Prevalence of helminth infections in patients with Celiac disease.

INTRODUCTION: To investigate the association between helminth infections and celiac disease (CeD), examining various demographic and clinical factors in CeD cases compared to controls. METHODS: We conducted a retrospective case-control study utilizing the electronic health records of Leumit Health Care Services. The study encompassed individuals with CeD and a matched control group. We analyzed demographic and clinical characteristics, examining their association with helminth infections. RESULTS: We observed CeD cases and controls had similar mean ages (17.8 years vs. 18.0 years, p = 0.565) and gender distributions (64.0% females in both groups, p = 0.999). There were no significant differences in socio-economic status and ethnic distribution between the two groups. Most of the helminthiases in the CeD group were due to intestinal helminthiases, and most of the intestinal helminthiases were nematode (roundworm) infections. Enterobiasis (the pinworm Enterobius vermicularis) is involved in most cases (odds ratio 1.32, 95% confidence interval 1.20 to 1.45, p < 0.001). While the prevalence of ascariasis and anisakiasis was also higher in the CeD group, these differences were not statistically significant (p = 0.115 and p = 0.174, respectively). No significant differences were found in the prevalence of other specific helminth infections, such as echinococcosis, cestode infections, and strongyloidiasis. CONCLUSIONS: This study reveals an unexpected association between CeD and helminth infections, challenging prevailing hypotheses, particularly within the context of the hygiene hypothesis. These findings warrant further investigation to elucidate the mechanisms underlying this intriguing relationship.

Drug Survival on First Biologic Therapy Among Late-Onset Rheumatoid Arthritis Patients Compared to Early-Onset Patients: A Population-Based Cohort Study.

INTRODUCTION: Rheumatoid arthritis (RA) patients can be divided according to the age of disease onset and classified as late-onset RA ≥ 60 years old or early-onset RA < 60 years old. Current treatment guidelines do not stipulate any preference regarding the biologic that should be used first in the late-onset group. This study aims to compare the drug survival times on first biological treatment between late and early-onset RA patients. METHODS: This is a population based cohort study using the medical records of Leumit healthcare services. We included all eligible RA patients between 2000 and 2017. RA patients were divided into late- and early-onset RA groups and compared according to drug survival time on the first biological therapy. RESULTS: The final cohort included 3814 RA patients, 2807 (73.6%) of whom had early-onset RA. Overall, biologic disease-modifying anti-rheumatic drugs (bDMARDs) were used more often among early-onset compared to late-onset patients (16.9% vs. 7.8%, p < 0.001). Among early-onset patients, etanercept was associated with the longest drug survival time on the first biologic, and adalimumab and infliximab were associated with the longest drug survival times among late-onset patients. No differences were observed in drug survival times between late and early-onset patients on the first bDMARD, except for abatacept and golimumab with longer drug survival time among early-onset patients. CONCLUSION: Late-onset RA patients were treated with biologics to a lesser extent than early-onset patients, but no differences were observed in drug survival times at the first bDMARD between the two groups.

Acute urticaria and cardiovascular diseases.

BACKGROUND: Acute urticaria (AU), characterized by sudden skin wheals, has been associated with various triggers. While chronic urticaria's cardiovascular comorbidities have been studied, AU's associations remain largely unexplored. OBJECTIVE: This study aimed to identify prevalent cardiovascular comorbidities in AU patients and assess their clinical significance. METHODS: A retrospective cohort study used data from Leumit Health Services, matching AU patients with controls. Demographic, clinical, and laboratory data were analyzed. Statistical analyses included Fisher's Exact Test and Mann-Whitney U test. RESULTS: The AU group (72,851 individuals) showed no sex/ethnic distribution differences from controls (291,404 individuals). Systolic blood pressure, weight, BMI, glucose, hemoglobin A1c, C-reactive protein, eosinophil counts, total IgE levels were higher in AU (p < 0.001). Several cardiovascular comorbidities showed significant associations with AU, including valvular heart diseases (aortic regurgitation, mitral regurgitation, and pulmonary valve stenosis), cardiac arrhythmias (atrial fibrillation and others), deep vein thrombosis, diseases of capillaries, peripheral artery disease, cerebrovascular disease, coronary artery disease, and inflammatory heart diseases (pericarditis, heart failure, and hypertension) (p < 0.05). Medications, including antihistamines and glucocorticoids, were more prevalent in the AU group (p < 0.001). CONCLUSION: This study's findings underscore the importance of recognizing cardiovascular comorbidities in AU patients and considering their implications for management. The observed associations provide insight into potential shared mechanisms between AU and cardiovascular diseases, though further research is needed to validate and expand upon these findings.

"A day in the life" - telemedicine in family medicine and its relationship with practicing physicians' satisfaction: a cross-sectional study.

BACKGROUND: Telemedicine has expanded rapidly in recent years, and many encounters that were conducted in person now take place remotely. This study aimed to assess primary care physicians' (PCPs) attitudes towards the different modalities of patient care. METHODS: This is a cross-sectional nationwide descriptive study conducted in Israel. We asked PCPs to document an entire workday and answer a short questionnaire after each visit. The questions addressed the type of visit (face-to-face, remote synchronous [telephone/video], or remote asynchronous [online requests]), the perceived quality of the visit, and the physicians' feelings at the end of each visit. Before documenting their working day, we asked the participants to answer a questionnaire about their general attitudes toward different modalities of medical visits and how they affect their well-being and burnout. RESULTS: Sixty physicians documented 2,025 visits, of which 39% took place in person, 36% stemmed from online patient requests, 18% were telephone meetings, < 1% were video meetings, and 6% consisted of other types of contact. Mixed effects logistic regressions were used to model the visits' evaluation. The odds ratios (ORs) for perceived medical quality of visits focused on medical tasks were lower for non-face-to-face visits: OR = 0.39, 95% CI 0.25-0.59 for remote synchronous, and OR = 0.14, 95% CI 0.09-0.23 for remote asynchronous. The perceived medical quality of visits focused on administrative tasks was lower for remote asynchronous than for face-to-face visits (OR = 0.31, 95% CI 0.14-0.65). We found no association between medical quality and patients, physicians, or clinic characteristics. The inappropriateness of the visit modality was also associated with lower medical quality (OR = 0.13, 95% CI 0.09-0.18). We found a correlation between perception of medical quality and physicians' feelings at the end of the visits, Spearman's r = 0.82 (p < 0.001). CONCLUSIONS: A substantial portion of the visits was dedicated to administrative tasks and remote medicine. In comparison, physicians rated face-to-face visits' quality higher than remote visits. Policymakers should intervene to minimize administrative work, reduce PCPs' administrative workload, and direct patients to the optimal visit modality for their complaints. These steps would increase medical quality, reduce burnout, and mitigate the shortage of PCPs.

Influence of cytochrome P450 2D6*10/*10 genotype on the risk for tramadol associated adverse effects: a retrospective cohort study.

Background: Tramadol is primarily metabolized by the highly polymorphic CYP2D6 enzyme, leading to a large spectrum of adverse events and clinical response. Ample evidence pointed a reduced CYPD26 activity score in individuals harboring the CYP2D6*10/*10 genotype, nevertheless, there is scarce studies on the impact of CYP2D6*10/*10 genetic polymorphism on long-term tramadol's adverse effects. Aim: To test the correlation between CYP2D6*10/*10 expression and the risk for tramadol-associated adverse effects. Method: Using a database of Leumit Healthcare Services in Israel, we retrospectively assessed the occurrence of adverse events in patients who were prescribed tramadol. A binary logistic regression model was applied to model the relationship between CYP2D6*10/*10 genotype and the occurrence of adverse effects. Results: Data from four hundred ninety-three patients were included in this study. Only 25 (5.1%) patients were heterozygous for the CYP2D6*10 variant, while 56 patients (11%) were tested positive to the CYP2D6*10/*10 genotype. Compared to carriers of other variants, patients with the CYP2D6*10/*10 variant exhibited a higher occurrence of adverse events (odds ratio [OR] = 6.14, 95% confidence interval 3.18-11.83); the odds ratio for central nervous system adverse events and gastrointestinal adverse events were 5.13 (95% CI 2.84-9.28), and 3.25 (95% CI 1.78-5.93), respectively. Conclusion: Among the different CYP2D6 genotypes, CYP2D6*10/*10 genotype carries the higher risk of tramadol related adverse events. Appreciating the frequency of this specific allele it seems prudent to pharmacogenetically screen patients considered for long term tramadol treatment for better tolerability and efficacy outcomes.

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.

Hepatitis B virus infection and risk of colorectal cancer: a large, population-based cohort study from Israel.

BACKGROUND: Recent population-based studies have suggested a possible link between hepatitis B (HBV) infection and extra-hepatic malignancies. We aimed to evaluate the association between HBV and colorectal cancer (CRC) using a large, population-based cohort study utilizing data from a large health maintenance organization (HMO). METHODS: The study included patients with non-cirrhotic HBV based on relevant ICD-9-CM codes and supportive serology identified from the HMO's database. Age-, sex-, ethnicity-, and BMI-matched non-HBV patients in a 1:10 ratio were included in the control group. We assessed the overall diagnosis rate of CRC and hepatocellular carcinoma (HCC) during the study period and calculated the diagnosis rate of CRC in each age category (≤50, 51-70, and ≥70) in both groups. RESULTS: A total of 3430 HBV patients and 34,300 controls were included in the study. The mean age, sex, BMI, and ethnic composition were similar, and the rates of family history of CRC did not differ between both groups. The overall follow-up period was 134±16 months. The diagnosis rate of HCC (1.6% vs. 0.1%; P<0.0001) was significantly higher in the HBV patients. However, the proportion of CRC was comparable for both groups (0.6% vs. 0.8%, P=0.404), which was evident in all age subgroups. CONCLUSIONS: Our findings suggest that HBV infection is associated with an increased risk of HCC diagnosis but is not linked to an elevated risk of CRC. These findings may inform future clinical practice and research regarding the relationship between HBV and extrahepatic malignancies.

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.

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.

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.

Effect of CYP2C19 Pharmacogenetic Testing on Predicting Citalopram and Escitalopram Tolerability and Efficacy: A Retrospective, Longitudinal Cohort Study.

Background-Various antidepressant agents are metabolized by the CYP2C19 enzyme, including Citalopram and Escitalopram. Variation in CYP2C19 expression might give rise to different plasma concentrations of the active metabolites, potentially affecting both drugs' efficacy and tolerability. Aim-The aim of this study was to evaluate differences in the Escitalopram and Citalopram efficacy and tolerability between different CYP2C19 genotype-based metabolizing categories in outpatients suffering from major depressive disorder (MDD). Methods-In a retrospective, longitudinal cohort study of electronic medical-record data, 283 patients with MDD who were prescribed Escitalopram or Citalopram with the available CYP2C19-genotyping test were enrolled. The primary efficacy end point was adverse drug reactions recorded in the medical files. A proportional-odds, multilevel-regression model for longitudinal ordinal data was used to estimate the relation between the CYP2C19 genotype and adverse drug reactions, adjusting for potential confounding variables and other explanatory variables. Latent-class analysis (LCA) was utilized to detect the presence of clinically significant subgroups and their relation to an individual's metabolizing status for CYP2D6/CYP2C19. Results-With poor CYP2C19 metabolizers as a reference, for each unit difference in the activity score of the CYP2C19 phenotype, the odds ratio for drug intolerability was lowered by 0.73 (95% credible intervals: 0.56-0.89), adjusting for significant covariates. In addition, applying LCA, we identified two qualitatively different subgroups: the first group (61.85%) exhibited multiple side effects, low compliance, and frequent treatment changes, whereas the second group (38.15%) demonstrated fewer side effects, good adherence, and fewer treatment changes. The CYP2C19 phenotype was substantially associated with the group membership. Conclusions-We found a positive association between the CYP2C19 activity scores, as inferred from the genotype, and both the efficacy of and tolerability to both Es/Citalopram. LCA enabled valuable insights into the underlying structure of the population; the CYP2C19 phenotype has a predictive value that discriminates between low-adherence, low-drug-tolerance, and low-response patients and high-adherence, high-drug-tolerance, and high-response patients. Personalized medicine based on CYP2C19 genotyping could evolve as a promising new avenue towards mitigating Escitalopram and Citalopram therapy and the associated side effects and enhancing treatment success.