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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To identify predicators of patients with fibromyalgia (FM) that are associated with a severe COVID-19 disease course. Methods: We utilized the data base of the Clalit Health Services (CHS); the largest public organization in Israel, and extracted data concerning patients with FM. We matched two subjects without FM to each subject with FM by sex and age and geographic location. Baseline characteristics were evaluated by t-test for continuous variables and chi-square for categorical variables. Predictors of COVID-19 associated hospitalization were identified using univariable logistic regression model, significant variables were selected and analyzed by a multivariable logistic regression model. Results: The initial cohort comprised 18,598 patients with FM and 36,985 matched controls. The mean age was 57.5± 14.5(SD), with a female dominance of 91%. Out of this cohort we extracted the study population, which included all patients contracted with COVID-19, and consisted of 571 patients with FM and 1008 controls. By multivariable analysis, the following variables were found to predict COVID-19 associated hospitalization in patients with FM: older age (OR, 1.25; CI, 1.13–1.39; p<0.001), male sex (OR, 2.63; CI, 1.18–5.88; p<0.05) and hypertension (OR, 1.75; CI, 1.04–2.95; p<0.05). Conclusion: The current population-based study revealed that FM per se was not directly associated with COVID-19 hospitalization or related mortality. Yet classical risk factors endangering the general population were also relevant among patients with FM. [ABSTRACT FROM AUTHOR]

Objective To assess the association between FMF and asthma. Methods This study was designed as a cross-sectional study. All patients diagnosed with FMF between 1 January 2000 and 31 December 2016 who were prescribed colchicine were included in the study. Controls were matched by sex, date of birth, residential socioeconomic status and country of birth. Logistic regression models were used to determine the odds ratio for asthma in FMF patients and controls. Results A total of 7098 FMF patients who were prescribed colchicine were identified. Of them, 3547 (50%) were females, 3632 (51%) were of low residential socioeconomic status and 6160 (87%) were born in Israel. Their median age at the end of follow-up was 37 years (23–54). In an unadjusted logistic regression, FMF was associated with asthma [odds ratio (OR)=1.33, 95% CI: 1.17, 1.51; P  <0.001]. The association persisted after adjusting for sex, socioeconomic status and country of birth (OR=1.33, 95% CI: 1.18, 1.52; P  <0.001) Conclusion FMF is positively associated with asthma. Further research is required to validate our results and explore possible explanations of this association. These findings cast doubt on previous studies implying FMF to be a protective factor from asthma. [ABSTRACT FROM AUTHOR]

Background: Dermatomyositis (DM) and polymyositis (PM) are two rare autoimmune disorders occasionally described with dysthyroidism; however, no solid evidence still proves such an association. Aim: To evaluate the prevalence of dysthyroidism among DM/PM patients. Design and setting: A nation-wide case-control study was conducted. Methods: From the Clalit Health Services health records database, we extracted 2085 (DM = 1475 (70.7%), PM = 610 (29.3%)) PM/DM cases and 10 193 sex-age matched controls in the period 2000-2018. Both univariate and multivariate analyses were performed to evaluate the link dysthyroidism and PM/DM. Survival analysis was also performed. Results: The rate of hyperthyroidism was significantly (P = .0097) higher in cases (n = 40, 1.9%) with respect to controls (n = 123, 1.2%). Similarly, the rate of hypothyroidism was significantly (P < .0001) associated with cases (n = 234, 11.2%) when compared to controls (n = 853, 8.4%). At the multivariate logistic regression analysis, both DM (OR 1.31 [95%CI 1.07-1.60], P = .0087) and PM (OR 1.54 [95%CI 1.21-1.95], P = .004) were significantly associated with hypothyroidism, whereas DM (OR 1.70 [95%CI 1.10-2.61], P = .0165) but not PM (OR 1.45 [0.83- 2.55], P = .1947) was found to be associated with hyperthyroidism. Subjects with PM and positive for anti-Sjögren's syndrome-related antigen A (SSA) auto-antibody displayed a significant risk of developing hyperthyroidism (OR 5.85 [95%CI 1.02- 33.74], P = .0480), whereas individuals with DM and positive for antinuclear antibody (ANA) had a higher risk of developing hyperthyroidism (OR 2.65 [95%CI 1.00-7.03], P = .0498). Conclusions: Physicians treating PM/DM patients should consider screening for thyroid dysfunction on a regular basis. [ABSTRACT FROM AUTHOR]

To evaluate the proportion and the long-term prognostic significance of heart failure (HF) in sarcoidosis patients. Data extracted from a large Israeli healthcare provider's database were used to study sarcoidosis patients and matched non-sarcoidosis controls since 2000 to 2016. The proportion of HF was compared between the groups, and the associations between sarcoidosis, HF, and all-cause mortality were assessed. Included were 3,993 sarcoidosis patients and 19,856 age- and sex-matched controls. The proportion of HF patients was higher among the former (10.9% and 5.3%, respectively). A logistic regression model for multivariable analysis for covariates found sarcoidosis to be independently associated with HF (Odds Ratio (OR) 2.09 confidence interval (CI) 1.83–2.39). A total of 710 sarcoidosis patients (17.8%) and 2,121 controls (10.7%) died during the study period (p < 0.001). A multivariable survival analysis found an estimated hazard ratio (HR) of 1.84 (95%CI 1.67–2.02), indicating a significant association between sarcoidosis and risk for all-cause mortality. Our analysis also revealed a significant association between HF and risk for all-cause mortality (HR 3.05, 95%CI 2.77–3.36). Sarcoidosis is independently associated with HF, and both are independently associated with all-cause mortality. [ABSTRACT FROM AUTHOR]

Background: Mood disorders, such as anxiety and depression, are extremely prevalent among patients with rheumatoid arthritis (RA). In this study, we assessed the impact of treatment with tocilizumab (TCZ), an IL‐6 antagonist, upon anxiety and depressive symptoms in a cohort of RA patients. Materials and Methods: Study participants were adults diagnosed with RA who received a weekly subcutaneous injection of tocilizumab for 24 weeks. We used the Hamilton Depression (HDRS) and Anxiety (HAMA) scores in order to assess the severity of depression and anxiety, respectively. RA disease activity indices and depression and anxiety levels were assessed at baseline, 4 weeks and study completion. Results: Ultimately, 91 patients were included in the study. The mean age was 54 years, and the majority were female (79%). The mean score in all disease activity indices as well as depression and anxiety levels decreased dramatically from baseline to study completion. Sixty patients (66%) demonstrated a significant decrease in anxiety and/or depression levels. When logistic regression was performed, an HDRS score indicative of depression at study baseline demonstrated an independent association with a significant psychiatric response whilst older age and increased baseline weight were negatively associated. HAMA and HDRA scores correlated with the following RA disease activity parameters, respectively; HAQ‐DI (r =.4,.42), DAS28 (r =.29,.32) and CDAI (0.28 and 0.33), all of them were statistically significant (P <.01). Conclusions: This study has demonstrated a favourable impact of TCZ therapy on parameters reflecting depression and anxiety severity in patients with RA. [ABSTRACT FROM AUTHOR]

Aims Of the Study: Familial Mediterranean fever (FMF) is a hereditary, auto-inflammatory disease, characterised by recurrent, self-limiting attacks of fever with inflammation of the serosal membranes, joints, and skin. Chronic inflammation was previously associated with increased risk for ischaemic heart disease (IHD). However, the association between FMF and IHD remains unclear. The objective of this study is to determine whether this association exists.Methods: Utilising the database of the largest health-care provider in Israel, a cross-sectional study was performed. The incidence of IHD was compared between patients diagnosed with FMF and age and sex-matched controls. Chi-square and t-test were used for categorial and continuous variables, and cox logistics regression model was used for multivariate analysis. Survival analysis was made using Kaplan-Meier plots and log-rank test.Results: The study included 7670 patients diagnosed with FMF and an equal number of controls without FMF. In a univariate analysis FMF was found to be associated with higher prevalence of IHD (OR 1.33) and increased mortality (OR 1.29). In a multivariate analysis FMF was found to be independently associated with increased risk for IHD (OR 1.44).Conclusion: The study shows that FMF is associated with both increased risk for IHD and higher mortality rates. An early diagnosis and treatment of this disease can potentially improve patients' life expectancy and decrease cardiac comorbidities. [ABSTRACT FROM AUTHOR]

Background and objectives: Rheumatoid arthritis (RA) is the most common inflammatory joint disorder presenting also with extra-articular manifestations. As many other autoimmune diseases, it has been suggested that infectious diseases might contribute to its emergence. Hepatitis viruses were suggested by several reports as a trigger of RA onset. We aimed to assess the association between RA and chronic hepatitis B viral infection (HBV). Methods: Patients with RA were compared with age- and sex-matched controls regarding the proportion of chronic HBV infection in a case-control study. The chi-square and t tests were used for univariate analysis, whereas a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services. Results: There was a significantly higher proportion of chronic HBV infection in RA patients compared with controls (1.19% vs 0.63%, respectively; p < 0.001). In a multivariate logistic regression analysis, RA was significantly associated with chronic HBV infection (OR = 1.89, 95%CI 1.55–2.29, p < 0.001). Conclusions: Patients with RA have a greater proportion of chronic HBV infection than matched controls. Screening for HBV infection among RA patients may be warranted. [ABSTRACT FROM AUTHOR]

Objectives: Several epidemiological studies have investigated the link between silicone breast implants (SBIs) and autoimmune/rheumatic disorders, reporting inconsistent results. We aimed to evaluate the association between SBIs and the most clinically relevant autoimmune/rheumatic disorders using a large, population-based database.Methods: In this cross-sectional study, we used the computerized databases of Maccabi Healthcare Services (MHS), which include up to 20 years of data on 2 million members. Women with SBIs were identified by procedure and diagnosis codes, clinical breast examinations and mammography referrals. Autoimmune/rheumatic disorders were identified using the International Classification of Diseases 9th revision (ICD-9) codes. Multivariable logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). A Cox's proportional hazards model was used to calculate the hazard ratios (HRs) and 95% CIs among a subgroup of SBI recipients for whom the year of SBIs insertion was available.Results: We included 24 651 SBI recipients and 98 604 matched SBI-free women. The adjusted OR between SBIs and being diagnosed with any autoimmune/rheumatic disorders was 1.22 (95% CI 1.18-1.26). The strongest association with SBIs (OR > 1.5, p < 0.001) was recorded for Sjögren's syndrome, systemic sclerosis (SSc) and sarcoidosis (OR of 1.58, 1.63 and 1.98, respectively). Similar results were calculated when analysis was limited to women with no breast cancer history. A multivariable Cox regression model yielded a HR of 1.45 (95% CI 1.21-1.73) for being diagnosed with at least one autoimmune/rheumatic disorder in women with SBI compared with those without.Conclusions: SBIs seem to be associated with higher likelihood of autoimmune/rheumatic disorders diagnosis. [ABSTRACT FROM AUTHOR]

Background Association between antiphospholipid syndrome in systemic lupus erythematosus ( SLE) and valvular heart disease ( VHD) is well reported, but relatively few studies have been carried out to establish the linkage between VHD and SLE itself. We aimed to investigate link between VHD and SLE and to evaluate the association of diverse factors with VHD among these patients in a large-scale population-based study. Materials and methods We used the databases of the largest state-mandated health service organization in Israel. All SLE patients were included ( n = 5018) as well as their age and sex-matched controls ( n = 25 090), creating a cross-sectional population-based study. Medical records of all subjects were analysed for documented VHD and the presence of antiphospholipid antibodies ( aPLs). A logistic regression model was carried out to evaluate the diverse factors including SLE and aPLs as independent risk factors for VHD. Results Valvular heart disease were found to be more frequent among SLE group when compared to controls (aortic stenosis, 1·08% vs. 0·35% respectively, P < 0·001; aortic insufficiency, 1·32% vs. 0·29% respectively, P < 0·001; mitral stenosis, 0·74% vs. 0·21% respectively, P < 0·001; mitral insufficiency, 1·91% vs. 0·39% respectively, P < 0·001). Male sex, hypertension, aPLs and SLE were found to be significant independent risk factors for VHD. Conclusion All VHD are more prevalent among SLE patients when compared to controls. SLE and aPLs are independent risk factor for VHD ( OR of 2·46 and 1·7, respectively). Physicians must be aware of such significant association, and routine echocardiography should be considered in SLE patients regardless of their aPL status. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate if association exist between rheumatoid arthritis and malignant diseases.Methods: A cross-sectional study was conducted comparing rheumatoid arthritis patients with age and gender matched controls regarding the proportion of patients with comorbid malignant conditions. Chi-square tests and t-tests were used for univariate analysis. A logistic regression model was used for multivariate analysis. The study was performed utilising the medical database of Clalit Health Services.Results: The study group included 11 782 rheumatoid arthritis patients and 57 973 controls. The total proportion of malignancies was significantly higher in the study group than in the control group (21.4% vs 11.2%; P<.001). The disease for which there was the strongest association among patients with rheumatoid arthritis was non-Hodgkin's lymphoma (1.1% vs 0.6%; P<.01). After multivariate analysis, lung cancer was not found to be significantly associated with rheumatoid arthritis.Conclusion: Rheumatoid arthritis is associated with several malignant disorders, in particular non-Hodgkin's lymphoma. Appropriate measures for non-Hodgkin's lymphoma screening in this patient population should be considered. [ABSTRACT FROM AUTHOR]

Objective. To assess the adherence and persistence with allopurinol therapy among gout patients and to identify risk factors for therapy discontinuation.Methods. The study population included adults in Maccabi Healthcare Services, a 2-million member health maintenance organization in Israel, who were diagnosed with gout between 2002 and 2008. Adherence with allopurinol was retrospectively assessed by calculating the proportion of days covered of dispensed prescriptions. Persistence was assessed by calculating the mean proportion of follow-up days covered with allopurinol for every study participant.Results. A total of 7644 patients were identified. Among men, the incidence of gout was strongly associated with age, ranging from 0.5 per 1000 among adults younger than 45 years to more than 36 per 1000 among elderly men aged 85 or older). A total of 1331 gout patients (17% of the study population) were adherent to allopurinol therapy, 36% and 47% had partial and poor adherence, respectively. Persistence analysis indicated that the average duration until therapy was discontinued was similar among men (358 days) and women (379 days). Women aged 45–64 years, non-married individuals, those of low socioeconomic status and those with lower body weight were more likely to discontinue therapy. Logistic regression (n = 2471, 32% of the study sample) showed a 4.5 risk of non-compliance among 45- to 65-year-old women. Better compliance was achieved among those with comorbidities, particularly among patients with concomitant cardiovascular disease.Conclusion. Only one out of six gout patients is adherent with allopurinol. Intervention programmes to increase adherence with treatment should focus on high-risk populations. [ABSTRACT FROM PUBLISHER]

Background: Systemic sclerosis (SSc) can clinically present with psychological symptoms, including pain, depression, and distress about disfigurement, physical and social functioning. The existing small studies have reported a prevalence of depression ranging from 36% to 65% among SSc patients, likely reflecting the disease impact on the patient's self-image and function.Aim Of the Study: To investigate the association between SSc and depression using big data analysis methods.Methods: We designed a nation-wide epidemiological survey relying on a large database of 2500 SSc patients and explored the relationship between SSc and depression, but also the impact of depression on the survival of SSc patients. Chi-squared and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis.Results: The proportion rate of depression among SSc patients was significantly higher than controls (16.2% vs 10.9%), and this proportion was even higher in female SSc patients and of low socioeconomic status. At the multivariate logistic regression, SSc was found to be an independent risk factor for depression with an OR of 1.55 (95%CI 1.29-1.88, p < 0.0001). No significant association was found between SSc-specific autoantibodies (anti-centromere, anti-Scl-70, anti-RNA polymerase III and anti-RNP) status and the risk of depression. Depression was not found to have a significant impact on the survival of SSc patients with an HR of 1.06 (0.80-1.42).Conclusions: This study provides further support for the high prevalence of depression in SSc patients and therefore, SSc patients may benefit from a screening approach and a broad supportive care program. [ABSTRACT FROM AUTHOR]

Background Behcet's disease (BD) is a multi-systemic chronic inflammatory disorder which involves the vasculature tree of all sizes. The current study's aim was to examine the association between BD and the development of ischemic heart disease (IHD) and its potential impact as a cardiovascular risk factor. Methods This study was conducted as a case-control study utilizing the database of Clalit Health Services. The proportion of IHD was compared between patients diagnosed with BD and age- and gender-matched controls. Univariate analysis was performed using Chi-square and Student t -test and a multivariable analysis was performed using a logistic regression model. Results 871 BD patients and 4439 age- and gender-matched controls were included in this study. The proportion of IHD amongst BD patients was increased in comparison with controls (10.9% vs. 7.52% respectively, p -value = 0.001). BD was associated with IHD on multivariable analysis (odds ratio 1.485, 95% confidence interval 1.106–1.982). When the comparison between BD patients with IHD and controls with IHD was stratified according to risk factors, age younger than 70 and male gender were both found to be significantly elevated in the BD group. Conclusions BD patients have an increased proportion of IHD in comparison with matched controls. Our findings demonstrate that the population of BD patients with IHD has a higher proportion of younger males in comparison with controls with IHD. [ABSTRACT FROM AUTHOR]

Background: Psychiatric disorders occur in a considerable proportion of patients with rheumatoid arthritis (RA), often reflecting the difficulties of these patients in coping with a chronic debilitating disorder.Aim Of the Study: To evaluate the proportion of anxiety disorder in RA patients using a large database analysis.Methods: The study was designed as a case-control population-based study using data from the Clalit Health Services (CHS) database. Patients were defined as having RA or anxiety disorder when there was at least one documented diagnosis identified by the International Classification of Diseases-9 (ICD-9) from the medical records. The proportion of anxiety disorder was compared between RA patients and controls. A logistic regression model was used to estimate the association between RA and anxiety disorder in a multivariate analysis adjusted for age, gender and socioeconomic status (SES).Results: The study included 11,782 patients with RA and 57,973 age- and sex-frequency matched controls. The proportion of anxiety in RA patients was higher than in controls (7.1% vs 6.3%, p=0.001). In multivariate analysis, RA was found to be independently associated with anxiety (OR 1.11 [95%CI 1.03-1.20], p=0.01). Our study has some shortcomings, as its cross-sectional nature does not allow to make inferences about a causal relationship between RA and anxiety.Conclusion: Our study confirms the higher proportion of anxiety in RA patients, especially young women with low SES. Physicians should be aware of such findings and, therefore, apply proper screening strategies. [ABSTRACT FROM AUTHOR]

Background Over the last few decades, several studies have demonstrated the connection between Rheumatoid Arthritis (RA) and Ischemic Heart Disease (IHD). The additional risk for RA patients to also suffer from IHD varies based on the definition of the diseases in question, the populations evaluated, and the variables included in the studies. Objectives To quantify the association between RA and IHD according to certain demographics as well as traditional cardiovascular risk factors in order to determine their roles in the development of coronary artery disease among patients with RA. Methods Using data from the largest HMO in Israel, the Clalit Health Services, we selected for patients with RA. These patients were compared with age and sex matched controls with regards to the prevalence of IHD in a case–control study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. Results The study included 11,782 patients with RA and 57,973 age and sex matched controls. The prevalence of IHD in patients with RA was increased compared with the prevalence in controls (16.6% and 12.8% respectively, P < 0.001). In a multivariate analysis, RA was associated with higher proportions of IHD (OR 1.346, 95% confidence interval 1.255–1.431). [ABSTRACT FROM AUTHOR]