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Summary Background Baricitinib is an oral selective Janus kinase 1/2 inhibitor with known anti-inflammatory properties. This study evaluates the efficacy and safety of baricitinib in combination with standard of care for the treatment of hospitalised adults with COVID-19. Methods In this phase 3, double-blind, randomised, placebo-controlled trial, participants were enrolled from 101 centres across 12 countries in Asia, Europe, North America, and South America. Hospitalised adults with COVID-19 receiving standard of care were randomly assigned (1:1) to receive once-daily baricitinib (4 mg) or matched placebo for up to 14 days. Standard of care included systemic corticosteroids, such as dexamethasone, and antivirals, including remdesivir. The composite primary endpoint was the proportion who progressed to high-flow oxygen, non-invasive ventilation, invasive mechanical ventilation, or death by day 28, assessed in the intention-to-treat population. All-cause mortality by day 28 was a key secondary endpoint, and all-cause mortality by day 60 was an exploratory endpoint; both were assessed in the intention-to-treat population. Safety analyses were done in the safety population defined as all randomly allocated participants who received at least one dose of study drug and who were not lost to follow-up before the first post-baseline visit. This study is registered with ClinicalTrials.gov , NCT04421027 . Findings Between June 11, 2020, and Jan 15, 2021, 1525 participants were randomly assigned to the baricitinib group (n=764) or the placebo group (n=761). 1204 (79·3%) of 1518 participants with available data were receiving systemic corticosteroids at baseline, of whom 1099 (91·3%) were on dexamethasone; 287 (18·9%) participants were receiving remdesivir. Overall, 27·8% of participants receiving baricitinib and 30·5% receiving placebo progressed to meet the primary endpoint (odds ratio 0·85 [95% CI 0·67 to 1·08], p=0·18), with an absolute risk difference of −2·7 percentage points (95% CI −7·3 to 1·9). The 28-day all-cause mortality was 8% (n=62) for baricitinib and 13% (n=100) for placebo (hazard ratio [HR] 0·57 [95% CI 0·41–0·78]; nominal p=0·0018), a 38·2% relative reduction in mortality; one additional death was prevented per 20 baricitinib-treated participants. The 60-day all-cause mortality was 10% (n=79) for baricitinib and 15% (n=116) for placebo (HR 0·62 [95% CI 0·47–0·83]; p=0·0050). The frequencies of serious adverse events (110 [15%] of 750 in the baricitinib group vs 135 [18%] of 752 in the placebo group), serious infections (64 [9%] vs 74 [10%]), and venous thromboembolic events (20 [3%] vs 19 [3%]) were similar between the two groups. Interpretation Although there was no significant reduction in the frequency of disease progression overall, treatment with baricitinib in addition to standard of care (including dexamethasone) had a similar safety profile to that of standard of care alone, and was associated with reduced mortality in hospitalised adults with COVID-19. Funding Eli Lilly and Company. Translations For the French, Japanese, Portuguese, Russian and Spanish translations of the abstract see Supplementary Materials section.

Background There are few large population-based studies of outcomes after subarachnoid hemorrhage (SAH) than other stroke types. Methods We pooled data from 13 population-based stroke incidence studies (10 studies from the INternational STRroke oUtComes sTudy (INSTRUCT) and 3 new studies; N=657). Primary outcomes were case-fatality and functional outcome (modified Rankin scale score 3-5 [poor] vs. 0-2 [good]). Harmonized patient-level factors included age, sex, health behaviours (e.g. current smoking at baseline), comorbidities (e.g.history of hypertension), baseline stroke severity (e.g. NIHSS >7) and year of stroke. We estimated predictors of case-fatality and functional outcome using Poisson regression and generalized estimating equations using log-binomial models respectively at multiple timepoints. Results Case-fatality rate was 33% at 1 month, 43% at 1 year, and 47% at 5 years. Poor functional outcome was present in 27% of survivors at 1 month and 15% at 1 year. In multivariable analysis, predictors of death at 1-month were age (per decade increase MRR 1.14 [1.07-1.22]) and SAH severity (MRR 1.87 [1.50-2.33]); at 1 year were age (MRR 1.53 [1.34-1.56]), current smoking (MRR 1.82 [1.20-2.72]) and SAH severity (MRR 3.00 [2.06-4.33]) and; at 5 years were age (MRR 1.63 [1.45-1.84]), current smoking (MRR 2.29 [1.54-3.46]) and severity of SAH (MRR 2.10 [1.44-3.05]). Predictors of poor functional outcome at 1 month were age (per decade increase RR 1.32 [1.11-1.56]) and SAH severity (RR 1.85 [1.06-3.23]), and SAH severity (RR 7.09 [3.17-15.85]) at 1 year. Conclusion Although age is a non-modifiable risk factor for poor outcomes after SAH, however, severity of SAH and smoking are potential targets to improve the outcomes.

Background: Stroke population-based studies in the same setting comparing time trends of rates are a gold standard method to determine the primary prevention status of stroke. Twelve years ago, we measured the stroke incidence and mortality in Matão city, Southeast of Brazil. Objective: This second Matão stroke registry study aimed to determine the time trends in the incidence, mortality, case fatality, and functional status of patients with stroke. Methods: This was a prospective, population-based study known as the Matão Preventing Stroke (MAPS). We determined all incident stroke events that occurred between August 1, 2015, and July 31, 2016. Between the periods of November 1, 2003, to October 31, 2004, and August 1, 2015, to July 31, 2016, the rates were age adjusted to the Brazilian and world population. Functional status was measured by Barthel scale 1 year after the index event. Results: We registered 81 cases of incident stroke. Demographic and cardiovascular risk factors were similar in both periods. The mean age increased by 9%, from 65.2 (95% CI 62.6–67.8) to 71.0 (95% CI 68.1–73.8) years. Between 2003–2004 and 2015–2016, the age-adjusted incidence decreased by 39% (incidence rate ratio [IRR] 0.61; 95% CI 0.46–0.79) and mortality by 50% (IRR 0.50; 95% CI 0.31–0.94). The 1-year case fatality was 26%; approximately 56% of the patients were functionally independent, while 7% had a recurrent stroke. Compared with the results of our first registry study, these outcomes did not differ significantly. Conclusion: Our findings agree with those of previous studies, showing a decline in the incidence and mortality of stroke in Brazil. Improvements in local public health care might explain these declines.

Background: Outcomes after subarachnoid hemorrhage (SAH) have been rarely examined in large cohorts. Methods: This is an extension of the International Stroke Outcomes Study (INSTRUCT) pooling 13 ‘ideal’ stroke incidence studies (n=657 with SAH from 1993-2017, median age 56 years; 46% men). The primary outcomes were mortality and functional outcome (mRS score 3-5). Harmonized study factors included age, sex, behaviors (current smoking, alcohol intake), comorbidities (history of hypertension, ischemic heart disease, atrial fibrillation), stroke severity (e.g. NIHSS score) and year of stroke. In the pooled dataset, we estimated predictors of mortality using Poisson regression, to estimate incidence rate ratio (IRR) at 1 month (11 studies), 1 year (12 studies) and 5 years (7 studies). Generalized equation estimates in the log-binomial family were used to calculate risk ratios (RRs) for predictors of poor functional outcome at 1 month (5 studies) and 1 year (8 studies). Results: Mortality was 33% at 1 month, 43% at 1 year, and 47% at 5 years (Fig 1). Poor functional outcome was 25% at 1 month and 15% at 1 year (Fig 1). In multivariable analysis, age and stroke severity were associated with mortality at all time points, together with current smoking at 1 and 5 years, and history of hypertension at 5 years (Fig 2). Poor functional outcome was predicted by age (RR 1.03; 95% CI 1.01-1.04) at 1 month and by age (RR 1.04; 95% CI 1.00-1.08) and stroke severity (RR 1.94; 95% CI 1.02-2.87) at 1 year. Conclusion: Risk factors that predict SAH incidence including hypertension and smoking make outcomes worse. Better management of older patients and those with severe strokes could improve outcomes after SAH.

Summary Background S44819, a selective GABAA α5 receptor antagonist, reduces tonic post-ischaemic inhibition of the peri-infarct cortex. S44819 improved stroke recovery in rodents and increased cortical excitability in a transcranial magnetic stimulation study in healthy volunteers. The Randomized Efficacy and Safety Trial of Oral GABAA α5 antagonist S44819 after Recent ischemic Event (RESTORE BRAIN) aimed to evaluate the safety and efficacy of S44819 for enhancing clinical recovery of patients with ischaemic stroke. Methods RESTORE BRAIN was an international, randomised, double-blind, parallel-group, placebo-controlled, multicentre phase 2 trial that evaluated the safety and efficacy of oral S44189 in patients with recent ischaemic stroke. The study was done in specialised stroke units in 92 actively recruiting centres in 14 countries: ten were European countries (Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Poland, Spain, and the UK) and four were non-European countries (Australia, Brazil, Canada, and South Korea). Patients aged 18–85 years with acute ischaemic stroke involving cerebral cortex (National Institute of Health Stroke Scale [NIHSS] score 7–20) without previous disability were eligible for inclusion. Participants were randomly assigned to receive 150 mg S44819 twice a day, 300 mg S44819 twice a day, or placebo twice a day by a balanced, non-adaptive randomisation method with a 1:1:1 ratio. Treatment randomisation and allocation were centralised via the interactive web response system using computer-generated random sequences with a block size of 3. Blinding of treatment was achieved by identical appearance and taste of all sachets. Patients, investigators and individuals involved in the analysis of the trial were masked to group assignment. The primary endpoint was the modified Rankin Scale (mRS) score 90 days from onset of treatment, evaluated by shift analysis (predefined main analysis) or by dichotomised analyses using 0–1 versus 2–6 and 0–2 versus 3–6 cutoffs (predefined secondary analysis). Secondary endpoints were the effects of S44819 on the NIHSS and Montreal Cognitive Assessment (MoCA) scores, time needed to complete parts A and B of the Trail Making Test, and the Barthel index. Efficacy analyses were done on all patients who received at least one dose of treatment and had at least one mRS score taken after day 5 (specifically, on or after day 30). Safety was compared across treatment groups for all patients who received at least one dose of treatment. The study was registered at ClinicalTrials.gov , NCT02877615 . Findings Between Dec 19, 2016, and Nov 16, 2018, 585 patients were enrolled in the study. Of these, 197 (34%) were randomly assigned to receive 150 mg S44819 twice a day, 195 (33%) to receive 300 mg S44819 twice a day, and 193 (33%) to receive placebo twice a day. 189 (96%) of 197 patients in the 150 mg S44819 group, 188 (96%) of 195 patients in the 300 mg S44819 group, and 191 (99%) patients in the placebo group received at least one dose of treatment and had at least one mRS score taken after day 5, and were included in efficacy analyses. 195 (99%) of 197 patients in the 150 mg S44819 group, 194 (99%) of 195 patients in the 300 mg S44819 group, and 193 (100%) patients in the placebo group received at least one dose of treatment, and were included in safety analyses. The primary endpoint of mRS at day 90 did not differ between each of the two S44819 groups and the placebo group (OR 0·91 [95% CI 0·64–1·31]; p=0·80 for 150 mg S44819 compared with placebo and OR 1·17 [95% CI 0·81–1·67]; p=0·80 for 300 mg S44819 compared with placebo). Likewise, dichotomised mRS scores at day 90 (mRS 0–2 vs 3–6 or mRS 0–1 vs 2–6) did not differ between groups. Secondary endpoints did not reveal any significant group differences. The median NIHSS score at day 90 did not differ between groups (4 [IQR 2–8] in 150 mg S44819 group, 4 [2–7] in 300 mg S44819 group, and 4 [2–6] in placebo group), nor did the number of patients at day 90 with an NIHSS score of up to 5 (95 [61%] of 156 in 150 mg S44819 group, 106 [66%] of 161 in 300 mg S44819 group, and 104 [66%] of 157 in placebo group) versus more than 5 (61 [39%] in 150 mg S44819 group, 55 [34%] in 300 mg S44819 group, and 53 [34%] in placebo group). Likewise, the median MoCA score (22·0 [IQR 17·0–26·0] in 150 mg S44819 group, 23·0 [19·0–26·5] in 300 mg S44819 group, and 22·0 [17·0–26·0] in placebo group), time needed to complete parts A (50 s [IQR 42–68] in 150 mg S44819 group, 49 s [36–63] in 300 mg S44819 group, and 50 s [38–68] in placebo group) and B (107 s [81–144] in 150 mg S44819 group, 121 s [76–159] in 300 mg S44819 group, and 130 s [86–175] in placebo group) of the Trail Making Test, and the Barthel index (90 [IQR 60–100] in 150 mg S44819 group, 90 [70–100] in 300 mg S44819 group, and 90 [70–100] in placebo group) were similar in all groups. Number and type of adverse events were similar between the three groups. There were no drug-related adverse events and no drug-related deaths. Interpretation There was no evidence that S44819 improved clinical outcome in patients after ischaemic stroke, and thus S44819 cannot be recommended for stroke therapy. The concept of tonic inhibition after stroke should be re-evaluated in humans. Funding Servier.

BACKGROUND: Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.METHODS: This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS: Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).INTERPRETATION: Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding.FUNDING: Bayer AG.

Background— Women are reported to have greater mortality after stroke than men, but the reasons are uncertain. We examined sex differences in mortality at 1 and 5 years after stroke and identified factors contributing to these differences. Methods and Results— Individual participant data for incident strokes were obtained from 13 population-based incidence studies conducted in Europe, Australasia, South America, and the Caribbean between 1987 and 2013. Data on sociodemographics, stroke-related factors, prestroke health, and 1- and 5-year survival were obtained. Poisson modeling was used to estimate the mortality rate ratio (MRR) for women compared with men at 1 year (13 studies) and 5 years (8 studies) after stroke. Study-specific adjusted MRRs were pooled to create a summary estimate using random-effects meta-analysis. Overall, 16 957 participants with first-ever stroke followed up at 1 year and 13 216 followed up to 5 years were included. Crude pooled mortality was greater for women than men at 1 year (MRR 1.35; 95% confidence interval, 1.24–1.47) and 5 years (MRR 1.24; 95% confidence interval, 1.12–1.38). However, these pooled sex differences were reversed after adjustment for confounding factors (1 year MRR, 0.81; 95% confidence interval, 0.72–0.92 and 5-year MRR, 0.76; 95% confidence interval, 0.65–0.89). Confounding factors included age, prestroke functional limitations, stroke severity, and history of atrial fibrillation. Conclusions— Greater mortality in women is mostly because of age but also stroke severity, atrial fibrillation, and prestroke functional limitations. Lower survival after stroke among the elderly is inevitable, but there may be opportunities for intervention, including better access to evidence-based care for cardiovascular and general health.

Background Women have worse outcomes after stroke than men, and this may be partly explained by stroke severity. We examined factors contributing to sex differences in severity of acute stroke assessed by the National Institutes of Health Stroke Scale. Methods and Results We pooled individual participant data with National Institutes of Health Stroke Scale assessment (N=6343) from 8 population‐based stroke incidence studies (1996–2014), forming part of INSTRUCT (International Stroke Outcomes Study). Information on sociodemographics, stroke‐related clinical factors, comorbidities, and pre‐stroke function were obtained. Within each study, relative risk regression using log‐binominal modeling was used to estimate the female:male relative risk ( RR ) of more severe stroke (National Institutes of Health Stroke Scale>7) stratified by stroke type (ischemic stroke and intracerebral hemorrhage). Study‐specific unadjusted and adjusted RR s, controlling for confounding variables, were pooled using random‐effects meta‐analysis. National Institutes of Health Stroke Scale data were recorded in 5326 (96%) of 5570 cases with ischemic stroke and 773 (90%) of 855 participants with intracerebral hemorrhage. The pooled unadjusted female:male RR for severe ischemic stroke was 1.35 (95% CI 1.24–1.46). The sex difference in severity was attenuated after adjustment for age, pre‐stroke dependency, and atrial fibrillation but remained statistically significant (pooled RR adjusted 1.20, 95% CI 1.10–1.30). There was no sex difference in severity for intracerebral hemorrhage ( RR crude 1.08, 95% CI 0.97–1.21; RR adjusted 1.08, 95% CI 0.96–1.20). Conclusions Although women presented with more severe ischemic stroke than men, much although not all of the difference was explained by pre‐stroke factors. Sex differences could potentially be ameliorated by strategies to improve pre‐stroke health in the elderly, the majority of whom are women. Further research on the potential biological origin of sex differences in stroke severity may also be warranted.

Background: Around 30% of Brazilian population is hypertensive. Brazilian’s Family Health Strategy (FHS) is a community-based approach to provide primary health care and control chronic disease as hypertension. The aims of this pilot study were to study hypertension prevalence and awareness and to analyze the feasibility of FHS program with community healthy agents (CHA) to collect data about hypertensive subjects in Matao, Brazil. Methods: A cross-sectional study was conducted in subjects equal or older than 40 years old in a neighborhood belonging to FHS program. CHA were trained to collect data and to assess blood pressure (BP) with an automated device. Hypertension diagnosis was defined if systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg or subject had previous use of hypertensive drug. Chi-square test and univariate logistic regression analysis were applied with significance level of 5% and a confidence interval of 95%. Results: In 625 subjects, hypertension prevalence was 68.8% and women (71.9%) were more hypertensive than men (63.2%) (P = 0.02). Prevalence of hypertension increased with age group, from 46.3% (40 - 49 years) to 82.5% (70 - 79 years) (P < 0.001). The overall prevalence of pre-hypertension was 40.1%: stage 1, 25.7% and stage 2, 17.0%. Hypertension awareness was 81.8% and 79.8% reported use of anti-hypertensive drugs. BP was not controlled in 61.8% and 67.7% of them was using anti-hypertensive drugs. CHA reported no difficulties to collect data and BP assessment with the automated device. Conclusion: We observed a high hypertension prevalence rate, awareness, and subjects with uncontrolled hypertension even with use of anti-hypertensive drugs. CHA from FHS program are a feasible option to BP control in future studies involving larger populations. J Clin Med Res. 2016;8(7):524-530 doi: http://dx.doi.org/10.14740/jocmr2582w

BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease.METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS: Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, pINTERPRETATION: In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide.FUNDING: Bayer AG.

ObjectiveTo examine factors contributing to the sex differences in functional outcomes and participation restriction after stroke.MethodsIndividual participant data on long-term functional outcome or participation restriction (i.e., handicap) were obtained from 11 stroke incidence studies (1993–2014). Multivariable log-binomial regression was used to estimate the female:male relative risk (RR) of poor functional outcome (modified Rankin Scale score >2 or Barthel Index score ResultsIn unadjusted analyses, women experienced worse functional outcomes after stroke than men (1 year: pooled RRunadjusted 1.32, 95% confidence interval [CI] 1.18–1.48; 5 years: RRunadjusted 1.31, 95% CI 1.16–1.47). However, this difference was greatly attenuated after adjustment for age, prestroke dependency, and stroke severity (1 year: RRadjusted 1.08, 95% CI 0.97–1.20; 5 years: RRadjusted 1.05, 95% CI 0.94–1.18). Women also had greater participation restriction than men (pooled MDunadjusted −5.55, 95% CI −8.47 to −2.63), but this difference was again attenuated after adjustment for the aforementioned factors (MDadjusted −2.48, 95% CI −4.99 to 0.03).ConclusionsWorse outcomes after stroke among women were explained mostly by age, stroke severity, and prestroke dependency, suggesting these potential targets to improve the outcomes after stroke in women.

Background Hypertension is the main risk factor for most cardiovascular diseases. A coordinated and organized system from the Brazilian Ministry of Healthy involving Family Health Strategy (FHS), a program for the prevention of chronic disease, and the Popular Pharmacy Program (PPP), which subsidizes medications for the population, could allow an earlier identification and better blood pressure (BP) control. Matao Controlling Hypertension (MatCH) is a community-based population project that aims to apply an organized, integrated and coordinated program in the city of Matao, Brazil, involving FHS and PPP in order to actively search, treat and follow-up hypertensive subjects. Method This is a population community-based, interventional, follow-up study where all subjects aged ≥ 40 years assisted by the FHS program in Matao will have BP assessed monthly by trained Community Health Agents (CHA) during a domiciliary visit. Identified hypertensive subjects will be referred to FHS physicians for nonpharmacological and pharmacological treatment. Most of the hypertensive drugs used will be available through the PPP. Prevalence of hypertension, awareness, demographics and risk factors will be correlated with BP control. The population study is expected to involve approximately 18.600 subjects. The study period will be four years. Discussion Considering that hypertension is asymptomatic in most cases, to reduce the population burden of BP-related deaths and diseases it is essential to detect and treat early all hypertensive patients. If we achieve our large-scale BP control, this program can be applied to other populations from developing countries.

Introduction: As women suffer worse functional outcomes of stroke than men, they may also face more challenges with community reintegration but data are scarce. We examined sex differences in participation after stroke and which factors might account for these disparities. Methods: INSTRUCT is an individual participant data pooling study of incident strokes obtained from 13 population-based cohorts worldwide. Two of the cohorts (Melbourne ’96-‘99 and Auckland ’02-‘03) included assessment of participation at 5 years after stroke using the London Handicap Scale (LHS). The LHS is used to assess the individual’s perspective of their involvement in life situations including orientation (person’s awareness of surroundings), physical independence, mobility, occupation, social interaction and economic self-efficiency. The total score ranges from 0 (worst disadvantage) to 100 (no disadvantage). Linear regression was used to compare LHS total scores and sub-domains for women compared to men. Study-specific multivariable models incorporated adjustment for socio-demographics, stroke-related factors, pre-stroke health and post-stroke factors were combined using random-effects meta-analysis. Results: At 5 years after stroke, there were data on participation for 351/592 (59%) of survivors in Melbourne and 266/881 (30%) of survivors in Auckland. Women suffered greater participation restriction than men (total LHS, pooled mean difference, MD -5.55 [95% CI -8.47, -2.63]). The magnitude of the difference attenuated after adjusting for covariates (pooled MD -2.48 [-4.99, 0.03]). Significant confounders in study-specific models included age, stroke severity, pre-stroke dependency and pre-stroke dementia for Melbourne; and age, stroke severity and pre-stroke dependency for Auckland. In sub-dimensions, women had greater restriction than men in mobility, physical independence and occupation. Additionally, women in Melbourne experienced poorer social integration and orientation than men. Conclusion: Greater restriction in participation after stroke among women than men was mostly attributable to their advanced age and greater pre-stroke dependency. Interventions targeting participation could reduce the impact of stroke in women.

Motor rehabilitation of stroke survivors may include functional and/or nonfunctional strategy. The present study aimed to compare the effect of these two rehabilitation strategies by means of clinical scales and functional Magnetic Resonance Imaging (fMRI). Twelve hemiparetic chronic stroke patients were selected. Patients were randomly assigned a nonfunctional (NFS) or functional (FS) rehabilitation scheme. Clinical scales (Fugl-Meyer, ARA test, and modified Barthel) and fMRI were applied at four moments: before rehabilitation (P1) and immediately after (P2), 1 month after (P3), and three months after (P4) the end of rehabilitation. The NFS group improved significantly and exclusively their Fugl-Meyer scores at P2, P3, and P4, when compared to P1. On the other hand, the FS group increased significantly in Fugl-Meyer at P2, when compared to P1, and also in their ARA and Barthel scores. fMRI inspection at the individual level revealed that both rehabilitation schemes most often led to decreased activation sparseness, decreased activity of contralesional M1, increased asymmetry of M1 activity to the ipsilesional side, decreased perilesional activity, and decreased SMA activity. Increased M1 asymmetry with rehabilitation was also confirmed by Lateralization Indexes. Our clinical analysis revealed subtle differences between FS and NFS.

Background and Purpose— Stroke is the main cause of death in Brazil and no prospective population-based study has been conducted in the country. The purpose of this study was to determine the incidence of stroke, stroke subtypes, case fatality, and prognosis after 1 year of follow-up in the city of Matão, Brazil. Methods— Using overlapping methods of case ascertainment, all stroke cases that occurred in the city of Matão (population, 75 053) from November 1, 2003 to October 31, 2004 were followed-up at 1 month and 1 year after the episode. Standard criteria for population-based stroke studies were followed. Results— Of 141 suspect stroke cases identified, 81 were first-ever-in-a-lifetime strokes. All patients underwent a CT scan. The crude annual incidence rate per 100 000 per year was 108 (95% CI, 85.7–134.1) and the rate adjusted for sex and age to the Segi population was 137 (95% CI, 112.0 to 166.4) per 100 000 inhabitants per year. Ischemic stroke occurred in 69 (85.2%) subjects, intracerebral hemorrhage in 11 (13.6%), and subarachnoid hemorrhage in 1 (1.2%). The 30-day case fatality rate was 18.5 and the 1-year case fatality rate was 30.9%. After 1 year of follow-up, 43% of the patients were independent in activities of daily living, 49.4% had independent gait, and 15.9% had a recurrent stroke. Conclusions— The present results are similar to those obtained in other stroke population-based studies. Future studies in Matão will provide the opportunity to discover ways to decrease the stroke burden in Brazil.

Neurocysticercosis is a world public health problem. An increase in immunoglobulin G (IgG) concentration in the cerebrospinal fluid of patients with neurocysticercosis has been described but the reasons for this finding are unknown. Our hypothesis is that the increase in IgG concentration in cerebrospinal fluid is due to exclusive intrathecal synthesis of IgG and this process is associated with the inflammatory phases of the disease. We studied IgG concentration in cerebrospinal fluid in 16 patients with neurocysticercosis comparing with a control group of 19 patients to verify which pattern of increase in IgG concentration in cerebrospinal fluid occurs in neurocysticercosis. In the neurocysticercosis group, intrathecal synthesis of IgG was detected in 12 (75%) and 5 (31.2%) patients by quantitative and qualitative methods, respectively. When compared with the control group the neurocysticercosis patients had the same pattern of intrathecal synthesis of IgG as multiple sclerosis patients. Intrathecal synthesis of IgG was not associated with any variable indicative of an inflammatory process. We conclude that the increase in IgG concentration in neurocysticercosis is due to intrathecal synthesis, as is also the case for multiple sclerosis, and that this process is not related to the inflammatory stage of NCC.

Introduction - Moyamoya disease was first believed to be confined to Japan, but over the years it has been reported all over the world. We report seven cases from the University Hospital of the Faculty of Medicine of Ribeirao Preto, University of Sao Paulo with a review of the previously described cases in Brazil. Material and methods - The diagnosis was based on the diagnostic criteria of the Research Committee on Spontaneous Occlusion of the Circle of Willis. Results - Five patients presented ischemic and two hemorrhagic events. The meta-analysis of the six cases previously described in Brazil showed that only two were true moyamoya disease according to the diagnostic criteria. Conclusion - We can assume that the real frequency of moyamoya disease has been underestimated in Brazil.

Inpatient rehabilitation has been traditionally employed in developed countries, while in developing countries, outpatient rehabilitation is the rule. The purpose of this study was to compare the patterns of recovery of upper extremity (UE) function, global impairment and independence in activities of daily living (ADL) during the first month after ischaemic stroke in inpatient (United States) and outpatient (Brazil) rehabilitation settings. Design and Methods: This is a prospective cohort comparison study. Twenty patients from each country were selected using identical inclusion criteria. The study measures employed were the UE portion of the Fugl-Meyer scale, the Action Research Arm test, the National Institutes of Health Stroke Scale and Barthel Index. Changes from baseline to the end of treatment, efficiency and effectiveness of each treatment were compared. Results: Both populations exhibited significant improvement between the first and second evaluations in the four outcome scales (P 0.05). Conclusions: Substantially different treatment approaches after ischaemic stroke led to similar results in UE function, global impairment and ADL. Further studies in larger populations should be performed in order to confirm the present results.

Background: Recent studies have reported autonomic dysfunction (AD) in multiple sclerosis (MS), bladder and/or bowel dysfunction, orthostatic hypotension, and cardiac adaptation disorders have been observed in a wide range (15-80%). The primary aim of this study is to investigate the frequency and association of AD in MS patients, assessed by sympathetic skin reaction (SSR) and a symptoms questionnaire. The secondary aims of this study are to study the association of AD and disease disability assessed by expanded disability status scale (EDSS), as well as disease duration. Design and Methods: 100 clinically definite MS patients were evaluated for ANS dysfunction by use of an autonomic symptoms questionnaire and SSR testing. The relationship between these methods, AD and disease-related parameters, such as the expanded disability status scale (EDSS) and disease duration were all evaluated. Results: 65% of the patients presented with AD and 29% of these patients had abnormal SSR results. MS patients with high EDSS values (EDSS >4) and longer disease duration were more likely to have ANS dysfunction (p less than 0.0001). Conclusions. ANS dysfunction is not uncommon in CDMS patients and thus noninvasive investigations of AD are warranted to optimize AD evaluation and disease management.