Contemporaneous data on variations in outcome after first-ever-lifetime stroke between European populations are lacking. We compared differences in case fatality rates, functional outcome, and living ...conditions 3 months after stroke within the European Registers of Stroke Collaboration.
Population-based stroke registers were established in France (Dijon), Italy (Sesto Fiorentino), Lithuania (Kaunas), the United Kingdom (London), Spain (Menorca), and Poland (Warsaw). All patients with first-ever-lifetime stroke of all age groups from the source population (1,087,048 inhabitants) were included. Data collection took part between 2004 and 2006. The study investigated population variations in outcome at 3 months (death, institutionalization due to stroke, or Barthel Index below 12 points) using multivariable logistic regression analyses adjusted for age, sex, stroke severity, stroke subtype, and comorbidities.
A total of 2,034 patients with first-ever-lifetime stroke were included. Median age was 73 years, 52% were female. The mean weighted cumulative risk of death was 21.8% (95% confidence interval 20.0 to 23.6) with a 3-fold variation across populations. The weighted proportion of poor outcome was 41.3% (95% confidence interval 39.0 to 43.7) with a 2-fold variation across populations.
More than 40% of patients had a poor outcome, defined as being dead, dependent, or institutionalized 3 months after stroke. Substantial outcome variations were found between populations that were explained by case mix variables in this analysis, yet a trend toward a higher risk of poor outcome was present in Kaunas.
Stroke is a major global health problem. It is the third leading cause of death and the leading cause of adult disability. INTERHEART, a global case-control study of acute myocardial infarction in 52 ...countries (29,972 participants), identified nine modifiable risk factors that accounted for >90% of population-attributable risk. However, traditional risk factors (e.g. hypertension, cholesterol) appear to exert contrasting risks for stroke compared with coronary heart disease, and the etiology of stroke is far more heterogeneous. In addition, our knowledge of risk factors for stroke in low-income countries is inadequate, where a very large burden of stroke occurs. Accordingly, a similar epidemiological study is required for stroke, to inform effective population-based strategies to reduce the risk of stroke.
INTERSTROKE is an international, multicenter case-control study. Cases are patients with a first stroke within 72 h of hospital presentation in whom CT or MRI is performed. Proxy respondents are used for cases unable to communicate. Etiological and topographical stroke subtype is documented for all cases. Controls are hospital- and community-based, matched for gender, ethnicity and age (+/-5 years). A questionnaire (cases and controls) is used to acquire information on known and proposed risk factors for stroke. Cardiovascular (e.g. blood pressure) and anthropometric (e.g. waist-to-hip ratio) measurements are obtained at the time of interview. Nonfasting blood samples and random urine samples are obtained from cases and controls. Study Significance: An effective global strategy to reduce the risk of stroke mandates systematic measurement of the contribution of the major vascular risk factors within defined ethnic groups and geographical locations.
At 3 years after diagnosis, the risk of Alzheimer disease (AD) for patients with mild cognitive impairment (MCI) is estimated to be 18% to 30%. To improve treatment of patients at high dementia risk ...there is a need for a better prediction of the risk for transition from MCI to AD. Olfactory deficits are a hypothetical predictor of conversion form MCI to AD. Furthermore, several studies point at volumetric reduction of medial temporal lobe structures as predictors of conversion form MCI to AD. The primary aim of this study was to evaluate whether investigations of odor deficits in MCI combined with neuropsychological tests and MRI examinations can improve prediction of the development of dementia.
Changes in olfactory functions, cognitive functions, and volume of medial temporal lobe structures (hippocampus, parahippocampal gyrus, and amygdala) were evaluated in a 24-month follow-up study in 49 MCI patients and 33 controls.
In the MCI group, a prediction of strong cognitive functions deterioration based on poor performance in Olfactory Identification tests shows sensitivity of 57% and specificity of 88%. The test based on cognitive functions only shows a sensitivity of 44%, and 89%, respectively. Combined tests having a criteria of poor olfactory identification performance AND poor results of neuropsychological tests showed a sensitivity of 100% and specificity of 84%. Furthermore, correlation was found between the results of Olfactory Identification tests at baseline and deterioration of cognitive functions at follow up. Odor identification threshold did not appear to be a dementia predictor. A correlation of progress of cognitive function deterioration, odor identification deterioration, and decrease of volume of the hippocampus was also observed.
Prediction of MCI to dementia conversion can be improved by supplementing the neuropsychological tests with odor identification tests. A follow up study of hippocampus volume reduction, OI performance and cognitive functions deterioration will further increase prediction accuracy.
Summary Background Stroke is a leading cause of death and disability, especially in low-income and middle-income countries. We sought to quantify the importance of potentially modifiable risk factors ...for stroke in different regions of the world, and in key populations and primary pathological subtypes of stroke. Methods We completed a standardised international case-control study in 32 countries in Asia, America, Europe, Australia, the Middle East, and Africa. Cases were patients with acute first stroke (within 5 days of symptom onset and 72 h of hospital admission). Controls were hospital-based or community-based individuals with no history of stroke, and were matched with cases, recruited in a 1:1 ratio, for age and sex. All participants completed a clinical assessment and were requested to provide blood and urine samples. Odds ratios (OR) and their population attributable risks (PARs) were calculated, with 99% confidence intervals. Findings Between Jan 11, 2007, and Aug 8, 2015, 26 919 participants were recruited from 32 countries (13 447 cases 10 388 with ischaemic stroke and 3059 intracerebral haemorrhage and 13 472 controls). Previous history of hypertension or blood pressure of 140/90 mm Hg or higher (OR 2·98, 99% CI 2·72–3·28; PAR 47·9%, 99% CI 45·1–50·6), regular physical activity (0·60, 0·52–0·70; 35·8%, 27·7–44·7), apolipoprotein (Apo)B/ApoA1 ratio (1·84, 1·65–2·06 for highest vs lowest tertile; 26·8%, 22·2–31·9 for top two tertiles vs lowest tertile), diet (0·60, 0·53–0·67 for highest vs lowest tertile of modified Alternative Healthy Eating Index mAHEI; 23·2%, 18·2–28·9 for lowest two tertiles vs highest tertile of mAHEI), waist-to-hip ratio (1·44, 1·27–1·64 for highest vs lowest tertile; 18·6%, 13·3–25·3 for top two tertiles vs lowest), psychosocial factors (2·20, 1·78–2·72; 17·4%, 13·1–22·6), current smoking (1·67, 1·49–1·87; 12·4%, 10·2–14·9), cardiac causes (3·17, 2·68–3·75; 9·1%, 8·0–10·2), alcohol consumption (2·09, 1·64–2·67 for high or heavy episodic intake vs never or former drinker; 5·8%, 3·4–9·7 for current alcohol drinker vs never or former drinker), and diabetes mellitus (1·16, 1·05–1·30; 3·9%, 1·9–7·6) were associated with all stroke. Collectively, these risk factors accounted for 90·7% of the PAR for all stroke worldwide (91·5% for ischaemic stroke, 87·1% for intracerebral haemorrhage), and were consistent across regions (ranging from 82·7% in Africa to 97·4% in southeast Asia), sex (90·6% in men and in women), and age groups (92·2% in patients aged ≤55 years, 90·0% in patients aged >55 years). We observed regional variations in the importance of individual risk factors, which were related to variations in the magnitude of ORs (rather than direction, which we observed for diet) and differences in prevalence of risk factors among regions. Hypertension was more associated with intracerebral haemorrhage than with ischaemic stroke, whereas current smoking, diabetes, apolipoproteins, and cardiac causes were more associated with ischaemic stroke (p<0·0001). Interpretation Ten potentially modifiable risk factors are collectively associated with about 90% of the PAR of stroke in each major region of the world, among ethnic groups, in men and women, and in all ages. However, we found important regional variations in the relative importance of most individual risk factors for stroke, which could contribute to worldwide variations in frequency and case-mix of stroke. Our findings support developing both global and region-specific programmes to prevent stroke. Funding Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland (Sweden), AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network.
The Working Group was established at the initiative of the General Board of the Polish Society of Epileptology (PSE) to develop an expert position on the treatment of convulsive status epilepticus ...(SE) in adults and children in Poland. Generalized convulsive SE is the most common form and also represents the greatest threat to life, highlighting the importance of the choice of appropriate therapeutic treatment.
We present the therapeutic options separately for treatment during the early preclinical (>5–30min), established (30–60min), and refractory (>60min) SE phases. This division is based on time and response to AEDs, and indicates a practical approach based on pathophysiological data.
Benzodiazepines (BZD) are the first-line drugs. In cases of ineffective first-line treatment and persistence of the seizure, the use of second-line treatment: phenytoin, valproic acid or phenobarbital is required. SE that persists after the administration of benzodiazepines and phenytoin or another second-line AED at appropriate doses is defined as refractory and drug resistant and requires treatment in the intensive care unit (ICU). EEG monitoring is essential during therapy at this stage. Anesthesia is typically continued for an initial period of 24h followed by a slow reversal and is re-established if seizures recur. Anesthesia is usually administered either to the level of the “burst suppression pattern” or to obtain the “EEG suppression” pattern.
Experts agree that close and early cooperation with a neurologist and anesthetist aiming to reduce the risk of pharmacoresistant cases is an extremely important factor in the treatment of patients with SE. This report has educational, practical and organizational aspects, outlining a standard plan for SE management in Poland that will improve therapeutic efficacy.
Objective: Preclinical studies indicate that dopaminergic transmission in the basal ganglia may be involved in processing of both pleasant and unpleasant stimuli. Given this, the aim of the present ...study was to assess taste responses to sweet, bitter, sour, and salty substances in patients with Parkinson’s disease (PD). Methods: Rated intensity and pleasantness of filter paper discs soaked in sucrose (10–60%), quinine (0.025–0.5%), citric acid (0.25–4.0%), or sodium chloride (1.25–20%) solutions was evaluated in 30 patients with PD and in 33 healthy controls. Paper discs soaked in deionised water served as control stimuli. In addition, reactivity to 100 ml samples of chocolate and vanilla milk was assessed in both groups. Taste detection thresholds were assessed by means of electrogustometry. Sociodemographic and neuropsychiatric data, including cigarette smoking, alcohol consumption, tea and coffee drinking, depressive symptoms, and cognitive functioning were collected. Results: In general, perceived intensity, pleasantness, and identification of the sucrose, quinine, citric acid, or sodium chloride samples did not differ between the PD patients and controls. Intensity ratings of the filter papers soaked in 0.025% quinine were significantly higher in the PD patients compared with the control group. No inter-group differences were found in taste responses to chocolate and vanilla milk. Electrogustometric thresholds were significantly (p = 0.001) more sensitive in the PD patients. Conclusions: PD is not associated with any major alterations in responses to pleasant or unpleasant taste stimuli. Patients with PD may present enhanced taste acuity in terms of electrogustometric threshold.
Policy makers require evidence on the costs and outcomes of different ways of organizing stroke care. This study compared the costs and survival of different ways of providing stroke care.
...Hospitalized stroke patients from 13 European centers were included, with demographic, case-mix, and resource use variables measured for each patient. Unit costs were collected and converted into US dollars using the purchasing power parity (PPP) index. Cox and linear regression analyses were used to compare survival and costs between the centers adjusting for case mix.
A total of 1847 patients were included in the study. After case-mix adjustment, the mean predicted costs ranged from $466 95% CI 181 to 751 in Riga (Latvia) to $8512 7696 to 9328 in Copenhagen (Denmark), which reflected differences in unit costs, and resource use. The mean length of hospitalization ranged from 8.3 days in Menorca (Spain) to 36.8 days in Turku B (Finland). In the 3 Finnish centers at least 80% of patients were admitted to wards providing organized stroke care, which was not provided at the centers in Almada (Portugal), Menorca, or Riga. Patients in Turku A and Turku B were less likely to die than those in Riga, Warsaw (Poland), or Menorca. The adjusted hazard ratios were 0.18 0.10 to 0.32 for Turku A, 0.18 0.10 to 0.32 for Turku B, 0.68 0.48 to 0.96 for Warsaw, and 0.56 0.33 to 0.96 for Menorca, all compared with Riga.
The cost of stroke care varies across Europe because of differences in unit costs, and resource use. Further research is needed to assess which ways of organizing stroke care are the most cost-effective.
Aims
Selisistat, a selective SirT1 inhibitor is being developed as a potentially disease‐modifying therapeutic for Huntington's disease (HD). This was the first study of selisistat in HD patients and ...was primarily aimed at development of pharmacodynamic biomarkers.
Methods
This was a randomized, double‐blind, placebo‐controlled, multicentre exploratory study. Fifty‐five male and female patients in early stage HD were randomized to receive 10 mg or 100 mg of selisistat or placebo once daily for 14 days. Blood sampling, clinical and safety assessments were conducted throughout the study. Candidate pharmacodynamic markers included circulating soluble huntingtin and innate immune markers.
Results
Selisistat was found to be safe and well tolerated, and systemic exposure parameters showed that the average steady‐state plasma concentration achieved at the 10 mg dose level (125 nm) was comparable with the IC50 for SirT1 inhibition. No adverse effects on motor, cognitive or functional readouts were recorded. While circulating levels of soluble huntingtin were not affected by selisistat in this study, the biological samples collected have allowed development of assay technology for use in future studies. No effects on innate immune markers were seen.
Conclusions
Selisistat was found to be safe and well tolerated in early stage HD patients at plasma concentrations within the anticipated therapeutic concentration range.
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