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.

Hyperhidrosis and Hypermobility Spectrum Disorders Among Adolescents.

This cross-sectional study assesses the prevalence and risk of excessive sweating and joint hypermobility in Israeli adolescents aged 16 to 19 years.

Hearing Impairment and Severe Attention Deficit/Hyperactivity Disorder: A Nationwide Study.

BACKGROUND: The association between hearing impairment and attention-deficit/hyperactivity disorder (ADHD) is unclear. Therefore, we aimed to assess this association in Israel's national sample of over 1.1 million adolescents. METHODS: We conducted a nationwide, population-based, cross-sectional study of all Israeli adolescents (n = 1,175,534, 58% males; mean age, 17 yrs) who were examined before mandatory military service during 2004 to 2020. Board-certified specialists confirmed diagnoses of hearing impairment and severe ADHD. MAIN OUTCOMES AND MEASURES: We compared the prevalence of severe ADHD in adolescents with and without hearing impairment. Associations were analyzed using logistic regression models and sensitivity analyses accounting for hearing impairment type (sensorineural vs. conductive) and severity. RESULTS: Of the 8,769 adolescents with hearing impairment, 57 were diagnosed with severe ADHD (prevalence = 0.65%). Of the 1,166,765 adolescents without hearing impairment, 3,936 were diagnosed with severe ADHD (prevalence = 0.29%). We found a significant association between hearing impairment and severe ADHD (odds ratio = 1.93 [95% confidence interval, 1.47-2.49]), which persisted in a multivariable model adjusted to age, sex, socioeconomic status, educational status, cognitive performance, and immigration status (odds ratio = 1.70 [95% confidence interval, 1.29-2.20]). The association also persisted when stratified by hearing impairment type (sensorineural vs. conductive) and severity. CONCLUSIONS: Adolescents with hearing impairment had 70% increased odds of severe ADHD. Study findings suggest that active screening of patients with hearing impairment for ADHD should be considered.

Do Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio Need to Be Stratified for Age and Comorbidities in COVID-19 Disease? A Subgroup Analysis of Two Distinct Cohorts over Disease Course.

Several studies described neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) as markers of COVID-19 severity. In a recently published study, age and frailty affected NLR and PLR more than disease severity. The study compared two distinct cohorts. The first comprised older frailer patients positive for SARS-CoV-2, with mild or asymptomatic disease, admitted to designated COVID-19 departments in a large geriatric medical center (GMC). The second cohort comprised COVID-19 patients admitted to a large general hospital (GH) for symptomatic disease. This was a follow-up study comparing a subgroup of patients who had NLR and PLR values measured a week after admission. Only 100 of 177 patients in the original GMC cohort had a second NLR test compared to almost all (287 of 289) patients in the general hospital (GH) cohort. The subgroup baseline characteristics did not change significantly from that of the original cohort. Disease symptoms were more prevalent in the GH cohort. In the GMC group, the median second NLR rose from 3.9 to 4.6, while in the GH cohort, the NLR value dropped from 3.5 to 2.8, enhancing the NLR differences between the groups. Smaller changes were observed in the second PLR. These results strengthen the prior results that age and frailty seem to have a stronger impact on NLR and PLR than disease severity.

Adolescent Body Mass Index and Early Chronic Kidney Disease in Young Adulthood.

Importance: Despite increasing obesity rates in adolescents, data regarding early kidney sequelae are lacking. Objective: To assess the association between adolescent body mass index (BMI) and early chronic kidney disease (CKD) in young adulthood (<45 years of age). Design, Setting, and Participants: This cohort study linked screening data of mandatory medical assessments of Israeli adolescents to data from a CKD registry of a national health care system. Adolescents who were aged 16 to 20 years; born since January 1, 1975; medically evaluated for mandatory military service through December 31, 2019; and insured by Maccabi Healthcare Services were assessed. Individuals with kidney pathology, albuminuria, hypertension, dysglycemia, or missing blood pressure or BMI data were excluded. Body mass index was calculated as weight in kilograms divided by height in meters squared and categorized by age- and sex-matched percentiles according to the US Centers for Disease Control and Prevention. Follow-up started at the time of medical evaluation or January 1, 2000 (whichever came last), and ended at early CKD onset, death, the last day insured, or August 23, 2020 (whichever came first). Data analysis was performed from December 19, 2021, to September 11, 2023. Main Outcomes and Measures: Early CKD, defined as stage 1 to 2 CKD by moderately or severely increased albuminuria, with an estimated glomerular filtration rate of 60 mL/min/1.73 m2 or higher. Results: Of 629 168 adolescents evaluated, 593 660 (mean [SD] age at study entry, 17.2 [0.5] years; 323 293 [54.5%] male, 270 367 [45.5%] female) were included in the analysis. During a mean (SD) follow-up of 13.4 (5.5) years for males and 13.4 (5.6) years for females, 1963 adolescents (0.3%) developed early CKD. Among males, the adjusted hazard ratios were 1.8 (95% CI, 1.5-2.2) for adolescents with high-normal BMI, 4.0 (95% CI, 3.3-5.0) for those with overweight, 6.7 (95% CI, 5.4-8.4) for those with mild obesity, and 9.4 (95% CI, 6.6-13.5) for those with severe obesity. Among females, the hazard ratios were 1.4 (95% CI, 1.2-1.6) for those with high-normal BMI, 2.3 (95% CI, 1.9-2.8) for those with overweight, 2.7 (95% CI, 2.1-3.6) for those with mild obesity, and 4.3 (95% CI, 2.8-6.5) for those with severe obesity. The results were similar when the cohort was limited to individuals who were seemingly healthy as adolescents, individuals surveyed up to 30 years of age, or those free of diabetes and hypertension at the end of the follow-up. Conclusions and Relevance: In this cohort study, high BMI in late adolescence was associated with early CKD in young adulthood. The risk was also present in seemingly healthy individuals with high-normal BMI and before 30 years of age, and a greater risk was seen among those with severe obesity. These findings underscore the importance of mitigating adolescent obesity rates and managing risk factors for kidney disease in adolescents with high BMI.

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.

Body mass index and visual impairment in Israeli adolescents: A nationwide study.

BACKGROUND: Previous research on the association between body mass index (BMI) and visual impairment (VI) in youth has reported inconsistent findings. We aimed to investigate this association in a national cohort of Israeli adolescents. METHODS: This retrospective, population-based, cross-sectional study included 1 697 060 adolescents (56.4% men; mean age 17 years) who underwent mandatory pre-military service assessments from 1993 to 2017. BMI was classified based on the US age- and sex-matched percentiles. Unilateral or bilateral VI was classified as best-corrected visual acuity (BCVA) worse than 6/9 in either or both eyes, respectively. Sex-stratified regression models adjusted for sociodemographic variables were used to analyse the BMI-VI relationship. RESULTS: Overall, 17 871 (1.05%) and 5148 (0.30%) adolescents had unilateral and bilateral VI, respectively. Compared with high-normal BMI (50th to 85th percentile), adjusted odds ratios (ORs) for unilateral and bilateral VI gradually increased with higher BMI, reaching 1.33 (1.13-1.55) and 1.80 (1.37-2.35) in men with severe obesity, and 1.51 (1.24-1.84) and 1.52 (1.08-2.14) in women with severe obesity, respectively. Men with underweight also had increased ORs for unilateral and bilateral VI (1.23; 1.14-1.33 and 1.59; 1.37-1.84, respectively), a pattern not observed in women (0.96; 0.86-1.07 and 1.02; 0.83-1.25, respectively). Results were maintained when the outcome was restricted to mild VI, as well as in subgroups of adolescents with unimpaired health and those without moderate-to-severe myopia. CONCLUSIONS: Abnormal BMI, and particularly obesity, is associated with increased OR for VI in late adolescence.

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.

Hypermobility spectrum disorders and irritable bowel syndrome: A nationwide study of 1.6 million adolescents.

BACKGROUND AND AIM: The association between hypermobility spectrum disorders/hypermobile type Ehlers-Danlos syndrome (HDS/hEDS) and irritable bowel syndrome (IBS) is yet to be clarified. We aimed to assess this association in a national sample of adolescents. METHODS: A population-based cross-sectional study included 1 627 345 Israeli adolescents (58% male; mean age 17 years) who were medically assessed before compulsory military service during 1998-2020. Diagnoses of HSD/hEDS and IBS were confirmed by board-certified specialists. The prevalence and odds ratios (ORs) for IBS in adolescents with and without HSD/hEDS were computed. RESULTS: A total of 4686 adolescents (2553 male) with HSD/hEDS were identified, of whom 71 were diagnosed with IBS (prevalence = 1.5%). Of the 1 621 721 adolescents in the control group, 8751 were diagnosed with IBS (prevalence = 0.5%). Unadjusted logistic regression revealed a significant association between HSD/hEDS and IBS (OR = 2.16 [95% confidence interval, CI, 1.90-2.45]), which persisted in multivariable adjusted models (OR = 2.58 [95% CI, 2.02-3.24]), and in several sensitivity analyses. The association was evident in both male and female adolescents with ORs of 2.60 (95% CI, 1.87-3.49), and 2.46 (95% CI, 1.66-3.49), respectively. The association was accentuated in a sensitivity analysis accounting for other medical and psychiatric comorbidities. CONCLUSIONS: We found a significant association between HSD/hEDS and IBS in both male and female adolescents. Clinical awareness of the association can promote early diagnosis of IBS and appropriate multidisciplinary treatment. Further research is required to identify the common pathological pathways of the conditions and to develop new IBS treatment strategies for people with HSD/hEDS.

Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio, are they markers of COVID-19 severity or old age and frailty? A comparison of two distinct cohorts.

The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) are simple markers of systemic inflammatory responses. It has been previously suggested that they can predict COVID-19 severity. Age and frailty may also influence their values. This study aimed to evaluate the impact of COVID-19 severity versus age and frailty on NLR and PLR values. This was a retrospective, observational two cohorts' comparative study. The first cohort is comprised of patents positive for SARS-CoV-2, with mild or asymptomatic disease, admitted to designated COVID-19 departments in a large geriatric medical center (GMC). The second included patients with COVID-19 admitted to designated COVID-19 departments in a large general hospital for symptomatic disease from March 2020 to March 2021. We compared baseline characteristics including comorbidities and chronic medications, disease symptoms, laboratory tests and compared the NLR and PLR between the two groups. The 177 patients admitted to the COVID-designated department in the GMC were over three decades older than the 289 COVID-19 patients admitted to the general hospital care (HC). They had substantially more comorbidities and chronic medications. All common disease symptoms were significantly more common in the HC group. Almost two thirds of the GMC patients remained asymptomatic compared to 2.1% in the HC group. Inflammatory markers, such as CRP and LDH, were significantly higher in the HC group. The NLR and PLR were both significantly higher in the GMC cohort comprised of older frailer patients with milder disease. NLR and PLR seem to be affected more by age and frailty than COVID-19 severity.

Adolescent body mass index and cognitive performance: a nationwide study of 2.48 million Israeli adolescents.

IMPORTANCE: The increased incidence of adolescent obesity over recent decades may be associated with lower cognitive performance than the expected potential. OBJECTIVE: We aimed to assess the association between adolescent body mass index (BMI) and cognitive function. DESIGN: A nationwide, cross-sectional, population-based study. SETTING: Pre-recruitment evaluation for military service during 1967-2018. PARTICIPANTS: All Israeli-born adolescents, 1 459 522 males and 1 027 953 females aged 16 to ≤20 years. EXPOSURES: Weight and height were measured to calculate BMI. MAIN OUTCOME: Cognitive performance was assessed by using a validated intelligence-quotient-equivalent test and was standardized to the year- and sex-Z-score. For 445 385 persons, parental cognitive scores could be identified. Multinomial logistic regression models were applied. RESULTS: Among male adolescents with severe obesity, 29.4% achieved a cognitive score below the 25th percentile, compared with 17.7% among their normal-weight (50th-84th percentile) counterparts. A J-shaped relation was observed between BMI and the odds ratio (OR) for a low cognitive score among male adolescents: underweight, 1.45 (1.43-1.48); overweight, 1.13 (1.12-1.15); mild obesity, 1.36 (1.33-1.39); and severe obesity, 1.58 (1.52-1.64). Similar findings were observed in females. For both sexes, point estimates were overall consistent in models adjusted for sociodemographic confounders, coexisting morbidities, and parental cognitive scores. Examinees with abnormal BMI had higher ORs for a lower-than-expected cognitive score, based on their parents' data as adolescents, in a manner that depends on obesity severity. CONCLUSION AND RELEVANCE: Obesity, is associated with increased odds for a lower cognitive performance, and the inability to fully achieve cognitive potential, regardless of sociodemographic background.

Is There an Association between BMI, Height, and Gender and Long-Bone Fractures during Childhood and Adolescence? A Large Cross-Sectional Population Study of 911,206 Subjects.

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.

Hypermobility spectrum disorders and active migraine in Israeli adolescents: A nationwide study.

OBJECTIVE: To assess the association between hypermobility spectrum disorders/hypermobile type Ehlers Danlos Syndrome (HSD/hEDS) and migraine in a national sample of adolescents in Israel. BACKGROUND: The association between HSD/hEDS and migraine is unclear, even more so in pediatric populations. METHODS: This population-based, cross-sectional study included 1,627,345 Israeli adolescents (945,519/1,626,407 [58%] males; mean age 17 ± 0.5 years) who were medically assessed before mandatory military service during 1998-2020. Diagnoses of migraine with at least one attack per month (active migraine) and HSD/hEDS were confirmed by certified specialists. The prevalences of active migraine in adolescents with and without HSD/hEDS were computed and the association between HSD/hEDS and active migraine was examined. RESULTS: Active migraine was significantly more prevalent in adolescents with HSD/hEDS (307/4686 [6.5%]) compared to those without HSD/hEDS (51,931/1,621,721 [3.2%]) (OR = 2.16, 95% CI 1.90-2.45). The association between HSD/hEDS and active migraine persisted in a multivariable analysis (OR = 2.08, 95% CI 1.85-2.34) and in several sensitivity analyses. CONCLUSIONS: We found a significant association between HSD/hEDS and active migraine in both male and female adolescents. Clinical awareness of the association can promote early diagnosis and treatment of migraine. Further research is required to identify appropriate pharmacologic and nonpharmacologic migraine treatment strategies for individuals with HSD/hEDS.

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.

Glucose intolerance in pregnancy and risk of early-onset type 2 diabetes: a population-based cohort study.

BACKGROUND: The risk of type 2 diabetes among women with glucose intolerance during pregnancy that does not meet gestational diabetes criteria requires further investigation. We aimed to explore the associations between various degrees of gestational glucose intolerance and the risk of type 2 diabetes in young adulthood. METHODS: For this population-based cohort study, the national Israeli conscription database was linked to Maccabi Healthcare Services (MHS), the second-largest state-mandated health provider in Israel. We included 177 241 women who underwent a pre-recruitment evaluation at adolescence (age 16-20 years), 1 year before mandatory military service, and later underwent, from Jan 1, 2001, to Dec 31, 2019, two-step gestational diabetes screening with a 50 g glucose challenge test (GCT) based on a threshold of 140 mg/dL (7·8 mmol/L), followed as needed by a 100 g oral glucose tolerance test (OGTT). Abnormal OGTT values were defined according to the Carpenter-Coustan thresholds: 95 mg/dL (5·3 mmol/L) or higher in the fasting state; 180 mg/dL (10·0 mmol/L) or higher at 1 h; 155 mg/dL (8·6 mmol/L) or higher at 2 h; and 140 mg/dL (7·8 mmol/L) or higher at 3 h. The primary outcome was incident type 2 diabetes in the MHS diabetes registry. Cox proportional hazards models were applied to estimate adjusted hazard ratios (HRs) with 95% CIs for incident type 2 diabetes. FINDINGS: During a cumulative follow-up of 1 882 647 person-years, and with a median follow-up of 10·8 (IQR 5·2-16·4) years, 1262 women were diagnosed with type 2 diabetes. Crude incidence rates of type 2 diabetes were 2·6 (95% CI 2·4-2·9) per 10 000 person-years in women with gestational normoglycaemia, 8·9 (7·4-10·6) per 10 000 person-years in women with an abnormal GCT and normal OGTT, 26·1 (22·4-30·1) per 10 000 person-years in women with one abnormal OGTT value (in the fasting state or 1 h, 2 h, or 3 h post-challenge), and 71·9 (66·0-78·3) per 10 000 person-years in women with gestational diabetes. After adjustment for sociodemographic characteristics, adolescent BMI, and age at gestational screening, the risk of type 2 diabetes was higher, compared to the gestational normoglycaemia group, in women with an abnormal GCT and normal OGTT (adjusted hazard ratio [HR] 3·39 [95% CI 2·77-4·16]; p<0·0001), in women with one abnormal OGTT value (9·11 [7·64-10·86]; p<0·0001), and in women with gestational diabetes (24·84 [21·78-28·34]; p<0·0001). The risk of type 2 diabetes was modestly increased in women with isolated elevated fasting glucose (adjusted HR 11·81 [95% CI 8·58-16·25]; p<0·0001), and in women with gestational diabetes and an abnormal fasting glucose (38·02 [32·41-44·61]; p<0·0001). INTERPRETATION: Gestational glucose intolerance, including conditions not meeting gestational diabetes criteria of the two-step strategy, confers a high risk of type 2 diabetes in young adulthood. These conditions should be recognised as risk factors for type 2 diabetes, especially among women with abnormal fasting glucose concentrations during pregnancy. FUNDING: None.

Symptomatic Joint Hypermobility Is Associated with Low Back Pain: A National Adolescents Cohort Study.

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.

Varicocoele in adolescence and testicular cancer in young adulthood.

BACKGROUND: 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. OBJECTIVE: To explore the possible association between varicocoele at adolescence and the incidence of testicular cancer at adulthood. DESIGN, SETTING, AND PARTICIPANTS: 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. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The diagnosis of testicular cancer was ascertained from linkage of records to the the Israeli National Cancer Registry. Survival analysis was applied. RESULTS: 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). CONCLUSIONS: Varicocoele in adolescents was not found to be associated with testicular cancer in young adults. PATIENT SUMMARY: 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.

Persistent Asymptomatic Isolated Microscopic Hematuria in Adolescents is not Associated With an Increased Risk for Early Onset Urinary Tract Cancer.

OBJECTIVE: To elucidate the association between adolescent microscopic hematuria and early onset urothelial carcinoma and renal cell carcinoma. METHODS: 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. RESULTS: 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). CONCLUSION: Persistent asymptomatic isolated microscopic hematuria at adolescence was not associated with increased risk for urothelial carcinoma nor renal cell carcinoma.

Myopia and BMI: a nationwide study of 1.3 million adolescents.

OBJECTIVE: This study analyzed the association between adolescent BMI and myopia severity. METHODS: 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. RESULTS: 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 (pinteraction < 0.001), in whom the group with severe obesity did not reach statistical significance. CONCLUSIONS: BMI 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.

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.