A case-control study for comorbidity and laboratory factors associated with food-induced anaphylaxis.

Background: Food-induced anaphylaxis (FIA) is a serious and potentially life-threatening allergic reaction triggered by food allergens. Objective: This case-control study aimed to investigate comorbidities and laboratory factors associated with FIA in the pediatric population of Israel. Methods: Retrospective data from the electronic health records of Leumit Health Care Services were used to identify 711 pediatric patients with FIA and 2560 subjects with food allergy and without anaphylaxis matched for age, gender, and ethnicity. Comorbidities were identified based on medical billing diagnosis codes, and laboratory characteristics were compared between the two groups. Results: The mean ± standard deviation age of patients with FIA was 4.1 ± 4.1 years, and 37.3% were girls. Laboratory analysis revealed increased eosinophil counts (p < 0.001), elevated immunoglobulin E (IgE) (p < 0.001), and IgA levels (p = 0.001) in the FIA group compared with the controls. With regard to comorbidities, the FIA group had higher prevalence rates of allergic diseases, including allergic rhinitis (odds ratio [OR] 1.72; p < 0.001), allergic conjunctivitis (OR 1.84; p = 0.001), asthma (OR 1.36; p < 0.001), angioedema (OR 6.37; p < 0.001), atopic dermatitis (OR 1.77; p < 0.001), and contact dermatitis (OR 1.42; p = 0.001). There was a trend toward significance for chronic spontaneous urticaria (p = 0.051). There was a significant negative association between helminthiases, particularly enterobiasis, and FIA (OR 0.76 [95% confidence interval, 0.59-0.98]; p = 0.029). Conclusion: This study provides valuable epidemiologic evidence on the associations among FIA, comorbidities, and laboratory factors in the pediatric population.

Glucose-6-Phosphate Dehydrogenase Deficiency and Coronavirus Disease 2019.

In this cohort study conducted in a national healthcare organization in Israel, we found that individuals with glucose-6-phosphate dehydrogenase deficiency had an increased risk of coronavirus disease 2019 (COVID-19) infection and severity, with higher rates of hospitalization and diagnosed long COVID.

Greater temporal regularity of primary care visits was associated with reduced hospitalizations and mortality, even after controlling for continuity of care.

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.

Patient-level predictors of temporal regularity of primary care visits.

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.

Prevalence of neurological diseases among patients with selective IgA deficiency.

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.

Haemoglobin A1c is a predictor of COVID-19 severity in patients with diabetes.

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.

Factors associated with drug survival on first biologic therapy in patients with rheumatoid arthritis: a population-based cohort study.

Lack of sufficient head-to-head trials comparing biologic disease-modifying antirheumatic drugs (bDMARDs) in rheumatoid arthritis (RA), makes the choice of the first bDMARD a matter of rheumatologist's preference. Longer drug survival on the first bDMARD usually correlates with early remission. We aimed to identify factors associated with longer drug survival. We conducted a population-based retrospective longitudinal cohort study. We identified RA patients using the relevant International Classification of Disease 9th codes. "True" RA patients were defined as patients fulfilling, additionally, at least one of the following: receiving conventional DMARDs (cDMARDs), being positive for rheumatoid factor or anti-cyclic citrullinated peptide, or being diagnosed by a rheumatologist. We compared drug survival times and identified factors associated with longer drug survival. We identified 4268 true RA patients between the years of 2000-2017. 820 patients (19.2%) received at least one bDMARD. The most commonly prescribed bDMARDs were etanercept (352, 42.9%), adalimumab (143, 17.4%), infliximab (142, 17.3%) and tocilizumab (58, 7.1%). Infliximab was associated with the longest drug survival (47.1 months ± 46.3) while golimumab was associated with the shortest drug survival (14.9 months ± 15.1). Male gender [hazard ratio (HR) = 0.76, 95% confidence interval (CI), 0.63-0.86, p = 0.001], concurrent conventional DMARDs use (HR = 0.79, 95% CI 0.68 - 0.98, p = .031) and initiating bDMARD therapy in earlier calendric years (HR = 1.12, 95% CI 1.10 -1.18, p = 0.0001) were associated with longer drug survival. Male gender, concomitant cDMARDs and initiating biologic therapy at earlier calendric years are associated with longer drug survival.

[HEMOGLOBIN A1C AND MORTALITY FROM COVID-19].

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.

Factors associated with withdrawal from insulin pump therapy: A large-population-based study.

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.

Vitamin B12 screening in metformin-treated diabetics in primary care: were elderly patients less likely to be tested?

Low serum B12 level is a common occurrence in patients with type 2 diabetes (T2DM) treated with metformin. There is lack of evidence concerning blood testing of vitamin B12 and current clinical guidelines make no recommendations on the detection or prevention of vitamin B-12 deficiency during metformin treatment. Our objective was to examine the current practice and clinical determinants of vitamin B12 testing in metformin treated T2DM patients. Data were collected from health maintenance organization patients, and consisted of T2DM patients who were newly prescribed metformin from 2008 to 2013. Patients were randomly divided into two subgroups: referred for a vitamin B12 blood test, and did not receive a referral. The demographic data and medical characteristics were analyzed. 5131 patients began taking metformin during the study period. Of these 2332 (44.5 %) had vitamin B12 tested. Significant differences were found between the groups in regard to glycosylated hemoglobin, low density lipoprotein, systolic blood pressure, dyslipidemia, chronic renal failure, and disease duration. A significant positive association (p < .05) was found between vitamin B12 testing and insulin treatment, retinopathy, neuropathy and hypertension. Vitamin B12 in elderly (>75 years) patients was significantly lower (p < .01). Insulin treatment, hypertension, and chronic diabetic complications in metformin treated T2DM patients are associated with higher rates of vitamin B12 testing. T2DM patients 75 years and above were less likely to be tested for B12 deficiency.

Clinical characteristics and healthcare utilisation associated with undiagnosed cognitive impairment in elderly patients with diabetes in a primary care setting: a population-based cohort study.

OBJECTIVES: The objective of this study is to report the prevalence, clinical characteristics and healthcare utilisation of patients with type 2 diabetes (T2DM) and previously undiagnosed cognitive impairment who were identified as having a low Montreal Cognitive Assessment (MoCA) score. DESIGN: A population-based cohort study comparing clinical characteristics, medications, outpatient and inpatient care of patients with a MoCA score <19 to MoCA >26 using descriptive statistics, linear regression and multivariate logistic regression. SETTING: Electronic medical records of a large health maintenance organisation in Israel. PARTICIPANTS: 350 patients, age >65 with T2DM who participated in a cognitive function screening initiative using MoCA, and had a follow-up visit during the 12 months after screening. RESULTS: 130 (37.1%) had a MoCA score >26 and 68 (19.4%) <19. Patients with MoCA<19 had more diabetes-related complications, poorer glycaemic and lipid control, fewer visits to their main primary care physician (PCP; 3.9±3.2 vs 7.3±4.2 visits/year p=0.008), shorter duration of PCP visits (8.3±4.5 vs 4.0±3.5 min, p=0.007), fewer nutritionist and endocrinologist visits, and lower participation in diabetes or smoking cessation workshops. They were less likely to be treated with glucagon-like peptide-1 (GLP-1) agonists, dipeptidyl peptidase-4 inhibitor (DPP-4), or sodium-glucose transport protein 2 (SGLT-2) inhibitors and more likely to receive insulin or sulfonylurea. Moreover, they had more emergency room visits (ER; 15 (11.5%) vs 16 (23.5%), p=0.019), hospitalisations (8 (6.2%) vs 22 (32.4%), p=0.001), and longer hospital stays (4.3±3.2 vs 14.5±9.8, p=0.001). Using statistical models, MoCA<19 was identified as a risk factor for fewer and shorter PCP visits and more ER visits and hospitalisations. CONCLUSIONS: This study highlights the high prevalence of undiagnosed severe cognitive impairment in elderly patients with T2DM and its association with poor outpatient care. Appropriate interventions are needed to improve outcomes and prevent hospitalisation in this high-risk population.

Increased Rate of Familial Mediterranean Fever in Children With ADHD: A Population-Based Case-Control Study.

OBJECTIVE: There is growing evidence of involvement of inflammatory mechanisms in ADHD. Previous studies found significantly higher rates of ADHD among children with FMF. The present study examined the rate of exposure to FMF in children with a later (within a 5-year period) diagnosis of ADHD compared to non-ADHD children. METHODS: A population-based case-control study of all children (<18 years) registered in Leumit Health Services during 01.01.2006 to 06.30.2021. All cases met ICD-9/10 criteria for ADHD. They were matched by age, sex, and socioeconomic status on a 1:2 rate to randomly selected non-ADHD controls. RESULTS: Fifty-six (0.30%) children with ADHD (N = 18,756) were previously diagnosed with FMF compared to 65 of 37,512 controls (0.17%). A significant, independent association existed between a preceding FMF diagnosis and a later ADHD diagnosis [OR = 1.72 (95% CI 1.18-2.51); p = .003]. CONCLUSIONS: The mechanisms underlying the association w between FMF and later ADHD diagnosis merit further elucidation.

The Association Between Repeated Measured Febrile Episodes During Early Childhood and Attention Deficit Hyperactivity Disorder: A Large-Scale Population-Based Study.

OBJECTIVE: We examined the association between the number, magnitude, and frequency of febrile episodes during the 0 to 4 years of life and subsequent diagnosis of ADHD. METHODS: This population-based case-control study in an Israeli HMO, Leumit Health Services (LHS), uses a database for all LHS members aged 5 to 18 years between 1/1/2002 and 1/30/2022. The number and magnitude of measured fever episodes during the 0 to 4 years were recorded in individuals with ADHD (N = 18,558) and individually matched non-ADHD controls in a 1:2 ratio (N = 37,116). RESULTS: A significant, independent association was found between the number and magnitude of febrile episodes during the 0 to 4 years and the probability of a later diagnosis of ADHD. Children who never had a measured temperature >37.5°C had a significantly lower rate of ADHD (OR = 0.834, 95% CI [0.802, 0.866], p < .0001). CONCLUSIONS: Febrile episodes during 0 to 4 years are associated with a significantly increased rate of a later diagnosis of ADHD in a doseresponse relationship.

Identifying Diabetes Related-Complications in a Real-World Free-Text Electronic Medical Records in Hebrew Using Natural Language Processing Techniques.

BACKGROUND: Studies have demonstrated that 50% to 80% of patients do not receive an International Classification of Diseases (ICD) code assigned to their medical encounter or condition. For these patients, their clinical information is mostly recorded as unstructured free-text narrative data in the medical record without standardized coding or extraction of structured data elements. Leumit Health Services (LHS) in collaboration with the Israeli Ministry of Health (MoH) conducted this study using electronic medical records (EMRs) to systematically extract meaningful clinical information about people with diabetes from the unstructured free-text notes. OBJECTIVES: To develop and validate natural language processing (NLP) algorithms to identify diabetes-related complications in the free-text medical records of patients who have LHS membership. METHODS: The study data included 2.3 million records of 41 469 patients with diabetes aged 35 or older between the years 2012 and 2017. The diabetes related complications included cardiovascular disease, diabetic neuropathy, nephropathy, retinopathy, diabetic foot, cognitive impairments, mood disorders and hypoglycemia. A vocabulary list of terms was determined and adjudicated by two physicians who are experienced in diabetes care board certified diabetes specialist in endocrinology or family medicine. Two independent registered nurses with PhDs reviewed the free-text medical records. Both rule-based and machine learning techniques were used for the NLP algorithm development. Precision, recall, and F-score were calculated to compare the performance of (1) the NLP algorithm with the reviewers' comments and (2) the ICD codes with the reviewers' comments for each complication. RESULTS: The NLP algorithm versus the reviewers (gold standard) achieved an overall good performance with a mean F-score of 86%. This was better than the ICD codes which achieved a mean F-score of only 51%. CONCLUSION: NLP algorithms and machine learning processes may enable more accurate identification of diabetes complications in EMR data.

The Association of Weight Reduction and Other Variables after Bariatric Surgery with the Likelihood of SARS-CoV-2 Infection.

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.

The Association between Previous Antibiotic Consumption and SARS-CoV-2 Infection: A Population-Based Case-Control Study.

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.

The professional agenda and its effect on the implementation of telemedicine among primary care physicians: A qualitative study.

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.

A higher frequency of physical activity is associated with reduced rates of SARS-CoV-2 infection.

BACKGROUND: Physical activity (PA) is associated with health benefits. Previous studies have shown that regular PA decreases the incidence of viral respiratory tract infections, but data on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are unavailable. OBJECTIVES: The objective of this study is to examine the association between PA frequency and SARS-CoV-2 infection. METHODS: A population-based cross-sectional study was conducted on data from 1 February 2020 to 31 December 2020, using the registry of Leumit Health Services (LHS), a national health maintenance organisation in Israel. All LHS patients aged 18 to 80 years who underwent at least one RT-PCR test for SARS-CoV-2 during the study period were included. We examined the association between PA frequency (hours per week) and being tested positive for SARS-CoV-2. RESULTS: Of 113,075 subjects tested for SARS-CoV-2 by RT-PCR (mean age 41.6 years, 54.4% female), 17,465 (15%) were positive. In the SARS-CoV-2-negative group, significantly more subjects were engaged with PA than in the SARS-CoV-2-positive group [crude odds ratio (OR) for any PA 0.75 (95% confidence interval (CI) 0.72-0.77)]. After adjusting for possible confounders, PA frequency had a significant negative association with the likelihood of being SARS-CoV-2 positive (adjusted OR 0.67, 95% CI 0.64-0.68). Moreover, as the frequency of PA increased, the ORs of being SARS-CoV-2-positive decreased (occasional PA: OR 0.71, 95% CI 0.67-0.74; PA 1-3 times/week: OR 0.62, 95% CI 0.58-0.65 and PA > 3 times/week: OR 0.54, 95% CI 0.49 - 0.59). CONCLUSION: Our large population-based study in patients undergoing SARS-CoV-2 RT-PCR testing showed that a higher frequency of PA is associated with a lower rate of positive test results.

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency and Long-Term Risk of Immune-Related diseases.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive enzymatic disorder, particularly prevalent in Africa, Asia and the Middle East. In the US, about 14% of black men are affected. Individuals with G6PD deficiency are often asymptomatic but may develop hemolysis following an infection or upon consumption of specific medications. Despite some evidence that G6PD deficiency affects the immune system, the long- term health risks associated with G6PD deficiency had not been studied in a large population. METHODS: In this retrospective cohort study, health records from G6PD deficient individuals were compared to matched controls in a national healthcare provider in Israel (Leumit Health Services). Rates of infectious diseases, allergic conditions and autoimmune disorders were compared between groups. RESULTS: The cohort included 7,473 G6PD deficient subjects (68.7% men) matched with 29,892 control subjects (4:1 ratio) of the same age, gender, socioeconomic status and ethnic group, followed during 14.3±6.2 years.Significantly increased rates for autoimmune disorders, infectious diseases and allergic conditions were observed throughout this period. Notable increases were observed for rheumatoid arthritis (OR 2.41, p<0.001), systemic lupus erythematosus (OR 4.56, p<0.001), scleroderma (OR 6.87, p<0.001), pernicious anemia (OR=18.70, P<0.001), fibromyalgia (OR 1.98, p<0.001), Graves' disease (OR 1.46, P=0.001), and Hashimoto's thyroiditis (OR 1.26, P=0.001). These findings were corroborated with elevated rates of positive autoimmune serology and higher rates of treatment with medications commonly used to treat autoimmune conditions in the G6PD deficient group. CONCLUSION: G6PD deficient individuals suffer from higher rates of autoimmune disorders, infectious diseases, and allergic conditions.

The Association between Glucose 6-Phosphate Dehydrogenase Deficiency and Attention Deficit/Hyperactivity Disorder.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, impacting 4.9% of the population and more prevalent in Mediterranean communities, is a common enzymopathy with potential relevance to Attention Deficit/Hyperactivity Disorder (ADHD). This study investigated this association. METHODS: The clinical characteristics of 7473 G6PD-deficient patients and 29,892 matched case-controls (selected at a 1:4 ratio) from a cohort of 1,031,354 within the Leumit Health Services database were analyzed using Fisher's exact test for categorical variables and the Mann-Whitney U test for continuous variables. RESULTS: In total, 68.7% were male. The mean duration of follow-up was 14.3 ± 6.2 years at a mean age of 29.2 ± 22.3 years. G6PD deficiency was associated with an increased risk of being diagnosed with ADHD (Odds Ratio (OR) = 1.16 [95% CI, 1.08-1.25], p < 0.001), seeking care from adult neurologists (OR = 1.30 [95% CI, 1.22-1.38], p < 0.001), and consulting adult psychiatrists (OR = 1.12 [95% CI, 1.01-1.24], p = 0.048). The use of stimulant medications among G6PD-deficient individuals was 17% higher for the methylphenidate class of drugs (OR = 1.17 [95% CI, 1.08, 1.27], p < 0.001), and there was a 16% elevated risk for amphetamine use (OR = 1.16 [95% CI, 1.03, 1.37], p = 0.047). CONCLUSIONS: G6PD deficiency signals an increased risk of ADHD diagnosis, more severe presentations of ADHD and a greater need for psychiatric medications to treat ADHD.