of transient ischaemic stroke, acute ischaemic stroke (AIS) and intracerebral haemorrhage (ICH) was 45.0%, 32.0% and 27.5%, respectively. Those numbers were 36.9%, 27.9% and 22.3% 36.5%, 22.1% and 22.6% and 66.4%, 47.5% and 41.1% in mild, moderate and severe epidemic areas, respectively (all p .0001). For AIS, thrombolysis was moderate (20%–50% reduction) or severely impacted ( %), as reported by 54.4% of the respondents, while thrombectomy was 39.3%. These were 44.4%, 26.3% 44.2%, 39.4% and 78.2%, 56.5%, in mild, moderate and severe epidemic areas, respectively (all p .0001). For patients with acute ICH, 39.8% reported the impact was severe or moderate for those eligible for surgery who had surgery. Those numbers were 27.4%, 39.0% and 58.1% in mild, moderate and severe epidemic areas, respectively. For staff resources, about 20% (overall) to 55% (severe epidemic) of the respondents reported moderate or severe impact on the on-duty doctors and nurses. We found a significant reduction of admission for all types of patients with stroke during the pandemic. Patients were less likely to receive appropriate care, for ex le, thrombolysis/thrombectomy, after being admitted to the hospital. Stroke service in severe COVID-19 epidemic areas, for ex le, Wuhan, was much more severely impacted compared with other regions in China.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-09-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2022
Publisher: Frontiers Media SA
Date: 12-09-2022
DOI: 10.3389/FNEUR.2022.984599
Abstract: Studies indicate a trajectory relationship between baseline blood pressure (BP) and outcome in patients with acute ischemic stroke (AIS) eligible for both intravenous thrombolysis (IVT) with alteplase and endovascular treatment (EVT). We determined whether baseline BP modified the effect of IVT in successfully revascularized AIS patients who participated in the Direct Intra-Arterial Thrombectomy to Revascularize AIS Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals (DIECT-MT) trial. The association of baseline systolic BP, trichotomized as high (141–185 mmHg), middle (121–140 mmHg), and low (91–120 mmHg), and the outcomes of any intracerebral hemorrhage (ICH), symptomatic ICH (sICH), and mortality and functional outcome on the modified Rankin scale at 90 days were explored. Logistic regression models determined the interaction between clinical outcomes and baseline systolic and diastolic BP, and mean arterial pressure (MAP), at 10 mmHg intervals. Data are reported as odds ratios (OR) and 95% CI. A post-hoc analysis of DIRECT-MT, in 510 of the 656 randomized participants with successful revascularization underwent MT. The overall adjusted common OR of IVT and baseline BP on any ICH, sICH, and 90-day mortality and functional outcome were 0.884 (95%CI 0.613–1.274), 0.643 (95%CI 0.283–1.458), 0.842 (95%CI 0.566–1.252), and 1.286 (95%CI 0.772–2.142), respectively. No significant interaction between baseline blood pressure and intravenous thrombolysis with clinical outcome was observed. In patients with baseline SBP under 185 mmHg, baseline blood pressure does not alter the risk of hemorrhagic transformation and clinical outcome in successfully revascularized patients, regardless of intravenous alteplase usage. Future studies are needed to confirm our findings. URL: www.clinicaltrials.gov , Identifier: NCT03469206.
Publisher: SAGE Publications
Date: 19-02-2021
Abstract: An indwelling urinary catheter (IUC) is often inserted to manage bladder dysfunction, but its impact on prognosis is uncertain. We aimed to determine the association of IUC use on clinical outcomes after acute stroke in the international, multi-center, cluster crossover, Head Positioning in Acute Stroke Trial (HeadPoST). Data were analyzed on HeadPoST participants (n = 11,093) randomly allocated to the lying-flat or sitting-up head position. Binomial, logistic regression, hierarchical mixed models were used to determine associations of early insertion of IUC within seven days post-randomization and outcomes of death or disability (defined as “poor outcome,” scores 3–6 on the modified Rankin scale) and any urinary tract infection at 90 days with adjustment of baseline and post-randomization management covariates. Overall, 1167 (12%) patients had an IUC, but the frequency and duration of use varied widely across patients in different regions. IUC use was more frequent in older patients, and those with vascular comorbidity, greater initial neurological impairment (on the National Institutes of Health Stroke Scale), and intracerebral hemorrhage as the underlying stroke type. IUC use was independently associated with poor outcome (adjusted odds ratio (aOR): 1.40, 95% confidence interval (CI): 1.13–1.74), but not with urinary tract infection after adjustment for antibiotic treatment and stroke severity at hospital separation (aOR: 1.13, 95% CI: 0.59–2.18). The number exposed to IUC for poor outcome was 13. IUC use is associated with a poor outcome after acute stroke. Further studies are required to inform appropriate use of IUC.
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.JNS.2016.10.026
Abstract: 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.
Publisher: S. Karger AG
Date: 31-08-2023
DOI: 10.1159/000525869
Abstract: b i Introduction: /i /b The Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) showed that a low-dose alteplase was safe but not clearly non-inferior to standard-dose alteplase in acute ischemic stroke (AIS). Given the significant cost of this medicine, we undertook a cost-effectiveness analysis to determine the probability that low-dose is cost-effective relative to standard-dose alteplase in China. b i Methods: /i /b For ENCHANTED participants in China with available health cost data, cost-effectiveness and cost-utility analyses were undertaken in which death or disability (modified Rankin scale scores 2–6) at 90 days and quality-adjusted life-years (QALYs) were used as outcome measures, respectively. There was adherence to standard guidelines for health economic evaluations alongside non-inferiority trials and according to a health-care payer’s perspective. The equivalence margin for cost and effectiveness was set at USD 691 and −0.025 QALYs, respectively, for the base-case analysis. Probabilistic sensitivity analyses were used to evaluate the probability of low-dose alteplase being non-inferior. b i Results: /i /b While the mean cost of alteplase was lower in the low-dose group (USD 1,569 vs. USD 2,154 in the standard-dose group), the total cost was USD 56 (95% confidence interval [CI]: −1,000–1,113) higher compared to the standard-dose group due to higher hospitalization costs in the low-dose group. There were 462 (95% CI: 415–509) and 410 (95% CI: 363–457) patients with death or disability per 1,000 patients in the low-dose and standard-dose groups, respectively. The low-dose group had marginally lower (0.008, 95% CI: −0.016–0.001) QALYs compared to their standard-dose counterparts. The low-dose group was found to have an 88% probability of being non-inferior based on cost-effectiveness versus the standard-dose group. b i Conclusions: /i /b This health economic evaluation alongside the ENCHANTED indicates that the use of low-dose alteplase does not save overall healthcare costs nor lead to a gain in QALYs in the management of Chinese patients with AIS compared to the use of standard dose. There is little justification on economic grounds to shift from standard-of-care thrombolysis in AIS.
Publisher: Wiley
Date: 22-10-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-10-2021
Publisher: SAGE Publications
Date: 16-11-2023
DOI: 10.1177/17474930221135983
Abstract: The epidemiology of stroke is evolving in China as the population undergoes demographic, lifestyle, and economic transitions. An updated review is pertinent to providing feedback on current, and in planning future, prevention and management strategies. To identify high-quality epidemiological studies for quantifying the prevalence, incidence, mortality, and case fatality for stroke in China. A search was undertaken across a range of bibliographic databases on 30 November 2021 without time limitation. Assessments were made of the risk of bias of the included studies. The outcomes were synthesized using a random-effects model. Subgroup analysis and meta-regression models were used to define the source of heterogeneity. Of 9407 identified records, 26 population-based studies were included. Due to significant heterogeneity across the studies, the original range for crude rates of indices was wide. The pooled annual prevalence was 1329.5/100,000 (95% confidence interval (CI) 713.6–2131.9, p 0.001), incidence 442.1/100,000 (327.6–573.8, p 0.001), mortality 154.1/100,000 (52.6–308.8, I 2 = 100%, p 0.001), and case fatality 35.8% (26.1% to 46.1%, I 2 = 97%, p 0.001). The prevalence and incidence of stroke have increased, but stroke-related case fatality has declined in China over recent decades. There are significant regional and rural-urban differences in incidence rates. Despite improved public health policies and healthcare delivery, the burden of stroke remains high in China. Further coordinated efforts are required in prevention and community care to offset the likelihood of further expansion in the absolute number of stroke cases in this large population.
Publisher: SAGE Publications
Date: 21-06-2020
Abstract: Dysphagia is associated with aspiration pneumonia after stroke. Data are limited on the influences of dysphagia screen and assessment in clinical practice. To determine associations between a “brief” screen and “detailed” assessment of dysphagia on clinical outcomes in acute stroke patients. A prospective cohort study analyzed retrospectively using data from a multicenter, cluster cross-over, randomized controlled trial (Head Positioning in Acute Stroke Trial [HeadPoST]) from 114 hospitals in nine countries. HeadPoST included 11,093 acute stroke patients randomized to lying-flat or sitting-up head positioning. Herein, we report predefined secondary analyses of the association of dysphagia screening and assessment and clinical outcomes of pneumonia and death or disability (modified Rankin scale 3–6) at 90 days. Overall, 8784 (79.2%) and 3917 (35.3%) patients were screened and assessed for dysphagia, respectively, but the frequency and timing for each varied widely across regions. Neither use of a screen nor an assessment for dysphagia was associated with the outcomes, but their results were compared to “screen-pass” patients, those who failed had higher risks of pneumonia (adjusted odds ratio [aOR] = 3.00, 95% confidence interval [CI] = 2.18–4.10) and death or disability (aOR = 1.66, 95% CI = 1.41–1.95). Similar results were evidence for the results of an assessment for dysphagia. Subsequent feeding restrictions were related to higher risk of pneumonia in patients failed dysphagia screen or assessment (aOR = 4.06, 95% CI = 1.72–9.54). Failing a dysphagia screen is associated with increased risks of pneumonia and poor clinical outcome after acute stroke. Further studies concentrate on determining the effective subsequent feeding actions are needed to improve patient outcomes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2022
DOI: 10.1161/STROKEAHA.121.036143
Abstract: High blood pressure (BP) is common after ischemic stroke and associated with a poor functional outcome and increased mortality. The conundrum then arises on whether to lower BP to improve outcome or whether this will worsen cerebral perfusion due to aberrant cerebral autoregulation. A number of large trials of BP lowering have failed to change outcome whether treatment was started prehospital in the community or hospital. Hence, nuances on how to manage high BP are likely, including whether different interventions are needed for different causes, the type and timing of the drug, how quickly BP is lowered, and the collateral effects of the drug, including on cerebral perfusion and platelets. Specific scenarios are also important, including when to lower BP before, during, and after intravenous thrombolysis and endovascular therapy/thrombectomy, when it may be necessary to raise BP, and when antihypertensive drugs taken before stroke should be restarted. This narrative review addresses these and other questions. Although further large trials are ongoing, it is increasingly likely that there is no simple answer. Different subgroups of patients may need to have their BP lowered (eg, before or after thrombolysis), left alone, or elevated.
Publisher: Frontiers Media SA
Date: 12-09-2022
DOI: 10.3389/FPSYT.2022.927856
Abstract: Stroke is a major cause of mortality and long-term physical and cognitive impairment. This study aims to: (1) examine the prevalence of depressive symptoms, disability and pain among Chinese adults with stroke (2) test the associations of functional limitations and body pain with occurrence of depressive symptoms (3) investigate gender and urban-rural disparities in these associations. This study utilized the data from the China Health and Retirement Longitudinal Study in 2018, involving 969 patients with stroke among 17,970 participants aged ≥ 45 years. Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression (CES-D) Scale. We performed multivariable logistic regression models to estimate the associations between activities of daily life (ADL), instrumental activities of daily life (IADL) and pain with depressive symptoms. Depressive symptoms were found among 40.2% of stroke patients, with a higher prevalence in females (48.2%) than males (32.7%). Prevalence of ADL limitations, IADL limitations and pain among stroke patients were 39.2, 49.8 and 14.0%, respectively. ADL and IADL limitations and pain were more prevalent among females and residents in rural areas. Multivariable regression analyses showed a significant association between ADL limitation (OR = 1.535, 95% CI = 1.168, 2.018), IADL limitation (OR = 1.666, 95% CI = 1.260, 2.203) and pain (OR = 2.122, 95% CI = 1.466, 3.073) with depressive symptoms. Stratified analyses revealed stronger associations among urban residents. Females had a higher association of ADL and IADL with depressive symptoms but similar in that of pain to the males. The impact of ADL and IADL in male patients is higher than in females, but the impact of pain on depressive symptoms is higher in female patients. Depressive symptoms are common amongst post-stroke patients in China and are significantly associated with functional disability and physical pain. Our findings have implications for practitioners on the early assessment of pain and depression after stroke. Future research should explore effective intervention measures for physical-mental stroke complications.
Publisher: BMJ
Date: 25-06-2020
Abstract: Although the Head Positioning in acute Stroke Trial (HeadPoST) showed no effect of the flat head position (FP vs sitting up head position (SUP)) on functional outcome, we hypothesised that it could still offer benefits if commenced early in those with acute ischaemic stroke (AIS) of at least moderate severity. Subgroup analysis of HeadPoST in participants with National Institutes of Health Stroke Scale (NIHSS) scores ≥7, ≥10 and ≥14, randomised to FP or SUP .5 hours of AIS onset on functional outcomes defined by a shift in scores on the modified Rankin scale (mRS) and death/disability (mRS scores 3–6), and any cardiovascular serious adverse event. Logistic regression analyses were undertaken adjusted for study design and baseline risk factors. There was no significant differential treatment effect in patient subgroups defined by increasing baseline NIHSS scores: adjusted OR and 95% CI for ordinal shift and binary (3–6) mRS scores: for NIHSS ≥7 (n=867) 0.92 (0.67 to 1.25) and 0.74 (0.52 to 1.04) NIHSS ≥ 10 (n=606) 0.80 (0.58 to 1.10) and 0.77 (0.49 to 1.19) NIHSS ≥14 (n=378) 0.82 (0.54 to 1.24) and 1.22 (0.69 to 2.14). Early FP had no significant effect in patients with moderate–severe AIS. NCT02162017 .
Publisher: Elsevier BV
Date: 03-2023
Publisher: Springer Science and Business Media LLC
Date: 12-2021
DOI: 10.1186/S13063-021-05860-Y
Abstract: Early pre-hospital initiation of blood pressure (BP) lowering could improve outcomes for patients with acute stroke, by reducing hematoma expansion in intracerebral hemorrhage (ICH), and time to reperfusion treatment and risk of intracranial hemorrhage in ischemic stroke (IS). We present the design of the fourth INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4). A multi-center, ambulance-delivered, prospective, randomized, open-label, blinded endpoint (PROBE) assessed trial of pre-hospital BP lowering in 3116 hypertensive patients with suspected acute stroke at 50+ sites in China. Patients are randomized through a mobile phone digital system to intensive BP lowering to a target systolic BP of 140 mmHg within 30 min, or guideline-recommended BP management according to local protocols. After the collection of in-hospital clinical and management data and 7-day outcomes, trained blinded assessors conduct telephone or face-to-face assessments of physical function and health-related quality of life in participants at 90 days. The primary outcome is the physical function on the modified Rankin scale at 90 days, analyzed as an ordinal outcome with 7 categories. The s le size was estimated to provide 90% power ( α = 0.05) to detect a 22% reduction in the odds of a worse functional outcome using ordinal logistic regression. INTERACT4 is a pragmatic clinical trial to provide reliable evidence on the effectiveness and safety of ambulance-delivered hyperacute BP lowering in patients with suspected acute stroke. ClinicalTrials.gov NCT03790800. Registered on 2 January 2019 Chinese Trial Registry ChiCTR1900020534. Registered on 7 January 2019. All items can be found in this protocol paper.
Publisher: Springer Science and Business Media LLC
Date: 12-2021
DOI: 10.1186/S13063-021-05871-9
Abstract: Chronic subdural haematoma (CSDH) is a common condition in the elderly that often requires neurosurgical management. For small CSDH, evidence has emerged that statins may reduce haematoma volume and improve outcomes, presumably by reducing local inflammation and promoting vascular repair. We wish to extend this evidence in a study that aims to determine the efficacy and safety of atorvastatin combined with low-dose dexamethasone in patients with CSDH. The second ATorvastatin On Chronic subdural Hematoma (ATOCH-II) study is a multi-centre, randomized, placebo-controlled, double-blind trial which aims to enrol 240 adult patients with a conservative therapeutic indication for CSDH, randomly allocated to standard treatment with atorvastatin 20 mg combined with low-dose dexamethasone (or matching placebos) daily for 28 days, and with 152 days of follow-up. The primary outcome is a composite good outcome defined by any reduction from baseline in haematoma volume and survival free of surgery at 28 days. Secondary outcomes include functional outcome on the modified Rankin scale (mRS) and modified Barthel Index at 28 days, surgical transition and reduction in haematoma volumes at 14, 28 and 90 days. This multi-centre clinical trial aims to provide high-quality evidence on the efficacy and safety of the combined treatment of atorvastatin and low-dose dexamethasone to reduce inflammation and enhance angiogenesis in CSDH. ChiCTR, ChiCTR1900021659 . Registered on 3 March 2019, www.chictr.org.cn/showproj.aspx?proj=36157 .
Publisher: Instituto Nacional de Salud Publica
Date: 13-06-2022
DOI: 10.21149/12803
Abstract: Objective. A narrative overview of regional academic research collaborations to address the increasing burden and gaps in care for patients at risk of, and who suffer from, stroke in Latin America (LA). Materials and methods. A summary of experiences and knowledge of the local situation is presented. No systematic literature review was performed. Results. The rapidly increasing burden of stroke poses immense challenges in LA, where prevention and management strategies are highly uneven and inadequate. Clinical research is increasing through various academic consortia and networks formed to overcome structural, funding and skill barriers. However, strengthening the ability to generate, analyze and interpret randomized evidence is central to further develop effective therapies and healthcare systems in LA. Conclusions. Regional networks foster the conduct of multicenter studies –particularly randomized controlled trials–, even in resource-poor regions. They also contribute to the external validity of international studies and strengthen systems of care, clinical skills, critical thinking, and international knowledge exchange.
Publisher: SAGE Publications
Date: 07-01-2022
DOI: 10.1177/17474930211068671
Abstract: Patients who suffer intracerebral hemorrhage (ICH) are at very high risk of recurrent ICH and other serious cardiovascular events. A single-pill combination (SPC) of blood pressure (BP) lowering drugs offers a potentially powerful but simple strategy to optimize secondary prevention. The Triple Therapy Prevention of Recurrent Intracerebral Disease Events Trial (TRIDENT) aims to determine the effects of a novel SPC “Triple Pill,” three generic antihypertensive drugs with demonstrated efficacy and complementary mechanisms of action at half standard dose (telmisartan 20 mg, amlodipine 2.5 mg, and indapamide 1.25 mg), with placebo for the prevention of recurrent stroke, cardiovascular events, and cognitive impairment after ICH. An international, double-blind, placebo-controlled, randomized trial in adults with ICH and mild-moderate hypertension (systolic BP: 130–160 mmHg), who are not taking any Triple Pill component drug at greater than half-dose. A total of 1500 randomized patients provide 90% power to detect a hazard ratio of 0.5, over an average follow-up of 3 years, according to a total primary event rate (any stroke) of 12% in the control arm and other assumptions. Secondary outcomes include recurrent ICH, cardiovascular events, and safety. Recruitment started 28 September 2017. Up to 31 October 2021, 821 patients were randomized at 54 active sites in 10 countries. Triple Pill adherence after 30 months is 86%. The required s le size should be achieved by 2024. Low-dose Triple Pill BP lowering could improve long-term outcome from ICH.
Publisher: S. Karger AG
Date: 20-12-2022
DOI: 10.1159/000520669
Abstract: b i Background: /i /b The third INTEnsive care bundle with blood pressure Reduction in Acute Cerebral Haemorrhage Trial is an ongoing international, multicentre, stepped wedge, cluster-randomized trial to determine the effectiveness of a goal-directed care bundle (early intensive blood pressure [BP] lowering, glycaemic control, treatment of pyrexia, and reversal of anticoagulation), as compared to standard of care, on patient-centred outcomes after acute intracerebral haemorrhage (ICH). An embedded process evaluation aims to identify factors related to the uptake and implementation of the intervention. Herein, we present the process evaluation results for hospital sites in China. b i Methods/Design: /i /b A mixed methods approach, including surveys, focused group discussions and interviews with clinicians, routine monitoring, and recruitment logs were used to collect data across purposively s led hospitals. Medical Research Council guidance and normalization process theory were used as theoretical frameworks for design, data analysis, and synthesis. b i Results: /i /b Twenty quantitative surveys were completed with clinicians, and 26 interviews and 2 focus group discussions were conducted during 2019–2020. The care bundle was generally delivered as planned and acceptable by doctors and nurses, but difficulties were reported in achieving the protocol-defined target levels of BP and glycaemic control. Resistance to implementing the care bundle occurred for patients perceived to be at high risk of adverse effects. Common organizational contextual factors that impeded implementation included delayed processes and limited medication supply, while established background care procedures, expertise, and capacity influenced its integration into routine practice. Areas to facilitate implementation included optimizing workflow within available resources, having a dedicated team, and recognizing the potential benefits of the intervention. b i Conclusions: /i /b Varied established care protocols across sites, different levels of background expertise, and lack of staff capacity impeded the integration of goal-directed care bundle into routine practice for ICH patients in China. Ready identification, and efforts to address, these barriers could facilitate uptake of future guideline-recommended interventions for the management of patients with ICH.
Publisher: Elsevier BV
Date: 03-2019
Publisher: Frontiers Media SA
Date: 15-06-2022
Abstract: The third INTEnsive care bundle with blood pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT3) is an ongoing, international, multicenter, stepped-wedge cluster, prospective, randomized, open, blinded endpoint assessed trial evaluating the effectiveness of a quality improvement “care bundle” for the management of patients with acute spontaneous intracerebral hemorrhage (ICH) in low- and middle-income countries (LMICs). An embedded process evaluation aims to explore the uptake and implementation of the intervention, and understand the context and stakeholder perspectives, for interpreting the trial outcomes. The design was informed by Normalization Process Theory and the UK Medical Research Council process evaluation guidance. Mixed methods are used to evaluate the implementation outcomes of fidelity, reach, dose, acceptability, appropriateness, adoption, sustainability, and relevant contextual factors and mechanisms affecting delivery of the care bundle. Semi-structured interviews and non-participant observations are conducted with the primary implementers (physicians and nurses) and patients/carers to explore how the care bundle was integrated into routine care. Focus group discussions are conducted with investigators and project operational staff to understand challenges and possible solutions in the organization of the trial. Data from observational records, surveys, routine monitoring data, field notes and case report forms, inform contextual factors, and adoption of the intervention. Purposive s ling of sites according to pre-specified criteria is used to achieve s le representativeness. Implementation outcomes, and relevant barriers and facilitators to integrating the care bundle into routine practice, will be reported after completion of the process evaluation. The embedded process evaluation will aid understanding of the causal mechanisms between care bundle elements and clinical outcomes within complex health systems across erse LMIC settings. The INTERACT3 study is registered at ClinicalTrials.gov (NCT03209258).
Publisher: Frontiers Media SA
Date: 27-08-2021
DOI: 10.3389/FNEUR.2021.687862
Abstract: Background and Aims: Epidemiological studies show significant variations in hypertension management within and between countries. The level of regional variation in early blood pressure (BP) management after acute stroke is uncertain. Methods: Data are from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), a partial-factorial, international randomized controlled trial of thrombolysis-eligible acute ischemic stroke (AIS) patients with elevated systolic BP (SBP & mmHg) assigned to intensive (target SBP 130-140 mmHg) vs. guideline-recommended (SBP & mmHg) treatment BP management was compared among four regions: Western countries (Italy/United Kingdom/Spain/Australia), China (mainland), other Asia (Hong Kong/Taiwan/Singapore/Thailand/Vietnam/India), and South America (Chile/Brazil/Colombia). Results: These analyses included 2,196 AIS [38% women, mean age 67 (12) years] patients. Commonly used intravenous BP-lowering agents were labetalol, nitroglycerin, and topical nitrates in Western countries urapidil and sodium nitroprusside in China nicardipine in other Asian countries and sodium nitroprusside and labetalol in South America. Chinese patients were less likely to receive BP-lowering treatment in the first 24 h and be treated with multiple agents although they had smaller magnitude of SBP reduction and lower SBP variability. Conclusion: Regional variations in early BP management in acute stroke translated into differences in early BP control parameters.
Publisher: Hindawi Limited
Date: 27-03-2023
DOI: 10.1155/2023/2613413
Abstract: Men’s sheds are a community-based organisation that allows a space for a community of men to interact and engage with one another with hands-on activities. As such, men’s sheds form an appropriate setting to deliver health and wellbeing initiatives. This review aims to understand the role of Australian men’s sheds with respect to the health and wellbeing of their male participants. This review was conducted in accordance with the preferred reporting items for systematic reviews and meta-analysis (PRISMA) following a three-step process of planning, conducting, and reporting the review. All three authors reviewed all the eligible articles. There was significant methodological heterogeneity between the sources identified (n = 11). A narrative synthesis identified three key themes: health promotion, wellbeing, and socialisation intergenerational mentoring and Aboriginal and Torres Strait Islander men’s health. Men’s sheds serve as ideal locations for the delivery of initiatives that can positively impact on the health and wellbeing of their male participants. Furthermore, research is needed to explore the implementation and evaluation of these health and wellbeing initiatives for men in their respective communities.
Publisher: BMJ
Date: 22-05-2017
Abstract: The characteristics of patients with acute ischaemic stroke (AIS) and their management vary across regions, which may influence outcomes. We examined for differential patterns of outcome between China and non-China participants of the ENhanced Control of Hypertension And Thrombolysis strokE stuDy (ENCHANTED), which tested different alteplase doses in AIS. ENCHANTED was an international, multicentre, open, blinded-endpoint trial of the effects of low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) intravenous alteplase on 90-day disability outcomes and symptomatic intracerebral haemorrhage (sICH) in 3310 patients with AIS. Participants (n=1419, 48%) in China were younger, and more often male, hypertensive and with prior stroke and coronary artery disease, but less likely to have atrial fibrillation and use antihypertensive, antithrombotic and lipid-lowering agents, compared with non-China patients with AIS. Although China participants had more AIS due to large artery occlusion, were treated later and had differing ancillary management, there was no significant difference in 90-day modified Rankin scale scores 2–6 (55.6% vs 47.8% OR, adjusted for baseline and management factors 0.87 (95% CI 0.71 to 1.07 p=0.20)) and risk of sICH (Safe Implementation of Thrombolysis in Stroke-Monitoring Study criteria: 1.4% vs 1.8% p=0.12) compared with non-China participants. There was no heterogeneity in the treatment effects of low-dose versus standard-dose alteplase between China and non-China participants. Patients with AIS recruited to the ENCHANTED trial in China had similar outcomes in response to thrombolysis treatment despite significantly differing demographic, clinical and management factors to patients with AIS in other regions.
Publisher: Massachusetts Medical Society
Date: 22-06-2017
Publisher: S. Karger AG
Date: 2021
DOI: 10.1159/000512608
Abstract: b i Background: /i /b Patients with premorbid functional impairment are generally excluded from acute stroke trials. We aimed to determine the impact of including such patients in the Head Positioning in acute Stroke Trial (HeadPoST) and early additional impairment on outcomes. b i Methods: /i /b Post hoc analyses of HeadPoST, an international, cluster-randomized crossover trial of lying-flat versus sitting-up head positioning in acute stroke. Associations of early additional impairment, defined as change in modified Rankin scale (mRS) scores from premorbid levels (estimated at baseline) to Day 7 (“early ΔmRS”), and poor outcome (mRS score 3–6) at Day 90 were determined with generalized linear mixed model. Heterogeneity of the trial treatment effect was tested according to premorbid mRS scores 0–1 versus 2–5. b i Results: /i /b Of 8,285 patients (38.9% female, mean age 68 ± 13 years) with complete data, there were 1,984 (23.9%) with premorbid functional impairment (mRS 2–5). A significant linear association was evident for early ∆mRS and poor outcome (per 1-point increase in ΔmRS, adjusted odds ratio 1.20, 95% confidence interval 1.14–1.27 i /i & #x3c 0.0001). Patients with greater premorbid functional impairment were less likely to develop additional impairment, but their risk of poor 90-day outcome significantly increased with increasing (worse) premorbid mRS scores (linear trend i /i & #x3c 0.0001). There was no heterogeneity of the trial treatment effect by level of premorbid function. b i Conclusions: /i /b Early poststroke functional impairment that exceeded premorbid levels was associated with worse 90-day outcome, and this association increased with greater premorbid functional impairment. Yet, including premorbid impaired patients in the HeadPoST did not materially affect the subsequent treatment effect. b i Clinical Trial Registration: /i /b HeadPoST is registered at www.ClinicalTrials.gov (NCT02162017).
Publisher: American Medical Association (AMA)
Date: 09-08-2022
Publisher: BMJ
Date: 02-2021
Abstract: As studies vary in defining the prognostic significance of smoking in acute ischaemic stroke (AIS), we aimed to determine the relation of smoking and key outcomes in patient participants who had thrombolysed AIS of the international quasi-factorial randomised Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Post-hoc analyses of ENCHANTED, an international quasi-factorial randomised evaluation of intravenous alteplase-dose comparison and levels of blood pressure control in patients who had thrombolysed AIS. Multivariable logistic regression models with inverse probability of treatment weighting (IPTW) propensity scores were used to determine associations of self-reported smoking status and clinical outcomes, according to 90-day modified Rankin Scale (mRS) scores and symptomatic intracerebral haemorrhage (sICH). Of 4540 patients who had an AIS, there were 1008 (22.2%) current smokers who were younger and predominantly male, with more comorbidities of hypertension, coronary artery disease, atrial fibrillation and diabetes mellitus, and greater baseline neurological impairment, compared with non-smokers. In univariate analysis, current smokers had a higher likelihood of a favourable shift in mRS scores (OR 0.88, 95% CI 0.77 to 0.99 p=0.038) but this association reversed in a fully adjusted model with IPTW (adjusted OR 1.15, 95% CI 1.04 to 1.28 p=0.009). A similar trend was also apparent for dichotomised poor outcome (mRS scores 2–6: OR 1.18, 95% CI 1.05 to 1.33 p=0.007), but not with the risk of sICH across standard criteria. Smoking predicts poor functional recovery in patients who had thrombolysed AIS. NCT01422616 .
Publisher: S. Karger AG
Date: 2019
DOI: 10.1159/000504745
Abstract: b i Objective: /i /b To determine the extent to which the effects of intensive blood pressure (BP) lowering are modified by doses of alteplase in thrombolysis-eligible acute ischemic stroke (AIS) patients. b i Methods: /i /b Prespecified analyses of the Enhanced Control of Hypertension and Thrombolysis Stroke Study for patients enrolled in both arms: (i) low-dose (0.6 mg/kg body weight) or standard-dose (0.9 mg/kg) alteplase and (ii) intensive (target systolic BP [SBP] 130–140 mm Hg) or guideline-recommended (target SBP & #x3c mm Hg) BP management. The primary outcome was functional recovery, measured by a shift in scores on modified Rankin scale at 90 days. The safety outcome was any intracranial hemorrhage (ICH). b i Results: /i /b There were 925 participants (mean age 67 years, 39% female, 77% Asian) randomized to both arms: 242 randomly assigned to guideline/standard-dose (GS) 234 to guideline/low-dose (GL) 227 to intensive/standard-dose (IS) and 222 to intensive/low-dose (IL). Overall, average SBP levels within 24 h were lower in the low-dose compared to standard-dose alteplase group (146 and 144 vs. 151 and 150 mm Hg, for GS and GL vs. IS and IL, respectively, i /i & #x3c 0.0001). There was no heterogeneity of the effects of BP lowering (intensive vs. guideline) on functional recovery between standard-dose (OR 0.81, 95% CI 0.59–1.12) and low-dose alteplase (1.06, 0.77–1.47 i /i = 0.25 for interaction). Similar results were observed for ICH ( i /i = 0.50 for interaction). b i Conclusions: /i /b In thrombolysis-treated patients with predominantly mild-to-moderate severity AIS, intensive BP lowering neither improve functional recovery, either with low- or standard-dose intravenous alteplase, nor beneficially interact with low-dose alteplase in reducing ICH. b i Trial Registration: /i /b The trial is registered with ClinicalTrials.gov (NCT01422616).
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2019
DOI: 10.1161/STR.50.SUPPL_1.TP371
Abstract: Background and Purpose: Patient beliefs/values over illness/wellbeing are important considerations in health care delivery. We aimed to map function with health-related quality of life (HRQoL) to derive utility-weighted outcomes to test the efficacy of acute stroke trial interventions. Methods: Physical function and HRQoL were defined by modified Rankin scale (mRS) and EuroQol 5-dimensional questionnaire (EQ-5D) scores, respectively, for calculating utility-weighted mRS (UW-mRS) scores in pooled data from 5 international trials and externally validated in another trial database. UW-mRS was derived using ordinary least squares regression with mRS as a discrete ordinal explanatory dummy variable and EQ-5D as a continuous response variable. Linear regression was used to assess mean UW-mRS scores between intervention groups. Results: UW-mRS scores derived from 19338 acute stroke patients were 0.96, 0.92, 0.75, 0.58, 0.32, -0.093 for mRS scores 0, 1, 2, 3, 4 and 5, respectively. Both UW-mRS and ordinal mRS were statistically significant in INTERACT (P=0.04 and P=0.02 for UW-mRS and ordinal mRS, respectively) and ENCHANTED (0.04, P .0001). For HeadPoST (0.84, 0.41), SCAST (0.12, 0.22), ATTEND (0.42, 0.29) and COSSACS (0.77, 0.95), both UW-mRS and ordinal mRS scores captured ergent treatment effects in showing neutral results. Conclusions: UW-mRS as an outcome measure provides comparable statistical efficiency to ordinal analysis of mRS, but may better reflect patient and societal views on recovery. Greater HRQoL occurs where there is a large favourable shift away from high disability (mRS scores 3-5) interventions that achieve this provide the greatest benefit to patients.
Publisher: S. Karger AG
Date: 2021
DOI: 10.1159/000516487
Abstract: b i Background and Purpose: /i /b As outcomes for acute ischemic stroke (AIS) vary according to clinical profile and management approaches, we aimed to determine disparities in clinical outcomes between Asian and non-Asian participants of the international, Enhanced Control of Hypertension and Thrombolysis Stroke study (ENCHANTED). b i Methods: /i /b ENCHANTED was a multicenter, prospective, partial-factorial, randomized, open trial of low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) alteplase, and intensive (target systolic blood pressure [SBP] 130–140 mm Hg) or guideline-recommended (& #x3c mm Hg) BP management, in thrombolysis-eligible AIS patients. Logistic regression models were used to examine the associations with outcomes of death or disability (modified Rankin scale [mRS] scores 2–6), major disability (mRS 3–5), death, and intracranial hemorrhage (ICH), with adjustment prognostic factors, alteplase dose, and mean SBP over 1–24 h. b i Results: /i /b Among 4,551 thrombolyzed AIS patients (mean age 66.7 years, 37.8% female), there were 65.4% Asians who were younger, fewer female, and with less atrial fibrillation, hypercholesterolemia, premorbid symptoms, and concomitant antihypertensive, antithrombotic and statin treatment, and more prior stroke, compared to non-Asians. Frequencies of hypertension, coronary artery disease, and diabetes mellitus were comparable between groups. Asian patients were less likely to be admitted to an acute stroke unit and receive early mobilization by a therapist or rehabilitation but more likely to receive intensive care. There were no significant differences between Asians and non-Asians in functional outcome (defined by mRS scores 2–6 or 3–5 adjusted odds ratio [OR] 1.00, 95% confidence interval [CI] 0.85–1.19 [ i /i = 0.958] and OR 0.95, 95% CI 0.80–1.13 [ i /i = 0.572], respectively), or death (OR 1.25, 95% CI 0.95–1.65 i /i = 0.116), despite Asians having greater odds of ICH (OR 1.51, 95% CI 1.23–1.86 i /i = 0.0001) and neurological deterioration within 24 h (OR 1.58, 95% CI 1.18–2.12 i /i = 0.002). b i Conclusions: /i /b Within the context of an international clinical trial of thrombolyzed AIS patients, demography, risk factors, management, and odds of early neurological deterioration and ICH, all differ between Asian and non-Asian participants. However, patterns of functional recovery are similar between these major regional groups.
Publisher: Elsevier BV
Date: 11-2022
Publisher: Springer Science and Business Media LLC
Date: 12-2021
DOI: 10.1186/S13063-021-05881-7
Abstract: Early intensive blood pressure (BP) lowering remains the most promising treatment for acute intracerebral hemorrhage (ICH), despite discordant results between clinical trials and potential variation in the treatment effects by approach to control BP. As the third in a series of clinical trials on this topic, the INTEnsive care bundle with blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT3) aims to determine the effectiveness of a goal-directed care bundle protocol of early physiological control (intensive BP lowering, glycemic control, and pyrexia treatment) and reversal of anticoagulation, in acute ICH. INTERACT3 is a pragmatic, international, multicenter, stepped-wedge (4 phases/3 steps), cluster-randomized controlled trial to determine the effectiveness of a multifaceted care package in adult (age ≥ 18 years) patients (target 8360) with acute ICH ( 6 h of onset) recruited from 110 hospitals (average of 19 consecutive patients per phase) in low- and middle-income countries. After a control phase, each hospital implements the intervention (intensive BP lowering, target systolic 140 mmHg glucose control, target 6.1–7.8 mmol/L and 7.8–10.0 mmol/L in those without and with diabetes mellitus, respectively anti-pyrexia treatment to target body temperature ≤ 37.5 °C and reversal of anticoagulation, target international normalized ratio 1.5 within 1 h). Information will be obtained on demographic and baseline clinical characteristics, in-hospital management, and 7-day outcomes. Central trained blinded assessors will conduct telephone interviews to assess physical function and health-related quality of life at 6 months. The primary outcome is the modified Rankin scale (mRS) at 6 months analyzed using ordinal logistic regression. The s le size of 8360 subjects provides 90% power ( α = 0.05) to detect a 5.6% absolute improvement (shift) in the primary outcome of the intervention versus control standard care, with various assumptions. As the largest clinical trial in acute ICH, INTERACT3 is on schedule to provide an assessment of the effectiveness of a widely applicable goal-directed care bundle for a serious condition in which a clearly proven treatment has yet to be established. ClinicalTrials.gov NCT03209258. Registered on 1 July 2017. Chinese Trial Registry ChiCTR-IOC-17011787. Registered on 28 June 2017
Publisher: S. Karger AG
Date: 2020
DOI: 10.1159/000511394
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2021
DOI: 10.1161/STROKEAHA.120.030435
Abstract: We determined associations of physiological abnormalities (systolic blood pressure, glucose, and body temperature) and warfarin use with outcomes in spontaneous intracerebral hemorrhage. Post hoc analyses of INTERACT2 (Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial) comparing systolic blood pressure control ( versus mm Hg) in 2839 hypertensive patients with intracerebral hemorrhage (onset hours). Multivariable logistic regression defined associations of baseline scores assigned as 0 to 6 per 10 mm Hg systolic blood pressure increase (range, 150–220 mm Hg) and 0 or 1 for serum glucose (≤6.5 versus .5 mmol/L), body temperature (≤37.5 °C versus .5 °C), and warfarin use (no versus yes) and death or major disability (modified Rankin Scale scores 3–6 at 90 days). Baseline score distribution was 0 (7.7%), 1 (15.6%), 2 (19.0%), 3 (19.1%), 4 (15.2%), 5 (11.6%), 6 (8.9%), and 7 (2.9%). After adjustment for baseline neurological severity and potential confounders, significant linear associations were evident for increasing (per point) score and death or major disability (odds ratio, 1.12 [95% CI, 1.07–1.17]), death (odds ratio, 1.15 [95% CI, 1.07–1.23]), and major disability (odds ratio, 1.10 [95% CI, 1.05–1.15]). Combination of abnormal physiological parameters and warfarin use is associated with poor outcomes in intracerebral hemorrhage. Effects of their early control is under investigation in INTERACT3 (Intensive Care Bundle With Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial). URL: www.clinicaltrials.gov . Unique identifier: NCT00716079.
Publisher: SAGE Publications
Date: 24-08-2022
DOI: 10.1177/17474930221120345
Abstract: Uncertainty exists over the optimal level of blood pressure (BP) after mechanical thrombectomy (MT) for acute ischemic stroke (AIS). We aim to determine the effectiveness and safety of intensive BP-lowering following MT reperfusion of large-vessel occlusion (LVO)-related AIS. The second ENhanced Control of Hypertension ANd Thrombolysis strokE stuDy (ENCHANTED2) is an investigator-initiated, multicenter, prospective, randomized, open, blinded-endpoint (PROBE) trial of intensive systolic BP (SBP) control in reperfused (extended treatment in cerebral infarction (eTICI) classification 2b/2c/3) LVO-AIS patients with persistent hypertension (SBP ⩾ 140 mmHg) at 60+ sites in China, and Australia and the United Kingdom. Eligible patients are centrally randomly allocated to more- (target SBP ⩽ 120 mmHg within 1 h) or less-intensive (target SBP 140–180 mmHg) BP management, to be maintained for 72 h. Primary outcome is an ordinal shift analysis of scores on the modified Rankin scale (mRS) at 90 days. S le size of 2257 patients provides 90% power to detect a 6.5% absolute reduction in poor outcome from more-intensive BP-lowering using ordinal logistic regression. Recruitment started in China in July 2020. At a meeting of the independent Data and Safety Monitoring Board in March 2022 to review primary outcome data available for 347 patients, they recommended suspension of recruitment due to safety concerns in the more-intensive group which was implemented by the Trial Steering Committee (TSC) with 817 randomized patients only in China. The TSC then stopped recruitment after the safety concerns persisted on further review of the data in June 2022. The TSC will make a decision on restarting the trial with modification of the protocol when the results are made public. ENCHANTED2 will provide further randomized evidence on the role of intensive BP-lowering after reperfusion in MT-treated AIS patients. ClinicalTrials.gov NCT04140110 registered 25 October 2019.
Publisher: Frontiers Media SA
Date: 09-02-2023
Abstract: In China, a limited number of studies focus on women and examine the effect of cardiometabolic multimorbidity (defined as the presence of two or more cardiometabolic diseases) on health outcomes. This research aims to investigate the epidemiology of cardiometabolic multimorbidity and the association of cardiometabolic multimorbidity with long-term mortality. This study used data from the China Health and Retirement Longitudinal Study between 2011 and 2018, which includes 4,832 women aged 45 years and older in China. Poisson-distributed Generalized Linear Models (GLM) were applied to examine the association of cardiometabolic multimorbidity with all-cause mortality. Overall, the prevalence of cardiometabolic multimorbidity was 33.1% among the total s le of 4,832 Chinese women, and increased with age, ranging from 28.5% (22.1%) for those aged 45–54 years to 65.3% (38.2%) for those aged ≥75 years in urban (rural) areas. Compared with the group of none and single disease, cardiometabolic multimorbidity was positively associated with all-cause death (RR = 1.509, 95% CI = 1.130, 2.017), after adjusting socio-demographic and lifestyle behavioral covariates. Stratified analyses revealed that the association between cardiometabolic multimorbidity and all-cause death was only statistically significant (RR = 1.473, 95% CI = 1.040, 2.087) in rural residents, but not significant in urban residents. Cardiometabolic multimorbidity is common among women in China and has been associated with excess mortality. Targeted strategies and people-centered integrated primary care models must be considered to more effectively manage the cardiometabolic multimorbidity shift from focusing on single-disease.
Publisher: Elsevier BV
Date: 07-2023
Publisher: S. Karger AG
Date: 26-10-2023
DOI: 10.1159/000534761
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2022
DOI: 10.1161/STROKEAHA.121.034580
Abstract: In thrombolysis-eligible patients with acute ischemic stroke, there is uncertainty over the most appropriate systolic blood pressure (SBP) lowering profile that provides an optimal balance of potential benefit (functional recovery) and harm (intracranial hemorrhage). We aimed to determine relationships of SBP parameters and outcomes in thrombolyzed acute ischemic stroke patients. Post hoc analyzes of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study), a partial-factorial trial of thrombolysis-eligible and treated acute ischemic stroke patients with high SBP (150–180 mm Hg) assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) alteplase and intensive (target SBP, 130–140 mm Hg) or guideline-recommended (target SBP mm Hg) treatment. All patients were followed up for functional status and serious adverse events to 90 days. Logistic regression models were used to analyze 3 SBP summary measures postrandomization: attained (mean), variability (SD) in 1–24 hours, and magnitude of reduction in 1 hour. The primary outcome was a favorable shift on the modified Rankin Scale. The key safety outcome was any intracranial hemorrhage. Among 4511 included participants (mean age 67 years, 38% female, 65% Asian) lower attained SBP and smaller SBP variability were associated with favorable shift on the modified Rankin Scale (per 10 mm Hg increase: odds ratio, 0.76 [95% CI, 0.71–0.82] P .001 and 0.86 [95% CI, 0.76–0.98] P =0.025) respectively, but not for magnitude of SBP reduction (0.98, [0.93–1.04] P =0.564). Odds of intracranial hemorrhage was associated with higher attained SBP and greater SBP variability (1.18 [1.06–1.31] P =0.002 and 1.34 [1.11–1.62] P =0.002) but not with magnitude of SBP reduction (1.05 [0.98–1.14] P =0.184). Attaining early and consistent low levels in SBP mm Hg, even as low as 110 to 120 mm Hg, over 24 hours is associated with better outcomes in thrombolyzed acute ischemic stroke patients. URL: www.clinicaltrials.gov Unique identifier: NCT01422616.
Publisher: S. Karger AG
Date: 2020
DOI: 10.1159/000509226
Abstract: b i Background and Purpose: /i /b The influence of specific brain lesions on health-related quality of life (HRQoL) after acute ischemic stroke (AIS) is uncertain. We aimed to identify imaging predictors of poor HRQoL in alteplase-treated participants of the alteplase dose arm of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). b i Methods: /i /b ENCHANTED was an international trial of low- versus standard-dose intravenous alteplase in AIS patients, with functional outcome (modified Rankin scale [mRS]) and HRQoL on the 5-dimension European Quality of Life Scale (EQ-5D) assessed at 90 days post-randomization. Brain images were analyzed centrally by trained assessors. Multivariable logistic regression was undertaken in the study population randomly ided (2:1) into training (development) and validation (performance) groups, with age (per 10-year increase), ethnicity, baseline National Institutes of Health Stroke Scale (NIHSS) score, diabetes mellitus, premorbid function (mRS score 0 or 1), and proxy respondent, forced into all models. Data are presented with odds ratios (ORs) and 95% confidence intervals (CIs). b i Results: /i /b Eight prediction models were developed and validated in 2,526 AIS patients (median age 67.5 years 38.4% female 61.7% Asian) with complete brain imaging and 90-day EQ-5D utility score data. The best performance model included acute ischemic changes in the right (OR 1.69, 95% CI: 1.24–2.29) and deep (OR 1.50, 95% CI: 1.03–2.19) middle cerebral artery (MCA) regions. Several background features of brain frailty – atrophy, white matter change, and old infarcts – were significantly associated with adverse physical but not emotional HRQoL domains. b i Conclusions: /i /b In thrombolysed AIS patients, right-sided and deep ischemia within the MCA territory predict poor overall HRQoL, whilst features of old cerebral ischemia are associated with reduced physical HRQoL.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2020
DOI: 10.1161/STROKEAHA.119.028523
Abstract: Patient-centered care prioritizes patient beliefs and values towards wellbeing. We aimed to map functional status (modified Rankin Scale [mRS] scores) and health-related quality of life on the European Quality of Life 5-dimensional questionnaire (EQ-5D) to derive utility-weighted (UW) stroke outcome measures and test their statistical properties and construct validity. UW-mRS scores were derived using linear regression, with mRS as a discrete ordinal explanatory response variable in 8 large international acute stroke trials. Linear regression models were used to validate UW-mRS scores by assessing differences in mean UW-mRS scores between the treatment groups of each trial. To explore the variability in EQ-5D between in idual mRS categories, we generated receiver operator characteristic curves for EQ-5D to differentiate between sequential mRS categories and misclassification matrix to classify in idual patients into a matched mRS category based on the closest UW-mRS value to their observed in idual EQ-5D value. Among 22 946 acute stroke patients, derived UW-mRS across mRS scores 0 to 6 were 0.96, 0.83, 0.72, 0.54, 0.22, −0.18, and 0, respectively. Both UW-mRS and ordinal mRS scores captured ergent treatment effects across all 8 acute stroke trials. The s le sizes required to detect the treatment effects using UW-mRS scores as a continuous variable were almost half that required in trials for a binary cut point on the mRS. Area under receiver operator characteristic curves based on EQ-5D utility values varied from 0.66 to 0.81. Misclassification matrix showed moderate agreement between actual and matched mRS scores (kappa, 0.68 [95% CI, 0.67–0.68]). Medical strategies that target avoiding dependency may provide maximum benefit in terms of poststroke health-related quality of life. Despite variable differences with mRS scores, the UW-mRS provides efficiency gains as a smaller s le size is required to detect a treatment effect in acute stroke trials through use of continuous scores. URL: www.clinicaltrials.gov Unique identifiers: NCT00226096, NCT00716079, NCT01422616, NCT02162017, NCT00120003, NCT02123875. URL: ctri.nic.in Unique identifier: CTRI/2013/04/003557. URL: www.isrctn.com Unique identifier: ISRCTN89712435.
Publisher: S. Karger AG
Date: 05-09-2023
DOI: 10.1159/000526384
Abstract: The third INTEnsive care bundle with blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT3) is an international, multicenter, stepped-wedge (4 phases/3 steps) cluster randomized trial involving 110 hospitals in mainly low- and middle-income countries during 2017–2022. The aim is to determine the effectiveness of a goal-directed care bundle of intensive blood pressure (BP) lowering, glycemic control, antipyrexia, and anticoagulation reversal treatment versus usual standard of care, in patients with acute intracerebral hemorrhage (ICH). After a “usual care” period, hospitals were randomly allocated to implementing care-bundle protocols for control targets (systolic BP & #x3c mm Hg glucose 6.1–7.8/7.8–10.0 mmol/L according to diabetes mellitus status temperature ≤37.5°C normalization of anticoagulation). A s le size of 8,360 patients (mean 19 per phase per site) provides 90% power (α = 0.05) for a 5.6% absolute improvement in the primary outcome of scores on the modified Rankin scale at 6 months, analyzed by ordinal logistic regression. A detailed statistical analysis plan (SAP) was developed to prespecify the method of analysis for all outcomes and key variables collected in the trial. The primary analysis will use ordinal logistic regression adjusted for the stepped-wedge design. The SAP also includes planned sensitivity analyses, including covariate adjustments, missing data imputations, and subgroup analysis. This SAP allows transparent, verifiable, and prespecified analyses in consideration of the challenges in conducting the study during the COVID pandemic. It also avoids analysis bias arising from prior knowledge of the findings in determining the benefits and harms of a care bundle in acute ICH.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2020
DOI: 10.1161/STR.51.SUPPL_1.WP390
Abstract: Background and Aims: Epidemiological studies show significant variations in hypertension management within and between countries. The level of regional variation in early blood pressure (BP) management after acute stroke is uncertain. Methods: Data are from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), a partial-factorial, international randomized controlled trial (RCT) of thrombolysis-eligible acute ischemic stroke (AIS) patients with systolic BP (SBP mmHg) assigned to intensive (target SBP 130-140 mmHg) vs. guideline-recommended (SBP mmHg) treatment and INTERACT2, an international RCT of patients with spontaneous intracerebral hemorrhage (ICH) ( hours) with elevated SBP randomized to intensive (target SBP mmHg) or guideline-recommended (SBP mmHg) treatment. BP management was compared between five participating regions of these RCTs: west (Europe/Australia/US), China, other Asia (South Korea, Singapore, Thailand, Vietnam), India (India and Pakistan), and South America (Argentina, Chile, Brazil, Colombia). Results: There were 2196 AIS (38% women, mean age 67[12] years) and 2829 acute ICH (37% women, mean age 63[13] years) patients in these analyzes. Commonly used intravenous BP lowering agents are labetalol, nitroglycerin, and topical Nitrates in western countries mannitol, urapidil, and sodium nitroprusside in China nicardipine in other Asian countries and sodium nitroprusside and labetalol in South America. Western patients were more likely to receive BP lowering treatment in the first 24 hours and treated with multiple agents, and had larger magnitude of SBP reduction and greater SBP variability. BP control parameters over 2-7 days were comparable between regions. Conclusion: Regional variations in early BP management in acute stroke translated into differences in magnitude of SBP reduction and SBP variability in patients.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2020
DOI: 10.1161/STR.51.SUPPL_1.TMP15
Abstract: Purpose: We aimed to determine differences in demographics, management and outcomes between Asian and non-Asian participants with acute ischemic stroke (AIS) in the Enhanced Control of Hypertension and Thrombolysis Stroke study (ENCHANTED). Methods: ENCHANTED was a partial-factorial trial in thrombolysis-eligible AIS patients randomly assigned to: (i) low-dose (0.6mg/kg) or standard-dose (0.9mg/kg) alteplase and (ii) intensive (target systolic blood pressure [SBP] 130-140 mmHg) or guideline-recommended mmHg) BP management. Functional outcomes included death or disability (mRS 2-6), disability (mRS 3-5) and death key safety outcome was any intracranial hemorrhage (ICH). Results: Among 4562 patients (mean age 66.6 years, 37.8% female, 65.5% Asian) Asian patients were younger and less likely to have atrial fibrillation and hypercholesterolemia and taking fewer antihypertensive, warfarin, aspirin and statin therapy compared to non-Asians. They were also less likely to receive thromboembolic prophylaxis, be admitted to an acute stroke unit, be mobilized by therapist, and receive any rehabilitation over the first 7 days. Despite Asian patients having an increased risk of ICH (adjusted odds ratio 1.48, 95% confidence interval 1.22-1.8 P=0.0001), there were no significant differences compared to non-Asians for overall functional outcomes after adjustment for baseline imbalances. However, Asians had greater disability (1.48, 1.19-1.85 P=0.0005) but less deaths (0.38, 0.27-0.55 P .0001) after further adjustment for management differences. Conclusions: Compared to non-Asians, Asian patients were at increased risk of ICH and residual disability after thrombolysis treatment for AIS, suggesting the need to access more evidence-based care in acute management.
Publisher: Elsevier BV
Date: 11-2022
Publisher: Elsevier BV
Date: 08-2021
DOI: 10.1016/J.CLINEURO.2021.106796
Abstract: Uncertainty exists over the prognostic significance of low arterial oxygen saturation (SaO Post-hoc analyzes of HeadPoST, a pragmatic cluster-crossover randomized trial of lying flat versus sitting up head positioning in 11,093 patients (age ≥18 years) with acute stroke at 114 hospitals in 9 countries during 2015-2016. Associations of the lowest recorded SaO There was an inverse J-shaped association between SaO Any change in SaO HeadPoST is registered at ClinicalTrials.gov (NCT02162017).
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-07-2019
Abstract: The uptake of proven stroke treatments varies widely. We aimed to determine the association of evidence‐based processes of care for acute ischemic stroke ( AIS ) and clinical outcome of patients who participated in the HEADPOST (Head Positioning in Acute Stroke Trial), a multicenter cluster crossover trial of lying flat versus sitting up, head positioning in acute stroke. Use of 8 AIS processes of care were considered: reperfusion therapy in eligible patients acute stroke unit care antihypertensive, antiplatelet, statin, and anticoagulation for atrial fibrillation dysphagia assessment and physiotherapist review. Hierarchical, mixed, logistic regression models were performed to determine associations with good outcome (modified Rankin Scale scores 0–2) at 90 days, adjusted for patient and hospital variables. Among 9485 patients with AIS, implementation of all processes of care in eligible patients, or “defect‐free” care, was associated with improved outcome (odds ratio, 1.40 95% CI, 1.18–1.65) and better survival (odds ratio, 2.23 95% CI , 1.62–3.09). Defect‐free stroke care was also significantly associated with excellent outcome (modified Rankin Scale score 0–1) (odds ratio, 1.22 95% CI , 1.04–1.43). No hospital characteristic was independently predictive of outcome. Only 1445 (15%) of eligible patients with AIS received all processes of care, with significant regional variations in overall and in idual rates. Use of evidence‐based care is associated with improved clinical outcome in AIS . Strategies are required to address regional variation in the use of proven AIS treatments. URL : www.clinicaltrials.gov . Unique Identifier: NCT 02162017.
Publisher: SAGE Publications
Date: 24-03-2017
Abstract: There is evidence to indicate that the lying flat head position increases cerebral blood flow and oxygenation in patients with acute ischemic stroke, but how these physiological effects translate into clinical outcomes is uncertain. The Head Position in Stroke Trial aims to determine the comparative effectiveness of lying flat (0°) compared to sitting up (≥30°) head positioning, initiated within 24 h of hospital admission for patients with acute stroke. An international, pragmatic, cluster-randomized, crossover, open, blinded outcome assessed clinical trial. Each hospital with an established acute stroke unit (cluster) site was required to recruit up to 140 consecutive cases of acute stroke (one phase of head positioning before immediately crossing over to the other phase of head positioning), including both acute ischemic stroke and intracerebral hemorrhage, in each randomized head position as a ‘business as usual’ policy. To outline in detail the predetermined statistical analysis plan for the study. All accumulated data will be reviewed and formally assessed. Information regarding baseline characteristics of patients, their process of care and management will be outlined, and for each item, statistically relevant descriptive elements will be described. For the trial outcomes, the most appropriate statistical comparisons are described. A statistical analysis plan was developed that is transparent, verifiable, and predetermined before completion of data collection. We developed a predetermined statistical analysis plan for Head Position in Stroke Trial to avoid analysis bias arising from prior knowledge of the findings, in order to reliably quantify the benefits and harms of lying flat versus sitting up early after the onset of acute stroke. ClinicalTrials.gov identifier NCT02162017 ANZCTR identifier ACTRN12614000483651
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2019
Publisher: Elsevier BV
Date: 07-2023
Publisher: Elsevier BV
Date: 12-2020
Start Date: 2020
End Date: 2023
Funder: Medical Research Council
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