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Introduction: Studies show that physicians' attitudes are a major influential factor in the degree of implementation of telemedicine and that most of them identify much more opportunities in this type of visit than risks. These findings do not explain the observed decrease in the use of telemedicine in primary care with the decline of the COVID-19 pandemic. The aim of our study was to understand the gap between the attitudes that primary care physicians declare towards telemedicine and the extent to which they use it in practice., Methods: A qualitative research using a semi-structured phone interview with 33 primary care physicians experienced in telemedicine from Leumit Health Services, a health fund in Israel. A qualitative thematic analysis method was used to extract the main themes from all interviews, and descriptive statistical tests were used to analyze the demographic variables., Results: The attitude of the physicians depended on the perception of their professional identity and their sense of control over telemedicine implementation. The more established their professional identity and the stronger the support from the organization in the technology integration, the more positive the physician's attitude towards this type of visit., Discussion: Healthcare organizations that wish to improve the use of telemedicine in primary care should understand that this is more than just the implementation of new technology: they must find a way to properly support the profound change that doctors must undergo when defining their new role and professional status.

Background: There are no published epidemiologic studies with regard to the prevalence of neurologic diseases among subjects with selective immunoglobulin A (IgA) deficiency (sIgAD). Objective: To investigate the prevalence of neurologic diseases among the Israeli population with sIgAD. Methods: A population-based case-control study among members of a large nationwide health maintenance organization in Israel providing services to > 700,000 members. The sIgAD group included individuals ≥4 years of age with a serum IgA level of <0.07 g/L and with a diagnosis of sIgAD. The control group was randomly sampled from the entire study population with a case-control ratio of five controls for each case (1:5), with exact matching for age, gender, ethnic group, and socioeconomic status category. Results: A total of 796 subjects ages 20.58 ± 15.46 years; 391 female subjects (49.1%) were identified as having sIgAD. The control group was constituted of 3980 matched subjects. The sIgAD group was characterized by a higher prevalence of autism spectrum disorder and tic disorders. Migraine was less prevalent in the sIgAD group (19 [2.39%]) than in the control group (168 [4.22%]), odds ratio (OR) 0.55 (95% confidence interval {CI}, 0.34-0.90); p = 0.016]. More cases of subjects with epilepsy were observed in the sIgAD group (14 [1.76%]) than in the control group (31 [0.80%]), OR 2.28 (95% CI, 1.12 - 4.44; p = 0.015). Conclusion: Our observation raises the question of the role of IgA in noninfectious diseases of the central nervous system. Further basic studies are needed to explain our observation.

Background: Previous studies have shown that more temporally regular primary care visits are associated with improved patient outcomes., Objective: To examine the association of temporal regularity (TR) of primary care with hospitalizations and mortality in patients with chronic illnesses. Also, to identify threshold values for TR for predicting outcomes., Design: Retrospective cohort study., Participants: We used data from the electronic health record of a health maintenance organization in Israel to study primary care visits of 70,095 patients age 40 + with one of three chronic conditions (diabetes mellitus, heart failure, chronic obstructive pulmonary disease)., Main Measures: We calculated TR for each patient during a two-year period (2016-2017), and divided patients into quintiles based on TR. Outcomes (hospitalization, death) were observed in 2018-2019. Covariates included the Bice-Boxerman continuity of care score, demographics, and comorbidities. We used multivariable logistic regression to examine TR's association with hospitalization and death, controlling for covariates., Key Results: Compared to patients receiving the most regular care, patients receiving less regular care had increased odds of hospitalization and mortality, with a dose-response curve observed across quintiles (p for linear trend < 0.001). For example, patients with the least regular care had an adjusted odds ratio of 1.40 for all-cause mortality, compared to patients with the most regular care. Analyses stratified by age, sex, ethnic group, area-level SES, and certain comorbid conditions did not show strong differential associations of TR across groups., Conclusions: We found an association between more temporally regular care in antecedent years and reduced hospitalization and mortality of patients with chronic illness in subsequent years, after controlling for covariates. There was no clear threshold value for temporal regularity; rather, more regular primary care appeared to be better across the entire range of the variable., (© 2023. The Author(s).)

Background and Aims: Although obesity has been confirmed as a risk factor for SARS-CoV-2 infection and its severity, the role of post-bariatric surgery (BS) variables and the infection is unclear. We, therefore, aimed to study comprehensively the relationship between the extent of weight reduction after surgery and other demographic, clinical, and laboratory variables with the rates of SARS-CoV-2 infection., Methods: A population-based cross-sectional study was performed, utilizing advanced tracking methodologies on the computerized database of a nation-wide health maintenance organization (HMO). The study population included all HMO members aged ≥18 years that had been tested at least once for SARS-CoV-2 during the study period and underwent BS at least one year before their testing., Results: Of the total 3038 individuals who underwent BS, 2697 (88.78%) were positive for SARS-CoV-2 infection and 341 (11.22%) were negative. Multivariate regression analysis demonstrated that the body mass index and the amount of weight reduction after the BS were not related to the likelihood of SARS-CoV-2 infection. Post-operative low socioeconomic status (SES) and vitamin D3 deficiency were associated with significant and independent increased rates of SARS-CoV-2 infection (odds ratio [OR] 1.56, 95% confidence interval [CI], 1.19-2.03, p < 0.001; and OR 1.55, 95% CI, 1.18-2.02, p < 0.001; respectively). Post-operative physical activity > 3 times/week was associated with a significant and independent reduced rate of SARS-CoV-2 infection (OR 0.51, 95% CI, 0.35-0.73, p < 0.001)., Conclusion: Post-BS vitamin D3 deficiency, SES, and physical activity, but not the amount of weight reduction, were significantly associated with the rates of SARS-CoV-2 infection. Healthcare workers should be aware of these associations after BS and intervene accordingly.

Aim: To explore the implications for dentists and family doctors of the association between periodontal and systemic diseases and the role of dentists and family doctors in managing non-communicable diseases (NCDs) and promoting healthy lifestyles., Materials and Methods: The consensus reports of the previous Focused Workshops on the associations between periodontitis and diabetes (2017) and periodontitis and cardiovascular diseases (2019) formed the technical reviews to underpin discussions on both topics. For the association with respiratory diseases, a systematic review was specifically commissioned for the Workshop discussions. Working groups prepared proposals independently, and then the proposals were discussed and approved at plenary meetings., Results: Periodontitis is independently associated with cardiovascular diseases, diabetes, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea and COVID-19 complications. Dentists and family doctors should collaborate in managing NCDs, implementing strategies for early detection of periodontitis in primary care centres and of cardiovascular diseases or diabetes in dental settings. Family doctors should be informed about periodontal diseases and their consequences, and oral health professionals (OHPs) should be informed about the relevance of NCDs and the associated risk factors., Conclusions: Closer collaboration between OHPs and family doctors is important in the early detection and management of NCDs and in promoting healthy lifestyles. Pathways for early case detection of periodontitis in family medicine practices and of NCDs in dental practices should be developed and evaluated., (© 2023 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Background: Patients with chronic diseases should meet with their primary care doctor regularly to facilitate proactive care. Little is known about what factors are associated with more regular follow-up., Methods: We studied 70,095 patients age 40 + with one of three chronic conditions (diabetes mellitus, heart failure, chronic obstructive pulmonary disease), cared for by Leumit Health Services, an Israeli health maintenance organization. Patients were divided into the quintile with the least temporally regular care (i.e., the most irregular intervals between visits) vs. the other four quintiles. We examined patient-level predictors of being in the least-temporally-regular quintile. We calculated the risk-adjusted regularity of care at 239 LHS clinics with at least 30 patients. For each clinic, compared the number of patients with the least temporally regular care with the number predicted to be in this group based on patient characteristics., Results: Compared to older patients, younger patients (age 40-49), were more likely to be in the least-temporally-regular group. For example, age 70-79 had an adjusted odds ratio (AOR) of 0.82 compared to age 40-49 (p < 0.001 for all findings discussed here). Males were more likely to be in the least-regular group (AOR 1.18). Patients with previous myocardial infarction (AOR 1.07), atrial fibrillation (AOR 1.08), and current smokers (AOR 1.12) were more likely to have an irregular pattern of care. In contrast, patients with diabetes (AOR 0.79) or osteoporosis (AOR 0.86) were less likely to have an irregular pattern of care. Clinic-level number of patients with irregular care, compared with the predicted number, ranged from 0.36 (fewer patients with temporally irregular care) to 1.71 (more patients)., Conclusions: Some patient characteristics are associated with more or less temporally regular patterns of primary care visits. Clinics vary widely on the number of patients with a temporally irregular pattern of care, after adjusting for patient characteristics. Health systems can use the patient-level model to identify patients at high risk for temporally irregular patterns of primary care. The next step is to examine which strategies are employed by clinics that achieve the most temporally regular care, since these strategies may be possible to emulate elsewhere., (© 2023. The Author(s).)

Background : The susceptibility to SARS-CoV-2 infection is complex and not yet fully elucidated, being related to many variables; these include human microbiome and immune status, which are both affected for a long period by antibiotic use. We therefore aimed to examine the association of previous antibiotic consumption and SARS-CoV-2 infection in a large-scale population-based study with control of known confounders. Methods: A matched case-control study was performed utilizing the electronic medical records of a large Health Maintenance Organization. Cases were subjects with confirmed SARS-CoV-2 infection ( n = 31,260), matched individually (1:4 ratio) to controls without a positive SARS-CoV-2 test ( n = 125,039). The possible association between previous antibiotic use and SARS-CoV-2 infection was determined by comparing antibiotic consumption in the previous 6 and 12 months between the cases and controls. For each antibiotic consumed we calculated the odds ratio (OR) for documented SARS-CoV-2 infection, 95% confidence interval (CI), and p -value using univariate and multivariate analyses. Results: The association between previous antibiotic consumption and SARS-CoV-2 infection was complex and bi-directional. In the multivariate analysis, phenoxymethylpenicillin was associated with increased rate of SARS-CoV-2 infection (OR 1.110, 95% CI: 1.036-1.191) while decreased rates were associated with previous consumption of trimethoprim-sulfonamides (OR 0.783, 95% CI: 0.632-0.971) and azithromycin (OR 0.882, 95% CI: 0.829-0.938). Fluroquinolones were associated with decreased rates (OR 0.923, 95% CI: 0.861-0.989) only in the univariate analysis. Previous consumption of other antibiotics had no significant association with SARS-CoV-2 infection. Conclusions: Previous consumption of certain antibiotic agents has an independent significant association with increased or decreased rates of SARS-CoV-2 infection. Plausible mechanisms, that should be further elucidated, are mainly antibiotic effects on the human microbiome and immune modulation.

Background: Poland is witnessing a migration crisis caused by the ongoing military conflict in Ukraine. In addition to housing and necessities, 1.8 million Ukrainians that had taken refuge in Poland must have access to medical care. We aim to propose a strategy for implementing the changes in the Polish health care system in response to the Ukrainian refugee crisis., Methods: A literature review on organizational changes in the functioning of health care systems during the migration crises worldwide in recent years and brainstorming in order to develop a strategy for implementing changes in the Polish health care system in response to the Ukrainian refugee crisis., Results: The proposed strategy for implementing the changes in the Polish health care system is based on building health care resilience and adaptation to different crises. The operational objectives of organization-related activities are: (1) preparation of medical facilities to provide help for refugees, (2) development and implementation of the communication system, (3) implementation of available digital solutions, (4) organization of the diagnostic and medical services, (5) and implementation of changes in the management of medical facilities., Conclusions: Urgent reorganization is required to respond to an unavoidable increase in the demand for health care services.

Objective: Infectious diseases (IDs) pose a heavy burden on children. An association between pediatric attention-deficit/hyperactivity disorder (ADHD) and specific IDs has been documented. Our objective was to test the possibility that ADHD is associated with increased likelihood for pediatric IDs at large., Method: A population-based case-control study was conducted using Electronic Medical Records (EMRs) of a national Health Maintenance Organization, Leumit Health Services (LHS). ICD-9/10 criteria were used for all diagnoses. The study population consisted of all children and adolescents (aged 5-18 years), members of LHS between January 1, 2006-June 30, 2021. Case patients met International Classification of Diseases (ICD-9/10) criteria for ADHD. Controls included randomly selected persons without ADHD (2:1 ratio), matched individually by demographic indices. The EMRs retrieved 3 exposure categories: pediatric ID, anti-infective medications use, and number of physician visits. The study was approved by the review board of Shamir Medical Center and the Research Committee of LHS., Results: Cases patients comprised 18,756 participants, with a mean age of 8.3 ± 2.6 years and a male/female ratio of 63%:37%. Matched controls comprised 37,512 participants, with a mean age of 8.3 ± 2.6 years and a male/female ratio of 63%:37%. Demographic variables were similar between the groups. The rates of all IDs were significantly higher in participants with ADHD than in controls and were not restricted to a single body system, including acute respiratory infection (OR = 1.4, 95% CI = 1.3-1.4, p < .001), acute gastroenteritis (OR = 1.3,95% CI 1.3-1.4, p < .001), salmonellosis (OR = 2.8, 95% CI = 2.3-3.5, p < .001), and urinary tract infection (OR = 1.3, 95% CI = 1.2-1.4, p < .001). All anti-infective agents were prescribed significantly more often to children with ADHD. There were significantly higher rates of physician visits for participants with ADHD., Conclusion: Study findings suggest an association between ID and pediatric ADHD Health care providers should be aware of this potential association., Clinical Trial Registration Information: The Health and Economic Impact of Treated and Untreated ADHD; https://www.shamir.org/; 005-18-LEU., (Copyright © 2022 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

COVID-19 is a worldwide pandemic caused by SARS-CoV-2, to which adults are usually more susceptible than children. Growth hormone (GH) levels differ between children and adults and decrease with age. There is bidirectional crosstalk between the GH/insulin-like growth factor-1 (IGF-1) pathway and the immune system that plays a significant role in SARS-CoV-2 infection. We evaluated the association between somatotropin treatment (GH replacement therapy) and the risk for SARS-CoV-2 positivity (a marker for COVID-19 infection) in children with growth hormone issues (GHI): growth hormone deficiency (GHD) and idiopathic short stature (ISS). A population-based cross-sectional study in Leumit Health Services (LHS) was performed using the electronic health record (EHR) database. The rates of SARS-CoV-2 positivity were evaluated among children with GHI, treated or untreated with somatotropin. Higher rates of SARS-CoV-2 positivity were found in GHI children, influenced by the same confounders reported in the pediatric population. A lower prevalence of SARS-CoV-2 PCR positivity was found among the somatotropin-treated children. A multivariate analysis documented that somatotropin treatment was associated with a reduced risk of SARS-CoV-2 positivity (Odds Ratio (OR) = 0.47, Confidence Interval (CI) 0.24-0.94, p = 0.032). Thus, somatotropin might be a protective factor against SARS-CoV-2 infections, possibly related to its immunomodulatory activity.

Background: The COVID-19 pandemic had a major impact on primary care and primary care physicians (PCPs) in Israel and around the world. There is paucity of information regarding treatment of patients with COVID-19 in the community, since most research was performed in hospitals. The aim of this study was to describe the Israeli PCPs' experience., Methods: This study is a part of an international cross-sectional study, the PRICOV-19. A translated version of the questionnaire was distributed among Israeli PCPs from December 2020 to July 2021. In this study, we describe the Israeli results and compare them to the international results., Results: 5,961 respondents from 29 countries answered the questionnaire, 94 from Israel, with an Israeli response rate of 16%. Israeli PCPs reported an increase in use of telemedicine from 11 to 49% during the COVID epidemic. PCPs also reported a decline in their wellbeing; absence of secured time slots for keeping updated; perception that the Ministry of Health guidelines were a threat to the staff wellbeing and organization of practice and delays in the examination of non-COVID urgent cases., Conclusions: The findings of this study raise concerns regarding the PCPs experience and may form the basis for an improved process of care. Guidelines for proper usage of telemedicine, substitutes for the physical examination and procedures for minimizing delayed patient examination for urgent conditions should be developed. Government directives and clinical guidelines should be communicated in a timely manner, with secured timeslots for physicians' self-learning or updating. Ensuring physicians' well-being in general should be an organization priority., (© 2022. The Author(s).)

Vaccines have allowed for a significant decrease in COVID-19 risk, and new antiviral medications can prevent disease progression if given early in the course of the disease. The rapid and accurate estimation of the risk of severe disease in new patients is needed to prioritize the treatment of high-risk patients and maximize lives saved. We used electronic health records from 101,039 individuals infected with SARS-CoV-2, since the beginning of the pandemic and until 30 November 2021, in a national healthcare organization in Israel to build logistic models estimating the probability of subsequent hospitalization and death of newly infected patients based on a few major risk factors (age, sex, body mass index, hemoglobin A1C, kidney function, and the presence of hypertension, pulmonary disease, and malignancy) and the number of BNT162b2 mRNA vaccine doses received. The model's performance was assessed by 10-fold cross-validation: the area under the curve was 0.889 for predicting hospitalization and 0.967 for predicting mortality. A total of 50%, 80%, and 90% of death events could be predicted with respective specificities of 98.6%, 95.2%, and 91.2%. These models enable the rapid identification of individuals at high risk for hospitalization and death when infected, and they can be used to prioritize patients to receive scarce medications or booster vaccination. The calculator is available online.

This study examines the demographic, clinical and socioeconomic factors associated with diagnosis of long COVID syndrome (LCS). Data of 20,601 COVID-19-positive children aged 5 to 18 years were collected between 2020 and 2021 in an Israeli database. Logistic regression analysis was used to evaluate the adjusted odds ratio for the characteristics of the COVID-19 infection and pre-COVID-19 morbidities. Children with LCS were significantly more likely to have been severely symptomatic, required hospitalization, and experienced recurrent acute infection within 180 days. In addition, children with LCS were significantly more likely to have had ADHD, chronic urticaria, and allergic rhinitis. Diagnosis of LCS is significantly associated with pre-COVID-19 ADHD diagnosis, suggesting clinicians treating ADHD children who become infected with COVID-19 remain vigilant for the possibility of LCS. Although the risk of severe COVID-19 infection and LCS in children is low, further research on possible morbidity related to LCS in children is needed.

Background: Immune protection following either vaccination or infection with SARS-CoV-2 decreases over time. Objective: We aim to describe clinical and sociodemographic characteristics associated with COVID-19 infection at least 14 days after booster vaccination in the Israeli population. Methods: We conducted a population-based study among adult members of Leumit Health Services (LHS) in Israel. Nasopharyngeal swabs were examined for SARS-CoV-2 by real-time RT-PCR. The hematological and biochemical parameters in the peripheral blood before booster vaccination were evaluated. Results: Between 1 February 2021 and 30 November 2021, 136,683 individuals in LHS were vaccinated with a booster (third dose) of the BNT162b2 vaccine. Of these, 1171 (0.9%) were diagnosed with COVID-19 by testing positive for SARS-CoV-2 RT-PCR at least >14 days after the booster vaccination. The COVID-19-positive group was characterized by higher rates of chronic kidney disease than the matched COVID-19-negative group (43 (3.7%) vs. 3646 (2.7%); p = 0.039). Anemia, lower peripheral blood lymphocytes, monocytes, basophils, C3 Complement, cholesterol, and prothrombin time were also associated with COVID-19 after booster vaccination. Conclusion: People with chronic kidney disease and anemia should be included in possible future annual SARS-CoV-2 vaccination recommendations.

Background: Pharmacist medication review has been implemented in many health organizations throughout the world in an attempt to alleviate the underlying risk of polypharmacy in elderly patients. These consultations are often frequent and prolonged, and are thus associated with increased costs. To date, data regarding the most effective way to utilize pharmacist consultations for the improvement of health status is scant., Aim: To evaluate the effectiveness of a single pharmacist consultation on changes in chronic medication regimes and on selected outcomes of diabetes 1-year after the consultation., Methods: A case-control study included an intervention group of 740 patients who had pharmacist consultations and a reference group of 1476 matched patients who did not have a pharmacist consultation. 1-year outcome measures were compared including changes in medications, improved safety, and objective variables such as Hba1c, blood pressure, and lipid profile., Results: In the pharmacist consultation group, there were significantly more treatment changes ([mean 1.5 vs. 0.7, p < 0.001 medications were stopped], and [mean 1.3 vs. 0.4, p < 0.05 medications were started]). Patient safety improved with a general reduction in opiates and benzodiazepines ([50.0% vs. 31.6%, p < 0.05 opioids were stopped] and [58.8% vs 43.8%, p < 0.001 benzodiazepines were stopped]). Sulfonylurea treatment reduced (10.7% vs. 3.6%, p < 0.05 patients who stopped Sulfonylurea) and Glucagon-like peptide-1 receptor agonists (GLP-1) increased (16.4% vs. 11.2%, p < 0.001 patients who started GLP-1). Additionally, HbA1c levels showed a small decrease in the pharmacist consultation group ([- 0.18 ± 1.11] vs. [- 0.051 ± 0.80], p = 0.0058) but no significant differences were found regarding blood pressure or lipids profile., Conclusion: A single pharmacist consultation beneficially impacted specific clinical and patient safety outcomes. Pharmacist consultations may thus help resolve polypharmacy complexities in primary care., (© 2022. The Author(s).)

Background: Denmark and Israel both have highly rated and well-performing healthcare systems with marked differences in funding and organization of primary healthcare. Although better population health outcomes are seen in Israel, Denmark has a substantially higher healthcare expenditure. This has caused Danish policy makers to take an interest in Israeli community care organization. Consequently, we aim to provide a more detailed insight into differences between the two countries' healthcare organization and cost, as well as health outcomes., Methods: A comparative analysis combining data from OECD, WHO, and official sources. World Health Organization (WHO) and the Organisation for Economic Co-operation and Development (OECD) statistics were used, and national official sources were procured from the two healthcare systems. Literature searches were performed in areas relevant to expenditure and outcome. Data were compared on health care expenditure and selected outcome measures. Expenditure was presented as purchasing power parity and as percentage of gross domestic product, both with and without adjustment for population age, and both including and excluding long-term care expenditure., Results: Denmark's healthcare expenditure is higher than Israel's. However, corrected for age and long-term care the difference diminishes. Life expectancy is lower in Denmark than in Israel, and Israel has a significantly better outcome regarding cancer as well as a lower number of Years of Potential Life Lost. Israelis have a healthier lifestyle, in particular a much lower alcohol consumption., Conclusion: Attempting to correct for what we deemed to be the most important influencing factors, age and different inclusions of long-term care costs, the Israeli healthcare system still seems to be 25% less expensive, compared to the Danish one, and with better health outcomes. This is not necessarily a function of the Israeli healthcare system but may to a great extent be explained by cultural factors, mainly a much lower Israeli alcohol consumption., (© 2022. The Author(s).)

Objective: Patients with ADHD are at increased risk of acquiring COVID-19. The present study assessed the possibility that ADHD also increases the risk of severe COVID-19 infection., Method: We assessed 1,870 COVID-19 positive patients, aged 5 to 60 years, registered in the database of Leumit Health Services (LHS, Israel), February to -June 2020, of whom 231 with ADHD. Logistic regression analysis models evaluated the association between ADHD and the dependent variables of being symptomatic/referral to hospitalization, controlling for demographic and medical variables., Results: Age, male sex, and BMI were confirmed to be significant risk factors for increased COVID-19 severity. ADHD was found to be associated with increased severity of COVID-19 symptoms ( OR  = 1.81, 95% CI [1.29, 2.52], p  < .05) and referral to hospitalization ( OR =1.93, 95% CI [1.06, 3.51], p  = .03)., Conclusion: ADHD is associated with poorer outcomes in COVID-19 infection.

Background: Use of medical cannabis (MC) in Israel has increased since its regulatory approval in 2016. Currently, more than 1% of Israeli adults are treated with MC; this requires primary care physicians (PCPs) to be familiar with this treatment option., Objectives: We assessed the attitudes and knowledge of Israeli PCPs toward MC and evaluated their willingness to prescribe it for different medical conditions., Methods: A cross-sectional survey which was distributed to PCPs in Israel. Physicians were asked about their opinions, knowledge, and willingness to prescribe MC., Results: Two hundred and one PCPs answered the questionnaire. Their average age was 47 years (±11.2), 71% were specialists. 51% of the respondents thought that MC is an effective treatment. 63% replied that they had little knowledge and 75% indicated that they would like to deepen it. 61% of the respondents were willing to initiate an MC treatment for a dying patient, while less than 50% were willing to initiate MC treatment for various other conditions. Most respondents indicated that they were willing to renew a prescription for any approved medical condition. Willingness to prescribe MC increased for physicians who agreed that MC was effective (odds ratio [OR] 21.9, 95% confidence interval [CI] 2.40-200.85), for physicians who strongly agreed with the statement that they had sufficient knowledge (OR 5.0, 95% CI 1.58-15.83) and for residents compared with specialists (OR 4.0, 95% CI 1.52-10.73)., Conclusions: Our survey revealed PCPs' differing opinions and insufficient knowledge regarding treatment with MC. These findings suggest that continuing medical education regarding MC is needed., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

The Bacillus Calmette-Guérin (BCG) vaccine affords indirect protection against COVID-19, which is presumably due to priming of the innate immune system. It was hypothesized that the live attenuated Varicella Zoster (LAVZ) vaccine, recommended for the elderly population, would also protect against COVID-19 infection. A retrospective population-based cross-sectional study was conducted using the Leumit Health Services (LHS) database. LAVZ-vaccinated patients were matched with controls based on a propensity score model using 1:9 nearest-neighbor matching. Matching was based on age, gender, and the presence of some chronic disorders, which were selected according to their association with COVID-19 infection. Multivariate logistic regression analyses, adjusted for sex, age, smoking status, comorbidities, and chronic medications associated with COVID-19 risk, were used to estimate the association between LAVZ vaccination and COVID-19 RT-PCR results. Subjects (625) vaccinated with LAVZ and RT-PCR-tested for COVID-19 were identified. After 1:9 matching of subjects who received the LAVZ vaccine, 6250 subjects were included in the study. Multivariate logistic regression analysis demonstrated a significant and independent negative association between having received the LAVZ vaccine and the likelihood of COVID-19 infection (adjusted OR = 0.47 (95% CI 0.33-0.69, p < 0.001)). This association was further strengthened after separate analysis based on the time of LAVZ vaccination before COVID-19 RT-PCR testing. Individuals aged ≥50 years vaccinated with LAVZ had a decreased likelihood of being tested positive for COVID-19.

Background: The factors that trigger and exacerbate chronic spontaneous urticaria (CSU) are well known, but it is not unclear whether messenger RNA (mRNA) vaccination against severe acute respiratory syndrome coronavirus 2 can trigger new cases of CSU or a relapse of CSU after long-term remission. Objective: To study the clinical cases of patients with new-onset CSU and CSU in remission who relapsed within 3 months after BNT162b2 mRNA vaccination. Methods: All patients with a CSU diagnosis within 12 weeks of BNT162b2 mRNA vaccination were retrospectively identified and included in the new-onset CSU and the relapsed CSU groups. The first control group (CSU control group) retrospectively consisted of patients diagnosed with CSU in complete clinical remission for ≥ 6 months, with no CSU relapse after vaccination. The second control group (healthy control group) consisted of subjects who were fully vaccinated and without CSU, matched 1:2 for age and sex with patients with CSU. Results: Twenty-seven patients were included in the relapsed CSU group, 32 patients in the new-onset CSU group, 179 patients in the CSU control group, and 476 subjects in the healthy control group. The relapsed CSU and new-onset CSU groups had more allergic comorbidities overall (19 [70.4%] and 13 [40.6%], respectively) than the CSU control group and the healthy control group (50 [27.9%] and 110 [23.1%], respectively; p < 0.001). Multiple logistic regression analysis showed that a positive autologous serum skin test result, overall allergic comorbidities, and basopenia were positively associated with the probability of CSU relapse within 3 months after BNT162b2 mRNA vaccination (odds ratio [OR] 5.54 [95% confidence interval {CI}, 2.36-13.02], p < 0.001); OR 6.13 [95% CI, 2.52-14.89], p = 0.001; and OR 2.81 [95% CI, 1.17-6.72, p = 0.020, respectively). Conclusion: It is possible that BNT162b2 mRNA vaccination serves as a provoking and/or relapsing factor of CSU in individuals with allergic diseases and/or predisposed autoimmunity.

Immune protection following either vaccination or infection with SARS-CoV-2 is thought to decrease over time. We designed a retrospective study, conducted at Leumit Health Services in Israel, to determine the kinetics of SARS-CoV-2 IgG antibodies following administration of two doses of BNT162b2 vaccine, or SARS-CoV-2 infection in unvaccinated individuals. Antibody titers were measured between 31 January 2021, and 31 July 2021 in two mutually exclusive groups: (i) vaccinated individuals who received two doses of BNT162b2 vaccine and had no history of previous infection with COVID-19 and (ii) SARS-CoV-2 convalescents who had not received the vaccine. A total of 2653 individuals fully vaccinated by two doses of vaccine during the study period and 4361 convalescent patients were included. Higher SARS-CoV-2 IgG antibody titers were observed in vaccinated individuals (median 1581 AU/mL IQR [533.8-5644.6]) after the second vaccination than in convalescent individuals (median 355.3 AU/mL IQR [141.2-998.7]; p < 0.001). In vaccinated subjects, antibody titers decreased by up to 38% each subsequent month while in convalescents they decreased by less than 5% per month. Six months after BNT162b2 vaccination 16.1% subjects had antibody levels below the seropositivity threshold of <50 AU/mL, while only 10.8% of convalescent patients were below <50 AU/mL threshold after 9 months from SARS-CoV-2 infection. This study demonstrates individuals who received the Pfizer-BioNTech mRNA vaccine have different kinetics of antibody levels compared to patients who had been infected with the SARS-CoV-2 virus, with higher initial levels but a much faster exponential decrease in the first group.

Telemedicine is the use of telecommunication and information technologies to support the delivery of healthcare at a distance, guaranteeing patients healthcare by facilitating access where barriers exist; the COVID-19 pandemic has attracted worldwide interest in this field.The purpose of this paper is to highlight the main pros and cons of telemedicine, which serve as the basis of the WONCA Europe Statement at the WHO Europe 70th Regional Meeting on 14 September 2020.Pros of telemedicine include virtual healthcare at home, where patients receive support in certain conditions without leaving their houses. During a pandemic, it can be adopted to limit physical human interaction. Unfortunately, it can negatively affect the quality of the doctor-patient relationship, the quality of the physical examination, and the quality of care. Telemedicine requires effective infrastructure and robust investments to be feasible and effective.

Objectives: To determine whether time elapsed since the second injection of the Pfizer-BioNTech BNT162b2 mRNA vaccine was significantly associated with the risk of covid-19 infection after vaccination in people who received two vaccine injections., Design: Test negative design study., Setting: Electronic health records of a large state mandated healthcare organisation, Israel., Participants: Adults aged ≥18 years who had received a reverse transcription polymerase chain reaction (RT-PCR) test between 15 May 2021 and 17 September 2021, at least three weeks after their second vaccine injection, had not received a third vaccine injection, and had no history of covid-19 infection., Main Outcome Measures: Positive result for the RT-PCR test. Individuals who tested positive for SARS-CoV-2 and controls were matched for week of testing, age category, and demographic group (ultra-orthodox Jews, individuals of Arab ancestry, and the general population). Conditional logistic regression was adjusted for age, sex, socioeconomic status, and comorbid conditions., Results: 83 057 adults received an RT-PCR test for SARS-CoV-2 during the study period and 9.6% had a positive result. Time elapsed since the vaccine injection was significantly longer in individuals who tested positive (P<0.001). Adjusted odds ratio for infection at time intervals >90 days since vaccination were significantly increased compared with the reference of <90 days: 2.37 (95% confidence interval 1.67 to 3.36) for 90-119 days, 2.66 (1.94 to 3.66) for 120-149 days, 2.82 (2.07 to 3.84) for 150-179 days, and 2.82 (2.07 to 3.85) for ≥180 days (P<0.001 for each 30 day interval)., Conclusions: In this large population of adults tested for SARS-CoV-2 by RT-PCR after two doses of mRNA BNT162b2 vaccine, a gradual increase in the risk of infection was seen for individuals who received their second vaccine dose after at least 90 days., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from Leumit Health Services and the Intramural Research Program, National Institutes of Health, National Cancer Institute, Centre for Cancer Research for the submitted work; the authors declare no competing interests; AI, EMe, AAS, YS, IG, AG-C, EMa,and SV are employees of Leumit Health Services; all authors declare that they have no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: ADHD limits the ability to comply with Covid-19 prevention recommendations. We hypothesized that ADHD constitutes a risk factor for Covid-19 infection and that pharmacotherapy may lower that risk. Methods: Study population included all subjects ( N  = 14,022) registered with Leumit Health Services between February 1st and April 30, 2020, who underwent at least one Covid-19 test. Data were collected from the electronic health records. Purchasing consecutively at least three ADHD-medication-prescriptions during past year was considered drug-treatment. Results: A total of 1,416 (10.1%) subjects (aged 2 months-103 years) were Covid-19-positive.They were significantly younger, and had higher rates of ADHD (adjOR 1.58 (95% CI 1.27-1.96, p  < .001) than Covid-19-negative subjects. The risk for Covid-19-Positive was higher in untreated-ADHD subjects compared to non-ADHD subjects [crudeOR 1.61 (95% CI 1.36-1.89, p  < .001)], while no higher risk was detected in treated ones [crudeOR 1.07 (95% CI 0.78-1.48, p  = .65)]. Conclusion: Untreated ADHD seems to constitute a risk factor for Covid-19 infection while drug-treatment ameliorates this effect.

Background: Although the short-term neurological complications of Shigella spp. are well described, potential neuropsychiatric outcomes have not been studied yet. We investigated the association between early childhood shigellosis and subsequent ADHD., Methods: This is a retrospective population-based cohort. Using a large Health Maintenance Organization database, the prevalence of ADHD was investigated among children aged 5-18 years who underwent stool culture prior to the age of 3 years., Results: Of 52,761 children with a stool culture examined, 5,269 (9.98%) had Shigella -positive results. The rate of ADHD was 10.6% and 8.6% among children with Shigella- positive and Shigella- negative stool cultures, respectively ( p < .001). Adjusted odds ratio for ADHD after controlling for gender and socioeconomic status was 1.21 (CI 1.13-1.29, p < .001). The younger the child was during Shigella gastroenteritis, the higher was the association with ADHD ( p < .001)., Conclusion: Early childhood shigellosis is associated with an increased rate of long-term ADHD.

It has recently been shown that children with early shigellosis are at increased risk of attention deficit/hyperactivity disorder (ADHD). This study aimed to evaluate the association between antibiotic treatment of shigellosis with long-term ADHD rates. A retrospective cohort study was conducted that included all the Leumit Health Services (LHS) enrollees aged 5-18 years between 2000-2018 with a documented Shigella -positive gastroenteritis before the age of 3 years. Of the 5176 children who were positive for Shigella gastroenteritis before the age of 3 years, 972 (18.8%) were treated with antibiotics early (<5 days), 250 (4.8%) were treated late (≥5 days), and 3954 children (76.4%) were not prescribed antibiotics. Late antibiotic treatment was associated with significantly increased rates of ADHD (adjusted OR = 1.61; 95% CI, 1.1-2.3). Early treatment with antibiotics was not associated with increased ADHD rates (adjusted OR = 1.02; 95% CI, 0.8-1.3). In conclusion, late antibiotic treatment of early childhood shigellosis was associated with increased rates of ADHD.

Introduction: People with diabetes mellitus are at increased risk of developing a more severe disease or death when contracting coronavirus disease 2019 (COVID-19 ) but the effect of pre-COVID-19 infection glycemic control on disease outcomes is still unclear. In a previous study that we published from Leumit Health Services (LHS) including 183 patients with diabetes, pre-COVID-19 infection HbA1c>9% was associated with the need for hospitalization during the disease. In the current study we present the clinical characteristics of patients who died from COVID-19 in LHS and demonstrate a significant link to pre-infection HbA1c., Methods: We collected demographic, clinical and laboratory information regarding all patients insured in LHS who contracted COVID-19 between 1st February and 31st May 2020 and had diabetes or pre-diabetes. To better understand the contribution of pre-infection glycemic control on COVID-19 mortality we conducted a case control study at a 1:5 ratio between patients who had died and survivors, adjusting for age, sex and socioeconomic status., Results: We identified 888 patients of whom 24 (2.7%) died from COVID-19 . Patients who died were older, had more chronic disease, higher HbA1c and creatinine and lower hemoglobin, iron and vitamins B12 and D. In the case control study, patients who died had more obesity, dementia, cerebrovascular disease, congestive heart failure, use of SGLT-2 inhibitors and fewer smokers. In a multivariate logistic regression analysis we found that HbA1c and prior cerebrovascular disease significantly increased the risk of death and normal levels of vitamin D, iron and an estimated glomerular filtration rate >60ml/min were associated with a protective effect., Conclusions: Pre- COVID-19 HbA1c levels and prior cerebrovascular disease are associated with an increased risk of mortality. Identifying pre-infection clinical parameters which predict COVID-19 mortality may improve risk stratification and vaccine prioritization for at-risk populations. Further study is needed to understand the potential mechanism and causality of poor glycemic control on COVID-19 death.

This patient guideline is intended for all patients at risk of or living with non-alcoholic fatty liver disease (NAFLD). NAFLD is the most frequent chronic liver disease worldwide and comes with a high disease burden. Yet, there is a lot of unawareness. Furthermore, many aspects of the disease are still to be unravelled, which has an important impact on the information that is given (or not) to patients. Its management requires a close interaction between patients and their many healthcare providers. It is important for patients to develop a full understanding of NAFLD in order to enable them to take an active role in their disease management. This guide summarises the current knowledge relevant to NAFLD and its management. It has been developed by patients, patient representatives, clinicians and scientists and is based on current scientific recommendations, intended to support patients in making informed decisions., Competing Interests: SMF has a senior clinical research mandate from the Fund for Scientific Research (FWO) Flanders (1802154 N) and has acted as advisor and/or lecturer for Roche, Gilead, Abbvie, Bayer, BMS, MSD, Janssen, Actelion, Astellas, Genfit, Inventiva, Intercept, Genentech, Galmed, Promethera, Coherus, NGM Bio and Julius Clinical. GM served as Advisory Board member for Sanofi, Novartis, Astra-Zeneca, Intercept and Pfizer, and participated in clinical trials by Sanofi, Eli Lilly, Gilead, GENFIT and Intercept. AK has received project grants from Novartis and Intercept. MW has nothing to disclose in relation to this publication. RD has received project grants from Novartis and Intercept. JVL received research grants from Gilead Sciences and MSD, and speaker fees from Genfit, Gilead Sciences, MSD, Intercept Pharmaceuticals and Janssen, outside of this work. SZS has nothing to disclose in relation to this publication. KH has nothing to disclose in relation to this publication. LB serves as an Advisory Board member for Novo Nordisk. GF has nothing to disclose in relation to this publication. DD served as Advisory Board member and lecture for Novo Nordisk, Sanofi, BI, Astra-Zeneca, and participated in clinical trials by, Novo Nordisk, Eli Lilly, Sanofi and BI. EW has nothing to disclose in relation to this publication. MK has nothing to disclose in relation to this publication. JW has nothing to disclose in relation to this publication. GK has nothing to disclose in relation to this publication. SV has nothing to disclose in relation to this publication. MU has nothing to disclose in relation to this publication. JM has nothing to disclose in relation to this publication. CL has nothing to disclose in relation to this publication. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2021 The Authors.)

Acetylsalicylic acid (aspirin) is commonly used for primary and secondary prevention of cardiovascular diseases. Aspirin use is associated with better outcomes among COVID-19 positive patients. We hypothesized that the aspirin use for primary cardiovascular disease prevention might have a protective effect on COVID-19 susceptibility and disease duration. We conducted a retrospective population-based cross-sectional study, utilizing data from the Leumit Health Services database. The proportion of patients treated with aspirin was significantly lower among the COVID-19-positive group, as compared to the COVID-19-negative group [73 (11.03%) vs. 1548 (15.77%); P = 0.001]. Aspirin use was associated with lower likelihood of COVID-19 infection, as compared to nonusers (adjusted OR 0.71 (95% CI, 0.52 to 0.99; P = 0.041). Aspirin users were older (68.06 ± 12.79 vs. 56.63 ± 12.28 years of age; P < 0.001), presented a lower BMI (28.77 ± 5.4 vs. 30.37 ± 4.55; P < 0.0189), and showed higher prevalence of hypertension (56, 76.71%), diabetes (47, 64.38%), and COPD (11, 15.07%) than the aspirin nonusers (151, 25.64%, P < 0.001; 130, 22.07%, P < 0.001; and 43, 7.3%, P = 0.023, respectively). Moreover, COVID-19 disease duration (considered as the time between the first positive and second negative COVID-19 RT-PCR test results) among aspirin users was significantly shorter, as compared to aspirin nonusers (19.8 ± 7.8 vs. 21.9 ± 7.9 P = 0.045). Among hospitalized COVID-positive patients, a higher proportion of surviving subjects were treated with aspirin (20, 19.05%), as opposed to 1 dead subject (14.29%), although this difference was not significant (P = 0.449). In conclusion, we observed an inverse association between the likelihood of COVID-19 infection, disease duration and mortality, and aspirin use for primary prevention., (© 2021 Federation of European Biochemical Societies.)

Only 30% of patients with major depressive disorder (MDD) reach full recovery or remission. Treatment-resistant depression (TRD) is MDD that does not respond to adequate treatment attempts with at least two antidepressants. TRD is associated more with immune activation than with treatment responsive depression. The current retrospective population-based cross-sectional study, utilizing data from a large nation-wide health maintenance organization in Israel which provides services to estimated 725,000 members, aimed to assess the clinical signs and laboratory markers of autoimmune comorbidity and low-grade inflammation, in patients with TRD. Included were participants aged 18-70 years, diagnosed twice within one year with ICD-9-CM MDD and two control groups, MDD responders (MDD-r) consisting of people with MDD and no TRD and a non-MDD group that included people with no MDD or TRD. The case (570 subjects in TRD group) to control ratio in both control groups (2850 subjects in MDD-r and 2850 subjects in non-MDD control group) was 1:5. Compared to MDD-r, the overall proportion of allergic diseases was higher among the TRD than among the MDD-r [OR 1.52 (1.19-1.94); p ​< ​0.001]. Any systemic autoimmune disease was associated with increased likelihood of MDD-r [OR 1.52 (1.04-2.24); p ​= ​0.03] or TRD [OR 2.22 (1.30-3.78); p ​= ​0.003]. Higher rates of positive (>1:80) antinuclear antibodies [33 (5.79%)] were found among the TRD than among the MDD-r [98 (3.44%); p ​= ​0.011). More allergy and autoimmune comorbidities and presence of low-grade inflammation biomarkers, were found mainly in TRD., (© 2021 Published by Elsevier Inc.)

Studies have shown similarities in the structure of influenza and coronaviruses, in their binding receptors and in patterns of immune responses; and that influenza vaccine can induce cross-immunity. We examined the association of previous influenza vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, resulting in coronavirus disease-2019 (COVID-19), among 715,164 members of a health maintenance organization. In a multivariate regression model, the odds ratios for SARS-CoV-2 infection among individuals vaccinated for influenza in 2018-2019, 2019-2020, and in both seasons, compared to non-vaccinated individuals, were 0.82 (95% CI 0.68-0.99, p = .048), 0.79 (95% CI 0.67-0.98, p = .005), and 0.76 (95% CI 0.61-0.97, p = .004), respectively. Based on our findings, administration of influenza vaccine before the influenza season is highly recommended to reduce the burden of influenza, which is critical in scenarios of outbreaks of both influenza and SARS-CoV-2 infections, and also regarding its association with reduced rate of COVID-19.

Aim: Poor outcomes of coronavirus disease 2019 (COVID-19) have been linked to diabetes, but its relation to pre-infection glycaemic control is still unclear., Materials and Methods: To address this question, we report here the association between pre-infection Haemoglobin A1c (HbA1c) levels and COVID-19 severity as assessed by need for hospitalization in a cohort of 2068 patients with diabetes tested for COVID-19 in Leumit Health Services (LHSs), Israel, between 1 February and 30 April 2020. Using the LHS-integrated electronic medical records system, we were able to collect a large amount of clinical information including age, sex, socio-economic status, weight, height, body mass index, HbA1c, prior diagnosis of ischaemic heart disease, depression/anxiety, schizophrenia, dementia, hypertension, cerebrovascular accident, congestive heart failure, smoking, and chronic lung disease., Results: Of the patients included in the cohort, 183 (8.85%) were diagnosed with COVID-19 and 46 were admitted to hospital. More hospitalized patients were female, came from higher socio-economic background and had a higher baseline HbA1c. A prior diagnosis of cerebrovascular accident and chronic lung disease conferred an increased risk of hospitalization but not obesity or smoking status. In a multivariate analysis, controlling for multiple prior clinical conditions, the only parameter associated with a significantly increased risk for hospitalization was HbA1c ≥ 9%., Conclusion: Using pre-infection glycaemic control data, we identify HbA1c as a clear predictor of COVID-19 severity. Pre-infection risk stratification is crucial to successfully manage this disease, efficiently allocate resources, and minimize the economic and social burden associated with an undiscriminating approach., (© 2020 John Wiley & Sons Ltd.)

Aims: In 2011 the central district of Leumit Health Services (LHS) (a health maintenance organization in Israel) implemented a chronic care program to improve diabetes care in general practice: MESSAGE program (Motivation, Education, Skills and Supervision to Achieve better diabetes care in General practice Environment), included training phase and ongoing time allocation for diabetes care., Methods: A population-based retrospective analysis of LHS Electronic Medical Records of all patients with diabetes in LHS between 1 June 2015 and 31 May 2018. Data was processed according to the definitions of the Israeli national program for quality indicators in community healthcare. ~442,000 adults were included, ~49,000 in MESSAGE engaged clinics., Results: The prevalence of diabetes in LHS was ~9.7-9.31% during study period. Over 3 years follow up, the prevalence of patients with A1C ≥ 9% declined in all districts of LHS but to a significantly greater extent in MESSAGE clinics [2015: MESSAGE 12.4%, LHS-combined 13.09%; OR 0.92 (0.83-1.01) p = 0.075; 2018: MESSAGE 8.51%, LHS-combined 10.85%; 0.76 (0.69-0.85) p < 0.001]. Other indicators of diabetes care did not change., Conclusion: The MESSAGE intervention program resulted in improved glycemic control. It is currently being modified to address all aspects of diabetes care and is implemented across all districts of LHS in Israel., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to assess the extent of thyroid function control among pregnant women who had previously undergone a therapeutic thyroidectomy., Design: Retrospective cohort study., Setting: The largest health maintenance organization in Israel., Participants: All female patients who were pregnant between May, 2001 and September, 2012 and had a medical history of thyroid surgery., Main Outcome Measure: The thyroid-stimulating hormone (TSH) levels throughout the pregnancy were compared to recommended trimestral values. A multivariate analysis was performed to determine risk factors for not attaining TSH recommended range., Results: A total of 477 females with a history of thyroid surgery had given 701 births during the study period. Forty-three percent (n = 203), had thyroidal malignancy. Nearly half of the women underwent total thyroidectomy (43.4%, n = 207). The women's TSH values were within the recommended range in only 60% (n = 350) of the pregnancies during the first trimester (0.1-2.5 mIU/L), in 61% (n = 335) during the second trimester (0.2-3 mIU/L), and in 70% (n = 338) during the third trimester (0.3-3 mIU/L). In multivariate analysis, women that underwent a total thyroidectomy due to a benign thyroid disease, were at the highest risk for not attaining target TSH levels., Conclusions: This very large cohort of pregnant women with a past history of thyroid surgery demonstrated a significant percentage of pregnancies with TSH values above the recommended range. Women that underwent a total thyroidectomy due to benign thyroid disease were at the highest risk for gestational hypothyroidism., (© 2021 John Wiley & Sons Ltd.)

Background: Bronchial asthma has not been adequately assessed in coronavirus disease 2019 (COVID-19). Respiratory allergy is associated with significant reductions in the expression of angiotensin-converting enzyme 2 receptor, which is the entry receptor for COVID-19., Objective: To observe COVID-19 susceptibility in patients with bronchial asthma, analyze the prevalence of asthma in a large cohort of consecutive outpatient subjects who were tested with the RT-PCR assay for COVID-19., Methods: This was a retrospective population-based cross-sectional study using data from a large nationwide health maintenance organization in Israel. All health maintenance organization enrollees who had been tested for COVID-19 from February to June 2020 were included. Differences in demographic and clinical characteristics between the subjects with negative and positive COVID-19 RT-PCR test results and between COVID-19 RT-PCR-positive subjects with and without asthma were analyzed., Results: A total of 37,469 subjects were tested for COVID-19 RT-PCR, and results for 2,266 (6.05%) of them were positive. A significantly higher proportion of smokers was observed in the COVID-19-negative group than in the COVID-19-positive group (4734 [13.45%] vs 103 [4.55%]; P < .001). Asthma was found in 153 (6.75 %) subjects of the COVID-19-positive group and in 3388 (9.62%) subjects of the COVID-19-negative group (P < .001). No significant impact of antileukotrienes, inhaled corticosteroids, and long-acting beta-blockers use was revealed on COVID-19 positivity proportions. Multiple logistic regression analysis adjusted for sex, age, smoking, and comorbidity revealed a negative association of asthma with the likelihood of being positive for COVID-19 (odds ratio, 0.71; 95% CI, 0.58-0.87; P = .001)., Conclusions: We observed lower COVID-19 susceptibility in patients with preexisting asthma., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this study is to forward the implementation of an operational evidence-based state screening program of common diseases in Ukraine, where currently no state-based and evidence-based screening (EBS) exists. EBS should be performed by Family Doctors in a primary care setting and concern prevalent diseases in adults, such as: obesity (BMI), hypertension (BP measurement), diabetes (glycaemia), dyslipidemia (cholesterol/lipids), colon cancer (FOBT/colonoscopy), breast cancer (mammography), STIs (chlamydia, syphilis), HIV, HBV, HCV (i.e. serology or other rapid tests), HPV (swabs), cervical cancer (test Pap). depression (i.e., PHQ-9), and smoking (i.e., Fagerstrom)., Methods: Four needs-based research actions were led among citizens and healthcare professionals, based on multidimensional empowerment. Internal Strengths and Weaknesses of the ongoing implementation process were identified through these studies, whereas external Opportunities and Threats were determined by the present socio-cultural and political context. This SWOT analysis is likely to guide future state-based initiatives to accomplish EBS implementation in Ukraine., Results: Internal Strengths are the bottom-up multidimensional empowerment approach, teaching of EBS and the development of an internet-based platform "Screening adviser" to assist shared decision making for person-centred EBS programs. Internal Weaknesses identified for the Family Doctors are a heterogeneous screening and the risk of decreasing motivation to screen. External Opportunities include the ongoing PHC reform, the existent WONCA and WHO support, and the existence of EBS programs in Europe. External Threats are the lack of national guidelines, not fully introduced gate keeping system, the vulnerable socio-economic situation, the war situation in the East of Ukraine and the Covid-19 pandemic., Conclusions: We started EBS implementation through research actions, based on a multidimensional empowerment of citizens, HCP and in EBS pathways involved stakeholder teams, to foster a sustainable operational human resource to get involved in that new EBS pathway to implement. The presented SWOT-analysis of this ongoing implementation process allows to plan and optimize future steps towards a state based and supports EBS program in Ukraine.

Background: General practitioners (GPs) should regularly review patients' medications and, if necessary, deprescribe, as inappropriate polypharmacy may harm patients' health. However, deprescribing can be challenging for physicians. This study investigates GPs' deprescribing decisions in 31 countries., Methods: In this case vignette study, GPs were invited to participate in an online survey containing three clinical cases of oldest-old multimorbid patients with potentially inappropriate polypharmacy. Patients differed in terms of dependency in activities of daily living (ADL) and were presented with and without history of cardiovascular disease (CVD). For each case, we asked GPs if they would deprescribe in their usual practice. We calculated proportions of GPs who reported they would deprescribe and performed a multilevel logistic regression to examine the association between history of CVD and level of dependency on GPs' deprescribing decisions., Results: Of 3,175 invited GPs, 54% responded (N = 1,706). The mean age was 50 years and 60% of respondents were female. Despite differences across GP characteristics, such as age (with older GPs being more likely to take deprescribing decisions), and across countries, overall more than 80% of GPs reported they would deprescribe the dosage of at least one medication in oldest-old patients (> 80 years) with polypharmacy irrespective of history of CVD. The odds of deprescribing was higher in patients with a higher level of dependency in ADL (OR =1.5, 95%CI 1.25 to 1.80) and absence of CVD (OR =3.04, 95%CI 2.58 to 3.57)., Interpretation: The majority of GPs in this study were willing to deprescribe one or more medications in oldest-old multimorbid patients with polypharmacy. Willingness was higher in patients with increased dependency in ADL and lower in patients with CVD.

COVID-19 outbreak has significantly changed all aspects of general practice in Europe. This article focuses on the academic challenges for the discipline, mainly in the field of education, research, and quality assurance. The efforts of the European Region of the World Organisation of National Colleges, Academies, and Academic Associations of General Practitioners/Family Physicians (WONCA Europe) to support academic sustainability of the discipline in the time of pandemic are presented. Medical education was affected by the pandemic, threatening both its productivity and quality. Emerging new educational methods might be promising, but the results of their rapid implementation remain uncertain. A relatively small number of publications related to COVID-19 and general practice is available in the medical literature. There is a shortage of original data from general practice settings. This contrasts with the crucial role of GPs in fighting a pandemic. COVID-19 outbreak has opened widely new research areas, which should be explored by GPs. Maintaining the quality of care and safety of all patients during the COVID-19 pandemic is the utmost priority. Many of them suffer from poor access or inadequate management of their problems. Rapid implementation of telemedicine brought both threats and opportunities. The COVID-19 pandemic also challenged doctors' safety and well-being. These aspects will require discussion and remedy to prevent deterioration of the quality of primary care. WONCA Europe is making a multi-faceted effort to support GPs in difficult times of the pandemic. It is ready to support future efforts to uphold the integrity of family medicine as an academic discipline.

Vitamin D deficiency is a worldwide pandemic. The aim of this study was to evaluate associations of plasma 25(OH)D levels with the likelihood of coronavirus disease 2019 (COVID-19) infection and hospitalization. The study population included the 14 000 members of Leumit Health Services, who were tested for COVID-19 infection from February 1 st to April 30 th , 2020, and who had at least one previous blood test for the plasma 25(OH)D level. 'Suboptimal' or 'low' plasma 25(OH)D level was defined as plasma 25-hydroxyvitamin D, or 25(OH)D, concentration below the level of 30 ng/mL. Of 7807 individuals, 782 (10.02%) were COVID-19-positive, and 7025 (89.98%) COVID-19-negative. The mean plasma vitamin D level was significantly lower among those who tested positive than negative for COVID-19 [19.00 ng/mL (95% confidence interval (CI) 18.41-19.59) vs. 20.55 (95% CI: 20.32-20.78)]. Univariate analysis demonstrated an association between the low plasma 25(OH)D level and increased likelihood of COVID-19 infection [crude odds ratio (OR) of 1.58 (95% CI: 1.24-2.01, P < 0.001)], and of hospitalization due to the SARS-CoV-2 virus [crude OR of 2.09 (95% CI: 1.01-4.30, P < 0.05)]. In multivariate analyses that controlled for demographic variables, and psychiatric and somatic disorders, the adjusted OR of COVID-19 infection [1.45 (95% CI: 1.08-1.95, P < 0.001)] and of hospitalization due to the SARS-CoV-2 virus [1.95 (95% CI: 0.98-4.845, P = 0.061)] were preserved. In the multivariate analyses, age over 50 years, male gender and low-medium socioeconomic status were also positively associated with the risk of COVID-19 infection; age over 50 years was positively associated with the likelihood of hospitalization due to COVID-19. We concluded that low plasma 25(OH)D levels appear to be an independent risk factor for COVID-19 infection and hospitalization., (© 2020 Federation of European Biochemical Societies.)

Objective: To explore dementia management from a primary care physician perspective., Design: One-page seven-item multiple choice questionnaire; free text space for every item; final narrative question of a dementia case story. Inductive explorative grounded theory analysis. Derived results in cluster analyses. Appropriateness of dementia drugs assessed by tertiary care specialist., Setting: Twenty-five European General Practice Research Network member countries., Subjects: Four hundred and forty-five key informant primary care physician respondents of which 106 presented 155 case stories., Main Outcome Measures: Processes and typologies of dementia management. Proportion of case stories with drug treatment and treatment according to guidelines., Results: Unburdening dementia - a basic social process - explained physicians' dementia management according to a grounded theory analysis using both qualitative and quantitative data. Unburdening starts with Recognizing the dementia burden by Burden Identification and Burden Assessment followed by Burden Relief . Drugs to relieve the dementia burden were reported for 130 of 155 patients; acetylcholinesterase inhibitors or memantine treatment in 89 of 155 patients - 60% appropriate according to guidelines and 40% outside of guidelines. More Central and Northern primary care physicians were allowed to prescribe, and more were engaged in dementia management than Eastern and Mediterranean physicians according to cluster analyses. Physicians typically identified and assessed the dementia burden and then tried to relieve it, commonly by drug prescriptions, but also by community health and home help services, mentioned in more than half of the case stories., Conclusions: Primary care physician dementia management was explained by an Unburdening process with the goal to relieve the dementia burden, mainly by drugs often prescribed outside of guideline indications. Implications: Unique data about dementia management by European primary care physicians to inform appropriate stakeholders. Key points Dementia as a syndrome of cognitive and functional decline and behavioural and psychological symptoms causes a tremendous burden on patients, their families, and society. •We found that a basic social process of Unburdening dementia explained dementia management according to case stories and survey comments from primary care physicians in 25 countries. •First, Burden Recognition by Identification and Assessment and then Burden Relief - often by drugs. •Prescribing physicians repeatedly broadened guideline indications for dementia drugs. The more physicians were allowed to prescribe dementia drugs, the more they were responsible for the dementia work-up. Our study provides unique data about dementia management in European primary care for the benefit of national and international stakeholders.

Background: The best management of hypertension in frail oldest-old (≥80 years of age) remains unclear and we still lack guidelines that provide specific recommendations. Our study aims to investigate guideline use in general practitioners (GPs) and to examine if guideline use relates to different decisions when managing hypertension in frail oldest-old., Design/setting: Cross-sectional study among currently active GPs from 29 countries using a case-vignettes survey., Methods: GPs participated in a survey with case-vignettes of frail oldest-olds varying in systolic blood pressure (SBP) levels and cardiovascular disease (CVD). GPs from 26 European countries and from Brazil, Israel and New Zealand were invited. We compared the percentage of GPs reporting using guidelines per country and further stratified on the most frequently mentioned guidelines. To adjust for patient characteristics (SBP, CVD and GPs' sex, years of experience, prevalence of oldest-old and location of their practice), we used a mixed-effects regression model accounting for clustering within countries., Results: Overall, 2,543 GPs from 29 countries were included. 59.4% of them reported to use guidelines. Higher guideline use was found in female (p = 0.031) and less-experienced GPs (p<0.001). Across countries, we found a large variation in self-reported guideline use, ranging from 25% to 90% of the GPs, but there was no difference in hypertension treatment decisions in frail oldest-old patients between GPs that did not use and GPs that used guidelines, irrespective of the guidelines they used., Conclusion: Many GPs reported using guidelines to manage hypertension in frail oldest-old patients, however guideline users did not decide differently from non-users concerning hypertension treatment decisions. Instead of focusing on the fact if GPs use guidelines or not, we as a scientific community should put an emphasis on what guidelines suggest in frail and oldest-old patients., Competing Interests: The authors declare that they have no competing interests.

Background: Although, number of diabetic patients received insulin pump (IP) therapy is increasing; there are limited data regarding factors associated with IP withdrawal., Methods: We conducted a cross-sectional study using data from an Israeli health maintenance organization. All patients, 21 or older, with type 1 (T1DM) or type 2 (T2DM) diabetes, who received IP therapy for a 7-year period were identified. Patients who did not purchase IP maintenance supplies for at least six consecutive months were defined as withdrawn (N = 355). Patients who purchased supplies were defined as adherent (N = 352)., Results: In both T1DM and T2DM patients, withdrawal from IP therapy was positively associated with duration of diabetes longer than 5 years (odds ratio [OR] = 13.26 [CI, 7.16-23.34; P < .001] and OR = 10.92 [CI, 5.64-21.14; P < .001], respectively), nonadherence to dietician follow-up (OR = 5.78 [CI, 3.65-9.14; P < .001] and OR = 3.41 [CI, 1.99-5.85; P < .001], respectively), and poor glycaemic control prior to IP treatment (OR = 4.04 [CI, 2.18-7.48; P < .001] and OR = 4.59 [CI, 2.71-7.81; P < .001], respectively]. Co-morbid neuro-psychiatric disorders were also risk factors for IP withdrawal: diagnosis of depression (OR = 2.22 [CI, 1.16-4.27; P = .017] and Attention Deficit Hyperactivity Disorder (ADHD) OR = 2.45 [CI, 1.003-5.087; P = .043]) among T1DM patients; and diagnosis of depression (OR = 1.85 [CI, 1.05-5.27; P = .046] and dementia OR = 4.03 [CI, 1.03-19.77; P = .048]) among T2DM patients., Conclusion: In our large real-world population-based study, we found that smoking, obesity, poor glycaemic control, and co-morbid neuro-psychiatric disorders were associated with a high rate of withdrawal from IP therapy. Health care providers ought to familiarize themselves with patient characteristics predictive of nonadherence and should intensify patient follow-up when incorporating this new, costly, and challenging technology., (© 2020 John Wiley & Sons Ltd.)