Adolescent Hypertension Is Associated With Stroke in Young Adulthood: A Nationwide Cohort of 1.9 Million Adolescents.

BACKGROUND: Adult hypertension is a well-established risk factor for stroke in young adults (aged <55 years), and the effects are even more deleterious than at an older age. However, data are limited regarding the association between adolescent hypertension and the risk of stroke in young adulthood. METHODS: A nationwide, retrospective cohort study of adolescents (aged 16-19 years) who were medically evaluated before compulsory military service in Israel during 1985 to 2013. For each candidate for service, hypertension was designated after constructed screening, and the diagnosis was confirmed through a comprehensive workup process. The primary outcome was ischemic and hemorrhagic stroke incidence as registered at the national stroke registry. Cox proportional-hazards models were used. We conducted sensitivity analyses by excluding people with a diabetes diagnosis at adolescence or a new diabetes diagnosis during the follow-up period, analysis of adolescents with overweight, and adolescents with baseline unimpaired health status. RESULTS: The final sample included 1 900 384 adolescents (58% men; median age, 17.3 years). In total, 1474 (0.08%) incidences of stroke (1236 [84%] ischemic) were recorded, at a median age of 43 (interquartile range, 38-47) years. Of these, 18 (0.35%) occurred among the 5221 people with a history of adolescent hypertension. The latter population had a hazard ratio of 2.4 (95% CI, 1.5-3.9) for incident stroke after adjustment for body mass index and baseline sociodemographic factors. Further adjustment for diabetes status yielded a hazard ratio of 2.1 (1.3-3.5). We found similar results when the outcome was ischemic stroke with a hazard ratio of 2.0 (1.2-3.5). Sensitivity analyses for overall stroke, and ischemic stroke only, yielded consistent findings. CONCLUSIONS: Adolescent hypertension is associated with an increased risk of stroke, particularly ischemic stroke, in young adulthood.

Hospitalizations in older-adults newly diagnosed with dementia: A population-based longitudinal study in Israel.

OBJECTIVES: To compare inpatient burden (i.e. likelihood of hospitalization, number of admissions and length of stay) in persons with newly diagnosed dementia to the general population without dementia. Additionally, to evaluate whether inpatient burden is increased during the years prior to and post dementia diagnosis, and to identify factors associated with increased inpatient burden. METHOD: The Israeli National Dementia Dataset (2016) was cross-linked with the National Hospital Discharge Database of the Israeli Ministry of Health (2014-2018). Dementia definition was based on documented dementia diagnoses and/or the purchase of medications during 2016. Mixed-effects models were applied to identify demographic and health characteristics associated with inpatient burden in the one and 2 years prior to and after dementia diagnosis. RESULTS: The dataset included 11,625 individuals aged ≥65 years, identified as incident dementia cases. Compared to the general population of older-adults without dementia, those with newly diagnosed dementia had a higher age-standardized proportion of hospitalizations (26.4% vs. 40%). The odds for hospitalization were highest during the year preceding dementia diagnosis (OR = 3.19, 95% CI 2.51-4.06) compared to 2 years prior to diagnosis, and remained high (although slightly decreased) after dementia diagnosis. Older age was associated with inpatient burden after, but not prior to dementia diagnosis. CONCLUSIONS: Older persons with dementia are a vulnerable population group with increased utilization of inpatient burden compared to those without dementia, particularly in the years surrounding dementia diagnosis. Sociodemographic risk factors may differ with respect to the time surrounding dementia diagnosis.

Obesity in late adolescence and incident type 1 diabetes in young adulthood.

AIMS/HYPOTHESIS: Studies in children have reported an association between increased BMI and risk for developing type 1 diabetes, but evidence in late adolescence is limited. We studied the association between BMI in late adolescence and incident type 1 diabetes in young adulthood. METHODS: All Israeli adolescents, ages 16-19 years, undergoing medical evaluation in preparation for mandatory military conscription between January 1996 and December 2016 were included for analysis unless they had a history of dysglycaemia. Data were linked with information about adult onset of type 1 diabetes in the Israeli National Diabetes Registry. Weight and height were measured at study entry. Cox proportional models were applied, with BMI being analysed both as a categorical and as a continuous variable. RESULTS: There were 777 incident cases of type 1 diabetes during 15,819,750 person-years (mean age at diagnosis 25.2±3.9 years). BMI was associated with incident type 1 diabetes. In a multivariable model adjusted for age, sex and sociodemographic variables, the HRs for type 1 diabetes were 1.05 (95% CI 0.87, 1.27) for the 50th-74th BMI percentiles, 1.41 (95% CI 1.11, 1.78) for the 75th-84th BMI percentiles, 1.54 (95% CI 1.23, 1.94) for adolescents who were overweight (85th-94th percentiles), and 2.05 (95% CI 1.58, 2.66) for adolescents with obesity (≥95th percentile) (reference group: 5th-49th BMI percentiles). One increment in BMI SD was associated with a 25% greater risk for incidence of type 1 diabetes (HR 1.25, 95% CI 1.17, 1.32). CONCLUSIONS: Excessively high BMI in otherwise healthy adolescents is associated with increased risk for incident type 1 diabetes in early adulthood.

The contribution of potentially modifiable risk factors to acute ischemic stroke burden - Comparing young and older adults.

Stroke is a leading cause of death and disability. In order to estimate the contribution of five modifiable risk factors to acute ischemic stroke (AIS) incidence in Israel, we conducted a case-control study based on first AIS cases aged 21-90 reported to the Israeli National Stroke Registry during 2014-2015, and controls from a national health survey conducted between 2013 and 2015. We calculated the population attributable risk (PAR) of each risk factor and the combined PAR for all risk factors (hypertension, diabetes, current smoking, obesity and hyperlipidemia), in all study population and by subgroups of young adults (age < 55) and older adults (age ≥ 55). The final analysis included 571, 577 and 500 matched pairs for all study population, young adults and older adults, respectively. Among young adults, current smoking and hypertension were the two most contributing risk factors for AIS, accounting for 33.6% (95% CI 27.3-39.9) and 28.9% (95% CI 22.1-35.7) of AIS cases, respectively. Among older adults, hypertension was the single most contributing risk factor for AIS and diabetes was the second most contributing risk factor for AIS, accounting for 64.9% (95% CI 57.3-72.5) and 25.7% (95% CI 17.5-33.9) of AIS cases, respectively. The combined PAR was significantly lower among young adults (PAR = 67.9%), compared with older adults (PAR = 80.7%). The combined PAR for all study population was 80.1% (95% CI 74.0-86.2), indicating that five common and modifiable risk factors explain ~80% of AIS incidence in Israel. Primary prevention strategies targeting these risk factors have the potential to drastically reduce stroke related morbidity and mortality.

Premature mortality attributable to COVID-19: potential years of life lost in 17 countries around the world, January-August 2020.

BACKGROUND: Understanding the impact of the burden of COVID-19 is key to successfully navigating the COVID-19 pandemic. As part of a larger investigation on COVID-19 mortality impact, this study aims to estimate the Potential Years of Life Lost (PYLL) in 17 countries and territories across the world (Australia, Brazil, Cape Verde, Colombia, Cyprus, France, Georgia, Israel, Kazakhstan, Peru, Norway, England & Wales, Scotland, Slovenia, Sweden, Ukraine, and the United States [USA]). METHODS: Age- and sex-specific COVID-19 death numbers from primary national sources were collected by an international research consortium. The study period was established based on the availability of data from the inception of the pandemic to the end of August 2020. The PYLL for each country were computed using 80 years as the maximum life expectancy. RESULTS: As of August 2020, 442,677 (range: 18-185,083) deaths attributed to COVID-19 were recorded in 17 countries which translated to 4,210,654 (range: 112-1,554,225) PYLL. The average PYLL per death was 8.7 years, with substantial variation ranging from 2.7 years in Australia to 19.3 PYLL in Ukraine. North and South American countries as well as England & Wales, Scotland and Sweden experienced the highest PYLL per 100,000 population; whereas Australia, Slovenia and Georgia experienced the lowest. Overall, males experienced higher PYLL rate and higher PYLL per death than females. In most countries, most of the PYLL were observed for people aged over 60 or 65 years, irrespective of sex. Yet, Brazil, Cape Verde, Colombia, Israel, Peru, Scotland, Ukraine, and the USA concentrated most PYLL in younger age groups. CONCLUSIONS: Our results highlight the role of PYLL as a tool to understand the impact of COVID-19 on demographic groups within and across countries, guiding preventive measures to protect these groups under the ongoing pandemic. Continuous monitoring of PYLL is therefore needed to better understand the burden of COVID-19 in terms of premature mortality.

Body Mass Index in 1.9 Million Adolescents and Stroke in Young Adulthood.

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, 1.2­1.6), 2.0 (95% CI, 1.6­2.4), and 3.4 (95% CI, 2.7­4.3) 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 (1.1­1.5), 1.6 (1.3­2.0), and 2.4 (1.9­3.1). 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.

Reduction in Acute Stroke Admissions during the COVID-19 Pandemic: Data from a National Stroke Registry.

INTRODUCTION: The COVID-19 pandemic overwhelmed health-care systems worldwide, and medical care for other acute diseases was negatively impacted. We aimed to investigate the effect of the COVID-19 outbreak on admission rates and in-hospital care for acute stroke and transient ischemic attack (TIA) in Israel, shortly after the start of the pandemic. METHODS: We conducted a retrospective observational study, based on data reported to the Israeli National Stroke Registry from 7 tertiary hospitals. All hospital admissions for acute stroke or TIA that occurred between January 1 and April 30, 2020 were included. Data were stratified into 2 periods according to the timing of COVID-19 restrictions as follows: (1) "pre-pandemic" - January 1 to March 7, 2020 and (2) "pandemic" - March 8 to April 30, 2020. We compared the weekly counts of hospitalizations between the 2 periods. We further investigated changes in demographic characteristics and in some key parameters of stroke care, including the percentage of reperfusion therapies performed, time from hospital arrival to brain imaging and to thrombolysis, length of hospital stay, and in-hospital mortality. RESULTS: 2,260 cases were included: 1,469 in the pre-COVID-19 period and 791 in the COVID-19 period. Hospital admissions significantly declined between the 2 periods, by 48% for TIA (rate ratio [RR] = 0.52; 95% CI 0.43-0.64) and by 29% for stroke (RR = 0.71; 95% CI 0.64-0.78). No significant changes were detected in demographic characteristics and in most parameters of stroke management. While the percentage of reperfusion therapies performed remained unchanged, the absolute number of patients treated with reperfusion therapies seemed to decrease. Higher in-hospital mortality was observed only for hemorrhagic stroke. CONCLUSION: The marked decrease in admissions for acute stroke and TIA, occurring at a time of a relatively low burden of COVID-19, is of great concern. Public awareness campaigns are needed as patients reluctant to seek urgent stroke care are deprived of lifesaving procedures and secondary prevention treatments.

[DIABETIC FOOT IN ISRAEL - CURRENT STATUS AND FUTURE PERSPECTIVES].

INTRODUCTION: Diabetic foot ulcers and amputations are the most dreaded diabetes complications. The annual incidence of diabetic foot ulcers in Israel is estimated at 1.8% of all patients with diabetes. The number of patients with diabetes undergoing major amputation in the recent decade has been relatively stable in Israel, and in 2018, 887 patients with diabetes had undergone a major amputation. The proportion of patients undergoing a vascular intervention in the year prior to a major amputation has remained steady over the recent decade, and ranges between 20-40% depending on the patient's age. Aiming to reduce amputation rate, efforts should be made at three levels: 1) Primary care - increasing awareness of patients and health care teams to diabetic foot complications, the means to avoid them, and the delivery of preliminary care. Efforts to further increase awareness should be undertaken. Identification of the foot at-risk and incorporation of professional teams in the care of these patients, as well as provision of appropriate preventive offloading footwear should be sought. 2) Secondary clinics - these multidisciplinary clinics tend to all complications which cannot be adequately addressed in primary care. The professional standard of these clinics should be determined, and the access to these clinics improved. Adequate equipment in these clinics is mandatory as well. 3) Tertiary hospitals - care for the patients who require hospitalization. A national standard for inpatient diabetic foot care should be implemented and multi-disciplinary departments incorporating internists, orthopedists and vascular surgeons should be established aiming to address the medical and surgical complexity of these patients. Qualified nursing staff as well as additional health care professionals including physiotherapists, dieticians, clinical pharmacists, social workers, occupational therapists and others should also be included. Documentation of diabetic foot ulcers is lacking, both in the community and in hospitals. Use of uniform diagnostic codes should be implemented to enable close monitoring of disease trends.

Adolescent BMI and early-onset type 2 diabetes among Ethiopian immigrants and their descendants: a nationwide study.

BACKGROUND: We assessed in a nationwide cohort the association between adolescent BMI and early-onset (< 40 years) type 2 diabetes among Israelis of Ethiopian origin. METHODS: Normoglycemic adolescents (range 16-20 years old), including 93,806 native Israelis (≥ 3rd generation in Israel) and 27,684 Israelis of Ethiopian origin, were medically assessed for military service between 1996 and 2011. Weight and height were measured. Data were linked to the Israeli National Diabetes Registry. Incident type 2 diabetes by December 31, 2016 was the outcome. Cox regression models stratified by sex and BMI categories were applied. RESULTS: 226 (0.29%) men and 79 (0.18%) women developed diabetes during 992,980 and 530,814 person-years follow-up, respectively, at a mean age of 30.4 and 27.4 years, respectively. Among native Israeli men with normal and high (overweight and obese) BMI, diabetes incidence was 9.5 and 62.0 (per 105 person-years), respectively. The respective incidences were 46.9 and 112.3 among men of Ethiopian origin. After adjustment for sociodemographic confounders, the hazard ratios for type 2 diabetes among Ethiopian men with normal and high BMI were 3.4 (2.3-5.1) and 15.8 (8.3-30.3) respectively, compared to third-generation Israelis with normal BMI. When this analysis was limited to Israeli-born Ethiopian men, the hazard ratios were 4.4 (1.7-11.4) and 29.1 (12.9-70.6), respectively. Results persisted when immigrants of other white Caucasian origin were the reference; and among women with normal, but not high, BMI. CONCLUSIONS: Ethiopian origin is a risk factor for early-onset type 2 diabetes among young men at any BMI, and may require selective interventions.

High ambient temperature in summer and risk of stroke or transient ischemic attack: A national study in Israel.

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.

Validity of diagnostic codes and estimation of prevalence of diabetic foot ulcers using a large electronic medical record database.

AIMS: To assess the validity of the diagnostic codes relating to diabetic foot ulcer (DFU) in the electronic medical records of a large integrated care provider and to assess the prevalence of DFU among its members. MATERIALS AND METHODS: Data were obtained from the diabetes registry of Maccabi Healthcare Services (MHS), a 2.1-million-member sick-fund in Israel, which included 125 665 patients in 2015. We randomly selected and reviewed ~400 patient files from each of the following categories during study period: (1) had a diagnostic code of DFU; (2) had a diagnostic code, or clinical condition suggestive of DFU including: leg-ulcer, amputation, DFU in quartiles proximate to 2015 or abnormality reported by nurse; (3) patients at high risk for DFU (age > 35 and one of the following: peripheral artery disease, neuropathy, DFU during 2011-2014, eGFR<30 mL/min/m2 or foot deformity). The patients' charts were reviewed by study physicians, and DFU was validated or refuted. RESULTS: Relying upon diagnostic codes entered by physicians, the positive predictive value (PPV) was 73.1% (95% CI 67.6-78.2), and the sensitivity was 48.2% (95% CI 45.8-50.7%). The PPV of the diagnostic codes listed by podiatrists were significantly lower, while that of codes listed by nurses was higher but with lower sensitivity. The estimated annual prevalence of DFU in the diabetes registry of MHS was 1.2% (95%CI 1.0-1.5%). CONCLUSIONS: Diagnostic codes alone cannot be used reliably to create a DFU registry. Nevertheless, the data collected provide an estimate of the prevalence of DFU among patients included in the MHS diabetes registry.

[THE ISRAELI NATIONAL STROKE REGISTRY - A TOOL FOR MONITORING MORBIDITY AND ACUTE STROKE CARE IN ISRAEL].

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.

New onset diabetes in adulthood is associated with a substantial risk for mortality at all ages: a population based historical cohort study with a decade-long follow-up.

BACKGROUND: Diabetes has been reported to be associated with an increased relative risk for mortality, with estimates ranging from 1.1 to 2.1. Findings are inconsistent regarding modification of the risk by gender and by age. The aim of this study was to estimate the mortality risk associated with new-onset diabetes in adulthood, by age group and gender. METHODS: From the database of a large health care provider, we identified 31,987 individuals diagnosed with diabetes during 2003-2005; and 162,656 individuals without diabetes, group-matched by age. We used Cox regression to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for overall mortality adjusted for age, gender, socioeconomic (SE) level, obesity, smoking and comorbidities at baseline. RESULTS: During a median follow-up of 9.5 years, 4464 (14%) of persons with diabetes and 13,327 (8.2%) of those without died. Among persons with incident diabetes, the proportion of men, smokers, obese and patients of low SE level was higher, as was the prevalence of cardiovascular disease and renal impairment at baseline. Incident diabetes was associated with an adjusted HR for mortality of 1.38 (95% CI 1.32-1.43). Mortality HR for DM was comparable with hypertension (1.42; 1.37-1.46), smoking (1.65; 1.58-1.71) and atherosclerosis (1.40; 1.35-1.46). Diabetes associated mortality HR was somewhat higher among women 1.78 (95% CI 1.58-2.08) as compared with men 1.51 (95% CI 1.41-1.62). CONCLUSIONS: Incident diabetes in adults is associated with a substantial risk for mortality, especially in younger adults. Further efforts should be allocated to diabetes primary prevention.

Variations in death certification practices distort international comparisons of mortality from diabetes.

Background: Israel is ranked second among OECD countries in diabetes mortality despite good performance on diabetes care measures. This study assessed whether variations in death certification practices could explain differences in diabetes mortality rates between countries, using a comparison between the USA and Israel as an example. Methods: Multiple cause mortality data for Israel and the USA were analyzed. The proportions of cases with diabetes coded as the underlying cause of death (UCOD), of all certificates with diabetes listed as one of the multiple causes of death (MCOD), were calculated by age-group, and compared between the USA and Israel, with emphasis on cases in which cardiovascular events were reported in part I of the certificate. Results: The diabetes UCOD/MCOD ratio was higher in Israel for all age groups. The differences in proportions were larger when cardiovascular events were reported in part I. Diabetes mortality rate ratio between the countries would be 49% lower if the UCOD/MCOD ratios in US data were applied to the Israeli data. Conclusions: Half of the difference in the reported diabetes mortality rate between the USA and Israel is explained by different coding practices. International comparisons could be improved by using multiple cause data or by clarifying guidelines regarding certification of diabetes deaths.

The accuracy of suicide statistics: are true suicide deaths misclassified?

PURPOSE: Official suicide statistics often produce an inaccurate view of suicide populations, since some deaths endorsed as being of uncertain manner are in fact suicides; it is common, therefore, in suicide research, to account for these deaths. We aimed to test the hypothesis that non-suicide death categories contain a large potential reservoir of misclassified suicides. METHODS: Data on undetermined intent and ill-defined death causes, and official suicide deaths recorded in the district of Tel Aviv for the years 2005 and 2008 were extracted. Based on supplementary data, cases regarded as probable suicides ("suicide probable") were then compared with official suicides ("suicide verdicts") on a number of socio-demographic variables, and also in relation to the mechanism of death. RESULTS: Suicide rates were 42 % higher than those officially reported after accounting for 75 probable suicides (erroneously certified under other cause-of-death categories). Both death classifications ("suicide probable" and "suicide verdicts") had many similarities, significantly differing only with respect to method used. Logistic regression confirmed that the most powerful discriminator was whether the mechanism of death was considered "less active" or "more active" (p < 0.001). Indeed, deaths among the less active group were 4.9 times as likely to be classified as "suicide probable" than were deaths among the more active group. CONCLUSIONS: Caution is needed when interpreting local area data on suicide rates, and undetermined and ill-defined deaths should be included in suicide research after excluding cases unlikely to be suicides. Improving suicide case ascertainment, using multiple sources of information, and uniform reporting practices, is advised.

Significant cross reactive antibodies to influenza virus in adults and children during a period of marked antigenic drift.

BACKGROUND: Little is known about the development of cross-reactive antibodies following natural exposure to pathogens. Such knowledge is critical in the development of new universal influenza vaccines. METHODS: To study the possibility of the presence of cross-reactive antibodies to influenza viruses which underwent a major antigenic drift between the years 1999 and 2007 sera from samples of 80 children and 400 adults were selected at random from the Israeli national serum bank. The sera was obtained in 2002 and in 2007, two time points that followed a major drift in the infectious H3N2 influenza virus strain (A/Panama/2007/99 to A/Wisconsin/67/2005). RESULTS: In the summer of 2002, 13% of the children had Hemagglutination Inhibition (HI) antibody titers of at least 40 and these antibodies recognized both A/Panama/2007/99 and A/Wisconsin/67/2005, where the latter strain only began to circulate in Israel in 2006. In 2007, 29% of the children had HI antibody titers of at least 40 directed against both A/Wisconsin/67/2005 and A/Panama/2007/99, even though they had never been exposed to the latter virus. Anti-A/Panama/2007/99 antibodies were detected in 58% and 68% of the 2002 and 2007 adult samples, respectively, while 8% and 39% had antibodies against A/Wisconsin/67/2005, respectively. CONCLUSIONS: The presence of naturally occurring cross-reactive influenza virus antibodies in a significant percentage of children has important implications for the development of a universal influenza vaccine.

Age-dependent seasonality in the incidence of stroke: A 21-year population-based study.

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.

Identifying Diabetes Related-Complications in a Real-World Free-Text Electronic Medical Records in Hebrew Using Natural Language Processing Techniques.

BACKGROUND: Studies have demonstrated that 50% to 80% of patients do not receive an International Classification of Diseases (ICD) code assigned to their medical encounter or condition. For these patients, their clinical information is mostly recorded as unstructured free-text narrative data in the medical record without standardized coding or extraction of structured data elements. Leumit Health Services (LHS) in collaboration with the Israeli Ministry of Health (MoH) conducted this study using electronic medical records (EMRs) to systematically extract meaningful clinical information about people with diabetes from the unstructured free-text notes. OBJECTIVES: To develop and validate natural language processing (NLP) algorithms to identify diabetes-related complications in the free-text medical records of patients who have LHS membership. METHODS: The study data included 2.3 million records of 41 469 patients with diabetes aged 35 or older between the years 2012 and 2017. The diabetes related complications included cardiovascular disease, diabetic neuropathy, nephropathy, retinopathy, diabetic foot, cognitive impairments, mood disorders and hypoglycemia. A vocabulary list of terms was determined and adjudicated by two physicians who are experienced in diabetes care board certified diabetes specialist in endocrinology or family medicine. Two independent registered nurses with PhDs reviewed the free-text medical records. Both rule-based and machine learning techniques were used for the NLP algorithm development. Precision, recall, and F-score were calculated to compare the performance of (1) the NLP algorithm with the reviewers' comments and (2) the ICD codes with the reviewers' comments for each complication. RESULTS: The NLP algorithm versus the reviewers (gold standard) achieved an overall good performance with a mean F-score of 86%. This was better than the ICD codes which achieved a mean F-score of only 51%. CONCLUSION: NLP algorithms and machine learning processes may enable more accurate identification of diabetes complications in EMR data.

Cognitive function in adolescence and the risk of early-onset stroke.

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.

Particulate Air Pollution Exposure and Stroke among Adults in Israel.

Stroke is the second most common cause of death and disability in the world. Many studies have found fine particulate matter (PM2.5) exposure to be associated with an increased risk of atherosclerotic cardiovascular disease, mostly focusing on ischemic heart disease and acute myocardial infarction. In a national analysis conducted in Israel-an area with unique climate conditions and high air pollution levels, we estimated the association between short-term PM2.5 exposure and ischemic stroke, intracerebral hemorrhage (ICH), or transient ischemic attacks (TIA). Using the Israeli National Stroke Registry, we obtained information on all stroke cases across Israel in 2014-2018. We obtained daily PM2.5 exposures from spatiotemporally resolved exposure models. We restricted the analytical data to days in which PM2.5 levels did not exceed the Israeli 24 h standard (37.5 µg/m3). We repeated the analysis with a stratification by sociodemographic characteristics and comorbidities. For all outcomes, the exposure-response curves were nonlinear. PM2.5 exposure was associated with a higher ischemic stroke risk, with larger effect estimates at higher exposure levels. Although nonsignificant, the exposure-response curve for TIA was similar. The associations with ICH were nonsignificant throughout the PM2.5 exposure distribution. The associations with ischemic stroke/TIA were larger among women, non-Jewish individuals, older adults, and individuals with diabetes, hypertension, and ischemic heart disease. In conclusion, short-term PM2.5 exposure is associated with a higher risk for ischemic stroke and possibly TIA, even when PM2.5 concentrations do not exceed the Israeli air quality guideline threshold. Vulnerability to the air pollution effects differed by age, sex, ethnicity, and comorbidities.