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This study analyzed the association between adolescent BMI and myopia severity.This cross-sectional study comprised 1,359,153 adolescents who were medically examined before mandatory military service. Mild-to-moderate and high myopia were defined based on right-eye refractive data. BMI was categorized based on the US age- and sex-matched percentiles. Logistic regression models were applied separately for women and men to estimate odds ratios (ORs) for myopia per BMI category.A total of 318,712 adolescents had mild-to-moderate myopia and 23,569 had high myopia. Compared with low-normal BMI (reference group), adjusted ORs for mild-to-moderate and high myopia increased with increasing BMI status, reaching 1.39 (95% CI: 1.23-1.57) and 1.73 (95% CI: 1.19-2.51) for men with severe obesity, respectively, and 1.19 (95% CI: 1.12-1.27) and 1.38 (95% CI: 1.14-1.65) for women with mild obesity, respectively. ORs for mild-to-moderate and high myopia were also higher in men with underweight (OR = 1.20; 95% CI: 1.18-1.23 and OR = 1.39; 95% CI: 1.30-1.47) and women with underweight (OR = 1.06; 95% CI: 1.03-1.09 and OR = 1.12; 95% CI: 1.04-1.22). The overall size effect was greater for men than women (pBMI was associated with myopia in a J-shaped pattern, with the size effect being greater for adolescent men than women. This study indicates that both low BMI and high BMI are associated with mild-to-moderate and severe myopia.

Since the beginning of the Sever Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, school closure as a mitigating measure was at the center of a public and professional debate. While the negative effects of school closure cannot be ignored, accumulating data suggested that it is necessary for reducing community transmission. Our study presents an optional strategy for safe school opening during a pandemic, implemented in selected Israeli high schools by a special task force constructed by the Sheba Medical Center (SMC).The study took place between November 2020 and April 2021. Three schools from different areas of Israel were enrolled. The participants were asked to undergo bi-weekly SARS-CoV-2 rapid diagnostic antigen tests (Ag-RDT). Those who tested positive were requested to self-isolate, whereas their school contacts were tested daily by Ag-RDT. Participants with a previously documented SARS-CoV-2 infection or who were found to be SARS-CoV-2 seropositive upon enrollment were exempted from screening.Of a total of 361 participants who enrolled in the study, 12.3% were found to be seropositive. Fourteen SARS-CoV-2 cases were detected (3.5%), 12 of them in one single school located in an endemic area for SARS-CoV-2. The 14 cases resulted in 84 days of COVID-19-related absence from school, comparing with 1775 potential days of COVID-19-related absence under a strategy implementing self-isolation instead of testing.Safe continuation of academic routine during the pandemic is possible when using rapid Ag-RDT as a screening tool, while allowing swab collection by trained students and teachers.

Background: Recent guidelines classified blood pressure above 130/80 mm Hg as hypertension. However, outcome data were lacking. Objective: To determine the association between blood pressure in adolescence and the risk for early kidney damage in young adulthood. Methods: In this nationwide cohort study, we included 629 168 adolescents aged 16 to 20 who underwent medical examinations before mandatory military service in Israel. We excluded 30 466 adolescents with kidney pathology, hypertension, or missing blood pressure or anthropometric data at study entry. Blood pressure measurements at study entry were categorized according to the Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents: group A (2 ) or over. Results: Of 598 702 adolescents (54% men), 2004 (0.3%) developed early kidney damage during a mean follow-up of 15.1 (7.2) years. The adjusted hazard ratios for early kidney damage in blood pressure group C were 1.17 (1.03–1.32) and 1.51 (1.22–1.86) among adolescents with lean (body mass index Conclusions: Blood pressure of ≥130/80 mm Hg was associated with early kidney damage in young adulthood, especially in adolescents with overweight and obesity.

Background Elevated blood pressure among adolescents has been shown to be associated with future adverse cardiovascular outcomes and early onset diabetes. Most data regarding systolic and diastolic blood pressure trends are based on surveys of selected populations within 10–20-year periods. The goal of this study was to characterize the secular trend of blood pressure given the rising prevalence of adolescent obesity. Methods This nationwide population-based study included 2,785,515 Israeli adolescents (41.6% females, mean age 17.4 years) who were medically evaluated and whose weight, height and blood pressure were measured, prior to mandatory military service between 1977 and 2020. The study period was divided into 5-year intervals. Linear regression models were used to describe the P for trend along the time intervals. Analysis of covariance was used to calculate means of blood pressure adjusted for body mass index. Results During the study period, the mean body mass index increased by 2.1 and 1.6 kg/m2 in males and females, respectively (P for trend Conclusion Despite the increase in body mass index over the last four decades, diastolic blood pressure decreased in both sexes while systolic blood pressure increased slightly in males and decreased in females.

ImportanceThe BNT162b2 two-dose vaccine (BioNTech/Pfizer) has high effectiveness that wanes within several months. The third dose is effective in mounting a significant immune response, but its durability is unknown.ObjectiveTo compare antibody waning after second and third doses and estimate the association of antibody kinetics with susceptibility to infection with the Omicron variant of SARS-CoV-2.Design, Setting, and ParticipantsIn a prospective longitudinal cohort study in a tertiary medical center in Israel, health care workers who received the BNT162b2 vaccine were followed up monthly for IgG and neutralizing antibody levels. Linear mixed models were used to compare antibody titer waning of second and third doses and to assess whether antibody dynamics were associated with Omicron transmission. Avidity, T cell activation, and microneutralization of sera against different variants of concern were assessed for a subgroup.ExposureVaccination with a booster dose of the BNT162b2 vaccine.Main Outcomes and MeasuresThe primary outcome was the rate of antibody titer change over time, and the secondary outcome was SARS-CoV-2 Omicron variant infection, as confirmed by reverse transcriptase–polymerase chain reaction.ResultsOverall, 4868 health care workers (mean [SD] age, 46.9 [13.7] years; 3558 [73.1%] women) and 3972 health care workers (mean [SD] age, 48.5 [14.1] years; 996 [74.9%] women) were followed up for 5 months after their second and third vaccine doses, respectively. Waning of IgG levels was slower after the third compared with the second dose (1.32%/d [95% CI, 1,29%/d to 1.36%/d] vs 2.26% [95% CI, 2.13%/d 2.38%/d]), as was waning of neutralizing antibody levels (1.32%/d [95% CI, 1.21%/d to 1.43%/d] vs 3.34%/d [95% CI, 3.11%/d to 3.58%/d]). Among 2865 health care workers assessed for Omicron incidence during an additional 2 months of follow-up, lower IgG peak (ratio of means 0.86 [95% CI, 0.80-0.91]) was associated with Omicron infection, and among participants aged 65 years and older, faster waning of IgG and neutralizing antibodies (ratio of mean rates, 1.40; [95% CI, 1.13-1.68] and 3.58 [95% CI, 1.92-6.67], respectively) were associated with Omicron infection. No waning in IgG avidity was observed 112 days after the third dose. Live neutralization of Omicron was lower compared with previous strains, with a geometric mean titer at the peak of 111 (95% CI, 75-166), compared with 942 (95% CI, 585-1518) for WT, 410 (95% CI, 266-634) for Delta; it demonstrated similar waning to 26 (95% CI, 16-42) within 4 months. Among 77 participants tested for T cell activity, mean (SD) T cell activity decreased from 98 (5.4) T cells/106 peripheral blood mononuclear cells to 59 (9.3) T cells/106 peripheral blood mononuclear cells.Conclusions and RelevanceThis study found that the third vaccine dose was associated with greater durability than the second dose; however, Omicron was associated with greater resistance to neutralization than wild type and Delta variants of concern. Humoral response dynamics were associated with susceptibility to Omicron infection.

Elevated intrascrotal temperature has been suggested as a risk factor for testicular cancer, which is the most common neoplasm among young men. Varicocoele was linked to increased intrascrotal temperature, but whether it is associated with testicular cancer is unclear.To explore the possible association between varicocoele at adolescence and the incidence of testicular cancer at adulthood.This nationwide, population-based, historical cohort study includes 1,521,661 Israeli male adolescents (mean age 17.5 ± 0.4 years), who were screened for varicocoele during the years 1967-2012, as part of their medical assessment prior to compulsory military service. The mean follow-up was 18 ± 4.2 years.The diagnosis of testicular cancer was ascertained from linkage of records to the the Israeli National Cancer Registry. Survival analysis was applied.In total, 53,210 adolescents were diagnosed with varicocoele stages 2 and 3 prior to military service. Of 1988 (0.13% of the total cohort) men who were diagnosed with testicular cancer during follow-up, 54 (0.1%) had varicocoele prior to military service, while 1934 (99.9%) did not; p = 0.213. The age at cancer diagnosis and the distribution of seminomas versus non-seminomas did not differ significantly between those with and without varicocoele in adolescence. In a multivariable analysis controlling for sociodemographic factors, varicocoele was not associated with testicular cancer; odds ratio = 0.816 (CI: 0.615-1.083).Varicocoele in adolescents was not found to be associated with testicular cancer in young adults.In light of the theoretical association between varicocoele and testicular cancer, we conducted this large population study. We found no association between varicocoele in young adulthood and testicular cancer later in life.

OBJECTIVE Gestational hyperglycemia is associated with deleterious neonatal outcomes, but long-term risks for offspring obesity are less clear. We estimated the odds for offspring adolescent overweight and obesity among mothers with gestational glucose intolerance. RESEARCH DESIGN AND METHODS In a mother-offspring historical cohort, the Israel military conscription data set was linked to a large health maintenance organization. Included were women who were evaluated at adolescence and underwent two-step gestational diabetes screening (mean age, 31 years) with a 50-g glucose challenge test (GCT), followed by a 100-g oral glucose tolerance test (OGTT) if the result was abnormal. Glucose tolerance categories included gestational normoglycemia, abnormal GCT with normal OGTT, impaired glucose tolerance (IGT; one abnormal OGTT value), and gestational diabetes. The primary outcome was offspring overweight/obesity (BMI ≥85th percentile) at adolescence, measured prior to military conscription. Logistic regression models were applied. RESULTS Of 33,482 mother-offspring pairs, overweight and obesity were observed in 6,516 offspring. Across increasing categories of pregnancy glycemia, the proportions of offspring with adolescent overweight/obesity increased: normoglycemia, 19%; abnormal GCT with normal OGTT, 22%; gestational IGT, 24%; and gestational diabetes, 25% (P < 0.0001). Corresponding odds ratios after adjustment for the mother’s late adolescent characteristics (sociodemographic confounders and BMI) and pregnancy age were 1.2 (95% CI 1.1–1.4), 1.3 (1.2–1.5), and 1.4 (1.3–1.6), respectively. Further adjustment for offspring birth weight percentile and sociodemographic variables did not materially change results. Associations were more pronounced with increasing obesity severity. CONCLUSIONS Gestational glucose intolerance, including categories not meeting the gestational diabetes threshold, was associated with increased odds for offspring overweight/obesity at late adolescence.

Anticipating the need for a COVID-19 treatment centre in Israel, a designated facility was established at Sheba Medical Center—a quaternary referral centre. The goals were diagnosis and treatment of patients with COVID-19 while protecting patients and staff from infection and ensuring operational continuity and treatment of patients with non-COVID. Options considered included adaptation of existing wards, building a tented facility and converting a non-medical structure. The option chosen was a non-medical structure converted to a hospitalisation facility suited for COVID-19 with appropriate logistic and organisational adaptations. Operational principles included patient isolation, unidirectional workflow from clean to contaminated zones and minimising direct contact between patients and caregivers using personal protection equipment (PPE) and a multimodal telemedicine system. The ED was modified to enable triage and treatment of patients with COVID-19 while maintaining a COVID-19-free environment in the main campus. This system enabled treatment of patients with COVID-19 while maintaining staff safety and conserving the operational continuity and the ability to continue delivery of treatment to patients with non-COVID-19.

In the context of growing prevalence of hip fractures and hip fracture surgery in the elderly, it is unknown if surgical trainee autonomy in the operating room conflicts with optimal health care provision and safety of patients. We hypothesized that surgery performed solely by residents, without supervision or participation of an attending surgeon, can provide similar outcomes to surgery performed by trauma or joint reconstruction fellowship-trained orthopaedic surgeons. A single-center cohort was retrospectively reviewed for all hip fracture cases, surgically treated with hemiarthroplasty or internal fixation during 2016. Data were analyzed and compared between surgery performed solely by post-graduate-year 4 to 6 residents, and surgery performed by trauma or joint replacement fellowship-trained surgeons. Demographics, time to surgery, and American Society of Anesthesiologists Physical Status Classification System (ASA), surgical parameters, preoperative and postoperative radiographs as well as primary (mortality, complications and revision surgery) and secondary outcome variables were collected and analyzed. Univariate analysis and Kaplan–Meier survival analysis were performed to evaluate outcomes. Out of 478 cases, 404 (84.5%) were included in this study. Non-operative cases, techniques used solely by attending surgeons, such as total hip replacement, were excluded. The average follow-up time was 26.1 months (SD 10.9). Analysis of internal fixation and hemiarthroplasty groups demonstrated no significant difference between residents and attendings in complications (p = 0.353, 0.850, respectively), and mortality (p = 0.796, 0.734, respectively). In both groups, surgery time was significantly longer in the resident group (p

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.

Background Increasing cancer incidence among children alongside improved treatments has resulted in a growing number of pediatric cancer survivors. Despite childhood cancer survivors' exposure to various factors that compromise kidney function, few studies have investigated the association between childhood cancer and future kidney disease. Methods To assess the risk of ESKD among childhood cancer survivors, we conducted a nationwide, population-based, retrospective cohort study that encompassed all Israeli adolescents evaluated for mandatory military service from 1967 to 1997. After obtaining detailed histories, we divided the cohort into three groups: participants without a history of tumors, those with a history of a benign tumor (nonmalignant tumor with functional impairment), and those with a history of malignancy (excluding kidney cancer). This database was linked to the Israeli ESKD registry to identify incident ESKD cases. We used Cox proportional hazards models to estimate the hazard ratio (HR) of ESKD. Results Of the 1,468,600 participants in the cohort, 1,444,345 had no history of tumors, 23,282 had a history of a benign tumor, and 973 had a history of malignancy. During a mean follow-up of 30.3 years, 2416 (0.2%) participants without a history of tumors developed ESKD. Although a history of benign tumors was not associated with an increased ESKD risk, participants with a history of malignancy exhibited a substantially elevated risk for ESKD compared with participants lacking a history of tumors, after controlling for age, sex, enrollment period, and paternal origin (adjusted HR, 3.2; 95% confidence interval, 1.3 to 7.7). Conclusions Childhood cancer is associated with an increased risk for ESKD, suggesting the need for tighter and longer nephrological follow-up.

Objective To compare pain during laminaria insertion after lidocaine spray versus placebo spray anesthesia in women about to undergo a surgical abortion procedure. Study design A double blind, randomized, placebo-controlled trial of women at 12–24 weeks gestation one day prior to surgical uterine evacuation procedure. Participants received lidocaine 10% or placebo (saline 0.9%) spray to the endocervix and ectocervix two minutes before laminaria insertion. The primary outcome was participants’ pain score immediately after initial laminaria insertion, measured using a 10 cm visual analog scale (VAS). Secondary outcomes included scores at speculum removal and 15 min after speculum insertion. Results From 7/2016 through 8/2018, we enrolled 68 and 66 women to the lidocaine and placebo groups, respectively. Baseline characteristics were similar in both groups. The primary outcome did not differ between lidocaine and placebo groups (median VAS 2.0 vs. 2.0 respectively, p = 0.69). Reported VAS after speculum removal and 15 min from speculum insertion were similar in the lidocaine and placebo groups (median 2.0, p = 0.99; median 1.0 vs. 1.5 respectively, p = 0.32). In multivariate analyses, lidocaine use was associated with decreased VAS score at 15 min from speculum insertion [95%CI −0.96 (−1.74 to −0.18), p = 0.016]. Reported VAS ≥7 at 1st laminaria insertion did not differ between lidocaine and placebo groups (5.88% vs. 10.61% respectively, p = 0.362). Conclusion In women scheduled for laminaria insertion prior to surgical uterine evacuation at 12–24 weeks gestation, topical application of lidocaine spray to the cervix before insertion did not result in lower reported pain as compared with placebo. Implications Our results imply that physicians should not use topical application of lidocaine spray to the cervix before laminaria insertion to reduce women’s pain. Continued efforts must be made to find means to relieve pain by using simple, effective analgesia or adjusting the technique, and not using a tenaculum whenever possible.

Objectives To assess the association between sleep disorders prevalence and obesity in Israeli adolescents. Methods A nationwide, population-based, cross-sectional study of 1,348,817 Israeli adolescents (57% males) who were medically examined prior to military service between 1997 and 2015; height and weight were measured along with assessment of medical status at age 17.3⬰±⬰0.4 years. The diagnosis of a sleep disorder was made based on objective diagnostic criteria. The prevalence and odds ratio (OR) for a sleep disorder were computed across BMI subgroups and were adjusted for socio-demographic confounders. Results Overall sleep disorders prevalence was 1.8:1000 (males) and 0.45:1000 (females), with a total of 1601 cases. There was a gradual increase in the odds ratio for sleep disorders with increasing BMI. Multivariable-adjusted ORs for sleep disorders were 1.29 (95% CI 1.10⬜1.52), 1.44 (1.18⬜1.75), 3.03 (2.32⬜3.96) and 3.38 (1.98⬜5.75) for overweight, obese class I, II and III, respectively (5th⬜49th BMI percentile was the reference). Results persisted in extensive sensitivity analyses including limiting the study sample to participants with unimpaired health. Conclusions We found a higher prevalence of sleep disorders in males and a dose-dependent association between sleep disorders and adolescent BMI in both sexes. Our findings warrant clinical awareness among healthcare providers, given the rise in obesity in teenagers, and particularly in light of the obesity epidemic that we are experiencing in this era. Sleep related complaints should be actively screened in adolescents who suffer obesity.

We investigated changes in receptor-binding domain IgG and neutralizing antibodies against the omicron and delta variants, vs the wild-type virus, in response to a fourth BNT162b2 dose in 90 heart transplant (HT) recipients. The fourth dose induced anti-RBD IgG antibodies and a higher neutralization efficiency against the wild-type virus and the variants; however, neutralization efficiency against the omicron variant was lower than that against the delta variant (the latter demonstrating efficacy similar to that against the wild-type virus). Notably, while IgG anti-RBD antibodies were detectable in80% of the HT recipients, only about half demonstrated neutralization efficiency against the omicron variant. A SARS-CoV-2-specific-T-cell response following the fourth dose was evident in the majority of transplant recipients. Boosting vulnerable groups improves antibody responses (including neutralizing responses) and cellular immunity, but the incomplete immunological response, particularly for omicron, suggests continued preventive measures and optimization of vaccination strategies that elicit strong, and long-lasting immune responses, in this high-risk population, should remain a priority.

To elucidate the association between adolescent microscopic hematuria and early onset urothelial carcinoma and renal cell carcinoma.Nationwide, population-based, retrospective cohort study using medical data of 970,366 adolescents aged 16 through 19 years (58.6% male) examined for fitness for military service between 1980 and 1997. Diagnoses of persistent isolated microscopic hematuria were given after thorough work up process excluding any other renal abnormalities. Incident cases of urothelial carcinoma and renal cell carcinoma diagnosed during the years of 1982-2012 were retrieved from the Israeli National Cancer Registry. Cox proportional hazards models were used to estimate the hazard ratio (HR) separately for urothelial carcinoma and renal cell carcinoma.During a cumulative follow-up of 22,115,629 person-years (median follow-up, 22.8), persistent isolated microscopic hematuria was diagnosed among 5509 (0.6%) adolescents. Urothelial carcinoma and renal cell carcinoma developed in 332 (3 among those with persistent isolated microscopic hematuria) and 292 (2) individuals, respectively. The adjusted HR for incident urothelial carcinoma among adolescents with isolated microscopic hematuria was 1.17 (95% CI, 0.38-3.66) and the adjusted HR for renal cell carcinoma was 1.02 (95% CI, 0.25-4.12).Persistent asymptomatic isolated microscopic hematuria at adolescence was not associated with increased risk for urothelial carcinoma nor renal cell carcinoma.

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.

BackgroundPersonality disorders are prevalent in 6–10% of the population, but their risk for cause-specific mortality is unclear. The aim of the study was to assess the association between personality disorders diagnosed in late adolescence and all-cause as well as cause-specific (cardiovascular-related, external-related) mortality.MethodsWe performed a longitudinal study on a historical prospective cohort based on nationwide screening prior to recruitment to the Israeli army. The study participants were 16–19-year-old persons who attended the army screening (medical and cognitive, including screening for psychiatric disorders) between 1967 and 2006. Participants were followed from 1967 till 2011.ResultsThe study included 2 051 606 subjects, of whom 1 229 252 (59.9%) were men and 822 354 (40.1%) were women, mean age 17.36 years. There were 55 508 (4.5%) men and 8237 (1.0%) women diagnosed with personality disorders. The adjusted hazard ratio (HRs) for coronary, stroke, cardiovascular, external-related causes and all-cause mortality among men with personality disorders were 1.34 (1.03–1.74), 1.82 (1.20–2.76), 1.45 (1.23–1.71), 1.41 (1.30–1.53) and 1.44 (1.36–1.51), respectively. The absolute rate difference for all-cause mortality was 56.07 and 13.19 per 105 person-years among men and women, respectively. Among women with personality disorders, the adjusted HRs for external-related causes and all-cause mortality were 2.74 (1.87–4.00) and 2.01 (1.56–2.58). Associations were already evident within 10 years of follow-up.ConclusionsPersonality disorder in late adolescence is associated with increased risk of cardiovascular, external- and all-cause mortality. Increased cardiovascular mortality is evident before the age of 40 years and may point to the importance of lifestyle education already in youth.

The durability of the immune response following the 3-dose BNT162b2 vaccination is unknown. The complexity of the situation is enhanced by the threat that highly transmissible variants may further accelerate the decline in the protection afforded by mRNA vaccines.One hundred and three 3-dose-vaccinated heart transplant recipients were longitudinally assessed for the kinetics of variant-specific neutralization (Cohort 1, n = 60) and SARS-CoV-2-specific-T-cell response (Cohort 2, n = 54) over 6 months. Neutralization and T-cell responses were compared between paired samples at 2 time points, using the Kruskal-Wallis test followed by Dunn's multiple comparison test for continuous variables and McNemar's test for dichotomous variables. The Bonferroni method of p values adjustment for multiple comparison was applied.The third dose induced high neutralization of the wild-type virus and delta variant (geometric mean titer [GMT], 137.2 [95% CI, 84.8-221.9] and 80.6, [95% CI, 49.3-132.0], respectively), and to a lesser degree of the omicron variant (GMT, 10.3 [95% CI, 5.9-17.9]). At 6 months, serum neutralizing activity declined but was still high for the wild-type virus and for the delta variant (GMTs 38.1 [95% CI, 21.2-69.4], p = 0.011; and 28.9 [95% CI, 16.6-52.3], p = 0.022, respectively), but not for the omicron variant (GMT 5.9 [95% CI, 3.4-9.8], p = 0.463). The percentages of neutralizing sera against the wild-type virus, delta and omicron variants increased from 70%, 65%, and 38%, before the third dose, to 93% (p0.001), 88% (p0.001), and 48% (p = 0.021) at 3 weeks after, respectively; and remained high through the 6 months for the wild-type (80%, p = 0.06) and delta (77%, p = 0.102). The third dose induced the development of a sustained SARS-CoV-2-specific-T-cell population, which persisted through 6 months.The third BNT162b2 dose elicited a durable SARS-CoV-2-specific T-cell response and induced effective and durable neutralization of the wild-type virus and the delta variant, and to a lesser degree of the omicron variant.

Immigration from one cultural milieu to another has been associated with a greater risk for incident cardio-metabolic morbidity among adults. In this nationwide, population-based, cross-sectional study of data recorded from 1992 to 2016, we assessed the association between body mass index and blood pressure levels among adolescent immigrants, aged 16 to 19 years, of Ethiopian origin, and their secular trend of overweight and obesity. Adolescents of Ethiopian origin were classified as Israeli-born (n=16 153) or immigrants (N=23 487), with stratification by age at immigration. Adolescents whose fathers were at least 3 generations in Israel (n=277 789) served as a comparative group. Hypertensive-range blood pressure values adjusted for age, sex, and height served as outcome. Among adolescents of Ethiopian origin, overweight and obesity (body mass index ≥85th percentile), increased by 2.5 and 4-fold in males and females, respectively, during the study period, compared with a 1.5-fold increase among native Israeli-born males and females. The odds for hypertensive-range measurements increased with the length of residence in Israel: 7.3%, 10.6%, and 14.4% among males who immigrated at ages 12 to 19, 6 to 11.9, and 0 to 5.9 years, respectively; and 11.5%, 16.7%, and 19.3%, respectively, among females. Israeli-born Ethiopians had a significantly higher risk for hypertensive-range measurements at any body mass index level compared with native Israeli-born examinees, after adjusting for sociodemographic factors and health status. In conclusion, among Ethiopian Israeli adolescents, abnormal blood pressure correlates directly with the time-lapse since immigration. Immigrant populations require targeted surveillance and appropriate intervention.

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.

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.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.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).Excessively high BMI in otherwise healthy adolescents is associated with increased risk for incident type 1 diabetes in early adulthood.

Immune responses of solid organ transplant recipients to 2 doses of the BNT162b2 mRNA anti-SARS-CoV-2 vaccine are impaired. The immunogenicity and safety of a third dose among liver transplant (LT) recipients are unknown. This work aimed to evaluate the immune response of LT recipients to a third dose of the BNT162b2 mRNA vaccine.Consecutive LT recipients (n = 61) in follow-up at Sheba Medical Center were included. Receptor binding domain (RBD) IgG, neutralizing antibody (NA) titers, and T-cell levels before and 21-28 days after a third vaccine dose were determined. Adverse effects after the third dose were monitored.The median age of LT recipients was 65 years and 57.4% were male. The humoral immune response rate improved significantly, with 56% of patients showing a response before the third vaccine dose compared to 98% after the third dose. The cellular response in 12 evaluated patients improved significantly (p = 0.008). The geometric mean of anti-RBD IgG levels, NA levels, and T-cell count also increased significantly after the third dose. NA titers after the third dose negatively correlated with age (p = 0.03), mycophenolate mofetil treatment (p = 0.005), and combined immunosuppression as opposed to calcineurin inhibitor monotherapy (p = 0.001). After the third dose, adverse effects were reported by 37% of recipients and were mostly mild (local pain and fatigue).After a third BNT162b2 mRNA vaccine, the immune response improved significantly among LT recipients, without serious adverse effects. Further studies are needed to evaluate immune response durability and to determine the optimal number and schedule of booster vaccine doses.The Pfizer-Biotech BNT162b2SARS-CoV-2 vaccine induced significant immunity among liver transplant recipients after a third dose. The majority of the patients developed sufficient levels of both humoral and cellular immune responses. Factors that predict non-response were older age and immunosuppressive medications.

BACKGROUND The repeated waves of the COVID-19 pandemic have highlighted the necessity to optimize vaccine responses in immunocompromised populations. We investigated the safety and immunogenicity of a third, booster, dose of the Pfizer BNT162b2 vaccine in heart transplant (HT) patients. METHODS The cohort comprised 96 adult HT patients who received a third homologous dose of the BNT162b2 vaccine 168 days after the second dose. The vaccine-induced antibody responses of both receptor-binding domain (RBD) IgG and neutralizing antibodies were assessed in all patients, with a positive antibody response being defined as the presence of either IgG anti-RBD or neutralizing antibodies. For a subset of patients, T cell response was also studied. RESULTS The third dose was associated with a low rate of adverse events, mostly mild pain at the injection site. No serious adverse events were recorded, and there were no episodes of rejection. At 18 days following the third dose of the vaccine, the positive antibody response increased from 23% to 67%, with a corresponding increase in neutralizing capacity. The third dose elicited SARS-CoV-2 neutralization titers >9-fold and IgG anti-RBD antibodies >3-fold of the range achieved after the two primary doses. Mycophenolate use, lower eGFR and higher C-reactive protein were independently associated with a reduced likelihood of generating an immune response. Importantly, a specific T-cell response following the third dose was evident in the majority of transplant recipients. CONCLUSIONS An homologous third booster dose of the BNT162b2 vaccine gave overall consistent tolerability and a good safety profile, while eliciting humoral and cellular immune responses.

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 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.

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

Israel's response during the containment phase of the COVID-19 outbreak in early 2020 led to a delay in sustained community transmission and effective mitigation. During February-April 2020, a total of 15,981 confirmed cases resulted in 223 deaths. A total of 179,003 persons reported electronically to self-quarantine and were entitled to paid sick leave.

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.

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.

Diabetes mellitus poses major public health and economic challenges which necessitate national-level intervention. The ultimate goal of the Israel National Diabetes Program is to ensure that all people with diabetes, or at high risk of developing diabetes, will live well and have access to high-quality services that meet their individual needs. The integrated National Diabetes Program in Israel was established in 2014. Prevailing needs were identified and working groups assigned to delineate deficiencies and propose mode of action. Program leaders summarized and prioritized the needs, and identified main targets of action for the preliminary years. The program was achieved by a combined approach: top-bottom, having the Director General of the Ministry of Health (MoH) personally involved, and bottom-up, by routine meetings with representatives of the health organizations, clinical experts, patient representatives and other stakeholders. Main achievements during the first five years of the program included setting up a novel funding mechanism for diabetes prevention, substantiating the field of diabetes education in Israel, designing the infrastructure of diabetic foot care in Israel, updating the national health-budget allocation formula with incentives to improve provision of services, and promoting a mandatory system for judgemental labelling of food products. The program is in progress with ongoing monitoring, evaluation and improvement with particular emphasis on translational learning. Although there is much to be done, diabetes care in Israel has taken an enormous step forward in the past five years.

Sheba Medical Center, Tel Hashomer, is a tertiary hospital located in the center of Israel. It is the largest hospital in Israel and was the first to face coronavirus disease-2019 (COVID-19) patients in the country at the beginning of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic.To describe our experience with the COVID-19 pandemic, focusing on our triage method in the emergency department (ED). Our goal was to keep the main hospitalization buildings clean of infection by separating COVID-19 positive patients from COVID-19 negative patients.We divided our ED into two separate sections: a regular non-COVID-19 ED and an advanced biological ED. We created clear protocols of triage for suspected and confirmed COVID-19 patients. We reviewed the data of patients admitted to our ED during the month of March and analyzed the results of our triage method in separating COVID-19 positive from negative patients.During the month of March 2020, 7957 patients were referred to our ED. Among them 2004 were referred to the biological ED and 5953 were referred to the regular ED. Of the 2004 patients referred to the biological ED, 1641 (81.8%) were sampled for SARS-CoV-2 polymerase chain reaction of whom 143 (8.7%) were positive. Only two COVID-19 positive patients unintentionally entered the main clean hospital, making our triage almost full proof.Our triage method was successful in separating COVID-19 positive from negative patients and maintained the regular hospital clean of COVID-19 allowing treatment continuation of regular non-COVID-19 patients.

The COVID-19 pandemic substantially impacted countries' democratic election. On March 2020 Israel held a general parliamentary elections. The participation rate was 71.5%, compared with a 70% rate on the previous elections held in September 2019. We review Israel's actions which lead to a safe elections process and enhanced participation rate.

Background Physicians play a crucial frontline role in the COVID‐19 pandemic, which may involve high levels of anxiety. We aimed to investigate the association between pandemic‐related stress factors (PRSF) and anxiety and to evaluate the potential effect of resilience on anxiety among physicians. Methods A self‐report digital survey was completed by 1106 Israeli physicians (564 males and 542 females) during the COVID‐19 outbreak. Anxiety was measured by the 8‐item version of the Patient‐Reported Outcomes Measurement Information System. Resilience was evaluated by the 10‐item Connor–Davidson Resilience Scale. Stress was assessed using a PRSF inventory. Results Physicians reported high levels of anxiety with a mean score of 59.20 ± 7.95. We found an inverse association between resilience and anxiety. Four salient PRSF (mental exhaustion, anxiety about being infected, anxiety infecting family members, and sleep difficulties) positively associated with anxiety scores. Conclusions Our study identified specific PRSF including workload burden and fear of infection that are associated with increased anxiety and resilience that is associated with reduced anxiety among physicians.

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

Introduction In a nationwide population of adolescents, we investigated the sex-specific association of socioeconomic position (SEP) with severe obesity, and trends over time. Methods The cohort comprises all Israeli adolescents (mean ± SD age 17.3 ± 0.5 years) who were medically examined, before mandatory military service during 2000 to 2015. Of 1 120 362 adolescents, 239 816 (21.4%) were classified with overweight or with obesity classes I to III using the International Obesity Task Force criteria. Data were compared between 2000 to 2009 and 2010 to 2015. Results Considering more advantaged residential SEP as the reference group, the respective odds ratios (ORs ± 95%CI) of less advantaged SEP for obesity classes I to III in 2010 to 2015 were 1.48 (1.40-1.56), 1.66 (1.51-1.83), and 1.73 (1.45-2.08) for males; and 1.72 (1.60-1.84), 1.89 (1.66-2.15), and 2.62 (2.04-3.37) for females. All point estimates were higher than in the preceding decade. Considering female inductees from the more advantaged SEP as the reference group, ORs were higher for males in the more advantaged SEP group, for overweight, 1.31 (1.27-1.36); class I obesity, 1.29 (1.20-1.38); class II obesity, 1.34 (1.18-1.53); and class III obesity, 1.60 (1.24-2.07). Similarly, in the less and medium advantaged SEP groups, increased ORs for males compared with females were observed in all obesity groups. Results persisted using United States Centers for Disease Control and Prevention growth charts. Conclusions Adolescents with less rather than more advantaged residential SEP are at greater risk of severe obesity. Adolescent males, of all residential SEP groups had higher odds than females for all classes of obesity.

Severe obesity among children and adolescents is a significant global public health concern. The prevalence has markedly increased over the last decades, becoming common in many countries. Overwhelming rates of obesity among youth have prompted efforts to identify an evidence-based immediate- and long-term cardiometabolic risk factor profile in childhood-onset severe obesity, and to highlight gaps that require further investigation. The PubMed database was systematically searched in accordance with PRISMA guidelines. The search yielded 831 results, of which 60 fulfilled stringent criteria and were summarized in this review. The definition of severe obesity was variable, with only one half the publications using the definition BMI > 120% of the 95th percentile. Point estimates of the prevalence of at least one cardiometabolic risk factor in children with severe obesity reportedly range from 67 to 86%. Cross-sectional studies indicate that children and adolescents with severe obesity are at greater risk than those with mild obesity for type 2 diabetes, hypertension, fatty liver disease and dyslipidemia, already at childhood and adolescence. Robust epidemiological data on the long-term risk and actual point estimates in adulthood are lacking for these diseases as well as for other diseases (coronary heart disease, stroke, chronic kidney disease and cancer). Recent longitudinal studies indicate an increased risk for cardiomyopathy, heart failure, cardiovascular mortality and all-cause mortality in adulthood for adolescents with severe obesity compared to those with mild obesity. Given the alarming increase in the prevalence of severe obesity, the persistence of adiposity from childhood to adulthood and the precarious course of young adults with chronic comorbidities, the economic and clinical services burden on the healthcare system is expected to rise.

BackgroundEndovascularly retrieved clots are a potential resource for diagnosing stroke etiology, which may influence secondary prevention treatment. In this study we measured thrombin activity eluted by serially washing clots.MethodsClots were retrieved from 68 patients with acute ischemic stroke, freshly frozen and classified by standard criteria into proven atrial fibrillation (AF, 18 patients), atherosclerotic origin (AS, 15 patients), cryptogenic stroke (Cr, 17 patients) and other known causes (18 patients). Thawed clot samples were washed by transferring them into 1 mL buffer in seven hourly cycles and a fluorescent substrate assay was used to measure secreted thrombin activity. The clots were also examined histologically. Artificial fibrin and red blood cell-rich clots were similarly assayed for wash-eluted thrombin activity as an external control.ResultsThrombin activity eluted from clots of AF origin decreased significantly with time in contrast to steady levels eluted from AS origin thrombi (PConclusionsAn assay measuring the change in thrombin in clots retrieved during acute stroke endovascular thrombectomy procedures may serve as a diagnostic marker of the origin of the clot. The suggested mechanism for these differences may be the clot location before its retrieval, with high blood flow causing thrombin washout in atherosclerotic clots, in contrast to atrium appendage low blood flow retaining high thrombin levels.

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 (Pinteraction = 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.

Diabetic kidney disease (DKD) is becoming increasingly common among children. We aimed to estimate the risk of end-stage renal disease (ESKD) and mortality among adolescents with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) and normal renal function compared with non-diabetics. We hypothesized that childhood onset T1DM vs. T2DM would be associated with a different risk profile for developing ESKD and its complications.A nationwide, population-based, retrospective cohort study, including 1,500,522 adolescents examined for military service between 1967 and 1997, which were classified according to the presence and type of diabetes. Data were linked to the Israeli ESKD registry. Cox proportional-hazards models were used to estimate the hazard ratio (HR) for ESKD.At study enrolment, 1183 adolescents had T1DM and 196 had T2DM. ESKD developed in 2386 non-diabetic individuals (0.2%) compared with 72 individuals (6.1%) with T1DM and 8 individuals (4.1%) with T2DM. Participants with T1DM were younger at ESKD onset than participants with T2DM (median age, 36.0 vs. 40.5 years, P0.05). In a multivariate model adjusted for age, sex, paternal origin, enrollment year, BMI, and blood pressure, T1DM and T2DM were associated with HR of 36.4 (95% CI 28.3-46.9) and 19.3 (95% CI 9.6-38.8) for ESKD, respectively. Stratification according to sex, ethnicity, immigration, and socioeconomic status did not materially change the HR. During the follow-up period, mortality rates were higher in T2DM as compared with T1DM and controls (8.7 %, 2.2%, and 2.7% respectively).T1DM and T2DM in adolescents with normal renal function confer a significantly increased risk for ESKD. T1DM is associated with younger age at ESKD onset while T2DM is associated with higher mortality rate.

Stress is defined as the pscyophysiological reaction in which the steady state is disturbed or threatened. Stress is not always perceived as a negative response. Stress results when environmental demands exceed an individuals' adaptive capacities. Autoimmune diseases are heterogeneous group of chronic diseases which occur secondary to loss of self antigen tolerance. The etiopathogenesis of autoimmune disease is uncertain. Genetic factors as well as environmental factors appear to interplay, leading to a cascade of events resulting in disease onset. Stress has been postulated to play a role in disease onset in the genetically susceptible patients. During the stress response, catecholamines and glucocorticoids are released from locus coeruleus and adrenal gland. These biomolecules exert control over various immune cells in the innate and adaptive arms of the immune system, thereby altering the cytokine profile released. The increase of IL-4 promotes T-helper 2 (Th2) cell differentiation, while the decrease in IL-12 and the increased IL-10 production reduce the number of T-helper 1 (Th1) cells. The relationship between stress and autoimmune diseases is intricate. Stress has been shown to be associated with disease onset, and disease exacerbations in rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, Graves' disease as well as other autoimmune conditions. In certain conditions such as psoriasis, stress has been implicated in delaying lesion clearance upon the application of standard treatment regimes. Finally, psychological therapy and cognitive behavioral therapy aimed to reduce stress levels was shown to be effective in influencing better outcomes in many autoimmune diseases. The purpose of this paper is to closer inspect the clinical evidence regarding the role of stress on influencing the various aspects of disease entities.

Severe obesity is rising among adolescents, but data on the prevalence of metabolic abnormalities among this group are limited. We assessed the secular trend of severe obesity and its association with major cardio-metabolic morbidities. A total of 2,785,227 Israeli adolescents (aged 17.2 ± 0.5 years) who underwent a pre-recruitment medical examination including routine measurements of weight, height and blood pressure between 1967 and 2015 were included. In all, 230,639 adolescents with abnormally excessive BMI were classified into overweight, classes I, II, and III (severe) obesity. Logistic regression was applied to determine the association between BMI groups and prehypertension, high blood pressure and type 2 diabetes (T2DM). There was 45-fold increase in the prevalence of class III obesity during study period. Severe obesity was recorded in 2060 males and 1149 females, in whom nearly 35 and 43% had prehypertension or high blood pressure, respectively. Compared with adolescents with overweight, the odds ratios (ORs) for high blood pressure in classes II and III obesity groups, respectively, were 2.13 (95% CI, 2.04–2.23) and 2.86 (2.60–3.15) in males, and 2.59 (2.43–2.76) and 3.44 (3.04–3.90) in females, whereas the ORs for T2DM were 19.1 (12.3–29.6) and 38.0 (22.6–64.0) in males, and 15.1 (11.4–20.0) and 24.8 (17.2–35.7) in females. Results persisted in extensive sensitivity analyses including a longitudinal follow-up (median: males, 3.4 years; females, 4.9 years). Severe obesity showed a marked secular increase and was associated with significantly higher risk for abnormal blood pressure and T2DM than lower degrees of obesity, in both males and females.

We investigated whether obesity and sociodemographic factors at adolescence are associated with incident gastroenteropancreatic neuroendocrine tumors (GEP-NET).Our cohort included 2.3 million Israeli adolescents examined at ages 16 to 19 years between 1967 and 2010. The baseline database included sex, country of birth, residential socioeconomic status (SES), body-mass index (BMI) and height. Participants were followed through linkage with the National Cancer Registry up to 2012. We identified 221 cases of GEP-NET (66 pancreatic, 52 gastric, 39 rectal, 27 appendiceal, 23 small bowel and 14 colonic). Immigration from the Former Soviet Union (FSU) was associated with the risk of small bowel and rectal NET's, [Hazard Ratio (HR) 4.79, 95% Confidence Interval (CI) 1.37-16.76 and 3.43, 95% CI 1.20-9.83, respectively].Height >75th percentile and BMI ≥ 85th percentile were associated with increased risk of gastric NET (HR 2.25 95% CI 1.14-4.42 and HR 2.38, 95% CI 1.19-4.75, respectively). Female sex was associated with appendiceal NET (HR 2.30, 95% CI 1.06-4.96) while male gender was associated with an increased risk for NET of the small bowel [HR 4.72 (95% CI 1.10-20.41)].In conclusion, our findings suggest different risk factor associations with the various GEP-NETS: immigrants from the FSU were at increased risk for small bowel and rectal NET; increased height and weight were associated with the risk of gastric NET and females were at increased risk for appendiceal NET. Further focus on the FSU population is indicated in addition to studies verifying the association of BMI and height with gastric NET.

Summary Background Obesity has been established as a causal factor for several types of cancer, and adolescent obesity is increasing worldwide. We examined associations between measured body-mass index (BMI) at age 17 years and cancer incidence, and with mortality among those who developed cancer. Methods In a nationwide, population-based cohort of adolescents, height and weight were measured at pre-recruitment mandatory medical examination during 1967–2010. BMI was classified according to US Center for Disease Control and Prevention percentiles. We applied Cox proportional hazard models to estimate the hazard ratios (HRs) and 95% CIs for incident cases of cancer using the 5th–49th BMI percentile group as a reference. The primary outcome was any cancer diagnosis between Jan 1, 1967, and Dec 31, 2012, as recorded in the Israeli National Cancer Registry. Participants with a diagnosis of cancer at baseline (before military recruitment assessment) were excluded from this analysis. The secondary outcome of this study was all-cause mortality among cohort members who had cancer, between Jan 1, 1967, and Dec 31, 2017. Findings Of the 2 458 170 participants examined between Jan 1, 1967, and Dec 31, 2010, 160 040 were excluded. 2 298 130 participants of which 928 110 were women and 1 370 020 were men. During 29 542 735 person-years of follow-up in men, 26 353 incident cases of cancer were recorded and in 18 044 863 person-years of follow-up in women, 29 488 incident cases of cancer were recorded. Cancer incidence increased gradually across BMI percentiles. The adjusted HR was 1·26 (95% CI 1·18–1·35) among men with adolescent obesity. Among women, we found no association between obesity and overall cancer, driven by inverse associations of obesity with cervical and breast cancers. When these cancers were excluded, the adjusted HR for cancer was 1·27 (1·13–1·44) among women with adolescent obesity. In both sexes, high BMI (≥85th percentile) was associated with an increased cancer risk after 10 years. This association was accentuated in the late period of the cohort versus the early period of the cohort. BMI was positively associated with a higher risk of mortality. The projected population attributable risk for high BMI was 5·1% (4·2–6·1) for men and 5·7% (4·2–7·3) for women. Interpretation The increasing prevalence of adolescent obesity and the possible association between adolescent BMI and cancer incidence might increase the future burden of obesity-related cancers. BMI among adolescents could constitute an important intervention target for cancer prevention. Funding None.

Our aim was to report the prevalence of knee varus-valgus malalignment (KVVM) and its association with body mass index (BMI) and body height in a healthy and fit young adult population. Information on the disability codes associated with KVVM according to the Regulations of Medical Fitness Determination was retrieved from a medical database containing records of 17-year-old males and females before their recruitment into mandatory military service. Logistic regression models assessed the association between the BMI and body height to KVVM. The study cohort included 821,381 subjects (460,674 males and 360,707 females). The prevalence of KVVM was 0.9% in males and 0.6% for females. Under/overweight subjects were associated with higher prevalence of KVVM. The odds ratios (ORs) had a “J” curve pattern, increasing for underweight males and females, and even more so for above-normal BMIs (for obese males and for both overweight and obese females). The strongest association was between obese females and KVVM: an obese female had an OR of 22.864 (confidence interval [CI] = 20.683–25.725, p

The long-term risk associated with childhood kidney disease that had not progressed to chronic kidney disease in childhood is unclear. We aimed to estimate the risk of future end-stage renal disease (ESRD) among adolescents who had normal renal function and a history of childhood kidney disease.We conducted a nationwide, population-based, historical cohort study of 1,521,501 Israeli adolescents who were examined before compulsory military service in 1967 through 1997; data were linked to the Israeli ESRD registry. Kidney diseases in childhood included congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease; all participants included in the primary analysis had normal renal function and no hypertension in adolescence. Cox proportional-hazards models were used to estimate the hazard ratio for ESRD associated with a history of childhood kidney disease.During 30 years of follow-up, ESRD developed in 2490 persons. A history of any childhood kidney disease was associated with a hazard ratio for ESRD of 4.19 (95% confidence interval [CI], 3.52 to 4.99). The associations between each diagnosis of kidney disease in childhood (congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease) and the risk of ESRD in adulthood were similar in magnitude (multivariable-adjusted hazard ratios of 5.19 [95% CI, 3.41 to 7.90], 4.03 [95% CI, 3.16 to 5.14], and 3.85 [95% CI, 2.77 to 5.36], respectively). A history of kidney disease in childhood was associated with younger age at the onset of ESRD (hazard ratio for ESRD among adults40 years of age, 10.40 [95% CI, 7.96 to 13.59]).A history of clinically evident kidney disease in childhood, even if renal function was apparently normal in adolescence, was associated with a significantly increased risk of ESRD, which suggests that kidney injury or structural abnormality in childhood has long-term consequences.

BACKGROUND Influenza-related morbidity impacts healthcare systems, including hospitals. OBJECTIVE To obtain a quantitative assessment of hospitalization burden in pediatric and internal medicine departments during influenza seasons compared with the summer months in Israel. METHODS Data on pediatric and internal medicine hospitalized patients in general hospitals in Israel during the influenza seasons between 2005 and 2013 were analyzed for rate of hospitalizations, rate of hospitalization days, hospital length of stay (LOS), and bed occupancy and compared with the summer months. Data were analyzed for hospitalizations for all diagnoses, diagnoses of respiratory or cardiovascular disease (ICD9 390-519), and influenza or pneumonia (ICD9480-487), with data stratified by age. The 2009-2010 pandemic influenza season was excluded. RESULTS Rates of monthly hospitalizations and hospitalization days for all diagnoses were 4.8% and 8% higher, respectively, during influenza seasons as compared with the summers. The mean LOS per hospitalization for all diagnoses demonstrated a small increase during influenza seasons as compared with summer seasons. The excess hospitalizations and hospitalization days were especially noticed for the age groups under 1 year, 1-4 years, and 85 years and older. The differences were severalfold higher for patients with a diagnosis of respiratory or cardiovascular disease and influenza or pneumonia. Bed occupancy was higher during influenza seasons compared with the summer, particularly in pediatric departments. CONCLUSIONS Hospital burden in pediatric and internal medicine departments during influenza seasons in Israel was associated with age and diagnosis. These results are important for optimal preparedness for influenza seasons.

Immigration studies can shed light on diabetes pathogenesis and risk factors. To this end, we investigated the association between age at immigration and diabetes occurrence at adolescence among immigrants to Israel. We analysed cross-sectional data on 2,721,767 Jewish adolescents assessed for mandatory military service at approximately 17 years of age between 1967 and 2014. The study population comprised 430,176 immigrants with origins in Ethiopia, former USSR, Middle East and North Africa (ME/NA) and western countries. ORs for diabetes were calculated for men and women, grouped according to age at immigration, with Israel-born participants as controls. Unadjusted and fully adjusted models were made to account for possible confounders. Additionally, the study population was stratified by origin and each immigrant group was referenced to Israel-born participants of the same origin. There was a graded decrease in OR for diabetes across the study groups in the fully adjusted model. Immigrants arriving at age 0–5 years had comparable OR for diabetes to the Israeli-born reference group; those arriving at age 6–11 years had an OR of 0.82 (95% CI 0.70, 0.97; p = 0.017) and recent immigrants, arriving at age 12–19 years, had the lowest OR of 0.65 (95% CI 0.54, 0.77; p

In an attempt to address severe medical manpower shortages in several medical disciplines, the Israeli Ministry of Health offered grants to residents who chose one of these fields.A total of 220 residents from various disciplines were surveyed on demographic, academic, and professional data, and asked to rank considerations in the choice of their field of residency.Residents in targeted fields attributed significantly more importance to the grant in their decision-making process (U = 3704.5, p 0.001). This effect remained significant in a multivariate model (OR 1.67, 95%CI 1.32-2.10, p 0.001). Higher age (OR 1.15, 95%CI 1.01-1.31, p = 0.031) and attribution of significance to the working conditions compared to other residency fields (OR 1.69, 95%CI 1.23-2.32, p = 0.001) were significantly associated with receptivity toward the grant in a multivariate analysis.Receptivity toward the offered grants correlated with real-life data shows a rise in physician in these fields, and the weak association between such receptivity and most variables tested may suggest that the grants were perceived as a property of the specific choice rather than a special bonus.Grants may be useful in diverting medical manpower. Further analysis and modeling are required to determine causal relationship and budgetary feasibility.