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Several health organizations recommend low sodium intake (below 2.3 g/day, 5.8 g/day of salt) for entire populations, on the premise that lowering of sodium intake, irrespective of its level of intake, will lower blood pressure and, in turn, will result in a lower incidence of cardiovascular disease. These guidelines were developed without effective interventions to achieve long term sodium intakes at low levels in free-living individuals and without high-quality evidence that low sodium intake reduces cardiovascular events (compared with average levels of intake). In this review, we examine whether advice to consume low amounts of sodium is supported by robust evidence. We contend that current evidence indicates that most people around the world consume a moderate range of dietary sodium (3 to 5 g/day), that this level of intake is associated with the lowest risk of cardiovascular disease and mortality, and that the risk of adverse health outcomes increases when sodium intakes exceeds 5 g/day or is below 3 g/day. While the current evidence has limitations, it is reasonable, based upon prospective cohort studies, to suggest a mean target of below 5 g/day in populations, while awaiting the results of large randomized controlled trials of sodium reduction on cardiovascular disease and death.

PurposeIncreasing potassium intake, especially in populations with low potassium intake and high sodium intake, has emerged as an important population-level intervention to reduce cardiovascular events. Current guideline recommendations, such as those made by the World Health Organisation, recommend a potassium intake of > 3.5 g/day. We sought to determine summary estimates for mean potassium intake and sodium/potassium (Na/K) ratio in different regions of the world.MethodsWe performed a systematic review and meta-analysis. We identified 104 studies, that included 98 nationally representative surveys and 6 multi-national studies. To account for missingness and incomparability of data, a Bayesian hierarchical imputation model was applied to estimating summary estimates of mean dietary potassium intake (primary outcome) and sodium/potassium ratio.ResultsOverall, 104 studies from 52 countries were included (n = 1,640,664). Mean global potassium intake was 2.25 g/day (57 mmol/day) (95% credible interval (CI) 2.05–2.44 g/day), with highest intakes in Eastern and Western Europe (mean intake 3.53g/day, 95% CI 3.05–4.01 g/day and 3.29 g/day, 95% CI 3.13–3.47 g/day, respectively) and lowest intakes in East Asia (mean intake 1.89 g/day; 95% CI 1.55–2.25 g/day). Approximately 31% (95% CI, 30–41%) of global population included have an estimated potassium intake > 2.5 g/day, with 14% (95% CI 11–17%) above 3.5 g/day.ConclusionGlobal mean potassium intake (2.25 g/day) falls below current guideline recommended intake level of > 3.5 g/day, with only 14% (95% CI 11–17%) of the global population achieving guideline-target mean intake. There was considerable regional variation, with lowest mean potassium intake reported in Asia, and highest intake in Eastern and Western Europe.

Although stroke is the second leading cause of death worldwide, no comprehensive and comparable assessment of incidence, prevalence, mortality, disability, and epidemiological trends has been estimated for most regions. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to estimate the global and regional burden of stroke during 1990–2010. We searched Medline, Embase, LILACS, Scopus, PubMed, Science Direct, Global Health Database, the WHO library, and WHO regional databases from 1990 to 2012 to identify relevant studies published between 1990 and 2010. We applied the GBD 2010 analytical technique (DisMod-MR), based on disease-specific, pre-specified associations between incidence, prevalence, and mortality, to calculate regional and country-specific estimates of stroke incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) lost by age group (<75 years, ≥75 years, and in total) and country income level (high-income, and low-income and middle-income) for 1990, 2005, and 2010. We included 119 studies (58 from high-income countries and 61 from low-income and middle-income countries). From 1990 to 2010, the age-standardised incidence of stroke significantly decreased by 12% (95% CI 6–17) in high-income countries, and increased by 12% (–3 to 22) in low-income and middle-income countries, albeit non-significantly. Mortality rates decreased significantly in both high income (37%, 31–41) and low-income and middle-income countries (20%, 15–30). In 2010, the absolute numbers of people with first stroke (16·9 million), stroke survivors (33 million), stroke-related deaths (5·9 million), and DALYs lost (102 million) were high and had significantly increased since 1990 (68%, 84%, 26%, and 12% increase, respectively), with most of the burden (68·6% incident strokes, 52·2% prevalent strokes, 70·9% stroke deaths, and 77·7% DALYs lost) in low-income and middle-income countries. In 2010, 5·2 million (31%) strokes were in children (aged <20 years old) and young and middle-aged adults (20–64 years), to which children and young and middle-aged adults from low-income and middle-income countries contributed almost 74 000 (89%) and 4·0 million (78%), respectively, of the burden. Additionally, we noted significant geographical differences of between three and ten times in stroke burden between GBD regions and countries. More than 62% of new strokes, 69·8% of prevalent strokes, 45·5% of deaths from stroke, and 71·7% of DALYs lost because of stroke were in people younger than 75 years. Although age-standardised rates of stroke mortality have decreased worldwide in the past two decades, the absolute number of people who have a stroke every year, stroke survivors, related deaths, and the overall global burden of stroke (DALYs lost) are great and increasing. Further study is needed to improve understanding of stroke determinants and burden worldwide, and to establish causes of disparities and changes in trends in stroke burden between countries of different income levels. Bill & Melinda Gates Foundation.

AbstractObjectiveTo assess the effectiveness and safety of dual agent antiplatelet therapy combining clopidogrel and aspirin to prevent recurrent thrombotic and bleeding events compared with aspirin alone in patients with acute minor ischaemic stroke or transient ischaemic attack (TIA).DesignSystematic review and meta-analysis of randomised, placebo controlled trials.Data sourcesMedline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Library, ClinicalTrials.gov, WHO website, PsycINFO, and grey literature up to 4 July 2018.Eligibility criteria for selecting studies and methodsTwo reviewers independently screened potentially eligible studies according to predefined selection criteria and assessed the risk of bias using a modified version of the Cochrane risk of bias tool. A third team member reviewed all final decisions, and the team resolved disagreements through discussion. When reports omitted data that were considered important, clarification and additional information was sought from the authors. The analysis was conducted in RevMan 5.3 and MAGICapp based on GRADE methodology.ResultsThree eligible trials involving 10 447 participants were identified. Compared with aspirin alone, dual antiplatelet therapy with clopidogrel and aspirin that was started within 24 hours of symptom onset reduced the risk of non-fatal recurrent stroke (relative risk 0.70, 95% confidence interval 0.61 to 0.80, I2=0%, absolute risk reduction 1.9%, high quality evidence), without apparent impact on all cause mortality (1.27, 0.73 to 2.23, I2=0%, moderate quality evidence) but with a likely increase in moderate or severe extracranial bleeding (1.71, 0.92 to 3.20, I2=32%, absolute risk increase 0.2%, moderate quality evidence). Most stroke events, and the separation in incidence curves between dual and single therapy arms, occurred within 10 days of randomisation; any benefit after 21 days is extremely unlikely.ConclusionsDual antiplatelet therapy with clopidogrel and aspirin given within 24 hours after high risk TIA or minor ischaemic stroke reduces subsequent stroke by about 20 in 1000 population, with a possible increase in moderate to severe bleeding of 2 per 1000 population. Discontinuation of dual antiplatelet therapy within 21 days, and possibly as early as 10 days, of initiation is likely to maximise benefit and minimise harms.

Cryptogenic (of unknown cause) ischaemic strokes are now thought to comprise about 25% of all ischaemic strokes. Advances in imaging techniques and improved understanding of stroke pathophysiology have prompted a reassessment of cryptogenic stroke. There is persuasive evidence that most cryptogenic strokes are thromboembolic. The thrombus is thought to originate from any of several well established potential embolic sources, including minor-risk or covert cardiac sources, veins via paradoxical embolism, and non-occlusive atherosclerotic plaques in the aortic arch, cervical, or cerebral arteries. Accordingly, we propose that embolic strokes of undetermined source are a therapeutically relevant entity, which are defined as a non-lacunar brain infarct without proximal arterial stenosis or cardioembolic sources, with a clear indication for anticoagulation. Because emboli consist mainly of thrombus, anticoagulants are likely to reduce recurrent brain ischaemia more effectively than are antiplatelet drugs. Randomised trials testing direct-acting oral anticoagulants for secondary prevention of embolic strokes of undetermined source are warranted.

23% of the total global burden of disease is attributable to disorders in people aged 60 years and older. Although the proportion of the burden arising from older people (≥60 years) is highest in high-income regions, disability-adjusted life years (DALYs) per head are 40% higher in low-income and middle-income regions, accounted for by the increased burden per head of population arising from cardiovascular diseases, and sensory, respiratory, and infectious disorders. The leading contributors to disease burden in older people are cardiovascular diseases (30·3% of the total burden in people aged 60 years and older), malignant neoplasms (15·1%), chronic respiratory diseases (9·5%), musculoskeletal diseases (7·5%), and neurological and mental disorders (6·6%). A substantial and increased proportion of morbidity and mortality due to chronic disease occurs in older people. Primary prevention in adults aged younger than 60 years will improve health in successive cohorts of older people, but much of the potential to reduce disease burden will come from more effective primary, secondary, and tertiary prevention targeting older people. Obstacles include misplaced global health priorities, ageism, the poor preparedness of health systems to deliver age-appropriate care for chronic diseases, and the complexity of integrating care for complex multimorbidities. Although population ageing is driving the worldwide epidemic of chronic diseases, substantial untapped potential exists to modify the relation between chronological age and health. This objective is especially important for the most age-dependent disorders (ie, dementia, stroke, chronic obstructive pulmonary disease, and vision impairment), for which the burden of disease arises more from disability than from mortality, and for which long-term care costs outweigh health expenditure. The societal cost of these disorders is enormous.

There is conflicting evidence regarding the outcomes of acute stroke patients who present to hospital within normal working hours ('in-hours') compared with the 'out-of-hours' period. This study aimed to assess the effect of time of stroke presentation on outcomes within the Irish context, to inform national stroke service delivery. A secondary analysis of data from the Irish National Audit of Stroke (INAS) from Jan 2016 to Dec 2019 was carried out. Patient and process outcomes were assessed for patients presenting 'in-hours' (8:00-17:00 Monday-Friday) compared with 'out-of-hours' (all other times). Data on arrival time were available for 13,996 patients (male 56.2%; mean age 72.5 years), of which 55.7% presented 'out-of-hours'. In hospital mortality was significantly lower among those admitted 'in-hours' (11.3%, n = 534) compared with 'out-of-hours' (12.8%, n = 749); (adjusted Odds Ratio (OR) 0.82; 95% Confidence Interval CI [95% CI] 0.72-0.89). Poor functional outcome at discharge (Modified Rankin Scale ≥ 3) was also significantly lower in those presenting 'in-hours' (adjusted OR 0.79; 95% CI 0.68-0.91). In patients receiving thrombolysis, mean door to needle time was shorter for 'in-hours' presentation at 55.8 mins (n = 562; SD 35.43 mins), compared with 'out-of-hours' presentation at 80.5 mins (n = 736; SD 38.55 mins, p < .001). More than half of stroke patients in Ireland present 'out-of-hours' and these presentations are associated with a higher mortality and a lower odds of functional independence at discharge. It is imperative that stroke pathways consider the 24 hour period to ensure the delivery of effective stroke care, and modification of 'out-of-hours' stroke care is required to improve overall outcomes.

Objective To evaluate the relative risk of pulmonary disease among patients with psoriasis, psoriatic arthritis, and inflammatory bowel disease treated with methotrexate.Data sources PubMed, Cochrane central register of controlled trials, and Embase to 9 January 2014.Study selection Double blind randomised controlled trials of methotrexate versus placebo or active comparator agents in adults with psoriatic arthritis, psoriasis, or inflammatory bowel disease. Studies with fewer than 50 participants or of less than 12 weeks’ duration were excluded.Data synthesis Two investigators independently searched both databases. All authors reviewed selected studies. We compared relative risk differences using the Mantel-Haenszel random effects method to assess total respiratory adverse events, infectious respiratory adverse events, non-infectious respiratory adverse events, interstitial lung disease, and death.Results Seven studies met our inclusion criteria, six with placebo as the comparator. Heterogeneity across the studies was not significant (I2=0%), allowing combination of trial results. 504 respiratory adverse events were documented in 1630 participants. Methotrexate was not associated with an increased risk of adverse respiratory events (relative risk 1.03, 95% confidence interval 0.90 to 1.17), respiratory infections (1.02, 0.88 to 1.19), or non-infectious respiratory events (1.07, 0.58 to 1.96). No pulmonary deaths occurred.Conclusions Findings suggested that there was no increased risk of lung disease in methotrexate treated patients with non-malignant inflammatory diseases. Given the limitations of the study, however, we cannot exclude a small but clinically important risk.

What is the role of dual antiplatelet therapy after high risk transient ischaemic attack or minor stroke? Specifically, does dual antiplatelet therapy with a combination of aspirin and clopidogrel lead to a greater reduction in recurrent stroke and death over the use of aspirin alone when given in the first 24 hours after a high risk transient ischaemic attack or minor ischaemic stroke? An expert panel produced a strong recommendation for initiating dual antiplatelet therapy within 24 hours of the onset of symptoms, and for continuing it for 10-21 days. Current practice is typically to use a single drug

Background: Short-term changes in levels of fine ambient particulate matter (PM 2.5 ) may increase the risk of acute ischemic stroke; however, results from prior studies have been inconsistent. We examined this hypothesis using data from a multicenter prospective stroke registry. Methods: We analyzed data from 9202 patients hospitalized with acute ischemic stroke, having a documented date and time of stroke onset, and residing within 50 km of a PM 2.5 monitor in 8 cities in Ontario, Canada. We evaluated the risk of ischemic stroke onset associated with PM 2.5 in each city using a time-stratified case-crossover design, matching on day of week and time of day. We then combined these city-specific estimates using random-effects meta-analysis techniques. We examined whether the effects of PM 2.5 differed across strata defined by patient characteristics and ischemic stroke etiology. Results: Overall, PM 2.5 was associated with a -0.7% change in ischemic stroke risk per 10-μg/m 3 increase in PM 2.5 (95% confidence interval = -6.3% to 5.1%). These overall negative results were robust to a number of sensitivity analyses. Among patients with diabetes mellitus, PM 2.5 was associated with an 11% increase in ischemic stroke risk (1% to 22%). The association between PM 2.5 and ischemic stroke risk varied according to stroke etiology, with the strongest associations observed for strokes due to large-artery atherosclerosis and small-vessel occlusion. Conclusions: These results do not support the hypothesis that short-term increases in PM 2.5 levels are associated with ischemic stroke risk overall. However, specific patient subgroups may be at increased risk of particulate-related ischemic strokes.