Stuttering in adolescence and the risk for dysglycemia in early adulthood.

AIMS: To investigate the association between stuttering during adolescence and the onset of dysglycemia (prediabetes or type 2 diabetes) in early adulthood among men and women. MATERIALS AND METHODS: This cohort study included Maccabi Health Services members assessed for mandatory military service at ages 16-19 during 1990-2019 and followed until 31 December 2020. Stuttering status was recorded in the baseline medical evaluation. Incident cases of dysglycemia were identified systematically using prediabetes and diabetes registries. Cox proportional hazard models were applied for men and women separately, adjusting for sociodemographics and medical status. RESULTS: The study cohort comprised 866,304 individuals (55% men; 0.21% with stuttering) followed for a total of 12,696,250 person-years. During the study period, 7.6% (n = 36,603) of men and 9.0% (n = 34,723) of women were diagnosed with dysglycemia. The mean ages at diagnosis were 34 and 32 years for men and women, respectively. Women with stuttering exhibited the highest dysglycemia incidence rate (102.3 per 10,000 person-years) compared with the other groups (61.4, 69.0, and 51.9 per 10,000 person-years for women without stuttering, men with stuttering, and men without stuttering, respectively). For both men and women, those with stuttering showed an increased risk of being diagnosed with dysglycemia compared with those without (adjusted hazard ratios 1.18 [1.01-1.38] and 1.61 [1.15-2.26], respectively). The associations persisted in extensive sub-analyses. CONCLUSIONS: Stuttering in adolescence is associated with a higher risk of dysglycemia in early adulthood for men and women. Screening and targeted prevention in this population, especially women, may be beneficial.

Blepharoptosis and cognitive performance: a population-based study of 1.4 million adolescents.

The purpose of this study is to examine the association between blepharoptosis and cognitive performance in late adolescence. This population-based, retrospective, cross-sectional study included 1,411,570 Israeli-born adolescents (620,107 women, 43.9%) aged 16-19 years who were medically examined before compulsory military service between 1993 and 2017. The diagnosis of blepharoptosis was verified by an ophthalmologist. Cognitive performance was assessed by a validated intelligence-quotient-equivalent test, comprising four domains (problem-solving, verbal abstraction and categorization, verbal comprehension, and mathematical abilities). Cognitive Z-scores were calculated and categorized as high (≥ 1 standard deviation (SD)), medium (- 1 to < 1 SD), and low (less than - 1 SD). Relationships were analyzed using regression models adjusted for sociodemographic variables including sex, year of birth, residential socioeconomic status, education level, body mass index, and familial country of origin. A total of 577 (41 per 100,000, 32.2% women) adolescents were diagnosed with blepharoptosis. The proportions of unilateral and bilateral visual impairment among adolescents with blepharoptosis were 13.0% and 3.5%, respectively. In a multivariable analysis, blepharoptosis was associated with a 0.18 SD reduction in cognitive Z-score (p < 0.001). The adjusted odds ratios for low and high cognitive Z-scores in adolescents with blepharoptosis were 1.54 (1.25-1.89) and 0.80 (0.62-1.04), respectively. This relationship persisted when adolescents with normal best-corrected visual acuity or unimpaired health status were analyzed separately.  Conclusions: Blepharoptosis is associated with reduced cognitive performance determined in late adolescence. Future prospective studies should investigate the causes of this link and their underlying mechanisms. What is Known: • While earlier investigations have examined the effects of blepharoptosis on vision and quality of life, the association between blepharoptosis and cognitive outcomes in youth has remained unexplored. What is New: • This nationwide study involving 1.4 million Israeli adolescents found a correlation between blepharoptosis and reduced cognitive performance. • Our findings suggest a potential interplay between blepharoptosis and cognitive development in the pediatric population, calling for increased focus on the educational needs of affected individuals.

Visual impairment and cognitive performance: A nationwide study of 1.4 million adolescents.

PURPOSE: Previous research highlights the adverse effects of visual impairment (VI) on academic achievement in children, yet its impact on cognitive performance among adolescents and young adults remains under-studied. Therefore, this investigation aimed to analyse this association in a nationwide sample of Israeli adolescents. METHODS: A retrospective population-based cross-sectional study was conducted among 1,410,616 Israeli-born adolescents aged 16-19 years, who were assessed before mandatory military service between 1993 and 2017. The definition of VI was based on best-corrected visual acuity (BCVA) measurements using a standard Snellen chart. Adolescents with BCVA worse than 6/9 in either or both eyes were classified as having unilateral or bilateral VI, respectively. Cognitive performance was measured using the General Intelligence Score (GIS), based on a validated four-domain test. Relationships were analysed using regression models yielding adjusted odds ratios (ORs) for low (<-1 standard deviation [SD]) and high (≥1 SD) cognitive Z-scores. RESULTS: Of 1,410,616 adolescents (56.1% men), 13,773 (1.0%) had unilateral and 3980 (0.3%) had bilateral VI. Unilateral VI was associated with adjusted ORs for low and high cognitive Z-scores of 1.24 (1.19-1.30) and 0.84 (0.80-0.89), respectively. ORs were accentuated for bilateral VI, reaching 1.62 (1.50-1.75) and 0.81 (0.74-0.90) for low and high cognitive Z-scores, respectively. Cognitive performance subscores mirrored these results, with the visual-spatial functioning subtest demonstrating the greatest effect size. These associations persisted in sub-analyses restricted to adolescents with amblyopia-related VI, mild VI and unimpaired health status. CONCLUSIONS: Visual impairment, including mild and unilateral cases, is associated with reduced cognitive performance scores assessed in late adolescence. Further research is required to gain a comprehensive understanding of the dynamics underlying this relationship.

[MEDICAL EDUCATION IN THE 21ST CENTURY - "BACK TO THE FUTURE"].

INTRODUCTION: The change in the world of medicine and in the future generation of doctors, also requires the world of medical education and training to change, so that we do not find ourselves extinct like the dinosaurs. As Charles Darwin famously once said, "It is not the strongest of the species that survive, nor the most intelligent, but the one most adaptable to change".

Adolescent Hypertension Is Associated With Stroke in Young Adulthood: A Nationwide Cohort of 1.9 Million Adolescents.

BACKGROUND: Adult hypertension is a well-established risk factor for stroke in young adults (aged <55 years), and the effects are even more deleterious than at an older age. However, data are limited regarding the association between adolescent hypertension and the risk of stroke in young adulthood. METHODS: A nationwide, retrospective cohort study of adolescents (aged 16-19 years) who were medically evaluated before compulsory military service in Israel during 1985 to 2013. For each candidate for service, hypertension was designated after constructed screening, and the diagnosis was confirmed through a comprehensive workup process. The primary outcome was ischemic and hemorrhagic stroke incidence as registered at the national stroke registry. Cox proportional-hazards models were used. We conducted sensitivity analyses by excluding people with a diabetes diagnosis at adolescence or a new diabetes diagnosis during the follow-up period, analysis of adolescents with overweight, and adolescents with baseline unimpaired health status. RESULTS: The final sample included 1 900 384 adolescents (58% men; median age, 17.3 years). In total, 1474 (0.08%) incidences of stroke (1236 [84%] ischemic) were recorded, at a median age of 43 (interquartile range, 38-47) years. Of these, 18 (0.35%) occurred among the 5221 people with a history of adolescent hypertension. The latter population had a hazard ratio of 2.4 (95% CI, 1.5-3.9) for incident stroke after adjustment for body mass index and baseline sociodemographic factors. Further adjustment for diabetes status yielded a hazard ratio of 2.1 (1.3-3.5). We found similar results when the outcome was ischemic stroke with a hazard ratio of 2.0 (1.2-3.5). Sensitivity analyses for overall stroke, and ischemic stroke only, yielded consistent findings. CONCLUSIONS: Adolescent hypertension is associated with an increased risk of stroke, particularly ischemic stroke, in young adulthood.

High BMI and the risk for incident type 1 Diabetes Mellitus: a systematic review and meta-analysis of aggregated cohort studies.

BACKGROUND: There is uncertainty regarding the role of obesity in type 1 diabetes development. The aim of this systematic review and meta-analysis was to collect and synthesize evidence regarding BMI and the risk of developing type 1 diabetes. METHODS: A systematic review and meta-analysis were conducted to assess the association between BMI and incident type 1 diabetes. Databases were searched up to June 2022. Cohort studies were included reporting the association between overweight and/or obesity, as measured by BMI after age 2 years, with incident type 1 diabetes. Independent reviewers extracted data and assessed study quality. Risk estimates were pooled using a random-effects model. RESULTS: Ten cohort studies met the inclusion criteria. The seven studies that classified BMI into categories were of high quality and involved 1,690,660 individuals and 1979 incident type 1 diabetes cases. The pooled risk ratio (RR) for type 1 diabetes was 1.35 (95% CI 0.93-1.97) among people with overweight (3 studies); 2.17 (95% CI 1.75-2.69) among people with obesity (5 studies); and 1·87 (95% CI 1.52-2.29) among people with overweight/obesity (two studies merged the categories). These point estimates persisted in sensitivity analyses that addressed the duration of follow-up, variability in baseline risk for incident type 1 diabetes, and potential misclassifications related to exposure or outcome definitions. People with overweight/obesity had a 2.55 (95% CI 1.11-5.86) greater risk for incident type 1 diabetes with positive islet autoantibodies. CONCLUSION: This systematic review and meta-analysis of high-quality observational cohort studies indicated an association between high BMI and the risk of type 1 diabetes, in a graded manner.

Body mass index and migraine in adolescence: A nationwide study.

BACKGROUND: The association between body mass index (BMI) and migraine in adults has been well established. However, studies in children and adolescents are inconclusive. We aimed to study the association between BMI and migraine using a national dataset that comprises the electronic medical records of more than two million adolescents. METHODS: This study included all Israeli adolescents (57.7% males, 42.3% females; mean age 17 years) who were medically assessed before mandatory military service during 1990-2020. As part of the pre-recruitment medical assessment, all the adolescents were screened for migraine and their height and weight were measured. Diagnoses of migraine were confirmed by board-certified neurologists. Prevalences and odds ratios (ORs) for migraine were computed across BMI subgroups. Spline models were applied. RESULTS: A total of 2,094,862 adolescents were included, of whom 57,385 (2.8%) had active migraine. Among males, the adjusted ORs for migraine were 1.11 (95% confidence interval, 1.06-1.16), 1.13 (1.08-1.17), and 1.24 (1.19-1.30), for the underweight, overweight, and obesity subgroups, respectively, compared to the reference group of low-normal BMI (5th-49th percentile). Among females, the respective adjusted ORs were 1.12 (1.05-1.19), 1.23 (1.19-1.28), and 1.38 (1.31-1.46). Results persisted in sensitivity analyses accounting for other medical and psychiatric comorbidities and parental history of migraine. Spline models demonstrated a J-shaped relation between BMI and migraine. CONCLUSIONS: Both adolescent obesity and underweight were associated with migraine in a sex-dependent manner. This association peaked in female adolescents with overweight and obesity.

BNT162b2-vaccine-induced neutralization responses are immune correlates of clinical protection against SARS-CoV-2 in heart transplant recipients.

BACKGROUND: Defining immune correlates of protection against COVID-19 is pivotal for optimizing the use of COVID-19 vaccines, predicting the impact of novel variants on clinical outcomes, and advancing the development of immunotherapies and next-generation vaccines. We aimed to identify vaccine-induced immune correlates of protection against COVID-19-related hospitalizations in a highly vaccinated heart transplant (HT) cohort. METHODS: In a case-control study of HT recipients vaccinated with the BNT162b2 vaccine, patients were prospectively assessed for vaccine-induced neutralization of the wild-type virus, and the Delta and Omicron BA.1, BA.2, BA.4, and BA.5 variants. Comparative analyses with controls were conducted to identify correlates of protection against COVID-19 hospitalization. ROC analyses were performed. Primary outcomes were COVID-19 hospitalizations and severity of SARS-CoV-2 breakthrough infection. RESULTS: The study cohort comprised 59 HT recipients aged 58 (49,65) years with breakthrough infections after three or four monovalent BNT162b2 doses; 41 (69.5%) were men. Thirty-six (61%) patients with COVID-19 were hospitalized; most cases were non-severe (58, 98%). For hospitalized (vs. non-hospitalized) COVID-19 patients, vaccine-induced neutralization titers were significantly lower against all SARS-CoV-2 variants (p < .005). Vaccine-induced neutralization of the wild-type virus and delta and omicron BA.1, BA.2, BA.4, and BA.5 variants was associated with a reduced risk for COVID-19-related hospitalization. The optimal neutralization titer thresholds that were predictive of COVID-19 hospitalizations were 96 (wild-type), 48 (delta), 12 (BA.1), 96 (BA.2), 96 (BA.4), and 48 (BA.5). CONCLUSIONS: BNT162b2-vaccine-induced neutralization responses are immune correlates of protection and confer clinical protection against COVID-19 hospitalizations.

The effects of Covid-19 mRNA vaccine on adolescence gynecological well-being.

KEY MESSAGE: Menstruation of adolescent girls might be influenced by Covid-19 mRNA vaccine, however, the ovarian reserve estimated by AMH is not compromised. BACKGROUND: Recent studies have suggested that the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine causes menstrual abnormalities which led to concerns regarding its influence on the reproductive system. This study aims to investigate the influence of the SARS-CoV-2 mRNA vaccine on gynecologic well-being and future fertility of adolescent girls. METHODS: This is a prospective cohort study conducted at a university affiliated medical center between June and July 2021. Adolescent girls aged 12-16 years who were vaccinated by two Pfizer-BioNTech Covid-19 vaccines (21 days apart) were included in the study. All participants completed a computerized questionnaire regarding their general medical and gynecological background at recruitment and 3 months later. Blood samples were collected for AMH levels before and 3 months following the first mRNA vaccine RESULTS: The study group consisted of 35 girls, and of them, follow-up was completed by questionnaire and AMH sampling in 35 (90%) and 22 (56%) girls, respectively. Among the 22/35 girls who reported regular menstruation before vaccination, seven (31.8%) experienced irregularities post-vaccination. Four of the eight pre-menarche girls included in the study reported on menarche on follow-up. Median AMH levels were 3.09 (IQR 1.96-4.82) µg/L and 2.96 (2.21-4.73) µg/L at baseline and after 3 months, respectively (p = 0.07). After controlling for age, BMI and presentation of side effects, no association was demonstrated to the change in AMH levels (AMH2-AMH1). CONCLUSIONS: Although menstruation of adolescent girls might be influenced by Covid-19 mRNA vaccine, it seems that the ovarian reserve estimated by AMH is not compromised. CLINICAL TRIAL REGISTRATION: National Institutes of Health (NCT04748172).

Obesity in late adolescence and incident type 1 diabetes in young adulthood.

AIMS/HYPOTHESIS: Studies in children have reported an association between increased BMI and risk for developing type 1 diabetes, but evidence in late adolescence is limited. We studied the association between BMI in late adolescence and incident type 1 diabetes in young adulthood. METHODS: All Israeli adolescents, ages 16-19 years, undergoing medical evaluation in preparation for mandatory military conscription between January 1996 and December 2016 were included for analysis unless they had a history of dysglycaemia. Data were linked with information about adult onset of type 1 diabetes in the Israeli National Diabetes Registry. Weight and height were measured at study entry. Cox proportional models were applied, with BMI being analysed both as a categorical and as a continuous variable. RESULTS: There were 777 incident cases of type 1 diabetes during 15,819,750 person-years (mean age at diagnosis 25.2±3.9 years). BMI was associated with incident type 1 diabetes. In a multivariable model adjusted for age, sex and sociodemographic variables, the HRs for type 1 diabetes were 1.05 (95% CI 0.87, 1.27) for the 50th-74th BMI percentiles, 1.41 (95% CI 1.11, 1.78) for the 75th-84th BMI percentiles, 1.54 (95% CI 1.23, 1.94) for adolescents who were overweight (85th-94th percentiles), and 2.05 (95% CI 1.58, 2.66) for adolescents with obesity (≥95th percentile) (reference group: 5th-49th BMI percentiles). One increment in BMI SD was associated with a 25% greater risk for incidence of type 1 diabetes (HR 1.25, 95% CI 1.17, 1.32). CONCLUSIONS: Excessively high BMI in otherwise healthy adolescents is associated with increased risk for incident type 1 diabetes in early adulthood.

A third dose of the BNT162b2 mRNA vaccine significantly improves immune responses among liver transplant recipients.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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. LAY SUMMARY: 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.

Personality disorders and cause-specific mortality: a nationwide study of 2 million adolescents.

BACKGROUND: Personality 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. METHODS: We 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. RESULTS: The 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. CONCLUSIONS: Personality 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.

Childhood Cancer and the Risk of ESKD.

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.

Gender bias in the evaluation of interns in different medical specialties: An archival study.

INTRODUCTION: The field of medicine is characterized by within-field gender segregation: Gender ratios vary systematically by subdisciplines. This segregation might be, in part, due to gender bias in the assessment of women and men medical doctors. METHODS: We examined whether the assessments, i.e. overall score, department scores and skills scores, interns receive by their superiors during their internship year, vary as a function of their gender and the representation of women in the field. We analyzed an archival data set from a large hospital in Israel which included 3326 assessments that were given to all interns who completed their internship year between 2015 and 2019. RESULTS: Women received lower department scores and skills scores in fields with a low (versus high) representation of women. Men received higher scores in fields with a high (versus low) representation of men, yet there was no difference in their skills scores. CONCLUSIONS: Women are evaluated more negatively in fields with a low representation of women doctors. Similarly, men are evaluated more negatively in fields with a low representation of men, yet this cannot be explained by their skills. This pattern of results might point to a gender bias in assessments. A better understanding of these differences is important as assessments affect interns' career choices and options.

In-thrombus thrombin secretion: a new diagnostic marker of atrial fibrillation in cryptogenic stroke.

Endovascularly retrieved clots may be a potential resource for diagnosing stroke etiology. This method may influence secondary prevention treatment. We measure thrombin activity eluted by serially washing clots. We concluded that an 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.

Orthopaedic residents' autonomy in hip fracture surgery: what is the effect on patient outcomes?

BACKGROUND: 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. METHODS: 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. RESULTS: 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 < 0.001). CONCLUSION: The current study demonstrates that hip fracture surgery performed by adequately trained orthopaedic surgery residents can provide similar results to surgery performed by fellowship-trained attendings. LEVEL OF EVIDENCE: Level III-retrospective cohort study.

Body Mass Index in 1.9 Million Adolescents and Stroke in Young Adulthood.

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, 1.2­1.6), 2.0 (95% CI, 1.6­2.4), and 3.4 (95% CI, 2.7­4.3) 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 (1.1­1.5), 1.6 (1.3­2.0), and 2.4 (1.9­3.1). 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.

History of Childhood Kidney Disease and Risk of Adult End-Stage Renal Disease.

BACKGROUND: The long-term risk associated with childhood kidney disease that had not progressed to chronic kidney disease in childhood is unclear. We aimed to estimate the risk of future end-stage renal disease (ESRD) among adolescents who had normal renal function and a history of childhood kidney disease. METHODS: We conducted a nationwide, population-based, historical cohort study of 1,521,501 Israeli adolescents who were examined before compulsory military service in 1967 through 1997; data were linked to the Israeli ESRD registry. Kidney diseases in childhood included congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease; all participants included in the primary analysis had normal renal function and no hypertension in adolescence. Cox proportional-hazards models were used to estimate the hazard ratio for ESRD associated with a history of childhood kidney disease. RESULTS: During 30 years of follow-up, ESRD developed in 2490 persons. A history of any childhood kidney disease was associated with a hazard ratio for ESRD of 4.19 (95% confidence interval [CI], 3.52 to 4.99). The associations between each diagnosis of kidney disease in childhood (congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease) and the risk of ESRD in adulthood were similar in magnitude (multivariable-adjusted hazard ratios of 5.19 [95% CI, 3.41 to 7.90], 4.03 [95% CI, 3.16 to 5.14], and 3.85 [95% CI, 2.77 to 5.36], respectively). A history of kidney disease in childhood was associated with younger age at the onset of ESRD (hazard ratio for ESRD among adults <40 years of age, 10.40 [95% CI, 7.96 to 13.59]). CONCLUSIONS: A history of clinically evident kidney disease in childhood, even if renal function was apparently normal in adolescence, was associated with a significantly increased risk of ESRD, which suggests that kidney injury or structural abnormality in childhood has long-term consequences.

The opposing trends of body mass index and blood pressure during 1977-2020; nationwide registry of 2.8 million male and female adolescents.

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 < 0.001 in both sexes). The mean diastolic blood pressure decreased by 3.6 mmHg in males and by 2.9 mmHg in females (P < 0.001 in both sexes). The mean systolic blood pressure increased by 1.6 mmHg in males and decreased by 1.9 mmHg in females. These trends were also consistent when blood pressure values were adjusted to body mass index. 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.

Five years into the Israeli National Diabetes Program - are we on the right track?

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.