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Infection and lockdowns resulting from COVID-19 have been suggested to increase the prevalence and treatment rates of Attention Deficit/Hyperactivity Disorder (ADHD). To accurately estimate the pandemic's effects, pre-pandemic data can be used to estimate diagnosis and treatment rates during the COVID-19 years as if the COVID-19 pandemic did not occur. However, accurate predictions require a broad dataset, both in terms of the number of cases and the pre-pandemic timeframe. In the current study, we modeled monthly ADHD diagnosis and treatment rates over the 18 years preceding the COVID-19 pandemic. The dataset included ∼3 million cases for individuals aged 6 to 18 from the Clalit Health Services' electronic database. Using a trained model, we projected monthly rates for post-lockdown and post-infection periods, enabling us to estimate the expected diagnosis and treatment rates without the COVID-19 pandemic. We then compared these predictions to observed data, stratified by age groups, gender, and socioeconomic status. Our findings suggest no influence of the COVID-19 pandemic on ADHD diagnosis or treatment rates. We show that a narrower timeframe for pre-COVID-19 data points can lead to incorrect conclusions that COVID-19 affected ADHD diagnosis rates. Findings are discussed, given the assumed impact of the COVID-19 pandemic on ADHD., Competing Interests: Declaration of competing interest The authors declare no conflicts or competing interests relevant to this article., (Copyright © 2024. Published by Elsevier B.V.)

Benign transient hyperphosphatasemia is a condition characterized by greatly increased serum alkaline phosphatase (ALP) without laboratory or clinical evidence of underlying bone or liver disease. It is usually identified incidentally during routine blood testing. We describe the demographic and clinical characteristics of benign transient hyperphosphatasemia in a cohort of healthy infants and children. We performed a retrospective review of electronic medical records on all children aged 1 day to 18 years with a diagnosis of benign transient hyperphosphatasemia, who were registered at 3 central districts in Israel from January 1, 2000, to December 31, 2020. The demographic and clinical characteristics were retrieved from the medical files. The study group comprised 382 infants and children aged from 2 months to 14 years who had serum ALP > 1000 U/L (mean 2557 U/L, range 1002-14,589 U/L). The majority of participants (87%) were aged up to 24 months (median age 14 months, IQR 10-18 months). Fifty-four percent of the study participants were male. In many patients, there was a history of recent fever, gastroenteritis or diarrhea, acute otitis media, and viral infection. A seasonal peak was observed in autumn-early winter, but this may be a detection bias., Conclusion: Benign transient hyperphosphatasemia seems to be a disorder described among otherwise healthy infants and children, which resolves spontaneously. Other known causes of markedly elevated serum ALP should be excluded, especially bone and liver disease. Higher awareness and recognition of this benign condition are important in order to avoid unnecessary tests and parental anxiety., What Is Known: • Benign transient hyperphosphatasemia is a benign condition characterized by greatly increased serum alkaline phosphatase without laboratory or clinical evidence of underlying bone or liver disease, which usually resolves spontaneously, with no intervention., What Is New: • In the case of an incidental finding of high serum alkaline phosphatase in an otherwise healthy infant or child with no other clinical or laboratory suspicion of bone or liver disease, we recommend repeating the alkaline phosphatase level within a few months in order to confirm the resolution of this condition. • When benign transient hyperphosphatasemia is suspected, a "wait and see" approach is optimal in order to avoid unnecessary investigations and parental anxiety., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Group A Streptococcus (GAS), the predominant bacterial pathogen of pharyngitis, is sometimes difficult to distinguish clinically from viral pharyngitis. Despite the high prevalence of viral pharyngitis in children, antibiotic treatment is common., Objectives: To investigate the effectiveness of an antibiotic stewardship program (ASP) on antibiotic prescription in children with GAS pharyngitis (GAS-P) at a large pediatric community clinic., Methods: Antibiotic prescription data were collected from October 2016 to March 2017 (pre-intervention period) and from October 2017 to March 2018 (post-intervention period). The intervention was a one-day seminar for primary care pediatricians on the diagnosis and treatment of GAS-P in children according to national guidelines., Results: The overall prevalence of testing differed between the two time periods. There was a decrease in children who did not undergo any testing (from 68% to 63%), an increase in streptococcal rapid antigen detection testing (28% to 32%), and a slight increase in throat cultures (3% to 4%) (P = 0.02). There was no change in the types of antibiotics prescribed before and after the intervention (P = 0.152)., Conclusions: The ASP resulted in a slight reduction in the percentage of children who did not undergo laboratory testing for GAS-P and a slight reduction in the percentage of children who received antibiotic treatment. The ASP did not reduce the use of broad-spectrum antibiotics and macrolides.

Objective: To compare the rate of the administration of the Pfizer-BioNTech COVID-19 vaccinations between adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD) and non-ADHD subjects., Method: A retrospective chart review was performed on all adolescents aged 12-17 years registered at a central district in Israel from January 1 st 2021 to October 31 st 2021., Results: Of the 46,544 subjects included in the study, 8241 (17.7%) were diagnosed with ADHD. Of them, 3% were PCR-COVID-19 positive. Among the patients with ADHD, the older adolescents were more likely to be vaccinated: 48.8% of those aged 12-15 years were vaccinated versus 59.6% of patients aged 16-17 years. The ultra-orthodox Jewish and Arab adolescents in the ADHD group were far less likely to be vaccinated (22.9% and 34.6%, respectively), compared to the adolescents with ADHD in the general population (60.5%). Girls were also somewhat more likely to be vaccinated., Conclusions: Adolescents diagnosed with ADHD had a higher COVID-19 vaccination rate compared to their non-ADHD counterparts. The vaccine uptake was lower amongst Arab and ultra-orthodox Jewish populations.

Objective: Three aims: to elucidate determinants associated with COVID-19 vaccine uptake in children and the association with parental vaccination; to compare rates of PCR-positive SARS-CoV-2 results between vaccinated and unvaccinated children; to estimate the rate of parental COVID-19 vaccination and its association with the vaccination rate of their children., Methods: We performed a retrospective chart review of all children aged 5-11 years registered at a central district in Israel from November 21st, 2021 to April 30th, 2022, and characterized COVID-19 vaccinated vs. unvaccinated individuals. Data retrieved from the electronic medical files included: demographics [age, gender, sector, socioeconomic status (SES)]; COVID-19 vaccination (first and second doses) and influenza vaccination status; co-morbidities; and parental vaccinations for COVID-19. We divided the population into three distinct demographic groups: non-ultra-orthodox Jews (43,889 children), ultra-orthodox Jews (13,858 children), and Arabs (4,029 children)., Results: Of the 61,776 children included in the study, 20,355 (32.9%) received at least one dose of the COVID-19 vaccine. Vaccination rates were similar amongst males and females and were higher in children aged 9-11 years compared to children aged 5-6 years. Multivariate analysis identified five independent determinants that were significantly ( p  < 0.001) associated with low vaccination rates: Arab and ultra-orthodox sectors (odds ratios: 0.235 and 0.617, respectively); children aged 5-8 years; children of low SES; and children who had not received previous seasonal influenza vaccination. Relatively high vaccination rates were noted amongst children with the following medical co-morbidities: treatment with biological agents (42.9%); solid tumor transplantation (42.9%); type 1 diabetes mellitus (38.5%), asthma (38.2%), and attention deficit and hyperactivity disorder (ADHD) (37.6%). Regarding the uptake of two vaccine doses among children with co-morbidities, it was highest in those with type 1 diabetes mellitus, heart failure, treatment with biological agents, asthma and obesity., Conclusion: This study highlights several pediatric sub-populations with low and high vaccine uptake. It is essential to focus on determinants associated with low vaccination rates., Competing Interests: The 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. The reviewer [CL] declared a past co-authorship with one of the authors [SA] to the handling editor,, (© 2023 Hoshen, Shkalim Zemer, Ashkenazi, Grossman, Gerstein, Yosef, Cohen and Cohen.)

Introduction: Previous studies have shown disruption of glycometabolic control and new diabetes mellitus (DM) diagnosis among patients with COVID-19. It is still unclear how the association of COVID-19 and new-onset DM may be modified by disease severity or vary over time, during acute and post-acute phases., Research Design and Methods: In this retrospective matched cohort study, 157 936 patients with COVID-19 (aged ≥25 years, diagnosis date between March 01, 2020 and August 31, 2021) were compared with individuals without COVID-19, separately for non-hospitalized, hospitalized, and severe hospitalized patients. Stratified Cox proportional hazards models, with changing baseline time (starting at the date of COVID-19 diagnosis, and at 1, 2, 3, and 4 months afterwards), were used to evaluate the occurrence of new DM in relation to COVID-19 infection in different time frames-from each landmark date until end of study., Results: During mean follow-up time of 10.9 months, there were 1145 (0.72%) new diagnoses of DM compared with 1013 (0.64%) in the individuals without COVID-19 (p=0.004). Non-hospitalized patients with COVID-19 were not at higher risk of new DM neither during the acute phase nor afterward. Hospitalized patients with COVID-19 had a higher risk of developing DM, with the highest risk among severe hospitalized patients. This risk among hospitalized patients was highest in the acute phase (HR 2.47 (95% CI 1.86 to 3.29)), attenuated over time, but remained significant at 4-month landmark analysis (HR 1.60 (95% CI 1.12 to 2.29))., Conclusions: Acute and post-acute COVID-19 were associated with new DM only among hospitalized patients, with the highest risk among those hospitalized with severe disease. Those patients should be followed and monitored post-discharge for new DM. Patients who were not hospitalized did not have higher risk of new-onset DM., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

During the COVID-19 pandemic, postexposure-vaccine-prophylaxis is not a practice. Following exposure, only patient isolation is imposed. Moreover, no therapeutic prevention approach is applied. We asked whether evidence exists for reduced mortality rate following postexposure-vaccine-prophylaxis. To estimate the effectiveness of postexposure-vaccine-prophylaxis, we obtained data from the Israeli Ministry of Health registry. The study population consisted of Israeli residents aged 12 years and older, identified for the first time as PCR-positive for SARS-CoV-2, between December 20th, 2020 (the beginning of the vaccination campaign) and October 7th, 2021. We compared "recently injected" patients-that proved PCR-positive on the same day or on 1 of the 5 consecutive days after first vaccination (representing an unintended postexposure-vaccine-prophylaxis)s-to unvaccinated control group. Among Israeli residents identified PCR-positive for SARS-CoV-2, 11 687 were found positive on the day they received their first vaccine injection (BNT162b2) or on 1 of the 5 days thereafter. In patients over 65 years, 143 deaths occurred among 1412 recently injected (10.13%) compared to 255 deaths among the 1412 unvaccinated (18.06%), odd ratio (OR) 0.51 (95% confidence interval [CI]: 0.41-0.64; p < 0.001). A significant reduction in the death toll was observed among the 55-64 age group, with 8 deaths occurring among the 1320 recently injected (0.61%) compared to 24 deaths among the 1320 unvaccinated control (1.82%), OR 0.33 (95% CI: 0.13-0.76; p = 0.007). Postexposure-vaccine-prophylaxis is effective against death in COVID-19 infection., (© 2022 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: We aimed to elucidate variables associated with coronavirus disease 2019 (COVID-19) vaccine compliance in adolescents and devise targeted interventions. Our secondary aim was to compare the rates of severe acute respiratory syndrome coronavirus 2 infection, hospitalizations and deaths between vaccinated and unvaccinated adolescents., Methods: A retrospective review of electronic medical records was performed on all adolescents 12-17 years of age registered at Clalit Health District in Israel during January 1, 2021, to November 18, 2021, with characterization by vaccination status against COVID-19. Univariate and multivariable analyses were employed to identify predictors of vaccination., Results: Of the 43,919 subjects included in the study, 28,207 (64.2%) were vaccinated. Non-ultraorthodox Jewish adolescents had a higher vaccination rate than the minorities Arabs or ultraorthodox Jews (72.5%, 66.2% and 40.5%, respectively, P &lt; 0.001). Adolescents of high socioeconomic status had nearly 2-fold higher vaccination rates than those of low socioeconomic status (80.4% vs 42.3%; P &lt; 0.0001). Adolescents 16-17 years old had a higher rate of COVID-19 vaccination than those 12-15 years old (72.5% vs 60.6%, P &lt; 0.001), as were girls versus boys (64.7% vs 63.8%, P = 0.047). Multivariate analysis identified 3 independent variables that were significantly ( P &lt; 0.001) associated with low vaccination: ultraorthodox sector, Arab population, and underlying obesity (hazard rations 0.42, 0.72 and 0.84, respectively). Vaccination was significantly associated with reduced severe acute respiratory syndrome coronavirus 2 infection, hospitalization and death ( P &lt; 0.001)., Conclusion: This study highlights several pediatric populations with low COVID-19 vaccine compliance. Targeted interventions aimed at these populations are suggested with consideration of their special cultural, social and societal characteristics., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: We evaluated whether persistent-positive celiac serology is associated with the risk of hypothyroidism., Methods: We extracted a cohort of subjects aged 1-80 years with a positive IgA anti-tissue transglutaminase between January 1, 2008, and December 31, 2012, and a repeat anti-tissue transglutaminase test within 6-36 months from a large population-based electronic medical record database. Based on serology tests, we categorized the pediatric (age &lt;21 years) and adult cohorts into normalized or persistent-positive serology groups. All subjects were followed up for incident diagnosis of hypothyroidism from the last serology date up to December 31, 2017. Hazard ratio (HR) along 95% confidence intervals (CIs) were prepared to evaluate the association of celiac serology group with a diagnosis of hypothyroidism, crude, and adjusted for age, sex, and diagnosis of type 1 diabetes mellitus., Results: Among the pediatric cohort (n = 2,687), during a median follow-up of 64 months (interquartile range 48-80), 2.3% (16/681) of the persistent-positive serology group and 1.0% (20/2,006) of the normalized serology group developed hypothyroidism (HR 2.07 [95% CI 1.07-4.44], adjHR 1.77 [95% CI 0.91-3.46]). The rate among the pediatric cohort with an established diagnosis of celiac disease was 3.4% (10/486) vs 1.0% (5/481), HR 2.83 (0.96-8.32). In the adult cohort (n = 1,286), 4.5% (20/442) of the persistent-positive group and 3.9% (33/811) of the normalized serology group developed hypothyroidism (HR 1.13 [95% CI 0.65-1.97])., Discussion: In this retrospective, age-stratified analysis, we report that persistent-positive serology may be associated with the risk of hypothyroidism among the pediatric population. Prospective cohorts are needed to validate our findings., (Copyright © 2022 by The American College of Gastroenterology.)

Background: The oral protease inhibitor nirmatrelvir has shown substantial efficacy in high-risk, unvaccinated patients infected with the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data regarding the effectiveness of nirmatrelvir in preventing severe coronavirus disease 2019 (Covid-19) outcomes from the B.1.1.529 (omicron) variant are limited., Methods: We obtained data for all members of Clalit Health Services who were 40 years of age or older at the start of the study period and were assessed as being eligible to receive nirmatrelvir therapy during the omicron surge. A Cox proportional-hazards regression model with time-dependent covariates was used to estimate the association of nirmatrelvir treatment with hospitalization and death due to Covid-19, with adjustment for sociodemographic factors, coexisting conditions, and previous SARS-CoV-2 immunity status., Results: A total of 109,254 patients met the eligibility criteria, of whom 3902 (4%) received nirmatrelvir during the study period. Among patients 65 years of age or older, the rate of hospitalization due to Covid-19 was 14.7 cases per 100,000 person-days among treated patients as compared with 58.9 cases per 100,000 person-days among untreated patients (adjusted hazard ratio, 0.27; 95% confidence interval [CI], 0.15 to 0.49). The adjusted hazard ratio for death due to Covid-19 was 0.21 (95% CI, 0.05 to 0.82). Among patients 40 to 64 years of age, the rate of hospitalization due to Covid-19 was 15.2 cases per 100,000 person-days among treated patients and 15.8 cases per 100,000 person-days among untreated patients (adjusted hazard ratio, 0.74; 95% CI, 0.35 to 1.58). The adjusted hazard ratio for death due to Covid-19 was 1.32 (95% CI, 0.16 to 10.75)., Conclusions: Among patients 65 years of age or older, the rates of hospitalization and death due to Covid-19 were significantly lower among those who received nirmatrelvir than among those who did not. No evidence of benefit was found in younger adults., (Copyright © 2022 Massachusetts Medical Society.)

Objective: Third-generation cephalosporins resistant Enterobacteriaceae (3GCR-EB) are a major threat in severely ill neonates hospitalized in Neonatal Intensive Care Units. Still, the particular impact of 3GCR-EB on outcomes in the wide neonatal population is not well-appreciated. We aimed to study the impact of 3GCR-EB on the length of hospital stay and mortality of a general population of neonates and young infants., Study Design: This was a retrospective cohort study of neonates and young infants born in eight Israeli hospitals between 2009 and 2013, with a culture taken within three months after birth that tested positive for Enterobacteriaceae (EB). Data for this study were taken from centralized electronic health records included inpatient, outpatient, socio-demographic, administrative and laboratory information. The main outcomes were length of stay and mortality. The main explanatory variable was an isolation of 3GCR-EB in any bacterial culture taken from a neonate or young infant., Results: Cultures were taken for 31,921 neonates and young infants; 2647 (8.3%) tested positive for EB and 290 (11%) tested positive for 3GCR-EB. Length of stay for those who tested positive was 2.8 times longer (95%CI: 2.70-2.91, p ˂ .001) than patients who tested positive for 3GC-susceptible EB. 3GCR-EB were also associated with increased mortality (OR: 12.06, 95%CI: 4.92-32.29)., Conclusions: Neonates with third-generation cephalosporins resistant Enterobacteriaceae had extended hospitalization and increased mortality, which was mostly significant in normal gestational weight newborns.

We aimed to examine rates of COVID-19 vaccination to elucidate the need for targeted public health interventions. We retrospectively reviewed the electronic medical files of all adults registered in a central district in Israel from 1 January 2021 to 31 March 2022. The population was characterized by vaccination status against COVID-19 and the number of doses received. Univariate and multivariable analyses were used to identify predictors of low vaccination rates that required targeted interventions. Of the 246,543 subjects included in the study, 207,911 (84.3%) were vaccinated. The minority groups of ultra-Orthodox Jews and Arabs had lower vaccination rates than the non-ultra-Orthodox Jews (68.7%, 80.5% and 87.7%, respectively, p < 0.001). Adults of low socioeconomic status (SES) had lower vaccination rates compared to those of high SES (74.4% vs. 90.8%, p < 0.001). Adults aged 20−59 years had a lower vaccination rate than those ≥60 years (80.0% vs. 92.1%, p < 0.0001). Multivariate analysis identified five independent variables that were significantly (p < 0.001) associated with low vaccination rates: minority groups of the ultra-Orthodox sector and Arab population, and underlying conditions of asthma, smoking and diabetes mellitus (odds ratios: 0.484, 0.453, 0.843, 0.901 and 0.929, respectively). Specific targeted public health interventions towards these subpopulations with significantly lower rates of vaccination are suggested.

Objective: To postulate that ADHD is a potential risk factor for COVID-19 infection; to evaluate the COVID-19 risk factor on drug-treated ADHD subjects., Methods: A retrospective chart review was performed on ADHD subjects aged 6 to 18 years in Israel, who had undergone at least one COVID-19 test during the study period., Results: Of the 64,409 subjects included in the study, 6,207 (9.64%) had at least one positive COVID-19 test result, 13,300 (20.65%) were diagnosed with ADHD, and of whom 1,751 (13%) had purchased at least two ADHD medications 3 months prior to COVID-19 testing and were defined as being medically treated. Medically-treated ADHD subjects had a significantly lower likelihood to be infected with COVID-19 than untreated subjects., Conclusion: Untreated ADHD patients seem to constitute a risk group for COVID-19 infection. Drug treatment ameliorates risk of spreading COVID-19 infection within the pediatric population and secondary spread in the general population.

Aims: Management of patients with a single CHA 2 DS 2 -VASc score risk factor is controversial. We attempt to identify the "truly low risk" AF patients who will not benefit from oral anticoagulation (OAC) treatment., Methods: Retrospective cohort analysis, all incident non-valvular AF (NVAF) cases between 2004 and 2015, and age 21 and older, with up to one thromboembolic risk factor besides sex (CHA 2 DS 2 -VASc score of up to 1 for men and up to 2 for women). A "low risk" score was created for these patients using a logistic regression model on the incidence of stroke within 30-2500 days following the NVAF diagnosis., Results: We identified 15,621 patients. Average age was 53.7 ± 12.3 years, 56.6% male. Mean follow-up was 5.5 years. Significant predictors of ischemic stroke were age 65-74 and diabetes (2 points each), hypertension, vascular disease, and chronic kidney disease stage 2-3 (1 point each). Stroke incidence ranged from 0.8% for score 0 and up to 3.4% for scores ≤ 2. Odds ratio for stroke among patient group with a score ≤ 2 was 4.3 (2.9-6.6) compared with score 0. Our risk score's area-under-the-curve (AUC) for prediction of stroke was 0.68 (0.65-0.71), compared with 0.60 (0.57-0.62) for the CHAD 2 S 2 -VASc score, within this low-risk group., Conclusion: Patients considered at low or intermediate risk using traditional risk stratification schemes, with ≥ 2 points using this proposed low-risk index (65-74 years old, diabetics or a combination of chronic renal failure and an additional risk factor), had an overall stroke risk that may justify anticoagulation therapy., (© 2021. Royal Academy of Medicine in Ireland.)

Background: A decline in cardiovascular hospitalizations was observed during the initial phases of the COVID-19 pandemic. We examine the continuous effect of the COVID-19 pandemic in reducing cardiovascular hospitalization and associated mortality rates during the first year of the pandemic in Israel., Methods: We conduct a retrospective cohort study using the data of Clalit Health Services, the largest healthcare organization in Israel. We divide the Corona year into six periods (three lockdowns and three post-lockdowns) and compare the incidence rates of cardiovascular hospitalizations and 30-day all-cause mortality during each period to the previous three years., Results: The number of non-STEMI hospitalizations during the first year of the pandemic was 13.7% lower than the average of the previous three years (95% CI 11-17%); STEMI hospitalizations were 15.7% lower (95% CI 13-19%); CHF (Congestive heart failure) hospitalizations were 23.9% lower (95%, CI 21-27%). No significant differences in 30-day all-cause mortality rates were observed among AMI (acute myocardial infarction) patients during most of the periods, whereas the annual 30-day all-cause mortality rate among CHF patients was 23% higher., Conclusions: AMI and CHF hospitalizations were significantly lower during the first year of the pandemic relative to 2017-9. Mortality rates were higher in the case of CHF patients but not in the case of AMI patients, possibly due to a change in the clinical acuity of patients arriving at the hospitals. We conclude that targeted public health messaging should be implemented together with proactive monitoring, in order to identify residual disability in patients who may have received non-optimal treatment during the pandemic.

Background: Most studies estimate hepatitis C virus (HCV) disease prevalence from convenience samples. Consequently, screening policies may not include those at the highest risk for a new diagnosis., Methods: Clalit Health Services members aged 25-74 as of 31 December 2009 were included in the study. Rates of testing and new diagnoses of HCV were calculated, and potential risk groups were examined., Results: Of the 2 029 501 included members, those aged 45-54 and immigrants had lower rates of testing (12.5% and 15.6%, respectively), higher rates of testing positive (0.8% and 1.1%, respectively), as well as the highest rates of testing positive among tested (6.1% and 6.9%, respectively)., Discussion: In this population-level study, groups more likely to test positive for HCV also had lower rates of testing. Policy makers and clinicians worldwide should consider creating screening policies using on population-based data to maximize the ability to detect and treat incident cases., (© The Author(s) 2020. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Schizophrenia patients have shorter life expectancy often owing to preventable physical illnesses and sub-optimal utilization of medical services. However, the association between service-utilization and mortality has not been explored., Aim: To assess whether medical service-utilization moderates the association between physical morbidity and premature mortality in a nation-wide cohort., Methods: A population representative database of the largest health provider in Israel was analyzed. All electronic health records of patients with schizophrenia diagnosis (ICD code F.20) (n = 24,679) were followed-up between 2012 and 2015, and compared to the general population (n = 2,232,804), in terms of metabolic and cardiovascular morbidity, all-cause mortality, primary medical and specialist health service-utilization and general hospitalizations., Results: Schizophrenia was associated with increased mortality risk (adjusted hazard ratio (aHR) = 3.52, 95%CI 3.35-3.72). Most deaths were related to physical illnesses. Metabolic syndrome components, except chronic hypertension, were more prevalent among patients. They were referred more frequently to primary and less to secondary services (aHR = 1.05, 95%CI 1.04-1.06, aHR = 0.95, 95%CI 0.94-0.97, respectively), with higher hospitalization rates (0.23 ± 0.90 vs 0.10 ± 0.50 per year), and longer mean duration of hospitalization (2.02 ± 10.24 vs 0.68 ± 5.51 days, P < 0.001). More contacts with primary care physicians or specialists positively moderated the association between mortality and metabolic disturbances in patients with schizophrenia; more contacts were associated with better outcomes., Conclusions: An association between premature mortality and metabolic syndrome was found among schizophrenia patients while utilization of primary/secondary medical services moderated the lethal effects of metabolic dysregulation. Increased integrative primary care and a national monitoring system are warranted to reduce mortality rate in this population., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Depression and anxiety have been associated with type 2 diabetes mellitus and metabolic syndrome, major causes of cardiovascular morbidity and mortality. The effect of antidepressants in this association is unknown. This study aimed to examine the association between adherence to selective serotonin receptor inhibitors (SSRIs) and all-cause mortality among individuals with metabolic syndrome components (hypertension, obesity, and diabetes mellitus)., Methods: Data on 201 777 patients who were prescribed SSRIs during the years 2008-2011 were analyzed retrospectively. Adherence was measured using prescription purchase records. The moderating effect of SSRI and statin adherence on the association between metabolic syndrome load and mortality hazard risk (HR) during the study period were analyzed. The Cox-proportional hazard model adjusted to background variables was used to this end., Results: During the study period, the maximal metabolic load was associated with mortality HR=1.89 (95% CI: 1.79-2) compared to participants without metabolic risk factors. A slight reduction in mortality HR was demonstrated among those with low and moderate SSRI adherence rates. Adherence to statins was negatively associated with the risk of mortality across all levels of adherence. A significant association (r=0.214, p<0.01) was found between adherence to statins and adherence to SSRIs, with higher rates of adherence to statins across all metabolic load categories., Discussion: While a high metabolic load is associated with a higher risk of mortality, adherence to SSRIs only partially moderated the risk of mortality, in contrast to the protective effect of statins. Adherence differences to statins and SSRIs among individuals prescribed both medications merit further investigation., Competing Interests: The authors declare that they have no conflict of interest, (Thieme. All rights reserved.)

Purpose: This study assessed associations of the use of statins for primary prevention with cardiovascular outcomes among adults ages ≥70 years., Methods: In a retrospective population-based cohort study, new users of statins without cardiovascular disease or diabetes mellitus were stratified by ages ≥70 years and <70 years. Using a time-dependent approach, adherence to statins was evaluated according to the proportion of days covered: <25%, 25%-50%, 50%-75%, and ≥75%. We assessed associations of statin therapy with increased risk of new-onset diabetes mellitus and with decreased risks of major adverse cardiovascular events and all-cause mortality., Results: Of 42,767 new users of statins, 5970 (14%) were ages ≥70 years. The incident rates of major adverse cardiovascular events, all-cause mortality, and new-onset diabetes mellitus in the highest to lowest proportion of days covered categories were 16.9%, 16.7%, and 9.4% and 6.3%, 1.7%, and 9.4%, respectively. For the older group, the adjusted hazard ratios of major adverse cardiovascular events and mortality were significantly decreased for the highest adherence group (proportion of days covered ≥75%): 0.71 (0.57-0.88) and 0.68 (0.54-0.84), respectively. The respective hazard ratios were less favorable for the younger group: 0.80 (0.68-0.93) and 0.74 (0.58-1.03). The risk of new-onset diabetes mellitus was increased for the younger but not the older group., Conclusions: Statin use for primary prevention was associated with cardiovascular benefit in adults ages ≥70 years without a significant risk for the development of diabetes. These data may support the use of statin therapy for primary prevention in the elderly., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Data are sparse regarding the survival benefit of bariatric surgery on mortality among persons with diabetes. We aimed to investigate the association of bariatric surgery, compared with usual care, on all-cause mortality in individuals who underwent surgery and matched controls, stratified by the presence of diabetes., Research Design and Methods: This retrospective cohort study utilized population-based electronic medical record data. Individuals who underwent one of three types of bariatric surgery during 2005-2014 were included. For each surgical patient, three non-surgical individuals were matched according to age, sex, body mass index, and diabetes status. The cohort comprised 9564 individuals with diabetes and 23,976 individuals without diabetes., Results: During a median follow-up of 4.2 years, adjusted hazard ratios (HRs) for mortality for non-surgery vs. surgery were 2.38 (95%CI: 1.75, 3.26) and 1.73 (95%CI: 1.26, 2.36) among individuals with diabetes and individuals without diabetes, respectively. Considered separately, HRs for mortality for laparoscopic banding, gastric bypass, and laparoscopic sleeve gastrectomy were 2.83 (95%CI: 1.73, 4.63), 2.30 (95%CI: 1.25, 4.25), and 1.89 (95%CI: 1.1, 3.32) among patients with diabetes; and 1.74 (95%CI: 1.20, 2.52), 2.66 (0.81, 8.76), and 1.16 (0.51, 2.65) among patients without diabetes., Conclusion: The survival advantage of bariatric surgery after a median follow-up of 4.2 years was greater among individuals with than without diabetes for the three types of surgery performed. Longer follow-up is needed to examine the effect on survival in individuals without diabetes who undergo bariatric surgery. These results suggest priority considerations for bariatric surgery candidates.

Aims: The Choosing Wisely Campaign identifies procedures and treatments that lack clinical justification for routine use according to expert opinion and evidence-based medicine. This study describes the rates and features of two such examples over a 10-year period., Methods: This is a cross-sectional rolling cohort study between 2008 and 2017 in Clalit Health Services, the largest healthcare delivery system in Israel, with seven main hospitals and over 4.5 million members nationwide. All adult members who visited a Clalit Emergency Department (ED), and all children members who visited a Clalit ED for abdominal pain or appendicitis were eligible to be included in this study. Our measures were routine chest radiograph (CXR) in the context of pre-admission assessment for adults and abdominal computed tomography (CT) to rule out appendicitis for children., Results: Of the 3 689 869 adult visits without a clinical indication for a CXR, 9.1% or 337 058 of them received a chest radiograph. Of the 35 973 children visits for presumed appendicitis, 7.2% of them had no imaging performed, 82.3% had an ultrasound (US), 6.9% had an US followed by a CT, and 3.6% or 1293 of them received a CT. There were several independent risk factors such as BMI, hospital, sex, year and diagnosis that are associated with having imaging that is not clinically indicated., Conclusions: Overall, this study found that diagnostic imaging practices are applied inconsistently by hospital and by population. Intervention efforts should be focused on subpopulations at greatest risk to further reduce exposure to such imaging., (© 2020 John Wiley & Sons Ltd.)

Clozapine is the only antipsychotic compound indicated for refractory-schizophrenia. However, it is associated with emergent metabolic dysregulation and cardiovascular risk which may lead to mortality. In this study we aimed to explore predictors for mortality in a large cohort of schizophrenia patients treated with long-term clozapine, using the electronic medical records of the largest health care provider in Israel. Among 27,929 patients diagnosed with schizophrenia, 1817 were prescribed clozapine during the years 2012-2014. We compared patients who survived (n=1705) and patients who died (n=112) during the 3-year follow-up period. Socio-demographic background, cardiovascular morbidity, medication prescriptions and health-care utilization were compared between groups. Cox proportional hazard models were used to assess the association of variables with survival. Chronic hypertension was found to be the only metabolic factor associated with significant hazard ratio (HR) for mortality (HR: 1.55 95% CI: 1.03-2.34). Moreover, those who died had more prevalent ischemic heart disease (14% vs 3%, p<0.005) as well as more frequent hospitalizations (0.01±0.02 vs 0.11±0.18 average per month, p<0.005), for longer periods (2.22±9.87 vs 20.38±33.76 days per month, p<0.005). Among those who died, less patients received prescriptions of statins for hyperlipidemia (13.7% vs. 52.9% in survivors, p<0.005) and hypoglycemics for diabetes mellitus (16.3% vs. 67.1% in survivors, p<0.005). Inadequate treatment of metabolic syndrome, under chronic clozapine treatment, was found to be an independent predictor for mortality. Adequate rigorous regimen for diagnosis and treatment of metabolic risk factors, especially hyperlipidemia and diabetes mellitus, might lower complications rate and prolong life expectancy among this population., Competing Interests: Conflict of Interest All authors declare no conflict of interests., (Copyright © 2020. Published by Elsevier B.V.)

Aim: To evaluate the clinical and health behavioural outcomes of a large sample of participants from the Diabetes Conversation Map™ Program., Design: A matched-case-control study that was performed on a retrospective cohort study., Methods: Participants were 11,053 Clalit Health Services members with type 2 diabetes who enrolled in the Diabetes Conversation Map™ Program between January 2010 - April 2016. The matched-control group was formulated using sequential matching, by matching cases to controls at a ratio of 1:3, based on age, sex, and HbA1c level. The associations between the programme group and annual clinical and health behaviours were assessed between cases and controls at five time points using linear and Poisson regression analyses., Results: The intervention group had significantly lower HbA1c, glucose, and low-density lipoprotein levels and more frequent glucose blood testing each year up to 36 month post-enrolment compared with the matched controls. Other outcomes were significantly different for shorter time periods, including higher high-density lipoprotein and lower triglyceride levels at 6- and 12-month follow-up and lower diastolic blood pressure and greater medication adherence at 6-month follow-up., Conclusions: Enrolment in the programme was associated with improved clinical and health behaviour outcomes for at least 6 months and most outcomes persisted for up to 36 months., Impact: This is the first study to evaluate the Diabetes Conversation Map™ Program with a large sample over long period of time. This nurse-led group intervention evaluation adds to the literature on health outcomes on the lives of patients with type 2 diabetes., Study Registration: This study was registered retrospectively to the Open Science Framework, the registration form can be found at: https://osf.io/63cse., (© 2020 John Wiley & Sons Ltd.)

Introduction: Oral anticoagulation (OAC) therapy reduces the risk of ischemic stroke in patients with atrial fibrillation (AF) while increasing the risk of bleeding. Recently, non-vitamin K antagonist oral anticoagulants (NOACs) have become available with lower rates of intracranial bleeding, and some of them have presented a reduced risk of major bleeding. The purpose of this study is to evaluate the change in purchasing patterns of OACs (both warfarin and NOACs) over time in patients with AF according to stroke and bleeding risk, in the first 3 months after diagnosis., Methods and Results: We conducted a historical cohort study using the Clalit Health Services electronic medical records database. The study population included all members aged ≥21 years, with a new diagnosis of nonvalvular AF between 2008 and 2015. A total of 58 385 cases were identified. The mean age was 73.1 (±14.1) years, and 52.3% of the patients were women. The median CHA 2 DS 2 -VASc score was 4 (interquartile range, 3-5). OACs were purchased by 19 705 patients (33.8%) within the first 3 months of first diagnosis of AF, with patients at higher embolic risk as stratified by the CHA 2 DS 2 -VASc score and having higher purchasing rates (37.1%). Between 2008 and 2010, 29% of patients purchased a vitamin K antagonist, the only available OAC at the time. OAC purchasing increased to 41.4% between 2014 and 2015, with half of the patients purchasing an NOAC., Conclusion: In this real-world, population-based cohort study of patients with newly diagnosed AF, we found a lower than expected rate of OAC prescription within 3 months of diagnosis but an encouraging increase in OAC purchasing over time. The use of NOACs has risen exponentially within just a few years, accounting for a greater pool of patients with being prescribed an OAC., (© 2020 Wiley Periodicals, Inc.)

Objective: To evaluate whether a woman's age at first birth is associated with cardiovascular risk and metabolic health outcomes (cardiometabolic outcomes) by age 45. Methods: This is a retrospective, population-based cohort study that uses electronic health record data from the largest health fund in Israel. Women aged 34-39 at baseline (2004-2006) free of chronic diseases were identified as nulliparous at baseline and were followed up to 10 years (through 2016). The cohort was divided into three groups based on their age at first birth: younger parturients (ages 35-39), older parturients (ages 40-44), and never had children. The percentage of adverse pregnancy events and cardiometabolic outcomes at age 45 were compared across these three groups as well as to women in the general population. Cardiovascular risk and metabolic health outcomes were defined as: Type 2 diabetes, obesity, hypertension, cardiovascular disease, and Framingham risk score. Methods and results: Out of a group of 126,121 women aged 34-39 at baseline, 9979 were nulliparous and free of comorbidities. Over the course of the follow-up, there were 952 younger parturients and 673 older parturients who had their first birth, and 8354 women who remained persistent nulliparous. While older parturients had more adverse pregnancy events, there was no difference in rates of cardiometabolic outcomes between the two parturient groups, and they both had lower rates than the persistent nulliparous and the general population. Conclusions: Parturients free of major chronic diseases who give birth at a later age do not have increased cardiometabolic outcomes in midlife as compared to a general population of women in a large retrospective cohort. Our results may support clinicians when counseling healthy women who are seeking advice regarding delaying their first pregnancy without a tradeoff on health outcomes.

Objectives: This study assessed rates of ambulatory care-sensitive condition (ACSC) admissions within a healthcare system to identify areas for intervention., Study Design: This was a multiyear cross-sectional study using the data warehouse of Clalit Health Services (Clalit), the largest payer/provider healthcare system in Israel, with complete clinical records for more than 4 million members. All admissions from 2009 to 2014 were included in the study. Discharge diagnoses were identified using International Classification of Diseases, Ninth Revision codes., Methods: We provide adjusted rates (per 100,000 Clalit population adjusted by age and sex to the 2005 Organisation for Economic Co-operation and Development population) for all admissions, by discharge diagnoses, for each year. We identify the highest adjusted rates (relative and absolute) by both catchment area and hospital affiliation (Clalit or non-Clalit)., Results: ACSC-related admissions made up 16.2% of all admissions for the 5 years studied, and the overall rate increased by 26.8% from 2009 to 2014. The conditions with the highest admission rates in all years and all catchment areas were pneumonia and congestive heart failure. There was extreme variation among catchment areas for hypertension-related admissions. Within the Clalit hospitals, ACSCs accounted for 20.5% of admissions; within non-Clalit hospitals, ACSCs accounted for 13.6% of admissions., Conclusions: In evaluating the rates of ACSC-related admissions, this study demonstrates the contribution of a single, longitudinal benchmark. This study also suggests that hypertension, congestive heart failure, and pneumonia may be areas for future intervention in Clalit.

Background: Although coeliac disease is common worldwide, little is known regarding screening patterns in unselected populations, and on real-life adherence to professional guidelines for coeliac disease diagnosis and management., Objective: To explore current practices in the diagnosis and management of coeliac disease, using data from a large Health Maintenance Organization in Israel that covers 54% of the population., Methods: A population-based electronic database of about 4.5 million individuals was reviewed during the period of 1 January 2008 to 31 December 2015. Rates and results of coeliac disease serology testing and endoscopy procedures were examined. Subgroup analysis was performed by age, sex, ethnicity and socioeconomic status., Results: Coeliac disease serology cumulative testing rate was 17.1% and 8.9% in the paediatric and adult population, respectively. The cumulative incidence of positive coeliac disease serology was 0.45% in children and 0.17% in adults, and was associated with age, sex, ethnicity and socioeconomic status sub-groups (P-value < 0.01). Gastrointestinal endoscopies were not subsequently performed in 44.1% of children and 47.1% of adults with positive coeliac disease serology. Within the study period, 36% of children and 56% of adults never achieved coeliac disease serology normalization., Conclusion: In a large real-life database, screening for coeliac disease was common. However, confirmatory intestinal biopsies were under-utilized, and coeliac disease serology often remained positive over a long period time in both children and adults.

Third-generation-cephalosporin resistant Enterobacteriaceae (3GCR-EB) carriage in pregnant women poses challenges for infection control and therapeutic decisions. The factors associated with multidrug resistant Enterobacteriaceae carriage in the gestational period are not well documented. The aim of our study was to identify risk factors associated with 3GCR-EB isolation in gestational urine cultures. The study was designed as retrospective cohort based on centralized electronic health records database. Women delivered in Clalit Health Services hospitals in Israel in 2009-2013 and provided urine culture(s) during pregnancy were included. Multivariable analysis using the Generalized Estimating Equations model was used to assess risk factors for 3GCR-EB isolation in gestational urine cultures. The study included 15,282 pregnant women with urine cultures yielding Enterobacteriaceae (EB). The proportion of 3GCR-EB in EB isolates was 3.9% (n = 603). The following risk factors were associated with 3GCR-EB isolation: multiple hospital admissions during the year before delivery (OR,1.47;95% CI,1.21-1.79), assisted fertilization procedure (OR,1.53; 95% CI,1.12-2.10), Arab ethnicity (OR,1.22; 95% CI,1.03-1.45), multiple antibiotic courses (OR,1.76; 95% CI,1.29-2.40), specifically, cephalosporins (OR,1.56; 95% CI,1.26-1.95), fluoroquinolones (OR,1.34; 95% CI,1.04-1.74), or nitrofurantoin (OR,1.29; 95% CI,1.02-1.64). The risk factors identified by this study for 3GCR-EB in gestation, can be easily generalized for pregnant women in the Israeli population. Moreover, these risk factors, other than ethnicity, are applicable to pregnant women worldwide. The information of previous antibiotic treatments, hospitalization in the last year and assisted fertilization procedure can be easily accessed and used for appropriate infection control practices and antimicrobial therapy., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Atrial fibrillation (AF) and chronic kidney disease (CKD) are both associated with increased risk of stroke, and CKD carries a higher bleeding risk. Oral anticoagulation (OAC) treatment is used to reduce the risk of stroke in patients with nonvalvular AF (NVAF); however, the risk versus benefit of OAC for advanced CKD is continuously debated. We aim to assess the management and outcomes of NVAF patients with impaired renal function within a population-based cohort., Methods: We conducted a retrospective observational cohort study using ICD-9 healthcare coding. Patients with incident NVAF between 2004 and 2015 were identified stratified by CKD stage. We compared treatment strategies and estimated risks of stroke, death, or any major bleeding based on CKD stages and OAC treatment., Results: We identified 85,116 patients with incident NVAF. Patients with impaired renal function were older and had more comorbidities. OAC was most common among stage 2 CKD patients (49%) and least in stages 4-5 CKD patients (27.6%). Higher CKD stages were associated with worse outcomes. Stroke rates increased from 1.04 events per 100 person-years (PY) in stage 1 CKD to 3.72 in stages 4-5 CKD. Mortality increased from 3.42 to 32.95 events/100 PY, and bleeding rates increased from 0.89 to 4.91 events/100 PY. OAC was associated with reduced stroke and intracranial bleeding risk regardless of CKD stage, and with a reduced mortality risk in stages 1-3 CKD., Conclusion: Among NVAF patients, advanced renal failure is associated with higher risk of stroke, death, and bleeding. OAC was associated with reduced stroke and intracranial bleeding risk, and with improved survival in stages 1-3 CKD., (© 2020 S. Karger AG, Basel.)

Introduction: Bariatric surgery is associated with lower all-cause mortality, but many studies exclude smokers. We sought to determine if the association of mortality and bariatric surgery differs between smokers and non-smokers., Materials and Methods: We conducted a retrospective cohort study in a large Israeli integrated payer/provider health care organization. A total of 7747 adult patients who underwent bariatric surgery between January 1, 2005, and December 31, 2014, were selected and compared with non-surgical patients (and were matched on age, sex, diabetes, and BMI using a sequential/simultaneous stratification matching). A total of 30,742 patients with a median follow-up of 4.3 years were included in this study with less than 1% lost to follow-up. The type of bariatric surgery (gastric banding, Roux-en-Y gastric bypass, or sleeve gastrectomy) and smoking status were determined from electronic health records. The rate of all-cause mortality in matched surgical and non-surgical patients was compared in smoking and non-smoking subgroups, adjusted for key potential confounders., Results: There was a statistically significantly higher mortality associated with not having bariatric surgery in both smoking (HR, 1.99; 95% CI, 1.54-2.56) and non-smoking (HR, 1.93; 95% CI, 1.12-3.34) subgroups. Although smokers had higher rates of mortality overall (2.6% in smokers compared with 1.7% in non-smokers), the mortality hazard ratio (comparing matched non-surgical patients to surgical patients) did not differ significantly between smokers and non-smokers (p for interaction = .67)., Conclusions: Bariatric surgery was associated with significantly lower mortality in both smokers and non-smokers.

Background: Depression and anxiety are common in cancer and antidepressants (AD) are efficacious treatment. The relationship between AD adherence and mortality in cancer is unclear. This study aimed to evaluate the association between adherence to AD and all-cause mortality in a population-based cohort of patients with cancer., Materials and Methods: We conducted a 4-year historical prospective cohort study including 42,075 patients with cancer who purchased AD at least once during the study period. Adherence to AD was modeled as nonadherence (<20%), poor (20-50%), moderate (50-80%), and good (>80%) adherence. We conducted multivariable survival analyses adjusted for demographic and clinical variables that may affect mortality., Results: During 1,051,489 person-years at risk follow-up, the adjusted hazard ratios (HR) for mortality were 0.89 (95% confidence interval [CI]: 0.83-0.95), 0.77 (95% CI: 0.66-0.72), and 0.80 (95% CI: 0.76-0.85) for the poor, moderate, and good adherence groups, respectively, compared to the nonadherent group. Analysis of the entire sample and a subgroup with depression, for cancer subtypes, revealed similar patterns for breast, colon, lung, and prostate cancers, but not for melanoma patients. Multivariate predictors of premature mortality included male gender (HR 1.48 [95% CI: 1.42-1.55]), current/past smoking status (HR 1.1, [95% CI: 1.04-1.15]; P < .0001), low socioeconomic status (HR 1.1, [95% CI: 1.03-1.17]; P < .0001) and more physical comorbidities., Conclusions: The present study is the first to demonstrate that higher adherence to AD is associated with a decrease of all-cause mortality in a large nationwide cohort of cancer patients. Our data add to the pressing need to encourage adherence to AD among cancer patients., (© 2019 Wiley Periodicals, Inc.)

Methylphenidate (MPH) is a common and effective treatment for attention deficit hyperactivity disorder (ADHD), but little is known about the relationship between early childhood intake of MPH and onset of antidepressant treatment during adolescence. The study aimed to examine whether adherence to MPH during early childhood predicts the initiation of antidepressants during adolescence. This is a 12-year historical prospective nationwide cohort study of children enrolled in an integrated care system who were first prescribed MPH between the ages of 6 and 8 years (N = 6830). We tested for an association between their adherence to MPH during early childhood (as indicated by medication possession ratio from MPH onset through the age of twelve) and the likelihood of being prescribed any antidepressant during adolescence (age 13-18). As all country citizens are covered by mandatory health insurance, and full services are provided by one of the four integrated care systems, data regarding patients' diagnoses, prescriptions, and medical purchases are well documented. Logistic regression analysis indicated that those with higher adherence to MPH had a 50% higher risk (95% CI 1.16-1.93) of receiving antidepressants during adolescence when controlling for other comorbid psychiatric conditions and parental use of antidepressants. In this large-scale longitudinal study, MPH adherence during early childhood emerged as a predictor for antidepressant treatment during adolescence, which may reflect increased emotional and behavioral dysregulation in this group. The highly adherent patients are at higher risk and should be clinically monitored more closely, particularly into adolescence.

Background: Recurrent asthma-like symptoms are common in infants, but few population studies describe diagnostic and treatment practice., Methods: Using the electronic data repository of Clalit Health Services, the largest integrated health care provider in Israel, we evaluated children born 2005-2012, who before 3 years of age had >3 episodes of asthma-like symptoms and/or >2 bronchodilator purchases within a year. We described health care utilization and the odds ratio for subsequent utilization after 3 and 12 months' controller therapy. The primary outcome measure was respiratory-related doctor visits. Linear and categorical regression analysis measured overall effectiveness of therapy., Results: Among 689 171 infants, 262 900 (38.1%) had > 3 asthma-like episodes/year during at least 1 year. Of those, 26 108 (10%) purchased controller therapy: 20 316 (77.8%) inhaled corticosteroids (ICS) with or without leukotriene receptor antagonists (LTRA), and 5792 (22.2%) LTRA alone. For these 26 108 over 3 months there were 93 845 respiratory-related doctor visits, 3110 hospital admissions, 5568 diagnoses of pneumonia, 9960 chest X-rays, 37 127 purchases for oral steroids, and 45 142 for antibiotics courses. Healthcare utilization decreased following ICS ± LTRA and LTRA alone, respectively, as follows: doctor visits 7% and 3%, chest X-rays 16% and 17%, bronchodilators 20% and 11%, systemic steroids 17% and 12%, and antibiotics by 35% and 22%, (P < .001 for all). Twelve months' therapy remained effective., Conclusions: Asthma-like symptoms are common in infants. Health care utilization is very high and physician practices should be reassessed. Following controller therapy, health care utilization decreased. Yet controllers were prescribed in only a minority of eligible children., (© 2019 Wiley Periodicals, Inc.)

Background: The effect of labor epidural analgesia (LEA) on successful breastfeeding has been evaluated in several studies with divergent results. We hypothesized that LEA would not influence breastfeeding status 6 weeks postpartum in women who intended to breastfeed in an environment that encourages breastfeeding., Methods: In this prospective observational cohort study, a total of 1204 women intending to breastfeed, delivering vaginally with or without LEA, were included; breastfeeding was recorded at 3 days and 6 weeks postpartum. Primary outcome was breastfeeding at 6 weeks, and the χ test was used for comparisons between women delivering with and without LEA, according to parity status and previous breastfeeding experience. Total epidural fentanyl dose and oxytocin use (yes/no) were recorded. A multivariable logistic regression was performed to assess factors affecting breastfeeding at 6 weeks., Results: The overall breastfeeding rate at 6 weeks was 76.9%; it was significantly lower among women delivering with LEA (74.0%) compared with women delivering without LEA (83.4%; P < .001). Among 398 nulliparous women, 84.9% delivered with LEA, compared with 61.8% of multiparous women (P < .001). Multiparous women (N = 806) were more likely to breastfeed at 6 weeks (80.0% vs 70.6% nullipara; P < .001). Using multivariable logistic regression that accounted for 14 covariates including parity, and an interaction term between parity and LEA use, LEA was significantly associated with reduced breastfeeding at 6 weeks (odds ratio, 0.60; 95% confidence interval, 0.40-0.90; P = .015). In a modified multivariable logistic regression where parity was replaced with previous breastfeeding experience, both as a covariate and in the interaction term, only previous breastfeeding experience was associated with increased breastfeeding at 6 weeks (odds ratio, 3.17; 95% confidence interval, 1.72-5.80; P < .001)., Conclusions: In our mixed-parity cohort, delivering with LEA was associated with reduced likelihood of breastfeeding at 6 weeks. However, integrating women's previous breastfeeding experience, the breastfeeding rate was not different between women delivering with and without LEA among the subset of multiparous women with previous breastfeeding experience. Therefore, our findings suggest that offering lactation support to the subset of women with no previous breastfeeding experience may be a simple approach to improve breastfeeding success. This concept subscribes to the notion that women at risk for an undesired outcome be offered tailored interventions with a personalized approach.

Currently, clinicians rely mostly on population-level treatment effects from RCTs, usually considering the treatment's benefits. This study proposes a process, focused on practical usability, for translating RCT data into personalized treatment recommendations that weighs benefits against harms and integrates subjective perceptions of relative severity. Intensive blood pressure treatment (IBPT) was selected as the test case to demonstrate the suggested process, which was divided into three phases: (1) Prediction models were developed using the Systolic Blood-Pressure Intervention Trial (SPRINT) data for benefits and adverse events of IBPT. The models were externally validated using retrospective Clalit Health Services (CHS) data; (2) Predicted risk reductions and increases from these models were used to create a yes/no IBPT recommendation by calculating a severity-weighted benefit-to-harm ratio; (3) Analysis outputs were summarized in a decision support tool. Based on the individual benefit-to-harm ratios, 62 and 84% of the SPRINT and CHS populations, respectively, would theoretically be recommended IBPT. The original SPRINT trial results of significant decrease in cardiovascular outcomes following IBPT persisted only in the group that received a "yes-treatment" recommendation by the suggested process, while the rate of serious adverse events was slightly higher in the "no-treatment" recommendation group. This process can be used to translate RCT data into individualized recommendations by identifying patients for whom the treatment's benefits outweigh the harms, while considering subjective views of perceived severity of the different outcomes. The proposed approach emphasizes clinical practicality by mimicking physicians' clinical decision-making process and integrating all recommendation outputs into a usable decision support tool., Competing Interests: Competing interestsThe authors declare no competing interests.

Background: About a third of schizophrenia patients would not have sufficient clinical response to antipsychotic treatment. The only drug approved for this population is clozapine, yet worldwide reports suggest underuse of clozapine and significant delay in initiating treatment., Objectives: To assess, for the first time in Israel, the rate of clozapine use in patients with schizophrenia., Methods: A retrospective cohort study of "Clalit Health Services" electronic records was conducted. People diagnosed with schizophrenia (F.20 ICD 10 code) who had at least one prescription filled for clozapine were followed up between 2012 and 2014., Results: Of 28,983 people diagnosed with schizophrenia, clozapine was prescribed and purchased by 1817 (6.5%) patients during the study period. In addition, 60% of patients with clozapine had polytherapy with other antipsychotic compound or lithium. Polytherapy was associated with HR of 2.1 for morality during the follow-up period., Conclusions: Clozapine is underutilized in Israel, similar to reports from other countries. Moreover, the data suggests that when treatment is given it is not optimized, as reflected by high rates of polytherapy associated with increased mortality. Using therapeutic drug monitoring, now available in Israel, for clozapine might increase clozapine dosage optimization.

Background: Some individuals with diabetes fast during Ramadan despite medical concerns for risk of adverse outcomes. The Managing Diabetes During Ramadan Conversation Map is a self-management education group-based intervention for Muslim individuals with type 2 diabetes, specifically addressing diabetes management during Ramadan., Objective: The aim of this study was to evaluate the effectiveness of the Managing Diabetes During Ramadan Conversation Map intervention in improving short-term clinical outcomes and reducing healthcare utilization following Ramadan., Design: This was a retrospective rolling cohort study., Settings: Participants were Clalit Health Services members with type 2 diabetes who participated in the intervention between 2014 and 2017 across Israel., Participants: This study included 1732 participants who enrolled in the intervention over the five-year study period. The cohort was mainly between the ages of 45 and 74 years (83.3%), female (71.9%), of lower socioeconomic status (92.1%), with a diabetes duration of 10 years or more (51.7%), obese (64.0%), and had never smoked (73.8%)., Methods: The data used in this study came from Clalit Health Services' electronic health records, which are integrated in a central data warehouse. We used a difference-in-differences (self-comparison) design to examine the effect of the intervention on changes in laboratory results and healthcare utilization over a six month baseline and follow-up. Mixed model linear regressions and Poisson regressions were used to estimate continuous and count outcomes, respectively., Results: Post intervention, participants experienced a reduction of 8.61 mg/dL in their glucose levels (p = 0.005) and 0.34% in their HbA1c levels (p < 0.001). In a sub-group analysis of participants with HbA1c > 7%, larger reductions in glucose (17.02 mg/dL [p < 0.001]) and HbA1c (0.63% [p < 0.001]) levels were recorded. This sub-group also experienced a reduction of 4.83 mg/dL in LDL level (p = 0.007) and had 0.2 fewer primary care visits (p < 0.001)., Conclusions: Participation in the Managing Diabetes During Ramadan Conversation Map improved patient glucose and HbA1c levels. A greater benefit was reported in those individuals with HbA1c > 7%. These findings hold important global health implications for the millions of individuals with type 2 diabetes for whom Ramadan can pose a challenge in disease control., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Most of readmission prediction models are implemented at the time of patient discharge. However, interventions which include an early in-hospital component are critical in reducing readmissions and improving patient outcomes. Thus, at-discharge high-risk identification may be too late for effective intervention. Nonetheless, the tradeoff between early versus at-discharge prediction and the optimal timing of the risk prediction model application remains to be determined. We examined a high-risk patient selection process with readmission prediction models using data available at two time points: at admission and at the time of hospital discharge., Methods: An historical prospective study of hospitalized adults (≥65 years) discharged alive from internal medicine units in Clalit's (the largest integrated payer-provider health fund in Israel) general hospitals in 2015. The outcome was all-cause 30-day emergency readmissions to any internal medicine ward at any hospital. We used the previously validated Preadmission Readmission Detection Model (PREADM) and developed a new model incorporating PREADM with hospital data (PREADM-H). We compared the percentage of overlap between the models and calculated the positive predictive value (PPV) for the subgroups identified by each model separately and by both models., Results: The final cohort included 35,156 index hospital admissions. The PREADM-H model included 17 variables with a C-statistic of 0.68 (95% CI: 0.67-0.70) and PPV of 43.0% in the highest-risk categories. Of patients categorized by the PREADM-H in the highest-risk decile, 78% were classified similarly by the PREADM. The 22% (n = 229) classified by the PREADM-H at the highest decile, but not by the PREADM, had a PPV of 37%. Conversely, those classified by the PREADM into the highest decile but not by the PREADM-H (n = 218) had a PPV of 31%., Conclusions: The timing of readmission risk prediction makes a difference in terms of the population identified at each prediction time point - at-admission or at-discharge. Our findings suggest that readmission risk identification should incorporate a two time-point approach in which preadmission data is used to identify high-risk patients as early as possible during the index admission and an "all-hospital" model is applied at discharge to identify those that incur risk during the hospital stay.

Several stroke risk stratification scores have been developed to guide clinical decision-making in patients with nonvalvular atrial fibrillation (AF). The aim of this study was to compare the performance of the CHADS 2 , CHA 2 DS 2 -VASc and R 2 CHADS 2 risk scores to predict stroke. This retrospective cohort study was based on electronic medical records from Clalit Health Services (CHS), the largest payer provider healthcare organization in Israel. Data of CHS members with AF diagnosis between 2004 and 2015 were extracted. Demographic and co-morbidity data were used to calculate the 3 risk scores, and the performance of the scores to predict stroke were compared using area under the curve and net reclassification index. Of the 89,213 CHS members with AF, 52.3% were women and median age was 76 years. The proportions of patients at high risk were 66.2%, 86.7%, and 71.1% in the CHADS 2, CHA 2 DS 2 -VASc, and R 2 CHADS 2 , respectively, with stroke incidence rates of 2.91, 2.35, and 2.80 per 100 person-years, respectively. Area under the curves for stroke prediction were 0.61 for both CHADS 2 and CHA 2 DS 2 -VASc and 0.59 for R 2 CHADS 2 . Net reclassification index analysis demonstrated a net improvement of 0.089 in the index when CHA 2 DS 2 -VASc was compared with CHADS 2 and a net reduction of 0.083 when R 2 CHADS 2 was compared with CHADS 2 . In conclusion, current stroke stratification scores have comparable but limited ability to predict stroke in patients with AF. Stroke prevention strategies may vary depending on the applied stratification. There is a need for a better stroke risk stratification score for patients with AF., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: In Israel, coronary heart disease mortality rates are significantly higher among the Arab population than the Jewish population. Dyslipidemia prevention should begin in childhood., Objectives: To identify sociodemographic disparities in the preventive health measurement of lipid profile testing and lipoprotein levels among Israeli children and adolescents., Methods: A cross-sectional analysis of 1.2 million children and adolescents insured by Clalit Health Services between 2007 and 2011 was conducted using sociodemographic data and serum lipid concentrations., Results: Overall, 10.1% individuals had undergone lipid testing. Those with male sex (odds ratio [OR] = 0.813, 95% confidence interval [95%CI] 0.809-0.816), Arab ethnicity (OR = 0.952, 95%CI 0.941-0.963), and low socioeconomic status (SES) (OR = 0.740, 95%CI 0.728-0.752) were less likely to be tested. By 2010, differences among economic sectors narrowed and Arab children were more likely to be tested (OR = 1.039, 95%CI 1.035-1.044). Girls had higher total cholesterol, triglyceride, low-density lipoprotein-cholesterol, and non-high-density lipoprotein-cholesterol levels compared to boys (P < 0.001). Jewish children had higher cholesterol and low-density and high-density lipoprotein-cholesterol, as well as lower triglyceride levels than Arabs (P < 0.001). Children with low SES had lower cholesterol, low-density and high-density lipoprotein-cholesterol, and non-high-density lipoprotein-cholesterol levels (P < 0.001)., Conclusions: We found that boys, Arab children, and those with low SES were less likely to be tested. Over time there was a gradual reduction in these disparities. Publicly sponsored healthcare services can diminish disparities in the provision of preventive health among diverse socioeconomic groups that comprise the national population.

Background: Falls while turning are associated with increased risk of hip fracture in older adults. Reliable and clinically valid methods for turn ability assessments are needed., Objectives: To explore the inter-observer reliability and known group validity of the TURN 180 test., Methods: We divided 78 independent older adults (mean age 76.6 ± 6.5 years) into three groups: non-fallers, infrequent fallers (1-2 falls per year), and recurrent fallers (> 2 falls per year). Participants underwent performance-based tests: Timed Up and Go (TUG), Performance Oriented Mobility Assessment (POMA), and Berg Balance Scale (BBS). TUG was videotaped for later analysis of the TURN 180 test by two blinded observers., Results: A significant difference was found in the TURN 180 test parameters among the groups (P < 0.04). TURN 180 was highly correlated with TUG (r = 0.81-0.89, P < 0.001) and BBS (r = -0.704-0.754, P < 0.0001) and moderately with POMA (r = -0.641-0.698, P < 0.0001). The number of steps was found to be the strongest parameter to determine fallers among older adults (specificity 96.3%, sensitivity 40%). Inter-rater reliability (intraclass correlation coefficient 0.91-0.96, P < 0.0001) was found to be excellent for the number of steps, time taken to accomplish a turn, and total test score categories., Conclusions: The TURN 180 test is highly reliable and can identify the older adults who fall. Our results show that the TURN 180 test can serve as a good performance-based examination for research or clinical setting.

Background: Oral anticoagulation (OAC) is effective in stroke prevention in elderly patients with nonvalvular atrial fibrillation (AF), but older patients are also at higher risk of bleeding., Objective: We aimed to examine whether OAC has net clinical benefit (NCB) in elderly patients with AF., Methods: This is a retrospective cohort study of patients with AF, aged 75 years and older, who were diagnosed from January 1, 2013, through December 31, 2015. Incidences of stroke and intracranial hemorrhage (ICH) were estimated as the number of events per 100 person-years. The NCBs were estimated with respect to time in therapeutic range (TTR) (<60% or ≥60%) and treatment type (warfarin and low or high dose of direct oral anticoagulants [DOACs])., Results: We included 11,760 patients, of whom 4982 (42.4%) were treated with OACs: 2042 (17.4%) with warfarin and 2940 (25.0%) with DOACs. Among patients treated with warfarin, those who achieved TTR ≥ 60% had a lower incidence of stroke (2.54 per 100 person-years vs 5.21 per 100 person-years; P = .01) but without a statistically significant lower incidence of ICH (0.68 per 100 person-years vs 1.10 per 100 person-years; P = .45) and a higher NCB (9.78 vs 6.52) than did those with TTR < 60%. Among patients treated with DOACs, patients treated with the high dose had a statistically significant similar incidence of stroke (8.40 per 100 person-years vs 9.81 per 100 person-years; P = .67), a statistically significant lower incidence of ICH (0.33 per 100 person-years vs 1.20 per 100 person-years; P = .02), and a higher NCB (4.42 vs 1.78) than did patients treated with the low dose., Conclusion: A large proportion of elderly patients are not treated with OACs. We found that the NCB of OAC in the elderly is positive, with the highest benefit in elderly patients treated with warfarin who achieved TTR ≥ 60% or high dose of DOACs., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aim: To investigate the characteristics of participants in the Diabetes Conversation Map™ (Map™) program who had higher vs. lower compliance to the program, to determine if program tailoring and monitoring is needed among these groups., Methods: This was a retrospective cohort study of 8990 patients enrolled in the Map™ program (low compliance [attending 0-1 sessions, n = 2759] and high compliance [attending ≥2 sessions, n = 6231]). Socio-demographic, clinical, health behaviors, and healthcare utilization characteristics were extracted. Multivariable stepwise logistic regression was used as the analysis strategy., Results: Those who were of higher socio-economic status (OR = 1.567, 95%CI:1.317-1.865), who lived in urban area (OR = 1.501, 95%CI:1.254-1.798), with greater frequency of primary care visits (OR = 1.012, 95%CI:1.002-1.021), with medium (OR = 1.176, 95%CI:1.013-1.365) or high oral medication adherence (OR = 1.198, 95%CI:1.059-1.356), and with a greater frequency of blood glucose tests (OR = 1.102, 95%CI:1.033-1.175) had greater odds of being in the high compliance group. Conversely, those aged 35-44 (OR = 0.538, 95%CI:0.402-0.721) and 45-54 years (OR = 0.763, 95%CI:0.622-0.937), with longer Type 2 diabetes duration (OR = 0.980, 95%CI:0.967-0.993), with higher blood glucose levels (OR = 0.999, 95%CI:0.998-1.000), and current (OR = 0.659, 95%CI:0.569-0.762) or former smokers (OR = 0.831, 95%CI:0.737-0.938) had reduced odds for being in the higher compliance group., Conclusions: Instructors in advance can target sub-groups to increase their attendance rates, and consequently improve their outcomes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Worse renal function, even in the normal or mildly impaired range, is associated with incident cardiovascular disease (CVD). Whether this association exists in both sexes across all ages is not known., Methods: A population based cohort of individuals >22 years with no prior CVD and with an eGFR 60-130 ml/min/1.73 m 2 . eGFR was calculated using the CKD-EPI formula. Incident CVD was defined as either myocardial infarction, unstable angina pectoris, coronary revascularization, or cerebrovascular event. Incident CVD was examined separately in men and women in 3 age-groups (young, 22-40 years; middle-aged, 41-60 years; and elderly, ≥61 years), during a median follow-up of 96.0 months., Results: Among 1,341,400 individuals (57% women, mean age 49.2 ± 16.6 years), men had more incident CVD as compared to women (34,968 vs. 23,515 total incident CVD) in all age-groups (0.6% vs. 0.2% in young; 6.2% vs. 2.0% in middle-aged; 13.4% vs. 8.4% in elderly, respectively). After adjustment for CVD risk factors, an increment of 10 units in eGFR was independently associated with a decrease of 5.4%, 3.4% and 5.4% in incident CVD in young, middle-aged and elderly men (p < 0.001 for each) and a decrease of 6.3%, 3.4% and 6.8% in the same age-groups in women (p < 0.001 for each). There was no significant age-sex interaction in the association between eGFR and incident CVD., Conclusion: Although incident CVD differs in men and women, as well as in different age-groups, a higher eGFR even in the normal or mildly impaired range is associated with lesser incident CVD in men and women of all ages., (Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Introduction: Adalimumab (ADA) is a medication used in the treatment of several autoimmune diseases. Despite the beneficial effects of ADA, its adherence and persistence rates are low. Patients treated with ADA from Clalit Health Services (CHS) can enroll in AbbVie's patient support program (PSP), which aims to improve ADA adherence and persistence. Therefore, we examine whether PSP participation is associated with a longer persistence and/or an improved adherence to ADA., Methods: A real-world retrospective cohort study of all new ADA users from CHS, comparing those enrolled in the offered PSP to those not enrolled. The data regarding PSP users can be tracked using CHS's data warehouse. The index date was defined as the date of the patients' first purchase of ADA occurring between August 1, 2012 and December 31, 2014. The follow-up data were collected at 12, 24, and 36 months. Persistence was assessed using survival analyses of time until discontinuation, and adherence was assessed using medication possession ratio (MPR)., Results: There were 1520 patients in the study, 755 (49.7%) of whom were PSP users. PSP users were 54.3% female vs. 51.9% among non-PSP users (p = 0.355) and they were significantly younger than non-PSP users (mean age 42.3 vs. 45.0 years, p = 0.002) The PSP and non-PSP users' persistence was 673 and 574 days, respectively (p < 0.001). Further, the PSP users were more likely than the non-PSP users to be persistently taking medication at the 12-month follow-up (57.5% vs. 45.6%, p < 0.001). The 12-month mean adherence rate among those with at least 12 months of persistence was significantly improved for the PSP users compared to the non-PSP users (94.1% vs. 92.9%, p = 0.026)., Conclusion: The AbbVie PSP provided to CHS patients was associated with a longer persistence among new users of ADA. It was also associated with significantly higher adherence rate within the first 12 months., Funding: AbbVie Inc.

Background: Postpartum depression (PPD) is associated with pain during and after delivery, with studies showing reduced rates among women delivering with labor epidural analgesia (LEA). We hypothesized that women who intend to deliver with LEA but do not receive it are at higher risk for PPD at 6 weeks due to the combined experience of untreated labor pain and unmatched expectations during labor, and evaluated the interaction between labor plans related to LEA, satisfaction with pain control when actually delivering with LEA, and PPD at 6 weeks after delivery., Methods: A total of 1497 women with a vaginal delivery were enrolled into this prospective longitudinal study. Women's initial intention to deliver with or without LEA, how they subsequently delivered, and satisfaction with pain relief were recorded on postpartum day 1. Primary aim was selected as PPD at 6 weeks among women intending to deliver with but subsequently delivering without LEA compared with the rest of the cohort. Primary outcome was PPD at 6 weeks using the Edinburgh Postnatal Depression Scale; PPD was defined with a score ≥10 (scale from 0 to 30). Demographic and obstetric data were recorded. Fisher exact test was used for comparisons between groups. The interaction between intention and actual delivery with regard to LEA and PPD was tested., Results: Overall, 87 of 1326 women completing the study at 6 weeks had PPD (6.6%). For the primary aim, 439 (29.3%) delivered without LEA, of which 193 (12.9%) had intended to deliver with LEA; the PPD rate among these women was 8.1%, which was not statistically different from the rest of the cohort (6.3%; odds ratio [OR], 1.30; 95% confidence interval [CI], 0.72-2.38; P = .41). A total of 1058 women (70.7%) delivered with LEA and 439 (29.3%) delivered without; therefore, 1169 (78.1%) delivered as intended and 328 (21.9%) did not (unmatched expectations). Evaluating the interaction between effects, there was a strong negative additive interaction between intending to deliver without LEA and actually delivering with LEA (risk difference = -8.6%, 95% CI, 16.2%-1.6%; P = .014) suggesting that unmatched intention effect is significantly associated with negative outcome. In multiple regression analysis, while intending to deliver with LEA (OR, 1.06; 95% CI, 1.01-1.11; P = .029) and actually delivering with LEA (OR, 1.07; 95% CI, 1.01-1.13; P = .018) both increased the odds for PPD, the multiplicative interaction was protective (OR, 0.92; 95% CI, 0.86-0.99; P = .022), after adjusting for cofactors., Conclusions: Our study results did not demonstrate a significant increase in the odds for PPD at 6 weeks among women who intended to deliver with LEA but subsequently delivered without. However, we identified a protective interaction between intended LEA use and actual use on the incidence of PPD. Our data suggest an increased risk when women do not deliver as intended, particularly when not initially intending to deliver with LEA. The relationship between unplanned LEA and PPD may be mediated by a physically difficult delivery rather than or in addition to negative emotions related to unmet expectations or a sense of personal failure; therefore, counseling women after delivery to address any negative perceptions may be useful.

Objectives: This study sought to identify the differences in stroke, mortality, and bleeding between men and women with atrial fibrillation (AF)., Background: There are inconsistent data regarding the thromboembolic risk difference between men and women with AF. The authors assessed the risk of stroke, death, and bleeding in men and women with incident AF., Methods: The authors employed a prospective historical cohort using an electronic database from a large health maintenance organization. All members with incident AF between 2004 and 2015 were included. Primary endpoints were ischemic stroke, death, and major bleeding., Results: The authors identified 89,213 members with incident nonvalvular atrial fibrillation (NVAF), 52.3% of whom were women. Women were older, with a higher prevalence of hypertension, whereas more men had diabetes, heart failure, and ischemic heart disease than the women did. Ischemic stroke occurred in 6.4% of the patients: 7.0% of women and 5.8% of men. Sex did not affect adjusted stroke risk (hazard ratio [HR]: 0.91; 95% confidence interval [CI]: 0.77 to 1.06; p = 0.22). However, women 75 years of age and older were at an increased risk (HR: 1.25; 95% CI: 1.17 to 1.34). Mortality rates were higher among women (33.5% vs. 32%; p < 0.001); however, women had a significantly lower adjusted mortality risk (HR: 0.78; 95% CI: 0.71 to 0.86). Women had lower risk of intracranial hemorrhage (HR: 0.81; 95% CI: 0.76 to 0.87) and major gastrointestinal bleeding (HR: 0.78; 95% CI: 0.70 to 0.87)., Conclusions: Men and women with AF had a similar risk of ischemic stroke, except for women 75 years of age or older, who had a higher risk. Our findings support using a similar anticoagulation strategy for prevention of stroke in men and women with a similar number of risk factors., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Disparity-reduction programs have been shown to vary in the degree to which they achieve their goal; yet the causes of these variations is rarely studied. We investigated a broad-scale program in Israel's largest health plan, aimed at reducing disparities in socially disadvantaged groups using a composite measure of seven health and health care indicators., Methods: A realistic evaluation was conducted to evaluate the program in 26 clinics and their associated managerial levels. First, we performed interviews with key stakeholders and an ethnographic observation of a regional meeting to derive the underlying program theory. Next, semi-structured interviews with 109 clinic teams, subregional headquarters, and regional headquarters personnel were conducted. Social network analysis was performed to derive measures of team interrelations. Perceived team effectiveness (TE) and clinic characteristics were assessed to elicit contextual characteristics. Interventions implemented by clinics were identified from interviews and coded according to the mechanisms each clinic employed. Assessment of each clinic's performance on the seven-indicator composite measure was conducted at baseline and after 3 years. Finally, we reviewed different context-mechanism-outcome (CMO) configurations to understand what works to reduce disparity, and under what circumstances., Results: Clinics' inner contextual characteristics varied in both network density and perceived TE. Successful CMO configurations included 1) highly dense clinic teams having high perceived TE, only a small gap to minimize, and employing a wide range of interventions; (2) clinics with a large gap to minimize with high clinic density and high perceived TE, focusing efforts on tailoring services to their enrollees; and (3) clinics having medium to low density and perceived TE, and strong middle-management support., Conclusions: Clinics that achieved disparity reduction had high clinic density, close ties with middle management, and tailored interventions to the unique needs of the populations they serve.

Importance: Bariatric surgery is an effective and safe approach for weight loss and short-term improvement in metabolic disorders such as diabetes. However, studies have been limited in most settings by lack of a nonsurgical group, losses to follow-up, missing data, and small sample sizes in clinical trials and observational studies., Objective: To assess the association of 3 common types of bariatric surgery compared with nonsurgical treatment with mortality and other clinical outcomes among obese patients., Design, Setting, and Participants: Retrospective cohort study in a large Israeli integrated health fund covering 54% of Israeli citizens with less than 1% turnover of members annually. Obese adult patients who underwent bariatric surgery between January 1, 2005, and December 31, 2014, were selected and compared with obese nonsurgical patients matched on age, sex, body mass index (BMI), and diabetes, with a final follow-up date of December 31, 2015. A total of 33 540 patients were included in this study., Exposures: Bariatric surgery (laparoscopic banding, Roux-en-Y gastric bypass, or laparoscopic sleeve gastrectomy) or usual care obesity management only (provided by a primary care physician and which may include dietary counseling and behavior modification)., Main Outcomes and Measures: The primary outcome, all-cause mortality, matched and adjusted for BMI prior to surgery, age, sex, socioeconomic status, diabetes, hyperlipidemia, hypertension, cardiovascular disease, and smoking., Results: The study population included 8385 patients who underwent bariatric surgery (median age, 46 [IQR, 37-54] years; 5490 [65.5%] women; baseline median BMI, 40.6 [IQR, 38.5-43.7]; laparoscopic banding [n = 3635], gastric bypass [n = 1388], laparoscopic sleeve gastrectomy [n = 3362], and 25 155 nonsurgical matched patients (median age, 46 [IQR, 37-54] years; 16 470 [65.5%] women; baseline median BMI, 40.5 [IQR, 37.0-43.5]). The availability of follow-up data was 100% for all-cause mortality. There were 105 deaths (1.3%) among surgical patients during a median follow-up of 4.3 (IQR, 2.8-6.6) years (including 61 [1.7%] who underwent laparoscopic banding, 18 [1.3%] gastric bypass, and 26 [0.8%] sleeve gastrectomy), and 583 deaths (2.3%) among nonsurgical patients during a median follow-up of 4.0 (IQR, 2.6-6.2) years. The absolute difference was 2.51 (95% CI, 1.86-3.15) fewer deaths/1000 person-years in the surgical vs nonsurgical group. Adjusted hazard ratios (HRs) for mortality among nonsurgical vs surgical patients were 2.02 (95% CI, 1.63-2.52) for the entire study population; by surgical type, HRs were 2.01 (95% CI, 1.50-2.69) for laparoscopic banding, 2.65 (95% CI, 1.55-4.52) for gastric bypass, and 1.60 (95% CI, 1.02-2.51) for laparoscopic sleeve gastrectomy., Conclusions and Relevance: Among obese patients in a large integrated health fund in Israel, bariatric surgery using laparoscopic banding, gastric bypass, or laparoscopic sleeve gastrectomy, compared with usual care nonsurgical obesity management, was associated with lower all-cause mortality over a median follow-up of approximately 4.5 years. The evidence of this association adds to the limited literature describing beneficial outcomes of these 3 types of bariatric surgery compared with usual care obesity management alone.

Objectives: Pediatric lipoprotein curves are based on population-based samples. As obesity, may alter lipoprotein levels, cutoffs not adjusted for body mass index (BMI) are potentially inappropriate. We aimed to develop distinct serum lipid curves based on sex- and BMI-percentiles for children and adolescents., Methods: Cross-sectional analysis included all healthy children and adolescents (age range 2-17 years) with available serum lipid concentrations (n = 152,820 of approximately 1.2 million children and adolescents per study year). These children and adolescents were categorized according to sex- and age-stratified BMI-percentiles: 100,375 normal weight (5th-85th percentile), 26,028 overweight (85th-95th percentile) and 26,417 obese (≥95th percentile) individuals. Excluded were individuals with hyperlipidemia, gastrointestinal disease, thyroid disease and lipid-lowering medications. Lambda-Mu-Sigma, smoothed percentile lipid curves were computed., Results: Obese children had a lipid profile pattern throughout childhood and adolescence similar to that of normal weight subjects but with a significant upward shift in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides (TGs) and a downward shift in high-density lipoprotein-cholesterol (HDL-C). Obese boys had 13 mg/dL higher TC levels (P < 0.001), 11 mg/dL higher LDL-C levels, 15 mg/dL higher non-HDL-C levels, and 5 mg/dL lower HDL-C levels (P < 0.001). Obese girls had 6 mg/dL higher TC levels, 7 mg/dL higher LDL-C levels, 11 mg/dl higher non-HDL-C levels, and 6 mg/dL lower HDL-C levels (P < 0.001)., Conclusions: Across a large, nationally representative cohort of children and adolescents, lipoprotein levels were found to vary in relation to weight status. On the basis of these findings, it is suggested that when evaluating the lipid profile in the pediatric population, in addition to sex-based curves, clinical decision making may require consideration of BMI-stratified curves.