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Background and purpose: Several studies reported worse outcome for stroke patients arriving on weekends. We compared working hours to off-work hours throughout the week as there is lack of experienced staff and special services during off-hours. Methods: A nationwide stroke survey project on acute stroke was carried out in all acute care hospitals in Israel during 2004, 2007 and 2010 (2-month each). 'On-hours' were defined as regular Israel working hours and the rest, including holidays, were defined as 'off-hours'. The modified Rankin scale (mRS) at discharge was used for the main analysis on outcome. Results: A total of 4827 acute strokes patients were analyzed (2139 arrived on-hours and 2688 during off-hours). 'Off-hours' patients were 1 year younger (mean 70 vs. 71 years in 'on-hours') had lower rates of prior cardiac interventions, but had higher admission blood pressure levels and had more intracerebral hemorrhages (ICH) (11% vs. 8% in 'on-hours' patients, P < 0.001). Death during hospitalization was recorded in 9% of 'off-hours' vs. 6% of 'on-hours' patient ( P = 0.004). Controlling for age, blood pressure, stroke type, pre-stroke mRS, admission NIHSS, and thrombolysis, the relative odds of poor outcome (i.e. mRS ≥ 2) amongst 'off-hours' admissions compared to on-hours was 1.09 (95% CI: 0.92-1.30). Odds ratio amongst ischaemic stroke patients was 1.08 (95% CI: 0.88-1.33). Conclusions: Off-hours stroke admissions were associated with higher short-term mortality rate, probably due to a higher rate of ICH. After controlling for the latter and other potential confounders, 'off-hours' admissions were not different from 'on-hours' with respect to poor outcome. [ABSTRACT FROM AUTHOR]

Background: We intended to determine ethnic differences in the characteristics, management and outcome of acute ischemic stroke between the Israeli Arab and Jewish populations. Methods: A national survey was conducted in 2004 at all 28 hospitals in Israel. Information on demographics, transportation, risk factors, clinical presentation, stroke severity, type and subtype, management and clinical outcome was obtained. Mortality during the 36 months after hospitalization was assessed by matching with national mortality data. Results: Of the 1,540 patients, 169 (11%) were Arabs and 1,371 (89%) were Jews. The mean age of Arab patients was 9 years younger than in Jewish patients (63 ± 11 vs. 72 ± 12 years). Also, Arabs were more likely to be obese (OR = 1.72; 95% CI: 1.19-2.50) and have diabetes (OR = 1.41; 95% CI: 1.01-1.96), while Jews were more likely to have dyslipidemia (OR = 1.56; 95% CI: 1.11-2.17). A greater percentage of the Arab patients arrived at the hospital independently (OR = 3.85; 95% CI: 2.56-5.56) and were less likely to arrive within 3 h of symptom onset (OR = 2.33; 95% CI: 1.39-3.85). Arabs suffered increased rates of lacunar stroke (OR = 1.67; 95% CI: 1.14-2.43) and were discharged home more often (OR = 2.40; 95% CI: 1.35-4.25). No differences in severity of stroke, management, complications, disability or mortality were found between the 2 groups. Conclusions: The unique characteristics of the Arab and Jewish populations should be considered when planning stroke-care services and culturally oriented public education programs. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Stroke is the third most common cause of death in Israel, similar to the United States and Europe. A decline in stroke mortality rates for the Israeli population is evident in the last decades. However, stroke is still a major health and economical burden in Israel and has recently been recognized by the Israeli health-care policy planners as a top priority disease. Action plans are being taken in order to establish a comprehensive infrastructure for the treatment of acute stroke patients. [ABSTRACT FROM AUTHOR]

Patients with chronic CAD and a history of cerebrovascular events were compared with patients without prior cerebrovascular events to assess the effect of these events on 5-year prognosis. Despite adjustment for older age and higher comorbidity among patients who had experienced a cerebrovascular event, a history of such an event was associated with an increased risk of 1.86 for total mortality. [ABSTRACT FROM AUTHOR]

Background: Underdiagnosis of relevant risk factors has contributed to the increasing stroke incidence in young adults. Blood pressure cut-off values for adolescents are neither sex specific nor based on cardiovascular outcomes., Methods: This nationwide, population-based, retrospective cohort study included all Israeli adolescents 16-19 years of age who were medically evaluated before compulsory military service from 1985 to 2013, including routine blood pressure measurements. The primary outcome was the first occurrence of a stroke (ischemic or hemorrhagic) at a young age (≤52 years), as documented in the Israeli National Stroke Registry. Cox proportional hazard models were stratified by sex and adjusted for birth year, sociodemographic variables, and adolescent body mass index., Results: The cohort comprised 1,897,048 adolescents (42.4% women). During 11,355,476 person-years of follow-up, there were 1470 first stroke events at a young age. In men, an adolescent diastolic blood pressure value of ≥80 mmHg, compared with the reference group (diastolic blood pressure value of <70 mmHg), was associated with an increased risk of stroke (adjusted hazard ratio 1.28; 95% confidence interval [CI], 1.04 to 1.58), while a diastolic blood pressure value of 70-79 mmHg was not associated with an increased risk of stroke (adjusted hazard ratio 1.11; 95% CI 0.90 to 1.34). Among women, an adolescent diastolic blood pressure value of ≥80 mmHg, compared with the reference group (diastolic blood pressure value of <70 mmHg) was associated with an increased risk of stroke at a young age (adjusted hazard ratio 1.38; 95% CI 1.03 to 1.88), as was a diastolic blood pressure value of 70-79 mmHg (adjusted hazard ratio 1.41; 95% CI 1.09 to 1.81). Elevated adolescent systolic blood pressure values (≥120 mmHg) were not associated with an increased risk of stroke., Conclusions: Diastolic blood pressure values of ≥80 mmHg in adolescence were associated with an increased risk of stroke at a young age in both men and women. No similar association was observed for elevated systolic blood pressure.

Background: Stroke is increasingly prevalent at younger ages but the risk factors are uncertain. We examined the association between adolescent cognitive function and early-onset stroke., Methods: This was a nationwide population-based cohort study of 1 741 345 Israeli adolescents (42% women) who underwent comprehensive cognitive function tests at age 16-20 years, before mandatory military service, during 1987-2012. Cognitive function (range: 1-9) was categorised as low (1-3, corresponding to IQ score below 89), medium (4-7, IQ score range: 89-118), or high (8-9, IQ score above 118). Participant data were linked to the Israeli National Stroke Registry. Cox proportional hazard models were used to estimate risks for the first occurrence of ischaemic stroke during 2014-2018., Results: During 8 689 329 person-years of follow-up, up to a maximum age of 50 years, 908 first stroke events occurred (767 ischaemic and 141 haemorrhagic). Compared with a reference group of people with high cognitive function, body mass index-adjusted and sociodemographic-adjusted HRs (95% CIs) for early-onset stroke were 1.78 (1.33-2.38) in medium and 2.68 (1.96-3.67) in low cognitive function groups. There was evidence of a dose-response relationship ( P for trend <0.0001) such that one-unit of lower cognitive function z-score was associated with a 33% increased risk of stroke (1.33; 1.23-1.42). These associations were similar for ischaemic stroke but lower for haemorrhagic stroke; persisted in sensitivity analyses that accounted for diabetes status and hypertension; and were evident before age 40 years., Conclusions: Alongside adolescent obesity and hypertension, lower cognitive function may be a risk factor for early-onset stroke., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Seasonality in the incidence of stroke has been examined in numerous studies, yet data on whether it differs with age are limited. To fill this gap, we utilized a largescale dataset from Israel., Patients and Methods: We retrieved data of all hospitalizations for ischemic stroke (IS), transient ischemic attack (TIA) and intra cerebral hemorrhage (ICH) from 2000 to 2020. We maintained separate datasets for IS/TIA and ICH, divided into five age groups: 18-49, 50-59, 60-69, 70-79, and 80+. We modeled the monthly incidence using a generalized additive model. The seasonal effect was defined by the rate ratio (RR) of each month compared to the annual mean., Results: The analysis included 317,586 and 23,789 events of IS/TIA and ICH respectively. We found an interaction between age and seasonality, accounting for a phase shift with age in the seasonal pattern of IS/TIA incidence. For cases under 70 years, the peak was during summertime and the RRs increased with decreasing age, reaching 1.11 (95% CI 1.09-1.13) at the youngest age group. In contrast, among the elderly, a winter peak was observed and the RRs increased with age to 1.07 (95% CI 1.06-1.08) at the oldest age group. For ICH, a winter/autumn peak was identified and the RRs increased with age to 1.20 (95% CI 1.16-1.24)., Conclusions: Our finding of age-dependent seasonal patterns in the occurrence of stroke, suggests closer monitoring of cardiovascular risk factors during wintertime among elderly individuals. The mechanism governing the seasonal phase shift with age in IS/TIA incidence, requires further investigation., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Diabetes is a major risk factor for ischemic stroke and may affect post-stroke survival. Previous large scale studies of long-term post-stroke survival are limited and most of them excluded older patients from the study population., Objectives: To compare the risk factors and sociodemographic characteristics between first ischemic stroke cases with and without diabetes and to assess the mortality risk associated with diabetes., Methods: Using population-based National Stroke Registry in Israel, all patients hospitalized for a first event of ischemic stroke between the years 2014-2018 were followed for all-cause mortality. Chi-square analysis was used to compare the differences in risk factors, sociodemographic profile and cumulative mortality between patients with and without diabetes. Cox proportional hazards models were used to estimate the hazard ratio for mortality in selected timeframes., Results: Among 41,639 patients with a first event of ischemic stroke, 44.5% were previously diagnosed with diabetes. Diabetic patients were more likely to be males, members of the Arab ethnic group, with lower socioeconomic status and a higher prevalence of cardiovascular comorbidities, anemia, leukocytosis and abnormal kidney function. Diabetes was associated with a higher mortality risk in the first year and long term, but not in the first month following stroke. Diabetes-associated mortality risk interacted with time and age, was higher in younger age and increased with time., Conclusions: Our findings suggest that diabetes is associated with a higher prevalence of comorbidities among patients with first ischemic stroke and with a higher risk for mortality in the mid and long term, which is more profound in younger age., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background and Purpose: There is a continuous rise in the prevalence of adolescent obesity and incidence of stroke among young adults in many Western countries, but the association between them is unclear., Methods: A nationwide population-based study of 1 900 384 Israeli adolescents (58% men; mean age, 17.3 years) who were evaluated before mandatory military service during 1985 and 2013. Body mass index was classified according to the US Center for Disease Control and Prevention percentiles. Primary outcome was a first stroke event as recorded by the Israeli National Stroke Registry between 2014 and 2018. Cox proportional hazard models were applied., Results: There were 1088 first stroke events (921 ischemic and 167 hemorrhagic; mean diagnosis age, 41.0 years). Adolescent body mass index was significantly associated with a graded increase in the risk for any stroke, ischemic stroke, but less so with hemorrhagic stroke. The hazard ratios for the first ischemic stroke event were 1.4 (95% CI, 1.2–1.6), 2.0 (95% CI, 1.6–2.4), and 3.4 (95% CI, 2.7–4.3) for the 50th to 84th percentile, overweight and obese groups, respectively, after adjustment for sex, age, and sociodemographic confounders with the 5th to 49th body mass index percentile group as the reference. The respective hazard ratios after further adjustment for diabetes status were 1.3 (1.1–1.5), 1.6 (1.3–2.0), and 2.4 (1.9–3.1). Results persisted when the cohort was divided by diabetes status and when ischemic stroke before age 30 was the outcome., Conclusions: High adolescent body mass index was associated with ischemic stroke in young adults with or without diabetes. The rising prevalence of adolescent obesity may increase the future burden of stroke in young adults.

Background: According to the latest reported data from the National Acute Stroke Israeli Survey (NASIS), around 18,000 strokes occur annually in Israel. Data regarding disparities in stroke care between the Jewish and the Arab populations in Israel are lacking., Aims: We wished to compare demographics, comorbidities, stroke characteristics and outcomes between Jewish and Arab stroke patients in Israel that were acutely treated with intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT), in order to test if there are disparities or any ethnic-specific parameters., Methods: The National Acute Stroke Israeli registry of patients undergoing revascularization (NASIS-REVASC) prospectively enrolled patients in six comprehensive stroke centers between 1/2014 and 3/2016. In this observational research, we compared demographics, comorbidities, time metrics, stroke characteristics and outcomes between Jewish and Arab patients enrolled., Results: NASIS-REVASC included 1432 patients out of which 143 (10%) were of Arab ethnicity and 1289 (90%) of Jewish ethnicity. Arab patients were significantly younger (66 ± 14 vs. 73 ± 29, p = 0·004), exhibited higher rates of smoking and diabetes (31% vs. 18% and 57% vs. 34%, p < 0·001 for both), and were less often treated with systemic thrombolysis (48% vs. 59%, p = 0·012). However, the rates of any interventional treatment with either intravenous thrombolysis or endovascular thrombectomy as well as the rates of favorable outcomes and mortality were comparable between groups., Conclusions: Despite several baseline differences between Arab and Jewish Israeli stroke patients, treatment allocations, survival and functional outcomes were similar indicating lack of disparity in stroke care among patients treated acutely with IVT and/or EVT in Israel., Data Access Statement: Full data is available following a formal request to the NASIS-REVASC registry at the Israeli Health Ministry., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Despite the impressive decline in mortality from atherosclerotic cardiovascular diseases (ASCVD), these diseases still account for a large proportion of the overall morbidity and mortality worldwide. A vast amount of research has demonstrated the key role played by circulating lipoproteins, and especially low-density lipoprotein (LDL), in the etiology of atherosclerosis, and numerous studies have proven the efficacy of interventions that lower the atherogenic lipoproteins in reducing morbidity and mortality from ASCVD. While previous guidelines placed an emphasis on the use HMG-CoA reductase inhibitors (statins) for the treatment of dyslipidemia, recent studies have shown that other LDL cholesterol lowering drugs, including ezetimibe and the PCSK9 inhibitors, can provide additional benefit when used in combination with (and in certain cases instead of) statins. These studies have also shown that blood LDL cholesterol levels lower than previously recommended targets provide additional benefit, without evidence of a threshold beyond which the benefit ceases and without excess adverse effects. The updated guidelines were formulated by a committee that consisted of representatives from the Israeli Society for the Research, Prevention and Treatment of Atherosclerosis, the Israel Society of Internal Medicine, the Israeli Heart Association, the Israeli Neurology Association and the Israel Association of Family Medicine. They provide recommendations for revised risk stratification of patients, novel target goals, and the use of evidence-based treatment and follow-up strategies with reference to specific patient sub-groups.

Introduction: Little is known about the association between obesity and sarcopenia - age-related loss of muscle mass and function - among patients with cardiovascular disease. We investigated the association between overweight, obesity, and sarcopenia among community-dwelling men in Israel with cardiovascular disease., Methods: A subset of 337 men (mean age at baseline 56.7 [SD, 6.5]) who previously (1990-1997) participated in the Bezafibrate Infarction Prevention trial underwent a neurovascular evaluation as part of the Bezafibrate Infarction Prevention Neurocognitive Study 15.0 (SD, 3.0) years after baseline and a sarcopenia evaluation 19.9 (SD, 1.0) years after baseline. We applied a multinomial logistic model to estimate odds ratios and 95% CIs for 3 categories of sarcopenia: no evidence of sarcopenia (ie, robust), probable sarcopenia, and sarcopenia., Results: We found sarcopenia among 54.3% of participants with obesity (body mass index [BMI, in kg/m 2 ] ≥30.0), 37.0% of participants who were overweight (25.0 ≤ BMI ≤29.9), and 24.8% of participants with normal weight (BMI 18.5 to 24.9). In a comparison of BMI ≥25.0 and BMI <25.0, adjusting for covariates, the odds ratio of having probable sarcopenia was 3.27 (95% CI, 1.68-6.36) and having sarcopenia was 5.31 (95% CI, 2.50-11.27)., Conclusion: We found a positive association between obesity and late-life sarcopenia and suggest that obesity might be an important modifiable risk factor related to sarcopenia among men with cardiovascular disease.

Objective: To examine whether high ambient temperature and diurnal temperature range during the summer are associated with risk of stroke/transient ischemic attack (TIA)., Methods: A time-stratified case-crossover study design was conducted. The study sample comprised all individuals aged ≥50 years who had a stroke/TIA reported to the Israeli National Stroke Registry between 2014 and 2016 during the summer season. Daily temperature data were retrieved from the Israel Meteorological Service. Conditional logistic regression models were used with relative humidity and air pollution as covariates., Results: The sample included 15,123 individuals who had a stroke/TIA during the summer season (mean age 73 ± 12 years; 54% males). High ambient temperature was associated with stroke/TIA risk starting from the day before the stroke event, and increasing in strength over a six-day lag (OR = 1.10 95%CI 1.09-1.12). Moreover, a larger diurnal temperature range prior to stroke/TIA occurrence was associated with decreased stroke/TIA risk (OR = 0.96 95%CI 0.95-0.97 for a six-day lag)., Conclusions: High ambient temperature may be linked to increased risk of cerebrovascular events in subsequent days. However, relief from the heat during the night may attenuate this risk., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aim: We investigated the relationship between midlife C-reactive protein (CRP) levels in men with coronary heart disease (CHD) and depressive symptoms at old age. CRP levels were measured in a subset of patients with CHD, who previously participated in a secondary prevention trial. Methods: Depressive symptoms were evaluated in survivors of the original cohort 15.0 ± 3 and 19.9 ± 1 years later (T1, n  = 463 and T2, n  = 314 respectively) using the Geriatric Depression Scale (GDS), 15-item version. Logistic regression was used to estimate ORs and 95%CIs for presence of potentially clinically significant depressive symptoms (GDS ≥5) at T1 and T2. Results: Adjusting for demographic and health-related variables, the OR (95%CI) for GDS ≥5 was 1.23 (0.65-2.33); p  = .53 at T1 and 2.36 (1.16-4.83); p  = .018 at T2 in the top CRP tertile compared to the others. Similarly, consistently high CRP levels in the top tertile at baseline and 2 years later, were associated with OR of 2.85 (95%CI 1.29-6.30); p  = .01 for GDS ≥5 at T2. Conclusions: Presence and persistence of low-grade inflammation in men with CHD during midlife are associated with increased risk of depressive symptoms twenty years later. Among middle aged men with CHD, low-grade inflammation may provide an important added value for prediction of depression in old age.

Background: Endovascular therapy (EVT) is currently the most effective treatment for emergent large vessel occlusion (ELVO) stroke. Earlier treatment is associated with a better clinical outcome. Our aim was to examine the association between onset-to-EVT (OTE) time and clinical outcomes using real-world nationwide data from the National Acute Stroke ISraeli (NASIS)-REVASC registry., Methods: Stroke patients undergoing EVT within the Endovascular Capable Centres (ECCs) in Israel between January 2014 and March 2016 were prospectively included. Several clinical and radiological outcomes were evaluated. The association between OTE time and outcomes was analyzed with logistic regression models using time as a continuous variable and then by OTE groups of <2, 2-4, 4-6, and >6 hours., Results: 299 patients with acute stroke were included in the analysis. OTE time was significantly associated with favorable outcomes. ORs for each hour of delay in EVT were 0.84 (95% CI 0.71 to 0.99) for significant early recovery, 0.80 (95% CI 0.68 to 0.94) for discharge to home, 0.80 (95% CI 0.66 to 0.95) for freedom from disability at discharge, and 0.78 (95% CI 0.67 to 0.91) for excellent reperfusion (Thrombolysis in Cerebral Ischemia 3). The <2 OTE group was significantly associated with better outcomes than the ≥2 OTE group including significant early recovery (OR 3.3, 95% CI 1.2 to 9.1), discharge to home (OR 3.32, 95% CI 1.3 to 8.5), and excellent reperfusion (OR 4.6, 95% CI 1.3 to 29.5). The same trend was observed for freedom from disability at discharge and 3 months (OR 2.08, 95% CI 0.7 to 5.7 and OR 2.57, 95% CI 0.8 to 8.3, respectively). Only 1% of transferred patients achieved an OTE time of <2 hours., Conclusions: Nationwide real-life registry data indicate that benefit from EVT is strongly associated with OTE time and is most prominent within the 'two golden hours' from stroke onset. This time goal may not be applicable in inter-hospital transfer patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Stroke is a leading cause of mortality, disability and functional impairment. We present clinical and patient-reported outcomes 3-months after stroke in patients from the National Acute Stroke Israeli registry (NASIS) 2016., Methods: The NASIS registry includes all patients with acute cerebrovascular events admitted during 2-month periods every 3-years, at all hospitals and departments admitting acute stroke patients in Israel. The current work presents findings on 710 survivors after ischemic stroke or intracerebral hemorrhage (ICH) in NASIS 2016. Outcomes at 3-months were assessed using the modified Rankin Scale (mRS), questions about dysfunction and patient-reported outcomes assessed with the PROMIS 10 scale., Results: Seven-hundred and ten patients were included, 696 (94.2%) with ischemic stroke and 41 (5.8%) with ICH. Mean age of participants was 70.2 years, 58% men. At 3-months, mRS scores were 0-1 for 43% of the patients, 2-3 for 29% and 4-5 for 28%. Functional impairment was more severe in patients with ICH than in ischemic stroke patients. Patients who were discharged from the hospital with functional impairment (mRS≥2) exhibited lower PROMIS 10 scores at 3-months compared to patients with no functional impairment at discharge. This finding was statistically significant in all the PROMIS 10 items, except for fatigue (p=0.874) and pain level (p=0.188)., Conclusions: More than half of the patients needed help with their daily functioning 3-months after stroke. Most stroke survivors with functional impairment at discharge reported poor patient-reported outcomes. Post-stroke rehabilitation programs should aim at improving outcomes that are valuable to patients.

Background: Stroke is a leading cause of death and disability worldwide. Due to the high burden caused by stroke, the Israeli Ministry of Health initiated a national program for the treatment and prevention of stroke, including the establishment of an Israeli National Stroke Registry (INSR). In this article we will demonstrate the use of the INSR as a tool for monitoring the treatment of acute cerebrovascular events (stroke or transient ischemic attack)., Objectives: 1. Assessing incidence rates of acute cerebrovascular events in Israel for the total population and by gender and ethnic group separately. 2. Presenting trends in a number of key indicators related to acute stroke care., Methods: The INSR is based on data retrieval from hospital electronic medical records of all adult cases discharged with acute cerebrovascular diagnosis from January 1, 2014 on. Included in the current analysis were all cases reported to the INSR until June 31, 2017., Results: The average annual incidence rate of cerebrovascular events in Israel was 3.2 cases per 1,000 people. Age-adjusted rates were significantly higher among Arabs, compared with the Jewish population. From 2014 to 2017 there was a moderate increase in the percentage of arrival by ambulance: from 43.2% to 49.0% and a significant increase in the percentage of head and neck vascular imaging performed: from 50.0% to 72.5%. Between 2014 and 2016 there was a significant increase in the percentage of t-PA administration, and in 2016-2017 the rates stabilized at 9.2%. The proportion of patients hospitalized in neurological wards was 38.0% - a slight increase from 35.0% in 2014., Conclusions: The INSR is an effective tool for monitoring morbidity and acute stroke care in Israel. Actions should be taken in order to raise public awareness of stroke warning signs and the establishment of stroke units with skilled multidisciplinary teams should become a priority., Discussion: Compared with other western countries, rates of t-PA administration and arrival by ambulance in Israel are slightly low, rates of hospitalization in the neurological ward are significantly lower, and the lack of stroke units is most prominent.

Background: Recent studies suggest that impaired cerebrovascular reactivity (CVR), a marker of cerebral microvascular damage, is associated with a higher risk of stroke, cognitive decline, and mortality. We tested whether abnormal cerebrovascular status is associated with late-life frailty among men with pre-existing cardiovascular disease., Methods: A subset of 327 men (mean age at baseline 56.7 ± 6.5 years) who previously participated in the Bezafibrate Infarction Prevention (BIP) trial (1990-1997) and then in the BIP Neurocognitive Study underwent a neurovascular evaluation 14.6 ± 1.9 years after baseline (T1) and were evaluated for frailty 19.9 ± 1.0 years after baseline (T2). CVR was measured at T1 using the breath-holding index and carotid large-vessel disease using ultrasound. Frailty status was measured at T2 according to the physical phenotype developed by Fried. Patients were categorized into CVR tertiles with cutoff points at ≤0.57, 0.58-0.94, and ≥0.95 and also as normal or impaired (<0.69) CVR. We assessed the change in the odds of being in the advanced rank of frailty status (normal, prefrail, and frail) using ordered logistic regression., Results: After adjustment, the estimated OR (95% confidence intervals) for increasing frailty in the lower tertile was 1.94 (1.09-3.46) and in the middle tertile 1.24 (0.70-2.19), compared with the higher CVR tertile. The estimated OR for increasing frailty for patients with impaired vs. normal CVR was 1.76 (1.11-2.80)., Conclusions: These findings provide support that cerebral microvascular dysfunction among patients with pre-existing cardiovascular disease is related to prefrailty and frailty and suggest an added value of assessing the cerebral vascular functional status for identifying patients at-risk of developing frailty.

Background and Purpose: Stroke is a leading cause of morbidity and disability. We assessed trends in rates of hospitalized stroke and stroke severity on admission in a prospective national registry of stroke from 2004 to 2013., Methods: All 6693 acute ischemic strokes and intracerebral hemorrhage in the National Acute Stroke Israeli participants ≥20 years old were included. Data were prospectively collected in 2004 (February-March), 2007 (March-April), 2010 (April-May), and 2013 (March-April). Rates of hospitalized stroke from 2004 to 2013 were studied using generalized linear models assuming a quasi-Poisson error distribution with a log link. Stroke severity on admission was determined using the National Institutes of Health Stroke Scale score and trends were studied. Analysis was performed for stroke overall and by sex and age-group as well as by stroke type., Results: Estimated average annual rates of hospitalized stroke decreased from 24.9/10 000 in 2004 to 19.5/10 000 in 2013. The age and sex-adjusted rates ratio (95% confidence interval) for hospitalized stroke overall was 0.82 (0.76-0.89) for 2007, 0.71 (0.65-0.77) for 2010, and 0.72 (0.66-0.78) for 2013 compared with 2004. Severity on admission decreased over time: rates (95% confidence interval) of severe stroke (National Institutes of Health Stroke Scale score of ≥11) decreased from 27% (25%-29%) in 2004 to 19% (17%-21%) in 2013, whereas rates (95% confidence interval) of minor stroke (National Institutes of Health Stroke Scale score of ≤5) increased from 46% (44%-49%) in 2004 to 60% (57%-62%) in 2013 ( P <0.0001). Findings were consistent by sex, age-group, and stroke type., Conclusions: Based on our national data, rates of hospitalized stroke and severity of stroke on admission have decreased from 2004 to 2013 overall and by stroke type, in men and women. Despite the observed declines in rates and severity, stroke continues to place a considerable burden to the Israeli health system., (© 2018 American Heart Association, Inc.)

Cardiovascular health (CVH) factors are associated with lower risk of cardiovascular disease, stroke, and mortality. We investigated the association between a modified CVH metrics score and change in cognitive functions 2 decades later in patients with pre-existing coronary artery disease. A subset of 200 men (mean age at baseline 57.3 ± 6.3 years) who previously participated in a secondary prevention trial (1990 to 1997) underwent cognitive evaluation 14.6 ± 1.9 years after baseline (mean age 72.3 ± 6.2 years, T1 evaluation), and were re-evaluated for cognitive performance 19.9 ± 1.0 years after baseline (mean age 77.2 ± 6.4 years, T2 evaluation). A CVH metrics score at baseline was calculated, including 3 health parameters and 4 health behaviors. We have scored each of these CVH metrics into best (2 points), intermediate (1 point), and poor (0 points) levels. Cognitive function was assessed using the NeuroTrax Computerized Battery. A linear mixed model was used to assess change in cognitive functions between T1 and T2 cognitive evaluations. Among the 200 patients, 68 (34.0 %) had ≤7 (bottom group), 85 (42.5%) had 8 to 9 (middle group), and 47 (23.5%) had ≥10 (top group) CVH metrics points. After adjustments, the top group of CVH score versus others was associated with slower decline in the overall cognitive performance composite z-score (0.23 ± 0.09, p = 0.009) and on tests of executive and visual spatial functions (0.23 ± 0.11, p = 0.047, and 0.49 ± 0.17, p = 0.004, respectively). In conclusion, an inverse association was observed between the score of best CVH metrics and cognitive decline. Lifestyle factors are important predictors of late-life decline in cognitive function among high-risk patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background and Purpose: Providing participants with evidence-based care for secondary prevention is an ethical and scientific priority for trials in stroke therapy. The optimal strategy, however, is uncertain. We report the performance of a new approach for delivering preventive care to trial participants., Methods: Participants were enrolled in the Insulin Resistance Intervention after Stroke trial, which examined the insulin sensitiser, pioglitazone versus placebo for prevention of stroke and myocardial infarction after ischaemic stroke or transient ischaemic attack. Preventive care was the responsibility of the participants' personal healthcare providers, but investigators monitored care and provided feedback annually. We studied achievement of 8 prevention goals at baseline and 3 annual visits, with a focus on 3 priority goals: blood pressure <140/90 mm Hg, low-density lipoprotein (LDL) cholesterol <2.59 mmol/L and antithrombotic therapy., Results: The proportion of participants achieving the priority goals was highest for antithrombotic use (96-99% in each year) and similar for blood pressure (66-72% in each year) and LDL (68-70% in each year). All 3 priority goals were achieved by 47-52% of participants in any given year. However, only 22% of participants achieved all 3 goals in each year., Conclusions: A strategy of monitoring care and providing feedback was associated with high average yearly achievement of 3 priority secondary prevention goals, but the majority of trial participants did not persist in being at goal over time., Trial Registration Number: NCT00091949., Competing Interests: Competing interests: JJS reports personal fees from Acorda Therapeutics. CMV has a consulting agreement with Takeda to examine selected IRIS data. SEI reports personal fees from Merck, Janssen, Novo Nordisk, Sanofi, Intarcia, Lexicon, Poxel, Boehringer Ingelheim, Eli Lilly and AstraZeneca, and other support from Takeda outside the IRIS trial. In addition, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Abbott, Merck and Sanofi have provided continuing medical education (CME) funding to SEI employer, Yale University, for projects in which he has been involved. GAF reports personal fees from Lundbeck, Cerevast, Pfizer, Athersys, AstraZeneca, Boehringer Ingelheim and Daiichi Sankyo.

Background: Recent guidelines recommended different approaches to hypertension therapy. Our aim was to evaluate trends in blood pressure (BP) management among patients admitted with acute stroke over the past decade., Methods: The study population comprised 6279 consecutive patients, admitted with an acute stroke, and included in a national registry of three consecutive periods conducted during the years 2004-2010. We compared patients' characteristics and temporal trends of antihypertensive therapy utilization before hospital admission., Results: Among 4727 hypertensive patients, 3940 (83%) patients have taken antihypertensive drug therapy - 1430 (30.2%) a single agent, 1500 (31.7%) two agents and 1010 (21.4%) three or more antihypertensive agents. The most common class used was renin-angiotensin system (RAS) blockers (n = 2575; 54%) followed by beta-blockers (n = 2033; 43%). The same pattern was observed in patients treated with monotherapy. The use of RAS blockers and beta-blockers has increased over the years (p < 0.001 for both), whereas the use of diuretics decreased and the use of calcium antagonists remained stable. Among those who were treated with a single agent, the use of diuretics and calcium antagonists decreased and the use of RAS blockers increased, whereas the use of beta-blockers remained unchanged., Conclusions: RAS blockers and beta-blockers are the most common antihypertensive agents used in Israel. Over time, the use of RAS blockers and beta-blockers has increased, whereas the use of diuretics decreased.

Background and Purpose: Previous overt stroke and subclinical stroke are frequent in patients with stroke; yet, their clinical significance and effects on stroke outcome are not clear. We studied the burden and outcome after acute ischemic stroke by prevalent ischemic brain disease in a national registry of hospitalized patients with acute stroke., Methods: Patients with ischemic stroke in the National Acute Stroke Israeli prospective hospital-based registry (February to March 2004, March to April 2007, and April to May 2010) with information on previous overt stroke and subclinical stroke per computed tomography/MRI (n=3757) were included. Of them, a subsample (n=787) was followed up at 3 months. Logistic regression models were computed for outcomes in patients with prior overt stroke or subclinical stroke, compared with patients with first stroke, adjusting for age, sex, vascular risk factors, stroke severity, and clinical classification., Results: Two-thirds of patients had a prior overt stroke or subclinical stroke. Death rates were similar for patients with and without prior stroke. Adjusted odds ratios (OR; 95% confidence interval [CI]) for disability were increased for patients with prior overt stroke (OR, 1.31; 95% CI, 1.03-1.66) and subclinical stroke (OR, 1.45; 95% CI, 1.16-1.82). Relative odds of Barthel Index≤60 for patients with prior overt stroke (OR, 2.04; 95% CI, 1.14-3.68) and with prior subclinical stroke (OR, 2.04; 95% CI, 1.15-3.64) were twice higher than for patients with a first stroke. ORs for dependency were significantly increased for patients with prior overt stroke (OR, 1.95; 95% CI, 1.19-3.20) but not for those with subclinical stroke (OR, 1.36; 95% CI, 0.84-2.19)., Conclusions: In our national cohort of patients with acute ischemic stroke, nearly two thirds had a prior overt stroke or subclinical stroke. Risk of poor functional outcomes was increased for patients with prior stroke, both overt and subclinical.

Background: The importance of gender as an independent risk factor for poor outcome is not clear. We examined gender differences in patients' characteristic, management and outcome at discharge and 3-months after acute stroke in a national hospital-based registry., Methods: Data were derived from the triennial two-month national Acute Stroke Israeli Registry (Feb-March 2004, March-April 2007, April-May 2010). Unselected patients in all Israeli hospitals (n = 28) were included. Outcome at 3-month was assessed in a sub-sample. Logistic regression models were used in the study of gender as an independent risk factor for poor outcome., Results: In total, 5034 patients (88.5% ischemic stroke, 9.6% ICH and 1.9% undetermined stroke) were included, of them 2285 (45.4%) women. Follow-up at 3-month was completed for 1040 patients, 41.9% women. Women showed higher rates of cardiovascular risk factors in-hospital death (p = 0.007) and poor functional outcome (p < 0.0001). Following adjustment for age, prior disability, NIHSS, prior stroke and risk factors, risk estimates (ORs, 95%CI) for women compared to men were 0.72 (0.55-0.96) for in-hospital death, 1.03 (0.83-1.29) for discharge to a nursing home or death, and 1.01 (0.86-1.20) for disability. Poor outcomes at 3-month were significantly more common in women; however, adjusted risk estimates were not significantly increased: OR 0.95 (95%CI 0.50-1.81) for death at 3-months, 1.41 (0.99-2.01) for Barthel Index ≤ 60, 1.24 (0.90-1.72) for dependency and 0.88 (0.55-1.39) for living in a nursing home or death., Conclusion: Gender-differences in risk of death and poor functional outcome after stroke are mainly explained by dissimilarities in patients' characteristics and stroke severity., (© 2013.)

Objectives: The objective of this study is to examine the association between perceived hardships and long-term stroke mortality among a large cohort of middle-aged men., Background: Unlike cardiovascular morbidity and mortality, much less is known about the relationship between psychosocial factors and risk of stroke., Methods: A cohort of 10,059 men aged ≥ 40 years at study inclusion that were tenured civil servants or municipal employees were followed for mortality over a median of 28.1 years (IQR 18.9-34.3). During follow-up 6528 (64.9%) men died, 665 of stroke and 1769 of coronary heart disease (CHD). A composite score of perceived hardships was calculated based on a structured psychosocial questionnaire filled at baseline, assessing domains of work, family, and finance. Cox proportional hazard models were used adjusting for traditional risk factors and socio-economic status., Results: At baseline, subjects with higher hardship scores were slightly older, smoked more cigarettes, had higher prevalence of CHD, lower systolic blood pressure, higher anxiety levels and lower socio-economic status. Compared with the bottom tertile, the middle (HR 1.26, 95% CI 1.04-1.53) and top tertiles of the hardship score (HR 1.33, 95% CI 1.07-1.64) exhibited higher risk of stroke mortality (P for trend=0.008), while no significant association was found with long-term mortality from CHD. The magnitude of the association was comparable to that of diabetes (HR 1.30, 95% CI 1.02-1.66)., Conclusion: Perceived hardships measured at midlife in a large cohort of apparently healthy men independently predict stroke mortality over long-term follow-up., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Patients with transient ischemic attack (TIA) at a high risk of stroke can be identified and should be managed urgently., Objectives: To investigate whether recognized recommendations are being implemented in Israel., Methods: An Israeli nationwide registry (NASIS) on patients admitted with stroke and TIA was conducted in all acute care hospitals within 2 successive months during 2004, 2007 and 2010. A revised ABCD2 score was applied retrospectively. Patients with TIA were divided into a low risk group (LRG, 0-3 points) and a high risk group (HRG, 4-6 points) and were compared to patients with minor ischemic strokes (MIS, NIHSS score < or = 5 points)., Results: A total of 3336 patients were included (1023 with TIA: LRG 484, HRG 539, and MIS 2313). LRG patients were younger and had lower rates of most traditional risk factors as compared with HRG and MIS patients. Brain imaging was performed in almost all the patients. Ancillary tests (vascular and cardiac) were overall underused, yet were performed more in LRG (53.2% and 26.9% respectively) than in HRG patients (41.6%, 18.9%). Between periods there was no change in usage of ancillary tests for the LRG and a modest increase in both HRG and MIS patients. For performance of vascular investigations overall, the odds ratio was 1.69 (95% confidence interval 1.42-2.00) comparing 2010 with 2004, but 0.7 (95% CI 0.5-0.9) comparing HRG with LRG. Between periods an increase in statin usage was observed in all groups (OR 2.69, 95% CI 2.25-3.21) but was more marked in MIS patients (OR 3.06, 95% CI 2.47-3.8)., Conclusions: The approach to TIA risk stratification and management in Israeli hospitals does not follow standards set by current guidelines. Standardized protocols for TIA should be used to assure effective management.

Transient ischemic attack (TIA) is associated with early stroke risk and thus should be considered as an emergency. Early diagnosis and prompt evaluation and treatment are the key in reducing the stroke risk. Recently, with the recognition of several clinical scores as well as a few imaging modalities that identify those with higher risks, it is likely to be easier to reduce risks. In this position paper the evidence, including the clinical scores, is reviewed and suggested guidelines for prompt diagnosis and treatment of patients with TIA's is proposed by a committee of the Israeli Neurological Association.

Background and Purpose: Improving stroke management, guideline adherence, and outcome is a global priority. Our aim was to examine trends in nationwide use of reperfusion therapy, stroke in-hospital management, and outcome., Methods: Data were based on the triennial 2-month period of the National Acute Stroke Israeli registry (February to March 2004, March to April 2007, April to May 2010). The registry includes unselected patients admitted to all hospitals nationwide. There were in total 6279 patients: ischemic stroke, 4452 (70.9%); intracerebral hemorrhage, 485 (7.7%); undetermined stroke, 97 (1.6%); and transient ischemic attacks, 1245 (19.8%)., Results: Overall use of reperfusion therapy for acute ischemic stroke increased from 0.4% in 2004% to 5.9% in 2010 (P<0.001; adjusted OR, 17.0; 95% CI, 7.5-38.7). Use of CT or MR angiography for ischemic events increased from 2.1% in 2004% to 16.6% in 2010 (P<0.001; adjusted OR, 9.7; 95% CI, 6.8-13.9). Overall use of antithrombotics and anticoagulation for atrial fibrillation did not differ between periods, whereas clopidogrel use increased nearly 3-fold to 41% and statin use nearly 2-fold to 68%. The relative odds of providing reperfusion therapy, using CT or MR angiography, and prescribing anticoagulants for atrial fibrillation were higher among hospitals with large as compared with small stroke patient volumes. In-hospital mortality after acute ischemic stroke decreased from 7.2% in 2004 to 3.9% in 2010 (P<0.001; adjusted OR, 0.7; 95% CI, 0.4-1.0), whereas there was no significant change in odds of poor functional outcome., Conclusions: Based on a nationwide stroke registry, use of reperfusion therapy, vascular imaging, and statins is steadily increasing, whereas in-hospital mortality is decreasing.

Background: High cholesterol has been associated with better stroke outcomes. Conversely, a protective effect of prestroke statin use in the acute phase of stroke has been reported. The effect of low cholesterol on outcome in patients with and without prestroke statin treatment has not been studied. We assessed the association between low cholesterol and ischemic stroke short- and long-term outcomes and studied potential interactions with statin treatment in patients with a first-ever ischemic stroke in a prospective national registry., Methods: Ischemic stroke patients in the National Acute Stroke Israeli (NASIS) registry with a first-ever stroke and no previous disability, dementia or cancer admitted in all hospitals nationwide during 2-month periods in 2004, 2007 and 2010 were included (n = 1,895). Cholesterol levels ≤155 mg/dl (1st quintile) were defined as low cholesterol and patients treated with statins for at least 7 days before stroke onset were categorized as prestroke statin treated. Severe stroke (NIHSS ≥11), total anterior circulation infarction, poor functional outcome (defined as discharged to a nursing facility or modified Rankin Scale >3 or death), and mortality at discharge and at 3 years were the study outcomes. Associations between low cholesterol and outcomes at discharge were assessed separately in patients with and without prestroke statin treatment using multiple logistic regression analyses. Mortality at 3 years was assessed in a subset of 681 patients with Cox proportional hazard models., Results: Patients were 67.4 ± 13.5 years old on average; 43.1% were women. Low cholesterol was associated with higher rates of stroke risk factors. Controlling for age, sex, hypertension, diabetes, current smoking, ischemic heart disease, congestive heart failure and atrial fibrillation, low cholesterol was significantly associated with severe stroke, total anterior circulation infarction and poor functional outcome in patients with and without statin treatment. There were no interactions between low cholesterol and prestroke statin therapy in association with outcomes. Short- and long-term mortality rates were increased for patients with low cholesterol (5.2% at discharge and 35% at 3-years) compared with higher levels (2.5% at discharge and 20.5% at 3 years). Adjusted mortality risks were increased for patients with low cholesterol; however, this finding was statistically significant only for patients not on statins before the stroke., Conclusions: Low cholesterol is associated with increased stroke severity and poorer functional outcome in patients with and without prestroke statin use. Low-cholesterol statin-naive patients show increased risks of mortality. 'Reverse epidemiology' in the association between cholesterol and outcome is possible in patients with ischemic stroke., (Copyright © 2012 S. Karger AG, Basel.)

Background: Epidemiological and clinical features of very elderly patients with stroke are still uncertain. Our aim was to study the patient characteristics and outcomes in the very elderly (aged ≥85 years) with a first-ever ischemic stroke in the National Acute Stroke Israeli Survey (NASIS) registry., Methods: The NASIS registry is a nationwide prospective hospital-based study performed triennially (2004, 2007, 2010). Patients with ischemic stroke aged ≥85 years were compared with those 65-84 years old regarding their baseline characteristics, stroke severity, etiology of stroke and stroke outcomes. Logistic regression analyses were used to adjust for potential confounders. Stroke severity was determined according to the National Institute of Health Stroke Scale (NIHSS) score., Results: The proportion of very elderly (≥85 years) patients among the NASIS population increased from 18.3% in 2004 to 19.9% in 2007 and 24.5% in 2010 (p for trend = 0.005). The percentage of women was higher in patients aged ≥85 years (p < 0.0001). Atrial fibrillation, congestive heart disease and prior disability were significantly more common, while diabetes, current smoking and dyslipidemia were less frequent in the very elderly. The very elderly presented with more severe strokes: 36.3% of the ≥85-year-old patients had an NIHSS score ≥11 compared with 22.0% in the younger age group (p < 0.05)., Conclusions: There is an increasing proportion of very elderly subjects, mostly women, among first-ever ischemic stroke patients. Current information on age-specific aspects of stroke in the very elderly is crucial to set up successful prevention pathways and implementing well-organized stroke care for this population., (Copyright © 2012 S. Karger AG, Basel.)

Background: Atrial fibrillation (AF) is a major risk factor of ischemic stroke. We tested whether the adoption of the CHADS(2) score in clinical guidelines has impacted treatment strategies for stroke prevention, and examined how AF affects stroke outcome., Methods: In the setting of two national surveys [National Acute Stroke Israeli Surveys; all patients hospitalized for stroke in Israel during February-March 2004, and March-April 2007] data of patients with and without AF were analyzed with respect to patient characteristics, use of anticoagulation, stroke severity, clinical course, and long-term outcome., Results: Of 3040 patients with acute ischemic stroke, 586 patients (19%) had a history of AF. Severe strokes on admission were significantly more frequent in patients with AF, as was the proportion of total anterior circulation strokes. Ischemic stroke associated with AF predicted poor outcome at discharge (adjusted OR 1.56; 95%CI 1.24-1.96) and higher mortality rates throughout follow-up. Among patients with a CHADS(2) score ≥ 2 prior to the index stroke and without known contraindications, 41% received anticoagulation. This proportion increased to only 62% after the index stroke, even after excluding patients with severe disability and no significant increase between 2004 and 2007 was detectable. Increasing age, in-hospital infectious complications, and unfavorable functional status at discharge were independently associated with decreased likelihood of receiving anticoagulation., Conclusions: In deviation from current recommendations and in spite of the introduction of CHADS(2) criteria, anticoagulation for stroke prevention remains underutilized, despite the particularly poor outcome of strokes associated with AF., (Copyright © 2011. Published by Elsevier Ireland Ltd.)

Background: Data linking neighborhood socioeconomic status (SES) to stroke risk are scarce. We examined long-term stroke incidence according to neighborhood SES in a population-based cohort of patients hospitalized with first myocardial infarction (MI)., Methods: Consecutive patients aged 65 years or less, discharged from 8 hospitals in central Israel after incident MI in 1992-1993, were followed for stroke through 2005. Individual demographic, socioeconomic, and clinical data were obtained at study entry. We estimated neighborhood SES through a composite census-derived index developed by the Israel Central Bureau of Statistics., Results: During a median follow-up of 13 years, 196 incident ischemic strokes occurred in 1410 patients. Accounting for death as a competing risk, patients residing in disadvantaged neighborhoods had higher rates of ischemic stroke (cumulative survival estimates: 81%, 88%, and 89% in increasing tertiles of neighborhood SES). Upon multivariable adjustment for individual SES measures (including income, education, and employment), cardiovascular risk factors, MI characteristics and severity indices, and acute management, the overall hazard ratio for stroke in the lower versus upper tertile of neighborhood SES was 1.5 (95% confidence interval [CI] = 1.0-2.3); after 13 years, the adjusted absolute risk difference was 7.9 incident stroke cases per 100 participants with MI (95% CI = 1.7-14.1)., Conclusions: Poor neighborhood SES is associated with increased risk of ischemic stroke post-MI. The association is only partly attributable to individual SES and other baseline characteristics. The potential mechanisms for this association require further study.

Background: Calcium concentrations in serum are maintained within an exquisitely narrow range. Our aim was to examine the association between serum calcium and albumin-adjusted calcium (calcium(adj)) levels and stroke outcome in a cohort of unselected patients with acute stroke., Methods: Consecutive patients hospitalized due to acute stroke (ischemic or intracerebral hemorrhage) throughout a large medical center were systematically assessed and followed for 1 year. Baseline total calcium and calcium(adj) levels were collapsed into groups of low (<8.6 mg/dl), normal (8.7-9.9 mg/dl) and high (>10 mg/dl) levels and linear and quadratic relations with outcome were examined., Result: Among 784 patients (mean age 70.7 ± 12.5 years, 42.5% females), the mean ± SD total calcium level was 9.3 ± 0.6 mg/dl. For total calcium, the adjusted hazard ratio (HR) for all-cause death over 1 year was 1.83 [95% confidence interval (CI) 1.22-2.75] among patients with low versus normal levels. For calcium(adj), the adjusted HR for all-cause death among women was over 3-fold higher among patients with high calcium(adj) levels versus those with normal levels (3.31; 95% CI 1.70-6.46), while no such associations were observed among men. In models developed to estimate the linear and quadratic relations, each unit increment in total calcium squared was associated with an increased adjusted HR of all-cause death over 1 year (p = 0.02) confirming nonlinear associations, and each unit increment in calcium(adj) squared was associated with an increased adjusted HR of all-cause death over 1 year among women (p < 0.001) but not among men (p = 0.70)., Conclusions: Serum calcium concentrations are a marker of mortality in acute stroke patients, but the associations are not linear, increasing at both extremes of calcium levels. Our findings suggest that long-term survival is optimal in a distinct range of serum calcium levels., (Copyright © 2010 S. Karger AG, Basel.)

Background: Length of stay (LOS) is the main cost-determining factor of hospitalization of stroke patients. Our aim was to derive and validate a simple score for the assessment of the risk of prolonged LOS for acute stroke patients in a national setting., Methods: Ischemic stroke (IS) and intracerebral hemorrhage (ICH) patients in the National Acute Stroke Israeli Surveys (NASIS 2004 and 2007) were included. Predictors of prolonged LOS (LOS > or =7 days) in the NASIS 2004 (n = 1,700) were identified with logistic regression analysis and used for the derivation of the Prolonged Length of Stay (PLOS) score. The score was validated in the NASIS 2007 (n = 1,648)., Results: Median (interquartile range) LOS was 6 (3-10) days in the derivation cohort (42.3% prolonged LOS) and 5 (3-8) in the validation cohort (35.7% prolonged LOS). The derivation cohort included 54.8% men, 90.8% IS and 9.2% ICH, with a mean (SD) age of 71.2 (12.5) years. Stroke severity was the strongest multivariable predictor of prolonged LOS: odds ratio (95% confidence interval [CI]) increased from 2.6 (2.0-3.3) for NIH Stroke Scale score (NIHSS) 6-10 to 4.9 (3.0-8.0) for NIHSS 16-20, compared with NIHSS < or =5. Stroke severity and type, decreased level of consciousness on admission, history of congestive heart failure, and prior atrial fibrillation were used for the derivation of the PLOS score (c statistics 0.692, 95% CI 0.666-0.718). The score performed similarly well in the validation cohort (c statistics 0.680, 95% CI 0.653-0.707)., Conclusion: A simple prolonged length of stay score, based on available baseline information, may be useful for tailoring policy aimed at better use of resources and optimal discharge planning of acute stroke patients.

Although the benefit of antithrombotic therapy for stroke prevention in atrial fibrillation (AF) is well recognized, its potential effect on stroke severity and outcome is less well established. Our objective was to examine the effect of preadmission antithrombotic therapy on stroke severity and outcome in patients with AF within a large comprehensive nationwide stroke survey. The data from consecutive patients with AF admitted with acute ischemic stroke or transient ischemic attack during a 2-month period were collected. The patients were categorized into 4 groups according to the use of preadmission antithrombotic therapy: no antithrombotic therapy, antiplatelet therapy, warfarin with an admission international normalized ratio (INR) <2 and INR of > or = 2. Of 1,938 patients presenting with acute brain ischemia, 329 (17%) had AF. The age-adjusted rate of more severe stroke (baseline National Institutes of Health stroke scale score >5) stratified by antithrombotic therapy use was 70% for no antithrombotic therapy use, 55% for antiplatelet therapy use, 59% for warfarin with an INR <2, and 38% for warfarin with an INR of > or = 2 (p = 0.01). Compared to warfarin therapy with an admission INR of > or = 2, the adjusted odds ratio for more severe strokes was 4.0 (95% confidence interval [CI] 1.7 to 10.0) for no antithrombotic therapy, 2.2 (95% CI 1.0 to 9.4) for antiplatelet therapy, and 2.7 (95% CI 1.1 to 6.7) for warfarin therapy with an INR of <2. Similarly, graded associations of antithrombotic medication were observed with severe disability (modified Rankin Scale score >3) or death at discharge, with corresponding adjusted odds ratios of 4.1 (95% CI 1.8 to 9.9), 2.1 (95% CI 1.0 to 4.6), and 1.5 (95% CI 0.6 to 3.5), and 1-year mortality, with corresponding adjusted ORs of 2.4 (95% CI 0.9 to 6.7), 1.9 (95% CI 0.8 to 5.0), and 2.2 (95% CI 0.8 to 6.2). In conclusion, in addition to its established benefit for stroke prevention, effective anticoagulation therapy is associated with decreased stroke severity and better functional outcome and survival in patients with AF presenting with acute brain ischemia., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: Despite declining age-adjusted stroke mortality rates, the disease remains the third most common cause of death in Israel. Based on a national survey, we examined mortality rates during the first 3 years after a first-ever acute ischemic stroke (IS) and the major predictors of short-term (1 month) and long-term (3 years) mortality., Methods: In the National Acute Stroke Israeli Survey (NASIS 2004), data were collected on all hospitalized stroke patients in Israel during a 2-month period. Mortality rates for first-ever IS were assessed at 1 month and 3 years and predictors of death were evaluated using the Cox proportional hazard model., Results: A total of 1,079 first-ever IS patients were included. Survival data were complete for over 99% of patients. Cumulative mortality rates were 9.9% at 1 month and 31.1% at 3 years. Of the survivors at 1 month, 23.5% did not survive for 3 years. At 1 month, the hazard ratio (HR) for death significantly increased with stroke severity. One-month mortality was also associated with a decreased level of consciousness (HR 2.9, 95% CI 1.7-5.1), total anterior circulation infarction (TACI); HR 4.9, 95% CI 1.6-15.2), temperature on admission (HR 1.5, 95% CI 1.1-2.1 per 1 degrees C), age (HR 1.04, 95% CI 1.02-1.07 per year) and glucose levels on admission (HR 1.003, 95% CI 1.001-1.006 per 1 mg/dl). Age-adjusted proportions of diabetes and chronic heart failure were considerably higher in the deceased compared with survivors at 3 years (48 vs. 38 and 21 vs. 9%, respectively). In the multivariate survival analyses, predictors of death at 1 month also predicted death at 3 years; however, history of dementia (HR 1.5, 95% CI 1.0-2.4), diabetes (HR 1.6, 95% CI 1.0-2.4), peripheral artery disease (HR 1.7, 95% CI 1.1-2.8), chronic heart failure (HR 1.6, 95% CI 1.1-2.4) and malignancy (HR 1.7, 95% CI 1.1-2.7) were additional predictors of long-term mortality for patients surviving the first month after stroke., Conclusions: Approximately one third of patients did not survive 3 years after the first-ever IS. While age and markers of severe stroke were the major predictors of death at 1 month, comorbidities and variables associated with atherosclerotic vascular disease predicted long-term mortality. Improved control of these factors can potentially reduce long-term mortality in stroke victims., (Copyright 2009 S. Karger AG, Basel.)

Background: The incidence of stroke varies among ethnically and culturally diverse groups., Objectives: To examine the ethnic-geographic patterns of stroke incidence in men and women with coronary heart disease in Israel, focusing on the extent to which this variability can be explained by known differences in risk factors for stroke., Methods: Patients with documented coronary heart disease were followed for 6-8 years for incident cerebrovascular events. Baseline medical evaluation included assessment of vascular risk factors and measurements of blood lipids. Among 15,052 patients, 1110 were identified with any incident ischemic cerebrovascular event by ICD-9 codes, of whom 613 had confirmed ischemic stroke or transient ischemic attack., Results: A major excess of ischemic cerebrovascular events among Israeli Arab women as compared to males, and an inverse finding among Israeli born Jews, were noted. The high risk in the Arab population in Israel reflected an unfavorable risk profile, since predicted rates by multivariate analysis and observed rates were 69 and 68 per 1000, respectively. High ischemic cerebrovascular event rates were identified among patients born in the Balkan countries and North Africa (89 and 90 per 1000), but unfavorable risk factor levels of these individuals did not explain them. Most trends appeared similar in male and female patients. A comparison of observed and accepted-according-to-risk-profile rates of ischemic cerebrovascular events yielded significant differences (P = 0.04), consistent with an additional role of geographic/ethnic origin resulting from factors that remain unrecognized, or with variables unassessed in this study., Conclusions: We identified an ethnic diversity in stroke risk among the Israeli born in different parts of the world beyond what could be expected on the basis of differences in known risk factors. These findings call for detailed research aimed at identifying additional differences in the risk profile of patients with atherothrombotic disease exposed to an increased risk of stroke.

Background and Purpose: Intracerebral hemorrhage (ICH) is a deadly form of stroke. Pretreatment with statins exerts protective effects in patients with ischemic stroke, but their effects in patients with ICH remains unclear., Methods: The National Acute Stroke Israeli Surveys (NASIS) included all patients admitted with acute stroke to any of the 28 hospitals nationwide during February through March 2003 and March through April 2007. We compared stroke severity and outcomes of ICH patients who received statins before the index event with those who did not, using multivariable logistic regression models adjusting for the propensity to use statins before the event., Results: Among 3212 stroke patients, 312 had ICH and 89 of them were receiving statins at the time of the ICH. Patients on statins before ICH had lower baseline NIHSS scores, less systemic complications, higher proportions of good outcome (modified Rankin scale 0 to 3), lower death rates, and higher rates of discharge home or to a rehabilitation facility. On logistic regression analyses statin use before the event was associated with odds ratios of 0.46 for having a severe stroke defined as baseline NIHSS >15 (95% CI; 0.23 to 0.93), 2.97 for having good outcome (95% CI; 1.25 to 7.35) at discharge, and 0.25 for death or nursing facility disposition (95% CI; 0.09 to 0.63)., Conclusions: Use of statins before ICH is associated with reduced mortality and neurological disability and with a higher chance for good outcome, suggesting that statins may be protective in the setting of ICH.

Low high-density lipoprotein (HDL) cholesterol is a strong independent predictor of cardiovascular risk. The present study was designed to assess the relation between the clinical response to HDL cholesterol modification and serum levels of low-density lipoprotein (LDL) cholesterol in patients with coronary artery disease (CAD). The risk for a major cardiac event (defined as nonfatal myocardial infarction or cardiac death) during a median 7.9-year follow-up period in 3,020 patients with CAD enrolled in the Bezafibrate Infarction Prevention (BIP) trial was related to changes in lipid levels during the study. Baseline LDL cholesterol levels were categorized according to National Cholesterol Education Program Adult Treatment Panel III criteria. Multivariate analysis demonstrated that the benefit of HDL cholesterol increase was most pronounced in patients with low baseline LDL cholesterol (or=160 mg/dl; hazard ratio 0.94, 95% confidence interval 0.75 to 1.17, p = 0.14). A similar relation was shown for risk reduction-associated triglyceride decrements, whereas the benefit of LDL cholesterol reduction was more pronounced in patients with baseline LDL cholesterol >or=130 mg/dl. In conclusion, these data suggest that the clinical response to HDL cholesterol and triglyceride modification is inversely related to baseline LDL cholesterol levels. Thus, combined assessment of baseline and follow-up lipid levels to direct therapeutic goals in patients with CAD may provide incremental prognostic information to secondary prevention that is based solely on LDL cholesterol modification.

Stroke is the third most common cause of death in Israel. Stroke is a leading cause of severe long-term disability and is associated with staggering economic costs. Ethnic variations observed in stroke mortality rates support that undetermined inherent genetic or sociocultural differences act to increase stroke mortality rates in immigrants from Asia and North Africa over that predicted from their profile of traditional risk factors. In accordance with other Western countries, there has been a decline in mortality rates from stroke, concomitantly with a decline observed in coronary heart disease mortality. With the aging of the population, the burden of stroke is projected to further increase. Moreover, brain infarcts detected by brain imaging are 5-times more common than the clinical syndrome of acute stroke, detected in about 20% of healthy elderly and up to 50% of high risk patients. Estimates of the incidence of stroke, characteristics of patients, management and outcome became available from the tri-annual national acute stroke Israeli survey (NASIS) program, initiated during 2004. The annual incidence of hospitalized acute cerebrovascular events is approximately 13,000 and rates, particularly in women, seem even higher than those observed for acute myocardial infarction. Findings also highlight critical deficiencies in acute stroke units and systems for urgent evaluation and intervention in acute stroke. Action plans are urgently required, in accordance with the experience from other countries, in order to upgrade the stroke infrastructure nationwide for more effective prevention and management of acute stroke.

Stroke is a major cause of morbidity and mortality in Israel and the main cause for neurological disability among adults. Continued efforts for its prevention and treatment began a long time ago and currently persist. During the last decade, these efforts have resulted in a number of significant breakthroughs. Consequently, several new guidelines and consensus statements from Europe and North America have been published. In Israel, up to date, guidelines have been published only for acute stroke treatment, as well as for its prevention by medical means. The present guideline is supplemental to the previous papers and focuses on the invasive options to treat specific risk factors and conditions, when appropriate, for primary and secondary stroke prevention.

Inherited disorders of hemostasis are natural models for investigating mechanisms of thrombosis and development of antithrombotic therapy. Because mice with total factor XI deficiency are protected against ischemic stroke and do not manifest excessive bleeding, we investigated the incidence of ischemic stroke in patients with severe inherited factor XI deficiency. Incidence of ischemic stroke in 115 patients aged 45 years or more with severe factor XI deficiency (activity less than 15 U/dL) was compared with incidence in the Israeli population as estimated from a stroke survey of 1528 patients. Adjustment for major risk factors of stroke (hypertension, diabetes mellitus, hypercholesterolemia, current smoking) was based on comparison of their prevalence in the stroke survey to an Israeli health survey of 9509 subjects. Incidence of myocardial infarction in the factor XI cohort was also recorded. After adjustment for the 4 major risk factors of ischemic stroke, the expected incidence of ischemic stroke was 8.56 compared with one observed (P = .003). The reduced 1:115 incidence of ischemic stroke contrasted with a 19:115 incidence of myocardial infarction, similar to the expected incidence. Thus, severe factor XI deficiency probably is protective against ischemic stroke but not against acute myocardial infarction.

Objective: To investigate predictive factors for disposition after acute stroke., Design: A nationwide survey (2004 National Acute Stroke Israeli Survey)., Setting: All 28 primary general medical centers operating in Israel., Participants: Acute stroke patients (n=1583) admitted during February and March 2004 and discharged from the primary hospital., Interventions: Data collected on baseline characteristics, stroke presentation, type and severity, in-hospital investigation and complications, discharge disability, acute hospital disposition, and mortality follow-up., Main Outcome Measure: Hospital disposition to home, acute rehabilitation, or nursing facility., Results: Among patients, 58.9% (n=932) were discharged home, 33.7% (n=534) to rehabilitation departments, and only 7.4% (n=117) to nursing facilities. Admission neurologic status was a good predictor of hospital disposition. Patients with severe strokes were mostly discharged to rehabilitation facilities. Patients with significant functional decline before the index stroke, resulting from a previous stroke or another cause, were sent to inpatient rehabilitation less frequently. Disability level at discharge from acute hospitalization had high predictive value in hospital disposition after stroke. In the northern region of Israel, a higher proportion of patients were sent home and a lower proportion to rehabilitation and nursing facilities, probably because of lower availability of rehabilitation care in this region of Israel., Conclusions: This nationwide survey shows that most stroke survivors in Israel are discharged home from the acute primary hospital. Good functional status before the index stroke is an important predictor for being sent to acute inpatient rehabilitation. Severity of neurologic impairment and level of disability after the stroke at discharge from the primary hospital are strong predictors for disposition after stroke in Israel. Our data may be useful in discharge planning for stroke patients by policy-makers and health care providers in Israel.

Stroke is a major cause of morbidity and mortality in Israel, the third most common cause of death and the main cause for neurological disability among adults. During the last decade several significant breakthroughs have occurred in the management of stroke and consequently several new guidelines and consensus statements from Europe and North America have been published. The new data necessitate a reappraisal of our approach to the management of stroke as well as to its primary prevention. The present guidelines focus on primary and secondary stroke prevention by medical means and provide detailed, updated, clinical guidelines for most specific risk factors and conditions, ways to investigate the underlying stroke mechanism and its preferred medical treatment. Invasive (surgical, stent insertion, correction of cardiac anomalies etc.) will be dealt with separately.

Background: Mild renal insufficiency is increasingly recognized as an independent risk factor for cardiovascular disease. However, few data exist regarding its relation to risk of ischemic stroke., Methods: Patients with chronic coronary heart disease and measured serum creatinine levels (n = 6,685) were followed up for incident ischemic stroke or TIA over 4.8 to 8.1 years. Glomerular filtration rate was estimated by the Cockroft-Gault equation and by the four-component Modification of Diet in Renal Disease (MDRD) equation and a rate < or =60 mL/minute/1.73 m2 defined chronic kidney disease (CKD)., Results: Among 6,685 patients, a quarter of patients had CKD. Adjusting for conventional risk factors and related medications, patients with CKD exhibited 1.54-fold hazard ratios (95% CI 1.13 to 2.09) of incident ischemic stroke or TIA by the Cockroft-Gault equation (1.53; 95% CI 1.16 to 2.01 by the MDRD equation). The corresponding adjusted hazard ratio associated with an increment of 1 SD in GFR was 0.71 (95% CI 0.57 to 0.88) when estimated by the Cockroft-Gault equation (0.84; 95% CI 0.75 to 0.95 estimated by the MDRD equation)., Conclusions: Mild degrees of renal dysfunction are associated with increased risk of incident ischemic stroke or TIA in patients with pre-existing atherothrombotic disease. These findings expand the recommendation that patients with renal dysfunction should be considered as a high-risk group for cardiovascular disease and for ischemic stroke.

Background and Purpose: C-reactive protein (CRP) has emerged as an important predictor of cardiovascular disease, but there are few prospective data on its association with risk of ischemic stroke in patients at high risk., Methods: We examined the association between CRP levels and subsequent risk of incident ischemic stroke among 2979 patients with stable coronary heart disease included in a controlled clinical trial (Bezafibrate Infarction Prevention) that assessed the efficacy of bezafibrate, a fibric acid derivative, versus placebo for secondary prevention. CRP was measured by a high-sensitivity assay in plasma samples collected before randomization and again at the second follow-up year of an overall mean follow-up of 6.2 years., Results: Risk of ischemic stroke per 1000 person-years increased from 4.1% for baseline CRP in the lowest tertile (<2.3 mg/L; n=982) to 5.9% for levels at the middle tertile (2.3 to 5.4 mg/L; n=1013) and 10.5% for CRP levels at the upper tertile (>5.4 mg/L; n=984; P<0.001). With adjustment for potential confounders, baseline CRP levels in the top versus bottom tertile were associated with a 2.16-fold increased hazard (95% CI, 1.32 to 3.53) for ischemic stroke, and CRP levels measured after 2 years were associated with a hazard ratio of 2.43 (95% CI, 1.30 to 4.57). The risk of an incident ischemic stroke did not differ between the bezafibrate group compared with the placebo group regardless of baseline CRP levels., Conclusions: These findings, based on a large prospective study, demonstrate the risk prediction for incident ischemic stroke conferred by CRP levels in patients at high risk.

Background: CD40 ligand (CD40L) is a trimeric, transmembrane protein of the tumor necrosis factor family and together with its receptor CD40 is an important contributor to the inflammatory processes that lead to atherosclerosis, plaque destabilization, and thrombosis., Methods: In order to assess the association between serum concentrations of CD40 ligand (CD40L) and risk of future ischemic stroke and coronary events among patients with chronic CHD, we obtained baseline serum samples from patients (n = 3090) with chronic CHD enrolled in a secondary prevention trial. With a prospective nested case-control design, we measured baseline CD40L concentration in sera of patients who subsequently developed myocardial infarction, sudden cardiac death or ischemic stroke during follow-up (cases, n = 233) and in 233 age- and gender-matched pairs without any subsequent cardiovascular events., Results: Relative odds for recurrent cardiovascular events per one natural log unit difference of CD40L were 0.97 (95%CI, 0.82-1.16). No increase in relative odds for recurrent cardiovascular events was observed per increasing quartiles of CD40L concentrations. In analysis for individual end-points, different trends of risks were observed beyond the 95 percentile for ischemic stroke (OR 2.22; 95%CI, 0.46-12.5) and for recurrent coronary events (OR 0.35; 95%CI, 0.07-1.37), but falling short of statistical significance., Conclusion: High serum concentrations of CD40L were not associated with increased risk of ischemic stroke or coronary events in patients with chronic coronary heart disease.

Background: There are no national data on the burden and management of acute cerebrovascular disease in Israel., Objectives: To delineate the burden, characteristics, management and outcomes of hospitalized patients with acute cerebrovascular disease in Israel, and to examine adherence to current guidelines., Methods: We prospectively performed a national survey in all 28 hospitals in Israel admitting patients with acute cerebrovascular events (stroke or transient ischemic attacks) during February and March 2004., Results: During the survey period 2174 patients were admitted with acute cerebrovascular disease (mean age 71 +/- 13 years, 47% women; 89% ischemic stroke or TIA, 7% intracerebral hemorrhage and 4% undetermined stroke). Sixty-two percent of patients were admitted to departments of medicine and a third to neurology, of which only 7% were admitted to departments with a designated stroke unit. Head computed tomography was performed during hospitalization in 93% of patients. The overall rate of urgent thrombolytic therapy for acute ischemic stroke was 0.5%. Among patients with ischemic stroke or TIA, 94% were prescribed an antithrombotic medication at hospital discharge, and among those with atrial fibrillation about half were prescribed warfarin. Carotid duplex was performed in 30% and any vascular imaging study in 36% of patients with ischemic events. The mean (+/-SD) length of hospital stay was 12 +/- 27 days for ICH and 8 +/- 11 days for ischemic stroke. Among patients with ICH, 28% died during hospitalization and 66% died or remained with severe disability while for ischemic stroke the corresponding rates were 7% and 41% respectively. Mortality rates within 3 months were 34% for ICH and 14% for ischemic stroke., Conclusions: This national survey demonstrates the high burden of acute stroke in Israel and reveals discordance between existing guidelines and current practice. The findings highlight important areas for which reorganization is imperative for patients afflicted with acute stroke.

Background: Clinical trials have demonstrated the superiority of managing acute stroke in a dedicated stroke unit over conventional treatment in general medical wards. Based on these findings, nationwide stroke unit care programs have been implemented in several countries., Objective: To assess the effect of establishing a new dedicated acute stroke unit within a department of neurology on indicators of process of care and outcome of acute stroke in a routine clinical setting in Israel., Methods: Stroke patients admitted to the Sheba Medical Center during the period March 2001 to June 2002 were included in a prospective study according to selection criteria. Data on demographics, risk factors, co-morbidities and stroke severity were collected. Indicators of process of care and outcome were assessed at hospital discharge and 30 days follow-up. Comparison between outcome variables by hospitalization ward was done using logistic regression analysis adjusting for confounders., Results: Of 616 acute stroke patients (mean age 70 years, 61% men, 84% ischemic stroke), 353 (57%) were admitted to general wards and 263 (43%) to the stroke unit. Diagnostic procedures were performed more often and the infection rate was lower in the setting of the stroke unit. Poor outcome (modified Rankin scale > or = 3 or death) was present less often in patients managed in the stroke unit both at hospital discharge (adjusted odds ratio 0.5, 95% confidence interval 0.3-0.8) and at 30 day follow-up (adjusted OR 0.6, 95%CI 0.3-0.9). A Functional Independence Measure score < or = 90 or death at 30 day follow-up was less frequent among patients managed in the stroke unit than in general wards (adjusted OR 0.5, 95%CI 0.2-0.8)., Conclusions: Improved outcomes and higher adherence to guidelines were observed in patients treated in a stroke unit within a department of neurology. The results suggest that patients with acute stroke should have access to treatment in a dedicated stroke unit.

Background: Stroke and its long-term neurological sequelae can be prevented by management of risk factors and seeking medical care as early as possible following the onset of stroke symptoms., Aims: This study aimed to investigate the scope of knowledge on stroke, and to assess the perceived risk of stroke among the Israeli population., Methods and Results: A telephone survey was conducted of a sample study of 300 men and women, 40 years of age or older, that represent the Hebrew speaking population in Israel of this age range. The best known risk factor for stroke was arterial hypertension, but 24% of the study population could not spontaneously recall any risk factor. Nearly half of the study sample (46%) was aware of the fact that a healthy lifestyle may contribute to stroke prevention, but only 24% mentioned that medical follow-up and control of hypertension, dyslipidemia and diabetes mellitus reduce the risk of stroke. Among interviewed subjects who reported the existence of at least one risk factor of stroke, only 14% recognized that they belong to a group at risk of having a stroke. Awareness of neurological disabilities resulting from stroke was relatively high, with only 15% of responders unable to name any disability., Conclusion: Our study demonstrates the lack of knowledge on stroke among the Israeli population. Knowledge is particularly poor regarding the possibility of stroke prevention through risk factor management, and with respect to recognition of symptoms of acute stroke. A program directed at raising the awareness and knowledge of stroke by the Israeli public is required for effective stroke prevention and therapy.