Adherence to metformin and the onset of rheumatoid arthritis: a population-based cohort study.

Objective: The aim of this retrospective cohort study was to examine whether adherence to metformin treatment may be associated with lower onset of rheumatoid arthritis (RA).Method: Using the computerized databases of a 2.3-million state-mandated health services organization in Israel, we identified incident RA cases among a cohort of 113 749 adult patients who initiated metformin therapy between 1998 and 2014. Adherence was assessed by calculating the mean proportion of follow-up days covered (PDC) with metformin.Results: During the 18 year study period, there were 558 incident RA cases (61 per 100 000 person-years). Adherence to metformin treatment was associated with a lower risk of developing RA, with the lowest risk recorded among patients with a PDC of 40-59% [adjusted hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.45-0.84] compared with non-adherent patients (PDC < 20%). A mean daily metformin dose of 2550 mg or more was also associated with a lower risk of developing RA (adjusted HR 0.62, 95% CI 0.46-0.84) compared to a daily dose of 850 mg or less. In stratified analyses by gender, the negative association between adherence and the risk of RA was limited to women alone.Conclusions: Adherence to metformin treatment is associated with a reduced risk of developing RA in women. Further studies are needed to assess the effect of metformin on RA development in other patient populations.

Chronic urticaria and osteoporosis: a longitudinal, community-based cohort study of 11 944 patients.

BACKGROUND: Chronic urticaria (CU) carries many risk factors for osteoporosis, but data on the relationships between CU and osteoporosis are lacking. OBJECTIVES: To evaluate the association between CU and osteoporosis in a large community-based study. METHODS: A nationwide observational longitudinal cohort study was conducted. CU was defined as four pairs of urticaria diagnoses; each pair was recorded within a period of 6 weeks and was registered by physicians in a primary-care setting. Patients with CU and their age- and sex- matched controls were followed for the incidence of osteoporosis and other laboratory data between 2002 and 2017. Data regarding systemic steroid exposure and other relevant risk factors for osteoporosis were obtained. Analyses of risk for osteoporosis were performed in Cox regression models adjusted for age, sex, exposure to systemic corticosteroids, obesity, smoking and hyper- and hypothyroid disease. RESULTS: The study included 11 944 patients with CU and 59 829 controls. During the study's observation period, 1035 (8·7%) patients with CU were diagnosed with osteoporosis, compared with 4046 (6·8%) controls. The adjusted multivariate analysis demonstrated that CU was significantly associated with a higher risk for osteoporosis (hazard ratio 1·23, 95% confidence interval 1·10-1·37, P < 0·001). CONCLUSIONS: CU may impose a risk for osteoporosis. Appropriate targeted screening should be considered.

Chronic urticaria and the metabolic syndrome: a cross-sectional community-based study of 11 261 patients.

BACKGROUND: Emerging evidence suggests that chronic urticaria (CU) is associated with chronic, low-grade, inflammatory process. OBJECTIVE: To evaluate the association between CU and metabolic syndrome and its components in a large community-based medical database. METHODS: A cross-sectional study of CU patients and matched controls was performed. CU was defined as eight urticaria diagnoses (with each two diagnoses registered within a period of 6 weeks) from 2002 to 2012. Data regarding the prevalence of metabolic syndrome, its components and possible complications were collected. RESULTS: The study included 11 261 patients with CU and 67 216 controls. In a univariate analysis, CU was significantly associated with higher body mass index (BMI) and a higher prevalence of obesity, diabetes, hyperlipidaemia, hypertension, metabolic syndrome, chronic renal failure and gout. Multivariate analysis demonstrated a significant association between CU and metabolic syndrome (OR = 1.12, 95% CI 1.1-1.2, P < 0.001) and its components - obesity (OR = 1.2, 95% CI 1.1-1.3, P < 0.001), diabetes (OR = 1.08, 95% CI 1.01-1.15, P = 0.001), hyperlipidaemia (OR = 1.2, 95% CI 1.1-1.2, P < 0.001) and hypertension (OR = 1.1, 95% CI 1.1-1.2, P < 0.001). CONCLUSIONS: CU patients may have one or more undiagnosed components of metabolic syndrome despite their young age. Thus, appropriate targeted screening is advised.

The association between systemic lupus erythematosus and bipolar disorder - a big data analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease that has a wide variety of physical manifestations, including neuropsychiatric features. Bipolar disorder (BD) is a chronic, episodic illness, that may present as depression or as mania. The objective of this study was to investigate the association between SLE and BD using big data analysis methods. METHODS: Patients with SLE were compared with age- and sex-matched controls regarding the prevalence of BD 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, adjusting for confounders. The study was performed utilizing the chronic disease registry of Clalit Health Services medical database. RESULTS: The study included 5018 SLE patients and 25,090 matched controls. BD was found in a higher prevalence among SLE patients compared to controls (0.62% vs. 0.26%, respectively, P<0.001). BD patients had a greater prevalence of smokers compared to non-BD patients (62.5% vs 23.5%, respectively, P<0.001). In a multivariate analysis, smoking and SLE were both found to be significantly associated with BD. CONCLUSIONS: SLE was found to be independently associated with BD. These findings may imply that an autoimmune process affecting the central nervous system among SLE patients facilitates the expression of concomitant BD.

Schizophrenia among patients with systemic lupus erythematosus: population-based cross-sectional study.

AIMS: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease involving multiple organs, including the central nervous system. Evidence of immune dysfunction exists also in schizophrenia, a psychiatric illness involving chronic or recurrent psychosis. The aim of our study was to investigate if there is an epidemiological association between SLE and schizophrenia. METHOD: A cross-sectional study was conducted comparing patients with SLE with age and gender-matched controls regarding the proportion of patients with comorbid schizophrenia. χ 2- and t-tests were used for univariate analysis, and interaction of schizophrenia with SLE across strata of covariates was checked. A logistic regression model was used for multivariate analysis. The study was performed utilising the medical database of Clalit Health Services in Israel. RESULTS: The study included 5018 patients with SLE and 25 090 controls. SLE patients had a female predominance, and a higher proportion of smoking compared with age and sex-matched controls. In multivariate analysis, SLE was found to be independently associated with schizophrenia while controlling for age, gender, socioeconomic status (SES) and smoking (OR 1.33, p = 0.042). CONCLUSIONS: We found a positive association between SLE and schizophrenia across patients of different age, gender and SES. This association can contribute to understanding the pathophysiology of the two disorders and may also have clinical implications for earlier as well as better diagnosis and treatment.

Aortic aneurysm association with SLE - a case-control study.

OBJECTIVES: Aortic aneurysm is a life threatening cardiovascular complication in patients with systemic lupus erythematosus (SLE).The purpose of this study was to investigate the association between SLE and occurrence of aortic aneurysms. METHODS: Patients with SLE were compared with age- and sex-matched controls regarding the proportion of aortic aneurysm 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. The study was performed utilizing the medical database of Clalit Health Services. RESULTS: The study included 5018 patients with SLE and 25,090 age- and sex-matched controls. The proportion of aortic aneurysm in patients with SLE was increased compared with the proportion in controls (0.6% and 0.1%, respectively, p < 0.001). In a multivariate analysis SLE was associated with the coexistence of aortic aneurysms (odds ratio 2.06, 95% confidence interval 1.21-3.51). CONCLUSIONS: Patients with SLE have a higher proportion of aortic aneurysms as compared with matched controls. Therefore, physicians treating patients with SLE should be aware of this life threatening association.