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Objectives: To assess adherence to the Dietary Approaches to Stop Hypertension (DASH) diet over a decade among community-dwelling older adults, with and without hypertension and to examine associated factors., Study Design: Cross-sectional study., Methods: Data from two cross-sectional Israel National Health and Nutrition Surveys (NHNS) for older adults, from 2005 to 2006 (NHNS1) and 2014-2015 (NHNS2) were analysed. Trained personnel conducted face-to-face interviews and collected demographic, health, and lifestyle data, along with anthropometric measurements. Adherence to the DASH diet was determined from a single 24-h dietary recall using Mellen's DASH score. Logistic regression analyses were applied to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for high DASH adherence (scores ≥4.5) versus low adherence (scores <4.5). Individual nutrient targets of the DASH diet were also assessed., Results: The dataset was comprised of 1722 participants from NHNS1 and 916 from NHNS2. Following adjustment for potential confounders, the OR for DASH adherence among participants in NHNS2 was 1.65 (95 % CI 1.34-2.04) compared to NHNS1. NHNS2 participants reported better adherence to DASH nutrient recommendations for saturated fatty acids, total fat, protein, dietary fibre, and calcium among individuals with and without hypertension. No statistically significant differences were found for cholesterol, potassium, and sodium target intakes between surveys., Conclusions: A positive trend towards healthier dietary patterns was identified among both the hypertensive and non-hypertensive older adults over a 10-year period. This underscores the importance of ongoing monitoring to appropriately address changing population needs and promote healthy dietary practices., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

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.)

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., 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: 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., Competing Interests: Disclosures None.

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., (© 2023 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Objective: To investigated the cross-sectional association between peripheral sensory nerve function and frailty among community-dwelling men, and examine whether type 2 diabetes (T2D) modifies this association., Methods: A sample of 349 men [mean age = 77.1 ± 6.4 years; 37 % with T2D] who previously (1990-1998) participated in the Bezafibrate Infarction Prevention (BIP) trial, underwent assessment of frailty and legs vibratory thresholds (LVT), a measure of peripheral sensory nerve function, as part of the BIP Neurocognitive study during 2011-2013. LVT was assessed using a graduated tuning fork and frailty was assessed using the Fried criteria. An ordered logistic regression model was used to assess the link between LVT and degrees of frailty and to test for effect modification by T2D., Results: Overall, 117 (33.5 %) of patients were non-frail, 134 (38.4 %) pre-frail, and 98 (28.1 %) frail. A significant interaction between LVT and T2D with regard to frailty was found. Among men with T2D, estimated OR (95%CI) for increasing frailty at the 1st, 2nd, and 3rd as compared to the top LVT quartile were 13.5 (3.4-54.3), 5.9 (1.5-23.5), and 4.4 (1.20-16.0), respectively. Among men without T2D, the estimated ORs for increasing frailty in patients at the 1st, 2nd, and 3rd quartiles compared to the top LVT quartile were 2.8 (1.1-7.4), 1.6 (0.6-4.1), and 2.5 (1.0-6.5), respectively., Conclusion: Frailty is significantly associated with worsening peripheral sensory nerve function, particularly among men with T2D., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Context: A correlation between myopia and insulin resistance has been suggested., Objective: We investigated the association between myopia in adolescence and type 2 diabetes (T2D) incidence in young adulthood., Methods: This population-based, retrospective, cohort study comprised 1 329 705 adolescents (579 543 women, 43.6%) aged 16 to 19 years, who were medically examined before mandatory military service during 1993 to 2012, and whose data were linked to the Israel National Diabetes Registry. Myopia was defined based on right-eye refractive data. Cox proportional models were applied, separately for women and men, to estimate hazard ratios (HRs) for T2D incidence per person-years of follow-up., Results: There was an interaction between myopia and sex with T2D (P < .001). For women, T2D incidence rates (per 100 000 person-years) were 16.6, 19.2, and 25.1 for those without myopia, and with mild-to-moderate and high myopia, respectively. These corresponded to HRs of 1.29 (95% CI, 1.14-1.45) and 1.63 (1.21-2.18) for women with mild-to-moderate and high myopia, respectively, compared to those without myopia, after adjustment for age at study entry, birth year, adolescent body mass index, cognitive performance, socioeconomic status, and immigration status. Results persisted in extensive sensitivity and subgroup analyses. When managed as a continuous variable, every 1-diopter lower spherical equivalent yielded a 6.5% higher adjusted HR for T2D incidence (P = .003). There was no significant association among men., Conclusion: For women, myopia in adolescence was associated with a significantly increased risk for incident T2D in young adulthood, in a severity-dependent manner. This finding may support the role of insulin resistance in myopia pathogenesis., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The association of long-term HbA1c variability with mortality has been previously suggested. However, the significance of HbA1c variability and trends in different age and HbA1c categories is unclear., Research Design and Methods: Data on patients with diabetes listed in the Israeli National Diabetes Registry during years 2012-2016 (observation period) were collected. Patients with >4 HbA1c measurements, type 1 diabetes, eGFR < 30mg/ml/min, persistent HbA1c < 6% or malignancy were excluded. Utilizing machine learning methods, patients were classified into clusters according to their HbA1c trend (increasing, stable, decreasing). Mortality risk during 2017-2019 was calculated in subgroups defined by age (35-54, 55-69, 70-89 years) and last HbA1c (≤7% and >7%) at end of observation period. Models were adjusted for demographic, clinical and laboratory measurements including HbA1c, standard deviation (SD) of HbA1c and HbA1c trend., Results: This historical cohort study included 293,314 patients. Increased HbA1c variability (high SD) during the observation period was an independent predictor of mortality in patients aged more than 55 years (p < 0.01). The HbA1c trend was another independent predictor of mortality. Patients with a decreasing versus stable HbA1c trend had a greater mortality risk; this association persisted in all age groups in patients with HbA1c > 7% at the end of the observation period (p = 0.02 in age 35-54; p < 0.01 in aged >55). Patients with an increasing versus stable HbA1c trend had a greater mortality risk only in the elderly group (>70), yet in both HbA1c categories (p < 0.01)., Conclusions: HbA1c variability and trend are important determinants of mortality risk and should be considered when adjusting glycaemic targets., (© 2021 John Wiley & Sons Ltd.)

Backgrounds and aims: Evidence from recent years highlighted the importance of the Mediterranean diet for brain health. We investigated the association between adherence to Mediterranean diet and change in cognitive functions two decades later in patients with cardiovascular disease (CVD). Methods: Participants were men with a history of CVD, who previously participated in the Bezafibrate Infarction Prevention (BIP) trial between 1990 and 1997, had a food diary record, and underwent cognitive evaluations 14.6 ± 1.9 years (T1) and 19.9 ± 1.0 years after baseline (T2) as part of the BIP Neurocognitive study ( n  = 200, mean age at 57.3 ± 6.3 years). Adherence to the Mediterranean diet was determined from the self-administered 4-day food diary record, with patients categorized into high, middle and poor levels of adherence if they received >5, 4-5 and <4 points, respectively. Cognitive function was assessed using the NeuroTrax computerized battery. Linear mixed models were applied. Results: Among the 200 patients, 52 (26%) had poor adherence, 98 (49%) had middle adherence and 50 (25%) had high levels of adherence to the Mediterranean diet. Those categorized to the poor adherence level had poorer cognitive function at T1 compared to the other groups. Additionally, poor vs. high level of adherence was associated with a greater decline in overall cognitive performance [ z -score = -0.23 and 95% confidence interval (CI), -0.43;-0.04; p  = 0.021] and in visual spatial functions (-0.46 95% CI, -0.86;-0.06; p  = 0.023). Conclusion: This study stresses the possible role of the Mediterranean diet in men with a high vascular burden and may set the ground for future intervention to reduce their risk for cognitive decline.

Background: Data on the rate of dementia is essential for planning and developing appropriate services at the national level., Objective: We report the prevalence and incidence of dementia, based on electronic health records available for the whole population., Methods: This national dementia dataset was established as a part of the National Program to Address Alzheimer's and Other Types of Dementia. Data from medical health records for all persons aged 45+ in Israel, for 2016, were extracted from the databases of the four health maintenance organizations. Dementia cases were identified based on either recorded dementia diagnosis, through International Classification of Diseases (ICD-9 and ICD-10) or dispensation of anti-dementia drugs. The date of first diagnosis was determined by the earliest recording., Results: A total of 65,951 persons with dementia, aged 45+, were identified from electronic health data. Based on both ICD codes and anti-dementia drugs, the prevalence rates of dementia among individuals aged 45+ and 65+ in 2016 were 2.5%and 6.4%, respectively, and the incidence rates were 0.49%and 1.3%, respectively. Based on ICD codes alone, the prevalence rates of dementia among individuals aged 45+ and 65+ in 2016 were 2.1%and 5.4%respectively, and the incidence rates were 0.36%and 0.96%respectively. The rates were higher among females compared to males and paradoxically lower in lower socioeconomic status compared to higher statuses., Conclusion: This data collection reflects the present access of dementia patients to medical care resources and provides the basis for service planning and future dementia policies.

Background: The prevalence of both asthma and early-onset diabetes is on the rise; however, the association between them remains unclear. We examined a possible association of asthma at adolescence with type 2 diabetes in young adulthood., Methods: This is a nationwide, population-based study of 1 718 541 Israeli adolescents (57% males; mean age 17.3 years; range 16-19 years), examined before compulsory military service between 1992 and 2016, with data linked to the Israeli National Diabetes Registry. Asthma diagnosis and severity were determined by a board-certified pulmonologist and based on spirometry tests., Results: Type 2 diabetes developed in 58/9090 (0.64%), 507/97 059 (0.52%), 114/23 332 (0.49%), and 7095/1 589 060 (0.44%) persons with moderate-to-severe, mild, inactive, and no history of asthma, respectively, during a mean follow-up >13 years. The respective odds ratios (ORs) were 1.33 (95% CI, 1.02-1.74), 1.17 (1.06-1.28), and 1.09 (0.9-1.31), considering those without asthma history as the reference, in a model adjusted for birth year, sex, body mass index, and other sociodemographic variables. The association persisted when the analysis accounted for coexisting morbidities, and when persons without asthma, individually matched by age, sex, birth year, and body mass index were the reference. Both mild and moderate-to-severe asthma were associated with type 2 diabetes before age 35 years: ORs 1.18 (1.05-1.34) and 1.44 (1.05-2.00), respectively. The strength of the association was accentuated over time. The effect was unchanged when adjusted for oral and inhaled glucocorticoid use., Conclusion: Adolescents with active asthma have higher risk to develop type 2 diabetes. This seems related to disease severity, independent of adolescent obesity status, apparent before age 35 years, and more pronounced in recent years., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Cognitive function among apparently healthy adolescents has been associated with cardiovascular morbidity and mortality. We examined the relationship between global and subdomain cognitive scores in adolescence and early-onset type 2 diabetes (T2D) in men and women., Methods: A nationwide, population-based study of 971,677 Israeli born adolescents (56% men; mean age 17.4 years) who were medically examined and their cognitive performance was assessed before compulsory military service during 1992-2010. Data included global and subdomain cognitive Z -scores (problem-solving, verbal abstraction and categorization, verbal comprehension, and mathematical abilities). Data were linked to the Israeli National Diabetes Registry. The relations between global and subdomain scores and incident T2D was determined using Cox proportional hazard models and logistic regression models. Analyses were conducted separately for men and women., Findings: During 16,095,122 person-years, 3,570 individuals developed T2D. After adjustment, those in the low compared to the high quintile of global cognitive Z -score had the highest risk for T2D; HR 2.46, (95% CI 2.10-2.88) for men and 2.33 (95% CI 1.88-2.89) for women. A one-unit lower global cognitive Z -score was associated with 1.41 (95% CI 1.34-1.48) and 1.46 (95% CI 1.36-1.56) increased risks for men and women, respectively. The relationship was noted for the cognitive subdomains scores as well as for the global cognitive score, with no heterogeneity across cognitive subdomains., Interpretation: This large nationally representative cohort suggests relationship between global, as well as subdomain cognitive scores in late adolescence, and incident early onset T2D in both sexes, which was independent of socioeconomic status., Competing Interests: All authors have completed the ICMJE uniform disclosure form and declare: no support from any organization for the submitted article. Dr Gerstein reports grants from Sanofi, personal fees from Sanofi, grants from Eli Lilly , personal fees from Eli Lilly, grants from Astra Zeneca, grants from Boehringer Ingelheim, personal fees from Boehringer Ingelheim, personal fees from Abbott, grants from Novo Nordisk, personal fees from Novo Nordisk, grants from Merck, personal fees from Merck, grants from Abbott, personal fees from Kowa Research Institute , personal fees from Pfizer, personal fees from Zuellig, personal fees from DKSH, personal fees from Covance, personal fees from Roche, outside the submitted work. Dr. Raz reports other from AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme, Novo Nordisk, Inc, Sanofi, other from AstraZeneca, Insuline Medical, Medial EarlySign Ltd, CamerEyes Ltd, Exscopia, Orgenesis Ltd, BOL, Glucome Ltd, DarioHealth, Diabot, Concenter BioPharma, other from AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme, Novo Nordisk, Inc., Sanofi, other from Glucome Ltd, Orgenesis Ltd, DarioHealth, CamerEyes Ltd, Diabot, BOL, outside the submitted work. All the other authors have no conflicts to declare., (© 2021 The Author(s).)

Context: Thyroid hormones play a key role in systemic metabolism, yet the relationship between thyroid dysfunction and risk for type 2 diabetes is unclear., Objective: To assess type 2 diabetes risk in adulthood among adolescents with thyroid disorders., Design and Setting: A nationwide, population-based study of Israeli adolescents who were examined before military recruitment during 1988 to 2007 and were followed until December 31, 2016., Participants: 1 382 560 adolescents (mean age 17.3 years)., Interventions: The diagnosis of thyroid disorders was based on recent thyroid function tests. Data were linked to the Israeli National Diabetes Registry. Cox proportional hazard models were applied., Main Outcome Measures: Type 2 diabetes incidence., Results: During a mean follow-up of 18.5 years, 1.12% (69 of 6,152) of adolescents with thyroid disorders were diagnosed with type 2 diabetes vs 0.77% of adolescents without thyroid disorders. The hazard ratio (HR) for type 2 diabetes was 2.3 (95% CI, 1.8-2.9) among those with thyroid disorders, after adjustment for sex, birth-year, body mass index, and sociodemographic confounders. The increased diabetes risk was observed in both men and women, with the presence or absence of obesity, and in the absence of other health conditions and was associated with different types of thyroid disorders. It was also similar when the outcome was defined as type 2 diabetes diagnosed at or before the age of 30 years (HR 2.3, 95% CI, 1.5-3.5)., Conclusions: Thyroid disorders diagnosed in adolescence are a risk factor for early-onset type 2 diabetes in both men and women., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Falls and fear of falling are a major problem for older people and a leading cause of functional decline and institutionalization. There is limited data on the prevalence of falls in a 12-month period among Israeli older adults. Our main objective was to evaluate the prevalence of falls among Israeli community-dwelling older people aged ≥65 years and to identify factors associated with falls and fear of falling., Methods: A national cross-sectional interview survey was conducted between February 2018 and April 2019 by the Israeli Center for Disease Control. The prevalence of falls was assessed by asking participants about falling within the 12 months prior to the survey. Fear of falling was assessed by asking participants about the fear of future falls. Multivariate analysis was used to identify factors associated with falls and with fear of falling., Results: From 5281 households that were eligible for inclusion in this study, 3242 participants (61.4%) completed the survey. Falling at least once in the past year was reported by 23.8% of the respondents and fear of falling by 48.2%. The majority of the participants (91.1%) reported that they had never received any instruction about fall prevention from their medical care provider. In the multivariate analysis, falls and fear of falling were each a risk factor for the other; and were also significantly associated with female gender, major functional difficulties, the use of walking aids, cardiac disease, diabetes mellitus and psychotropic medications., Conclusion: The prevalence of falls and fear of falling among Israeli community-dwelling older people is comparable to the rates published in other countries. Efforts should be made to increase awareness about falls and their health consequences among older people. The development of specific interventions to target those at higher risk for falls and fear of falling is strongly recommended.

Purpose: To investigate the association between stuttering in adolescence and incident type 2 diabetes in young adulthood., Methods: This nationwide population-based study included 2 193 855 adolescents of age 16 to 20 years who were assessed for military service between 1980 and 2013. Diagnoses of stuttering in adolescence were confirmed by a speech-language pathologist. Diabetes status for each individual as of December 31, 2016, was determined by linkage to the Israeli National Diabetes Registry. Relationships were analyzed using regression models adjusted for socioeconomic variables, cognitive performance, coexisting morbidities, and adolescent body mass index., Results: Analysis was stratified by sex (Pinteraction = 0.035). Of the 4443 (0.4%) adolescent men with stuttering, 162 (3.7%) developed type 2 diabetes, compared with 25 678 (2.1%) men without stuttering (adjusted odds ratio [OR] 1.3; 95% CI, 1.1-1.6). This relationship persisted when unaffected brothers of men with stuttering were used as the reference group (adjusted OR = 1.5; 95% CI, 1.01-2.2), or when the analysis included only adolescents with unimpaired health at baseline (adjusted OR = 1.4; 95% CI, 1.1-1.7). The association was stronger in later birth cohorts, with an adjusted OR of 2.4 (1.4-4.1) for cases of type 2 diabetes before age 40. Of the 503 (0.1%) adolescent women with stuttering 7 (1.4%) developed type 2 diabetes, compared with 10 139 (1.1%) women without stuttering (OR = 2.03; 95% CI, 0.48-2.20)., Conclusions: Adolescent stuttering is associated with an increased risk for early-onset type 2 diabetes among men., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Holocaust victims experienced extreme physical and mental stress that could lead to prolonged deficits in psychological and physiological well-being. We aimed to examine whether exposure to Holocaust conditions is associated with cognitive function and decline in a sample of old male adults with coronary heart disease (CHD)., Methods: The sample included 346 individuals with CHD who participated in a clinical trial in 1990-1997 (mean age 56.7 ± 6.5 y). During 2004-2008 (mean age 71.8 ± 6.5 y) and 2011-2013 (mean age 77.1 ± 6.4 y) participants underwent computerized cognitive assessments. Exposure to Holocaust conditions was based on self-report at the second assessment. Linear regression and mixed-effect models were conducted to evaluate the associations between Holocaust survivorship and subsequent cognitive performance and rate of cognitive decline., Results: Forty-Three participants (12%) survived concentration camps/ghettos, 69 (20%) were Holocaust survivors who escaped concentration camps/ghettos, and 234 (68%) were not Holocaust survivors. After adjustment for potential confounders, concentration camp/ghetto survivors had poorer global cognitive performance and poorer attention (β = -3.90; 95%CI: 7.11;-0.68 and β = -4.11; 95%CI: 7.83;-0.38, respectively) compared to individuals who were not exposed to Holocaust conditions. Additionally, participants who reported being at concentration camps/ghettoes had increased cognitive decline in global performance and executive function (β = -0.19; 95%CI: 0.37;-0.008 and β = -0.29; 95%CI: 0.53;-0.06, respectively) compared to participants who were not Holocaust survivors. Lastly, those who were Holocaust survivors but not in concentration camps/ghettos had greater decline in attention (β = -0.11; 95%CI: 0.21;-0.01)., Discussion: Exposure to Holocaust conditions in early-life may be linked with poorer cognitive function and greater cognitive decline decades later in old-adults with CHD., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Context: The long-term risk of type 2 diabetes in adolescents with nonalcoholic fatty liver disease (NAFLD) is unclear., Objective: To assess type 2 diabetes risk among adolescents with NAFLD., Design and Setting: A nationwide, population-based study of Israeli adolescents who were examined before military service during 1997-2011 and were followed until December 31, 2016., Participants: A total of 1 025 796 normoglycemic adolescents were included., Interventions: Biopsy or radiographic tests were prerequisite for NAFLD diagnosis. Data were linked to the Israeli National Diabetes Registry., Main Outcome Measures: Type 2 diabetes incidence., Results: During a mean follow-up of 13.3 years, 12 of 633 adolescents with NAFLD (1.9%; all with high body mass index [BMI] at baseline) were diagnosed with type 2 diabetes compared with 2917 (0.3%) adolescents without NAFLD. The hazard ratio (HR) for type 2 diabetes was 2.59 (95% confidence interval [CI], 1.47-4.58) for the NAFLD vs. the non-NAFLD group after adjustment for BMI and sociodemographic confounders. The elevated risk persisted in several sensitivity analyses. These included an analysis of persons without other metabolic comorbidities (adjusted HR, 2.75 [95% CI, 1.48-5.14]) and of persons with high BMI; and an analysis whose outcome was type 2 diabetes by age 30 years (adjusted HR, 2.14 [95% CI, 1.02-4.52]). The results remained significant when a sex-, birth year-, and BMI-matched control group was the reference (adjusted HR, 2.98 [95% CI, 1.54-5.74])., Conclusions: Among normoglycemic adolescents, NAFLD was associated with an increased adjusted risk for type 2 diabetes, which may be apparent before age 30 years., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.

Background: Communication between health authorities and healthcare providers is an essential element of the response to public health emergencies. Although call centers can facilitate such communication, no published reports describing their outcomes exist. In advance of the expected COVID-19 outbreak in Israel, the Israel Center for Disease Control established a call center dedicated to queries from healthcare professionals., Methods: The call center operated from February 5, 2020 (week 6) to May 14, 2020 (week 20). Data on calls received, including date and time, caller characteristics, questions and responses were recorded in a database designed for this purpose. The volume, sources and content of queries were analyzed., Results: In 15 weeks of operation, the call center responded to 6623 calls. The daily number of calls ranged from 1 to 371 (mean 79.8, median 40), peaking on week 12, 2 weeks prior to a peak in new COVID-19 cases. Callers were predominantly physicians (62.4%), nurses (18.7%) and administrators (4.4%). Most worked in primary care clinics (74.2%) or hospitals (8.7%). Among physicians, 42.3% were family physicians or internists, and 10.0% were pediatricians. The issues most commonly addressed were home quarantine (21.6%), criteria for suspected cases (20.6%), and SARS-CoV2 testing (14.1%). Twenty-five percent of questions involved requests for clarifications of MOH guidelines regarding travel restrictions, clinic management, triage of symptomatic patients, routine medical and dental care, recommended precautions for health care workers with preexisting medical conditions, and other matters. A total of 119 queries were not resolved on the basis of existing guidelines and were referred to MOH headquarters., Conclusions: This is the first report of a call center established to serve the needs of healthcare providers seeking guidance on COVID-19 management, and to facilitate communication of providers' concerns to the central health authority. Our work indicates that a central call center for healthcare providers can facilitate the development, implementation and amendment of guidelines and should be an integral element of the early response to public health emergencies. Real-time analysis of the call data may reveal important trends requiring prompt attention.

Objective: We investigated the association between severity of angina pectoris (AP) and subsequent late-life frailty among men with cardiovascular disease (CVD)., Method: A subset of 351 men (mean age at baseline 56.7 ± 6.5 years) who previously participated in the Bezafibrate Infarction Prevention, BIP trial (1990-1997) underwent a neurovascular evaluation as part of the BIP Neurocognitive study 15.0 ± 3.0 years after baseline (T1) and a frailty evaluation according to Fried 19.9 ± 1.0 years after baseline (T2). Severity of AP was assessed at baseline of the BIP trial using the Canadian Cardiovascular Society angina classification. We assessed the odds of being in the advanced rank of frailty status (robust, pre-frail, and frail) using ordered logistic regression., Results: Among 351 participants, 134 (38.2%) were classified as pre-frail and 100 (28.5%) as frail. Frailty was found among 42% participants in the AP class ≥2 and among 26% participants in the AP class <2. Adjusting for demographic, health-related and cognitive variables, odds ratio (OR), and 95% confidence interval (95% CI) for advanced rank of frailty was 2.68 (95% CI: 1.29-5.59) comparing AP class ≥2 to AP class <2., Discussion: Among men with CVD, severity of AP should be taken into risk consideration due to its strong association with late-life frailty, particularly among inactive participants and participants with cerebral microvascular damage.

Background: Autonomic imbalance is linked with multiple health conditions, yet its associations with frailty were rarely studied. We assessed the relationship of resting heart rate (RHR) and visit-to-visit heart rate variability (HRV) with future frailty among elderly men with coronary heart disease (CHD)., Methods: Three-hundred-six community-dwelling men with CHD who participated in the Bezafibrate Infarction Prevention (BIP) trial (1990-1998; mean age 56.6 ± 6.5 years) underwent assessment of physical frailty in 2011-2013 (mean age 77.0 ± 6.4 years). Mean RHR and visit-to-visit HRV were calculated from electrocardiogram as indicators of autonomic imbalance. Nominal logistic and linear regression models were used to assess the relationships of RHR and HRV with frailty status and its components (i.e. gait speed, grip strength, weight loss, exhaustion and activity), respectively. Adjustments were made for various demographic, clinical and metabolic covariates., Results: Of the 306 men, 81 (26%) were frail and 117 (38%) were prefrail. After controlling for potential confounders, RHR, but not visit-to-visit HRV, was associated with higher odds of being prefrail [OR = 1.44 (95%CI 1.15, 1.79)] and frail [OR = 1.35 (95%CI 1.03, 1.77)]. Each 5-bpm increase in RHR was associated with weaker grip (β= -1.12 ± 0.32 kg; p -value < .001) and slower gait speed (β = 0.19 ± 0.08s/m; p -value = .022)., Conclusions: Midlife RHR may be associated with late-life frailty in men with CHD.

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 10 5 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.

Objective: Type 2 diabetes (T2D) is increasingly diagnosed at younger ages. We investigated the association of adolescent obesity with incident T2D at early adulthood., Research Design and Methods: A nationwide, population-based study evaluated 1,462,362 adolescents (59% men, mean age 17.4 years) during 1996-2016. Data were linked to the Israeli National Diabetes Registry. Weight and height were measured at study entry. Cox proportional models were applied., Results: During 15,810,751 person-years, 2,177 people (69% men) developed T2D (mean age at diagnosis 27 years). There was an interaction among BMI, sex, and incident T2D ( P interaction = 0.023). In a model adjusted for sociodemographic variables, the hazard ratios for diabetes diagnosis were 1.7 (95% CI 1.4-2.0), 2.8 (2.3-3.5), 5.8 (4.9-6.9), 13.4 (11.5-15.7), and 25.8 (21.0-31.6) among men in the 50th-74th percentile, 75th-84th percentile, overweight, mild obesity, and severe obesity groups, respectively, and 2.2 (1.6-2.9), 3.4 (2.5-4.6), 10.6 (8.3-13.6), 21.1 (16.0-27.8), and 44.7 (32.4-61.5), respectively, in women. An inverse graded relationship was observed between baseline BMI and mean age of T2D diagnosis: 27.8 and 25.9 years among men and women with severe obesity, respectively, and 29.5 and 28.5 years among low-normal BMI (5th-49th percentile; reference), respectively. The projected fractions of adult-onset T2D that were attributed to high BMI (≥85th percentile) at adolescence were 56.9% (53.8-59.9%) and 61.1% (56.8-65.2%) in men and women, respectively., Conclusions: Severe obesity significantly increases the risk for incidence of T2D in early adulthood in both sexes. The rise in adolescent severe obesity is likely to increase diabetes incidence in young adults in coming decades., (© 2020 by the American Diabetes Association.)

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.

Objective: The relationship between acute pancreatitis and incident diabetes is unclear. We assessed whether a resolved single event of acute pancreatitis in childhood was associated with incident diabetes in adulthood., Research Design and Methods: A nationwide, population-based study of 1,802,110 Israeli adolescents (mean age 17.4 years [range 16-20]) who were examined before compulsory military service between 1979 and 2008 and whose data were linked to the Israeli National Diabetes Registry (INDR). Resolved pancreatitis was defined as a history of a single event of acute pancreatitis with normal pancreatic function at enrollment. Logistic regression analysis was applied., Results: Incident diabetes developed in 4.6% of subjects with resolved pancreatitis (13 of 281; none of these cases were identified as type 1 diabetes) and 2.5% among the unexposed group (44,463 of 1,801,716). Resolved acute pancreatitis was associated with incident diabetes with an odds ratio (OR) of 2.23 (95% CI 1.25-3.98) with adjustment for age, sex, and birth year. Findings persisted after further adjustments for baseline BMI and sociodemographic confounders (OR 2.10 [95% CI 1.15-3.84]). Childhood pancreatitis was associated with a diagnosis of diabetes at a younger age, with 92% of diabetes case subjects diagnosed before 40 years of age compared with 47% in the unexposed group ( P = 0.002). The association accentuated when the study sample was limited to individuals of unimpaired health or normal BMI at baseline., Conclusions: A history of acute pancreatitis in childhood with normal pancreatic function in late adolescence is a risk factor for incident type 2 diabetes, especially at young adulthood., (© 2019 by the American Diabetes Association.)

Purpose: To estimate the 3-year incidence of blindness among diabetes patients aged ≥18 years; to compare blindness incidence rates of persons with and without diabetes; and to investigate risk factors associated with diabetic retinopathy (DR), age-related macular degeneration (ARMD), glaucoma, and cataract-related blindness., Design: Cohort study., Methods: The Israeli National Diabetes Registry for 2012 was cross-linked with the database of blindness certifications obtained from the National Registry of the Blind. Blindness was defined as the receipt of an official certificate of blindness (a visual acuity of 3/60 or worse, or a visual field loss of <20 degrees in the better eye.) Incidence rates of blindness, overall and by main cause of blindness, were calculated for the years 2013-2015. Standardized morbidity ratios (SMRs) for 2013 were calculated, using the nondiabetic population as a reference. A multinomial logistic model was used to identify covariates associated with the incidence of blindness by main cause of blindness., Results: The 3-year incidence rates were 31.0 and 8.4 per 10 000 for overall and DR-related blindness, respectively. The SMR for overall blindness in people with diabetes was significantly higher than in the general nondiabetic population (1.39; 95% confidence interval: 1.27-1.53); however, the SMRs for ARMD, glaucoma, and cataract were not statistically significant. Poor metabolic control, insulin treatment, long diabetes duration, and chronic kidney disease were associated with DR-related blindness. Low socioeconomic status (SES) was associated with both cataract and DR-related blindness., Conclusions: Optimum metabolic control of diabetes is important for prevention of DR-related blindness. SES-related disparities in blindness risk should be explored and reduced by directing efforts to provide appropriate treatment for all diabetic patients in order to prevent unnecessary blindness., (Copyright © 2018. Published by Elsevier Inc.)

Background: Lipid levels are associated with an increased risk of cardiovascular disease., Objective: We investigated the association between plasma lipids, apolipoproteins levels, apolipoprotein B/low-density lipoprotein cholesterol (Apo-B/LDL-C), and Apo-B/Apo-A ratios and rate of cognitive decline two decades later in men with coronary heart disease (CHD)., Methods: A subset of 337 men (mean age at baseline 56.6±6.4 years) who previously participated in the Bezafibrate Infarction Prevention (BIP) trial (1990-1997) underwent cognitive evaluations 15±3 years (T1) and 19.9±1 years after baseline (T2) as part of the BIP Neurocognitive study. Lipid and apolipoprotein fractions were measured at baseline. Cognitive function for memory, executive function, visual spatial, attention domains, and composite score were assessed using the NeuroTrax Computerized Battery at T1 and T2 evaluations. Linear mixed models were used to assess change in cognitive function between the two cognitive evaluations., Results: Controlling for confounders, the decline in composite cognitive score (β= -0.161±0.06; p = 0.013) as well as in memory (β= -0.269±0.10; p = 0.009) and visual spatial function (β= -0.304±0.12; p = 0.010) was greater among patients in the upper (≥105 mg/dL) Apo-B tertile as compared to counterparts with < 105 mg/dL. The decline in the composite cognitive score (β= -0.124±0.06; p = 0.043) was also greater among patients in the estimated LDL-C≥160 mg/dL group compared to counterparts with LDL-C<160 mg/dL. Upper tertile of Apo-B/LDL-C ratio (≥0.75) compared to the lower tertiles was significantly associated with change in memory score (β= -0.210±0.10; p = 0.041)., Conclusion: Our findings suggest that the plasma concentrations of Apo-B, LDL-C, and Apo-B/LDL-C ratio are potential predictors of accelerated late-life cognitive decline among men with CHD.

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.

Aims: To assess the relationship between physical frailty and cognitive function among elderly men with a history of cardiovascular disease (CVD)., Methods: Three-hundred-twenty-four community-dwelling men with chronic CVD (mean age 77.2 ± 6.4 years) who previously participated in the Bezafibrate Infarction Prevention (BIP) trial (1990-1998) underwent assessment of frailty and cognitive function between 2011 and 2013. Physical frailty was assessed using the Fried phenotypic model, and cognitive performance overall and in memory, executive function, visuospatial and attention domains was evaluated using a validated set of computerized cognitive tests. Linear regression models were used to assess the cross-sectional relationship of frailty status and its components (gait speed, grip strength, weight loss, exhaustion and activity) with cognitive function overall and in specific domains, adjusting for age, education, smoking status, physical activity, history of myocardial infarction, hypertension, diabetes and dyslipidemia, systolic blood pressure, BMI and depression., Results: Of the 324 men, 91 (28%) were frail and 121 (37%) were pre-frail. After controlling for potential confounders, severity of frailty was strongly associated with global cognitive function (β = -8.0, 95%CI = -11.9,-4.1 and β = -3.3, 95%CI = -6.0,-0.5 comparing frail and pre-frail to non-frail, respectively), with the most profound associations observed in executive function and attention. Gait speed was associated with overall cognitive performance and with all cognitive domains assessed in this study, and activity with none., Conclusion: Cognitive function is poor among frail and pre-frail men with CVD, particularly in non-memory domains. Future research is warranted to address mechanisms and to assess the efficacy of interventions to improve physical and cognitive health., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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.)

Aim: We investigated the possible inverse association between tall stature and subsequent late-life frailty., Methods: A subset of surviving men with coronary heart disease (n = 1232; mean age at baseline 57.0 ± 6.0 years), who previously participated in the Bezafibrate Infarction Prevention clinical trial (1990-1997) were reassessed during 2004-2008 (T1; n = 558) and 2011-2013 (T2; n = 351) at the mean ages of 72.6 ± 6.4 years and 77.2 ± 6.4 years, respectively. Frailty status was measured at T2 according to the physical phenotype developed by Fried, and was categorized into non-frail, prefrail and frail. We estimated the odds ratios of increasing frailty by tertiles of height at baseline., Results: Among 351 patients, 117 (33.3%) were classified as non-frail, 134 (38.2%) as prefrail and 100 (28.5%) as frail. Frailty was found among 21% of participants at the highest tertile, 33% at the middle tertile and 46% at the lowest tertile for height (P for trend = 0.002). Adjusting for age, weight, place of birth, education, blood pressure, New York Heart Association classification functional class and comorbidity score, the estimated OR for increasing frailty for participants in the highest tertile was 0.32 (95% CI 0.17-0.59) and for those at the middle tertile 0.46 (95% CI 0.27-0.79), as compared with the lowest tertile. An increment of 1 SD of height was associated with a 38% (95% CI 18-53%) decrease in frailty odds., Conclusion: Among men with coronary heart disease, tall stature was associated with lower adjusted odds of late-life frailty. Geriatr Gerontol Int 2017; 17: 1270-1277., (© 2016 Japan Geriatrics Society.)

Background: Nationwide data on the clinical profile and outcomes of ischemic stroke in younger adults are still scarce. Our aim was to analyze clinical characteristics and outcomes of young patients with first-ever ischemic stroke compared to older patients., Methods: The National Acute Stroke ISraeli registry is a nationwide prospective hospital-based study performed triennially. Younger adults, aged 50 years and younger, were compared with patients, aged 51-84 years regarding risk factors, clinical presentation, stroke severity, stroke etiology, and outcomes. A logistic model for stroke outcome was fitted for each age group., Results: 336 first-ever ischemic strokes were identified among patients aged 50 years and younger and 3,243 among patients 51-84 years. Younger adults had lower rates of traditional vascular risk factors, but 82.7% had at least one of these risk factors. Younger adults were more likely to be male (62.8%), current smokers (47.3%), and to have a family history of stroke (7.4%). They tended to have less common stroke presentation such as sensory disturbances or headache and were more likely to arrive at the hospital independently by car. The majority of young adults (70%) had a favorable outcome (modified Ranking Scale; mRS ≤ 1) at discharge, but 11.7% had poor outcome (mRS > 3) and 18.2% had an in-hospital complication. According to a multivariable regression model, in young adults, only baseline stroke severity (National Institute of Health Stroke Scale > 5) was associated with poor outcome at discharge ( p  < 0.001), whereas in older adults, stroke severity ( p  < 0.001), female gender (OR = 1.35, CI 95% 1.03-1.76), older age (OR = 1.08, CI 95% 1.01-1.16), atrial fibrillation (OR = 1.62, CI 95% 1.16-2.26), and anterior circulation territory (OR = 2.10, CI 95% 1.50-2.94) were all significantly associated with poor outcome., Conclusion: Our findings, in this nationwide registry, demonstrate the relatively high rate of smoking and family history of stroke, and the lower rate of hospital arrival by ambulance among young adults. This calls for increasing awareness to the possibility of stroke among young adults and for better prevention, especially smoking cessation.

Aims: To explore the association of C-reactive protein (CRP) plasma levels with subsequent cognitive performance and decline among elderly individuals with pre-existing cardiovascular disease (CVD), and to assess the role of cerebrovascular indices in this relationship., Methods: CRP levels were measured in a subgroup of individuals with chronic CVD, who previously participated in a secondary prevention trial. Cognitive performance was evaluated 14.7±1.9 and 19.9±1.0years after entry to the trial. A validated set of computerized cognitive tests was used (Neurotrax Computerized Cognitive Battery) to assess performance globally and in memory, executive function, visuospatial and attention domains. Linear regression and mixed models were used to assess the relationship of CRP plasma levels with cognitive scores and decline, respectively. In addition, we tested whether cerebrovascular reactivity, carotid intima media thickness and presence of carotid plaques modify these associations., Results: Among 536 participants (mean age at the first cognitive evaluation 72.6±6.4years; 95% males), CRP at the top tertile vs. the rest was associated with subsequent poorer performance overall (ß=-2.2±1.0; p=0.031) and on tests of executive function and attention (ß=-2.3±1.1; p=0.043 and ß=-2.0±1.4; p=0.047, respectively). Moreover, CRP levels were positively related to a greater decline in executive functions (ß=-2.4±1.1; p=0.03). These associations were independent of potential confounders and were not modified by cerebrovascular indices., Conclusion: Our findings suggest that systemic chronic inflammation, potentially associated with underlying atherosclerosis, is related to cognitive impairment and decline two decades later, in elderly individuals with pre-existing CVD., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: The role of insulin resistance (IR) in the pathogenesis of cognitive performance is not yet clear., Objective: To examine the associations between IR and cognitive performance and change in cognitive functions two decades later in individuals with cardiovascular disease with and without diabetes., Methods: A subset of 489 surviving patients (mean age at baseline 57.7±6.5 y) with coronary heart disease who previously participated in the secondary prevention Bezafibrate Infarction Prevention (BIP trial; 1990-1997), were included in the current neurocognitive study. Biochemical parameters including IR (using the homeostasis model of assessment; HOMA-IR) were measured at baseline. During 2004-2008, computerized cognitive assessment and atherosclerosis parameters were measured (T1; n = 558; mean age 72.6±6.4 years). A second cognitive assessment was performed during 2011-2013 (T2; n = 351; mean age 77.2±6.4 years). Cognitive function, overall and in specific domains, was assessed. We used linear regression models and linear mixed models to evaluate the differences in cognitive performance and decline, respectively., Results: Controlling for potential confounders, IR (top HOMA-IR quartile versus others) was associated with subsequent poorer cognitive performance overall (β= -4.45±Standard Error (SE) 1.54; p = 0.004) and on tests of memory and executive function among non-diabetic patients (β= -7.16±2.38; p = 0.003 and β= -3.33±1.84; p = 0.073, respectively). Moreover, among non-diabetic patients, IR was related to a greater decline overall (β= -0.17±0.06; p = 0.008), and in memory (β= -0.22±0.10; p = 0.024) and executive function (β= -0.19±0.08; p = 0.012). The observed associations did not differ after excluding subjects with prevalent stroke or dementia., Conclusion: IR is related to subsequent poorer cognitive performance and greater cognitive decline among patients with cardiovascular disease with and without diabetes.

Introduction: Studies have suggested that statins may inhibit tumor cell growth and possibly prevent carcinogenesis. The objective of this study was to investigate the association between persistent statin use and the risk of primary cancer in adults., Methods: This retrospective study was conducted by using the computerized data sets of a large health maintenance organization (HMO) in Israel. The study population was 202,648 enrollees aged 21 or older who purchased at least 1 pack of statin medication from 1998 to 2006. The follow-up period was from the date of first statin dispensation (index date) to the date of first cancer diagnosis, death, leaving the HMO, or September 1, 2007, whichever occurred first. Persistence was measured by calculating the mean proportion of follow-up days covered (PDC) with statins by dividing the quantity of statin dispensed by the total follow-up time., Results: During the study period, 8,662 incident cancers were reported. In a multivariable model, the highest cancer risk was calculated among nonpersistent statin users. A strong negative association between persistence with statin therapy and cancer risk was calculated for hematopoietic malignancies, where patients covered with statins in 86% or more of the follow-up time had a 31% (95% confidence interval, 0.55-0.88) lower risk than patients in the lowest persistence level (≤ 12%)., Conclusion: Our study demonstrated that persistent use of statins is associated with a lower overall cancer risk and particularly the risk of incident hematopoietic malignancies. In light of widespread statin consumption and increases in cancer incidence, the association between statins and cancer incidence may be relevant for cancer prevention.