| 71. |
- Mead, Gillian Elizabeth, et al.
(författare)
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Update to the FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke : statistical analysis plan for the trials and for the individual patient data meta-analysis
- 2020
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Ingår i: Trials. - : Springer Nature. - 1745-6215. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThree large trials of fluoxetine for stroke recovery (FOCUS (fluoxetine or control under supervision), AFFINITY (the Assessment oF FluoxetINe In sTroke recovery) and EFFECTS (Efficacy oF Fluoxetine-a randomisEd Controlled Trial in Stroke)) have been collaboratively designed with the same basic protocol to facilitate an individual patient data analysis (IPDM). The statistical analysis plan for the three individual trials has already been reported in Trials, including a brief description of the IPDM. In this protocol, we describe in detail how we will perform the IPDM.Methods/designData from EFFECTS and AFFINITY will be transferred securely to the FOCUS statistician, who will perform a one-stage IPDM and a two-stage IPDM. For the one-stage IPDM, data will be combined into a single data set and the same analyses performed as described for the individual trials. For the two-stage IPDM, the results for the three individual trials will be combined using fixed effects meta-analyses.The primary and secondary outcome domains for the IPDM are the same as for individual trials. We will also perform analyses according to several subgroups including country of recruitment, ethnicity and trial. We will also explore the effects of fluoxetine on our primary and secondary outcomes in subgroups defined by combinations of characteristics.We also describe additional research questions that will be addressed using the combined data set, and published subsequently, including predictors of important post-stroke problems such as seizures, low mood and bone fractures.DiscussionAn IPDM of our three large trials of fluoxetine for stroke recovery will allow us to provide the most precise estimates of any risks and benefits of fluoxetine vs placebo, to detect reliably a smaller overall effect size than those detectable by the individual trials, to better determine the effects of fluoxetine vs placebo in subgroups of patients and outcomes and to broaden the generalisability of the results. Also, we may identify differences in treatment effects between studies.Trial registrationFOCUS: ISRCTN ISRCTN83290762. Registered on 23 May 2012. EudraCT 2011-005616-29. Registered on 3 February 2012.AFFINITY: Australian New Zealand Clinical Trials Registry ACTRN12611000774921. Registered on 22 July 2011.EFFECTS: ISRCTN ISRCTN13020412. Registered on 19 December 2014. ClinicalTrials.gov NCT02683213. Registered on 2 February 2016. EudraCT 2011-006130-16. Registered on 8 August 2014.
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| 72. |
- Mead, Gillian, et al.
(författare)
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The FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke : a study protocol for three multicentre randomised controlled trials.
- 2015
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Several small trials have suggested that fluoxetine improves neurological recovery from stroke. FOCUS, AFFINITY and EFFECTS are a family of investigator-led, multicentre, parallel group, randomised, placebo-controlled trials that aim to determine whether routine administration of fluoxetine (20 mg daily) for 6 months after acute stroke improves patients' functional outcome.METHODS/DESIGN: The three trial investigator teams have collaboratively developed a core protocol. Minor variations have been tailored to the national setting in the UK (FOCUS), Australia and New Zealand (AFFINITY) and Sweden (EFFECTS). Each trial is run and funded independently and will report its own results. A prospectively planned individual patient data meta-analysis of all three trials will subsequently provide the most precise estimate of the overall effect of fluoxetine after stroke and establish whether any effects differ between trials and subgroups of patients. The trials include patients ≥18 years old with a clinical diagnosis of stroke, persisting focal neurological deficits at randomisation between 2 and 15 days after stroke onset. Patients are randomised centrally via web-based randomisation systems using a common minimisation algorithm. Patients are allocated fluoxetine 20 mg once daily or matching placebo capsules for 6 months. Our primary outcome measure is the modified Rankin scale (mRS) at 6 months. Secondary outcomes include the Stroke Impact Scale, EuroQol (EQ5D-5 L), the vitality subscale of the Short-Form 36, diagnosis of depression, adherence to medication, adverse events and resource use. Outcomes are collected at 6 and 12 months. The methods of collecting these data are tailored to the national setting. If FOCUS, AFFINITY and EFFECTS combined enrol 6000 participants as planned, they would have 90 % power (alpha 5 %) to detect a common odds ratio of 1.16, equivalent to a 3.7 % absolute difference in percentage with mRS 0-2 (44.0 % to 47.7 %). This is based on an ordinal analysis of mRS adjusted for baseline variables included in the minimisation algorithm.DISCUSSION: If fluoxetine is safe and effective in promoting functional recovery, it could be rapidly, widely and affordably implemented in routine clinical practice and reduce the burden of disability due to stroke.TRIAL REGISTRATION:FOCUS: ISRCTN83290762 (23/05/2012), AFFINITY: ACTRN12611000774921 (22/07/2011).EFFECTS: ISRCTN13020412 (19/12/2014).
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| 73. |
- Murphy, Robert, et al.
(författare)
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Variations in the prevalence of atrial fibrillation, and in the strength of its association with ischemic stroke, in countries with different income levels: INTERSTROKE case-control study
- 2024
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Ingår i: INTERNATIONAL JOURNAL OF STROKE. - 1747-4930 .- 1747-4949. ; 19:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: The contribution of atrial fibrillation (AF) to the etiology and burden of stroke may vary by country income level.Aims: We examined differences in the prevalence of AF and described variations in the magnitude of the association between AF and ischemic stroke by country income level.Methods: In the INTERSTROKE case-control study, participants with acute first ischemic stroke were recruited across 32 countries. We included 10,363 ischemic stroke cases and 10,333 community or hospital controls who were matched for age, sex, and center. Participants were grouped into high-income (HIC), upper-middle-income (subdivided into two groups-UMIC-1 and UMIC-2), and lower-middle-income (LMIC) countries, based on gross national income. We evaluated the risk factors for AF overall and by country income level, and evaluated the association of AF with ischemic stroke.Results: AF was documented in 11.9% (n = 1235) of cases and 3.2% (n = 328) of controls. Compared to HIC, the prevalence of AF was significantly lower in UMIC-2 (aOR 0.35, 95% CI 0.29-0.41) and LMIC (aOR 0.50, 95% CI 0.41-0.60) on multivariable analysis. Hypertension, female sex, valvular heart disease, and alcohol intake were stronger risk factors for AF in lower-income countries, and obesity a stronger risk factor in higher-income countries. The magnitude of association between AF and ischemic stroke was significantly higher in lower-income countries compared to higher-income countries. The population attributable fraction for AF and stroke varied by region and was 15.7% (95% CI 13.7-17.8) in HIC, 14.6% (95% CI 12.3-17.1) in UMIC-1, 5.7% (95% CI 4.9-6.7) in UMIC-2, and 6.3% (95% CI 5.3-7.3) in LMIC.Conclusion: Risk factors for AF vary by country income level. AF contributes to stroke burden to a greater extent in higher-income countries than in lower-income countries, due to a higher prevalence and despite a lower magnitude of odds ratio.
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| 74. |
- Pandian, Jeyaraj Durai, et al.
(författare)
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Strategies to Improve Stroke Care Services in Low- and Middle-Income Countries : A Systematic Review
- 2017
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Ingår i: Neuroepidemiology. - : S. Karger AG. - 0251-5350 .- 1423-0208. ; 49, s. 45-61
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Forskningsöversikt (refereegranskat)abstract
- Background: The burden of stroke in low- and middle-income countries (LMICs) is large and increasing, challenging the already stretched health-care services. Aims and Objectives: To determine the quality of existing stroke-care services in LMICs and to highlight indigenous, inexpensive, evidence-based implementable strategies being used in stroke-care. Methods: A detailed literature search was undertaken using PubMed and Google scholar from January 1966 to October 2015 using a range of search terms. Of 921 publications, 373 papers were shortlisted and 31 articles on existing stroke-services were included. Results: We identified efficient models of ambulance transport and pre-notification. Stroke Units (SU) are available in some countries, but are relatively sparse and mostly provided by the private sector. Very few patients were thrombolysed; this could be increased with telemedicine and governmental subsidies. Adherence to secondary preventive drugs is affected by limited availability and affordability, emphasizing the importance of primary prevention. Training of paramedics, care-givers and nurses in post-stroke care is feasible. Conclusion: In this systematic review, we found several reports on evidence-based implementable stroke services in LMICs. Some strategies are economic, feasible and reproducible but remain untested. Data on their outcomes and sustainability is limited. Further research on implementation of locally and regionally adapted stroke-services and cost-effective secondary prevention programs should be a priority.
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| 75. |
- Parmar, Priya, et al.
(författare)
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The Stroke Riskometer (TM) App: Validation of a data collection tool and stroke risk predictor
- 2015
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Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4949 .- 1747-4930. ; 10:2, s. 231-244
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe greatest potential to reduce the burden of stroke is by primary prevention of first-ever stroke, which constitutes three quarters of all stroke. In addition to population-wide prevention strategies (the mass' approach), the high risk' approach aims to identify individuals at risk of stroke and to modify their risk factors, and risk, accordingly. Current methods of assessing and modifying stroke risk are difficult to access and implement by the general population, amongst whom most future strokes will arise. To help reduce the burden of stroke on individuals and the population a new app, the Stroke Riskometer(TM), has been developed. We aim to explore the validity of the app for predicting the risk of stroke compared with current best methods. Methods752 stroke outcomes from a sample of 9501 individuals across three countries (New Zealand, Russia and the Netherlands) were utilized to investigate the performance of a novel stroke risk prediction tool algorithm (Stroke Riskometer(TM)) compared with two established stroke risk score prediction algorithms (Framingham Stroke Risk Score [FSRS] and QStroke). We calculated the receiver operating characteristics (ROC) curves and area under the ROC curve (AUROC) with 95% confidence intervals, Harrels C-statistic and D-statistics for measure of discrimination, R-2 statistics to indicate level of variability accounted for by each prediction algorithm, the Hosmer-Lemeshow statistic for calibration, and the sensitivity and specificity of each algorithm. ResultsThe Stroke Riskometer(TM) performed well against the FSRS five-year AUROC for both males (FSRS=750% (95% CI 723%-776%), Stroke Riskometer(TM)=740(95% CI 713%-767%) and females [FSRS=703% (95% CI 679%-728%, Stroke Riskometer(TM)=715% (95% CI 690%-739%)], and better than QStroke [males - 597% (95% CI 573%-620%) and comparable to females=711% (95% CI 690%-731%)]. Discriminative ability of all algorithms was low (C-statistic ranging from 051-056, D-statistic ranging from 001-012). Hosmer-Lemeshow illustrated that all of the predicted risk scores were not well calibrated with the observed event data (P<0006). ConclusionsThe Stroke Riskometer(TM) is comparable in performance for stroke prediction with FSRS and QStroke. All three algorithms performed equally poorly in predicting stroke events. The Stroke Riskometer(TM) will be continually developed and validated to address the need to improve the current stroke risk scoring systems to more accurately predict stroke, particularly by identifying robust ethnic/race ethnicity group and country specific risk factors.
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| 76. |
- Reddin, Catriona, et al.
(författare)
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Association of Psychosocial Stress With Risk of Acute Stroke.
- 2022
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Ingår i: JAMA network open. - : American Medical Association (AMA). - 2574-3805. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- Psychosocial stress is considered a modifiable risk factor for stroke. Given the prevalence of chronic and acute exposure to stress, it represents a potentially attractive target for population-health interventions.To determine the association of psychosocial stress with the risk of acute stroke and explore factors that might modify the association of stress with risk of acute stroke in a large international population.INTERSTROKE is an international retrospective case-control study of risk factors for first acute stroke in 32 countries in Asia, North and South America, Europe, Australia, the Middle East, and Africa. A total of 13462 patients with stroke and 13488 matched controls were recruited between January 11, 2007, and August 8, 2015. The present analyses were performed from June 1 to 30, 2021, and included 13350 cases and 13462 controls with available data on psychosocial stress.Psychosocial stress and occurrence of stressful life events within the preceding year were measured using a standardized questionnaire of self-reported stress at home and work.The association of stress with acute stroke and its subtypes was examined using multivariable conditional logistic regression and factors that might modify the association, particularly self-reported locus of control.Among 26812 participants included in the analysis, the mean (SD) age of cases was 62.2 (13.6) years; that of controls, 61.3 (13.3) years; 7960 cases (59.6%) and 8017 controls (59.6%) were men. Several periods of stress and permanent stress were reported for 2745 cases (20.5%) and 1933 controls (14.4%), with marked regional variation in prevalence, with the lowest in China (201 of 3981 [5.0%] among controls and 364 of 3980 [9.1%] among cases) and highest in South East Asia (233 of 855 [26.1%] among controls and 241 of 782 [30.8%] among cases). Increased stress at home (odds ratio [OR], 1.95 [95% CI, 1.77-2.15]) and at work (OR, 2.70 [95% CI, 2.25-3.23]) and recent stressful life events (OR, 1.31 [95% CI, 1.19-1.43]) were associated with an increased risk of acute stroke on multivariable analyses (vs no self-reported stress). Higher locus of control at home was associated with a reduced odds of all stroke (OR, 0.73 [95% CI, 0.68-0.79]), and higher locus of control both at work and at home were associated with a lower odds of acute stroke and significantly diminished the association with stress at work (OR, 2.20 [95% CI, 1.88-2.58]; P =.008 for interaction) and home (OR, 1.69 [95% CI, 1.44-1.98]; P < .001 for interaction) for acute stroke.Psychosocial stress is a common risk factor for acute stroke. The findings of this case-control study suggest that higher locus of control is associated with lower risk of stroke and may be an important effect modifier of the risk associated with psychosocial stress.
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| 77. |
- Reddin, Catriona, et al.
(författare)
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Blood pressure variability in acute stroke: Risk factors and association with functional outcomes at 1 month.
- 2024
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Ingår i: European journal of neurology. - 1468-1331.
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Tidskriftsartikel (refereegranskat)abstract
- Blood pressure variability, in acute stroke, may be an important modifiable determinant of functional outcome after stroke. In a large international cohort of participants with acute stroke, it was sought to determine the association of blood pressure variability (in the early period of admission) and functional outcomes, and to explore risk factors for increased blood pressure variability.INTERSTROKE is an international case-control study of risk factors for first acute stroke. Blood pressure was recorded at the time of admission, the morning after admission and the time of interview in cases (median time from admission 36.7h). Multivariable ordinal regression analysis was employed to determine the association of blood pressure variability (standard deviation [SD] and coefficient of variance) with modified Rankin score at 1-month follow-up, and logistic regression was used to identify risk factors for blood pressure variability.Amongst 13,206 participants, the mean age was 62.19 ±13.58years. When measured by SD, both systolic blood pressure variability (odds ratio 1.13; 95% confidence interval 1.03-1.24 for SD ≥20mmHg) and diastolic blood pressure variability (odds ratio 1.15; 95% confidence interval 1.04-1.26 for SD ≥10mmHg) were associated with a significant increase in the odds of poor functional outcome. The highest coefficient of variance category was not associated with a significant increase in risk of higher modified Rankin score at 1 month. Increasing age, female sex, high body mass index, history of hypertension, alcohol use, and high urinary potassium and low urinary sodium excretion were associated with increased blood pressure variability.Increased blood pressure variability in acute stroke, measured by SD, is associated with an increased risk of poor functional outcome at 1month. Potentially modifiable risk factors for increased blood pressure variability include low urinary sodium excretion.
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| 78. |
- Sharma, Mukul, et al.
(författare)
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Safety and efficacy of factorXIa inhibition with milvexian for secondary stroke prevention (AXIOMATIC-SSP) : a phase 2, international, randomised, double-blind, placebo-controlled, dose-finding trial
- 2024
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Ingår i: LANCET NEUROLOGY. - 1474-4422 .- 1474-4465. ; 23:1, s. 46-59
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Tidskriftsartikel (refereegranskat)abstract
- Background People with factor XI deficiency have lower rates of is chaemic stroke than the general population and infrequent spontaneous bleeding, suggesting that factor XI has a more important role in thrombosis than in haemostasis. Milvexian, an oral small-molecule inhibitor of activated factor XI, added to standard antiplatelet therapy, might reduce the risk of non-cardioembolic ischaemic stroke without increasing the risk of bleeding. We aimed to estimate the dose-response of milvexian for recurrent ischaemic cerebral events and major bleeding in patients with recent ischaemic stroke or transient ischaemic attack (TIA).Methods AXIOMATIC-SSP was a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial done at 367 hospitals in 27 countries. Eligible participants aged 40 years or older, with acute (<48 h) ischaemic stroke or high-risk TIA, were randomly assigned by a web-based interactive response system in a 1:1:1:1:1:2 ratio to receive one of five doses of milvexian (25 mg once daily, 25 mg twice daily, 50 mg twice daily, 100 mg twice daily, or 200 mg twice daily) or matching placebo twice daily for 90 days. All participants received clopidogrel 75 mg daily for the first 21 days and aspirin 100 mg daily for the first 90 days. Investigators, site staff, and participants were masked to treatment assignment. The primary efficacy endpoint was the composite of ischaemic stroke or incident covert brain infarct on MRI at 90 days, assessed in all participants allocated to treatment who completed a follow-up MRI brain scan, and the primary analysis assessed the dose-response relationship with Multiple Comparison Procedure-Modelling (MCP-MOD). The main safety outcome was major bleeding at 90 days, assessed in all participants who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov (NCT03766581) and the EU Clinical Trials Register (2017-005029-19).Findings Between Jan 27, 2019, and Dec 24, 2021, 2366 participants were randomly allocated to placebo (n=691); milvexian 25 mg once daily (n=328); or twice-daily doses of milvexian 25 mg (n=318), 50 mg (n=328), 100 mg (n=310), or 200 mg (n=351). The median age of participants was 71 (IQR 62-77) years and 859 (36%) were female. At 90 days, the estimates of the percentage of participants with either symptomatic ischaemic stroke or covert brain infarcts were 168 (902% CI 145-191) for placebo, 167 (148-186) for 25 mg milvexian once daily, 166 (148-183) for 25 mg twice daily, 156 (139-175) for 50 mg twice daily, 154 (134-176) for 100 mg twice daily, and 153 (128-197) for 200 mg twice daily. No significant dose-response was observed among the five milvexian doses for the primary composite efficacy outcome. Model-based estimates of the relative risk with milvexian compared with placebo were 099 (902% CI 091-105) for 25 mg once daily, 099 (087-111) for 25 mg twice daily, 093 (078-111) for 50 mg twice daily, 092 (075-113) for 100 mg twice daily, and 091 (072-126) for 200 mg twice daily. No apparent dose-response was observed for major bleeding (four [1%] of 682 participants with placebo, two [1%] of 325 with milvexian 25 mg once daily, two [1%] of 313 with 25 mg twice daily, five [2%] of 325 with 50 mg twice daily, five [2%] of 306 with 100 mg twice daily, and five [1%] of 344 with 200 mg twice daily). Five treatment-emergent deaths occurred, four of which were considered unrelated to the study drug by the investigator.Interpretation Factor XIa inhibition with milvexian, added to dual antiplatelet therapy, did not substantially reduce the composite outcome of symptomatic ischaemic stroke or covert brain infarction and did not meaningfully increase the risk of major bleeding. Findings from our study have informed the design of a phase 3 trial of milvexian for the prevention of ischaemic stroke in patients with acute ischaemic stroke or TIA.
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| 79. |
- Smyth, Andrew, et al.
(författare)
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Alcohol Intake as a Risk Factor for Acute Stroke: The INTERSTROKE Study.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:2
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Tidskriftsartikel (refereegranskat)abstract
- There is uncertainty about the association between alcohol consumption and stroke, particularly for low-moderate intake. We explored these associations in a large international study.INTERSTROKE, a case-control study, is the largest international study of risk factors for acute stroke. Alcohol consumption was self-reported and categorised by drinks/week as low (1-7), moderate (7-14 for females, 7-21 for males) or high (>14 for females, >21 for males). Heavy episodic drinking (HED) was defined as >5 drinks on ≥1 day per month. Multivariable conditional logistic regression was used to determine associations.We included 12,913 cases and 12,935 controls; 25.0% (n=6,449) were current drinkers, 16.7% (n=4,318) former and 58.3% (n=15,076) never drinkers. Current drinkers were younger, male, smokers, active and with higher-paid occupations. Current drinking was associated with all stroke (OR 1.14; 95% CI 1.04-1.26) and intracerebral hemorrhage (ICH) (OR 1.50, 95% CI 1.21-1.84) but not ischaemic stroke (OR 1.06; 95% CI 0.95-1.19). HED pattern was associated with all stroke (OR 1.39; 95% CI 1.21-1.59), ischaemic stroke (OR 1.29; 95% CI 1.10-1.51) and ICH (OR 1.76; 95% CI 1.31-2.36). High level of alcohol intake was consistently associated with all stroke, ischaemic stroke and ICH. Moderate intake was associated with all stroke and ICH, but not ischaemic stroke. Low alcohol intake was not associated with stroke overall but there were regional differences; low intake was associated with reduced odds of stroke in Western Europe/North America (OR 0.66; 95%CI 0.45-0.96) and increased odds in India (OR 2.18; 95%CI 1.42-3.36)(p-interaction 0.037). Wine consumption was associated with reduced odds of all stroke and ischaemic stroke but not ICH. The magnitudes of association were greatest in those without hypertension and current smokers.High and moderate intake were associated with increased odds of stroke, while low intake was not associated with stroke. However, there were important regional variations, which may relate to differences in population characteristics of alcohol consumers, types or patterns of consumption.
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| 80. |
- Smyth, Andrew, et al.
(författare)
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Tea and coffee consumption and risk of acute stroke: The INTERSTROKE Study
- 2024
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Ingår i: INTERNATIONAL JOURNAL OF STROKE. - 1747-4930 .- 1747-4949.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Stroke is a leading global cause of death and disability. Daily tea/coffee intake is consumed by > 50% of populations and may represent an important population-level exposure. Therefore, it is first essential that we better understand the associations between the tea/coffee intake and stroke. Aims: This research aims to generate hypotheses about the global associations between tea and coffee intake and stroke. These insights will identify interventions for stroke prevention that can be further explored using alternative study designs. Methods: INTERSTROKE is a large international matched case-control study of first stroke from 32 countries. Participants were asked "how many cups do you drink each day?" of coffee, green tea, black tea, and other tea. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between intake and stroke. Results: We included 13,462 cases and 13,488 controls from INTERSTROKE; mean age was 61.7 (13.4) years and 59.6% (n = 16,010) were male. Overall, 19.4% (n = 5239) did not consume tea/coffee, 47.0% (n = 12,666) consumed tea only, 14.9% (n = 4024) consumed coffee alone, and 18.6% (n = 5021) consumed both, with significant regional variations. After multivariable adjustment, there was no association between low/moderate coffee intake and stroke, but high consumption (> 4/day) was associated with higher odds of all stroke (OR = 1.37 (95% CI = 1.06-1.77)) or ischemic stroke (OR = 1.32 (95% CI = 1.00-1.74)). Tea consumption was associated with lower odds of all (OR = 0.81 (95% CI = 0.69-0.94) for highest intake) or ischemic stroke (OR = 0.81 (95% CI = 0.68-0.98) for highest intake). Conclusions: High coffee consumption was associated with higher odds of all or ischemic stroke; low-moderate coffee had no association with stroke. In contrast, tea consumption was associated with lower odds of stroke. These associations suggest that individuals consider avoiding high coffee consumption (>= five cups/day) to impact future stroke risk. Data Access Statement: The design and rationale of INTERSTROKE was published previously. Individual participant data, or other documents are not available.
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