Prevalence of Helminth Infections in Patients with Celiac Disease.

INTRODUCTION: The aim of this study was 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 Leumit Health Care Services' electronic health records. 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 socioeconomic 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 1.20-1.45, 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.

Low utility of serum folic acid blood tests in healthy children and adolescents, a nationwide cohort.

This study aimed to evaluate the utility of serum folic acid testing in children and adolescents in a developed country without mandatory folic acid food fortification and to identify patients at risk for folic acid deficiency. In this cross-sectional study, records from primary care and hospitals were reviewed for patients aged 0-18 years who underwent serum folic acid testing. Data were retrieved from the Leumit-Health-Services database over a ten-year period (January 2008 to December 2018). Clinical and laboratory data were compared between patients with folic acid deficiency to those with normal levels. Among 20,411 pediatric patients tested, 884 (4.3%) had folic acid deficiency, of whom only 26.3% had anemia. Only two patients (0.2%) had megaloblastic anemia. Multivariate analysis showed that male gender (odds ratio(OR)1.6, 95% CI 1.22-2.12), older age (OR 1.32, 95% CI 1.26-1.39), higher BMI percentile (OR 1.01, 95% CI 1-1.01), antipsychotic treatment (OR 3.23, 95% CI 1.52-6.84), celiac (OR 2.97, 95% CI 1.66-5.34), and Attention-Deficit-and-Hyperactivity-Disease (ADHD) treated with psychostimulants (OR 2.21, 95% CI 1.56-3.12) were associated with folic acid deficiency(all p < 0.01). Lower hemoglobin levels were independently associated with increased OR of folic acid deficiency (OR 0.77, 95% CI 0.66-0.90, p = 0.001), but anemia as a diagnosis was not. CONCLUSION: Pediatric folic acid deficiency rates were low in this nationwide cohort and not linked to megaloblastic anemia, likely due to concomitant iron deficiency anemia. Although retrospective, this might suggest low utility for routine serum folic acid testing in healthy children in developed countries, except in cases of celiac disease or specific medication use such psychostimulants or antipsychotics. WHAT IS KNOWN: • Folic acid deficiency is common among children in developing countries, causing megaloblastic anemia, growth delays, and cognitive impairments. In developed countries, the prevalence is considered low. WHAT IS NEW: • Of 20,411 pediatric patients tested for serum folate, in a developed country, only 4.3% had folate deficiency. • Risk factors for deficiency included celiac, antipsychotics, and psychostimulant treatment for ADHD. • Routine folate testing in developed countries may have limited utility; Targeted screening is recommended.

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.

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.

The impact of ethnicity on chronic hepatitis B infection course and outcome: big data analysis from Israel.

OBJECTIVES: The effect of ethnicity on chronic hepatitis B virus (CHB) infection's course and outcome has attracted little research. We aimed to compare different aspects of ethnic disparities in CHB patients, including prevalence, phenotypes, management, and outcome between two major ethnic groups in Israel. DESIGN: We conducted a large retrospective cohort study utilizing the Leumit-Health-Service database. Electronic reports of almost 700,000 members from different ethnicities and districts throughout Israel from 2000 to 2019 were reviewed. Patients' ethnicity was categorized based on the classification of the Israeli Central Bureau of Statistics into two main groups, Arabs and Jews. CHB diagnosis was based on ICD-9-CM codes and supportive serology results. Prevalence, clinical backgrounds, disease course, and patients' outcomes were compared between both groups. RESULTS: The prevalence of CHB in the Arab minority group was almost twice and a half-higher when compared to their Jewish counterparts (4.3% vs. 1.8%), but they had a lower rate of referral for HBsAg testing (7% vs. 7.9%). The Arab CHB patients were significantly younger at the time of diagnosis (37.6± 13.5 vs. 45.3± 15; P < 0.001). Male predominance was noted in both groups. The Arab patients had a higher rate of active hepatitis (HBeAg-positive and/or negative hepatitis) phase (36.4% vs. 29.8%; P = 0.01), as well as a significantly higher rate of HBeAg seroconversion (45.2% vs. 35.4%; P = 0.033). Nucleos/tide analogue treatment figures were similar, with most patients in both groups receiving a high barrier to resistance treatment. Patients' outcome was similar in both groups as the rate of hepatocellular carcinoma, cirrhosis, and advanced fibrosis (after stratification analysis) were comparable between both groups. CONCLUSION: Marked by a prominently higher prevalence of HBV infection, patients in the Arab ethnic group had a lower rate of referral for HBsAg testing but received comparable management and had a similar outcome compared to their Jewish counterparts.

A comparative study of chronic spontaneous urticaria and chronic mast cell mediated angioedema.

Background: Mast cell-mediated angioedema (MC-AE) is considered a form of chronic spontaneous urticaria (CSU). Objective: To investigate the clinical and laboratory features that distinguish MC-AE from antihistamine-responsive CSU (CSU), and antihistamine-resistant CSU (R-CSU) with and without concomitant AE. Methods: A retrospective observational study using the electronic patient record data base of patients with MC-AE, CSU, R-CSU, and sex- and age-matched control group (control), with a case-control ratio of 1:2. Results: A total of 986 subjects in the CSU group, 148 in the R-CSU group, 64 in the MC-AE group, and 1198 in the control group were compared. The R-CSU group without AE was characterized by lower total IgE levels (118.5 ± 84.7 IU/mL) and higher High sensitivity-C reactive protein (hs-CRP) levels (138.9 ± 94.2 IU/mL, p = 0.027; and 7.4 ± 6.9 mg/L versus 5.1 ± 6.8 mg/L, p = 0.001) than the CSU without AE group. The R-CSU group with AE was characterized by lower total IgE levels (112.1 ± 81.3 IU/mL) than the CSU group with AE (141.7 ± 89.5 IU/mL; p < 0.001), higher hs-CRP levels (7.1 ± 6.1 mg/L versus 4.7 ± 5.9 mg/L; p < 0.001). There were fewer female subjects in the MC-AE group (31 [48.4%]) than in the CSU with AE and in the R-CSU with AE 223 (67.8%) and 18 (66.7%), respectively; p = 0.012). MC-AE group was characterized by less eyelid/perioral/facial involvement and more limb involvement than in the CSU with AE and R-CSU with AE groups (p < 0.001). Conclusion: Low IgE in MC-AE and higher IgE in CSU may signify two distinct types of immune dysregulation. Due to clinical and laboratory differences between MC-AE and CSU, we suggest questioning the assumption that MC-AE is a form of CSU.

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.

Chronic spontaneous urticaria after BNT162b2 mRNA (Pfizer-BioNTech) vaccination against SARS-CoV-2.

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.

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.

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.

High rates of mood disorders in patients with chronic idiopathic eosinopenia.

Background: Mood disorders (MD) are multifactorial disorders. Identifying new biomarkers for the early diagnosis of MD and predicting response to treatment is currently a significant research topic. Both eosinopenia and MD are associated with increased activity of the hypothalamic-pituitary-adrenal axis. The present study, therefore, used a clear definition of chronic idiopathic eosinopenia (CIE) to determine the rate of MD in a large cohort of individuals with CIE. Methods: This retrospective population-based, case-control study uses data of seven consecutive years from the database of Leumit Health Services (LHS) - a nationwide health maintenance organization in Israel. Results: Participants were 13928 LHS members with CIE and 27858 negative controls. The CIE group exhibited significantly higher rates of MD than the control group throughout the whole study period, except for atypical depressive disorder at baseline. Conclusions: CIE might be associated with a higher prevalence of MD. Further basic research should elucidate the pathophysiologic mechanisms linking CIE and MD.

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.

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.

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.

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.