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

Introduction: Traumatic long-bone fractures (TLFs) among children and adolescents are relatively common, with morbidity and economic consequences. Obesity has become a significant global concern. Studies have found an association between TLFs and BMI in the past but not in a large cross-sectional population study. Our study objective was to measure the incidence of TLFs in the 17-year-old general population and evaluate its association with BMI, body height, and gender. Methods: Data from a medical database containing all 17-year-old candidates’ records before recruitment into mandatory military service were retrieved as BMI, height, gender, and history of TLFs. Logistic regression models assessed the association between BMI and height to TLFs. Results: The records of 911,206 subjects (515,339 males) were reviewed. In total, 9.65% had a history of TLFs (12.25% and 6.25% for males/females, respectively). Higher BMI was associated with TLF, with a linear trend in the odds ratio (OR) for having TLFs. The strongest association was found between obese females and TLFs (OR = 1.364, p < 0.0001). Height was an independent factor positively associated with TLFs. The OR for a TLF in the highest height quintile was 1.238 (p < 0.001) for males and 1.411 (p < 0.001) for females compared to the lowest quintile. Although TLFs were more common in males, the OR for TLFs was more prominent in females. Conclusions: There is an association between BMI, body height, and TLFs in healthy adolescents. TLFs are more common in males, but the strongest association between overweight and obesity is evident in females.

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.

The immune responses of liver transplant (LT) recipients after the third boost of the BNT162b2mRNA vaccine improved. This study evaluates the durability of the immune response of LT recipients after the third boost, its predictors, and the impact of emerging variants. The receptor-binding domain IgG was determined at median times of 22 (first test) and 133 days (second test) after the administration of the third boost. IgG antibody titers > 21.4 BAU/mL were defined as a positive response. The neutralization efficacies of the vaccine against the wild-type, Omicron, and Delta variants were compared in the first test. The 59 LT recipients were of a median age of 61 years (range 25–82); 53.5% were male. Following administration of the third dose, the positive immune response decreased from 81.4% to 76.3% between the first and second tests, respectively, (p < 0.0001). The multivariate analysis identified CNI monotherapy (p = 0.02) and hemoglobin > 12 g/dL (p = 0.02) as independent predictors of a maintained positive immune response 133 days after the third dose. The geometric mean titers of Omicron neutralization were significantly lower than the wild-type and Delta virus (21, 137, 128, respectively; p < 0.0001). The immune response after the third BNT162b2mRNA vaccine dose decreased significantly in LT recipients. Further studies are required to evaluate the efficacy of the fourth vaccine dose and the durability of the immune response.

The application of myopia definition varies considerably within the literature. The purpose of this study was to examine the relationship between different myopia and high myopia definitions and resultant prevalence estimates. A population-based cross-sectional study of 1,588,508 Israeli adolescents assessed for medical fitness before mandatory military service at the age of 17 years between 1993 through 2015. Participants underwent non-cycloplegic autorefraction. Nine definitions of myopia and seven definitions of high myopia were examined. Prevalence estimates for each definition were calculated and compared with the reference definition (right eye spherical equivalent (SE)≤-0.50D and ≤-6.00D for myopia and high myopia, respectively), to yield a rate ratio (RR) across definitions. Applying the right eye SE≤-0.50D reference definition yielded 31.0% myopia prevalence. While some definitions resulted in similar prevalence estimates, using the right eye SE of ≤-0.75D; ≤-1.00D or least minus meridian of ≤-0.75D definitions yielded 28.8%, 26.3%, and 26.9% myopia prevalence, respectively, which corresponded to a 7.1%, 15.1% and 13.4% reduction in myopia RR, respectively. The prevalence of high myopia demonstrated considerable alternations, with a 1.7-fold increase in prevalence for the narrower threshold of SE≤-5.00D compared with SE≤-6.00D reference definition (4.2% and 2.4%, respectively). The prevalence of myopia and especially high myopia varies between frequently applied definitions, considering diverse thresholds, eye lateralization, and spherical vs. astigmatic refractive components. This variability highlights the pressing need for standardization of myopia definition in ophthalmic research. The results of this study provide crude estimates of a “conversion rate” across data, allowing comparisons between studies that utilize different myopia definitions.

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.

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. Methods: In a mother-offspring, historical cohort, the Israel military conscription dataset was linked to a large health maintenance organization. Included were women who were evaluated at adolescence and performed 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 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 Conclusions: Gestational glucose intolerance, including categories not meeting the gestational diabetes threshold, were associated with increased odds for offspring overweight/obesity at late adolescence. Disclosure C.D.Bendor: None. Y.Lebenthal: Advisory Panel; Lilly, Novo Nordisk, Research Support; Novo Nordisk, Pfizer Inc., Speaker's Bureau; Pfizer Inc. A.Afek: None. G.Chodick: None. G.Twig: None. A.Bardugo: None. R.Rotem: None. E.Derazne: None. H.C.Gerstein: Advisory Panel; Abbott, Eli Lilly and Company, Hanmi Pharm. Co., Ltd., Novo Nordisk, Pfizer Inc., Sanofi, Viatris Inc., Consultant; Kowa Company, Ltd., Other Relationship; DKSH, Eli Lilly and Company, Sanofi, Zuellig Pharma Holdings Pte. Ltd., Research Support; AstraZeneca, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi. D.Tzur: None. O.Pinhas-hamiel: Advisory Panel; Novo Nordisk, Speaker's Bureau; Pfizer Inc. A.M.Tsur: None. T.Cukierman-yaffe: Research Support; European Association for the Study of Diabetes, Medtronic, Merck Sharp & Dohme Corp., Novo Nordisk, Speaker's Bureau; AstraZeneca, Eli Lilly and Company, Medtronic, Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi.

Background: Studies in children reported an association between increased body mass index (BMI) and risk for developing type 1 diabetes (T1D) . We studied the association between adolescent BMI and incident T1D in young adulthood in a nationwide cohort of 1,462,362 adolescents which was recently used to assess the association between adolescent BMI and early-onset type 2 diabetes (Diabetes Care 2020 Jul;43 (7) :1487-1495) . Methods: All Israeli adolescents, ages 16-19, 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 dysglycemia. Data were linked to information about adult onset of T1D in the Israeli National Diabetes Registry. Weight and height were measured at the study entry. Cox proportional models were applied, with BMI analyzed both as a categorical and as a continuous variable. Islet autoantibody data were available for a subpopulation of the cohort. Results: There were 777 incident cases of T1D during 15,810,751 person-years (mean age at diagnosis 25.2±3.9 years) . BMI was associated with incident T1D. In a multivariable model adjusted for age, sex and socio-demographic variables, the hazard ratios (HRs) for T1D were 1. (95% CI 0.87-1.27) for the 50th-74th BMI percentiles, 1.41 (1.11-1.78) for the 75th-84th BMI percentiles, 1.54 (1.23-1.94) for adolescents with overweight (85th-94th percentiles) , and 2. (1.58-2.66) for adolescents with obesity (BMI≥95th percentile) . One increment in BMI standard deviation was associated with 25% greater risk for incidence of T1D (HR=1.25, 95%CI 1.17-1.32) . Association persisted when the definition of T1D included the presence of islet autoantibodies; when the study population was restricted to those with unimpaired health. Conclusions: Excessively high BMI in apparently healthy adolescents is associated with increased risk for incident T1D in early adulthood. Disclosure I.Zucker: None. D.Tzur: None. C.Melzer cohen: None. O.Pinhas-hamiel: Advisory Panel; Novo Nordisk, Speaker's Bureau; Pfizer Inc. G.Chodick: None. I.Raz: None. A.Afek: None. H.C.Gerstein: Advisory Panel; Abbott, Eli Lilly and Company, Hanmi Pharm. Co., Ltd., Novo Nordisk, Pfizer Inc., Sanofi, Viatris Inc., Consultant; Kowa Company, Ltd., Other Relationship; DKSH, Eli Lilly and Company, Sanofi, Zuellig Pharma Holdings Pte. Ltd., Research Support; AstraZeneca, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi. A.Tirosh: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Novo Nordisk, Sanofi, Consultant; Bayer AG, DreaMed Diabetes, Ltd., Research Support; Medtronic, Speaker's Bureau; Eli Lilly and Company. G.Twig: None. Y.Zloof: None. A.Bardugo: None. A.M.Tsur: None. M.Lutski: None. Y.Cohen: None. T.Cukierman-yaffe: Research Support; European Association for the Study of Diabetes, Medtronic, Merck Sharp & Dohme Corp., Novo Nordisk, Speaker's Bureau; AstraZeneca, Eli Lilly and Company, Medtronic, Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi. N.Minsky: None. E.Derazne: None. Funding This work was partially supported by an internal grant from the Israel Defense Forces Medical Corps.

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.

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.

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.

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.

ObjectiveTo identify COVID-19 work-related stressors and experiences associated with sleep difficulties in HCW, and to assess the role of depression and traumatic stress in this association.MethodsA cross-sectional study of HCW using self-report questionnaires, during the first peak of the pandemic in Israel (April 2020), conducted in a large tertiary medical center in Israel. Study population included 189 physicians and nurses working in designated COVID-19 wards and a comparison group of 643 HCW. Mean age of the total sample was 41.7 ± 11.1, 67% were female, 42.1% physicians, with overall mean number of years of professional experience 14.2 ± 20. The exposure was working in COVID-19 wards and related specific stressors and negative experiences. Primary outcome measurement was the Insomnia Severity Index (ISI). Secondary outcomes included the Primary Care-Post Traumatic Stress Disorder Screen (PC-PTSD-5); the Patient Health Questionnaire-9 (PHQ-9) for depression; the anxiety module of the Patient-Reported Outcomes Measurement Information System (PROMIS); Pandemic-Related Stress Factors (PRSF) and witnessing patient suffering and death.ResultsCompared with non-COVID-19 HCW, COVID-19 HCW were more likely to be male (41.3% vs. 30.7%) and younger (36.91 ± 8.81 vs. 43.14 ± 11.35 years). COVID-19 HCW reported higher prevalence of sleep difficulties: 63% vs. 50.7% in the non-COVID group (OR 1.62, 95% CI 1.15–2.29, p = 0.006), mostly difficulty maintaining sleep: 26.5% vs. 18.5% (OR 1.65, 95% CI 1.11–2.44, p = 0.012). Negative COVID-19 work-related experiences, specifically witnessing patient physical suffering and death, partially explained the association. Although past psychological problems and current depression and PTSD were associated with difficulty maintaining sleep, the main association remained robust also after controlling for those conditions in the full model.Conclusion and RelevanceCOVID-19 frontline HCW were more likely to report sleep difficulties, mainly difficulty maintaining sleep, as compared with non-COVID-19 HCW working at the same hospital. Negative patient-care related experiences likely mediated the increased probability for those difficulties. Future research is needed to elucidate the long-term trajectories of sleep difficulties among HCW during large scale outbreaks, and to identify risk factors for their persistence.

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.

Supplementary Material Supplementary table 1. The association between adolescent body mass index (BMI) and myopia for men– methodological sensitivity and subgroup analyses Supplementary table 2. The association between adolescent body mass index (BMI) and myopia for women– methodological sensitivity and subgroup analyses

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.

The immune response of liver transplant (LT) recipients to a third dose of the BNT162b2 mRNA vaccine significantly waned after four months. We aimed to evaluate the immune response and breakthrough infection rates of a fourth dose against the Omicron variants among LT recipients. LT recipients who had no past or active SARS-CoV-2 infection and received three doses of the BNT162b2mRNA vaccine were included. Of the 73 LT recipients, 50 (68.5%) received a fourth dose. The fourth dose was associated with a significantly higher positive immune response than the third dose. Receptor-binding domain (RBD) IgG and Omicron BA.1 and BA.2 neutralizing antibodies were determined at a median of 132 and 29 days after the third and fourth vaccines. They were 345 binding antibody units per milliliter (BAU/mL) vs. 2118 BAU/mL (p < 0.0001), 10 vs. 87 (p < 0.0001), and 15 vs. 149 (p = 0.001), respectively. Breakthrough infections were documented among nine (18%) LT recipients after the fourth dose and among seven (30.4%) patients following the third dose (p = 0.2); 93.5% of breakthrough infections were mild. The infection rate after the fourth dose was higher among diabetic vs. nondiabetic recipients (33.3% vs. 6.9%, respectively; p = 0.02). Further studies are needed to evaluate additional factors influencing the breakthrough infection rate among LT recipients.

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.

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 …

Background: Low back pain (LBP) is a widespread medical complaint affecting many people worldwide and costing billions. Studies suggest a link between LBP and joint hypermobility. This study aimed to examine the association between symptomatic joint hypermobility (SJH), LBP, and gender. Methods: Data were obtained from a medical database containing 17-year-old candidates’ records before recruitment into mandatory military service. According to the Regulations of Medical Fitness Determination, information on disability codes associated with LBP and SJH was retrieved. Results: According to this national survey, the prevalence of SJH is 0.11% (1355 cases out of 1,220,073 subjects). LBP was identified in 3.7% of the cohort (44,755 subjects). Subjects were further subdivided into LBP without objective findings (LBPWF) (3.5%) and LBP with objective findings (LBPOF) (0.2%). The association between SJH and LBP was examined: the Odds Ratio (OR) was 2.912 (p < 0.0001). The odds rations for LBPWF and LBPOF were further calculated to be 2.914 (p < 0.000) and 2.876 (p < 0.000), respectively. Subjects with SJH were almost three times more prone to LBPWF and LBPOF. Conclusion: SJH is strongly associated with LBP in young adults. Further pathophysiological research is needed.

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.