Increased prevalence of metabolic syndrome in female patients with overactive bladder: A population-based study.

OBJECTIVES: To assess the association between overactive bladder syndrome (OAB) and the metabolic syndrome (MetS). PATIENTS AND METHODS: A population-based study was conducted to compare OAB patients with age-, sex- and ethnicity-matched control subjects regarding the prevalence of the parameters of the MetS, with respect to obesity, hyperlipidemia, hypertension and diabetes mellitus. The characteristics of the OAB population were assessed. Adjusted odds ratios (OR) were calculated by logistic regression. RESULTS: 110 024 OAB patients and 220 455 controls. were identified. OAB was associated with a higher prevalence of MetS (35.4% vs. 27.5%, p < 0.001). The fully adjusted OR for MetS in patients with OAB compared to controls was 1.44; 95% confidence interval (CI) 1.42-1.46; p < 0.001. Among metabolic parameters, obesity was found to be the strongest factor associated with OAB (OR 1.55, 95% CI 1.53-1.58, p < 0.001), and higher high-density lipoprotein cholesterole levels (>50) had a protective effect on the risk of OAB (OR 0.75, 95% CI 0.73-0.76, p < 0.001). CONCLUSIONS: Data from this cohort suggest that OAB is positively associated with MetS. Clinicians approaching patients with OAB should be aware of this association. A multimodal treatment focusing on the MetS may be considered in these patients.

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.

Hidradenitis Suppurativa Incidence and Prevalence Rates Are Increasing: A Population-based Study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory skin disease associated with a heavy burden of morbidity and cost. OBJECTIVES: To provide standardized estimates of trends in HS incidence and prevalence among patients in Israel between 2016 and 2019. METHODS: We conducted a population-based analysis of routinely collected electronic health records data from Clalit Health Services, the largest nationwide public health service provider in Israel. Age- and sex-adjusted rates were reported by using the standard European population as a reference. RESULTS: The study included 3488 HS incident cases. The mean ± SD age of onset was 30.3 years and was similar in males and females. HS was more common among Jews with low and medium socioeconomic status. The annual HS incidence rate increased throughout the study period. HS prevalence increased from 0.12% in 2016 to 0.17% in 2019. CONCLUSIONS: HS prevalence and incidence rates steadily rose among the Israeli population between 2016 and 2019. Awareness of these findings can help provide an optimal allocation of healthcare resources by policymakers and health service providers and prevent delays in diagnosis.

A Comparison of Hidradenitis Suppurativa Characteristics Among Israeli Arabs and Jews: Analysis of Two Cohorts.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease involving apocrine gland-bearing regions. There is an under-representation of non-Caucasians in epidemiologic studies of HS. The characteristics of HS in Israeli Arabs have not yet been studied. OBJECTIVES: To investigate the demographic and clinical profile of HS in the Israeli Arab population. METHODS: A retrospective analysis was conducted in two cohorts of patients with HS in Israel. The patients were derived from the database of a large health management organization (n=4191, 639 Arabs; population-based) and a major tertiary medical center (n=372, 49 Arabs). Demographic and clinical data were compared between ethnic groups. RESULTS: The prevalence of HS in Israeli Arabs was found to be 0.5%, fivefold higher than in Jews. Arab patients were younger (35.3 vs. 40.5 years, P < 0.001) and mostly male (52% vs. 35.7%, P < 0.001), with lower rates of co-morbidities, including smoking (40.8% vs. 55.7%, P < 0.001), hyperlipidemia, and depression as well as a higher rate of dissecting cellulitis (10.2% vs. 1.9%, P = 0.008). HS was more severe in Arabs, but of shorter duration, with mainly axillary involvement (79.6% vs. 57.9%, P = 0.004). Treatment with hormones was more common in Jews, and with biologic agents in Arabs. CONCLUSIONS: The findings suggest a different phenotype of HS in Arabs, warranting further study.

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.

Vitiligo and Crohn's disease form an autoimmune cluster: insights from a population-based study.

BACKGROUND: While the coexistence of vitiligo and Crohn's disease (CD) has been reported in individual patients, the epidemiological association between these autoimmune conditions remains inconclusive. OBJECTIVE: To assess the bidirectional association between vitiligo and CD. 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 CD. Adjusted hazard ratios (HRs) and adjusted odds ratios (ORs) were calculated by multivariable Cox regression and logistic regression, respectively. RESULTS: The incidence rate of new-onset CD was evaluated at 3.6 (95% CI, 2.7-4.9) cases per 10,000 person-years (PY) in patients with vitiligo and 2.4 (95% CI, 2.0-2.9) cases per 10,000 PY in controls. Patients with vitiligo experienced an elevated risk of CD (fully adjusted HR, 1.60; 95% CI, 1.10-2.34; p = 0.015). Congruently, a history of preexisting CD predicted elevated odds of having subsequent vitiligo (fully adjusted OR, 1.49; 95% CI, 1.15-1.93; p = 0.002). Compared to other patients with vitiligo, those with vitiligo and comorbid CD were older and had a higher prevalence of diabetes mellitus, hyperlipidemia, and hypertension but a comparable all-cause mortality rate. CONCLUSIONS: The current study depicts a robust bidirectional association between vitiligo and CD. This knowledge is of clinical implication for physicians managing patients with both conditions. The diagnostic threshold for CD should be lowered in vitiligo patients with compatible symptoms.

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.

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.

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.

Vitiligo and systemic sclerosis: Are they associated?- Lessons from a population-based study.

BACKGROUND: The epidemiological relationship of vitiligo with systemic sclerosis (SSc) remains to be precisely evaluated. OBJECTIVE: To investigate the bidirectional association between vitiligo and SSc. METHODS: A population-based study was carried out 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 SSc. Adjusted hazard ratios (HRs) and adjusted odds ratios (ORs) were calculated by the Cox regression and logistic regression, respectively. RESULTS: The incidence rate of new-onset SSc was calculated at 2.4 (95% CI, 1.6-3.4) and 0.4 (95% CI, 0.3-0.6) cases per 10,000 person-years among patients with vitiligo and controls, respectively. Patients with vitiligo had an increased risk of SSc (fully adjusted HR, 5.37; 95% CI, 3.03-9.54; p < 0.001). Correspondingly, a history of SSc predicted elevated odds of developing vitiligo (fully adjusted OR, 2.09; 95% CI, 1.23-3.55; p = 0.006). Relative to other patients with vitiligo, those with vitiligo and comorbid SSc were older and had a higher prevalence of ischaemic heart disease, hyperlipidaemia, and hypertension. CONCLUSIONS: A robust bidirectional association exists between vitiligo and SSc. This knowledge is valuable for physicians managing patients with both conditions. Patients with vitiligo and comorbid SSc might be monitored for cardiovascular and metabolic comorbidities.

Association of anti-Ro seropositivity with cardiac rhythm and conduction disturbances.

AIMS: Anti-Ro/La autoantibodies are especially prevalent in autoimmune diseases but are also relatively frequent in healthy adults. Their arrhythmogenic effect on the immature cardiac conductive system is well established, with substantial evidence demonstrating an increased risk for congenital atrioventricular block in neonates of seropositive mothers. Despite their wide distribution and their arrhythmogenic potential effect, there are no large population studies conducted in seropositive adults. Thus, this is the first large population-based study to examine the association of anti-Ro/La seropositivity with cardiac rhythm and conduction disturbances. METHODS AND RESULTS: This cross-sectional designed study involved the electronic health records of the largest health maintenance organization in Israel. All subjects that were tested positive for anti-Ro/anti-La antibodies between the years 2002 and 2019 were included and were matched by age, gender, and place of residence, with controls. Rates of different cardiac rhythm and conduction disturbances were compared between groups. Sensitivity analyses were performed using propensity score matching. The study population included 17 231 anti-Ro/La seropositive subjects and 84 368 controls. Anti-Ro seropositive patients had higher rates of conduction disturbances (3.0 vs. 1.7%, P < 0.001) and rhythm disturbances (10.5 vs. 7.0%, P < 0.001). Patients who tested positive for anti-La alone did not demonstrate a significant association with arrhythmias. Multivariate logistic regression analysis, controlling for possible confounders, showed an increased risk for cardiac conduction disturbances [odds ratio (OR) 1.44, 95% confidence interval (CI) 1.25-1.66, P < 0.001], as well as for cardiac rhythm disturbances (OR 1.21, 95% CI 1.11-1.31, P < 0.001) among anti-Ro seropositive patients. However, the association with rhythm disturbances was more robust in certain subgroup analyses. CONCLUSIONS: Anti-Ro seropositivity is positively associated with adult cardiac conduction disturbances and, to a lesser extent, cardiac rhythm disturbances, regardless of the presence of concurrent autoimmune disease.

The risk, predictors and outcomes of amyloidosis in ankylosing spondylitis: a longitudinal population-based cohort study.

OBJECTIVES: The risk of amyloidosis during the course of AS is yet to be firmly established. We aimed to evaluate the risks, predictors and prognostic outcomes of amyloidosis among patients with AS. METHODS: A population-based cohort study was conducted comparing AS patients (n = 5911) with age-, sex- and ethnicity-matched control subjects (n = 29 007) with regard to incident cases of amyloidosis. Hazard ratios (HRs) and odds ratios (ORs) were estimated by Cox regression and logistic regression analyses, respectively. RESULTS: The incidence rate of amyloidosis was 2.15 (95% CI 1.09, 2.82) and 0.35 (95% CI 0.16, 0.66) per 10 000 person-years among patients with AS and controls, respectively. The risk of incident amyloidosis was >6-fold higher among patients with AS relative to control subjects [adjusted HR 6.16 (95% CI 2.43, 15.62); P < 0.001]. A higher comorbidity burden [OR 1.36 (95% CI 1.08, 1.73); P = 0.010] was found to predict an increased susceptibility to amyloidosis in AS patients. Compared with other patients with AS, those with AS and comorbid amyloidosis had a 14-fold increased risk of end-stage renal disease necessitating dialysis [adjusted HR 14.7 (95% CI 2.0, 107.2); P = 0.008], but comparable risk of all-cause mortality [adjusted HR 2.16 (95% CI 0.69, 6.71); P = 0.174]. CONCLUSIONS: Patients with AS are at an increased risk of amyloidosis. AS-associated amyloidosis is associated with an elevated risk of dialysis dependence. Awareness of the burden and consequences of this complication may be of help for rheumatologists managing patients with AS.

Ankylosing Spondylitis and the Risk of Hip Fractures: a Matched Cohort Study.

BACKGROUNDS: It has been hypothesized that ankylosing spondylitis is associated with an increased risk of incident hip fractures due to osteoporosis and risk of falls but the supporting evidence is limited and mixed. OBJECTIVES: To assess the risk of hip fractures in a large cohort of patients with ankylosing spondylitis compared to a matched cohort. DESIGN: A retrospective cohort study. SUBJECTS: Men and women diagnosed with ankylosing spondylitis from 1 January 2002 to 31 December 2018. Matching in a 5:1 ratio was based on age and sex. Follow-up ended on 23 June 2019. MAIN MEASURES: Cox regression models adjusting for confounders defined in a causal inference framework were used to determine the hazard ratio for hip fractures. KEY RESULT: The final cohorts included 5,909 ankylosing spondylitis patients and 28,671 matched patients. The ankylosing spondylitis cohort had a mean age of 49 (17) years and was composed of 3,762 (64%) men, 3,638 (62%) patients born in Israel, and 1,532 (26%) patients of low residential socioeconomic status. During 45,388 and 224,192 cumulative person-years of follow-up, the ankylosing spondylitis and matched cohorts had 2.47 and 1.63 cases of hip fractures per 1,000 person-years, respectively. Ankylosing spondylitis patients also developed hip fractures earlier (74 [13] vs. 79 [10] years, p = 0.002). Ankylosing spondylitis was associated with hip fractures in the unadjusted (HR = 1.52, 95% CI [1.23-1.88]) and adjusted (HR = 1.56, 95% CI [1.27-1.93]) models. The association was evident in men (HR = 1.65, 95% CI [1.25-2.18]) and women (HR = 1.48, 95% CI [1.07-2.05]). CONCLUSION: This study found that ankylosing spondylitis patients developed hip fractures earlier and more often compared to a matched cohort. This study suggests that ankylosing spondylitis patients might benefit from more proactive screening, mitigation, and prevention of risk factors for hip fractures.

Factors associated with treatment satisfaction in patients with hidradenitis suppurativa: results from the Global VOICE project.

BACKGROUND: Nearly half of patients with hidradenitis suppurativa (HS) report dissatisfaction with their treatment. However, factors related to treatment satisfaction have not been explored. OBJECTIVES: To measure associations between treatment satisfaction and clinical and treatment-related characteristics among patients with HS. METHODS: Treatment satisfaction was evaluated utilizing data from a cross-sectional global survey of patients with HS recruited from 27 institutions, mainly HS referral centres, in 14 different countries from October 2017 to July 2018. The primary outcome was patients' self-reported overall satisfaction with their current treatments for HS, rated on a five-point scale from 'very dissatisfied' to 'very satisfied'. RESULTS: The final analysis cohort comprised 1418 patients with HS, most of whom were European (55%, 780 of 1418) or North American (38%, 542 of 1418), and female (85%, 1210 of 1418). Overall, 45% (640 of 1418) of participants were either dissatisfied or very dissatisfied with their current medical treatment. In adjusted analysis, patients primarily treated by a dermatologist for HS had 1·99 [95% confidence interval (CI) 1·62-2·44, P < 0·001] times the odds of being satisfied with current treatment than participants not primarily treated by a dermatologist. Treatment with biologics was associated with higher satisfaction [odds ratio (OR) 2·36, 95% CI 1·74-3·19, P < 0·001] relative to treatment with nonbiologic systemic medications. Factors associated with lower treatment satisfaction included smoking (OR 0·78, 95% CI 0·62-0·99; active vs. never), depression (OR 0·69, 95% CI 0·54-0·87), increasing number of comorbidities (OR 0·88 per comorbidity, 95% CI 0·81-0·96) and increasing flare frequency. CONCLUSIONS: There are several factors that appear to positively influence satisfaction with treatment among patients with HS, including treatment by a dermatologist and treatment with a biologic medication. Factors that appear to lower treatment satisfaction include active smoking, depression, accumulation of comorbid conditions and increasing flare frequency. Awareness of these factors may support partnered decision making with the goal of improving treatment outcomes. What is already known about this topic? Nearly half of patients with hidradenitis suppurativa report dissatisfaction with their treatments. What does this study add? Satisfaction with treatment is increased by receiving care from a dermatologist and treatment with biologics. Satisfaction with treatment is decreased by tobacco smoking, accumulation of comorbid conditions including depression, and higher flare frequency. What are the clinical implications of this work? Awareness of the identified factors associated with poor treatment satisfaction may support partnered decision making and improve treatment outcomes.

TNF inhibitors have a protective role in the risk of dementia in patients with ankylosing spondylitis: Results from a nationwide study.

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic progressive and debilitating form of arthritis with associated extra-articular features including uveitis, intestinal and lung apical inflammation and psoriasis. Putative associations between AS and neurologic disorders has been relatively overlooked. The purpose of this study is to assess the link between AS and major neurologic disorders and whether treatment with Tumor-Necrosis-Factor inhibitors (TNFi) has an impact on that association. METHODS: A retrospective cross-sectional study was carried out based on the Clalit Health Services (CHS) computerized database. AS patients were compared to age- and gender-matched controls with respect to the proportion of Alzheimer's disease (AD), Parkinson's disease (PD), epilepsy, and multiple sclerosis (MS). The impact of AS therapy (biologic vs conventional therapy) was assessed as well. RESULTS: 4082 AS patients and 20,397 age- and gender-matched controls were identified. AS was associated with a higher prevalence of AD (odds-ratio(OR) 1.46 [95%Confidence-interval(CI) 1.13-1.87], p = 0.003), epilepsy (OR 2.33 [95%CI 1.75-3.09] p < 0.0001) and PD (OR 2.75 [95%CI 2.04-3.72], p < 0.0001), whereas no statistically significant association was found for MS. Association with PD remained significant in the multivariate analysis (OR 1.49 [95%CI 1.05-2.13],p = 0.027). Within AS patients, the use of TNFi (OR 0.10 [95%CI 0.01-0.74], p = 0.024) were associated with a lowered risk of developing AD. CONCLUSION: AS is positively associated with AD, PD, and epilepsy but not MS. AS patients treated with TNFi have lower rates of AD.

Psoriasis and Renal Disorders: A Large-Scale Population-Based Study in Children and Adults.

BACKGROUND: Psoriasis is a systemic disease with associated comorbidities. An association between renal diseases and psoriasis has previously been reported in adult patients, but little is known about renal diseases in pediatric patients. OBJECTIVE: To determine whether there is an association between psoriasis and renal comorbidities in adult and pediatric patients. METHODS: This cross-sectional study analyzed the database of the largest health care maintenance organization in Israel. Logistic regression was used to calculate odds ratios to compare 68,836 psoriatic patients and 68,836 controls with respect to renal comorbidities. RESULTS: In adults, an inverse association emerged between psoriasis and dialysis (OR, 0.69; 95% CI, 0.58-0.83) and kidney transplantation (OR, 0.60; 95% CI, 0.43-0.83), a positive association with other kidney diseases (OR, 1.09; 95% CI, 1.05-1.13), and no association between psoriasis and chronic kidney disease (OR, 1.03; 95% CI, 0.98-1.09). Comparing 9,127 pediatric patients and 9,478 controls, no association was found between psoriasis and renal comorbidities, chronic kidney disease (OR, 0.90; 95% CI, 0.33-2.48), dialysis (OR, 2.06; 95% CI, 0.19-22.69), kidney transplantation (OR, 0.34; 95% CI, 0.04-3.29), or other kidney diseases (OR, 0.98; 95% CI, 0.79-1.23), even after a multivariate analysis adjusting for putative confounders. CONCLUSION: As opposed to adult patients, pediatric patients with psoriasis were not shown at risk of kidney diseases.

Atopic Dermatitis and Infertility: A Nationwide Retrospective Cohort Study.

BACKGROUND: Given that common pathophysiological factors play a role in atopic dermatitis (AD) and infertility, we assumed that the 2 conditions might demonstrate an epidemiological association. Large-scale epidemiological data on this topic are lacking. OBJECTIVES: The aim of this work was to evaluate the potential association between AD and infertility in a broad community-based population. METHODS: A nationwide retrospective cohort study was conducted, analyzing the association between AD and infertility. We compared AD patients diagnosed by a dermatologist between 2002 and 2018 and a matched control group. The study population was subdivided according to age into adults (age ≥18 years) and children (age <18 years), and was further subdivided according to AD severity, classified as either mild or moderate-to-severe according to AD-related drug use and healthcare services utilization. RESULTS: The study included 127,150 patients with AD and 127,071 comparison enrollees. AD was associated with a higher prevalence of infertility than that of the control group (1.4 and 1.1%, respectively). The prevalence of infertility, per 1,000 patient-years, was increased in patients with AD compared to that of the control group (2.17 and 1.7, respectively). Multivariate analysis for infertility demonstrated that AD was a key risk factor for infertility in both males and females with mild AD and moderate-to-severe AD. CONCLUSION: A significant association between AD and infertility was observed. This association suggests that infertility may be an additional manifestation of AD. Further studies are warranted to evaluate the impact of AD management in the setting of infertility and vice versa.

Alopecia Areata as a Proximal Risk Factor for the Development of Comorbid Depression: A Population-based Study.

Alopecia areata and depression tend to co-occur; however, their temporal association has not been comprehensively investigated. The aim of this study was to examine the temporal association between alopecia areata and depression. The study included only cases with a comorbid presentation of alopecia areata and depression (n = 1,936), extracted from the databases of the Clalit Health Services, Israel. Survival analyses were used to assess the cumulative probability of receiving alopecia areata as comorbid diagnosis in the years following depression, and vice versa, compared with the opposite trajectory. The results indicate that patients with alopecia areata had greater odds of subsequent depression within 2 years from alopecia areata diagnosis, and showed a steeper increase in cumulative probability of depression as time progressed (log-rank =336.38, p < 0.001), compared with the opposite trajectory. All patients with alopecia areata had comorbid depression within 10 years of alopecia areata, compared with 70% of depression patients receiving diagnoses of comorbid alopecia areata within the same time-frame.

Increased risk of venous thromboembolism among patients with familial Mediterranean fever.

INTRODUCTION: Familial Mediterranean Fever (FMF) is an auto inflammatory disease characterized by acute febrile attacks, serositis, arthritis and skin rash. Previous studies have identified an association between venous thromboembolism (VTE) and various inflammatory and autoimmune disorders, driven in large part by inflammatory processes. Despite these established associations, there remains a paucity of data linking FMF to VTE. The purpose of this study is to evaluate the association between VTE in patients with FMF compared to matched controls. METHOD: A population based cross-sectional study was performed utilizing the electronic medical database of Israel's largest healthcare provider, Clalit Health Services. Using this database, we looked at the prevalence of VTE in a cohort of FMF patients compared to matched controls. Univariate logistic regression was used to evaluate the association between FMF and VTE. Multivariate analysis was conducted to adjust for age, sex, socioeconomic status and comorbidities associated with VTE. RESULTS: A total of 6534 FMF patients were identified and matched with an equal number of controls. In univariate analysis the cumulative percent of VTE was higher in FMF patient compared to matched controls (FMF 3%, Control 2%). In a multivariate logistic regression analysis FMF was found to be independently associated with VTE (HR 1.96, P < 0.001). CONCLUSION: FMF is associated with increased risk of VTE. This association is likely the result of a chronic and persisting inflammatory state. Physicians should be aware of this sequela and care must be undertaken to control unbalanced disease.