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Background: The skin–gut axis, characterized by bidirectional communication between the skin and gut, plays a crucial role in the pathogenesis of psoriasis and inflammatory bowel diseases (IBD). Objectives: We aimed to explore the association between psoriasis and IBD and identify predictors associated with IBD development among patients with psoriasis. Design: Retrospective cohort study. Methods: A retrospective study which utilized an electronic database from the Meuhedet Health Maintenance Organization (MHMO) in Israel. Psoriasis was categorized as severe if any systemic agent or phototherapy was administered. Univariate and multivariate logistic regressions were used to identify specific predictors for IBD, with adjustments made for potential confounders. The study received approval from the Ethical Committee of the MHMO. Results: In total, 61,003 adult patients who were diagnosed with psoriasis between 2000 and 2022 were included. Among them, 1495/61,003 patients (2.4%) were diagnosed with IBD, as compared to 3834/244,012 patients (1.6%) in the non-psoriasis group [adjusted odds ratio (OR): 1.47; 95% confidence interval (CI): 1.37–1.56; p < 0.001]. Increased age (OR: 1.01; 95% CI: 1.01–1.02; p < 0.001), male gender (OR: 1.22; 95% CI: 1.03–1.45; p = 0.024), and Jewish ethnicity (OR: 2.5; 95% CI: 1.2–4.1; p < 0.001) were identified as significant risk factors for IBD. Spondyloarthropathies, including psoriatic arthritis (OR: 2.27; 95% CI: 1.86–2.77; p < 0.001) and ankylosing spondylitis (OR: 2.82; 95% CI: 1.5–5.32; p < 0.05), were associated with a higher prevalence of IBD. Furthermore, severe psoriasis was significantly associated with a higher likelihood of IBD, compared to mild psoriasis (OR: 16.03; 95% CI: 11.02–23.34; p < 0.001). Conclusion: A significant association between psoriasis and IBD was demonstrated, including its subtypes: Crohn's disease and ulcerative colitis. Moreover, such association may depend on psoriasis severity as determined by the treatment used. This association warrants further investigation and implies a potential need for closer monitoring of patients with severe psoriasis. Plain language summary: Association between psoriatic disease severity and risk of inflammatory bowel diseases 1- Gut and skin barrier play an integral role in psoriasis and inflammatory bowel disease (IBD) development. 2- Shared genetic and environmental factors could explain the association between both diseases. 3- We report increased association between psoriasis and IBD, a relationship that is more pronounced in patients with severe psoriasis. 4- Patients with spondyloarthritis related diseases have a stronger association with IBD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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]

Anti-PLA2R antibodies (Ab) are a diagnostic and prognostic biomarker in primary membranous nephropathy (PMN). We assessed the relationship between the levels of anti-PLA2R Ab at diagnosis and different variables related to disease activity and prognosis in a western population of PMN patients. Forty-one patients with positive anti-PLA2R Ab from three nephrology departments in Israel were enrolled. Clinical and laboratory data were collected at diagnosis and after one year of follow-up, including serum anti-PLA2R Ab levels (ELISA) and glomerular PLA2R deposits on biopsy. Univariable statistical analysis and permutation-based ANOVA and ANCOVA tests were performed. The median [(interquartile range (IQR)) age of the patients was 63 [50–71], with 28 (68%) males. At the time of diagnosis, 38 (93%) of the patients had nephrotic range proteinuria, and 19 (46%) had heavy proteinuria (≥8 gr/24 h). The median [IQR] level of anti-PLA2R at diagnosis was 78 [35–183] RU/mL. Anti-PLA2R levels at diagnosis were correlated with 24 h proteinuria, hypoalbuminemia and remission after one year (p = 0.017, p = 0.003 and p = 0.034, respectively). The correlations for 24 h proteinuria and hypoalbuminemia remained significant after adjustment for immunosuppressive treatment (p = 0.003 and p = 0.034, respectively). Higher levels of anti-PLA2R Ab at diagnosis in patients with active PMN from a western population are associated with higher proteinuria, lower serum albumin and remission one year after the diagnosis. This finding supports the prognostic value of anti-PLA2R Ab levels and their possible use in stratifying PMN patients. [ABSTRACT FROM AUTHOR]

Introduction: The exact pathogenesis of fibromyalgia (FM) syndrome is unclear. However, various infectious have been implicated with the development of FM after their acute phase. We aimed to investigate the incidence of FM syndrome among convalesced individuals following hospitalization for Acute Coronavirus Disease-2019 (COVID-19). Methods: We performed a cross-sectional study on patients who were discharged after COVID-19 hospitalization from the Sheba Medical Center, Israel, between July 2020 to November 2020. A phone interview was performed consisting of the following questionnaires: the Fibromyalgia Survey Diagnostic Criteria Questionnaire, Sense of Coherence Questionnaire to evaluate resilience, and the Subjective Traumatic Outlook Questionnaire to assess the associated psychological aspects of the trauma. The incidence of post-COVID FM was calculated and regression models were performed to identify predictors. Results: The study population consisted of 198 eligible patients who completed the phone interview. The median age was 64 (52–72) and 37% were women. The median follow-up was 5.2 months (IQR 4.4–5.8). The incidence of FM was 15% (30 patients) and 87% (172 patients) had at least one FM-related symptom. Female gender was significantly associated with post-COVID FM (OR 3.65, p = 0.002). In addition, high median Subjective Traumatic Outlook scores and low median Sense of Coherence scores were both significantly associated with post-COVID FM (OR 1.19, p<0.001 and OR 0.92, p<0.001, respectively). Conclusions: FM is highly prevalent among COVID-19 convalescent patients. Our finding suggests that a significant subjective traumatic experience and a low resilience are highly associated with post-COVID FM. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Objectives: Polymyositis and dermatomyositis (PM/DM) are classified as polygenic autoimmune diseases, whereas inflammatory bowel disease (IBD) is considered a polygenic autoinflammatory disease. In the literature, several cases exist reporting the co-occurrence of both conditions. At the molecular level, PM/DM and IBD share common genetic determinants including interferon regulatory factor and vitamin D receptor susceptibility loci. Accumulating evidence underline several indicators that confer poor prognosis in IBD, including antinuclear antibody positivity and the presence of other autoimmune diseases, therefore the aim of this study is to assess the association between these entities. Materials and Methods: This is a population-based retrospective study using data retrieved from a large electronic medical record in Israel, the Clalit health registry. The sample included PM/DM patients and age- and sex-frequency matched controls. The prevalence of IBD in PM/DM was compared between the two groups and logistic regression was applied to control for confounding variables. Predictors of IBD in patients with PM/DM were also explored. Results: Our study included 12,278 subjects with 2085 PM/DM patients and 10,193 age- and sex- frequency-matched controls. The incidence of IBD in patients with PM/DM was significantly higher even after controlling for various confounding variables (OR of 1.73, 95% CI 1.05–2.86, p-value = 0.033). Anti-nuclear antibodies (ANA) positivity was found to be an independent predictor for IBD diagnosis in patients with PM/DM (OR 3.67, 95% CI 1.01–13.36, p = 0.048). Conclusion: Our analysis reports an association between IBD and PM/DM. Such association could point towards a common pathophysiological background. Further research is needed to further describe the clinical courses and whether a unique therapeutic approach is warranted. [ABSTRACT FROM AUTHOR]

Background: Personality disorders are prevalent in 6–10% of the population, but their risk for cause-specific mortality is unclear. The aim of the study was to assess the association between personality disorders diagnosed in late adolescence and all-cause as well as cause-specific (cardiovascular-related, external-related) mortality. Methods: We performed a longitudinal study on a historical prospective cohort based on nationwide screening prior to recruitment to the Israeli army. The study participants were 16–19-year-old persons who attended the army screening (medical and cognitive, including screening for psychiatric disorders) between 1967 and 2006. Participants were followed from 1967 till 2011. Results: The study included 2 051 606 subjects, of whom 1 229 252 (59.9%) were men and 822 354 (40.1%) were women, mean age 17.36 years. There were 55 508 (4.5%) men and 8237 (1.0%) women diagnosed with personality disorders. The adjusted hazard ratio (HRs) for coronary, stroke, cardiovascular, external-related causes and all-cause mortality among men with personality disorders were 1.34 (1.03–1.74), 1.82 (1.20–2.76), 1.45 (1.23–1.71), 1.41 (1.30–1.53) and 1.44 (1.36–1.51), respectively. The absolute rate difference for all-cause mortality was 56.07 and 13.19 per 105 person-years among men and women, respectively. Among women with personality disorders, the adjusted HRs for external-related causes and all-cause mortality were 2.74 (1.87–4.00) and 2.01 (1.56–2.58). Associations were already evident within 10 years of follow-up. Conclusions: Personality disorder in late adolescence is associated with increased risk of cardiovascular, external- and all-cause mortality. Increased cardiovascular mortality is evident before the age of 40 years and may point to the importance of lifestyle education already in youth. [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: Systemic lupus erythematosus (SLE) is a systemic autoimmune inflammatory disease characterized by antibody production against a myriad of autoantigens. Familial Mediterranean fever (FMF) is a genetic autoinflammatory disorder, triggered by FMF-associated point genes mutations. It has been hypothesized that the two conditions rarely coexist. Aim: The aim of this study was to examine the proportions of FMF among SLE patients compared with the general population without SLE. We hypothesized that the proportion of FMF among SLE patients might be higher than the general population. Methods: To conduct this cross-sectional study, data of adult patients with a physician diagnosis of SLE were retrieved from Clalit Health Services database, the largest Health Maintenance Organization in Israel, serving 4,400,000 members. Chi-square and T-test was used for univariate analysis. Results: The study population included 4,886 SLE patients and 24,430 age and sex matched controls. Within the SLE group we detected a significantly higher proportion of FMF patients compared with non-SLE controls (0.68% and 0.21% respectively; p < 0.001). Conclusions: Our study indicated that FMF is more prevalent in an Israeli population of SLE patients. [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]

Ankylosing spondylitis (AS) and gout are common inflammatory arthropathies. It had been claimed previously that the two conditions rarely coexist. The aim of this study was to compare the prevalence of gout in a population of AS patients to its prevalence in the general population. To conduct this population-based case–control study, data of adult patients with a physician diagnosis of AS were retrieved from the database of the largest health-care provider organization in Israel, Clalit Health Services. For each patient with AS, five age- and sex-matched subjects without AS were randomly selected from the same database. Different parameters including the existence of gout, hypertension, body mass index, socioeconomic status, and smoking were evaluated in both the AS and the control groups. The study included 3763 patients with AS and 19,214 controls. The proportion of gout in the AS group was higher than in the control group: 73 subjects in the AS group had gout, while only 107 subjects in the non-AS group had gout (1.94% and 0.56%, respectively, OR 3.53, P < 0.001). Logistic regression adjusting for possible confounding variables found that AS was independently associated with gout (OR 1.41, P = 0.037). Our study suggests that gout is not less common in AS patients in comparison with the general population, and that it might even be more common in AS patients. [ABSTRACT FROM AUTHOR]

Background: Vasculitides are a group of disorders characterized by inflammation of vessels. Vasculitides may have life-threatening complications with significant morbidity and mortality; however, information regarding the outcome and prognosis of patients with vasculitides requiring intensive care unit (ICU) is scarce. Methods: Data of patients with vasculitides admitted to the ICU of the Sheba Medical Center between the years 2000 and 2014 were retrieved retrospectively. Continuous variables were computed as mean (standard deviation), whereas categorical variables were recorded as percentages. In order to investigate the impact of clinical variables on mortality, Student t test and χ2 analyses were performed. Results: Twenty-five patients with vasculitides were admitted to the ICU during the study period with mean age of 52 ± 14 years and sex ratio of male/female: 12/13. The mortality rate among these patients was 48%. Leading causes for ICU admission were infection (64%), disease exacerbation (34%), and hemorrhage (16%), while respiratory or cardiovascular involvement accounted for the majority of mortality during admission. An elevated Sequential Organ Failure Assessment (SOFA) score was significantly associated with mortality (P =.041). Conclusion: Our study confirms the high mortality rate among patients with vasculitides who require ICU care as well as the roles of infection and disease flare-up as causes for admission. An elevated SOFA score was found to be predictive of mortality. [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 Both smoking and obesity have been demonstrated as risk factors in several autoimmune diseases. Little is known about the relationship between systemic lupus erythematosus ( SLE) and both smoking and obesity. Objectives To investigate the association between SLE, tobacco consumption and body mass index ( BMI). Materials and methods Using data from the largest Health Maintenance Organization ( HMO) in Israel, the Clalit Health Services, we searched for an association between SLE, smoking and obesity. Chi-square and t-test were used for univariate analysis, and a logistic regression model was used for multivariate analysis. Data available from Clalit Health Services database included age, sex, BMI, smoking status, socioeconomic status ( SES) and diagnoses of chronic diseases. Results The study included 5018 patients with SLE and 25 090 age- and sex-matched controls. In multivariate analysis, we found a significant association between smoking and SLE ( OR = 1·91). Conversely, there was no association between BMI and SLE. Conclusion In this study, we have shown that smoking is independently associated with SLE, whereas BMI scores were not. [ABSTRACT FROM AUTHOR]

(1) Background: Inflammation plays a pivotal role in atherosclerosis, and the association between chronic inflammatory states and ischemic heart disease (IHD) has been shown in several rheumatic diseases. Persistent inflammation might also be a risk factor for IHD in sarcoidosis patients. (2) Methods: Demographic and clinical data of 3750 sarcoidosis patients and 18,139 age- and sex-matched controls were retrieved from the database of Clalit Health Services, Israel's largest healthcare organization. Variables associated with IHD were assessed by a logistic regression model. To assess for variables that were related to increased risk of all-cause mortality, the Cox proportional hazards method was used, and a log-rank test was performed for survival analysis. (3) Results: Both groups were composed of 64% females with a median age of 56 years. An association between sarcoidosis and IHD was demonstrated by a multivariate analysis (adjusted odds ratio (OR) 1.5; 95% confidence interval (CI) 1.36–1.66). Long-term follow-up revealed increased mortality among sarcoidosis patients: 561 (15%) deaths compared to 1636 (9%) deaths among controls (p < 0.001). Survival analysis demonstrated that sarcoidosis patients were also at increased risk for all-cause mortality compared to controls (multivariate model, adjusted HR 1.93; 95% CI 1.76–2.13). [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: The beneficial effects of statins in rheumatoid arthritis (RA) have been suggested previously, but it is unclear whether statins may prevent its development. The aim of this retrospective cohort study was to explore whether persistent use of statins is associated with onset of RA. Methods and Findings: The computerized medical databases of a large health organization in Israel were used to identify diagnosed RA cases among adults who began statin therapy between 1998 and 2007. Persistence with statins was assessed by calculating the mean proportion of follow-up days covered (PDC) with statins for every study participant. To assess the possible effects of healthy user bias, we also examined the risk of osteoarthritis (OA), a common degenerative joint disease that is unlikely to be affected by use of statins. A total of 211,627 and 193,770 individuals were eligible for the RA and OA cohort analyses, respectively. During the study follow-up period, there were 2,578 incident RA cases (3.07 per 1,000 personyears) and 17,878 incident OA cases (24.34 per 1,000 person-years). The crude incidence density rate of RA among nonpersistent patients (PDC level of ,20%) was 51% higher (3.89 per 1,000 person-years) compared to highly persistent patients who were covered with statins for at least 80% of the follow-up period. After adjustment for potential confounders, highly persistent patients had a hazard ratio of 0.58 (95% confidence interval 0.52-0.65) for RA compared with nonpersistent patients. Larger differences were observed in younger patients and in patients initiating treatment with high efficacy statins. In the OA cohort analysis, high persistence with statins was associated only with a modest decrement in risk ratio (hazard ratio = 0.85; 0.81-0.88) compared to nonadherent patients. Conclusions: The present study demonstrates an association between persistence with statin therapy and reduced risk of developing RA. The relationship between continuation of statin use and OA onset was weak and limited to patients with short-term follow-up. [ABSTRACT FROM AUTHOR]

Abstract Background Sarcoidosis is a multisystem, chronic, progressive, granulomatous disease. Sarcoidosis-associated pulmonary hypertension is a well described, but not common, complication of sarcoidosis. In small scale studies, it has been previously described as manifestation of advanced disease and was found to be associated increased morbidity and mortality. This study sought to assess the long-term prognostic significance of sarcoidosis-associated pulmonary hypertension (SAPH) by using data obtained from a large population-based registry which contains longitudinal follow-up data. Methods Utilizing the records of the largest healthcare provider in Israel, we extracted a cohort consisting of sarcoidosis patients and age-and-sex matched controls. Dates of sarcoidosis registration, pulmonary hypertension and death, as well as anthropometric information and medical comorbidities, were extracted from the database. A multivariate logistic regression model was used to find variables associated with pulmonary hypertension. Cox proportional hazards method and log-rank test were used for survival analysis. Results The cohort included 3993 sarcoidosis patients and 19,856 controls. Pulmonary hypertension was observed among 269 sarcoidosis patients (6.74%) vs. 400 controls (2.01%). Sarcoidosis was found as independently associated with pulmonary hypertension (OR 3.17). After a mean follow-up of 7.49 years (median 7.24, maximum 17.88 years), 710 (17.8%) of the sarcoidosis patients and 2121 (10.7%) of the controls had died. Both sarcoidosis and pulmonary hypertension were found to be significantly associated with an increased risk of all-cause mortality (HR 1.82 and HR 2.31, respectively). Conclusions SAPH is associated with a poor prognosis. Proper screening methods may assess whether early identification and treatment improve life expectancy. [ABSTRACT FROM AUTHOR]

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: The fibromyalgia syndrome (FMS) is a chronic condition consisting of widespread musculoskeletal pain and tenderness together with mood and cognitive dysfunction. Diabetes mellitus (DM) is a common condition causing significant and detrimental morbidity and mortality. Data on the association between the two conditions is scarce and mainly based on small populations therefore lack solid evidence. Objectives: To evaluate the association of FMS with DM. Material and methods: This cross-sectional study used the Clalit Health Services database, the largest Health Maintenance Organization in Israel, serving 4,400,000 members. FMS patients were compared to age- and sex-matched controls regarding chronic comorbid conditions. χ² and student's t-tests were used for univariate analysis. Results: The study included 14,296 FMS patients and 71,324 age- and sex-matched controls. The FMS group had a significantly higher proportion of DM patients compared to non-FMS controls (19.8% and 17.4 respectively; OR 1.17, 95% CI: 1.12-1.23, p < 0.001). Conclusions: DM was found to be more common amongst FMS patients compared to matched controls to suggest that the pathophysiology of DM might lead a patient to develop FMS. Consequently, physicians treating DM patients should be aware of the possible risk and asses for clinical signs of FMS in order to diagnose and treat it in time to better their patients' quality of life and disease management. [ABSTRACT FROM AUTHOR]

Objective: In this large population-based study we aimed: 1) to assess mortality in patients with ankylosing spondylitis (AS) compared to the general population, considering demographics, comorbidities, and treatment, and 2) to assess factors associated with mortality within patients with AS., Methods: This study was designed as a retrospective cohort study using the electronic database of the largest health maintenance organization in Israel. All patients with AS diagnosed between 2002 and 2018 were included. Controls were matched by age, sex, clinic, and enrollment time. Follow-up continued until death or the end of the study., Results: The study comprised 5,930 AS patients and 29,018 matched controls who were followed up for a median period of 7.5 years. There were 667 deaths within the AS cohort and 2,919 deaths within controls; the mean age at death was 76.9 years and 77.1 years, respectively (P = 0.74). A total of 3,249 AS patients (54.8%) were treated only with nonsteroidal antiinflammatory drugs, 1,760 (29.7%) were treated with tumor necrosis factor inhibitors (TNFi), and 1,687 (28.4%) with disease-modifying antirheumatic drugs (DMARDs). Mortality rates were increased among AS patients compared to controls, with an age- and sex-adjusted hazard ratio (HR) of 1.19 (95% confidence interval [95% CI] 1.10-1.30). The association was significant for men (HR 1.15 [95% CI 1.04-1.27]) and women (HR 1.32 [95% CI 1.13-1.54]), and after adjusting for background comorbidities (HR 1.14 [95% CI 1.05-1.24]). AS patients treated with TNFi or with a combination of TNFi and DMARDs did not have significant difference in mortality rates compared to controls (HR 0.67 [95% CI 0.38-1.18] and HR 0.93 [95% CI 0.69-1.25], respectively). Age, male sex, mean C-reactive protein (CRP) levels and general comorbidities were predictors of mortality within the AS cohort., Conclusion: AS patients had an increased mortality risk compared to the general population after adjusting for age, sex, and baseline comorbidities. AS patients treated with TNFi did not demonstrate excess mortality compared to matched controls. Within the AS cohort, age, male sex, background comorbidities, and higher CRP levels were identified as risk factors for mortality., (© 2021 American College of Rheumatology.)

Objective: To evaluate the proportion and the long-term prognostic significance of heart failure (HF) in sarcoidosis patients., Methods: 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., Results: 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)., Conclusions: Sarcoidosis is independently associated with HF, and both are independently associated with all-cause mortality.

Background: Although studied in a few randomized controlled trials, the efficacy of medical cannabis (MC) for chronic pain remains controversial. Using an alternative approach, this multicentre, questionnaire-based prospective cohort was aimed to assess the long-term effects of MC on chronic pain of various aetiologies and to identify predictors for MC treatment success., Methods: Patients with chronic pain, licensed to use MC in Israel, reported weekly average pain intensity (primary outcome) and related symptoms before and at 1, 3, 6, 9 and 12 months following MC treatment initiation. A general linear model was used to assess outcomes and identify predictors for treatment success (≥30% reduction in pain intensity)., Results: A total of 1,045 patients completed the baseline questionnaires and initiated MC treatment, and 551 completed the 12-month follow-up. At 1 year, average pain intensity declined from baseline by 20% [-1.97 points (95%CI = -2.13 to -1.81; p < 0.001)]. All other parameters improved by 10%-30% (p < 0.001). A significant decrease of 42% [reduction of 27 mg; (95%CI = -34.89 to 18.56, p < 0.001)] from baseline in morphine equivalent daily dosage of opioids was also observed. Reported adverse effects were common but mostly non-serious. Presence of normal to long sleep duration, lower body mass index and lower depression score predicted relatively higher treatment success, whereas presence of neuropathic pain predicted the opposite., Conclusions: This prospective study provides further evidence for the effects of MC on chronic pain and related symptoms, demonstrating an overall mild-to-modest long-term improvement of the tested measures and identifying possible predictors for treatment success., (© 2020 European Pain Federation - EFIC®.)

Background: The reported mortality rates of patients with polymyositis and dermatomyositis are highly variable worldwide. The excess mortality of patients with polymyositis/dermatomyositis has not been evaluated in an Israeli population., Objectives: To investigate the overall mortality in a large and well-established cohort of patients with polymyositis/dermatomyositis as compared to the mortality expected in the matched general population in a tertiary medical center., Methods: In this retrospective cohort study, the mortality of 166 patients with polymyositis/dermatomyositis was compared to age- and sex-matched control subjects in the general population. All-cause standardized mortality ratios (SMRs) were estimated., Results: Overall, 47 (28.3%) deaths were observed among patients with polymyositis/dermatomyositis during a mean follow-up period of 5.8 ± 4.8 years, which was 7 times higher than in the control group (SMR 7.4, 95% confidence interval [95%CI] 5.5-9.8). The SMRs were comparable in patents with polymyositis (7.7, 95%CI 4.8-12.3) and dermatomyositis (7.2, 95%CI 5.0-10.3). The 1-, 5-, 10-, and 15-year overall survival rates were 90.0%, 82.8%, 51.5%, and 26.1%, respectively, in patients with polymyositis, and 80.3%, 59.6%, 40.0%, and 17.1%, respectively, in patients with dermatomyositis., Conclusions: The overall mortality among Israeli patients with polymyositis/dermatomyositis is 7.4 times greater than for the general population. Although long-term mortality was comparable between patients with dermatomyositis and polymyositis, patients in the former group died at a notably earlier stage.

Background: Some disease-modifying agents commonly used to treat patients with rheumatic diseases/autoimmune disorders, such as hydroxychloroquine and colchicine, are under investigation as potential therapies for the "coronavirus disease 2019" (COVID-19). However, the role of such agents as prophylactic tools is still not clear., Methods: This is a retrospective study based on a large healthcare computerized database including all patients that were screened for the "Severe Acute Respiratory Syndrome Coronavirus type 2" (SARS-CoV-2) in the study period from February 23rd 2020 to March 31st 2020. A comparison was conducted between subjects tested positive for SARS-CoV-2 and those found negative in terms of rate of administration of hydroxychloroquine/colchicine therapy., Results: An overall sample of 14,520 subjects were screened for SARS-CoV-2 infection and 1317 resulted positive. No significant difference was found in terms of rates of usage of hydroxychloroquine or colchicine between those who were found positive for SARS-CoV-2 and those who were found negative (0.23% versus 0.25% for hydroxychloroquine, and 0.53% versus 0.48% for colchicine, respectively)., Conclusion: These findings raise doubts regarding the protective role of these medications in the battle against SARS-CoV-2 infection., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In this study, we aimed to examine the effect of vitamin D deficiency on all-cause mortality in ankylosing spondylitis (AS) patients and in the general population. This is a retrospective-cohort study based on the electronic database of the largest health-maintenance organization in Israel. AS patients who were first diagnosed between 2002-2007 were included. Controls were matched by age, gender and enrollment-time. Follow-up continued until death or end of study follow-up on 1 July 2019. Laboratory measures of serum 25-hydroxyvitamin-D levels during the entire follow-up period were obtained. A total of 919 AS patients and 4519 controls with a mean time of follow-up of 14.3 years were included. The mean age at the time of enrollment was 52 years, and 22% of them were females. AS was associated with a higher proportion of vitamin D deficiency (odds ratio 1.27 [95% confidence-interval (CI) 1.03-1.58]). In AS patients, insufficient levels of vitamin D (< 30 ng/mL) were significantly associated with increased incidence of all-cause mortality (hazard ratio (HR) 1.59 [95% CI 1.02-2.50]). This association was more prominent with the decrease in vitamin D levels (< 20 ng/mL, HR 1.63 [95% CI 1.03-2.60]; <10 ng/mL, HR 1.79 [95% CI 1.01-3.20]) and among male patients (< 30 ng/mL, HR 2.11 [95% CI 1.20-3.72]; <20 ng/mL, HR 2.12 [95% CI 1.19-3.80]; <10 ng/mL, HR 2.23 [95% CI 1.12-4.43]). However, inadequate levels of vitamin D among controls were not associated with an increased all-cause mortality. Our study has shown that vitamin D deficiency is more common in AS patients than controls and is linked to an increased risk for all-cause mortality. These results emphasize the need for randomized-controlled trials to evaluate the benefits of vitamin D supplementation as a secondary prevention of mortality in patients with chronic inflammatory rheumatic disease., Competing Interests: The authors declare no conflict of interest.

Background: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic, relapsing, inflammatory diseases of the gastrointestinal tract with unknown etiology. IBD are complex, multi-factorial disorders, in which genetic factors play a major role, the so-called phenomenon of familial aggregation or clustering of IBD. A positive family history of IBD is often reported among CD and UC probands, with percentages depending on the geographic context in which the studies are carried out. Israel is a complex and pluralistic society comprising of two major ethno-national groups (Arabs and Jewish) and, as such, represents a unique living laboratory in which to test the role of genetic factors in the development of IBD as well as of associated autoimmune disorders (ADs). While some studies have found a lower prevalence of ADs among Arabs when compared to Jews, few studies directly compared the two ethnicities., Methods: The present case-control study was designed to compare the rate of ADs in first- and second-degree relatives of IBD patients, stratified according to Jewish or Arabic ethnicity., Results: We found that first-degree relatives of Jews patients had a higher risk of developing ADs (OR=1.89, P=0.0086). Classifying ADs into systemic and local (endocrinological, gastrointestinal, dermatological, and neurological) types, first-degree relatives of Jews patients had a higher OR of developing local ADs (OR=2.12, P=0.0056)., Conclusions: Israeli Jewish IBD patients had more first-degree relatives with local ADs as compared to Arab patients.

Objectives: Stress has extensively been shown to trigger fibromyalgia syndrome (FM). Nursing is associated with high levels of stress. Our hypothesis was that nurses suffer from an increased prevalence of FM symptoms, and that these symptoms correlate with the levels of stress to which they are exposed in the course of their occupation., Methods: The study was conducted as a targeted survey distributed to nursing staff in Soroka University Medical Centre, Beer-Sheva, Israel. Participants were asked to answer a questionnaire evaluating symptoms of FM, based on the current diagnostic criteria, which include the widespread pain index (WPI) and the symptom severity scale (SSS). Participants were further questioned regarding stressful experiences during their work and about post-traumatic symptoms as well as regarding work performance and motivation., Results: 206 participants completed the study questionnaire (84.5% females and 15.5% males). Twenty (9.7%) participants of the sample fulfilled criteria for diagnosis of FM reaching rates among females and males of 10.9% and 3.1% respectively. The prevalence of FM in our study was related to age with the highest prevalence in the older age groups (p=0.012). FM symptoms were strongly correlated with work related stress and were strongly correlated with Post Traumatic Stress Disorder (PTSD)-related symptoms. Work-performance parameters did not show a significant correlation with FM parameters., Conclusions: FM is highly prevalent among nursing staff. Our findings point towards the possibility that work-related stress and traumatic events may play a major role in the development of FM symptoms among nurses. With aging this association is more significant.

Background: A high prevalence of thyroid disorders has been reported in patients with autoimmune diseases. The link between hyperthyroidism and systemic sclerosis (SSc) has been relatively overlooked, and only a few studies utilizing small samples or case reports have been reported so far., Objectives: To investigate the association between SSc and hyperthyroidism., Methods: We designed a case-control study utilizing the medical database of the Clalit Health Services. Chi-square and t tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis., Results: The study included 2,431 SSc patients and 12,710 age- and sex-matched controls. The mean age of the study population was 63.32 ± 18.06 years (median 66 years), and female-to-male ratio was 4.5:1. Age (P < .0001, OR 1.03 [95% CI 1.02-1.04]), female sex (P = .0015, OR 1.86 [95% CI 1.27- 2.74]) and diagnosis of SSc (P = .0011, OR 1.81[95% CI 1.27-2.58]) were all independently associated with hyperthyroidism. Patients with SSc and hyperthyroidism had 1.54-fold increase of mortality rates during a mean follow-up of 17 years than SSc patients without hyperthyroidism, even though at the Cox multivariate survival analysis, only age (HR 1.06 [95% CI 1.06-1.07], P < .0001) and diagnosis of SSc (HR 2.35 [CI 2.06 to 2.69], P < .0001) resulted associated with a higher risk of mortality., Conclusions: Hyperthyroidism is highly prevalent among SSc patients and can negatively impact on their survival rates. Therefore, a pre-emptive screening may be warranted in all SSc patients. Further studies are needed to evaluate whether tight control and optimal treatment for hyperthyroidism may lead to a reduction of all-cause mortality in patients with SSc., (© 2019 Stichting European Society for Clinical Investigation Journal Foundation.)

Objectives: To test the hypothesis that familial Mediterranean fever (FMF)-associated autoinflammation may exaggerate the tendency toward adaptive immunopathology or spondyloarthritis (SpA)-associated disorders including major histocompatibility complex (MHC) class I associated disorders but not classical MHC class II-associated disorders that exhibit transplacental autoimmunity including myasthenia gravis and pemphigus. Methods: Seven thousand seven hundred forty-seven FMF patients and 10,080 age- and sex-matched controls in the Clalit Health Services medical database were identified and compared in terms of prevalence of SpA-associated disorders. We also evaluated four classical and strong MHC class II-associated disorders, namely, pemphigus vulgaris, myasthenia gravis, sarcoidosis, and pernicious anemia, to ascertain whether such associations with SpA-spectrum disease were specific or merely reflected the non-specific consequences of innate immune system activation on driving divergent types of immunity. The diagnosis of FMF was based on the medical records and not genetically proven. Results: FMF showed a strong association with MHC class I-related diseases: odds ratio (OR) of 28.58 [95% confidence interval (95% CI), 6.93-117.87; p < 0.0001] for Behçet's disease, OR of 10.33 (95% CI, 4.09-26.09; p < 0.0001) for ankylosing spondylitis, and OR of 1.67 (95% CI, 1.19-2.33; p = 0.0029) for psoriasis. For weakly MHC class I-linked diseases, an OR of 3.76 (95% CI, 2.48-5.69; p < 0.0001) for Crohn's disease and OR of 2.64 (95% CI, 1.52-4.56; p = 0.0005) for ulcerative colitis were found. No association was found between FMF and the four MHC class II-associated autoimmune disorders. Conclusion: FMF patients are associated with increased risk of SpA-related disease diagnosis including MHC-I-opathies but not MHC-II-associated autoimmune diseases, suggesting that tissue-specific dysregulation of innate immunity share between FMF and SpA spectrum disorders may drive adaptive immune MHC class I-associated conditions., (Copyright © 2019 Watad, Bragazzi, Adawi, Shoenfeld, Comaneshter, Cohen, McGonagle and Amital.)

Background: Patients with rheumatoid arthritis (RA) are at a high risk for life-threatening conditions requiring admission to the intensive care unit (ICU), but the data regarding the outcomes of these patients is limited. The present study investigated the clinical characteristics and outcomes of RA patients admitted to an ICU., Methods: This retrospective cohort study included RA patients admitted to the general ICU of the Sheba Medical Center during 2002-2018. The main outcome was 30-day mortality. Using Student's t test, χ 2 , and multivariable analyses, we compared the demographic, clinical, and laboratory parameters of the survivors and the non-survivors. Figures with p value < 0.05 were considered statistically significant., Results: Forty-three RA patients were admitted to the ICU during the study period (mean age, 64.0 ± 13.1 years; 74.4% female). The leading causes of ICU admission were infection (72.1%), respiratory failure (72.1%), renal failure (60.5%), and septic shock (55.8%). The 30-day mortality rate was 34.9%, with infection (9/15, 60%) as the most frequent cause. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were 19.7 ± 12.5 and 7.0 ± 4.5, respectively. Multivariable analysis showed that heart failure (p = 0.023), liver failure (p = 0.012), SOFA score (p = 0.007), and vasopressor treatment in ICU (p = 0.039) were significantly associated with overall mortality. SOFA score was linked with overall mortality (area under the curve (AUC) = 0.781 ± 0.085, p = 0.003) and mortality from respiratory failure (AUC = 0.861 ± 0.075, p = 0.002), while APACHE II score was only correlated with mortality from infection (AUC = 0.735 ± 0.082, p = 0.032)., Conclusions: Our study demonstrated a relatively high mortality rate among RA patients who were admitted to the general ICU. RA patients with risk factors such as heart failure, liver failure, elevated SOFA score, and vasopressor treatment in ICU should be promptly identified and treated accordingly. Key Points • The 30-day mortality rate of patients with RA that were admitted to the general ICU of a tertiary hospital was 34.9%. • The most common causes of ICU admission among patients with RA were infections and respiratory failure. Infections were the most common cause of death among these patients. • Patients with RA that present to the ICU with heart failure, liver failure, elevated SOFA score, and/or require vasopressor treatment in ICU should be promptly identified and treated accordingly.

Background: We investigated the pattern of reported immune diseases in the international ASIA syndrome registry., Methods: Data from 500 subjects exposed to adjuvants from the ASIA syndrome international registry were analysed., Results: The patient mean age was 43 ± 17 years and 89% were female. Within the reported immune diseases, 69% were well-defined immune diseases (autoimmune, autoinflammation, and mixed pattern diseases). Among the well-defined immune diseases following the exposure to adjuvants, polygenic autoimmune diseases were significantly higher than autoinflammatory disorders (92.7% vs 5.8%, respectively, p < 0.001). Polygenic autoimmune diseases such as connective tissue diseases were significantly linked to the exposure to HBV vaccine (OR 3.15 [95%CI 1.08-9.23], p = 0.036). Polygenic autoinflammatory diseases were significantly associated with the exposure to influenza vaccination (OR 10.98 [95%CI 3.81-31.67], p < 0.0001)., Conclusions: Immune conditions following vaccination are rare, and among these, polygenic autoimmune diseases represent the vast majority of the well-defined immune diseases reported under the umbrella ASIA syndrome. However, vaccines benefit outweighs their autoimmune side effects., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.

Background: Giant cell arteritis (GCA) is an autoimmune disorder which primarily affects large vessels, whilst inflammatory bowel diseases (IBD) mainly target the gut. Co-existence of the two maladies has been reported sporadically in the literature; therefore the purpose of this study was to assess the authenticity of such an association in a large, cross-sectional study., Methods: Utilizing data derived from the Clalit Health Services' registry, the largest health maintenance organization in Israel, we compared the proportion of CD and UC in GCA patients with age- and gender-matched controls. Univariate analysis was performed using Chi-square and student t-test and a multivariate analysis was performed using a logistic regression model., Results: The study included 3938 GCA patients and 21,623 age- and gender-matched controls. GCA patients had a significantly increased proportion of both CD and UC in comparison with controls (0.79% vs. 0.12% and 0.84% vs. 0.21%, P-value < .001, respectively). The strength of the association between GCA and IBD was negatively correlated with the patients' age; thus the association was more robust amongst middle-aged patients (ages 50-69, OR = 8.13) than in elderly patients (ages 70-85, OR = 3.81). The association between GCA and IBD remained significant when evaluated independently of confounding factors (OR = 2.63, P-value < .001)., Conclusions: The probability that GCA patients also suffer from IBD is increased in comparison with age- and gender-matched controls. Our findings indicate that this association is more prominent in middle-aged patients (50-69 years of age). Screening for IBD amongst GCA patients in this age group may be warranted., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Thyroid dysfunction appears to show increased prevalence in many autoimmune diseases; however, this comorbidity has not been properly investigated in patients with RA. This issue was addressed in this cross-sectional study. Using the database of the Clalit Health Services (CHS) in Israel, RA patients were paired with age- and sex-matched controls to compare the prevalence of hypothyroidism and hyperthyroidism. Chi-squared and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study included 11,782 patients with RA and 57,973 controls. The rate of thyroid dysfunction diseases in RA patients was increased compared with the prevalence in controls (16.0% and 11.7%, p < 0.001, for hypothyroidism; and 2.33% and 1.81%, p < 0.001 in hyperthyroidism, respectively). In a multivariate analysis, RA was associated with hypothyroidism (OR = 1.42, 95% CI 1.34-1.50) and hyperthyroidism (OR = 1.26, 95% CI 1.10-1.45). RA is associated with thyroid dysfunction. Therefore, physicians treating patients with RA should be aware of the possibility of comorbid thyroid dysfunction and treat accordingly., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Prolonged hospitalizations are a major challenge for any society and to the Israeli health system in particular. Identifications of predictors underlines the areas that require comprehensive interventions to prevent long hospital stays. Analysis of the literature points out that discharges from internal medicine wards should be preplanned and coordinated. It is obvious that the care of those with special needs such as the elderly, dependent, lonely, disabled and patients with comorbidities mandates the development of proper community-based care that will be a continuation of in-hospital therapy. It seems inevitable that this urgent need will require a medical professional whose main task will be coordination of care in and out of the hospital.

Aims: Published data on long-term adherence and persistence with adalimumab (Humira ® ) in clinical practice are scarce and often limited to selected patient populations. This study assessed adherence with adalimumab across different indications and identified correlates and outcomes of poor adherence., Methods: We analysed data originating from the electronic database of Maccabi Healthcare Services (MHS) that includes 2.1 million enrolees. We randomly selected patients with at least one dispense of adalimumab since it was included in the local health basket in Israel in 2008 until the end of 2013. Patients with the following indications (n = 1339) were included: Crohn's disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), psoriatic arthritis (PSA), ankylosing spondylitis (AS) and psoriasis. Adherence with therapy was assessed by the medication possession ratio (MPR) during the follow-up period., Results: Good adherence (MPR ≥ 80%) was observed among 80% of study patients and was associated with lower risk for ≥1 hospitalization per year of follow-up (adjusted-OR = 1.94, 95% CI:1.15-3.28). Patients with AS and CD persisted on adalimumab therapy the most, reaching median use of 27.0 and 26.7 months, respectively. Half (52.4%) of the patients discontinued treatment during a mean (SD) follow-up of 3.07 (1.71) years. High socioeconomic status was associated with lower risk for discontinuation (adjusted-HR = 0.74; 0.60-0.91). UC and concomitant prednisolone use were associated with increased risk for treatment discontinuation (HR = 1.31; 1.00-1.72, and HR = 1.40; 1.17-1.68, respectively)., Conclusion: Our results indicate encouraging persistence and adherence with adalimumab of patients with inflammatory conditions., (© 2017 The British Pharmacological Society.)

Objective: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting a wide range of systems including the peripheral and central nervous system. Cognitive impairment leading to dementia is one of the harmful central nervous system afflictions of SLE. The aim of this study was to investigate the association of SLE with dementia., Methods: A cross-sectional study was conducted using Clalit Health Care database, the largest health maintenance organization in Israel with more than 4.4 million enrollees. Systemic lupus erythematosus patients were compared in a 1:5 ratio to age- and sex-matched controls. Chi-square and t tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis., Results: The study included 4886 SLE patients and 24 430 age-frequency- and sex-frequency-matched controls without SLE. The proportion of dementia was higher among SLE patients compared to controls (1.56% and 0.51%, respectively; P < .001). This finding was consistent across all age groups by univariate analysis. In a multivariate logistic regression analysis, SLE was significantly associated with dementia (odds ratio = 1.51, 95% confidence interval, 1.11-2.04)., Conclusion: Systemic lupus erythematosus is significantly associated with dementia. This finding should give rise to search for SLE in patients with an ambiguous cause for dementia, especially those with an early onset cognitive decline., (Copyright © 2017 John Wiley & Sons, Ltd.)

Objective: Epilepsy is characterized by a relevant epidemiological and clinical burden. In the extant literature, an increased risk of seizures has been described in several inflammatory/autoimmune disorders, including systemic lupus erythematosus (SLE). However, so far, relatively few and small size-based studies have been conducted. We aimed to investigate the link between seizure and SLE utilizing a large sample of subjects and extensive data analysis., Methods: Patients with SLE were compared with age- and sex-matched controls regarding the prevalence of epilepsy in a cross-sectional study. Chi-square and t tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services., Results: The study included 5,018 patients with SLE and 25,090 age- and gender-frequency-matched controls. The proportion of epilepsy was found significantly higher among SLE patients (4.03 vs. 0.87%, p < 0.001). Using logistic regression, adjusting for multiple confounding factors, older age (≥70 years) resulted as negative predictor (OR 0.42 [95% CI 0.27-0.62], p <0.001), whereas the presence of SLE was a positive predictor of epilepsy (OR 4.70 [95% CI 3.94-5.82], p < 0.001). Interaction between SLE and elderly age resulted in high OR of 5.47 for epilepsy (95% CI 2.53-11.9)., Conclusion: Our study confirms the higher prevalence of epilepsy in SLE patients. Physicians should be aware of such findings and have a lower threshold for suspecting epileptic seizures in these patients. Further studies are needed to better elucidate the mechanisms by which SLE favors the insurgence of seizures., (© 2017 S. Karger AG, Basel.)

Syphilis is an infectious disease. It is unique and interesting, and even to this day it continues to be a major challenge to the medical community in the prevention of the spread, the diagnosis and treatment of the disease. In recent years in Israel, 200 new cases have been revealed annually. During this period, several reports were published on the outbreaks of the disease. We believe that due to the increase in the rate of patients with the disease there is a strong need to educate the medical staff about the disease and to raise awareness regarding the symptoms of the disease, methods of diagnosis, increased risk populations, and methods of treatment. In this article we present four cases of syphilis that we encountered in our institution, which presented relatively in different ways. Furthermore, in these cases the diagnosis was not simple. So it is important to be aware that this disease still exists and must be recognized in order to know how to diagnose it.

Context: The natural progression of metabolic abnormalities among patients with inherited autoinflammation is unclear., Objective: The objective of the study was to assess the cardiometabolic risk of participants with familial Mediterranean fever (FMF)., Design and Setting: This study included nationwide cross-sectional and longitudinal cohorts., Participants: The prevalence of components of the metabolic syndrome at age 17 years was assessed from the medical database of the Israeli Defense Force from 1973 through 1997. Included were 745 males with FMF, 902 healthy male siblings, and a control group of 787,714 participants. A prospective follow-up study traced the incidence of components of the metabolic syndrome to age 45 years among 57 FMF and 1568 control army personnel participants., Interventions: Body mass index (BMI) and blood pressure (BP) were measured at age 17 years (cross-sectional); lifestyle, anthropometric, and biochemical data were periodically recorded from age 25 years., Main Outcome Measures: Abnormal BMI or BP (age 17 y) and Adult Treatment Panel III criteria of the metabolic syndrome were measured., Results: In multivariable regression analysis adjusted for known confounders of obesity, FMF participants had an odds ratio of 0.65 for the occurrence of overweight [95% confidence interval (CI) 0.44-0.96, P = .03] and 0.66 (95% CI 0.48-0.92, P = .012) for hypertension-range BP; their siblings tended to obesity (odds ratio 1.48; 95% CI 1.04-2.11, P = .008). In the follow-up arm, a multivariable analysis adjusted for age, birth year, BMI, education, socioeconomic status, ethnicity, and physical activity yielded hazard ratios of 0.32 (95% CI 0.10-0.82, P = .002) for incident obesity, 0.49 (95% CI 0.25-0.95, P = .037) for incident triglycerides 150 mg/dL or greater, 0.56 (95% CI 0.31-0.98, P = .048) for low-density lipoprotein cholesterol 130 mg/dL or greater, and 2.14 (1.368-3.359, P = .001) for high-density lipoprotein cholesterol less than 40 mg/dL for FMF participants compared with controls. Incident elevated BP was lower among FMF participants (hazard ratio 0.49; 95% CI 0.23-1.00, P = .05), whereas dysglycemia incidence was comparable., Conclusions: FMF is associated with lower rates of most components of the metabolic syndrome compared with normal subjects, unlike other inflammatory conditions.

Objective: There are limited data on long-term comorbidities and mortality among patients with familial Mediterranean fever (FMF). Our objective was to evaluate comorbidities and death rates among individuals with FMF., Methods: We studied a nationwide, population-based, retrospective cohort of 1225 individuals with FMF (59% men) in a database of 1 244 350 adolescents (16-20 years of age) medically evaluated for military service between 1973 and 1997. This cohort was linked with the national mortality, cancer and end-stage renal disease (ESRD) registries in Israel. Study outcomes were all-cause mortality, occurrence of ESRD and malignancy by the age of 50 years., Results: During 30 years of follow-up, death rates were 8.73/10(4) versus 4.32/10(4) person-years in the FMF and control groups, respectively (p=0.002). In a multivariable analysis adjusted for age, birth year, socio-economic status, education, ethnicity and body mass index, FMF was associated with increased mortality in men (HR=1.705 (95% CI 1.059 to 2.745), p=0.028) and women (HR=2.48 (1.032 to 5.992), p=0.042). Renal amyloidosis accounted for 35% and 60% of deaths in men and women, respectively. FMF was not associated with an increased incidence of cancer., Conclusions: FMF is associated with increased all-cause mortality that is likely attributed to reduced colchicine compliance or responsiveness. Individuals with FMF do not have an increased incidence of cancer. These results support the awareness among medical community to decrease the higher than average mortality rate among participants with FMF.