Deaths from stroke in US young adults, 1989-2009.

ObjectiveTo determine what the trends in stroke mortality have been over 2 decades in young adults.MethodsIn this cohort study, we analyzed death certificate data for ischemic and hemorrhagic stroke (intracerebral hemorrhage [ICH] and subarachnoid hemorrhage [SAH]) in adults aged 20-44 in the United States for 1989 through 2009, covering approximately 2.2 billion person-years. Poisson regression was used to calculate and compare time trend data between groups and to compare trends in young adults to those in adults over age 45.ResultsMortality from stroke in young adults declined by 35% over the study period, with reductions in all 3 stroke subtypes (ischemic stroke decreased by 15%, ICH by 47%, and SAH by 50%). Black race was a risk factor for all 3 stroke subtypes (relative risk 2.4 for ischemic stroke, 4.0 for ICH, and 2.1 for SAH), but declines in all stroke subtypes were more dramatic in black compared to white participants (p < 0.001 for all stroke subtypes).ConclusionsAlthough hospitalizations for stroke in young patients have been increasing, the apparent decrease in mortality rates and in racial disparities suggests that recognition and treatment in this group may be improving

Recent trauma and acute infection as risk factors for childhood arterial ischemic stroke.

ObjectiveTrauma and acute infection have been associated with stroke in adults, and are prevalent exposures in children. We hypothesized that these environmental factors are independently associated with childhood arterial ischemic stroke (AIS).MethodsIn a case-control study nested within a cohort of 2.5 million children (≤19 years old) enrolled in an integrated health care plan (1993-2007), childhood AIS cases (n = 126) were identified from electronic records and confirmed through chart review. Age- and facility-matched controls (n = 378) were randomly selected from the cohort. Exposures were determined from review of medical records prior to the stroke diagnosis, or the same date for the paired controls; time windows were defined a priori.ResultsA medical encounter for head or neck trauma within the prior 12 weeks was an independent risk factor for childhood AIS (odds ratio [OR], 7.5; 95% confidence interval [CI], 2.9-19.3), present in 12% of cases (1.6% of controls). Median time from trauma to stroke was 0.5 days (interquartile range, 0-2 days); post hoc redefinition of trauma exposure (prior 1 week) was more strongly associated with AIS: OR, 39; 95% CI, 5.1-298. A medical encounter for a minor acute infection (prior 4 weeks) was also an independent risk factor (OR, 4.6; 95% CI, 2.6-8.2), present in 33% of cases (13% of controls). No single infection type predominated. Only 2 cases had exposure to trauma and infection.InterpretationTrauma and acute infection are common independent risk factors for childhood AIS, and may be targets for stroke prevention strategies

Cost-effectiveness of ticagrelor plus aspirin versus aspirin in acute ischaemic stroke or transient ischaemic attack: an economic evaluation of the THALES trial

Health economics; StrokeEconomía de la salud; IctusEconomia de la salut; IctusObjective THALES demonstrated that ticagrelor plus aspirin reduced the risk of stroke or death but increased bleeding versus aspirin during the 30 days following a mild-to-moderate acute non-cardioembolic ischaemic stroke (AIS) or high-risk transient ischaemic attack (TIA). There are no cost-effectiveness analyses supporting this combination in Europe. To address this, a cost-effectiveness analysis was performed. Methods Cost-effectiveness was evaluated using a decision tree and Markov model with a short-term and long-term (30-year) horizon. Stroke, mortality, bleeding and EuroQol-5 Dimension (EQ-5D) data from THALES were used to estimate short-term outcomes. Model transitions were based on stroke severity (disabling stroke was defined as modified Rankin Scale >2). Healthcare resource utilisation and EQ-5D data beyond 30 days were based on SOCRATES, another trial in AIS/TIA that compared ticagrelor with aspirin. Long-term costs, survival and disutilities were based on published literature. Unit costs were derived from national databases and discounted at 3% annually from a Swedish healthcare perspective. Results One-month treatment with ticagrelor plus aspirin resulted in 12 fewer strokes, 4 additional major bleeds and cost savings of €95 000 per 1000 patients versus aspirin from a Swedish healthcare perspective. This translated into increased quality-adjusted life-years (0.04) and reduced societal costs (−€1358) per patient over a lifetime horizon. Key drivers of cost-effectiveness were number of patients experiencing subsequent disabling stroke and degree of disability. Findings were robust over a range of input assumptions. Conclusion One month of treatment with ticagrelor plus aspirin is likely to improve outcomes and reduce costs versus aspirin in mild-to-moderate AIS or high-risk TIA.AstraZeneca funded the THALES trial and the cost-effectiveness analysis of this study

The TEAM trial: Safety and efficacy of endovascular treatment of unruptured intracranial aneurysms in the prevention of aneurysmal hemorrhages: A randomized comparison with indefinite deferral of treatment in 2002 patients followed for 10 years

The management of patients with unruptured aneurysms remains controversial. Patients with unruptured aneurysms may suffer intracranial haemorrhage, but the incidence of this event is still debated; endovascular treatment may prevent rupture, but involves immediate risks. Hence, the balance of risks and benefits of endovascular treatment is uncertain. Here, we report the design of the TEAM trial, the first international, randomized, controlled trial comparing conservative management with endovascular treatment. Primary endpoint is mortality and morbidity (modified Rankin Score ≥ 3) from intracranial haemorrhage or treatment. Secondary endpoints include incidence of hemorrhagic events, morbidity related to endovascular coiling, morphological results, overall clinical outcome and quality of life. Statistical tests compare between probabilities at 5- and 10-years of 1/mortality from haemorrhage related to the lesion, excluding per-operative complications; 2/mortality from haemorrhage or from complications of treatment; 3/combined disease or treatment related mortality and morbidity in the absence of other causes of death or disability. The study will be conducted in 60 international centres and will enrol 2,002 patients equally divided between the two groups, a size sufficient to achieve 80% power at a 0.0167 significance to detect differences in 1) disease or treatment-related poor outcomes from 7–9% to 3–5%; 2) overall mortality from 16 to 11%. Duration of the study is 14 years, the first three years being for patient recruitment plus a minimum of 10 years of follow-up. The TEAM trial thus offers a means to reconcile the introduction of a new approach with the necessity to acknowledge uncertainties

Platelet‐Oriented Inhibition in New TIA and Minor Ischemic Stroke ( POINT ) Trial: Rationale and design

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99014/1/ijs12129.pd

Cilostazol for Secondary Stroke Prevention: History, Evidence, Limitations, and Possibilities

Cilostazol is a phosphodiesterase III inhibitor with a long track record of safety that is FDA and EMA approved for the treatment of claudication in patients with peripheral arterial disease. In addition, cilostazol has been approved for secondary stroke prevention in several Asian countries based on trials that have demonstrated a reduction in stroke recurrence among patients with non-cardioembolic stroke. The onset of benefit appears after 60–90 days of treatment, which is consistent with cilostazol’s pleiotropic effects on platelet aggregation, vascular remodeling, blood flow, and plasma lipids. Cilostazol appears safe and does not increase the risk of major bleeding when given alone or in combination with aspirin or clopidogrel. Adverse effects such as headache, gastrointestinal symptoms and palpitations, however, contributed to a 6% increase in drug discontinuation among patients randomized to cilostazol in a large secondary stroke prevention trial (CSPS.com). Due to limitations of prior trials, such as open label design, premature trial termination, large loss to follow-up, lack of functional or cognitive outcome data, and exclusive enrollment in Asia, the existing trials have not led to a change in clinical practice or guidelines in Western countries. These limitations could be addressed by a double-blind placebo-controlled randomized trial conducted in a broader population. If positive, it would increase the evidence in support of long-term treatment with cilostazol for secondary prevention in the millions of patients worldwide who have suffered a non-cardioembolic ischemic stroke

NIH Disease Funding Levels and Burden of Disease

BACKGROUND: An analysis of NIH funding in 1996 found that the strongest predictor of funding, disability-adjusted life-years (DALYs), explained only 39% of the variance in funding. In 1998, Congress requested that the Institute of Medicine (IOM) evaluate priority-setting criteria for NIH funding; the IOM recommended greater consideration of disease burden. We examined whether the association between current burden and funding has changed since that time. METHODS: We analyzed public data on 2006 NIH funding for 29 common conditions. Measures of US disease burden in 2004 were obtained from the World Health Organization's Global Burden of Disease study and national databases. We assessed the relationship between disease burden and NIH funding dollars in univariate and multivariable log-linear models that evaluated all measures of disease burden. Sensitivity analyses examined associations with future US burden, current and future measures of world disease burden, and a newly standardized NIH accounting method. RESULTS: In univariate and multivariable analyses, disease-specific NIH funding levels increased with burden of disease measured in DALYs (p = 0.001), which accounted for 33% of funding level variation. No other factor predicted funding in multivariable models. Conditions receiving the most funding greater than expected based on disease burden were AIDS ($2474 M), diabetes mellitus ($390 M), and perinatal conditions ($297 M). Depression ($719 M), injuries ($691 M), and chronic obstructive pulmonary disease ($613 M) were the most underfunded. Results were similar using estimates of future US burden, current and future world disease burden, and alternate NIH accounting methods. CONCLUSIONS: Current levels of NIH disease-specific research funding correlate modestly with US disease burden, and correlation has not improved in the last decade

Duration of hospital participation in a nationwide stroke registry is associated with improved quality of care

BACKGROUND: There are several proven therapies for patients with ischemic stroke or transient ischemic attack (TIA), including prophylaxis of deep venous thrombosis (DVT) and initiation of antithrombotic medications within 48 h and at discharge. Stroke registries have been promoted as a means of increasing use of such interventions, which are currently underutilized. METHODS: From 1999 through 2003, 86 U.S. hospitals participated in Ethos, a voluntary web-based acute stroke treatment registry. Detailed data were collected on all patients admitted with a diagnosis of TIA or ischemic stroke. Rates of optimal treatment (defined as either receipt or a valid contraindication) were examined within each hospital as a function of its length of time in registry. Generalized estimating equations were used to adjust for patient and hospital characteristics. RESULTS: A total of 16,301 patients were discharged with a diagnosis of stroke or TIA from 50 hospitals that participated for more than 1 year. Rates of optimal treatment during the first 3 months of participation were as follows: 92.5% for antithrombotic medication within 48 h, 84.6% for antithrombotic medications at discharge, and 77.1% for DVT prophylaxis. Rates for all treatments improved with duration of participation in the registry (p < 0.05), with the most dramatic improvements in the first year. CONCLUSION: In a large cohort of patients with stroke or TIA, three targeted quality-improvement measures improved among hospitals participating in a disease-specific registry. Although the changes could be attributed to interventions other than the registry, these findings demonstrate the potential for hospital-level interventions to improve care for patients with stroke and TIA

Financing of U.S. Biomedical Research and New Drug Approvals across Therapeutic Areas

We estimated U.S. biomedical research funding across therapeutic areas, determined the association with disease burden, and evaluated new drug approvals that resulted from this investment.We calculated funding from 1995 to 2005 and totaled Food and Drug Administration approvals in eight therapeutic areas (cardiovascular, endocrine, gastrointestinal, genitourinary, HIV/AIDS, infectious disease excluding HIV, oncology, and respiratory) primarily using public data. We then calculated correlations between funding, published estimates of disease burden, and drug approvals. Financial support for biomedical research from 1995 to 2005 increased across all therapeutic areas between 43% and 369%. Industry was the principal funder of all areas except HIV/AIDS, infectious disease, and oncology, which were chiefly sponsored by the National Institutes of Health (NIH). Total (rho = 0.70; P = .03) and industry funding (rho = 0.69; P = .04) were correlated with projected disease burden in high income countries while NIH support (rho = 0.80; P = .01) was correlated with projected disease burden globally. From 1995 to 2005 the number of new approvals was flat or declined across therapeutic areas, and over an 8-year lag period, neither total nor industry funding was correlated with future approvals.Across therapeutic areas, biomedical research funding increased substantially, appears aligned with disease burden in high income countries, but is not linked to new drug approvals. The translational gap between funding and new therapies is affecting all of medicine, and remedies must include changes beyond additional financial investment