Search

BackgroundStudies of sex differences in the use and outcomes of endovascular treatment (EVT) for acute ischemic stroke report inconsistent resultsMethodsWe systematically searched PubMed and Embase databases for studies examining sex-specific utilization of EVT for acute ischemic stroke published before 31 December 2021. Estimates were compared by study type: randomized clinical trials (RCTs) and non-RCTs (hospital-based, registry-based or administrative data). Random effects odds ratios (ORs) were generated to quantify sex differences in EVT use. To estimate sex differences in functional outcome on the modified Rankin scale after EVT, the female:male ratio of ORs and 95% confidence intervals (CIs) were obtained from ordinal or binary analysis.Results6,396 studies were identified through database searching, of which 594 qualified for a full review. A total of 51 studies (36 non-RCT and 15 RCTs) reporting on sex-specific utilization of EVT were included, and of those 10 estimated the sex differences of EVT on functional outcomes. EVT use was similar in women and men both in non-RCTs (OR: 1.03, 95% CI: 0.96–1.11) and RCTs (1.02, 95% CI: 0.89–1.16), with consistent results across years of publication and regions of study, except that in Europe EVT treatment was higher in women than men (1.15, 95% CI: 1.13–1.16). No sex differences were found in the functional outcome by either ordinal and binary analyses (ORs 0.95, 95% CI: 0.68–1.32] and 0.90, 95% CI: 0.65–1.25, respectively).ConclusionsNo sex differences in EVT utilization or on functional outcomes were evident after acute ischemic stroke from large-vessel occlusion. Further research may be required to examine sex differences in long-term outcomes, social domains, and quality of life.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=226100, identifier: CRD42021226100.

BACKGROUND Aspirin is the only antiplatelet agent with a Class I recommendation for long-term prevention of cardiovascular events in patients with coronary artery disease (CAD). There is inconsistent evidence on how it compares with alternative antiplatelet agents. OBJECTIVES This study compared P2Y12 inhibitor monotherapy vs aspirin in patients with CAD. METHODS We conducted a patient-level meta-analysis of randomized trials comparing P2Y12 inhibitor monotherapy vs aspirin monotherapy for the prevention of cardiovascular events in patients with established CAD. The primary outcome was the composite of cardiovascular death, myocardial infarction, and stroke. Prespecified key secondary outcomes were major bleeding and net adverse clinical events (the composite of the primary outcome and major bleeding). Data were pooled in a 1-step meta-analysis. RESULTS Patient-level data were obtained from 7 trials. Overall, 24,325 participants were available for analysis, including 12,178 patients assigned to receive P2Y12 inhibitor monotherapy (clopidogrel in 7,545 [62.0%], ticagrelor in 4,633 [38.0%]) and 12,147 assigned to receive aspirin. Risk of the primary outcome was lower with P2Y12 inhibitor monotherapy compared with aspirin over 2 years (HR: 0.88; 95% CI: 0.79-0.97; P = 0.012), mainly owing to less myocardial infarction (HR: 0.77; 95% CI: 0.66-0.90; P < 0.001). Major bleeding was similar (HR: 0.87; 95% CI: 0.70-1.09; P = 0.23) and net adverse clinical events were lower (HR: 0.89; 95% CI: 0.81-0.98; P = 0.020) with P2Y12 inhibitors. The treatment effect was consistent across prespecified subgroups and types of P2Y12 inhibitors. CONCLUSIONS Given its superior efficacy and similar overall safety, P2Y12 inhibitor monotherapy might be preferred over aspirin monotherapy for long-term secondary prevention in patients with established CAD. (P2Y12 Inhibitor or Aspirin Monotherapy as Secondary Prevention in Patients With Coronary Artery Disease: An Individual Patient Data Meta-Analysis of Randomized Trials [PANTHER collaborative initiative]; CRD42021290774).

Additional file 1: Supplementary Table 1. Estimated change in sodium levels in the targeted food products before and during the intervention. Supplementary Table 2. The number of products, mean sodium content (mg/100g) and standard deviation for each food category before (2014-2016) and during the intervention (2017-2019).

Supplemental material, sj-docx-1-wso-10.1177_17474930211068671 for Triple Therapy Prevention of Recurrent Intracerebral Disease Events Trial: Rationale, design and progress by Craig S Anderson, Anthony Rodgers, H Asita de Silva, Sheila Ouriques Martins, Catharina JM Klijn, Bimsara Senanayake, Ruth Freed, Laurent Billot, Hisatomi Arima, Nguyen Huy Thang, Wan Asyraf Wan Zaidi, Tinatin Kherkheulidze, Kolawole Wahab, Urs Fisher, Tsong-Hai Lee, Christopher Chen, Octavio Pontes-Neto, Thompson Robinson, Jiguang Wang, Sharon Naismith, Lili Song, Floris H Schreuder, Richard I Lindley, Mark Woodward, Stephen MacMahon, Rustam Al-Shahi Salman, Clara K Chow and John Chalmers in International Journal of Stroke

Additional file 2. Intraclass correlation coefficients and kappa statistic by subgroups.

Supplemental material, sj-docx-1-wso-10.1177_17474930221090133 for Sex differences in the symptom presentation of stroke: A systematic review and meta-analysis by Sultana Shajahan, Lingli Sun, Katie Harris, Xia Wang, Else Charlotte Sandset, Amy YX Yu, Mark Woodward, Sanne AE Peters and Cheryl Carcel in International Journal of Stroke

Additional file 5. Research impact assessment quantitative summary score card.

Additional file 1. Interview guide for the evaluation planning consultations.

Supplemental material, sj-docx-1-wso-10.1177_17474930221090133 for Sex differences in the symptom presentation of stroke: A systematic review and meta-analysis by Sultana Shajahan, Lingli Sun, Katie Harris, Xia Wang, Else Charlotte Sandset, Amy YX Yu, Mark Woodward, Sanne AE Peters and Cheryl Carcel in International Journal of Stroke

Supplemental material, sj-docx-1-wso-10.1177_17474930211068671 for Triple Therapy Prevention of Recurrent Intracerebral Disease Events Trial: Rationale, design and progress by Craig S Anderson, Anthony Rodgers, H Asita de Silva, Sheila Ouriques Martins, Catharina JM Klijn, Bimsara Senanayake, Ruth Freed, Laurent Billot, Hisatomi Arima, Nguyen Huy Thang, Wan Asyraf Wan Zaidi, Tinatin Kherkheulidze, Kolawole Wahab, Urs Fisher, Tsong-Hai Lee, Christopher Chen, Octavio Pontes-Neto, Thompson Robinson, Jiguang Wang, Sharon Naismith, Lili Song, Floris H Schreuder, Richard I Lindley, Mark Woodward, Stephen MacMahon, Rustam Al-Shahi Salman, Clara K Chow and John Chalmers in International Journal of Stroke

Supplementary Material 2

Additional file 1.

Additional file 2: Supplementary table 2. Coding of stakeholder perspectives on gender considerations in nutrition and health related policy, and mapping to overarching themes.

Additional file 1.

Supplemental material, sj-docx-1-wso-10.1177_17474930211068671 for Triple Therapy Prevention of Recurrent Intracerebral Disease Events Trial: Rationale, design and progress by Craig S Anderson, Anthony Rodgers, H Asita de Silva, Sheila Ouriques Martins, Catharina JM Klijn, Bimsara Senanayake, Ruth Freed, Laurent Billot, Hisatomi Arima, Nguyen Huy Thang, Wan Asyraf Wan Zaidi, Tinatin Kherkheulidze, Kolawole Wahab, Urs Fisher, Tsong-Hai Lee, Christopher Chen, Octavio Pontes-Neto, Thompson Robinson, Jiguang Wang, Sharon Naismith, Lili Song, Floris H Schreuder, Richard I Lindley, Mark Woodward, Stephen MacMahon, Rustam Al-Shahi Salman, Clara K Chow and John Chalmers in International Journal of Stroke

Additional file 3. Interview guide for the research impact assessment.

Additional file 1. Criteria for assessing completeness of 24-hour urine samples.

Additional file 2. Data collection cards for each project stream and SUPI in general.

Additional file 4. Topic guide for the group discussions for the research impact assessment.

IMPORTANCE: The effect of glucocorticoids on major kidney outcomes and adverse events in IgA nephropathy has been uncertain. OBJECTIVE: To evaluate the efficacy and adverse effects of methylprednisolone in patients with IgA nephropathy at high risk of kidney function decline. DESIGN, SETTING, AND PARTICIPANTS: An international, multicenter, double-blind, randomized clinical trial that enrolled 503 participants with IgA nephropathy, proteinuria greater than or equal to 1 g per day, and estimated glomerular filtration rate (eGFR) of 20 to 120 mL/min/1.73 m(2) after at least 3 months of optimized background care from 67 centers in Australia, Canada, China, India, and Malaysia between May 2012 and November 2019, with follow-up until June 2021. INTERVENTIONS: Participants were randomized in a 1:1 ratio to receive oral methylprednisolone (initially 0.6-0.8 mg/kg/d, maximum 48 mg/d, weaning by 8 mg/d/mo; n = 136) or placebo (n = 126). After 262 participants were randomized, an excess of serious infections was identified, leading to dose reduction (0.4 mg/kg/d, maximum 32 mg/d, weaning by 4 mg/d/mo) and addition of antibiotic prophylaxis for pneumocystis pneumonia for subsequent participants (121 in the oral methylprednisolone group and 120 in the placebo group). MAIN OUTCOMES AND MEASURES: The primary end point was a composite of 40% decline in eGFR, kidney failure (dialysis, transplant), or death due to kidney disease. There were 11 secondary outcomes, including kidney failure. RESULTS: Among 503 randomized patients (mean age, 38 years; 198 [39%] women; mean eGFR, 61.5 mL/min/1.73 m(2); mean proteinuria, 2.46 g/d), 493 (98%) completed the trial. Over a mean of 4.2 years of follow-up, the primary outcome occurred in 74 participants (28.8%) in the methylprednisolone group compared with 106 (43.1%) in the placebo group (hazard ratio [HR], 0.53 [95% CI, 0.39-0.72]; P

Additional file 2. Multiple adjusted hazard ratios for systolic and diastolic blood pressure and dementia disaggregated by antihypertensive use, by sex.

Additional file 4. Multiple-adjusted hazard ratios and ratio of the hazard ratios (women-to-men) for risk factors and by dementia subtypes.

Supplemental material, sj-pdf-1-wso-10.1177_17474930211059298 for Sex differences in predictors for cognitive decline and dementia in people with stroke or transient ischemic attack in the PROGRESS trial by Jessica Gong, Katie Harris, Christophe Tzourio, Stephen Harrap, Sharon Naismith, Craig S Anderson, John Chalmers and Mark Woodward: On behalf of the NAVIGATE ESUS MRI Substudy Investigators in International Journal of Stroke

Additional file 6. Multiple adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for the association between risk factors and incident dementia, by socioeconomic status (SES) and sex.

Additional file 9. Multiple-adjusted sub-distribution hazard ratios (SHR) and ratio of the sub-distribution hazard ratios (women-to-men) for risk factors for dementia from competing risks analysis.

Additional file 1: Additional figures and tables.

Additional file 1: Post-hoc univariate analyses of the factors independently associated with radiographic osteoarthritis progression at two years: number (%) of people using NSAIDs and people not meeting physical activity guidelines, respectively. P values for association between independent variables and primary outcomes using Pearson χ2.

Supplemental material, sj-pdf-1-wso-10.1177_17474930211059298 for Sex differences in predictors for cognitive decline and dementia in people with stroke or transient ischemic attack in the PROGRESS trial by Jessica Gong, Katie Harris, Christophe Tzourio, Stephen Harrap, Sharon Naismith, Craig S Anderson, John Chalmers and Mark Woodward: On behalf of the NAVIGATE ESUS MRI Substudy Investigators in International Journal of Stroke

Additional file 7. Unadjusted rates of incident dementia (per 10,000 person years) by sex, and women-to-men difference of rate differences for each risk factor.

Additional file 1. Age-adjusted hazard ratios and ratio of the hazard ratios (women-to-men) for risk factors and dementia, by sex.

Additional file 3. Multiple-adjusted C-statistics with standard errors (se) for each risk factor in association with all-cause dementia.

Additional file 3: Supplemental Methods S3. Quality criteria according to a modified version of the Newcastle-Ottawa Quality assessment scale (*studies received one point for the achievement of these criteria).

Supplemental material, sj-pdf-1-wso-10.1177_1747493020938307 for Worse prognosis in women, compared with men, after thrombolysis: An individual patient data pooling study of Asian acute stroke registries by Xia Wang, Cheryl Carcel, Ruigang Wang, Jingwei Li, Hee-Joon Bae, Yilong Wang, Anxin Wang, Yongjun Wang, Kazunori Toyoda, Yi Sui, Tsong-Hai Lee, Jose C Navarro, Mu-Chien Sun, Craig S Anderson, Vijay Sharma, Else C Sandset and Mark Woodward: INDAGA Cardiologists Investigators in International Journal of Stroke

Supplemental material, sj-pdf-1-wso-10.1177_1747493020938307 for Worse prognosis in women, compared with men, after thrombolysis: An individual patient data pooling study of Asian acute stroke registries by Xia Wang, Cheryl Carcel, Ruigang Wang, Jingwei Li, Hee-Joon Bae, Yilong Wang, Anxin Wang, Yongjun Wang, Kazunori Toyoda, Yi Sui, Tsong-Hai Lee, Jose C Navarro, Mu-Chien Sun, Craig S Anderson, Vijay Sharma, Else C Sandset and Mark Woodward: INDAGA Cardiologists Investigators in International Journal of Stroke

Supplemental material, sj-pdf-1-eso-10.1177_2396987320957513 for Sex differences in treatment, radiological features and outcome after intracerebral haemorrhage: Pooled analysis of Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage trials 1 and 2 by Else Charlotte Sandset, Xia Wang, Cheryl Carcel, Shoichiro Sato, Candice Delcourt, Hisatomi Arima, Christian Stapf, Thompson Robinson, Pablo Lavados, John Chalmers, Mark Woodward and Craig S Anderson in European Stroke Journal

Additional file 1 Supplemental Table 1. PRISMA 2009 Checklist. Supplemental Table 2. Quality of included studies assessed with Newcastle-Ottawa Scale. Supplemental Table 3. Subgroup analyses of women-to-men ratio of relative risks for all-cause mortality associated with marital status. Supplemental Figure 1. Sex-specific relative risks (RRs) for all-cause mortality, comparing widowed, divorced/separated and never married to married people: (a) Sex-specific RRs for all-cause mortality, comparing widowed to married people; (b) Sex-specific RRs for all-cause mortality, comparing divorced/separated to married people; (c) Sex-specific RRs for all-cause mortality, comparing never married to married people. Supplemental Figure 2. Women-to-men ratios of relative risks (RRRs) for all-cause mortality comparing widowed, divorced/separated and never married to married people: (a) Women-to-men RRRs for all-cause mortality comparing widowed to married people; (b) Women-to-men RRRs for all-cause mortality comparing divorced/separated to married people; (c) Women-to-men RRRs for all-cause mortality comparing never married to married people. Supplemental Figure 3. Sex-specific relative risks (RRs) for cancer mortality, comparing non-married, widowed, divorced/separated and never married to married people: (a) Sex-specific RRs for cancer mortality, comparing non-married to married people; (b) Sex-specific RRs for cancer mortality, comparing widowed to married people; (c) Sex-specific RRs for cancer mortality, comparing divorced/separated to married people; (d) Sex-specific RRs for cancer mortality, comparing never married to married people. Supplemental Figure 4. Women-to-men ratios of relative risks (RRRs) for cancer mortality comparing non-married, widowed, divorced/separated and never married to married people: (a) Women-to-men RRRs for cancer mortality comparing non-married to married people; (b) Women-to-men RRRs for cancer mortality comparing widowed to married people; (c) Women-to-men RRRs for cancer mortality comparing divorced/separated to married people; (d) Women-to-men RRRs for cancer mortality comparing never married to married people. Supplemental Figure 5. Sex-specific relative risks (RRs) for cardiovascular (CV) mortality, comparing non-married, widowed, divorced/separated and never married to married people: (a) Sex-specific RRs for CV mortality, comparing non-married to married people; (b) Sex-specific RRs for CV mortality, comparing widowed to married people; (c) Sex-specific RRs for CV mortality, comparing divorced/separated to married people; (d) Sex-specific RRs for CV mortality, comparing never married to married people. Supplemental Figure 6. Women-to-men ratios of relative risks (RRRs) for cardiovascular (CV) mortality comparing non-married, widowed, divorced/separated and never married to married people: (a) Women-to-men RRRs for CV mortality comparing non-married to married people; (b) Women-to-men RRRs for CV mortality comparing widowed to married people; (c) Women-to-men RRRs for CV mortality comparing divorced/separated to married people; (d) Women-to-men RRRs for CV mortality comparing never married to married people. Supplemental Figure 7. Sex-specific relative risks (RRs) for coronary heart disease (CHD) mortality, comparing non-married, widowed, divorced/separated and never married to married people: (a) Sex-specific RRs for CHD mortality, comparing non-married to married people; (b) Sex-specific RRs for CHD mortality, comparing widowed to married people; (c) Sex-specific RRs for CHD mortality, comparing divorced/separated to married people; (d) Sex-specific RRs for CHD mortality, comparing never married to married people. Supplemental Figure 8. Women-to-men ratios of relative risks (RRRs) for coronary heart disease (CHD) mortality comparing non-married, widowed, divorced/separated and never married to married people: (a) Women-to-men RRRs for CHD mortality comparing non-married to married people; (b) Women-to-men RRRs for CHD mortality comparing widowed to married people; (c) Women-to-men RRRs for CHD mortality comparing divorced/separated to married people; (d) Women-to-men RRRs for CV mortality comparing never married to married people. Supplemental Figure 9. Sex-specific relative risks (RRs) for stroke mortality, comparing non-married, widowed, divorced/separated and never married to married people: (a) Sex-specific RRs for stroke mortality, comparing non-married to married people; (b) Sex-specific RRs for stroke mortality, comparing widowed to married people; (c) Sex-specific RRs for stroke mortality, comparing divorced/separated to married people; (d) Sex-specific RRs for stroke mortality, comparing never married to married people. Supplemental Figure 10. Women-to-men ratios of relative risks (RRRs) for stroke mortality comparing non-married, widowed, divorced/separated and never married to married people: (a) Women-to-men RRRs for stroke mortality comparing non-married to married people; (b) Women-to-men RRRs for stroke mortality comparing widowed to married people; (c) Women-to-men RRRs for stroke mortality comparing divorced/separated to married people; (d) Women-to-men RRRs for stroke mortality comparing never married to married people. Supplemental Figure 11. Meta-regression for mean age at baseline for pooled women-to-men ratios of relative risk for risk of all-cause mortality comparing non-married people to married people. Supplemental Figure 12. Subgroup analyses for all-cause mortality for pooled women-to-men ratios of relative risk (RRRs) for risk of all-cause mortality comparing widowed people to married people. Supplemental Figure 13. Begg’s publication bias plot for the pooled ratio of women-to-men relative risks: (a) Begg’s publication bias plot for CHD mortality in divorced/separated group; (b) Begg’s publication bias plot for all-cause mortality in widowed group; (c) Begg’s publication bias plot for all-cause mortality in never married group; Abbreviations: CHD: coronary heart disease; RR: relative risk; RRR: ratio of RR.

Additional file 10: Fig. S6. Meta-regression results show an increasing log(RRR) with increasing age, by 0.04 (standard error 0.02) for every additional year of age.

Additional file 1:Methods 1.

Additional file 1: Table S1. Number and percent of individuals with missing data on outcome, independent variables and confounders*, overall and by country. Table S2. Survey characteristics. Table S3. Characteristics of individuals with data on dietary behaviours, and data on waist circumference (n = 23,273) hypertension (n = 24,011), diabetes (n = 17,724) status. Table S4. Prevalence of dietary behaviours among participants with data on waist circumference (n = 23,273) hypertension (n = 24,011), or diabetes (n = 17,724) status. Figure S1. a. Weighted proportion of males (n = 8551) reporting positive dietary behaviours, in seven low-and middle-income countries. b. Weighted proportion of females (n = 14,960) reporting positive dietary behaviours, in seven low-and middle-income countries. Figure S2. a. Percentage (95% confidence interval) of males with undiagnosed hypertension, by the self-report of salt behaviour on a seven point scale*. b. Percentage (95% confidence interval) of females with undiagnosed hypertension, by the self-report of salt behaviour on a seven point scale*. Figure S3. a. Percentage (95% confidence interval) of males with undiagnosed hypertension, by the self-report of salt behaviour on a four point scale*.b. Percentage (95% confidence interval) of females with undiagnosed hypertension, by the self-report of salt behaviour on a four point scale*.

Additional file 2: Methods 2.

Additional file 5: Supplemental Table S1. Description of the characteristics of the studies included in the quantitative analysis.

Objectives: To examine sex differences in disease profiles, management, and survival at 1 and 5 years after ischemic stroke (IS) among people with atrial fibrillation (AF). Methods: We performed a systematic literature search of reports of AF at IS onset according to sex. We undertook an individual participant data meta-analysis (IPDMA) of nine population-based stroke incidence studies conducted in Australasia, Europe, and South America (1993-2014). Poisson regression was used to estimate women:men mortality rate ratios (MRRs). Study-specific MRRs were combined using random effects meta-analysis. Results: In our meta-analysis based on aggregated data from 101 studies, the pooled AF prevalence was 23\% (95\% confidence interval [CI]: 22\%-25\%) in women and 17\% (15\%-18\%) in men. Our IPDMA is of 1,862 IS-AF cases, with women (79.2 ± 9.1, years) being older than men (76.5 ± 9.5, years). Crude pooled mortality rate was greater for women than for men (1-year MRR 1.24; 1.01-1.51; 5-year 1.12; 1.03-1.22). However, the sex difference was greatly attenuated after accounting for age, prestroke function, and stroke severity (1-year 1.09; 0.97-1.22; 5-year 0.98; 0.84-1.16). Women were less likely to have anticoagulant prescription at discharge (odds ratio [OR] 0.94; 95\% CI: 0.89-0.98) than men when pooling IPDMA and aggregated data. Conclusions: AF was more prevalent after IS among women than among men. Among IS-AF cases, women were less likely to receive anticoagulant agents at discharge; however, greater mortality rate in women was mostly attributable to prestroke factors. Further information needs to be collected in population-based studies to understand the reasons for lower treatment of AF in women.

Additional file 4: Supplemental Methods S4. Quality assessment of the studies included in the meta-analyses.

Additional file 1: Supplemental Methods S1. Search strategies.

Publisher's version (útgefin grein), Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after 'recalibration', a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied. Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at 'high' 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29-39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22-24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44-51 such individuals using original algorithms, in contrast to 37-39 individuals with recalibrated algorithms. Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need., The work of the co-ordinating centre was funded by the UK Medical Research Council (G0800270), British Heart Foundation (SP/09/ 002), British Heart Foundation Cambridge Cardiovascular Centre of Excellence, UK National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council (268834), and European Commission Framework Programme 7 (HEALTH-F2-2012-279233). The Emerging Risk Factor Collaboration’s website https://www.phpc.cam.ac.uk/ceu/erfc/list-of-studies/ has compiled a list provided by investigators of some of the funders of the component studies in this analysis. I.W. was supported by the Medical Research Council Unit Programme MC_UU_12023/21. M.K. is supported by the Netherlands Organization for Scientific Research (NWO) Veni grant (Veni, 91616079). J.P. is supported by Erasmus Mundus Western Balkans (ERAWEB), a project funded by the European Commission.

Supplemental Material for Applicability of ENCHANTED trial results to current acute ischemic stroke patients eligible for intravenous thrombolysis in England and Wales: Comparison with the Sentinel Stroke National Audit Programme registry by Thompson G Robinson, Benjamin D Bray, Lizz Paley, Nikola Sprigg, Xia Wang, Hisatomi Arima, Philip M Bath, Joseph P Broderick, Alice C Durham, Jong S Kim, Pablo M Lavados, Tsong-Hai Lee, Sheila Martins, Thang H Nguyen, Jeyaraj D Pandian, Mark W Parsons, Octavio M Pontes-Neto, Stefano Ricci, Vijay K Sharma, Jiguang Wang, Mark Woodward, Anthony G Rudd, John Chalmers, Craig S Anderson and for the ENCHANTED Investigators and the SSNAP Collaboration in International Journal of Stroke

Developing agents that can quickly adapt their behavior to new tasks remains a challenge. Meta-learning has been applied to this problem, but previous methods require either specifying a reward function which can be tedious or providing demonstrations which can be inefficient. In this paper, we investigate if, and how, a "helper" agent can be trained to interactively adapt their behavior to maximize the reward of another agent, whom we call the "prime" agent, without observing their reward or receiving explicit demonstrations. To this end, we propose to meta-learn a helper agent along with a prime agent, who, during training, observes the reward function and serves as a surrogate for a human prime. We introduce a distribution of multi-agent cooperative foraging tasks, in which only the prime agent knows the objects that should be collected. We demonstrate that, from the emerged physical communication, the trained helper rapidly infers and collects the correct objects., Comment: The paper "Learning to Interactively Learn and Assist" (LILA), at arXiv:1906.10187, supersedes this paper. This preliminary workshop paper appeared in the Emergent Communication Workshop and Workshop on Learning by Instruction at NeurIPS 2018

Supplemental Material for Who will benefit more from low-dose alteplase in acute ischemic stroke? by Xia Wang, Keon-Joo Lee, Tom J Moullaali, Beom Joon Kim, Qiang Li, Hee-Joon Bae, Cheryl Carcel, Candice Delcourt, Hisatomi Arima, Shoichiro Sato, Thompson G Robinson, Lili Song, Guofang Chen, Jie Yang, John Chalmers, Craig S Anderson, Richard Lindley, Mark Woodward and for the ENCHANTED Investigators in International Journal of Stroke