Subacute Thyroiditis Following COVID-19 and COVID-19 Vaccination.

OBJECTIVE: COVID-19 infection and immunizations have been implicated in developing a range of thyroid diseases, including subacute thyroiditis (SAT). This study aimed to evaluate the association between COVID-19 infection and/or COVID-19 vaccination with SAT. METHODS: A population of 3 million adults insured by Clalit Health Services was evaluated from March 2020 to September 2022. Patients with a new diagnosis of SAT were identified and matched in a 1:10 ratio to a control group. Each control was assigned an index date that was identical to that of their matched case, defined as the date of SAT diagnosis. Multivariate conditional logistic regression models were used to evaluate the association between COVID-19 infection, vaccine, and thyroiditis. RESULTS: A total of 3221 patients with SAT were matched with 32 210 controls. Rates of COVID-19 vaccination (first, second, or third dose) and COVID-19 infection were evaluated prior to the date of SAT diagnosis (disease group) or index date (control group) to detect a possible association. No difference was detected between the groups in relation to vaccinations at the 30 days, 60 days, and 90 days of time points (P = .880/0.335/0.174, respectively). No difference was found between groups in relation to COVID-19 infection at these time points (P = .735/0.362/0.956, respectively). There was higher use of medications for the treatment of thyroiditis, including nonsteroidal anti-inflammatory drugs (28.6% vs 7.9%, P < .01), steroids (10.3% vs 1.8%, P < .01), and beta-blockers (18.3% vs 5.4%, P < .01). CONCLUSION: Based on this large population study, no association was found between COVID-19 infection and/or the COVID-19 vaccine and SAT.

Nationwide Evaluation of Quality of Care Indicators for Individuals with Severe Mental Illness and Diabetes Mellitus, Following Israel's Mental Health Reform.

Diabetes Mellitus (DM) is more common among individuals with severe mental illness (SMI). We aimed to assess quality-of-care-indicators in individuals with SMI following the 2015 Israel's Mental-Health-reform. We analyzed yearly changes in 2015-2019 of quality-of-care-measures and intermediate-DM-outcomes, with adjustment for gender, age-group, and socioeconomic status (SES) and compared individuals with SMI to the general adult population. Adults with SMI had higher prevalences of DM (odds ratio (OR) = 1.64; 95% confidence intervals (CI): 1.61-1.67) and obesity (OR = 2.11; 95% CI: 2.08-2.13), compared to the general population. DM prevalence, DM control, and obesity rates increased over the years in this population. In 2019, HbA1c testing was marginally lower (OR = 0.88; 95% CI: 0.83-0.94) and uncontrolled DM (HbA1c > 9%) slightly more common among patients with SMI (OR = 1.22; 95% CI: 1.14-1.30), control worsened by decreasing SES. After adjustment, uncontrolled DM (adj. OR = 1.02; 95% CI: 0.96-1.09) was not associated with SMI. Cardio-metabolic morbidity among patients with SMI may be related to high prevalences of obesity and DM rather than poor DM control. Effective screening for metabolic diseases in this population and social reforms are required.

Racial/ethnic and socioeconomic disparities in colorectal cancer screening in a large organization with universal insurance before and during the coronavirus disease 2019 pandemic.

OBJECTIVES: Israel is regarded as a country with a developed economy and a moderate income inequality index. In this population-based study, we aimed to measure the inequalities in colorectal cancer screening within Clalit Health, an organization with universal insurance, before and during the coronavirus disease 2019 pandemic. SETTING: Retrospective analysis within Clalit Health Services, Israel. METHODS: We evaluated the rate of being up to date with screening (having a colonoscopy within 10 years or a fecal occult blood test within 1 year) and the colonoscopy completion rate (having a colonoscopy within 6 months of a positive fecal occult blood test) among subjects aged 50-75 in 2019-2021. RESULTS: In 2019, out of 918,135 subjects, 61.3% were up to date with screening; high socioeconomic status: 65.9% (referent), medium-socioeconomic status: 60.1% (odds ratio 0.81, 95% confidence interval 0.80-0.82), low-socioeconomic status: 59.0% (odds ratio 0.75, 95% confidence interval 0.74-0.75); Jews: 61.9% (referent), Arabs: 59.7% (odds ratio 0.91, 95% confidence interval 0.90-0.92), Ultraorthodox-Jews: 51.7% (odds ratio 0.77, 95% confidence interval 0.75-0.78). Out of 21,308 with a positive fecal occult blood test, the colonoscopy completion rate was 51.8%; high-socioeconomic status: 59.8% (referent), medium-socioeconomic status: 54.1% (odds ratio 0.79, 95% confidence interval 0.73-0.86), low-socioeconomic status: 45.5% (odds ratio 0.60, 95% confidence interval 0.56-0.65); Jews: 54.7% (referent), Ultraorthodox-Jews: 51.4% (odds ratio 0.91, 95% confidence interval 0.90-0.92), Arabs: 44.7% (odds ratio 0.77, 95% confidence interval 0.75-0.78). In 2020-2021, there was a slight drop in the rate of being up to date with screening, while most of the discrepancies were kept or slightly increased with time. CONCLUSIONS: We report significant inequalities in colorectal cancer screening before and during the coronavirus disease 2019 pandemic in Israel, despite a declared policy of equality and universal insurance.

Pediatric overweight and obesity increased in Israel during the COVID-19 period.

Reports from many settings suggest that pediatric overweight and obesity increased in 2020 and 2021, presumably due to lifestyle changes associated with the COVID-19 pandemic. Many of these previous reports have relied on convenience samples or subsets of the population. Here, we present results of a longitudinal study of the entire population of Israel, a nation of approximately 9 million people, with the proportion with underweight, normal weight, overweight, and obesity at age 7 and at age 14-15, across the years 2017-2021. Our results show that the prevalence of overweight and obesity, which had been steady or improving through 2019, increased relatively quickly in 2020 and 2021. For example, among 7-year-olds, the percentage of children with obesity in 2019 was 6.8% (99% CI: 6.69-7.05), and by 2021, it had increased to 7.7% (99% CI: 7.53-7.93). There were important disparities in overweight and obesity based on SES; for example, the rate ratio for obesity comparing the poorest with the wealthiest 14-15-year-olds in 2019 was 1.63 (99% CI: 1.55-1.72). However, these disparities did not change meaningfully in 2020 and 2021, implying that while obesity did become more prevalent, this increase in prevalence was not differential across socioeconomic status. Like many other nations, Israel too experienced considerable increases in pediatric overweight and obesity in 2020-2021, erasing the improvements of the previous years among younger children.

The Risk and Predictors of Malignancies in Ankylosing Spondylitis Patients in Israel-A Retrospective Electronic Data-Based Study.

BACKGROUND: Previous studies demonstrated unclear and vast variability in the association between Ankylosing Spondylitis (AS) and the risk of cancer. OBJECTIVES: To assess the risk of overall and site-specific malignancies for AS patients in Israel, while examining the role of comorbidities and immunomodulatory therapy. METHODS: We conducted a retrospective electronic data-based study including all AS patients diagnosed between 2002 and 2018, with no history of cancer prior to enrollment, with 5:1 ratio matched-control by age, gender, and place of residence. The odds Ratios (OR) for site-specific malignancies, comparing AS patients and controls, were calculated using logistic regression. Risk factors for malignancies within the AS cohort were evaluated in the same manner. RESULTS: This study comprised 5825 AS patients and 28,356 matched controls. There was a higher overall risk of cancer in AS patients compared to controls (OR = 1.4, 95% CI 1.24-1.6), specifically for solid malignancies (OR = 1.5, 95% CI 1.3-1.7), CNS (OR = 3.72, 95% CI 1.29-10.7), kidney (OR = 2.06, 95% CI 1.12-3.8), and malignancy of unknown primary (OR = 3.06, 95% CI 2.35-3.98). Regarding predictors for malignancy within AS patients, older age at diagnosis (OR = 1.31, 95%,CI 1.25-2.36), diabetes (OR = 1.52, 95% CI 1.18-1.97), IBD (OR = 2.61, 95% CI 1.75-3.89), and treatment with DMARDs (OR = 2.17, 95% CI 1.65-2.83) were associated with a higher risk of solid malignancies, while NSAIDs treatment alone had a protective effect for solid malignancies (OR = 0.78, 95% CI 0.61-0.99). No significant association was found between anti-TNF therapy and the risk of solid or hematologic malignancies within the AS group. CONCLUSION: AS is associated with an increased risk of overall and site-specific malignancies, with independently higher risk for older age, comorbidity of DM, IBD, and treatment with DMARDs.

Ankylosing spondylitis is associated with increased prevalence of valvular heart diseases: a cross-sectional population-based study.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory arthritis primarily affecting the sacroiliac joint and axial skeleton with associated extra-articular involvement including cardiovascular system disease including aortic valve disease with variable reported prevalence. The aim of this study is to determine the prevalence of heart valve disorders in AS patients. METHODS: This was a retrospective, population-based, cross-sectional study that retrieved data from the Clalit Health Services registry. Cases were defined as having AS, whereas controls were frequency matched by age and sex in a ratio of 5:1. The prevalence of valvular heart diseases was compared between the two groups; a multivariate logistic regression model was applied to estimate the association after controlling for potential confounders. RESULTS: We included 4082 AS patients and 20 397 controls frequency matched by age and sex. AS patients had a significantly higher prevalence of cardiovascular risk factors (P < .001) and a higher prevalence of valvular heart disease. In the multivariate logistic regression model, adjusting for multiple confounding factors, AS was independently associated with aortic stenosis [odds ratio (OR): 2.25, 95% confidence interval (CI): 1.57-3.23, P < 0.001], aortic insufficiency (OR: 2.44, 95% CI: 1.50-3.94, P < 0.001), and mitral insufficiency (OR: 1.75, 95% CI: 1.17-2.61, P < 0.001) but not mitral stenosis (OR: 1.31, 95% CI: 0.60-2.70, P = 0.47). CONCLUSIONS: Our study reports the increased risk of valvular heart diseases in patients with AS, possibly due to the inflammatory milieu associated with the disease process and the result of biomechanical stress affecting the enthesis-like valvular structures.

Association of fibromyalgia with cancerous and non-cancerous gastrointestinal comorbidities: a cross-sectional study.

OBJECTIVES: Several studies have shown a higher prevalence of irritable bowel syndrome (IBS) among patients with fibromyalgia yet, data regarding association between fibromyalgia and other gastrointestinal disorders have been relatively overlooked. Our aim was to investigate the association between fibromyalgia and gastrointestinal disorders including both benign and malignant conditions. METHODS: We conducted a retrospective cross-sectional study based on the comprehensive electronic database of the largest health maintenance organisation in Israel. All subjects with a diagnosis of fibromyalgia in their medical records and age- and sex-matched controls were included in the study. We investigated the association of fibromyalgia with benign gastrointestinal disorders including IBS, gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), celiac disease, Crohn's disease, ulcerative colitis, and with gastrointestinal malignancies including colorectal, pancreatic, stomach, liver, and bile duct cancers. RESULTS: The study enrolled 18,598 patients with fibromyalgia and 36,985 controls. The mean age was 56.5 years (standard deviation=14) with a female predominance (91%). Fibromyalgia was significantly associated with IBS (OR 4.61, 95% CI 4.09-5.2, p<0.001), GERD (OR 2.62, 95% CI 2.5-2.75, p<0.001), PUD (OR 2.13, 95% CI 1.98-2.3, p<0.001), celiac disease (OR 2.08, 95% CI 1.63-2.65, p<0.001), Crohn's disease (OR 1.85, 95% CI 1.408-2.32, p<0.001) and ulcerative colitis (OR 1.81, 95%CI 1.4-2.33, p<0.001). Nonetheless, no significant differences were found regarding the prevalence of gastrointestinal malignancies between the fibromyalgia patients and controls. CONCLUSIONS: Our findings suggest that FM is positively associated with various benign but not malignant GI disorders.

Vitamin D Insufficiency is Associated with Higher Incidence of Dementia, a Large Community-Based Retrospective Cohort Study.

INTRODUCTION: Active metabolite of vitamin D has neuro-immunomodulatory and neuroprotective properties. However, there is still a debate about the potential association between low serum levels of hydroxy-vitamin D and increased risk for dementia. OBJECTIVES: To determine an association between hypovitaminosis D and dementia for different 25-hydroxyvitamin-D (25(OH)D) serum level cutoffs. METHODS: Patients were identified utilizing the database of Clalit Health Services (CHS), the largest healthcare provider in Israel. For each subject, all available values of 25(OH)D during the study period, which lasted from 2002 to 2019, were obtained. Rates of dementia were compared across different cutoffs of 25(OH)D levels. RESULTS: Cohort included 4278 patients, of whom 2454 (57%) were women. The mean age at the beginning of follow-up was 53 (±17). During the 17-year study period, a total of 133 patients (3%) were diagnosed with dementia. In a fully adjusted multivariate analysis, the risk for dementia was almost 2-fold higher in patients with an average of vitamin D insufficiency (<75 nmol/l) measurements (OR = 1.8, 95% C.I. = 1.0-3.2) compared to reference values (≥75 nmol/l). Patients with vitamin D deficiency (<50 nmol/l) demonstrated higher rates of dementia (OR = 2.6, 95% C.I. = 1.4-4.8). In our cohort, patients were diagnosed with dementia at a younger age in the deficiency (77 vs. 81 P-value = 0.05) and the insufficiency groups (77 vs. 81 P-value = 0.05) compared to the reference values (≥75 nmol/l). CONCLUSION: Insufficient levels of vitamin D are associated with dementia. Dementia is diagnosed at a younger age in patients with insufficient and deficient vitamin D levels.

The risk of osteoporosis in patients with ankylosing spondylitis-A large retrospective matched cohort study.

BACKGROUND: Ankylosing spondylitis (AS) is associated with increased bone turnover and systemic inflammation. Osteoporosis is common but frequently underappreciated in AS, studies regarding the incidence of osteoporosis in AS are limited and based on small cohorts. The aim of this study is to assess the risk of osteoporosis in patients with AS compared to matched controls. METHODS: A population based retrospective cohort study using data retrieved from a large electronic medical record in Israel, the Clalit health services. Included patients that were diagnosed with AS from January 2002 to December 2018 were followed for development of osteoporosis. The incidence of osteoporosis was compared between AS and controls and a logistic regression model was used to assess the interaction between AS and osteoporosis. RESULTS: The study included 5476 AS patients, and 27,657 age- and sex-frequency matched controls. The incidence of osteoporosis in AS patients was significantly higher than controls (4.7% vs 2.8%, p<0.001) in the whole cohort as well as when stratified by sex. Osteoporosis developed earlier in patients with AS versus controls (4.1 vs 5.2 years, p<0.001). In multivariate analysis and after adjustment to several potential confounders, AS was found to independently associated with osteoporosis (HR 1.83, 95%CI 1.58-2.11, p<0.0001). CONCLUSIONS: Our study confirms the higher incidence and earlier development of osteoporosis in patients with AS. Such finding highlights the increased need of awareness and earlier detection of such comorbidity allowing prompt treatment to prevent undesired sequalae including increased risk of fractures.

Dipeptidyl-peptidase IV inhibitor (DPP4i) confers increased odds of bullous pemphigoid even years after drug initiation.

The timing pattern in which dipeptidyl-peptidase IV inhibitors (DPP4i) confer the risk of bullous pemphigoid (BP) is unknown. To investigate the odds of BP following exposure to DPP4i and to perform a duration-response analysis evaluating the risk of BP in relation to the duration of exposure to the culprit drug. A population-based nested case-control study was performed comparing diabetic patients with BP (n = 1458) with age-, sex- and ethnicity-matched diabetic control subjects (n = 6051) with respect to the prevalence of exposure to DPP4i. Adjusted odds ratios (ORs) were estimated by logistic regression. Overall exposure to DPP4i was associated with an 80% increase in the odds of subsequent BP (OR, 1.81; 95% CI, 1.46-2.08; P < 0.001). In an intraclass analysis, the odds of BP were increased in association with vildagliptin (OR, 3.40; 95% CI, 2.69-4.29; P < 0.001) and sitagliptin (OR, 1.56; 95% CI, 1.33-1.84; P < 0.001). In a duration-response analysis, the highest likelihood of BP was found 1-2 years after commencing the drug (OR, 2.66; 95% CI, 1.97-3.59; P < 0.001). The odds of BP were increased across all time periods and retained its statistical significance even ≥ 6 years after the drug initiation (OR, 1.44; 95% CI, 1.09-1.91; P = 0.011). Relative to other diabetic patients with BP, patients with DPP4i-associated BP were more likely to be admitted to inpatient dermatologic wards (OR, 1.66; 95% CI, 1.30-2.13; P < 0.001) and had higher mean(SD) numbers of outpatient dermatologist visits (14.7[14.8] vs. 12.3[13.2], respectively; P = 0.006). DPP4i should be suspected as a predisposing factor for BP even numerous years after the drug initiation.

Psoriasis and hidradenitis suppurativa: A large-scale population-based study.

BACKGROUND: The coexistence of psoriasis and hidradenitis suppurativa (HS) has been described, but the association between these conditions is yet to be firmly established. OBJECTIVE: To study the association between psoriasis and HS by using a large-scale real-life computerized database. METHODS: A cross-sectional study was conducted to compare the prevalence of HS among patients with psoriasis with that among age-, sex- and ethnicity-matched control subjects. RESULTS: A total of 68,836 patients with psoriasis and 68,836 controls were included in the study. The prevalence of HS was increased in patients with psoriasis versus in those in the control group (0.3% vs 0.2%, respectively; odds ratio, 1.8; 95% confidence interval, 1.5-2.3; P < .001). In a multivariate analysis adjusting for smoking, obesity, and other comorbidities, psoriasis was still associated with HS (odds ratio, 1.8; 95% confidence interval, 1.4-2.2; P < .001). Patients with coexistent psoriasis and HS were significantly younger (39.0 ± 15.7 vs 42.6 ± 21.2 years [P = .015]) and had a higher prevalence of obesity (35.1% vs 25.3% [P = .001]) and smoking (58.5% vs 37.3% [P < .001]) compared with patients with psoriasis alone. LIMITATIONS: Retrospective data collection. CONCLUSIONS: A positive association was observed between HS and psoriasis. Further longitudinal observational studies are necessary to establish these findings in other study populations.

The association of uveitis with hepatitis B and hepatitis C viruses: a large-scale population-based study.

PURPOSE: To examine the association of uveitis with hepatitis B (HBV) and hepatitis C (HCV) chronic infections METHOD: This is a population-based cross-sectional study. The study encompassed 13,183 consecutive patients with uveitis and 65,331control subjects. The prevalence of chronic HBV and HCV infections was compared between patients diagnosed with uveitis and age-, sex-, and ethnicity-matched controls. Lifetime prevalence rates of HBV and HCV were calculated for patients with uveitis and control individuals. Odds ratio (OR) for HBV and HCV was evaluated across different strata. RESULTS: The lifetime prevalence rate of chronic HBV infection was greater in patients with uveitis than in controls (1.2% vs. 0.8%, respectively; P < 0.001). The association of HBV with uveitis was statistically significant among individuals older than 40 years of age, both sexes, and individuals of Jewish ethnicity. The lifetime prevalence of HCV was comparable between patients with uveitis and controls (0.8% vs. 0.7%, respectively; P = 0.189). Thus, no independently significant association was found between uveitis and HCV (fully-adjusted OR, 1.15; 95% CI, 0.93-1.42; P = 0.211). CONCLUSIONS: Uveitis is associated with HBV. The association was more prominent among older and Jewish patients. Patients with uveitis may benefit from screening for HBV. An association between uveitis and HCV has not been found.

Investigating the epidemiological relationship between vitiligo and psoriasis: a population-based study.

BACKGROUND: The association of vitiligo with psoriasis is inconsistent in the current literature. OBJECTIVE: To assess the bidirectional association between vitiligo and psoriasis. METHODS: A population-based study was performed to compare vitiligo patients (n = 20,851) with age-, sex- and ethnicity-matched control subjects (n = 102,475) regarding the incidence of new-onset and the prevalence of preexisting psoriasis. Adjusted hazard ratios (HRs) and adjusted odds ratios (ORs) were calculated by cox regression and logistic regression, respectively. RESULTS: The incidence rate of new-onset psoriasis was estimated at 7.9 (95% CI 6.4-9.7) and 4.7 (95% CI 4.1-5.3) cases per 10,000 person-years among patients with vitiligo and controls, respectively. Patients with vitiligo experienced an increased risk of psoriasis (fully-adjusted HR 1.71; 95% CI 1.35-2.17; P < 0.001). On the other hand, the odds of vitiligo were only marginally elevated among patients with preexisting psoriasis (fully-adjusted OR 1.19; 95% CI 1.01-1.40; P = 0.051). Compared to other patients with vitiligo, those with vitiligo and comorbid psoriasis were older at the onset of the disease and had a greater prevalence of metabolic and cardiovascular comorbidities. CONCLUSIONS: A diagnosis of vitiligo predisposes individuals to develop subsequent psoriasis. Clinicians managing dermatologic patients ought to be aware of this comorbidity. Further research is required to explicate the pathomechanism underlying this epidemiological observation.

Anxiety in Patients with Neovascular Age-related Macular Degeneration.

PURPOSE: The main objective of the study is to investigate the prevalence of anxiety in patients with neovascular age-related macular degeneration (nAMD). METHODS: A retrospective cross-sectional study of 3 304 nAMD patients and 16 515 age- and gender-matched controls. The proportions of patients with anxiety were compared between the groups using univariate analyses and a multivariate logistic regression model. Proportion of anxiety in patients with nAMD was compared with the proportion of anxiety in controls, matched for age and gender. Data was obtained from the largest health maintenance organization in Israel (Clalit Health Services) with 4 200 000 members. RESULTS: The mean age of patients was 79.7 years; 54.8% were females; Anxiety was more common in patients with nAMD (13.2%) compared to the control group (10.2%) (OR 1.3; 95%CI 1.2-1.5). Multivariate logistic regression analysis revealed a significant association between anxiety and nAMD (OR 1.3; 95% CI: 1.2-1.5), adjusted for age, gender, and socio-economic status. CONCLUSION: Our study demonstrated that anxiety is more common in patients with nAMD compared to a control group. Physicians treating patients with nAMD should be aware of this association, in order to provide appropriate care for the anxiety associated with nAMD.