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Orna Reges,1,2,* Hagay Weinberg,3,4,* Moshe Hoshen,1,5 Philip Greenland,2 Hana’a Rayyan-Assi,1 Meytal Avgil Tsadok,1 Asaf Bachrach,1 Ran Balicer,1,6 Morton Leibowitz,1 Moti Haim7,8 1Clalit Research Institute, Clalit Health Services, Tel Aviv, Israel; 2Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 3Internal Medicine Department, Meir Medical Center, Kfar-Saba, Israel; 4Department of Medicine, MidCentral District Health Board, Palmerston-North, New Zealand; 5National Information Systems, Computational Authority, Ministry of Health, Jerusalem, Isarel; 6Department of Epidemiology, Ben-Gurion University of the Negev, Beer-Sheva, Israel; 7Department of Cardiology, Soroka University Medical Center, Beer Sheva, Israel; 8Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel*These authors contributed equally to this workCorrespondence: Orna RegesDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 North Lake Shore Drive, Suite 1400, Chicago, IL 60611, USAEmail orna.reges@gmail.comPurpose: Previous studies have demonstrated differences in atrial fibrillation (AF) detection based on data from hospital sources without data from outpatient sources. We investigated the detection of documented diagnoses of non-valvular AF in a large Israeli health-care organization using electronic health record data from multiple sources.Patients and Methods: This was an open-chart validation study. Three distinct algorithms for identifying AF in electronic health records, differing in the source of their International Classification of Diseases, Ninth Revision code and use of the associated free text, were defined. Algorithm 1 incorporated inpatient data with outpatient data and the associated free text. Algorithm 2 incorporated inpatient and outpatient data regardless of the free text associated with AF diagnosis. Algorithm 3 used only inpatient data source. These algorithms were compared to a gold standard and their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. To establish the gold standard (documentation of arrhythmia based on electrocardiography interpretation or a cardiologist’s written diagnosis), 200 patients at highest risk for having non-valvular AF were randomly selected for open-chart validation by two physicians.Results: The algorithm that included hospital settings, outpatient settings, and incorporated associated free text in the outpatient records had the optimal balance between all validation measures, with a high level of sensitivity (85.4%), specificity (95.0%), PPV (81.4%), and NPV (96.2%). The alternative algorithm that combined inpatient and outpatient data without free text also performed better than the algorithm that included only hospital data (82.9%, 95.0%, 81.0%, and 95.6%, compared to 70.7%, 96.9%, 85.3%, and 92.8%, sensitivity, specificity, PPV, and NPV, respectively).Conclusion: In this study, involving a comprehensive data collection from inpatient and outpatient sources, incorporating outpatient data with inpatient data improved the diagnosis of non-valvular AF compared to inpatient data alone.Keywords: atrial fibrillation, validation, electronic health records

Abstract Background The development and propagation of malaria parasites in their vertebrate host is a complex process in which various host and parasite factors are involved. Sometimes the evolution of parasitaemia seems to be quelled by parasite load. In order to understand the typical dynamics of evolution of parasitaemia, various mathematical models have been developed. The basic premise ingrained in most models is that the availability of uninfected red blood cells (RBC) in which the parasite develops is a limiting factor in the propagation of the parasite population. Presentation of the hypothesis We would like to propose that except in extreme cases of severe malaria, there is no limitation in the supply of uninfected RBC for the increase of parasite population. Testing the hypothesis In this analysis we examine the biological attributes of the parasite-infected RBC such as cytoadherence and rosette formation, and the rheological properties of infected RBC, and evaluate their effects on blood flow and clogging of capillaries. We argue that there should be no restriction in the availability of uninfected RBC in patients. Implication of the hypothesis There is no justification for the insertion of RBC supply as a factor in mathematical models that describe the evolution of parasitaemia in the infected host. Indeed, more recent models, that have not inserted this factor, successfully describe the evolution of parasitaemia in the infected host.

Documentation of primary care teams' involvement in disparity reduction efforts exists, yet little is known about how teams interact or perceive their effectiveness. We investigated how the social network and structural ties among primary-care-clinic team members relate to their perceived team effectiveness (TE), in a large-scale disparity reduction intervention in Israel's largest insurer and provider of services. A mixed-method design of Social Network Analysis and qualitative data collection was employed. 108 interviews with medical, nursing, and administrative teams of 26 clinics and their respective managerial units were performed and information on the organizational ties, analyzing density and centrality, collected. Pearson correlations examined association between network measures and perceived TE. Clinics with strong intra-clinic density and high clinic–subregional-management density were positively correlated with perceived TE. Clinic in-degree centrality was also positively associated with perceived TE. Qualitative analyses support these findings with teamwork emerging as a factor which can impede or facilitate teams' ability to design and implement disparity reduction interventions. The study demonstrates that in an organization-wide disparity reduction initiative, cohesive intra-network structure and close relations with mid-level management increase the likelihood that teams perceive themselves as possessing the skills and resources needed to lead and implement disparity reduction efforts. List of abbreviations Team Effectiveness (TE); Clalit Health Services (Clalit); Social Network Analysis (SNA); Quality Improvement (QI); National Health Care Collaborative (NHPC); Tampa Bay Community Cancer Network (TBCCN) [ABSTRACT FROM AUTHOR]

Background: To support malaria control strategies, prior knowledge of disease risk is necessary. Developing a model to explain the transmission of malaria, in endemic and epidemic regions, is of high priority in developing health system interventions. We develop, fit and validate a non-spatial dynamic model driven by meteorological conditions that can capture seasonal malaria transmission dynamics at the village level in a malaria holoendemic area of north-western Burkina Faso. Methods: A total of 676 children aged 6-59 months took part in this study. Trained interviewers visited children at home weekly from December 2003 to November 2004 for Plasmodium falciparum malaria infection detection. Anopheles daily biting rate, mortality rate and growth rate were evaluated. Digital meteorological stations measured ambient temperature, humidity and rainfall in each site. Results: The overall P. falciparum malaria infection incidence was 1.1 episodes per person year. There was strong seasonal variation in P. falciparum malaria infection incidence with a peak observed in August and September, corresponding to the rainy season and a high number of mosquitoes. The model estimates of monthly mosquito abundance and the incidence of malaria infection correlated well with observed values. The fit was sensitive to daily mosquito survival and daily human parasite clearance. Conclusion: The model has demonstrated potential for local scale seasonal prediction of P. falciparum malaria infection. It could therefore be used to understand malaria transmission dynamics using meteorological parameters as the driving force and to help district health managers in identifying high-risk periods for more focused interventions. [ABSTRACT FROM AUTHOR]

Background: The development and propagation of malaria parasites in their vertebrate host is a complex process in which various host and parasite factors are involved. Sometimes the evolution of parasitaemia seems to be quelled by parasite load. In order to understand the typical dynamics of evolution of parasitaemia, various mathematical models have been developed. The basic premise ingrained in most models is that the availability of uninfected red blood cells (RBC) in which the parasite develops is a limiting factor in the propagation of the parasite population. Presentation of the hypothesis: We would like to propose that except in extreme cases of severe malaria, there is no limitation in the supply of uninfected RBC for the increase of parasite population. Testing the hypothesis: In this analysis we examine the biological attributes of the parasite-infected RBC such as cytoadherence and rosette formation, and the rheological properties of infected RBC, and evaluate their effects on blood flow and clogging of capillaries. We argue that there should be no restriction in the availability of uninfected RBC in patients. Implication of the hypothesis: There is no justification for the insertion of RBC supply as a factor in mathematical models that describe the evolution of parasitaemia in the infected host. Indeed, more recent models, that have not inserted this factor, successfully describe the evolution of parasitaemia in the infected host. [ABSTRACT FROM AUTHOR]

Purpose Few studies have investigated the association between religiosity and self-injurious thoughts and behaviors specifically in adolescents, yielding inconsistent results. To date, no study has examined this relationship in a Jewish adolescent cohort. Methods Self-injurious thoughts and behaviors, as well as depression, were assessed in a nationally representative sample of Jewish adolescents ( n = 620) and their mothers, using the Development and Well-Being Assessment Inventory (DAWBA) structured interview. Degree of religiosity was obtained by a self-report measure. Results Using multivariate analysis, level of religiosity was inversely associated with self-injurious thoughts and behaviors (Wald χ 2 = 3.95, P = 0.047), decreasing the likelihood of occurrence by 55% (OR = 0.45, 95% CI 0.2–0.99), after adjusting for depression and socio-demographic factors. This model (adjusted R 2 = 0.164; likelihood ratio χ 2 = 7.59; df = 1; P < 0.047) was able to correctly classify 95.6% of the patients as belonging either to the high or low risk groups. Conclusion This is the first study demonstrating religiosity to have a direct independent protective effect against self-injurious thoughts and behaviors in Jewish adolescents. This finding has clinical implications regarding risk assessment and suicide prevention. Further research can potentially elucidate the complex relationship between religiosity, self-injury and suicide in this population. [ABSTRACT FROM AUTHOR]

Mathematical modelling has been used to assess the level of malarial transmission, during the dry season, in Nouna province, in north–western Burkina Faso. The data used were collected, at four sites (one semi-urban and three rural), from 867 children aged 6–60 months who were randomly selected. Almost all of the children (850) completed the follow-up, which involved the active detection of malaria (i.e. febrile, smear-positive malarial infection) throughout a single dry season (December 2003–May 2004). Light traps were used to sample the local populations of Anopheles vectors, in order to estimate the daily biting rate. The mathematical model was then used to simulate the incidence of malaria, which was compared with the observed incidence. At all four study sites, new cases of malaria were observed throughout the dry season, although the level of transmission was low. The monthly incidence of malaria estimated using the mathematical model was very close to the observed incidence. The fit was sensitive to daily mosquito survival and daily human parasite clearance. In Nouna province, effective interventions to prevent malaria should not be confined to the rainy season but must continue throughout the year. The focus should be on the clearance of parasitaemias, by the use of effective drugs, and on decreasing vector survival, by the use of vector-control methods. [ABSTRACT FROM AUTHOR]

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.)