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Introduction Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common kidney diseases in childhood. Alterations in genes governing nephrogenesis may cause CAKUT, and in some cases may contribute to development of urinary tract (UT) tumors later in life. We aimed to assess the association between CAKUT and UT cancer in adulthood. Methods We conducted a population-based historical cohort study encompassing 1,510,042 recruits to the Israeli army between 1967 and 1997. CAKUT exposure was determined by army medical coding of CAKUT in childhood. Incidence of UT cancer (kidney, ureter, or bladder) was available through record linkage with the Israeli Cancer Registry. Recruits were followed from the prerecruitment assessment until cancer diagnosis, death, or study termination, in 2012. Cox proportional hazards models were constructed to estimate the hazard ratios (HRs) for UT cancer in participants with vs. without CAKUT. Results During a mean follow-up of 30.4 years, 2959 participants (2573 men and 386 women) developed UT cancer. Men with CAKUT exhibited an increased risk of UT cancer compared with men without CAKUT, yielding an adjusted HR of 1.98 (95% confidence interval [CI] 1.03-3.82). Among women CAKUT was associated with a HR of 5.88 (95% CI 2.19-15.76). Notably, upon stratification according to age of cancer diagnosis, the association between CAKUT and UT cancer was statistically significant only before 45 years of age in women and only after 45 years of age in men. Conclusion CAKUT is associated with a significantly increased risk of UT cancer, although the incidence and absolute risk remained quite low., Graphical abstract

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.

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.

Pyelonephritis is the most common serious bacterial infection during childhood. The long-term importance of kidney scarring is unclear. To assess the risk of end-stage kidney disease (ESKD) in adolescents and young adults with history of pyelonephritis. A nationwide, population-based, historical cohort study, including 1,509,902 persons (62% male) examined for military service between 1967 and 1997. Participants with a history of pyelonephritis were sub-grouped according to presence of kidney scarring and baseline kidney function. Data were linked to the Israeli ESKD registry to identify incident ESKD cases. Cox proportional hazards models were used to estimate the hazard ratio (HR) of treated ESKD (dialysis or kidney transplant). Pyelonephritis was diagnosed in 6979 participants (0.46%). 6479 had normal kidney function and no evidence of kidney scarring, 400 had normal kidney function with evidence of scarring, and 100 demonstrated reduced baseline kidney function. Treated ESKD developed in 2352 individuals (0.2%) without history of pyelonephritis, 58 individuals (0.9%) with normal kidney function, history of pyelonephritis and no kidney scarring, 14 individuals (3.5%) with normal kidney function, history of pyelonephritis and kidney scarring, and 23 individuals (23.0%) with history of pyelonephritis and reduced baseline kidney function, yielding HR of 3.3, 34.8 and 43.2, respectively, controlling for age, gender, paternal origin, enrollment year, body mass index, and blood pressure, and accounting for death as a competing risk. History of pyelonephritis was associated with significantly increased risk of treated ESKD, particularly when associated with kidney scarring or reduced baseline kidney function.

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, P < 0.05). 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.

Purpose Immigration studies can shed light on myopia development and reveal high-risk populations. To this end, we investigated the association among immigration, age at immigration, and myopia occurrence during adolescence. Design Population-based, retrospective, cross-sectional study. Participants Six hundred seven thousand eight hundred sixty-two adolescents, Israeli born and immigrants, with origins in the former Union of Soviet Socialist Republics (USSR), Ethiopia, or Israel, assessed for medical fitness for mandatory military service at 17 years of age between 1993 and 2016. Methods Myopia and high myopia were defined based on right eye refractive data. Age at immigration was categorized into 0 to 5 years of age, 6 to 11 years of age, and 12 to 19 years of age. Univariate and multivariate logistic regression models were created. Myopia odds ratios (ORs) were calculated according to immigration status, with Israeli-born natives as controls. Next, myopia ORs were calculated according to age at immigration, with Israeli-born of same origin as controls. Main Outcome Measures Myopia prevalence and ORs. Results Myopia was less prevalent among immigrants than Israeli-born controls. When stratified according to age at immigration, a decrease in myopia prevalence and ORs with increasing age at migration were observed, most prominent in immigrants arriving after 11 years of age, who also showed lower high-myopia ORs. The immigrants from the USSR and Ethiopia arriving after 11 years of age showed a myopia OR of 0.65 (95% confidence interval [CI], 0.63–0.67; P Conclusions Immigrants arriving after 11 years of age showed markedly lower ORs for myopia and high myopia relative to Israeli-born controls or those arriving during early childhood, likely because of environmental and lifestyle changes. Differences between immigrants arriving up to 5 years of age and those arriving between 6 and 11 years of age were relatively smaller, suggesting exposures at elementary school age play a greater role in this population.

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.

Background Cognitive function among apparently healthy adolescents has been associated with cardiovascular morbidity and mortality. We examined the relationship between global and subdomain cognitive scores in adolescence and early-onset type 2 diabetes (T2D) in men and women. Methods A nationwide, population-based study of 971,677 Israeli born adolescents (56% men; mean age 17.4 years) who were medically examined and their cognitive performance was assessed before compulsory military service during 1992–2010. Data included global and subdomain cognitive Z-scores (problem-solving, verbal abstraction and categorization, verbal comprehension, and mathematical abilities). Data were linked to the Israeli National Diabetes Registry. The relations between global and subdomain scores and incident T2D was determined using Cox proportional hazard models and logistic regression models. Analyses were conducted separately for men and women. Findings During 16,095,122 person-years, 3,570 individuals developed T2D. After adjustment, those in the low compared to the high quintile of global cognitive Z-score had the highest risk for T2D; HR 2.46, (95% CI 2.10–2.88) for men and 2.33 (95% CI 1.88–2.89) for women. A one-unit lower global cognitive Z-score was associated with 1.41 (95% CI 1.34–1.48) and 1.46 (95% CI 1.36–1.56) increased risks for men and women, respectively. The relationship was noted for the cognitive subdomains scores as well as for the global cognitive score, with no heterogeneity across cognitive subdomains. Interpretation This large nationally representative cohort suggests relationship between global, as well as subdomain cognitive scores in late adolescence, and incident early onset T2D in both sexes, which was independent of socioeconomic status. Funding None.

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.

Background: BNT162b2 was shown to be 92% effective in preventing COVID-19. Prioritizing vaccine rollout, and achievement of herd immunity depend on SARS-CoV-2 transmission reduction. The vaccine's effect on infectivity is thus a critical priority. Methods: Among all 9650 HCW of a large tertiary medical center in Israel, we calculated the prevalence of positive SARS-CoV-2 qRT-PCR cases with asymptomatic presentation, tested following known or presumed exposure and the infectious subset (N-gene-Ct-value

The incidence of adolescent hypertension is growing worldwide, mostly in conjunction with the growing obesity prevalence (1,2). Adolescent hypertension was shown to be a risk factor for cardiovascular and renal outcomes later in life, thus promoting current guidelines to screen all pediatric and adolescent population for hypertension (1,3). Here, we elucidate the association of adolescent hypertension and early-onset type 2 diabetes in a nationwide cohort of adolescents. In this population-based, retrospective cohort study we linked the Israeli Defense Forces conscription center database with the Israeli National Diabetes Registry (INDR). One year prior to mandatory military service at age 17 years, Israeli adolescents undergo comprehensive medical evaluation based on their medical history, an interview and physical examination that includes measurements of height, weight, and blood pressure. Included were adolescents who were examined between 1 January 1993 and 31 December 2016. Excluded were those with prior diagnosis of dysglycemia and those with missing baseline height or weight data (3.8% in total). Essential hypertension diagnosis was confirmed by a board-specified nephrologist based on a preexisting diagnosis or screening for hypertension as described previously (1). Briefly, adolescents with blood pressure measurement during the screening assessment of >140/90 mmHg were referred for further investigation. The final diagnosis was made when the average of 10 additional outpatient blood pressure measurements was >140/90 mmHg, when at least 50% of the measurements were above this level, and after exclusion of secondary hypertension. The primary outcome was incident type 2 diabetes as documented by the INDR, which captures all cases of diabetes in Israel with a sensitivity of 95.1% (2). Cox models were applied. Follow-up started at the day of the first medical examination and ended at the date of diabetes diagnosis, 31 December 2016, or death—whichever came first. Due to the previously described …

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.

Background/objectives It is unclear whether adolescent obesity is associated with limited linear growth. We assessed this association in a nationwide sample of adolescents. Methods We conducted a population-based, study of 2,785,227 Israeli adolescents (60% males) who were examined before military service since 1967 through 2015. Height and weight were measured along with assessment of medical status at age 17.4 ± 0.4 years. The secular trend of height was plotted using United States Center for Disease Control (US CDC) age- and sex-adjusted BMI percentile groups. We accounted for health status at enrollment and computed the expected height based on parental data that was available for 512,978 examinees. Results Over five decades, the mean height increased by 3.1 cm among males, but remained unchanged among females. Among males, gain in height was attained predominantly during the first 25 years and has stabilized since. Males with obesity were taller than their normal-weight and underweight counterparts. Underweight girls had a prominent increase in mean height during the first two decades, exceeding the mean height of their counterparts with obesity by over 2 cm. There was a gradual decrease in the difference between measured and expected height in males and females regardless of BMI status, with the exception of the underweight females who achieved consistently higher stature than expected (≥3 cm). Conclusions During five decades, excessive BMI was not a limiting factor in growth potential compared with normal BMI in both sexes. The only group that exceeded its growth potential, when accounting for expected mid-parental height, were underweight females with unimpaired health.

BACKGROUND There is growing concern regarding the impact of adolescent obesity on adult health. The objective of this study was to evaluate the association between body mass index (BMI) in late adolescence and the incidence of pancreatic cancer during adulthood. METHODS The authors analyzed a cohort of 1087,358 Israeli Jewish men and 707,212 Jewish women who underwent a compulsory physical examination between ages 16 and 19 years from 1967 to 2002. Pancreatic cancer incidence through December 31, 2012 was identified by linkage to the national cancer registry. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) for pancreatic cancer according to the US Centers for Disease Control and Prevention (CDC) BMI percentiles at baseline. RESULTS Over a median 23 year follow-up, 551 incident cases of pancreatic cancer cases occurred (423 men; 128 women). Compared with normal weight (5th to

Haifa Bay Area (HBA) contains Israel’s principal industrial area, and there are substantial public concerns about health effects from its emissions. We aimed to examine associations between exposure to air pollution from HBA industrial area with prevalent asthma and other atopic diseases at age 17. This is a cross-sectional study. The study population included all adolescents born in Israel and whose medical status was evaluated for mandatory military recruitment by the Israeli medical corps during 1967–2017. We analyzed prevalent asthma, allergic rhinitis, atopic dermatitis, and rhinoconjunctivitis. We estimated exposure to industrial air pollution by a kriging interpolation of historical SO2 observations and adjusted the associations to the year of birth, SES, school orientation, and traffic pollution. The study population included n = 2,523,745 adolescents, among which 5.9% had prevalent asthma and 4.6% had allergic rhinitis. Residency in HBA was associated with a higher adjusted risk of asthma, compared with non-HBA residency. Still, this association was limited to the three lowest exposure categories, while the highest exposure group had the lowest adjusted risk. Sensitivity analyses and other atopic diseases presented similar results. These results do not provide support for causal relationships between HBA industry-related emissions and prevalent atopic diseases.

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: BNT162b2 was shown to be 92% effective in preventing COVID-19. Prioritizing vaccine rollout, and achievement of herd immunity depend on SARS-CoV-2 transmission reduction. The vaccine’s effect on infectivity is thus a critical priority. Methods: In a cohort of all 9650 HCW of a large single tertiary medical center, we calculated the prevalence of positive SAR-CoV-2 qRT-PCR cases with an asymptomatic presentation, tested following known or presumed exposure and the infectious subset (N-gene-Ct-value

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.

Introduction Tobacco smoking has detrimental medical effects. However, whether late-adolescence tobacco smoking increases early mortality risk is unclear. The aim of our study was to determine the association between tobacco smoking among Israeli adolescents and mortality in young adulthood. Methods The Israeli Defense Forces (IDF) health survey enrolls annually random sample of 3–5% of IDF recruits who voluntarily report lifestyle and tobacco consumption habits (up to 10 cigarettes a day were defined as light smokers, 10–20 cigarettes a day and above 20 cigarettes a day as medium and heavy smokers respectively). Medical and sociodemographic variables (education, residential socioeconomic status, country of birth or origin) were included. Included in this study were 62,134 soldiers (56% men; average age 17.3 years) who enrolled in the study between 1981 and 2006. Data from the Israeli Ministry of Interior was obtained by linkage. Follow-up terminated at the earliest of December 31st 2018 or death. Cox proportional hazard models were applied. Results There were 42,013 (67.6%) never smokers, 2,108 (3.4%) past smokers, 6,886 (11.1%) light, 9,880 (15.9%) medium and 1,247 (2%) heavy smokers. During 1,348,517 person-years, 548 deaths were recorded (327 were never smokers, and 18,54,121 and 28 were past, light, medium and heavy smokers, respectively; mean age 31.3 years). The hazard ratios for all-cause mortality were 0.98 (0.61–1.58), 1.02 (0.76–1.36), 1.32 (1.06–1.64) and 1.53 (1.03–2.30) for past smokers, light, medium and heavy smokers, respectively, after adjustment for age, gender, BMI, enrollment year, education and intelligence score. There was no sex-specific association and mortality risk among heavy smokers persisted even when the outcome was set as death by the age of 30 years. Conclusion Late-adolescent smoking is associated with long-term all-cause mortality. A dose-response relationship was demonstrated between number of cigarettes consumed at the age of 17 and the future risk of death. Kaplan-Meier Plot Funding Acknowledgement Type of funding source: None

Background: While focusing on the management and care of COVID-19 patients, the mental health of these patients and their relatives is being overlooked. The aim of the current study was to measure anxiety and depression, and to assess their association with socio-demographic and pandemic-related stress factors in COVID-19 patients and their relatives during the initial stage of hospitalization. Methods: We assessed isolated hospitalized patients (N = 90) and their relatives (adults and children, N = 125) by phone, 25-72 h following patients' admission. The quantitative measures included the Anxiety and Depression modules of the Patient-Reported Outcomes Measurement Information System (PROMIS) and pandemic-related stress factors. Qualitative measures included questions exploring worries, sadness, and coping modes. Results: Both patients and relatives suffer from high levels of anxiety and related pandemic worries, with lower levels of depressive symptoms. Compared to adult relatives, child relatives reported significantly lower anxiety. The multivariable logistic regression analysis revealed an increased risk for anxiety among females and a decreased risk among ultra-orthodox participants. While increased anxiety among patients was associated with feelings of isolation, increased anxiety among relatives was associated with a feeling of not being protected by the hospital. Conclusions: Patients and relatives experience similar high anxiety levels which are more robust in women and lower in ultra-orthodox participants. Our findings indicate that anxiety symptoms of both patients and adult relatives should be addressed.

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.

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