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Background: Observational studies should not be used to infer causation as they are prone to confounding factors, selection bias, and reverse causality. Many observational studies of labor analgesia treated epidurals as an independent exposure and concluded that "epidurals" cause dystocia, despite multiple randomized controlled trials showing no effect. We highlight this problem using reductio ad absurdum. We explore whether people request reading glasses when their progressively increasing focal length equals or exceeds their fixed arm length., Methods: We designed a cross-sectional retrospective and prospective observational study to assess whether there is an association between arm length and age when first requesting reading glasses in presbyopia. We evaluated individuals aged 38-55 receiving their first reading glasses for presbyopia (either currently or within the past year). We recorded age at first request for reading glasses, the refractive correction (additions) in each eye, and we measured arm length., Results: Seventy subjects were included in the study. No association was found between arm length and the age at request for reading glasses or the severity of presbyopia at presentation., Conclusions: Even if this observational study had demonstrated a strong correlation between age at request for reading glasses and arm length, it would have been absurd to conclude that spectacles somehow cause our arms to shrink. Similarly, women in obstructed labor with a narrow pelvis are more likely to request neuraxial labor analgesia, but "epidurals" do not make their pelvis shrink. Making far-reaching causal inferences based on retrospective or observational data is very shortsighted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Hypothesis: The two apolipoprotein L1 ( APOL1 ) variants, G1 and G2, are common in populations of sub-Saharan African ancestry. Individuals with two of these alleles (G1 or G2) have an increased risk for a spectrum of non-diabetic chronic kidney diseases. However, these variants are typically not observed outside of populations that self-identify as current continental Africans or having clear recent African ancestry such as, most notably, African Americans, and other large population groups in the Americas and several European countries. We hypothesized that the diverse ethnic groups within the Israeli population may exhibit varying levels of recent African ancestry. Therefore, it is plausible that APOL1 risk alleles might be present even in individuals who do not self-identify as being of sub-Saharan African descent., Methods: We non-selectively screened people with kidney failure across Israel for APOL1 risk variants using restriction fragment length polymorphism., Results: We recruited 1744 individuals from 38 dialysis units in Israel. We identified eight patients of Moroccan Jewish, Bedouin, or Muslim Arab ancestry, who carry at least one G1 or G2 allele. None of the eight patients carried the protective APOL1 p.N264K variant. Furthermore, despite all Bedouin individuals being G2 heterozygous, the G2 minor allele frequency was significantly enriched in kidney failure cases compared to ethnically matched controls ( P  = .006)., Conclusions: These findings show that APOL1 G1 and G2 allelic variants are present in populations previously not appreciated to possess recent sub-Saharan ancestry and suggest that a single G2 risk variant may confer increased risk for chronic kidney disease in certain population contexts., Competing Interests: The authors declare that they have no relevant financial interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Childhood obesity is a major public health concern, and the global rate is rising. Rapid infant weight gain is a risk factor for later overweight. Studies have linked prenatal ambient temperature exposure to fetal growth, and preliminary evidence suggests postnatal exposure may be associated with infant weight gain., Methods: Using a population-based historical cohort study including 1 100 576 infants born 2011-2019, we assessed the relationship between prenatal and one-month postnatal ambient temperature exposure and rapid infant weight gain. We used a hybrid spatiotemporal model to assess temperatures at the family's recorded residence at birth. Repeated weight measurements between birth and 15 months were used to model the outcome using the SuperImposition by Translation and Rotation (SITAR) method. We employed generalized linear models and distributed lag models to estimate the association between prenatal and postnatal exposure and rapid infant weight gain, defined as the upper tertile of the SITAR growth velocity., Results: Overall, higher ambient temperatures were associated with rapid infant weight gain. The cumulative adjusted relative risk for the highest exposure quintile during pregnancy compared with the lowest quintile was 1.33 [95% confidence interval (CI): 1.25, 1.40], and the corresponding association for the first postnatal month was 1.19 (95% CI: 1.15, 1.23). Exposure to high ambient temperature during early and mid-pregnancy, as well as the first postnatal month, was associated with rapid weight gain, while during late pregnancy, exposure to low temperatures was associated with this outcome., Conclusions: Prenatal and postnatal ambient temperatures are associated with rapid infant weight gain., (© The Author(s) 2024; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: In the last three decades, much effort has been invested in measuring and improving the quality of diabetes care. We assessed the association between adherence to diabetes quality indicators and all-cause mortality in the primary care setting., Methods: A nationwide, population-based, historical cohort study of all people aged 45-80 with pharmacologically-treated diabetes in 2005 (n = 222,235). Data on annual performance of quality indicators (including indicators for metabolic risk factor management and glycemic control) and vital status were retrieved from electronic medical records of the four Israeli health maintenance organizations. Cox proportional hazards and time-dependent models were used to estimate hazard ratios (HRs) for mortality by degree of adherence to quality indicators., Results: During 2,000,052 person-years of follow-up, 35.8% of participants died. An inverse dose-response association between the degree of adherence and mortality was shown for most of the quality indicators. Participants who were not tested for proteinuria or did not visit an ophthalmologist during the first-5-years of follow-up had HRs of 2.60 (95%CI:2.49-2.69) and 2.09 (95%CI:2.01-2.16), respectively, compared with those who were fully adherent. In time-dependent analyses, not measuring LDL-cholesterol, blood pressure, HbA1c, or HbA1c>9% were similarly associated with mortality (HRs ≈1.5). The association of uncontrolled blood pressure with mortality was modified by age, with increased mortality shown for those with controlled blood pressure at older ages (≥65 years)., Conclusions: Longitudinal adherence to diabetes quality indicators is associated with reduced all-cause mortality. Primary care professionals need to be supported by health care systems to perform quality indicators., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Abdel-Rahman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: The authors declare that they do not have any conflicts of interest.

Hybrid immunity, acquired through vaccination followed or preceded by a COVID-19 infection, elicits robust antibody augmentation. We hypothesize that maternal hybrid immunity will provide greater infant protection than other forms of COVID-19 immunity in the first 6 months of life. We conducted a case-control study in Israel, enrolling 661 infants up to 6 months of age, hospitalized with COVID-19 (cases) and 59,460 age-matched non-hospitalized infants (controls) between August 24, 2021, and March 15, 2022. Infants were grouped by maternal immunity status at delivery: Naïve (never vaccinated or tested positive, reference group), Hybrid-immunity (vaccinated and tested positive), Natural-immunity (tested positive before or during the study period), Full-vaccination (two-shot regimen plus 1 booster), and Partial-vaccination (less than full three shot regimen). Applying Cox proportional hazards models to estimate the hazard ratios, which was then converted to percent vaccine effectiveness, and using the Naïve group as the reference, maternal hybrid-immunity provided the highest protection (84% [95% CI 75-90]), followed by full-vaccination (66% [95% CI 56-74]), natural-immunity (56% [95% CI 39-68]), and partial-vaccination (29% [95% CI 15-41]). Maternal hybrid-immunity was associated with a reduced risk of infant hospitalization for Covid-19, as compared to natural-immunity, regardless of exposure timing or sequence. These findings emphasize the benefits of vaccinating previously infected individuals during pregnancy to reduce COVID-19 hospitalizations in early infancy., (© 2024. The Author(s).)

Diabetes Mellitus (DM) is more common among individuals with severe mental illness (SMI). We aimed to assess quality-of-care-indicators in individuals with SMI following the 2015 Israel's Mental-Health-reform. We analyzed yearly changes in 2015-2019 of quality-of-care-measures and intermediate-DM-outcomes, with adjustment for gender, age-group, and socioeconomic status (SES) and compared individuals with SMI to the general adult population. Adults with SMI had higher prevalences of DM (odds ratio (OR) = 1.64; 95% confidence intervals (CI): 1.61-1.67) and obesity (OR = 2.11; 95% CI: 2.08-2.13), compared to the general population. DM prevalence, DM control, and obesity rates increased over the years in this population. In 2019, HbA1c testing was marginally lower (OR = 0.88; 95% CI: 0.83-0.94) and uncontrolled DM (HbA1c > 9%) slightly more common among patients with SMI (OR = 1.22; 95% CI: 1.14-1.30), control worsened by decreasing SES. After adjustment, uncontrolled DM (adj. OR = 1.02; 95% CI: 0.96-1.09) was not associated with SMI. Cardio-metabolic morbidity among patients with SMI may be related to high prevalences of obesity and DM rather than poor DM control. Effective screening for metabolic diseases in this population and social reforms are required., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Early life exposures affect offspring health across the life-course. We aimed to examine whether prevalent perinatal exposures and obstetric complications are independently associated with offspring overweight in adolescence. We then assessed whether shared maternal-offspring pathways drive the association of perinatal exposures with offspring overweight., Methods: Using data from the Jerusalem Perinatal Study birth cohort, two perinatal scores were constructed: obstetric complications (OC) and prevalent perinatal exposures (PPE) scores. PPE score, generated by principal component analysis, included three primary components. Logistic regressions were used to assess associations of scores with offspring overweight, with and without adjustment for maternal life-course survival., Results: OC and PPE scores were independently associated with offspring overweight (OR OC  = 1.15, 95%CI:1.07,1.25; OR PPE1- SEP and lifestyle  = 0.85, 95%CI:0.79,0.91; OR PPE2- Maternal body size  = 1.20, 95%CI: 1.13,1.28; OR PPE3-Fetal growth  = 1.18, 95%CI:1.11,1.26). Maternal survival was associated with offspring overweight (OR = 1.38, 95%CI:1.08,1.76), yet introducing PPE score to the same model attenuated this association (OR = 1.16, 95%CI:0.90, 1.49). When OC score and maternal survival were included in the same model, their associations with offspring overweight remained unchanged., Conclusions: Mother-offspring shared factors, captured by maternal life-course survival, underlie the effect of prevalent perinatal exposures on offspring overweight. However, the effect of obstetric complications was independent, highlighting the contribution of additional pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: For the past two decades, the assessment of the quality of diabetes care has mostly relied on clinical quality indicators. These have not included Patient-Reported Outcome Measures (PROMs) which provide information on outcomes deemed valuable by patients. We aimed to examine the potential utility of PROMs in type 2 diabetes care and to study the association of PROMs with patients' characteristics and clinical quality indicators., Methods: A cross-sectional survey of recently (≤ 4 years) diagnosed patients with type 2 diabetes (n = 392) in the setting of a large health plan. PROMs were based on two well-validated questionnaires, the Problem Areas in Diabetes (PAID) one-page questionnaire that measures diabetes-related distress, and the ten item PROMIS-10 global health questionnaire that measures general health. Additional items were added following a previous qualitative study among Israeli patients with diabetes. The survey was carried out using phone interviews, and data collected were linked to the electronic medical records. Multivariable regression models were used to assess the associations of socio-demographic variables and clinical quality indicators with the PROMs., Results: About a fifth of participants (22%) had high diabetes-related distress (PAID score ≥ 40), a third reported that they did not feel confident in self-management of diabetes and about a third reported having sexual dysfunction. Women, younger patients, and those with a low education level (≤ 12 years) reported worse general health, were more likely to experience high diabetes-related distress, and to have low confidence in diabetes self-management. Interestingly, performance of all seven diabetes quality indicators was associated with worse general health and high diabetes-related distress. Of note, levels of glycated hemoglobin, LDL-cholesterol, or blood pressure were not associated with PROMs., Conclusions: PROMs provide important information on patient self-reported health status and are likely to reflect aspects of the quality of care that are not otherwise available to clinicians. Thus, the use of PROMs has the potential to expand the evaluation of diabetes care and promote patient-centered care. We recommend that policy-makers in the Ministry of Health and health maintenance organizations implement PROMs for assessing and improving the care for patients with type 2 diabetes., (© 2024. The Author(s).)

Context: There are no reported data from prospective long-term studies on the relation of androgen levels in young women with development of metabolic syndrome (MetS) before menopause., Objective: We investigated associations of androgens and SHBG with incident MetS during 23 years of follow-up., Methods: We included 366 White and 375 Black women ages 20 to 32 years participating in the CARDIA study and CARDIA Women's study, free of MetS at baseline examination (1987-1988), and premenopausal 23 years later. Androgens and SHBG were categorized into quartiles. MetS was defined according to the American Heart Association/National Heart, Lung, and Blood Institute 2009 Joint Scientific Statement. Cox proportional hazards models were used., Results: By year 23, 30% of women developed MetS. Adjusting for baseline age, race, and education, hazard ratios (95% CI) of developing MetS were 1.46 (1.02-2.10) and 2.22 (1.53-3.21) for women in the highest vs lowest total testosterone (T) and free T quartile, respectively. The hazards of developing MetS were 47%, 59%, and 53% lower for women with SHBG in the second, third, and fourth quartiles (vs lowest quartile), respectively. Associations were attenuated for total T with further adjustments for smoking, physical activity, menstrual status, oral contraceptive/hormone (OCHM) use, insulin level, oligomenorrhea, and age at menarche, but remained statistically significant for free T and SHBG. Associations were similar for both Blacks and Whites, and OCHM nonusers, but not for OCHM users., Conclusion: High androgenicity in young premenopausal women is associated with higher risk of future MetS, suggesting that early assessment of androgens may contribute to prevention., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Childhood overweight and obesity is a global public health problem. Rapid infant weight gain is predictive of childhood overweight. Studies found that exposure to ambient air pollution is associated with childhood overweight, and have linked prenatal exposure to air pollution with rapid infant weight gain., Objectives: To examine the association between prenatal and postnatal ambient NO 2 exposure, a traffic-related marker, with rapid weight gain in infants., Methods: We carried out a population-based historical cohort study using data from the Israeli national network of maternal and child health clinics. The study included 474,136 infants born at term with birthweight ≥2500 g in 2011-2019 in central Israel. Weekly averages of NO 2 concentration throughout pregnancy (prenatal) and the first 4 weeks of life (postnatal) were assessed using an optimized dispersion model and were linked to geocoded home addresses. We modelled weight gain velocity throughout infancy using the SuperImposition by Translation and Rotation (SITAR) method, a mixed-effects nonlinear model specialized for modelling growth curves, and defined rapid weight gain as the highest velocity tertile. Distributed-lag models were used to assess critical periods of risk and to measure relative risks for rapid weight gain. Adjustments were made for socioeconomic status, population group, subdistrict, month and year of birth, and the alternate exposure period - prenatal or postnatal., Results: The cumulative adjusted relative risk for rapid weight gain of NO 2 exposure was 1.02 (95% confidence intereval [CI] 1.00, 1.04) for exposure throughout pregnancy and 1.02 (95% CI 1.01, 1.04) for exposure during the first four postnatal weeks per NO 2 interquartile range increase (7.3 ppb). An examination of weekly associations revealed that the critical period of risk for the prenatal exposure was from mid-pregnancy to birth., Conclusions: Prenatal and postnatal exposures to higher concentrations of traffic-related air pollution are each independently associated with rapid infant weight gain, a risk factor for childhood overweight and obesity., (© 2023 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Reports from many settings suggest that pediatric overweight and obesity increased in 2020 and 2021, presumably due to lifestyle changes associated with the COVID-19 pandemic. Many of these previous reports have relied on convenience samples or subsets of the population. Here, we present results of a longitudinal study of the entire population of Israel, a nation of approximately 9 million people, with the proportion with underweight, normal weight, overweight, and obesity at age 7 and at age 14-15, across the years 2017-2021. Our results show that the prevalence of overweight and obesity, which had been steady or improving through 2019, increased relatively quickly in 2020 and 2021. For example, among 7-year-olds, the percentage of children with obesity in 2019 was 6.8% (99% CI: 6.69-7.05), and by 2021, it had increased to 7.7% (99% CI: 7.53-7.93). There were important disparities in overweight and obesity based on SES; for example, the rate ratio for obesity comparing the poorest with the wealthiest 14-15-year-olds in 2019 was 1.63 (99% CI: 1.55-1.72). However, these disparities did not change meaningfully in 2020 and 2021, implying that while obesity did become more prevalent, this increase in prevalence was not differential across socioeconomic status. Like many other nations, Israel too experienced considerable increases in pediatric overweight and obesity in 2020-2021, erasing the improvements of the previous years among younger children., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Rose et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Endocrine disrupting chemicals (EDCs) such as phthalates, found in our daily environment, are nowadays suggested to be associated with adverse outcomes. Prenatal exposure was found associated with neurodevelopmental complications such as behavioral difficulties in school age children., Aim: To explore the association between intrauterine exposure to phthalates and emotional/behavioral development of 24 months old toddlers., Methods: Women were recruited at 11-18 weeks of gestation and provided spot urine samples, analyzed for phthalate metabolites (DEHP, DiNP, MBzBP). Offspring were examined at 24 months of age, using standard maternal report, regarding developmental and behavioral problems (CBCL, ASQ-3, HOME questionnaires) (N = 158). To explore the associations between metabolite levels and developmental outcomes, multivariate GLM analysis (General Linear Model) was used according to tertiles and developmental scores on each developmental outcome., Results: Associations of Di-(2-ethylhexyl) phthalate (DEHP) maternal exposure with behavioral-developmental outcomes were found only in boys. Compared with boys with lower DEHP maternal exposure, boys with high DEHP maternal exposure had lower developmental score in personal social abilities in the ASQ-3 questionnaire (50.68 + 8.06 and 44.14 + 11.02, high and low DEHP, respectively, p = 0.03), and more internalizing problems (for example, emotionally reactive score in high and low DEHP: 53.77 + 7.41 and 50.50 + 1.19, respectively, p = 0.029; anxious or depressed score: 53.38 + 5.01 and 50.75 + 1.34, respectively, p = 0.009; and somatic complaints scores 64.03 + 10.1 and 55.84 + 7.84, respectively, p = 0.003), and externalizing problems (49.28 + 8.59 and 43.33 + 9.11, respectively, p = 0.039). No differences were found in the development and behavior problems between high and low DEHP maternal exposure level in girls., Conclusion: Maternal DEHP metabolite concentrations measured in first trimester urine was associated with children's emotional/behavioral developmental problems in 24-months old boys, supporting accumulating evidence of DEHP as a potentially harming chemical and call for environmental attention., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Rapid weight gain during infancy is a strong predictor of childhood obesity and is affected by genetic and environmental factors. Identifying ages with low heritability will allow for targeted interventions that might be able to prevent the adverse effects of childhood obesity., Objectives: The objective of the study is to estimate the heritability of weight gain from birth to defined ages during infancy, as well as during 6-month periods from birth to 18 months of age. We address this by leveraging large-scale computerised anthropometric data from the state-run network of well-baby clinics in Israel., Methods: We performed a population-based twin study. We extracted weight measurements recorded between birth to 24 months from well-baby clinics for 9388 twin pairs born in Israel between 2011 and 2015. The reported sexes of the twins were used as a proxy for their zygosity status. We estimated the heritability of the weight z-score change from birth to specific ages and during particular periods in infancy. To assess the validity of the results, we repeated the analysis in a sub-cohort of twin pairs with complete weight measurements., Results: During the first 2 years of life, heritability was lowest for birthweight ( h 2 = 0.40 ± 0.11 ). Heritability for weight gain since birth was highest at 4 months ( h 2 = 0.87 ± 0.13 ), and then gradually decreased until age 18 months ( h 2 = 0.62 ± 0.13 ). Estimating the heritability in 6-month intervals from birth to 18 months, heritability was highest during the 6-12-month interval ( h 2 = 0.84 ± 0.14 ), and was substantially lower during the subsequent 12-18-month interval ( h 2 = 0.43 ± 0.16 )., Conclusions: Heritability of weight gain decreases substantially in the second year of life, suggesting that this period could be an appropriate time for interventions for infants who are at an increased risk of childhood obesity., (© 2023 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Introduction: Although prevalent, and variable geographically, there is little information on the incidence and risk factors for occupation hand trauma in our health care system. This pilot study was designed to determine the optimal data collection methods for transient risk factors locally METHODS: All adult patients with occupational hand trauma treated at an emergency department (ED) during a three-month period were interviewed, either in person or by phone, using a case crossover designed questionnaire, regarding occupation and exposure to potential transient risk factor., Results: Of 206 patients treated with occupational trauma during the study period, 94 had trauma distal to the elbow (46%). Patient compliance was high - 89% of the patients consented to phone interviews and 83% completed in-person ED interviews. In the 75 patients which participated in the study, several risk factors were found to be significant, including machine maintenance and being distracted, including by a cellular phone. We found lack of job experience, limited training on the job site and reports of previous injuries in these workplaces to be prevelent., Discussion: The risk factors implicated in this study are similar to those reported in previous studies at other locations and are modifiable although this is the first report linking cellular phone use and occupation trauma. This finding should be further examined in a larger group and according to occupational categories. Compliance with the study was high, in person or with phone interviews, making these options viable for further studies. Several minor changes to the questionnaire were suggested although it did conform with the case-crossover study design. According to this study, standard preventive measures may be lacking in Jerusalem and should be implemented more uniformly, including specific workplace safety plans and education and taking into consideration the risk factors documented here., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Infants are at a higher risk of Coronavirus Disease 2019 (COVID-19)-related hospitalizations compared to older children. In this study, we investigated the effect of the recommended third maternal dose of BNT162b2 COVID-19 vaccine during pregnancy on rates of infant COVID-19-related hospitalizations. We conducted a nationwide cohort study of all live-born infants delivered in Israel between 24 August 2021 and 15 March 2022 to estimate the effectiveness of the third booster dose versus the second dose against infant COVID-19-related hospitalizations. Data were analyzed for the overall study period, and the Delta and Omicron periods were analyzed separately. Cox proportional hazard regression models estimated hazard ratios and 95% confidence intervals (CIs) for infant hospitalizations according to maternal vaccination status at delivery. Among 48,868 live-born infants included in the analysis, rates of COVID-19 hospitalization were 0.4%, 0.6% and 0.7% in the third-dose, second-dose and unvaccinated groups, respectively. Compared to the second dose, the third dose was associated with reduced infant hospitalization with estimated effectiveness of 53% (95% CI: 36-65%). Greater protection was associated with a shorter interval between vaccination and delivery. A third maternal dose during pregnancy reduced the risk of infant hospitalization for COVID-19 during the first 4 months of life, supporting clinical and public health guidance for maternal booster vaccination to prevent infant COVID-19 hospitalization., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

In 1985 to 1986, the CARDIA (Coronary Artery Risk Development in Young Adults) study enrolled 5115 Black or White participants, including 2788 women, aged 18 to 30 years. Over the following 35 years, the CARDIA study amassed extensive longitudinal data on women's reproductive milestones, spanning menarche to menopause. Although not initially conceived as a study of women's health, >75 CARDIA study publications address relationships between reproductive factors and events with cardiovascular and metabolic risk factors, subclinical and clinical cardiovascular disease, and social determinants of health. The CARDIA study was one of the earliest population-based reports to note Black-White differences in age at menarche and associations with cardiovascular risk factors. Adverse pregnancy outcomes, particularly gestational diabetes and preterm birth, have been assessed along with postpartum behaviors, such as lactation. Existing studies have examined risk factors for adverse pregnancy outcomes and lactation, as well as their relationship to future cardiovascular and metabolic risk factors, diagnoses, and subclinical atherosclerosis. Ancillary studies examining components of polycystic ovary syndrome and ovarian biomarkers, such as anti-Müllerian hormone, have facilitated examination of reproductive health in a population-based cohort of young adult women. As the cohort transitioned through menopause, examination of the importance of premenopausal cardiovascular risk factors along with menopause has improved our understanding of shared mechanisms. The cohort is now aged in the 50s to mid-60s, and women will begin to experience a greater number of cardiovascular events as well as other conditions, such as cognitive impairment. Thus, in the next decade, the CARDIA study will provide a unique resource for understanding how the women's reproductive life course epidemiology informs cardiovascular risk, as well as reproductive and chronological aging.

Background: Childhood kidney failure is a rare condition with worldwide clinical variability. We used a nationwide multicenter analysis to study the pretransplant course of the entire Israeli pediatric kidney failure population over 30 years., Methods: In this nationwide, population-based, historical cohort study, we analyzed medical and demographic data of all children treated with KRT and reported to the Israeli kidney failure registry in 1990-2020. Statistical analysis was performed with incidence rate corrected for age, ethnicity, and calendar year, using the appropriate age-related general population as denominator., Results: During the last 30 years, childhood incidence of kidney failure decreased. Average incidence in 2015-2019 was 9.1 cases per million age-related population (pmarp). Arab and Druze children exhibited higher kidney failure incidence rates than Jewish children (18.4 versus 7.0 cases pmarp for minorities versus Jews). The most common kidney failure etiologies among Arab and Jewish children were congenital anomalies of the kidney and urinary tract (approximately 27%), followed by cystic kidney diseases among Arab children (13%) and glomerulonephritis among Jewish children (16%). The most common etiology among Druze children was primary hyperoxaluria type 1 (33%). Israel's national health insurance provides access to primary health care to all citizens. Accordingly, waiting time for deceased-donor transplantation was equal between all ethnicities. Living-donor kidney transplantation rates among minority populations remained low in comparison with Jews over the entire study period. Although all patient groups demonstrated improvement in survival, overall survival rates were mainly etiology dependent., Conclusions: In Israel, Arab and Druze children had a higher incidence of kidney failure, a unique etiological distribution, and a lower rate of living-donor kidney transplantations compared with Jewish children., (Copyright © 2023 by the American Society of Nephrology.)

Fecal incontinence (FI) has a significant long-term impact on patient quality of life for which there is a range of medical and surgical management alternatives. We report the preliminary outcome using the ForConti Contix Faecal Incontinence Management System (FIMS) in FI patients who had failed conservative therapy and who were recruited at 2 tertiary institutions between September 2018 and September 2020. Comparative assessments were made before and after 2 week periods of treatment using bowel diaries and subjective Wexner and Faecal Incontinence Quality of Life scores. Of 17 patients enrolled, 11 completed an 8-week assessment with a significant fall in the average percentage of FI days reported from 84% before treatment to 16.8% at the first posttreatment assessment and down to 13.2% by the second assessment period. This finding correlated with a similar reduction in the total weekly number of episodes of frank FI, minor soiling, and fecal urgency reported by patients along with concomitant improvements in the Wexner scores. For those using the device, there was less concern about accidental bowel leakage, high rates of satisfaction, and minimal problems with the device. Initial results are encouraging warranting further study.

The Centers for Disease Control (CDC) recommend a third dose of COVID-19 vaccine for pregnant women, although data regarding effectiveness during pregnancy are lacking. This national, population-based, historical cohort study of pregnant women in Israel, delivering between August 1, 2021 and March 22, 2022, aims to analyze and compare the third and second doses' vaccine effectiveness in preventing COVID-19-related hospitalizations during pregnancy during two COVID-19 waves (Delta variant in the summer of 2021 and Omicron, BA.1, variant in the winter of 2022). Time-dependent Cox proportional-hazards regression models estimate the hazard ratios (HR) and 95% confidence intervals (CI) for COVID-related outcomes according to vaccine dose, and vaccine effectiveness as 1-HR. Study includes 82,659 and 33,303 pregnant women from the Delta and Omicron waves, respectively. Compared with the second dose, the third dose effectively prevents overall hospitalizations with SARS-CoV-2 infections, with estimated effectiveness of 92% (95% CI 83-96%) during Delta, and enhances protection against significant disease during Omicron, with effectiveness of 92% (95% CI 26-99%), and 48% (95% CI 37-57%) effectiveness against hospitalization overall. A third dose of the BNT162b2 mRNA COVID-19 vaccine during pregnancy, given at least 5 months after the second vaccine dose, enhances protection against adverse COVID-19-related outcomes., (© 2022. The Author(s).)

Background: Patient-Reported Outcome Measures (PROMs) aim to evaluate the quality of care based on the perspectives of patients rather than clinical indicators. Qualitative research is needed to identify these perspectives in people with type 2 diabetes., Objective: To identify, for the first time in Israel, aspects valuable for people with type 2 diabetes that can be relevant for PROMs in diabetes care., Methods: A qualitative study included three focus groups totalling 19 people with type 2 diabetes. Inclusion criteria were: (1)type 2 diabetes, (2)diabetes duration of at least six months, and (3)adults aged 45-80 years. Purposive sampling enabled recruitment of heterogeneous participants. Also, two experts' panels with healthcare providers involved in diabetes care (n = 23) were conducted to provide triangulation of information (more testimony about what is valuable for people with type 2 diabetes). Discussions were recorded, transcribed and thematically analysed., Results: Four domains were deemed valuable for people with type 2 diabetes: (1)challenges of living with diabetes, including reduced physical function, healthy lifestyle struggles, sexual dysfunction, and financial burden, (2)mental health issues, including depression, distress, anxiety, frustration, and loneliness, (3)self-management ability, including management of lifestyle modifications and treatment, knowledge about the disease and treatment, and (4)patient-clinician relationships, including the devotion of clinicians, trust in clinicians and treatment, shared decision-making, and multidisciplinary care under one roof. Experts favour using PROMs in diabetes routine care and even acknowledged their necessity to improve the treatment process. However, only some of the domains raised by people with type 2 diabetes were identified by the experts., Conclusions: There are content gaps between perspectives of people with type 2 diabetes and their healthcare providers. PROMs are essential in addressing issues largely not addressed in routine diabetes care. We recommend that researchers and healthcare providers, who intend to utilize PROMs for diabetes care, consider the aforementioned domains., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Abdel-Rahman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background Evidence of the cardiovascular benefits of adherence to quality indicators in diabetes care over a period of years is lacking. Methods and Results We conducted a population-based, historical cohort study of 105 656 people aged 45 to 80 with pharmacologically treated diabetes and who were free of cardiac disease in 2010. Data were retrieved from electronic medical records of the 4 Israeli health maintenance organizations. The association between level of adherence to national quality indicators (2006-2010: adherence assessment) and incidence of cardiac outcome; ischemic heart disease or heart failure (2011-2016: outcome assessment) was estimated using Cox proportional hazards models. During 529 551 person-years of follow-up, 19 246 patients experienced cardiac disease. An inverse dose-response association between the level of adherence and risk of cardiac morbidity was shown for most of the quality indicators. The associations were modified by age, with stronger associations among younger patients (<65 years). Low adherence to low-density lipoprotein cholesterol testing (≤2 years) during the first 5 years was associated with 41% increased risk of cardiac morbidity among younger patients. Patients who had uncontrolled low-density lipoprotein cholesterol in all first 5 years had hazard ratios of 1.60 (95% CI, 1.49-1.72) and 1.23 (95% CI, 1.14-1.32), among patients aged <65 and ≥65 years, respectively, compared with those who achieved target level. Patients who failed to achieve target levels of glycated hemoglobin or blood pressure had an increased risk (hazard ratios, 1.50-1.69) for cardiac outcomes. Conclusions Longitudinal adherence to quality indicators in diabetes care is associated with reduced risk of cardiac morbidity. Implementation of programs that measure and enhance quality of care may improve the health outcomes of people with diabetes.

Background: During 2020, Israel experienced two COVID-19-related lockdowns that impacted the provision of primary and secondary preventive care., Methods: We examined the month-by-month performance of selected preventive care services using data from Israel's national Quality Indicators in Community Healthcare program. Process of care measures included hemoglobin A1c (HbA1c) testing, cholesterol testing, colon cancer screening and mammography. Intermediate outcome measures included low-density lipoprotein control and HbA1c control. Measures were stratified by sex and by area-level socioeconomic position (SEP). Diabetes and mammography are presented in this abstract due to space limitations., Results: Annual HbA1c testing among persons with diabetes decreased from 90.9% in 2019 to 88.0% in 2020. Performance of HbA1c tests during lockdown months was as low as half the usual amount. There were compensatory increases in testing during post-lockdown months that did not quite make up for the missed tests. In 2019, 9.0% of Israelis with diabetes had poor glycemic control (HbA1c ≥ 9.0); in 2020, it was 8.8%. In total, 4.5% fewer mammograms were performed in 2020 compared with 2019. Women in the lowest SEP level performed 10.4% fewer mammograms in 2020 than in 2019, while women in the highest SEP level performed 3.1% more mammograms., Conclusions: Prolonged COVID lockdowns in 2020 were associated with marked decreases in the performance of preventive health services during those months. Compensatory spikes following the end of lockdowns partly, but did not completely, make up for the missed care. COVID lockdowns may have exacerbated socioeconomic disparities in some preventive health services., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Pre- and perinatal events may be associated with an increased risk of inflammatory bowel disease [IBD]. We aimed to investigate the role of pre- and perinatal factors as potential risk factors for the development of IBD in a population with a follow-up of 50 years., Methods: We conducted a nested case-control study, reporting IBD incidence among individuals born in 1964-76, for whom pre- and perinatal exposures were reported as part of the Jerusalem Perinatal Study [JPS], by linking them to the database of the epidemiology group of the Israeli IBD Research Nucleus [epi-IIRN], including all IBD patients in Israel since 2005 and their matched controls., Results: We identified 2789 individuals within the epi-IIRN cohort who were also included in the JPS cohort [n = 90 079]: 746 IBD patients (405 with Crohn's disease [CD] and 341 with ulcerative colitis [UC]) and 2043 non-IBD controls. Those with a 'Non-western' family origin had decreased odds of developing CD and UC. High socioeconomic status was associated with CD but not UC. Low birth weight [≤2500 g] occurred less frequently in IBD cases compared to controls, especially in UC patients, showing a protective effect. Being the first born was associated with CD, and having older siblings lowered the odds of developing CD, decreasing 7% with each additional sibling. Smoking and breastfeeding data were available for a subset of individuals, but neither was associated with IBD development., Conclusion: This population-based study identifies several pre- and perinatal variables as predictors of IBD development. This information may be helpful to facilitate implementation of early diagnosis interventions and family follow-up protocols., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Studies assessing the associations between prenatal air pollution exposures and birth outcomes commonly use maternal addresses at the time of delivery as a proxy for residency throughout pregnancy. Yet, in large-scale epidemiology studies, maternal addresses commonly originate from an administrative source., Objective: This study aimed to examine the use of population registry addresses to assign exposure estimations and to evaluate the impact of inaccurate addresses on exposure estimates and association measures of prenatal exposures with congenital hypothyroidism., Methods: We used morbidity data for congenital hypothyroidism from the national program for neonatal screening for 2009-2015 and address data from two sources: population registry and hospital records. We selected neonates with geocoded addresses from both sources (N = 685,491) and developed a comparison algorithm for these addresses. Next, we assigned neonates with exposures from ambient air pollution of PM and NO 2 /NO X , evaluated exposure assessment differences, and used multivariable logistic regression models to assess the impact that these differences have on association measures., Results: We found that most of the exposure differences between neonates with addresses from both sources were around zero and had a leptokurtic distribution density, with most values being zero. Additionally, associations between exposure and congenital hypothyroidism were comparable, regardless of address source and when we limited the model to neonates with identical addresses., Conclusions: We found that ignoring residential inaccuracies results in only a small bias of the associations towards the null. These results strengthen the validity of addresses from population registries for exposure assessment, when detailed residential data during pregnancy are not available., Competing Interests: Declaration of competing interest The authors declared no conflict of interest., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Purpose: To identify factors responsible for variation in health among married individuals, we investigated the independent associations of gaps in spousal age and education (or "heterogamy") with all-cause and cause-specific mortality as well as with survival of cancer patients., Methods: Using over four decades of follow-up data on 36,717 couples from Jerusalem (1964-2016), we compared heterogamous with homogamous couples., Results: Having a less educated spouse was associated with an increased risk for several outcomes in both genders, such as all-cause mortality in males (hazard ratio [HR] = 1.18, 95% confidence interval [CI]: 1.12, 1.25) and in females (HR = 1.11, CI: 1.01, 1.22). Having a more educated spouse was associated with decreased all-cause mortality in males (HR = 0.93, CI: 0.87, 0.99), but not in females. Having an older spouse was detrimental for health of both genders. For example, increased all-cause mortality was seen in men (HR = 1.22, CI: 1.10, 1.34) and in women (HR = 1.10, CI: 1.02, 1.19). A younger spouse was beneficial for some of the outcomes in males, such as decreased cancer-specific mortality (HR = 0.88, CI: 0.78, 0.99), but not in females., Conclusions: Spousal gaps in education and age may be independently associated with health outcomes. The observed relationships may be driven by combined amounts of marital strain as well as shared spousal resources (such as knowledge or income) depending on gender., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: This study describes the characteristics of hand trauma treated in community-based emergency centers (CBECs) in Israel. It was hypothesized that the rate of hand trauma, as well as patient and injury characteristics, would differ from a recent study of patients treated in hospital emergency departments (EDs) in Jerusalem., Methods: Data on all hand injury patients treated at any of the CBECs belonging to a large nationwide chain in 2017 were retrieved from the electronic medical records of the treatment centers, including demographic and clinical characteristics., Results: Over the course of 2017, 53,574 individuals were treated for forearm, wrist and hand injuries (35% of all trauma patients treated during this period). The majority of the patients were male (62%). Contusions and fractures were common (80%) with a minority of lacerations (10%). Crush injuries and amputations were rare. Dog bites accounted for 1.5% of the injuries under the age of 10. Females were treated more with painkillers and opioids, especially over the age of 65, with variability between centers. Although the rate of fractures was similar between teens and the elderly, the elderly were treated with immobilization less frequently, and were referred to EDs for further care. Hospital referral rates differed significantly between centers., Discussion: A higher rate of hand trauma was found in the CBECs in comparison to the hospital ED report (35% vs. 20% of all trauma patients, respectively). Patients treated at the CBECs, in comparison to the ED, were less often male, less often young adults, and differed in terms of type of injury. In the CBECs there were more contusions, as well as fewer lacerations and open wound injuries. In contrast, dog bites in children were found to be much more prevalent than previously reported. Hospital referral indications, the use of immobilization and pain management were found to vary according to age, gender and treatment center. Due to the high rate of hand trauma in CBECs, specific protocols are needed for these patients. The use of opioids should be specifically addressed, considering recent changes in treatment protocols. Thus, the prevalence and characteristics of hand trauma may be biased in studies based on hospital records., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Parental lineage has been shown to increase the risk of Alzheimer's disease (AD) in the offspring, with greater risk attributed to maternal lineage. While 40 genes/loci have been linked to the risk of developing AD, none has been found on the X chromosome. We propose a new method to estimate the risk for developing AD mediated by the X chromosome in a subgroup of late-onset AD (LOAD) patients with amnestic mild cognitive impairment (aMCI) or early AD and unilateral ancestral history of AD or dementia, and pilot-test it on our clinic data. Records of patients aged 55-80 years presenting to our Memory Disorders Clinic with aMCI or early AD between May 2015 and September 2020, were reviewed, counting patients with a family history of AD or dementia and unilateral ancestral lineage. The X chromosome-attributable relative risk was estimated by calculating the following odds ratio (OR): (women with paternal lineage:women with maternal lineage)/(men with paternal lineage:men with maternal lineage). The proportion of genetic risk borne by the X chromosome is equal to (OR-1)/OR. 40 women aged 66.1 ± 5.1 years (mean ± standard deviation) and 31 men aged 68.1 ± 6.5 were identified. The OR was (18:22)/(6:25) = 3.4 (95% confidence interval 1.1-10.1; p = 0.027). The estimated proportion of genetic risk borne by the X chromosome in this population is 70% (95% CI 12-90%). This paper presents the first application of a new method. The numbers are small, the confidence intervals wide. The findings need to be replicated. The method may be generalizable to other diseases., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aims: There is conflicting evidence regarding the association between proton pump inhibitors (PPI) and the risk of acquisition and severity of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Aim: To evaluate the association between PPI exposure and infection and development of severe disease in patients infected with SARS-CoV2in a large population-based historical cohort. Methods: Data were extracted from a health maintenance organization database in Israel that insures over 1,200,000 individuals from across the country. All patients who underwent SARS-CoV-2 testing between March and November 2020 were included. Logistic regression and matched analyses were used to compare patients prescribed and exposed to PPIs to those not prescribed PPIs regarding SARS-CoV-2 positivity. In addition, among SARS-CoV-2 positive patients (n = 44,397) the likelihood of developing severe disease, defined by a composite endpoint of death, ICU admission and prolonged hospitalization, was compared in those exposed and not exposed to PPIs. Results: Among 255,355 adult patients who underwent SARS-CoV-2 testing by PCR, 44,397 (17.4%) were positive for SARS-CoV-2 and 12,066 (4.7%) patients were prescribed PPIs in the 3 months before testing. In a multivariable logistic regression model controlling for age, gender, smoking status, BMI, diabetes mellitus, hypertension, COPD, history of ischemic heart disease and fasting blood glucose (FBG) levels, no significant association was found between PPIs and SARS-CoV-2 positivity ( p = 0.09 aOR 0.94, 95% CI - 0.88-1.01). Among SARS-CoV-2 positive patients, 910 (2%) had a severe infection. Multivariate logistic regression controlling for the abovementioned confounders, showed no such association between PPIs and severe COVID-19 ( p = 0.28). Elevated FBG levels were significantly associated with both PPI exposure ( p < 0.001) and severe COVID-19 infection ( p < 0.001). These results were reinforced by a matched analysis (n = 655 pairs). Conclusion: PPIs are spuriously associated with severe COVID-19 due to the presence of elevated FBG as a confounder. Our study accounted for the FBG levels of patients and known risk factors for severe COVID-19 infection, which may be the reason for the discrepancy in prior studies. These results may aid in understanding potential confounders when evaluating potential associations of PPIs with other respiratory or viral diseases., Competing Interests: Authors AS and MB were employed by the company Meuhedet Health Medical Organization. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shafrir, Benson, Katz, Hershcovici, Bitan, Paltiel, Calderon-Margalit, Safadi and Shauly-Aharonov.)

Background: The global prevalence of childhood obesity has risen dramatically recently. Previous studies found an association between rapid infant weight gain and childhood overweight. Evidence suggests that exposure to high ambient air temperatures during prenatal life and during adulthood is associated with birthweight and obesity respectively., Objective: The objective of this study was to examine whether exposure to high ambient temperatures during infancy is associated with rapid infant weight gain in Israel., Methods: This is a population-based historical cohort study using data from the Israeli national public network of maternal and child health clinics between 2008 and 2013. We assessed exposure to ambient temperature in the first year of life using a high-resolution hybrid spatio-temporal model and calculated annual mean and minimum temperatures for each infant based on daily mean and minimum temperatures at the community clinic location. We defined rapid infant weight gain as a World Health Organization weight z-score difference >0.67 between birthweight and weight at age one year. We estimated these associations using log-linear and general additive models and adjusted for population group, district, maternal age, parental education, parity, sex, gestational age, birthweight, calendar year and calendar month of birth., Results: The study population included 217,310 singleton-term infants. Adjusted models demonstrated a positive association between ambient temperature exposure and rapid infant weight gain. Compared to the third quintile of minimum temperature, infants exposed to the first and second quintile had an adjusted relative risk of 0.98 (95% CI 0.96, 1.00) and 0.97 (95% CI 0.95, 0.98), respectively, while those exposed to the fourth and fifth quintiles had an adjusted relative risk of 1.06 (95% CI 1.04, 1.07) and 1.02 (95% CI 1.00, 1.04) respectively. The associations with mean temperature were similar but slightly weaker., Conclusions: Exposure to higher ambient temperatures, of emerging importance in the climate change era, is associated with rapid infant weight gain in Israel. Future studies should use additional exposure, covariate, and outcome data to analyse the nature and the source of this association in more detail., (© 2021 John Wiley & Sons Ltd.)

Adequate thyroid hormone availability is required for normal brain development. Studies have found associations between prenatal exposure to air pollutants and thyroid hormones in pregnant women and newborns. We aimed to examine associations of trimester-specific residential exposure to common air pollutants with congenital hypothyroidism (CHT). All term infants born in Israel during 2009-2015 were eligible for inclusion. We used data on CHT from the national neonatal screening lab of Israel, and exposure data from spatiotemporal air pollution models. We used multivariable logistic regression models to estimate associations of exposures with CHT, adjusting for ethnicity, socioeconomic status, geographical area, conception season, conception year, gestational age, birth weight, and child sex. To assess residual confounding, we used postnatal exposures to the same pollutants as negative controls. The study population included 696,461 neonates. We found a positive association between third-trimester nitrogen oxide exposure and CHT (per interquartile-range change, odds ratio = 1.23, 95% confidence interval: 1.08, 1.41) and a similar association for nitrogen dioxide. There was no evidence of residual confounding or bias by correlation among exposure periods for these associations., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We conducted a prospective study, aimed to study whether the prevalence of mental disorders after birth differs by country of origin. Parturient mothers of Ethiopian origin, Former-USSR (FSU) origin, or nonimmigrant, native-Israeli origin ( n = 974, all Jewish) were recruited in hospitals in Israel and were followed 6-8 weeks and one year after birth. General linear models were used to study the associations between origin and mental health, comparing Ethiopian and FSU origin with native-Israeli. Ethiopian and FSU mothers were more likely to report on somatic symptoms, compared with native-Israeli women. Ethiopian origin was negatively and significantly associated with anxiety in all three interviews (β = -1.281, β = -0.678 and β = -1.072, respectively; p < 0.05 in all). FSU origin was negatively associated with depression after birth (β = -0.709, p = 0.036), and negatively associated with anxiety after birth and one-year postpartum (β = -0.494, and β = -0.630, respectively). Stressful life events were significantly associated with all mental disorders in the three time points of interviews. Our findings suggest that immigrants tend to express higher mental distress with somatic symptoms. Additional tools are needed for mental distress screening among immigrants.

Conventional treatments of peripheral vascular disease and coronary artery disease have partial success but are still limited. Methods to deliver angiogenic factors into ischemic areas using gene, protein and cell therapies are faced with difficult issues such a delivery, effective concentration and duration of action. Tissue engineering offers the possibility of creating a functional self-contained three-dimensional (3D) unit that works as a coordinated biological pump that can secrete a whole range of angiogenic factors. We report a tissue engineering approach using decellularized micro-fragments and mesenchymal stem cells (MSCs) to create a vascular inducing device (VID). Proteomic analysis of the decellularized micro-fragments and of the VIDs reveals a large number of extracellular-matrix (ECM) proteins. Moreover, the VIDs were found to transcribe and secrete a whole repertoire of angiogenic factors in a sustained manner. Furthermore, preliminary results of implantation VIDs into non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice indicate formation of vascular network at the site within a week. We propose that those VIDs could serve as a safe, localized, simple and powerful method for the treatment of certain types of vascular diseases., (Copyright © 2021 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Background: Pyelonephritis is the most common serious bacterial infection during childhood. The long-term importance of kidney scarring is unclear., Objective: To assess the risk of end-stage kidney disease (ESKD) in adolescents and young adults with history of pyelonephritis., Study Design: 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)., Results: 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., Conclusion: History of pyelonephritis was associated with significantly increased risk of treated ESKD, particularly when associated with kidney scarring or reduced baseline kidney function., (© 2020. Italian Society of Nephrology.)

Purpose: Primary care physicians have an important role in encouraging adequate cancer screening. Disparities in cancer screening by socioeconomic status (SES) may affect presentation stage and cancer survival. This study aimed to examine whether breast, colorectal, and cervical cancer screening rates in women differed by SES and age, and whether screening rates and SES disparities changed after introduction of a primary care-based national quality indicator program., Methods: This repeated cross-sectional study spanning 2002-2017 included all female Israeli residents in age ranges appropriate for each cancer screening assessed. SES was measured both as an individual-level variable based on exemption from copayments and as an area-level variable using census data., Results: In 2017, the most recent year in the study period, screening rates among 1,529,233 women were highest for breast cancer (70.5%), followed by colorectal cancer (64.3%) and cervical cancer (49.6%). Women in the highest area-level SES were more likely to undergo cervical cancer screening compared with those in the lowest (odds ratio = 3.56; 99.9% CI, 3.47-3.65). Temporal trends showed that after introduction of quality indicators for breast and colorectal cancer screening in 2004 and 2005, respectively, rates of screening for these cancers increased, with greater reductions in disparities for the former. The quality indicator for cervical cancer screening was introduced in 2015, and no substantial changes have occurred yet for this screening., Conclusions: We found increased uptake and reduced socioeconomic disparities after introduction of cancer screening indicators. Recent introduction of a cervical cancer screening indicator may increase participation and reduce disparities, as has occurred for breast and colorectal cancer screening. These findings related to Israel's quality indicators program highlight the importance of primary care clinicians in increasing cancer screening rates to improve outcomes and reduce disparities., (© 2021 Annals of Family Medicine, Inc.)

Among the challenges presented by the SARS-CoV2 pandemic are those related to balancing societal priorities with averting threats to population health. In this exceptional context a group of Israeli physicians and public health scholars (multidisciplinary academic group on children and coronavirus [MACC]) coalesced, examining the role of children in viral transmission and assessing the necessity and consequences of restricted in-class education. Combining critical appraisal and analytical skills with public health experience, MACC advocated for safe and monitored school re-opening, stressing the importance of education as a determinant of health, continuously weighing this stance against evolving COVID-19-risk data. MACC's activities included offering research-based advice to government agencies including Ministries of Health, Finance, and Education. In a setting where government bodies were faced with providing practical solutions to both decreasing disease transmission and maintaining society's vital activities, and various advisors presented decision-makers with disparate views, MACC contributed epidemiological, clinical and health policy expertise to the debate regarding school closure as a pandemic control measure, and adaptations required for safe re-opening. In this paper, we describe the evolution, activities, policy inputs and media profile of MACC, and discuss the role of academics in advocacy and activism in the midst of an unprecedented public health crisis. A general lesson learned is that academics, based on the rigor of their scientific work and their perceived objectivity, can and should be mobilized to pursue and promote policies based on shared societal values as well as empiric data, even when considerable uncertainty exists about the appropriate course of action. Mechanisms should be in place to open channels to multidisciplinary academic groups and bring their input to bear on decision-making., (© 2021. The Author(s).)

Research on mortality associated with exposure to the Holocaust is relevant for a better understanding of the effects of genocides on survivors. To our knowledge, previous studies have not investigated the long-term cause-specific mortality of Holocaust survivors. We compared mortality rates among Israelis born in European countries controlled by the Nazis during World War II with those among Israelis of European descent who did not have this exposure. Records of 22,671 people (45% women; 5,042 survivors) from the population-based Jerusalem Perinatal Study (1964-1976) were linked to the Israeli Population Registry, which was updated through 2016. Cox models were used for analysis, with 2-sided tests of statistical significance. Risk of all-cause mortality was higher among exposed women (hazard ratio (HR) = 1.15, 95% confidence interval (CI): 1.05, 1.27) than in unexposed women. No association was found between Holocaust exposure and male all-cause mortality. In both sexes, survivors had higher cancer-specific mortality (HR = 1.17 (95% CI: 1.01, 1.35) in women and HR = 1.14 (95% CI: 1.01, 1.28) in men). Exposed men also had excess mortality due to coronary heart disease (HR = 1.39, 95% CI: 1.09, 1.77) and lower mortality from other known causes combined (HR = 0.86, 95% CI: 0.75, 0.99). In summary, experiencing the Holocaust was associated with excess all-cause and cancer-specific mortality in women and cancer- and coronary heart disease-specific mortality in men., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We recently developed a molecule (GT-73) that blocked leukocyte transendothelial migration from blood to the peripheral tissues, supposedly by affecting the platelet endothelial cell adhesion molecule (PECAM-1) function. GT-73 was tested in an LPS-induced acute respiratory distress syndrome (ARDS) mouse model. The rationale for this is based on the finding that the mortality of COVID-19 patients is partly caused by ARDS induced by a massive migration of leukocytes to the lungs. In addition, the role of tert -butyl and methyl ester moieties in the biological effect of GT-73 was investigated. A human leukocyte, transendothelial migration assay was applied to validate the blocking effect of GT-73 derivatives. Finally, a mouse model of LPS-induced ARDS was used to evaluate the histological and biochemical effects of GT-73. The obtained results showed that GT-73 has a unique structure that is responsible for its biological activity; two of its chemical moieties ( tert -butyl and a methyl ester) are critical for this effect. GT-73 is a prodrug, and its lipophilic tail covalently binds to PECAM-1 via Lys536. GT-73 significantly decreased the number of infiltrating leukocytes in the lungs and reduced the inflammation level. Finally, GT-73 reduced the levels of IL-1β, IL-6, and MCP-1 in bronchoalveolar lavage fluid (BALF). In summary, we concluded that GT-73, a blocker of white blood cell transendothelial migration, has a favorable profile as a drug candidate for the treatment of ARDS in COVID-19 patients.

Importance: Patients with diabetes are known to be at increased risk for infections including severe coronavirus disease 2019 (COVID-19) but the relationship between COVID-19 severity and specific pre-infection glucose levels is not known., Objective: To assess the differential effects of pre-infection glucose levels on the risk for severe COVID-19 amongst patients with and without diabetes., Design: Population based historical cohort study., Setting: National state-mandated HMO., Patients: All adult patients with a positive SARS-COV2 test between March-October 2020., Exposure: Recent fasting blood glucose (FBG) and glycated hemoglobin (HBA1C), age, gender, body mass index (BMI) and diagnoses of diabetes, hypertension, ischemic heart disease., Outcome: Risk for severe COVID-19, defined as resulting in ≥10 hospitalization days, ICU admission or death., Results: 37,121 patients with a positive SARS-COV2 test were identified; 707 defined as severe (1.9%). Unadjusted risk factors for severe disease were age (OR = 1.1 for every year increase; 95% CI 1.09-1.11, p < 0.001), male gender (OR = 1.34, 95% CI 1.06-1.68, p = 0.012); BMI (OR = 1.02 for 1 kg/m2 increase, 95% CI 1.00-1.04, p = 0.025). Controlling for these factors, we found an association between pre-infection FBG and the risk of severe COVID-19, with a differential effect in patients with and without a diagnosis of diabetes. For patients without diabetes, elevated FBG in the pre-diabetes range (106-125 mg/dl) was associated with severe COVID-19 (OR 1.55 95% CI 1.04-2.26 p = 0.027). For patients with a diagnosis of diabetes, we found a J-shaped association between pre-infection glucose control and the risk for severe COVID-19 where the lowest risk for was for patients with FBG 106-125 mg/dl; the risk increased with higher pre-infection glucose levels but strikingly also for patients with a low pre-infection FBG (<100mg/dl) or HbA1C (<5.7%)., Conclusions and Relevance: Elevated pre-infection blood glucose is a risk factor for severe COVID-19 even in non-diabetics. For patients with a diagnosis of diabetes both high as well as low pre-infection glucose levels are risk factors for severe COVID-19. Further research is required to assess whether these associations are causal, but we believe these findings can already have clinical implications for COVID-19 risk assessment and stratification., Competing Interests: The authors have declared that no competing interests exist.

Background: The coronavirus disease-2019 (COVID-19) pandemic forced drastic changes in all layers of life. Social distancing and lockdown drove the educational system to uncharted territories at an accelerated pace, leaving educators little time to adjust., Objectives: To describe changes in teaching during the first phase of the COVID-19 pandemic., Methods: We described the steps implemented at the Technion-Israel Institute of Technology Faculty of Medicine during the initial 4 months of the COVID-19 pandemic to preserve teaching and the academic ecosystem., Results: Several established methodologies, such as the flipped classroom and active learning, demonstrated effectiveness. In addition, we used creative methods to teach clinical medicine during the ban on bedside teaching and modified community engagement activities to meet COVID-19 induced community needs., Conclusions: The challenges and the lessons learned from teaching during the COVID-19 pandemic prompted us to adjust our teaching methods and curriculum using multiple online teaching methods and promoting self-learning. It also provided invaluable insights on our pedagogy and the teaching of medicine in the future with emphasis on students and faculty being part of the changes and adjustments in curriculum and teaching methods. However, personal interactions are essential to medical school education, as are laboratories, group simulations, and bedside teaching.

Chronic kidney disease (CKD) is a major public health challenge, affecting as much as 8 to 18% of the world population. Identifying childhood risk factors for future CKD may help clinicians make early diagnoses and initiation of preventive interventions for CKD and its attendant comorbidities as well as monitoring for complications. The purpose of this review is to describe childhood risk factors that may predict development of overt kidney disease later in life. Currently, there are multiple childhood risk factors associated with future onset and progression of CKD. These risk factors can be grouped into five categories: genetic factors (e.g., monogenic or risk alleles), perinatal factors (e.g., low birth weight and prematurity), childhood kidney diseases (e.g., congenital anomalies, glomerular diseases, and renal cystic ciliopathies), childhood onset of chronic conditions (e.g., cancer, diabetes, hypertension, dyslipidemia, and obesity), and different lifestyle factors (e.g., physical activity, diet, and factors related to socioeconomic status). The available published information suggests that the lifelong risk for CKD can be attributed to multiple factors that appear already during childhood. However, results are conflicting on the effects of childhood physical activity, diet, and dyslipidemia on future renal function. On the other hand, there is consistent evidence to support follow-up of high-risk groups.

Aims: Postpartum depression (PPD) is the most common complication women experience after delivery. We aimed to examine the association of maternal PPD with delays in child development, in a population-based study, in the first two years of life., Methods: A nation-wide population-based historical cohort study in the setting of the Mother and Child Health Clinics in Israel, where infants are routinely evaluated for growth and development. Data were retrieved on 96,623 infants born in 2014-2015 whose mothers had PPD screening. Logistic regressions were used to estimate the associations of PPD with the achievements of developmental milestones, controlling for potential confounders., Results: PPD was identified in 4,268 mothers (4.7%). PPD was associated with delays in language skills, including the production of voices in dialogue (OR=1.88, 95% CI: 1.41-2.52) and speaking 2-3 words (OR=1.24, 95% CI: 1.13-1.37). PPD was associated with about 1.5 times increased odds of delays in personal-social skills, including reacting to voices (OR=1.43, 95% CI: 1.22-1.67) and pointing to selected objects (OR=1.47 95% CI: 1.10-1.97). Associations were also seen with delays in fine motor and adaptive skills, such as pinching (OR=1.50, 95% CI: 1.20-1.86), and gross motor skills, such as ground crawling (OR=1.36, 95% CI: 1.15-1.60)., Conclusions: In this population-based large cohort study, PPD as estimated in a national screening program, was associated with delays in early child development, which were shown in all assessed domains. Future studies should confirm our results and intervention programs should be developed to effectively minimize these gaps., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: We planned an observational study to assess obstetric anesthesia services nationwide. We aimed to assess the effect of the anesthesia workload/workforce ratio on quality and safety outcomes of obstetric anesthesia care., Methods: Observers prospectively collected data from labor units over 72 h (Wednesday, Thursday and Friday). Independent variables were workload (WL) and workforce (WF). WL was assessed by the Obstetric Anesthesia Activity Index (OAAI), which is the estimated time in a 24-h period spent on epidurals and all cesarean deliveries. Workforce (WF) was assessed by the number of anesthesiologists dedicated to the labor ward per week. Dependent variables were the time until anesthesiologist arrival for epidural (quality measure) and the occurrence of general anesthesia for urgent Cesarean section, CS, (safety measure). This census included vaginal deliveries and unscheduled (but not elective) CS., Results: Data on 575 deliveries are from 12 maternity units only, primarily because a major hospital chain chose not to participate; eight other hospitals lacked institutional review board approval. The epidural response rate was 94.4%; 321 of 340 parturients who requested epidural analgesia (EA) received it. Of the 19 women who requested EA but gave birth without it, 14 (77%) were due to late arrival of the anesthesiologist. Median waiting times for anesthesiologist arrival ranged from 5 to 28 min. The OAAI varied from 4.6 to 25.1 and WF ranged from 0 to 2 per shift. Request rates for EA in hospitals serving predominantly orthodox Jewish communities and in peripheral hospitals were similar to those of the entire sample. More than a fifth (13/62; 21%) of the unscheduled CS received general anesthesia, and of these almost a quarter (3/13; 23%) were attributed to delayed anesthesiologist arrival., Conclusions: Inadequate WF allocations may impair quality and safety outcomes in obstetric anesthesia services. OAAI is a better predictor of WL than delivery numbers alone, especially concerning WF shortage. To assess the quality and safety of anesthetic services to labor units nationally, observational data on workforce, workload, and clinical outcomes should be collected prospectively in all labor units in Israel.

Objectives: To assess time trends in colorectal cancer screening uptake, time-to-colonoscopy completion following a positive fecal occult blood test and associated patient factors, and the extent and predictors of longitudinal screening adherence in Israel., Setting: Nation-wide population-based study using data collected from four health maintenance organizations for the Quality Indicators in Community Healthcare Program., Methods: Screening uptake for the eligible population (aged 50-74) was recorded 2003-2018 using aggregate data. For a subcohort (2008-2012, N = 1,342,617), time-to-colonoscopy following a positive fecal occult blood test and longitudinal adherence to screening guidelines were measured using individual-level data, and associated factors assessed in multivariate models., Results: The annual proportion screened rose for both sexes from 11 to 65%, increasing five-fold for age group 60-74 and >six-fold for 50-59 year olds, respectively. From 2008 to 2012, 67,314 adults had a positive fecal occult blood test, of whom 71% eventually performed a colonoscopy after a median interval of 122 (95% confidence interval 110.2-113.7) days. Factors associated with time-to-colonoscopy included age, socioeconomic status, and comorbidities. Only 25.5% of the population demonstrated full longitudinal screening adherence, mainly attributable to colonoscopy in the past 10 years rather than annual fecal occult blood test performance (83% versus 17%, respectively). Smoking, diabetes, lower socioeconomic status, cardiovascular disease, and hypertension were associated with decreased adherence. Performance of other cancer screening tests and frequent primary care visits were strongly associated with adherence., Conclusions: Despite substantial improvement in colorectal cancer screening uptake on a population level, individual-level data uncovered gaps in colonoscopy completion after a positive fecal occult blood test and in longitudinal adherence to screening, which should be addressed using focused interventions.

Introduction: Elective clerkships in low income countries have been an integral part of the curriculum in the majority of medical schools worldwide. These programs expose students to global challenges, to a diversity of cultures and healthcare systems, and have been shown to improve medical knowledge, as well as clinical and communication skills. In 2018 and 2019, the Faculty of Medicine at the Technion, in cooperation with the Department for Infectious Diseases in the Rambam Health Care campus and the "Brit Olam" nonprofit organization, offered a clinical clerkship in Kiboga hospital, Uganda. The elective took place in a public governmental hospital located in one of the poorest districts of Uganda. During a three-week period, the students accompanied by Israeli and Uganda tutors, participated in clinical rounds and other clinical activities in various departments of the hospital. This manuscript, describes the students' experiences in Kiboga. During the short elective, students had a unique opportunity to observe a different culture, immerse in a completely different healthcare system, learn about how a detailed medical history and a thorough physical examination can lead to diagnosis (without extensive diagnostic tests), and closely observe ethical challenges and difficult clinical decisions. The elective helped students develop personally and professionally and solidify their commitment to medicine. Currently, in Israeli medical schools, there are a few programs which expose students to medicine in low-resource countries. We believe that expanding the understanding of Global Health through courses and overseas opportunities in long-term partnerships, can improve the students' medical education.

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., (Copyright © 2021 by the American Society of Nephrology.)