Predictors of early versus delayed neurological deterioration after thrombolysis for ischemic stroke: ENCHANTED study.

BACKGROUND AND PURPOSE: We aimed to determine predictors of early (END) and delayed neurological deterioration (DND) and their association with functional outcome in patients with acute ischemic stroke (AIS) who participated in the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). METHODS: END and DND were defined as scores of a ≥2 point increase on the National Institutes of Health Stroke Scale (NIHSS) or ≥1 point decrease on Glasgow coma scale, or death, from baseline to 24 hours and 24 hours to 72 hours, respectively. Multivariable logistic regression models were used to determine independent predictors of END and DND and their association with 90-day outcomes (dichotomous scores on the modified Rankin scale [mRS] of 2-6 vs 0-1 and 3-6 vs 0-2, and death). RESULTS: Of 4496 patients, 871 (19.4%) and 302 (8.4%) patients experienced END and DND, respectively. Higher baseline NIHSS score, older age, large artery occlusion due to significant atheroma, cardioembolic stroke subtype, hemorrhagic infarction and parenchymatous hematoma within 24 hours, were all independent predictors for both END (all P ≤0.01) and DND (all P ≤0.024). Moreover, higher baseline systolic blood pressure (BP) (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02-1.12), higher diastolic BP variability within 24 hours (OR 1.07, 95% CI 1.04-1.09), patients from Asia (OR 1.25, 95% CI 1.03-1.52) were the only independent predictors for END. However, Asian ethnicity was negatively associated with DND (OR 0.64, 95% CI 0.47-0.86). Hemorrhagic infarction and parenchymatous hematoma within 24 hours were the key predictor of END across all stroke subtypes. END and DND were all associated with a poor functional outcome at 90 days (all P<0.001). CONCLUSIONS: We identified overlapping and unique demographic and clinical predictors of END and DND after thrombolysis for acute ischemic stroke. Both END and DND predict unfavorable outcomes at 90 days.

Intensive Ambulance-Delivered Blood-Pressure Reduction in Hyperacute Stroke.

BACKGROUND: Treatment of acute stroke, before a distinction can be made between ischemic and hemorrhagic types, is challenging. Whether very early blood-pressure control in the ambulance improves outcomes among patients with undifferentiated acute stroke is uncertain. METHODS: We randomly assigned patients with suspected acute stroke that caused a motor deficit and with elevated systolic blood pressure (≥150 mm Hg), who were assessed in the ambulance within 2 hours after the onset of symptoms, to receive immediate treatment to lower the systolic blood pressure (target range, 130 to 140 mm Hg) (intervention group) or usual blood-pressure management (usual-care group). The primary efficacy outcome was functional status as assessed by the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days after randomization. The primary safety outcome was any serious adverse event. RESULTS: A total of 2404 patients (mean age, 70 years) in China underwent randomization and provided consent for the trial: 1205 in the intervention group and 1199 in the usual-care group. The median time between symptom onset and randomization was 61 minutes (interquartile range, 41 to 93), and the mean blood pressure at randomization was 178/98 mm Hg. Stroke was subsequently confirmed by imaging in 2240 patients, of whom 1041 (46.5%) had a hemorrhagic stroke. At the time of patients' arrival at the hospital, the mean systolic blood pressure in the intervention group was 158 mm Hg, as compared with 170 mm Hg in the usual-care group. Overall, there was no difference in functional outcome between the two groups (common odds ratio, 1.00; 95% confidence interval [CI], 0.87 to 1.15), and the incidence of serious adverse events was similar in the two groups. Prehospital reduction of blood pressure was associated with a decrease in the odds of a poor functional outcome among patients with hemorrhagic stroke (common odds ratio, 0.75; 95% CI, 0.60 to 0.92) but an increase among patients with cerebral ischemia (common odds ratio, 1.30; 95% CI, 1.06 to 1.60). CONCLUSIONS: In this trial, prehospital blood-pressure reduction did not improve functional outcomes in a cohort of patients with undifferentiated acute stroke, of whom 46.5% subsequently received a diagnosis of hemorrhagic stroke. (Funded by the National Health and Medical Research Council of Australia and others; INTERACT4 ClinicalTrials.gov number, NCT03790800; Chinese Trial Registry number, ChiCTR1900020534.).

Process evaluation and its application in clinical research of acupuncture: preliminary considerations. / è¿‡ç¨‹è¯„ä»·åŠå ¶åœ¨é’ˆåˆºä¸´åºŠç ”ç©¶ä¸­åº”ç”¨çš„æ€è€ƒä¸Žå»ºè®®.

As an important supplementary approach to randomized controlled trial, process evaluation(PE) aims to evaluate implementation of complex intervention and contextual factors associated with variation in outcomes, in order to explain the observed results in a comprehensive manner. However, PE has not been well applied in the clinical research of acupuncture. Based on existing literature, this paper summarized the main methodological frameworks of PE, as well as the status-quo of its application in acupuncture research. Meanwhile, it explored the research perspectives and implementation factors that were potentially relevant to PE in parallel with acupuncture trials. In addition, the paper put forward preliminary considerations on key contents corresponding to each step during the development of PE for acupuncture trials, in order to provide useful reference and innovative pathway for future studies that strive for comprehensive evaluation of acupuncture's effect.

Implementation of low-intensity thrombolysis monitoring care in routine practice: process evaluation of the Optimal Post rtPA-IV Monitoring in Acute Ischemic Stroke (OPTIMISTmain) study in the United States.

INTRODUCTION: The ongoing OPTIMISTmain study, an international, multicenter, stepped-wedge cluster randomized trial, aims to determine effectiveness and safety of low-intensity versus standard monitoring in thrombolysis-treated patients with mild-to-moderate acute ischemic stroke (AIS). An embedded process evaluation explored integration and impact of the intervention on care processes at participating US sites. METHODS: A mixed-methods approach with quantitative and qualitative data were collected between September 2021 and November 2022. Implementer surveys were undertaken at pre- and post-intervention phases to understand the perceptions of low-intensity monitoring strategy. A sample of stroke care nurses were invited to participate in semi-structured interviews at an early stage of post-intervention. Qualitative data were analyzed deductively using the normalization process theory; quantitative data were tabulated. RESULTS: Interviews with 21 nurses at 8 hospitals have shown low-intensity monitoring was well accepted, as there were less time constraints and reduced workload for each patient. There were initial safety concerns over missing deteriorating patients and difficulties in changing established routines. Proper training, education, and communication, and changing the habits and culture of care, were key elements to successfully adopting the new monitoring care into routine practice. Similar results were found in the post-intervention survey (42 nurses from 13 hospitals). Nurses reported time being freed up to provide patient education (56%), daily living care (50%), early mobilization (26%), mood/cognition assessment (44%), and other aspects (i.e. communication, family support). CONCLUSIONS: Low-intensity monitoring for patients with mild-to-moderate acute ischemic stroke, facilitated by appropriate education and organizational support, appears feasible and acceptable at US hospitals.

Trends of mean systolic and diastolic blood pressure among adults in Shenzhen, China, 1997-2018: findings from three rounds of the population-based survey.

OBJECTIVE: To quantify the trends in systolic and diastolic blood pressure (BP) among adults in Shenzhen from 1997 to 2018. DESIGN: Cross-sectional study. SETTINGS: The data were collected from all districts in Shenzhen, China in the years of 1997, 2009 and 2018 by multistage cluster sampling procedure. PARTICIPANTS: Participants were residents aged 18-69 years in Shenzhen, China. A total of 26 621 people were included: 8266 people in 1997, 8599 people in 2009 and 9756 people in 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: All participants were surveyed about their sociodemographic and lifestyle information. BP was measured by trained physicians using a mercury sphygmomanometer. Hypertension was defined as systolic BP of at least 140 mm Hg and diastolic BP of at least 90 mm Hg, self-reported use of antihypertensive medications or both. Hypertension control was defined as systolic BP values of less than 140 mm Hg and diastolic BP values of less than 90 mm Hg. RESULT: Age-adjusted mean systolic BP increased from 117±16 mm Hg to 123±15 mm Hg (p<0.001) in males, and from 113±18 mm Hg to 115±16 mm Hg (p<0.001) in females from 1997 to 2018. Diastolic BP among males increased from 75 mm Hg (SD=11) to 79 mm Hg (SD=11) and increased from 71 mm Hg (SD=10) to 73 mm Hg (SD=10) among females between 1997 and 2018 (p<0.001). Rate of hypertension rose rapidly from 17.71% (95% CI: 16.60% to 18.90%) in 2009 to 24.01% (95% CI: 22.84% to 25.22%) in 2018 among males (p<0.001), whereas the prevalence among females remained stable at around 13.5% (p=0.98). Both awareness and treatment rates of hypertension among males and females showed a decreased trend between 2009 and 2018, while no significant changes were observed for control rates. CONCLUSIONS: The mean systolic BP and diastolic BP among adults in Shenzhen increased from 1997 to 2018, and no improvements in hypertension awareness, treatment and control rates were found.

Intensive blood pressure lowering and renal function in ischemic stroke patients: secondary analysis of ENCHANTED trial.

BACKGROUND: Renal failure is a major safety concern of intensive systolic blood pressure (SBP) lowering. We aimed to determine the effect of this treatment on early change in renal function in participants of the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). METHODS: Post-hoc analysis of the ENCHANTED BP-arm in which thrombolyzed patients with acute ischemic stroke (AIS) were randomized to intensive (target 130-140 mm Hg within 1 h) or guideline-recommended (target <180 mm Hg) management within 6 h of symptom onset. Primary outcome is early change in renal function, defined by a difference in estimated glomerular filtration rate (∆eGFR = 24 h - baseline eGFR), analyzed using linear regression with adjustment for clinical variables. Key SBP parameters were attained (mean), variability (standard deviation [SD]) and magnitude of reduction within 24 h. RESULTS: Of 2151 participants (mean age 66.9 years; 38% female) included with available baseline eGFR, there were significant differences in attained 144.3±10.2 vs 149.8±12.0 [5.5 mm Hg]; P<0.0001), variation (15.1±5.4 vs 14.0±5.6 mm Hg; P<0.0001) and magnitude of reduction (44.6±16.2 vs 38.7±17.6 mm Hg; P<0.0001) in SBP within 24 hours. 1718 (79.9%) participants with complete follow-up eGFR were included in the primary analysis, and there was no significant difference in ∆eGFR (adjusted mean difference -1.10, 95% confidence interval [CI] -3.14 to -0.94; P=0.29) between the intensive and guideline groups, respectively. The neutral effect on ∆eGFR was consistent in patients with different baseline eGFR stages and in sensitivity analysis after multiple imputation for missing follow-up eGFR. SBP variability was significantly associated with decreasing ∆eGFR (per 5 mm Hg increase by category: adjusted mean difference -1.35, 95%CI -2.43 to -0.28; P for trend=0.01). CONCLUSIONS: Intensive SBP lowering with a target of 130-140 mm Hg had no impact on early renal function in thrombolyzed AIS patients. Wide SBP variability was associated with a larger decline in eGFR. CLINICAL TRIAL REGISTRATION: ENCHANTED is registered at ClinicalTrials.gov (NCT01422616).

Optimum Baseline Clinical Severity Scale Cut Points for Prognosticating Intracerebral Hemorrhage: INTERACT Studies.

BACKGROUND: The optimal cut point of baseline National Institutes of Health Stroke Scale (NIHSS) and Glasgow Coma Scale scores for prognosticating acute intracerebral hemorrhage (ICH) is unknown. METHODS: Secondary analyses of participant data are from the INTERACT (Intensive Blood Pressure Reduction in Acute Intracerebral Hemorrhage Trials) 1 and 2 studies. Receiver operating characteristic analyses were used to compare the predictive performance of baseline NIHSS and Glasgow Coma Scale scores, ICH score, and max-ICH score. Optimal cut points for predicting 90-day clinical outcomes (death or major disability [defined as modified Rankin Scale scores 3-6], major disability [defined as modified Rankin Scale scores 3-5], and death alone) were determined using the Youden index. Logistic regression models were adjusted for age, sex, hematoma volume, and other known risk factors for poor prognosis. We validated our findings in the INTERACT1 database. RESULTS: There were 2829 INTERACT2 patients (age, 63.5±12.9 years; male, 62.9%; ICH volume, 10.96 [5.77-19.49] mL) included in the main analyses. The baseline NIHSS score (area under the curve, 0.796) had better prognostic utility for predicting death or major disability than the Glasgow Coma Scale score (area under the curve, 0.650) and ICH score (area under the curve, 0.674) and was comparable to max-ICH score (area under the curve, 0.789). Similar findings were observed when assessing the outcome of major disability. A cut point of 10 on baseline NIHSS optimally (sensitivity, 77.5%; specificity, 69.2%) predicted death or major disability (adjusted odds ratio, 4.50 [95% CI, 3.60-5.63]). The baseline NIHSS cut points that optimally predicted major disability and death alone were 10 and 12, respectively. The predictive effect of NIHSS≥10 for poor functional outcomes was consistent in all subgroups including age and baseline hematoma volume. Results were consistent when analyzed in the independent INTERACT1 validation database. CONCLUSIONS: In patients with mild-to-moderate ICH, a baseline NIHSS score of ≥10 was optimal for predicting poor outcomes at 90 days. Prediction based on baseline NIHSS is better than baseline Glasgow Coma Scale score. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT00226096 and NCT00716079.

Update on the INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4): progress and baseline features in 2053 participants.

BACKGROUND AND AIMS: Uncertainty persists over the effects of blood pressure (BP) lowering in acute stroke. The INTEnsive ambulance-delivered blood pressure Reduction in hyper-Acute stroke Trial (INTERACT4) aims to determine efficacy and safety of hyperacute intensive BP lowering in patients with suspected acute stroke. Given concerns over the safety of this treatment in the pre-hospital setting, particularly in relation to patients with intracerebral hemorrhage, we provide an update on progress of the study and profile of participants to date. METHODS: INTERACT4 is an ongoing multicentre, ambulance-delivered, randomized, open-label, blinded endpoint trial of pre-hospital BP lowering in patients with suspected acute stroke and elevated BP in China. Patients are randomized via a mobile phone digital system to intensive (target systolic BP [SBP] <140mmHg within 30 min) or guideline-recommended BP management. Primary outcome is an ordinal analysis of the full range of scores on the modified Rankin scale scores at 90 days. RESULTS: Between March 2020 and April 2023, 2053 patients (mean age 70 years, female 39%) were recruited with a mean BP 178/98 mmHg in whom 45% have a diagnosis of primary intracerebral hemorrhage upon arrival at hospital. At the time of presentation to hospital, the mean SBP was 160 and 170mmHg in the intensive and control groups (Δ10 mmHg), respectively. The independent data and safety monitoring board has not identified any safety concerns and recommended continuation of the trial. The sample size was reduced from 3116 to 2320 after meetings in August 2022 as the stroke mimic rate was persistently lower than initially estimated (6% vs 30%). The study is expected to be completed in late 2023 and the results announced in May 2024. CONCLUSIONS: INTERACT4 is on track to provide reliable evidence of the effectiveness of ambulance-delivered intensive BP lowering in patients with suspected acute stroke. TRIAL REGISTRATION: ClinicalTrials.gov NCT03790800 ; registered on 2 January 2019. Chinese Trial Registry ChCTR1900020534 , registered on 7 January 2019.

The main Optimal Post rTpa-Iv Monitoring in Ischemic Stroke Trial (OPTIMISTmain): protocol for a pragmatic, stepped wedge, cluster randomized controlled trial.

Introduction Careful monitoring of patients who receive intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) is resource-intensive, and potentially less relevant in those with mild degrees of neurological impairment who are at low-risk of symptomatic intracerebral hemorrhage (sICH) and other complications. \ Methods OPTIMISTmain is an international, multicenter, prospective, stepped wedge, cluster randomized, blinded outcome assessed trial aims to determine whether a less-intensity monitoring protocol is at least as effective, safe and efficient as standard post-IVT monitoring in patients with mild deficits post-AIS. Clinically-stable adult patients with mild AIS (defined by a NIHSS <10) who do not require intensive care within 2 hours post-IVT are recruited at hospitals in Australia, Chile, China, Malaysia, Mexico, UK, US and Vietnam. An average of 15 patients recruited per period (overall 60 patient participants) at 120 sites for a total of 7200 IVT-treated AIS patients will provide 90% power (one-sided α 0.025). The initiation of eligible hospitals is based on a rolling process whenever ready, stratified by country. Hospitals are randomly allocated using permuted blocks into 3 sequences of implementation, stratified by country and the projected number of patients to be recruited over 12 months. These sequences have four periods that dictate the order in which they are to switch from control (usual care) to intervention (implementation of low intensity monitoring protocol) to different clusters of patients in a stepped manner. Compared to standard monitoring, the low-intensity monitoring protocol includes assessments of neurological and vital signs every 15 minutes for 2 hours, 2 hourly (versus every 30 minutes) for 8 hours, and 4 hourly (versus every 1 hour) until 24 hours, post-IVT. The primary outcome measure is functional recovery, defined by the modified Rankin scale (mRS) at 90 days, a seven-point ordinal scale (0 [no residual symptom] to 6 [death]). Secondary outcomes include death or dependency, length of hospital stay, and health-related quality of life, sICH and serious adverse events. Conclusion OPTIMISTmain will provide Level I evidence for the safety and effectiveness of a low-intensity post-IVT monitoring protocol in patients with mild severity of AIS.

The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3): an international, stepped wedge cluster randomised controlled trial.

BACKGROUND: Early control of elevated blood pressure is the most promising treatment for acute intracerebral haemorrhage. We aimed to establish whether implementing a goal-directed care bundle incorporating protocols for early intensive blood pressure lowering and management algorithms for hyperglycaemia, pyrexia, and abnormal anticoagulation, implemented in a hospital setting, could improve outcomes for patients with acute spontaneous intracerebral haemorrhage. METHODS: We performed a pragmatic, international, multicentre, blinded endpoint, stepped wedge cluster randomised controlled trial at hospitals in nine low-income and middle-income countries (Brazil, China, India, Mexico, Nigeria, Pakistan, Peru, Sri Lanka, and Viet Nam) and one high-income country (Chile). Hospitals were eligible if they had no or inconsistent relevant, disease-specific protocols, and were willing to implement the care bundle to consecutive patients (aged ≥18 years) with imaging-confirmed spontaneous intracerebral haemorrhage presenting within 6 h of the onset of symptoms, had a local champion, and could provide the required study data. Hospitals were centrally randomly allocated using permuted blocks to three sequences of implementation, stratified by country and the projected number of patients to be recruited over the 12 months of the study period. These sequences had four periods that dictated the order in which the hospitals were to switch from the control usual care procedure to the intervention implementation of the care bundle procedure to different clusters of patients in a stepped manner. To avoid contamination, details of the intervention, sequence, and allocation periods were concealed from sites until they had completed the usual care control periods. The care bundle protocol included the early intensive lowering of systolic blood pressure (target <140 mm Hg), strict glucose control (target 6·1-7·8 mmol/L in those without diabetes and 7·8-10·0 mmol/L in those with diabetes), antipyrexia treatment (target body temperature ≤37·5°C), and rapid reversal of warfarin-related anticoagulation (target international normalised ratio <1·5) within 1 h of treatment, in patients where these variables were abnormal. Analyses were performed according to a modified intention-to-treat population with available outcome data (ie, excluding sites that withdrew during the study). The primary outcome was functional recovery, measured with the modified Rankin scale (mRS; range 0 [no symptoms] to 6 [death]) at 6 months by masked research staff, analysed using proportional ordinal logistic regression to assess the distribution in scores on the mRS, with adjustments for cluster (hospital site), group assignment of cluster per period, and time (6-month periods from Dec 12, 2017). This trial is registered at Clinicaltrials.gov (NCT03209258) and the Chinese Clinical Trial Registry (ChiCTR-IOC-17011787) and is completed. FINDINGS: Between May 27, 2017, and July 8, 2021, 206 hospitals were assessed for eligibility, of which 144 hospitals in ten countries agreed to join and were randomly assigned in the trial, but 22 hospitals withdrew before starting to enrol patients and another hospital was withdrawn and their data on enrolled patients was deleted because regulatory approval was not obtained. Between Dec 12, 2017, and Dec 31, 2021, 10 857 patients were screened but 3821 were excluded. Overall, the modified intention-to-treat population included 7036 patients enrolled at 121 hospitals, with 3221 assigned to the care bundle group and 3815 to the usual care group, with primary outcome data available in 2892 patients in the care bundle group and 3363 patients in the usual care group. The likelihood of a poor functional outcome was lower in the care bundle group (common odds ratio 0·86; 95% CI 0·76-0·97; p=0·015). The favourable shift in mRS scores in the care bundle group was generally consistent across a range of sensitivity analyses that included additional adjustments for country and patient variables (0·84; 0·73-0·97; p=0·017), and with different approaches to the use of multiple imputations for missing data. Patients in the care bundle group had fewer serious adverse events than those in the usual care group (16·0% vs 20·1%; p=0·0098). INTERPRETATION: Implementation of a care bundle protocol for intensive blood pressure lowering and other management algorithms for physiological control within several hours of the onset of symptoms resulted in improved functional outcome for patients with acute intracerebral haemorrhage. Hospitals should incorporate this approach into clinical practice as part of active management for this serious condition. FUNDING: Joint Global Health Trials scheme from the Department of Health and Social Care, the Foreign, Commonwealth & Development Office, and the Medical Research Council and Wellcome Trust; West China Hospital; the National Health and Medical Research Council of Australia; Sichuan Credit Pharmaceutic and Takeda China.

Incidence and outcomes for stroke in Ulaanbaatar, Mongolia, during 2019-21: a prospective population-based study.

BACKGROUND: In the absence of reliable data to quantify the burden of stroke, we aimed to determine the incidence and outcome of stroke through the conduct of a prospective population-based study in Ulaanbaatar, Mongolia, during 2019-21. METHODS: All cases of stroke were identified through surveillance of multiple overlapping sources of hospitalised, ambulatory, and deceased individuals, using standardised diagnostic criteria in adult (aged ≥16 years) residents of the six urban districts of Ulaanbaatar, Mongolia (population person-years, N=1 896 965) between Jan 1, 2019, and Dec 31, 2020. Data on sociodemography, medical history, and management were collected. Crude and standardised incidence were calculated for first-ever stroke and its major pathological subtypes, and reported with 95% CIs. Outcomes were 28-day case fatality ratios and functional recovery on the modified Rankin scale at 90 days and 1 year. FINDINGS: 3803 strokes in 3738 patients were identified, of which 2962 were first-ever incident cases (mean age 59 years [SD 13], 1161 [39·2%] females). Annual incidence of first-ever stroke (per 100 000) was 156·1 (95% CI 150·5-161·8) on a crude basis, 171·6 (157·5-185·6) when age-adjusted to the Mongolian population, and 140·3 (136·7-143·9) when age-adjusted to the world population. World-adjusted incidence of pathological subtypes were 66·6 (95% CI 64·8-68·3) for ischaemic stroke, 54·5 (53·0-56·1) for intracerebral haemorrhage, and 18·7 (18·3-19·1) for subarachnoid haemorrhage. Men were twice as likely to suffer ischaemic stroke and intracerebral haemorrhage as women, but the risks were similar for subarachnoid haemorrhage; these patterns were consistent across age-groups. The predominant risk factors were hypertension seen in 1363 (63·1%) of 2161, smoking in 596 (26·8%) of 2220, regular alcohol consumption in 533 (24·0%) of 2220, obesity in 342 (16·1%) of 2125, and diabetes in 282 (12·7%) of 2220. There was little use (0·9%) of thrombolysis for acute ischaemic stroke, partly due to delays in presentation after the onset of symptoms (median 16·0 h [IQR 3·0-48·0]). The 28-day case-fatality rate was 36·1% (95% CI 34·3-37·9) overall, and 14·8% (12·8-16·7) for ischaemic stroke, 52·9% (49·9-55·8) for intracerebral haemorrhage, and 54·3% (49·4-59·1) for subarachnoid haemorrhage. Corresponding figures for poor functional outcome at 1-year, defined by scores of 3-6 for death or dependency on the mRS, were 61·6% (95% CI 59·8-63·4), 47·5% (44·7-50·3), 77·0% (74·5-79·5), and 61·8% (57·0-66·5), respectively. INTERPRETATION: The urban population of Ulaanbaatar, Mongolia, has a high incidence of stroke, particularly for intracerebral haemorrhage and subarachnoid haemorrhage, from which half of patients die within 1 month and more than two-thirds are either dead or dependent at 90 days. Although the overall incidence of stroke is similar to other countries, it occurs at a mean age of 60 years, which is at least 10 years younger than in high-income countries. These epidemiological data can inform the implementation of future programmes and scale-up activities for the primary and secondary prevention of stroke, and in the organisation of systems of care. FUNDING: Science and Technology Foundation of the Ministry of Education, Culture, and Science of Mongolia and The George Institute for Global Health.

Effects of intensive blood pressure lowering on cerebral ischaemia in thrombolysed patients: insights from the ENCHANTED trial.

Background: Intensive blood pressure lowering may adversely affect evolving cerebral ischaemia. We aimed to determine whether intensive blood pressure lowering altered the size of cerebral infarction in the 2196 patients who participated in the Enhanced Control of Hypertension and Thrombolysis Stroke Study, an international randomised controlled trial of intensive (systolic target 130-140 mm Hg within 1 h; maintained for 72 h) or guideline-recommended (systolic target <180 mm Hg) blood pressure management in patients with hypertension (systolic blood pressure >150 mm Hg) after thrombolysis treatment for acute ischaemic stroke between March 3, 2012 and April 30, 2018. Methods: All available brain imaging were analysed centrally by expert readers. Log-linear regression was used to determine the effects of intensive blood pressure lowering on the size of cerebral infarction, with adjustment for potential confounders. The primary analysis pertained to follow-up computerised tomography (CT) scans done between 24 and 36 h. Sensitivity analysis were undertaken in patients with only a follow-up magnetic resonance imaging (MRI) and either MRI or CT at 24-36 h, and in patients with any brain imaging done at any time during follow-up. This trial is registered with ClinicalTrials.gov, number NCT01422616. Findings: There were 1477 (67.3%) patients (mean age 67.7 [12.1] y; male 60%, Asian 65%) with available follow-up brain imaging for analysis, including 635 patients with a CT done at 24-36 h. Mean achieved systolic blood pressures over 1-24 h were 141 mm Hg and 149 mm Hg in the intensive group and guideline group, respectively. There was no effect of intensive blood pressure lowering on the median size (ml) of cerebral infarction on follow-up CT at 24-36 h (0.3 [IQR 0.0-16.6] in the intensive group and 0.9 [0.0-12.5] in the guideline group; log Δmean -0.17, 95% CI -0.78 to 0.43). The results were consistent in sensitivity and subgroup analyses. Interpretation: Intensive blood pressure lowering treatment to a systolic target <140 mm Hg within several hours after the onset of symptoms may not increase the size of cerebral infarction in patients who receive thrombolysis treatment for acute ischaemic stroke of mild to moderate neurological severity. Funding: National Health and Medical Research Council of Australia; UK Stroke Association; UK Dementia Research Institute; Ministry of Health and the National Council for Scientific and Technological Development of Brazil; Ministry for Health, Welfare, and Family Affairs of South Korea; Takeda.

Increasing burden of stroke in China: A systematic review and meta-analysis of prevalence, incidence, mortality, and case fatality.

BACKGROUND: 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. AIMS: To identify high-quality epidemiological studies for quantifying the prevalence, incidence, mortality, and case fatality for stroke in China. METHODS: 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. RESULTS: 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, I2 = 100%, p < 0.001), and case fatality 35.8% (26.1% to 46.1%, I2 = 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. CONCLUSION: 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.

Statistical Analysis Plan for the INTEnsive Care Bundle with Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial: A Stepped-Wedge Cluster Randomized Controlled Trial.

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 <140 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 sample 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.

Sensitivity and specificity of 5 min cognitive screening tests in patients with acute coronary syndrome.

AIMS: This study aimed to determine the sensitivity and specificity of the National Institute of Neurological Disorders and Stroke (NINDS) and the Canadian Stroke Network (CSN) brief (5 min) screen composed of three items of the Montreal Cognitive Assessment (MoCA), in acute coronary syndrome (ACS) patients during hospital admission, relative to the full MoCA and potential alternative combinations of other items. METHODS AND RESULTS: Participants were consecutively recruited during ACS admission and administered the MoCA before discharge. The three NINDS-CSN screen items were extracted, collated and compared to the full MoCA. Receiver operator characteristic (ROC) curves were created to determine the sensitivity, specificity, and appropriate cut-off scores of the screens. The mean age of the sample (n = 81) was 63.49 [standard deviation (SD) 10.85] years and 49.4% screened positive for cognitive impairment. The NINDS-CSN mean score was 9.22 (SD 2.09 of the potential range 0-12). Area under the ROC (AUC) indicated high accuracy levels for screening for cognitive impairment (AUC = 0.89, P < 0.01, 95% confidence interval 0.82, 0.96) with none of the alternative combination screens performing better on both sensitivity and specificity. A cut-off score of ≤10 on the NINDS-CSN protocol provided 83% sensitivity and 80% specificity for classifying cognitive impairment. CONCLUSION: The NINDS-CSN protocol presents an accurate, feasible screen for cognitive impairment in patients following ACS for use at the bedside and potentially also for telephone screens. Diagnostic accuracy should be confirmed using a neurocognitive battery.

Cost-Effectiveness of Low-Dose Compared to Standard-Dose Alteplase for Acute Ischemic Stroke in China: A Within-Trial Economic Evaluation of the ENCHANTED Study.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Process evaluation of complex interventions in non-communicable and neglected tropical diseases in low- and middle-income countries: a scoping review.

OBJECTIVES: The aim of this review is to map out the use of process evaluation (PE) in complex interventions that address non-communicable diseases (NCDs) and neglected tropical diseases (NTDs) to identify gaps in the design and conduct, as well as strengths, limitations and implications, of this type of research in low- and middle-income countries (LMICs). DESIGN: Scoping review of PE studies of complex interventions implemented in LMICs. Six databases were searched focused on studies published since 2008. DATA SOURCES: Embase, PubMed, EbscoHost, Web of Science (WOS), Virtual Health Library (VHL) Regional Portal and Global Index Medicus: Regional Indexes AIM (AFRO), LILACS (AMRO/PAHO), IMEMR (EMRO), IMSEAR (SEARO), WPRIM (WPRO) Global Index Regional Indexes, MEDLINE, SciELO. ELIGIBILITY CRITERIA: Studies conducted in LMICs on PEs of randomised controlled trials (RCTs) and non-RCTs published between January 2008 and January 2020. Other criteria were studies of interventions for people at risk or having physical and mental NCDs, and/or NTDs, and/or their healthcare providers and/or others related to achieve better health for these two disease groups. Studies were excluded if they were not reported in English or Spanish or Portuguese or French, not peer-reviewed articles, not empirical research and not human research. DATA EXTRACTION AND SYNTHESIS: Data extracted to be evaluated were: available evidence in the utilisation of PE in the areas of NCDs and NTDs, including frameworks and theories used; methods applied to conduct PEs; and in a subsample, the barriers and facilitators to implement complex interventions identified through the PE. Variables were extracted and categorised. The information was synthesised through quantitative analysis by reporting frequencies and percentages. Qualitative analysis was also performed to understand facilitators and barriers presented in these studies. The implications for PEs, and how the information from the PE was used by researchers or other stakeholders were also assessed in this approach. RESULTS: 303 studies were identified, 79% were for NCDs, 12% used the label 'PE', 27% described a theory or framework for the PE, and 42% used mixed methods to analyse their findings. Acceptability, barriers and facilitators to implement the interventions, experiences and perceptions, and feasibility were the outcomes most frequently evaluated as part of the PEs. Barriers and facilitators themes identified were contextual factors, health system factors, human resources, attitudes and policy factors. CONCLUSIONS: PEs in NCDs and NTDs are used in LMICs with a wide variety of methods. This review identified many PEs that were not labelled by the authors as such, as well as a limited application of PE-related theories and frameworks, and heterogeneous reporting of this type of study.

The value of process evaluation for public health interventions: field-case studies for non-communicable disease prevention and management in five countries.

Complex interventions are needed to effectively tackle non-communicable diseases. However, complex interventions can contain a mix of effective and ineffective actions. Process evaluation (PE) in public health research is of great value as it could clarify the mechanisms and contextual factors associ-ated with variation in the outcomes, better identify effective components, and inform adaptation of the intervention. The aim of this paper is to demonstrate the value of PE through five case studies that span the research cycle. The interven-tions include using digital health, salt reduction strategies, use of fixed dose combinations, and task shifting. Insights of the methods used, and the implications of the PE findings to the project, were discussed. PE of complex interventions can refute or confirm the hypothesized mechanisms of action, thereby enabling intervention refinement, and identifying implementation strategies that can address local contextual needs, so as to improve service delivery and public health outcomes.

Antithrombotics prescription and adherence among stroke survivors: A systematic review and meta-analysis.

OBJECTIVES: We aimed to investigate the prescription of antithrombotic drugs (including anticoagulants and antiplatelets) and medication adherence after stroke. METHODS: We performed a systematic literature search across MEDLINE and Embase, from January 1, 2015, to February 17, 2022, to identify studies reporting antithrombotic medications (anticoagulants and antiplatelets) post stroke. Two people independently identified reports to include, extracted data, and assessed the quality of included studies according to the Newcastle-Ottawa scale. Where possible, data were pooled using random-effects meta-analysis. RESULTS: We included 453,625 stroke patients from 46 studies. The pooled proportion of prescribed antiplatelets and anticoagulants among patients with atrial fibrillation (AF) was 62% (95% CI: 57%-68%), and 68% (95% CI: 58%-79%), respectively. The pooled proportion of patients who were treated according to the recommendation of guidelines of antithrombotic medications from four studies was 67% (95% CI: 41%-93%). It was reported that 11% (95% CI: 2%-19%) of patients did not receive antithrombotic medications. Good adherence to antiplatelet, anticoagulant, and antithrombotic medications was 78% (95% CI: 67%-89%), 71% (95% CI: 57%-84%), and 73% (95% CI: 59%-86%), respectively. CONCLUSION: In conclusion, we found that less than 70% of patients were prescribed and treated according to the recommended guidelines of antithrombotic medications, and good adherence to antithrombotic medications is only 73%. Prescription rate and good adherence to antithrombotic medications still need to be improved among stroke survivors.