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Objective: To assess risk factors and rates of suicide and other external cause deaths, among suicide attempters compared to the total population, stratified by psychiatric hospitalization discharge and mental diagnosis., Methods: A national registry-based analysis of suicide and external cause mortality was performed among suicide attempters between 2006 and 2020 in Israel in the National Hospital ED database. Data was stratified by psychiatric hospitalization status by linking to the national psychiatric case registry. Age adjusted mortality rates were calculated.A multivariate cox regression model assessed the relative risk of demographic factors and psychiatric diagnosis and hospitalization on outcomes., Results: Among 57,579 first suicide attempters, of whom 16,874 had a psychiatric hospitalization, there were 853 suicides (1.5%) and 473 deaths from other external causes (0.8%), 485 suicides (2.9%) and 199 external cause deaths (1.2%) in the psychiatric group. Suicide risk was highest in the year after the attempt, but continued throughout the study, particularly in the psychiatric hospitalized group. Suicide rates within one year of first suicide attempt were 137 (95% CI 122-152) times higher than the total population, 190 (155-233) times in females and 128 (112-145) times in males, 178 (153-207), 243 (181-325) and 158 (132-190) times higher, respectively, in those with a psychiatric hospitalization., Conclusions: We found a greatly increased risk for suicide and significant increase for other external causes of death amongst a cohort of suicide attempters, compared to the total population, particularly those with a history of psychiatric hospitalization.

Background: In the last twenty years, there was a documented increase in prescription opioid procurement in Israel. However, there is still little evidence of the association between opioid procurement rates, health service utilisation in secondary care, and enrollment rates to substance use disorder treatment programmes. In this study, we show trends in the reports of opioid-related hospitalisations, emergency department visits, enrollment to community-based outpatient treatment for Prescription Opioid Use Disorder and opioid-related mortality rates. Additionally, we examine potential correlations between these health service utilisation rates and prescription opioid procurement rates at the population level, with a focus on transdermal fentanyl., Methods: A longitudinal study at the population level. We used seven-year data on indicators of opioid-related morbidity, prescription opioid procurement data for 2015-2021, and six-year opioid-related mortality data for 2015-2020. We measure the correlation between procurement rates of prescription opioids in Oral Morphine Equivalent per capita, and aggregated rates obtained from hospital administrative data for hospitalisations, emergency department visits, and patient enrolment in specialised prescription opioid use disorder outpatient treatment in the community setting., Results: Between 2015 and 2021, procurement rates in primary care per capita for all prescription opioids increased by 85%, while rates of transdermal fentanyl procurement increased by 162%. We found a significant positive correlation at the population level, between annual opioid procurement rates, and rates per population of opioid-related visits to emergency departments (r = 0.96, p value < 0.01, [CI 0.74-0.99]), as well as a positive correlation with the rates per population of patient enrolment in specialised prescription opioid use disorder outpatient treatment (r = 0.93, p value = 0.02, [CI 0.58-0.99]). Opioid-related mortality peaked in 2019 at 0.31 deaths per 100,000 but decreased to 0.20 deaths per 100,000 in 2020., Conclusion: Data shows that all-opioid and transdermal fentanyl procurement has increased yearly between 2015 and 2021. This increase is positively correlated with a growing demand for community-based Prescription Opioid Use Disorder outpatient treatment. Efforts to reduce opioid-related morbidity may require effective approaches toward appropriate prescribing, monitoring, and further increasing access to prescription opioid outpatient treatment., (© 2023. The Author(s).)

Previous studies on psychiatric patients infected with COVID-19 have reported a more severe course of disease and higher rates of mortality compared with the general population. This cohort study linked Israeli national databases including all individuals ever hospitalized for a psychiatric disorder (cases), and COVID-19 testing, infection, hospitalization, mortality, and vaccinations, between March 1 st 2020 and March 31 st 2021. Cases were 125,273 individuals aged 18 and above ever hospitalized in a psychiatric facility (ICD-10 F10-F69 or F90-F99), compared to the total population, n = 6,143,802. Compared with the total population, cases were less likely to be tested for COVID-19, 51.2% (95% CI: 50.8-51.7) vs 62.3% (95% CI 62.2-62.4) and had lower rates of confirmed COVID infection, 5.9% (95% CI: 5.8-6.1) vs 8.9% (95% CI: 8.9-8.9). Among those infected, risks for COVID-19 hospitalization, COVID-19 attributed mortality and all-cause mortality were higher for cases than the total population, adjusted odds ratios were 2.10; (95% CI: 1.96-2.25), 1.76; (95% CI: 1.54-2.01) and 2.02; (95% CI: 1.80-2.28), respectively. These risks were even higher for cases with non-affective psychotic disorders and bipolar disorder. Age adjusted rates of vaccination were lower in cases, 60.4% (95% CI: 59.9-60.8) vs 74.9% (95% CI: 74.8-75.0) in the total population, and particularly low for cases with non-affective psychotic disorders, 56.9% (95% CI: 56.3-57.6). This study highlights the need to increase testing for COVID-19 in individuals ever hospitalized for a psychiatric disorder, closely monitor those found positive, and to reach out to encourage vaccination., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Previous findings regarding European Holocaust survivors' suicide risk are conflicting. North African survivors' suicide risk was not previously studied. In this study, we aimed to determine suicide risk among European and North African Holocaust survivors. The study was based on the Israeli population census from 1972, followed until 2015 for suicide. European survivors were grouped into survivors of severe Nazi persecution (HS) and early HS. North African survivors were grouped into those from Algeria, Libya and Tunisia who were likely to have suffered more severe persecution (group 1) and those from Morocco who apparently suffered less persecution (group 2). Comparison groups were chosen according to similar ethnic origins who were not under Nazi control. Age standardized suicide rates, Standard Mortality Ratios (SMR) were calculated. Cox regression analysis was used to assess suicide risk. The age adjusted suicide rates (per 100,000) among Europeans were: HS 17.8 (95%CI 16.9-18.6), early HS 28.6 (95%CI 24.9-32.2), comparison group 20.3 (95%CI 18.5-22.1). Among North Africans: group 1, 6.9 (95%CI 5.6-8.2), group 2, 4.8 (95%CI 4.0-5.5), comparison group, 8.5 (95% CI 6.4-11.0). The SMRs with European comparisons were 0.88 (95%CI 0.84-0.92) for HS and 1.41 (95%CI 1.20-1.65) for early HS. SMRs with North African comparisons were 0.81 (95%CI 0.67-0.97) for group 1 and 0.57 (95%CI 0.48-0.66) for group 2. Cox regression models showed significantly higher suicide risk for European early HS vs comparisons (Hazard Ratio (HR) = 1.31, 95% CI 1.12-1.52), and lower risk for HS (0.89, 95%CI 0.80-0.98). North African group 2 had significantly lower HR (0.58, 95%CI 0.43-0.79). To conclude, higher resilience was found among European survivors of severe adversity, compared to those who suffered lesser persecution. No elevated risk was found among North African survivors.

Stem cells (SCs) play a key role in homeostasis and repair. While many studies have focused on SC self-renewal and differentiation, little is known regarding the molecular mechanism regulating SC elimination and compensation upon loss. Here, we report that Caspase-9 deletion in hair follicle SCs (HFSCs) attenuates the apoptotic cascade, resulting in significant temporal delays. Surprisingly, Casp9-deficient HFSCs accumulate high levels of cleaved caspase-3 and are improperly cleared due to an essential caspase-3/caspase-9 feedforward loop. These SCs are retained in an apoptotic-engaged state, serving as mitogenic signaling centers by continuously releasing Wnt3 and instructing proliferation. Investigating the underlying mechanism, we reveal a caspase-3/Dusp8/p38 module responsible for Wnt3 induction, which operates in both normal and Casp9-deleted HFSCs. Notably, Casp9-deleted mice display accelerated wound repair and de novo hair follicle regeneration. Taken together, we demonstrate that apoptotic cells represent a dynamic SC niche, from which emanating signals drive SC proliferation and tissue regeneration., Competing Interests: Declaration of interests M.T.-L. is a director of Denali Therapeutics and Regeneron Pharmaceuticals. Other authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Since 2000, the Israeli mental health system has undergone a reduction in hospital beds, initiation of community-based rehabilitation, and transfer of governmental services to health maintenance organizations. This study examined trends, predictors and outcomes of involuntary psychiatric hospitalizations (IPH), in particular for immigrants. All first psychiatric hospitalizations of adults, 2001-2018, in the National Psychiatric Case Registry were used. Involuntary and voluntary hospitalizations were analyzed by demographic and clinical characteristics, and age-adjusted rates calculated over time. Multivariate logistic regression models were used to investigate IPH predictors and first IPH as a risk factor for one-year suicide after last discharge, and a Cox multivariate regression model to examine its risk for all-cause mortality. Among 73,904 persons in the study, age-adjusted rates of IPH were higher between 2011 and 2015 and then decreased slightly until 2018. Ethiopian immigrants had the highest risk for IPH, immigrants from the former Soviet Union a lower risk, and that of Arabs was not significantly different, from non-immigrant Jews. IPH was not significantly associated with one-year suicide or all-cause mortality. These findings demonstrate the vulnerability of Ethiopian immigrants, typical of disadvantaged immigrants having a cultural gap with the host country and highlight the importance of expanding community mental health services., (Copyright © 2021. Published by Elsevier B.V.)

Background: To compare the underlying cause of death reported by the Israeli Central Bureau of Statistics (CBS) with diagnoses in the electronic health records (EHR) of a fully integrated payer/provider healthcare system., Methods: Underlying cause of death was obtained from the CBS for deaths occurring during 2009-2012 of all Clalit Health Service members in Israel. The final cohort consisted of members who had complete medical records. The frequency of a supportive diagnosis in the EHR was reported for 10 leading causes of death (malignancies, heart disease, cerebrovascular disease, diabetes, kidney disease, septicemia, accidents, chronic lower respiratory disease, dementia and pneumonia and influenza)., Results: Of the 45 680 members included in the study, the majority of deaths had at least one diagnosis in the EHR that could support the cause of death. The lowest frequency of supportive diagnosis was for septicemia (52.2%) and the highest was for malignancies (94.3%). Sensitivity analysis did not suggest an alternative explanation for the missing documentation., Conclusions: The underlying cause of death coded by the CBS is often supported by diagnoses in Clalit's EHR. Exceptions are septicemia or accidents that cannot be anticipated from a patient's EHR, and dementia which may be under-reported., (© The Author(s) 2019. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Suicide rates among Ethiopian immigrants to Israel (EI) are relatively high. This study sought to identify suicide-risk factors in this population in order to suggest some potentially preventive measures to mental health policymakers who are struggling to prevent suicide among EI., Method: Nationwide age-adjusted suicide rates were calculated for EI, Former Soviet Union immigrants (FSUI) and Israeli-born (IB) Jews by age, gender, and year of death and, for EI, by marital status and immigration period in the years 1985-2017 (1990-2017 for FSUI)., Results: Age-adjusted suicide rates for the period 1990-2017 confirmed the significantly higher rate among EI--3.1 times higher than for FSUI and 4.1 times higher than for IB. Similar rates were obtained for both genders, within each age group, and in all study years. Comparable male/female rate ratios were found among EI and IB (3.3, 3.6, respectively). Over the years of the study, only among the Ethiopian immigrants were there large fluctuations in suicide rates: a decrease (1992-2001), followed by an increase (2001-2006), and then a progressive decrease (from 2006). The secular changes differed greatly according to age. Among females, these fluctuations were smaller, the decrease began earlier and was greater, and the subsequent increase was much smaller. Marriage was found to be less protective for Ethiopian immigrants than for the other surveyed populations., Conclusions: The considerable gap between the EI's and FSUI's suicide rates highlights the critical role of immigrants' integration difficulties. These difficulties among EI lead to ongoing conflict within the family, which may explain why marriage is less protective for EI. Nevertheless, progressive integration is occurring as indicated by the decline in suicide rates since 2006. The fluctuations in EI suicide rates over time seem to be associated with modifications in social welfare allowances, which are crucial for EI of low socioeconomic status. Groups at risk, particularly EI men facing socioeconomic challenges and EI with considerable family conflict, typically identified by HMOs and welfare services, should be screened for suicide risk, and those identified as at risk referred to tailored workshops sensitive to Ethiopian culture.

Background: Excess all-cause mortality has been used in many countries as an estimate of mortality effects from COVID-19. What was the excess mortality in Israel in 2020 and when, where and for whom was this excess?, Methods: Mortality rates between March to November 2020 for various demographic groups, cities, month and week were compared with the average rate during 2017-2019 for the same groups or periods., Results: Total mortality rates for March-November were significantly higher by 6% in 2020, than the average of 2017-2019, 14% higher among the Arab population and 5% among Jews and Others. Significantly higher monthly mortality rates were found in August, September and October by 11%, 13% and 19%, respectively, among Jews and Others, and by 19%, 64% and 40% in the Arab population. Excess mortality was significant only at older ages, 7% higher rates at ages 65-74 and 75-84 and 8% at ages 85 and above, and greater for males than females in all ages and population groups. Interestingly, mortality rates decreased significantly among the younger population aged under 25. The cities with most significant excess mortality were Ramla (25% higher), Bene Beraq (24%), Bat Yam (15%) and Jerusalem (8%)., Conclusion: Israel has seen significant excess mortality in August-October 2020, particularly in the Arab sector. The excess mortality in March-November was statistically significant only at older ages, over 65. It is very important to protect this susceptible population from exposure and prioritize them for inoculations. Lockdowns were successful in lowering the excess mortality. The excess mortality is similar to official data on COVID-19 deaths.

Purpose: We sought to evaluate angiographic outcomes in ostial and distal LM lesions., Methods: 176 patients with LM disease undergoing PCI were retrospectively included in this study. 9 months of angiographic and 12 months of clinical follow-up was obtained. Quantitative coronary analysis (QCA) was performed for all lesions, using an 11-segment model. Clinical endpoint measure was a composite endpoint of cardiac death, myocardial infarction and target lesion revascularization (TLR)., Results: During 12 months follow up after successful PCI, the composite endpoint occurred more frequently in distal LM bifurcation lesions mainly driven by elevated TLR rates (14.1% in distal LM disease vs. 5.6% in ostial/midshaft LM disease, P = 0.20). Concordantly angiographic binary restenosis (8.2% compared to 0.0%) and late lumen loss (LLL, 0.42 ± 0.97 vs. 0.28 ± 0.34 mm) were increased in distal LM bifurcation lesions compared to ostial LM lesions. In distal lesions highest values for LLL were observed in segments adjacent to the bifurcation (0.37 ± 1.13 mm and 0.37 ± 0.73 mm). On cox proportional regression analysis the angiographic parameter LLL in a bifurcation segment (P = 0.03, HR 1.68 [1.1-2.7]) as well as presence of diabetes mellitus as a clinical parameter (P = 0.046, HR 2.77 [1.0-7.5]) were independent correlates for occurrence of MACE in distal LM bifurcations lesions., Conclusion: PCI of ostial LM in accomplished with low LLL (0.28 ± 0.34 mm) and binary restenosis rates. In distal left main lesions highest rates for LLL and binary restenosis were observed in segments nearest to the bifurcation and rather focused on the main vessel (0.42 ± 0.97 mm)., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Epidemiological studies have demonstrated a relationship between cognitive function in youth and the future risk of death. Less is known regarding the relationship with diabetes related death. This study assessed the relationship between cognitive function in late adolescence and the risk for diabetes, cardiovascular- (CVD) and all-cause mortality in adulthood., Methods: This retrospective study linked data from 2,277,188 16-19 year olds who had general intelligence tests (GIT) conducted during pre-military recruitment assessment with cause of death as coded by the Israel Central Bureau of Statistics. The associations between cognitive function and cause-specific mortality were assessed using Cox models., Results: There were 31,268 deaths that were recorded during 41,916,603 person-years of follow-up, with a median follow-up of 19.2 (IQR 10.7, 29.5) years. 3068, 1443, 514 and 457 deaths were attributed to CVD, CHD, stroke, and diabetes, respectively. Individuals in the lowest GIT vs. highest GIT quintiles in unadjusted models had the highest risk for all-cause mortality (HR 1.84, 95% CI 1.78, 1.91), total CVD (HR 3.32, 95% CI 2.93, 3.75), CHD (HR 3.49 95% CI 2.92, 4.18), stroke (HR 3.96 95% CI 2.85, 5.5) and diabetes-related (HR 6.96 95% CI 4.68, 10.36) mortality. These HRs were attenuated following adjustment for age, sex, birth year, body-mass index, residential socioeconomic status, education and country of origin for all-cause (HR 1.23, 95% CI 1.17, 1.28), CVD (HR 1.76, 95% CI 1.52, 2.04), CHD (HR 1.7 95% CI 1.37, 2.11), stroke (HR 2.03, 95% CI 1.39, 2.98) and diabetes-related (HR 3.14 95% CI 2.00, 4.94) mortality. Results persisted in a sensitivity analyses limited to participants with unimpaired health at baseline and that accounted competing risk., Conclusions: This analysis of over 2 million demonstrates a strong relationship between cognitive function at youth and the risk for diabetes, all-cause and CVD-related mortality independent of adolescent obesity.

Background: Previous studies have demonstrated the association between psychological distress (measured by the 12-item General Health Questionnaire, GHQ-12) and risks of all-cause mortality and deaths from cardiovascular, cancer and other causes. We hypothesised that in the Israeli population permanently exposed to war/terror stressors, this relationship is absent., Methods: We performed an analysis of data from participants in the Israel National Health Survey conducted in 2003-2004, who died during the follow-up decade. Subjects were assigned to groups based on GHQ-12 score: 0-10 (asymptomatic), 11-14 (subclinically symptomatic), 15-19 (symptomatic) and 20-36 (highly symptomatic). Data were weighted to the total population., Results: We analysed data from 4843 individuals, median age 40.5 (IQR 28-54); 473 participants died during the follow-up. We found a significant increase in total mortality, cardiovascular and other causes of mortality (but not cancer deaths) with increase in GHQ-12 score (P for linear trend of ungrouped GHQ scores <0.0001, 0.0015 and <0.0001, respectively). The age-sex-adjusted HR for the highest GHQ-12 compared with the lowest asymptomatic category was 2.1 (95% CI 1.6 to 2.7) for all-cause deaths, 2.3 (95% CI 1.3 to 4.1) for cardiovascular disease deaths and 2.7 (95% CI 1.9 to 3.9) for other deaths. The HR remained significant after adjustment for education, smoking, alcohol consumption and diabetes. The HR even increased after excluding participants with baseline cardiovascular diseases and cancer., Conclusion: Contrary to our hypothesis, psychological distress was associated with all-cause and cardiovascular but not cancer mortality. The absence of reverse causality provides evidence for the direct deleterious effects of psychological distress on mortality outcomes., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The association between Holocaust experience, suicide, and psychiatric hospitalization has not been unequivocally established. The aim of this study was to determine the risk of suicide among 3 Jewish groups with past or current psychiatric hospitalizations: Holocaust survivors (HS), survivors of pre-Holocaust persecution (early HS), and a comparison group of similar European background who did not experience Holocaust persecution. In a retrospective cohort study based on the Israel National Psychiatric Case Register (NPCR) and the database of causes of death, all suicides in the years 1981-2009 were found for HS (n = 16,406), early HS (n = 1,212) and a comparison group (n = 4,286). Age adjusted suicide rates were calculated for the 3 groups and a logistic regression model was built to assess the suicide risk, controlling for demographic and clinical variables. The number of completed suicides in the study period was: HS-233 (1.4%), early HS-34 (2.8%), and the comparison group-64 (1.5%). Age adjusted rates were 106.7 (95% CI 93.0-120.5) per 100,000 person-years for HS, 231.0 (95% CI 157.0-327.9) for early HS and 150.7 (95% CI 113.2-196.6) for comparisons. The regression models showed significantly higher risk for the early HS versus comparisons (multivariate model adjusted OR = 1.68, 95% CI 1.09-2.60), but not for the HS versus comparisons. These results may indicate higher resilience among the survivors of maximal adversity compared to others who experienced lesser persecution.

Background: Postpartum suicidality, a result of extreme distress or depression, is a tragedy for the woman, infant, and family. Screening for postpartum depression (PPD) is mandatory in Israel, including a question on suicidal ideation. This study presents and analyzes data regarding rates, trends and characteristics of postpartum women who considered, attempted, or completed suicide, to help direct services aimed at preventing these occurrences., Methods: Suicidal ideation data based on PPD screening was drawn from various publications and databases. Suicide attempt data was obtained from the Emergency Department database for 2006-2015 and matched with the National Birth Registry. Cause of death from the national database for those years were similarly linked to births to identify postpartum suicides and deaths. Postpartum and non-postpartum suicide attempt rates were computed by year, and by age and ethnic/immigrant group. A multivariate logistic model was used to estimate relative risk for postpartum attempts, controlling for age and ethnic group., Results: Suicidal ideation in recent years has been reported as 1% or less, with higher rates found in studies of Arab women. Suicide attempt rates for non-postpartum women were 3-5 times that of postpartum women, rising over the years, while remaining relatively stable for postpartum women. Adjusted risk of suicide attempt for non-postpartum women was significantly higher; adjusted odds ratio was 4.08 (95% CI 3.75-4.44). It was also significantly higher for Arabs and immigrants from the Former Soviet Union, compared to Israeli-born Jews/veteran immigrants, and for younger women compared to those aged 35-44. Seven postpartum suicides were recorded during 2006-2015, a rate of 0.43 per 100,000 births., Conclusion: Postpartum suicidality in Israel is low relative to other countries. Although relatively rare and lower than among non-postpartum women, health professionals should be attentive to risk factors, such as past psychiatric disorders, suicide attempts and current emotional distress, particularly among higher-risk populations. The universal screening program for PPD is a valuable opportunity for this, but increased resources should be allotted to implement and utilize it optimally. Prenatal screening should be added as an Israeli Quality Indicator, and postpartum completed suicides should be thoroughly investigated to guide prevention efforts.

Objective: This study aimed to evaluate the association of body mass index (BMI) in adolescence with mortality attributed to kidney disease., Methods: In this study, 2,294,139 Jewish Israeli adolescents with measured weight and height at 17 years old during the military fitness assessment were analyzed with a follow-up extending up to 45 years. All kidney-related outcomes, coded by the Central Bureau of Statistics from death notifications as the underlying cause of death, were obtained by linkage. Cox hazards models were applied., Results: During 42,297,007 person-years of follow-up (median 18.4 years), 226 deaths related to kidney disease were recorded. There was an increased risk for kidney-related death among adolescents with overweight and obesity with adjusted hazard ratios of 2.7 (95% CI: 1.8-3.9) and 8.4 (5.1-13.8), respectively, with BMI between 18.5 and 22.0 kg/m 2 as the reference. A 15% increased risk for kidney-related mortality (1.11-1.19) per unit increment in BMI was observed. Furthermore, a multivariable spline model indicated a minimum risk for kidney-related mortality starting at BMI of 18.6 kg/m 2 with significantly increased risk seen above values of 22.8 kg/m 2 . The results withstood extensive sensitivity analyses, including stratification of kidney-related death attributed to acute, chronic, and total kidney disease., Conclusions: Adolescent overweight and obesity are risk markers for kidney-related mortality over 4 decades., (© 2018 The Obesity Society.)

Context: As opposed to coronary heart disease (CHD) mortality, cardiovascular mortality attributed to non-CHD causes has increased., Objective: To evaluate the association of body mass index (BMI) in late adolescence with mortality attributed to non-CHD cardiovascular sequelae., Design and Setting: A nationwide cohort., Participants: A total of 2,294,139 adolescents examined between 1967 and 2010., Interventions: Height and weight were measured at age 17. All cardiovascular disease-specific outcomes, coded by the Central Bureau of Statistics from death notifications as the underlying cause of death, were obtained by linkage. Cox hazards models were applied., Main Outcome Measurements: Death attributed to fatal arrhythmias, hypertensive heart disease, cardiomyopathies, arterial disease, heart failure, and pulmonary embolism., Results: During 42,297,007 person-years of follow-up, there were 3178 deaths due to cardiovascular causes, of which 279, 122, 121, 114, 94, and 70 were attributed to the main outcomes, respectively. BMI was positively associated with all study outcomes with hazard ratios (HRs) per unit increment in BMI ranging from 1.09 [95% confidence interval (CI): 1.03 to 1.16] for arterial disease to 1.16 (95% CI: 1.11 to 1.21) for hypertensive heart disease. When BMI was treated as a categorical variable, a graded increase in risk was evident from the high-normal (22.0 to <25.0 kg/m2) to the overweight to the obese categories, with HRs of 1.4, 1.7, and 3.7 for arrhythmias; 1.9, 4.1, and 8.0 for hypertensive heart disease; 1.5, 2.4, and 4.0 for cardiomyopathies, 2.7, 5.0, and 3.5; for arterial disease, 1.7, 2.7, and 5.4 for heart failure; and 1.3, 1.8, and 3.0 for pulmonary embolism. Findings persisted in extensive sensitivity analyses., Conclusions: Adolescent BMI within the accepted normal range is associated with non-CHD nonstroke cardiovascular outcomes., (Copyright © 2017 Endocrine Society)

Aims: To explore previously unreported rates and trends in opioid-related mortality in Israel, 2005-2014., Methods: Data was obtained from the national database on causes of death. Drug poisoning deaths were divided into opioid-related deaths and deaths related to other drugs according to International Classification of Diseases (ICD)-10 code of underlying cause, and included drug poisoning of accidental, intentional or undetermined intent. Age-adjusted rates were calculated per 100,000 population. Rate ratios were calculated and a logistic model constructed to compare the risk of opioid-related deaths in both halves of the decade (2006-2009 and 2009-2013) and between various demographic groups., Results: While age-adjusted rates of deaths related to other drugs remained relatively stable, rates of opioid-related deaths significantly decreased during this period across all groups. During the study period, the number of opioid-related deaths in Israel declined from 1.3 to 0.3 per 100,000. Opioid-related deaths were more common among men, young adults and immigrants from the Former Soviet Union., Conclusions: Rates of opioid-related deaths in Israel were low compared to those reported in the United States and United Kingdom. In addition, the decline in opioid-related deaths in Israel is contrary to trends observed in the United States and United Kingdom. Factors that may contribute to these differences are discussed., (© 2017 S. Karger AG, Basel.)

Objective: The sequelae of increasing childhood obesity are of major concern. We assessed the association of BMI in late adolescence with diabetes mortality in midlife., Research Design and Methods: The BMI values of 2,294,139 Israeli adolescents (age 17.4 ± 0.3 years), measured between 1967 and 2010, were grouped by U.S. Centers for Disease Control and Prevention age/sex percentiles and by ordinary BMI values. The outcome, obtained by linkage with official national records, was death attributed to diabetes mellitus (DM) as the underlying cause. Cox proportional hazards models were applied., Results: During 42,297,007 person-years of follow-up (median, 18.4 years; range <1-44 years) there were 481 deaths from DM (mean age at death, 50.6 ± 6.6 years). There was a graded increase in DM mortality evident from the 25th to the 49th BMI percentile group onward and from a BMI of 20.0-22.4 kg/m 2 onward. Overweight (85th to 94th percentiles) and obesity (the 95th percentile or higher), compared with the 5th to 24th percentiles, were associated with hazard ratios (HRs) of 8.0 (95% CI 5.7-11.3) and 17.2 (11.9-24.8) for DM mortality, respectively, after adjusting for sex, age, birth year, height, and sociodemographic variables. The HR for the 50th through 74th percentiles was 1.6 (95% CI 1.1-2.3). Findings persisted in a series of sensitivity analyses. The estimated population-attributable fraction for DM mortality, 31.2% (95% CI 26.6-36.1%) for the 1967-1977 prevalence of overweight and obesity at age 17, rose to a projected 52.1% (95% CI 46.4-57.4%) for the 2012-2014 prevalence., Conclusions: Adolescent BMI, including values within the currently accepted "normal" range, strongly predicts DM mortality up to the seventh decade. The increasing prevalence of childhood and adolescent overweight and obesity points to a substantially increased future adult DM burden., (© 2016 by the American Diabetes Association.)

Background: In light of the worldwide increase in childhood obesity, we examined the association between body-mass index (BMI) in late adolescence and death from cardiovascular causes in adulthood., Methods: We grouped data on BMI, as measured from 1967 through 2010 in 2.3 million Israeli adolescents (mean age, 17.3±0.4 years), according to age- and sex-specific percentiles from the U.S. Centers for Disease Control and Prevention. Primary outcomes were the number of deaths attributed to coronary heart disease, stroke, sudden death from an unknown cause, or a combination of all three categories (total cardiovascular causes) by mid-2011. Cox proportional-hazards models were used., Results: During 42,297,007 person-years of follow-up, 2918 of 32,127 deaths (9.1%) were from cardiovascular causes, including 1497 from coronary heart disease, 528 from stroke, and 893 from sudden death. On multivariable analysis, there was a graded increase in the risk of death from cardiovascular causes and all causes that started among participants in the group that was in the 50th to 74th percentiles of BMI (i.e., within the accepted normal range). Hazard ratios in the obese group (≥95th percentile for BMI), as compared with the reference group in the 5th to 24th percentiles, were 4.9 (95% confidence interval [CI], 3.9 to 6.1) for death from coronary heart disease, 2.6 (95% CI, 1.7 to 4.1) for death from stroke, 2.1 (95% CI, 1.5 to 2.9) for sudden death, and 3.5 (95% CI, 2.9 to 4.1) for death from total cardiovascular causes, after adjustment for sex, age, birth year, sociodemographic characteristics, and height. Hazard ratios for death from cardiovascular causes in the same percentile groups increased from 2.0 (95% CI, 1.1 to 3.9) during follow-up for 0 to 10 years to 4.1 (95% CI, 3.1 to 5.4) during follow-up for 30 to 40 years; during both periods, hazard ratios were consistently high for death from coronary heart disease. Findings persisted in extensive sensitivity analyses., Conclusions: A BMI in the 50th to 74th percentiles, within the accepted normal range, during adolescence was associated with increased cardiovascular and all-cause mortality during 40 years of follow-up. Overweight and obesity were strongly associated with increased cardiovascular mortality in adulthood. (Funded by the Environment and Health Fund.).

Metastasis remains the primary cause of patient morbidity and mortality in solid tumors and is due to the action of a large number of tumor-autonomous and non-autonomous factors. Here we report the results of a genome-wide integrated strategy to identify novel metastasis susceptibility candidate genes and molecular pathways in breast cancer metastasis. This analysis implicates a number of transcriptional regulators and suggests cell-mediated immunity is an important determinant. Moreover, the analysis identified novel or FDA-approved drugs as potentially useful for anti-metastatic therapy. Further explorations implementing this strategy may therefore provide a variety of information for clinical applications in the control and treatment of advanced neoplastic disease.

Background: The effect of early hypertension on midlife cardiovascular (CV) mortality remains controversial. We assessed the association of established hypertension in late adolescence with subsequent CV mortality., Methods: Of 2,298,130 Israeli adolescents (60% males; age 17.4 ± 0.3 years) who underwent a compulsory medical examination prior to military service between 1967 and 2010, 8720 teenagers (0.4%) were formally diagnosed with persistent hypertension. Using Cox proportional hazards modeling, we compared the hypertensive group to the large normotensive group with regard to time to event analysis of midlife mortality due to cerebrovascular accidents (CVA), coronary heart disease (CHD), sudden death (SD) and their summation as cardiovascular disease (CVD)., Results: During 45,729,521 person-years of follow-up, we identified 2918 CV deaths-2879 and 39 among the 2,289,410 normotensive and 8720 hypertensive adolescents, respectively. Hypertension at a young age was associated with a threefold elevation of stroke mortality compared to normotension when adjusted for sex, age at examination, birth year, country of origin, socioeconomic status, education, body mass index (BMI) and height [hazard ratio (HR) 3.12; 95% confidence interval (CI) 1.76-5.54; p < 0.001]. There was no significant association of hypertension with CHD mortality or SD. An increased risk for overall CVD mortality among hypertensive youngsters (HR 1.51; 95 % CI 1.10-2.07) was attenuated after adjusting for BMI and other covariates (HR 1.24; 95% CI 0.90-1.72)., Conclusions: Established hypertension at a young age was independently associated with elevated stroke mortality in midlife. This finding warrants confirmatory large-scale long-term follow-up studies to address the distant effects of adolescent hypertension.

Background: The age-adjusted mortality rate in Israel is low compared to most Western countries although mortality rates from diabetes and renal failure in Israel are amongst the highest, while those from cardiovascular diseases (CVD) are amongst the lowest. This study aims to assess validity of choice of underlying causes (UC) in Israel by analyzing Israeli and international data on the prevalence of these diseases as multiple causes of death (MCOD) compared to UC, and data on comorbidity (MCOD based)., Methods: Age-adjusted death rates were calculated for UC and MCOD and the corresponding ratio of multiple to underlying cause of death (SRMU) for available years between 1999 and 2012. Comorbidity was explored by calculating cause of death association indicators (CDAI) and frequency of comorbid disease. These results were compared to data from USA, France, Italy, Australia and the Czech Republic for 2009 or other available year., Results: Mortality rates for all these diseases except renal failure have decreased in Israel between 1999 and 2012 as UC and MCOD. In 2009, the SRMU for diabetes was 2.7, slightly lower than other Western countries (3.0-3.5) showing more frequent choice as UC. Similar results were found for renal failure. In contrast, the SRMU for ischemic heart disease (IHD) and cerebrovascular disease were 2.0 and 2.6, respectively, higher than other countries (1.4-1.6 and 1.7-1.9, respectively), showing less frequent choice as UC. CDAI data showed a strong association between heart and cerebrovascular disease, and diabetes in all countries. In Israel, 40 % of deaths with UC diabetes had IHD and 24 % had cerebrovascular disease. Renal disease was less strongly associated with IHD., Conclusion: This international comparison suggests that diabetes and renal failure may be coded more frequently in Israel as UC, sometimes instead of heart and cerebrovascular disease. Even with some changes in coding, mortality rates would be high compared to other countries, similar to the comparatively high diabetes prevalence in Israel at older ages and high rate of end-stage renal failure. This study highlights the importance of physician training on death certification practice and need for further progress towards automation in recording and coding death causes.

Objectives: (1) To examine the trends in the incidence of dual diagnosis (DD) of severe mental illness and substance-related disorders among inpatients in Israel, and (2) the demographic and clinical correlates of DD patients., Method: Using data from the National Psychiatric Case Register, we identified 56,774 inpatients aged 15-64 whose first psychiatric hospitalization occurred between 1996 and 2010. We compared the characteristics of inpatients having DD with drugs, alcohol or drug/alcohol abuse with those with mental disorder only., Results: Over the period, DD with drugs decreased from 8.2% in 1996 to 6% in 2010; DD with alcohol increased from 3% to 4% and DD with drugs/alcohol from 2% to 4%. DD with drugs was highest, whereas DD with alcohol was lowest for the youngest age- group in 1996 but increased to the same as other age-groups in 2006-2010. Male gender, a previous suicide attempt, compulsory hospitalizations and marital status were positive predictors for all DD. Immigrant status was a positive predictor of DD with alcohol, but the opposite for DD with drugs; being Jewish and psychotic diagnosis was a positive predictor of DD with drugs, but negative for DD with alcohol., Conclusions: Over the study period, DD with drugs has decreased among young patients, although it is still higher than among older groups. However, DD with alcohol or drugs/alcohol has increased in the younger group. The clinical-demographic profile of DD patients was similar to that from the relevant literature, except for immigrant status that was negatively associated with DD with drugs., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)