Incidence Of Rheumatoid Arthritis Research Articles

Dental service use among adults with incident type 2 diabetes, rheumatoid arthritis or inflammatory bowel disease.

It is not clear if or how the incidence of systemic conditions like type 2 diabetes mellitus (DM2), rheumatoid arthritis (RA) or inflammatory bowel disease (IBD) affects dental service utilization. Using nationwide Danish register data, the aim of this study was to analyse the use of dental services 7 years before and after being diagnosed with DM2, RA or IBD between 1997 and 2011. Information about incident DM2 was obtained from the National Diabetes Register, and incident RA and IBD were defined based on diagnosis codes of hospital contacts identified through the National Patient Register. Separately, for each of the three conditions, each individual with the incident condition was matched to one control individual based on age, gender, country of origin, municipality of residence, highest completed education, the main source of income and income using coarsened exact matching in the year of incidence. The use of dental services and treatments received within each calendar year from 7 years before to 7 years after getting the condition were analysed with generalized estimating equations. People with incident DM2 were less likely (by seven percentage points) to be dental service users within a year than people without incident DM2 for a period extending from up to 7 years prior to 7 years after the diagnosis. This difference even slightly increased after the diagnosis. Those with incident IBD exhibited a consistently but modestly higher proportion of dental service use (three percentage points) than those without incident IBD before and after the diagnosis. Differences in the use of services between those with or without incident RA were minor. For all three systemic diseases, detected differences mainly mirrored differences in the provision of supragingival scaling and restorative treatment. The findings suggest that the impact of these three systemic conditions on dental service use was minor.

Sex-Related Differences in Dispensation of Rheumatic Medications in Older Patients With Inflammatory Arthritis: A Population-Based Study.

The aim of our study was to compare dispensation of rheumatic medications between older male and female patients with early rheumatoid arthritis (RA) and psoriatic arthritis (PsA). This retrospective cohort study was performed using health administrative data from Ontario, Canada (years 2010-2017), on patients with incident RA and PsA, who were aged ≥ 66 years at the time of diagnosis. Yearly dispensation of rheumatic drugs was compared between older male and female patients for 3 years after diagnosis using multivariable regression models, after adjusting for confounders. The groups of drugs included in the analysis were disease-modifying antirheumatic drugs (DMARDs) classified as conventional synthetic DMARDs (csDMARDs) and advanced therapy (biologic DMARDs and targeted synthetic DMARDs), nonsteroidal antiinflammatory drugs (NSAIDs), opioids, and oral corticosteroids. Results were reported as odds ratios (ORs) with 95% CIs. We analyzed 13,613 patients (64% female) with RA and 1116 patients (57% female) with PsA. Female patients with RA were more likely to receive opioids (OR 1.39, 95% CI 1.22-1.58 to OR 1.51, 95% CI 1.32-1.72) and NSAIDs (OR 1.14, 95% CI 1.04-1.25 to OR 1.16, 95% CI 1.04-1.30). Dispensation of DMARDs showed no sex difference in either group. Subgroup analyses showed more intense use of advanced therapy in the RA cohort and of csDMARDs in the PsA cohort when patient and physician sex was concordant. This study did not identify any sex difference in the use of DMARDs among older patients with RA and PsA. The reasons for the higher use of opioids and NSAIDs among female patients with RA warrant further research.

Rheumatoid arthritis epidemiology: a nationwide study in Poland

To assess the incidence and prevalence of rheumatoid arthritis (RA) in Poland for the period 2013–2021, total and dependent on gender, age, region and serological status. Information on reported National Health Fund (NHF) health services and reimbursed prescriptions were used, defining an RA patient as a person who had at least two visits in different quarters with ICD-10 code M05 or M06 and at the same time filled at least one reimbursed prescription for a drug whose active substance is methotrexate, sulfasalazine, leflunomide or was treated with biologic disease-modifying anti-rheumatic drugs (bDMRDs) or targeted synthetic DMARDs (tsDMARDs) as part of a drug program financed by the National Health Fund. The nationwide standardised incidence rate of RA in 2021 was 29 persons per 100,000 population (18 per 100,000 population of seropositive vs. 11 per 100,000 population of seronegative RA). The prevalence of RA in Poland in 2021 was 689.0 people per 100,000 population, a total of 0.7% (1.1% in women and 0.3% in men). The incidence of seronegative RA was approximately 38%. The majority of new RA diagnoses were in the sixth and seventh decades of life, irrespective of patients’ gender. The results allow RA to be classified as a disease with a significant social impact. A trend of later onset of RA has been observed, which requires special consideration of the needs of patients over 55 years of age.

P021 Uptake, safety, and effectiveness of pneumococcal vaccination in adults with immune mediated inflammatory diseases: a UK wide study using data from the Clinical Practice Research Datalink

Abstract Background/Aims The safety and effectiveness of pneumococcal vaccine in people with immune mediated inflammatory diseases (IMIDs) is not known, which may contribute to suboptimal uptake. We investigated UK wide pneumococcal vaccine uptake in adults with IMIDs, the association between pneumococcal vaccination and disease flares, and the effectiveness of pneumococcal vaccine in preventing pneumonia in this at-risk population. Methods Adults with incident rheumatoid arthritis (RA), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE) and spondyloarthritis (SpA) prior to 31st August 2018 in the Clinical Practice Research Datalink (CPRD) Gold were included. The study was approved by CPRD research data governance (Reference 21_000614). We calculated the proportion of patients vaccinated against pneumococcal pneumonia. To investigate the association between vaccination and IMID flare, we employed a self-controlled case series analysis, adjusted for season. The study period was up-to six-month before and six-month after the date of pneumococcal vaccination. This period was partitioned into induction (14 days pre-vaccination) and exposed periods (up-to 90 days post vaccination) with the remaining time considered unexposed. Incidence rate ratios (IRR) and 95% CI were calculated. We conducted a multivariable nested case-control study to assess vaccine effectiveness. Cases were patients hospitalised with pneumonia and were matched to up to ten controls for age and sex. Multivariable conditional logistic regression was used to calculate odds ratio (OR) and 95% CI. Results We included 32,277 IMID patients: 14,151 with RA, 13,631 with IBD, 3,804 with SpA and 691 with SLE. Overall uptake of pneumococcal vaccination was 50% (95% CI 49.4% -50.5%). Vaccination uptake was significantly lower in the under 45-year-olds, in patients with IBD and in those without additional indication for vaccination at 29.7%, 38.4%, 42.7% respectively. In the safety study, data for 1001, 854, 424 vaccinated patients with primary care consultations for joint pain, AIRD flare, and IBD flare respectively were included. Vaccination against pneumococcal pneumonia was not associated with AIRD flare (IRR (95% CI) 1.07 (0.93-1.22)), primary care consultations for joint pain (IRR (95% CI) 0.95 (0.83-1.10)), and IBD flare (IRR (95% CI) 0.82 (0.64-1.06)) in the 90-days post vaccination. The vaccine effectiveness study included 25,707 patients, either with (n = 2,771) or without (n = 22,936) a hospitalisation record for pneumonia after IMID diagnosis. Patients hospitalised for pneumonia compared with their matched controls, had higher odds of current smoking, deprivation, corticosteroid prescriptions, additional indication for vaccination, primary care consultations, hospital admissions and prescriptions. In the multivariable adjusted model, pneumococcal vaccination was associated with reduced odds of hospitalisation for pneumonia (OR (95% CI) 0.88 (0.78-0.98). Conclusion The uptake of pneumococcal vaccine is low in IMID patients. Pneumococcal vaccination is not associated with IMID flare and is protective against pneumonia. These findings call for promotion of pneumococcal vaccination in IMID by health professionals. Disclosure G. Nakafero: None. M.J. Grainge: None. C.D. Mallen: Grants/research support; NIHR, MRC, Versus Arthritis and BMS. T. Card: None. J.S. Nguyen Van-Tam: Consultancies; CSL Seqirus and Moderna. Royalties; AstraZeneca and Sanofi Pasteur. A. Abhishek: Consultancies; NGM Bio, Limbic and Inflazome.. Royalties; UpToDate, Springer, Cadilla Pharmaceuticals.. Grants/research support; AstraZeneca and Oxford Immunotech..

Global burden of rheumatoid arthritis among adolescents and young adults aged 10-24 years: A trend analysis study from 1990 to 2019.

In recent decades, there has been a global increase in the burden of rheumatoid arthritis (RA) among adolescents and young adults (AYAs), making it a significant public health issue. However, our understanding of the disease burden, harm, and influencing factors of RA in this population remains insufficient. This study aimed to assess the trends in RA burden among AYAs aged 10-24 years from 1990 to 2019 at the global, regional, and national levels. Incidence, prevalence, and disability-adjusted life years (DALYs) rate per 100,000 population, as well as average annual percentage changes (AAPCs), of RA among individuals aged 10-24 years were reported globally, regionally, and nationally based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019). These global trends were further analyzed by age, sex, and Sociodemographic index (SDI). Joinpoint regression analysis was used to determine the year in which the most significant changes in global trends occurred. Globally, the incidence of RA among AYAs increased from 4.98 per 100,000 population in 1990 to 5.41 per 100,000 population in 2019, with an AAPCs of 0.29 (95%CI: 0.26, 0.32, p < 0.001). The most significant increase occurred in 2000, while the most significant decrease occurred in 2014. The prevalence increased from 34.11 per 100,000 population in 1990 to 36.34 per 100,000 population in 2019, with an AAPCs of 0.22 (95%CI: 0.19, 0.24, p<0.001); The most significant increase was observed in 2000, and the most significant decrease occurred in 2014. DALYs rate with RA were 5.96 per 100,000 population in 1990 and 5.79 per 100,000 population in 2019 for AYAs, with an average decrease of 0.1 years per year (AAPCs = -0.1, 95%CI: -0.2, -0.01, p = 0.04). In terms of gender, the incidence, prevalence, and DALYs rate were higher for females compared to males during the same period. Regarding age, the incidence, prevalence, and DALYs rate increased with increasing age. Based on the SDI quintile, the incidence, prevalence, and DALYs rate of RA were highest in countries with high SDI and lowest in countries with low SDI from 1990 to 2019. However, the relationship between incidence and SDI is non-linear. In terms of regions, Tropical Latin America exhibited the highest incidence, prevalence, and DALYs rate, while Andean Latin America experienced the most rapid increase in incidence and prevalence. Southern Latin America saw the fastest growth in DALYs rate, whereas Southern Sub-Saharan Africa witnessed the most significant decline. In conclusion, the study revealed an overall increase in the incidence and prevalence of RA among adolescents and young adults (AYAs) over the past three decades, while DALYs rate remained relatively stable. Furthermore, the incidence, prevalence, and DALYs rate of RA were found to increase with age. Fortunately, recent proactive preventive measures and treatment methods have shown promising results. Moving forward, it is crucial to prioritize the female population and AYAs patients in order to further alleviate the global burden of RA.

MicroRNA-150 Deletion Reduces the Occurrence and Severity of Rheumatoid Arthritis by Inhibiting IL-17.

Understanding the effects of epigenetic factors on the pathogenesis of rheumatoid arthritis (RA) is important for the early diagnosis and therapeutic intervention of this disease. MicroRNA-150 (miR-150) exerts an important influence on the development and function of lymphocytes. However, the role of miR-150 in the pathogenesis of RA remains unclear. To explore the role of miR-150 in the pathogenesis of RA and the related immune mechanism. In this study, we used miR-150 knock-out (miR-150KO) and created animal models of RA. Flow cytometry, immunohistochemistry, and real-time RT-PCR were employed to assess the frequency of T cell subsets and cytokines expression. Compared to wild-type (WT) mice, the onset of RA was postponed and the incidence of RA was reduced in miR-150KO mice. The expression of IL-4 and IFN-γ significantly increased while the expression of IL-17 decreased significantly in NKT and CD4+ T cells of KO mice compared to that of WT mice after RA induction. In addition, the expression of IL-4 and IFN-γ increased while the expression of IL-17 decreased significantly in the joint tissues of KO mice compared to that of WT mice. Furthermore, the mRNA expression of TNF-α and IL-17 decreased significantly in the synovial fluid cells of KO mice compared to that of the WT mice after RA induction. MiR-150 deficiency decreases the expression of IL-17 in T cells and joint tissues, and alleviates the occurrence and progression of RA in mice.

Exploring the Link between Head and Neck Cancer and Elevated Risk of Rheumatoid Arthritis: A National Population-Based Cohort Study.

An increased risk of cancer among patients with rheumatoid arthritis (RA) has been reported. However, the risk of RA events among patients with head and neck cancer (HNC) is unknown. Therefore, we investigated the incidence and risk of RA among patients with HNC. This study was based on a cohort dataset. Overall, 2824 individuals without HNC and 706 patients with HNC were selected using propensity score matching. The overall RA event rate was 12.19 for patients with HNC and 7.60 for those without HNC. A significantly increased risk of developing RA was also observed among patients with HNC. The risk of developing RA over time was relatively high within the first year after HNC diagnosis; further, it increased significantly during the follow-up period. Moreover, middle-aged male patients with HNC exhibited an increased risk of developing RA compared with the controls; however, no significant difference was noted among female patients or other age groups. Notably, subgroup analysis according to cancer subtype revealed that only oral cancer survivors had an increased risk of developing RA. These results underscore the importance of vigilant monitoring by clinicians to promptly identify the onset of RA in patients with HNC.

The causal impact of saturated fatty acids on rheumatoid arthritis: a bidirectional Mendelian randomisation study.

The causal relationship between saturated fatty acids (SFAs) and rheumatoid arthritis (RA) remains poorly understood. This study aimed to determine whether SFAs are causally related to RA using Mendelian randomisation (MR) analyses. Genome-wide association study (GWAS) summary data for RA (ukb-d-M13_RHEUMA) and SFAs (met-d-SFA) were obtained from the Integrative Epidemiology Unit OpenGWAS database. A bidirectional MR analysis was performed using a suite of algorithms, namely the MR-Egger, weighted median, simple mode, weighted mode, and inverse-variance weighted (IVW) algorithms, all integrated using the "MR" function. The robustness of the MR findings was further evaluated through sensitivity analyses, including heterogeneity, horizontal pleiotropy, and leave-one-out tests. The IVW algorithm in the forward MR analysis indicated a causal link between SFAs and RA (p = 0.025), identifying SFAs as a risk factor for RA (odds ratio = 1.001). Sensitivity analyses indicated no significant heterogeneity, horizontal pleiotropy, or severe bias, reinforcing the credibility of the forward MR results. However, the reverse MR analysis revealed that RA does not causally affect SFA levels (p = 0.195), and this finding was supported by corresponding sensitivity analyses. The findings of this study substantiate the positive causal effect of SFAs on the incidence of RA through bidirectional MR analysis, thereby offering a consequential direction for future research on the diagnosis and treatment of RA.

Associations Between Thiazolidinediones Use and Incidence of Rheumatoid Arthritis: A Retrospective Population-Based Cohort Study.

Preclinical studies suggest that thiazolidinediones (TZDs) may have a protective effect on rheumatoid arthritis (RA), but evidence from population-based studies is scarce. This study aimed to assess the association between use of TZDs and incidence of RA in a retrospective cohort of patients with type 2 diabetes mellitus (T2DM). A retrospective cohort of patients with T2DM who were new users of TZDs or alpha glucosidase inhibitors (AGIs) was assembled. We applied the inverse probability of treatment weighted Cox model to estimate the hazard ratio (HR) of RA incidence associated with the use of TZDs compared with AGIs. The final analysis included 56,796 new users of AGIs and 14,892 new users of TZDs. The incidence of RA was 187.4 and 135.2 per 100,000 person-years in AGI users and TZD users, respectively. Compared with use of AGIs, TZD use was associated with a reduction in RA incidence, with an HR of 0.72 (95% confidence interval [95% CI] 0.59-0.89). HRs for cumulative use of TZDs for 0.51 to 4.0 years and more than 4 years with incidence of RA were 0.55 (95% CI 0.35-0.88) and 0.74 (95% CI 0.57-0.98), respectively. Various subgroup analyses and sensitivity analyses were consistent with the primary analysis. Use of TZDs is associated with a decreased risk of incident RA in patients with T2DM.

Associations of cereal fiber intake with rheumatoid arthritis mediated by dietary inflammatory index: insights from NHANES 2011–2020

Rheumatoid Arthritis (RA) is an increasingly prevalent inflammatory disorder worldwide. Its complex etiology has recently brought dietary factors, particularly fiber intake, into focus as potential influencers. Our study investigates the intricate relationship between various sources of dietary fiber and RA, emphasizing the mediating role of the Dietary Inflammatory Index (DII). Leveraging data from the National Health and Nutrition Examination Survey spanning 2011 to 2020. We meticulously assessed dietary fiber intake through dual 24 h dietary recall interviews, while RA diagnoses were established based on comprehensive medical surveys. The relationships between fiber intake, RA prevalence, and DII mediation were analyzed using sophisticated multivariate logistic regression and mediation analysis. Among our study cohort, 7% were diagnosed with RA. We observed a notable inverse correlation between increased total fiber intake, particularly 5 g/day increments, and the incidence of RA, with cereal fiber intake emerging as the primary mitigating factor. Intriguingly, the DII played a significant role in mediating this association, especially regarding cereal fiber. Our findings reveal a significant association between higher cereal fiber consumption and a reduced prevalence of RA. Additionally, the DII stands out as a pivotal mediator in this relationship, highlighting dietary management's critical role in preventing and managing RA.

Higher Risk of Rheumatoid Arthritis in Patients With Chronic Rhinosinusitis: Prospective Association in the U.K. Biobank and Genetic Evidence by Mendelian Randomization Analysis.

Previous studies have shown that respiratory diseases are associated with an increased risk of rheumatoid arthritis (RA). However, whether there is a correlation between chronic rhinosinusitis (CRS) and RA is not known. Due to the high incidence of CRS, it remains to be clarified whether we should pay additional attention to RA risk in the huge population of CRS. We used a 2-sample Mendelian randomization (MR) analysis to explore the causal effects of CRS on the incidence of RA. The inverse variance weighted (IVW) approach was used as the main analysis in the MR randomization study. Then, we used the data from the U.K. Biobank to examine the association between RA and CRS at the individual level in a prospective cohort. We identified patients with CRS at the time of recruitment and further followed the incidence of RA until 2021. The risk of developing RA in patients with CRS was determined by a multivariate Cox regression model. We used 3 multivariate Cox models to adjust for individual characteristics, lifestyle factors and concomitant diseases, respectively. The MR analysis by the IVW model suggested that the odds ratio of RA associated with genetically predicted CRS was 2.39 (95% CI [1.08-5.30]; p = .032). In the first multivariate model adjusting for individual characteristics, CRS was associated with a 47% increase of risk of developing RA (hazard ratio [HR] = 1.47; 95% CI [1.12-1.90]). In the second multivariate model adjusting for lifestyle factors, the HR of RA associated with CRS was 1.48 (95% CI [1.15-1.90]). In the third multivariate model, chronic sinusitis was associated with a 32% increase in RA risk (HR = 1.32; 95% CI [1.03-1.70]). CRS has a genetically causal effect on the incidence of RA, and the risk of RA is greatly higher in CRS at the individual level. This is the first study to reveal an association between CRS and RA. Due to the high incidence of CRS, it is recommended that additional attention should be paid to the increased RA risk in patients with CRS compared to that in common people.

Multiple morbidities are associated with serious infections in patients with rheumatoid arthritis

ObjectiveTo assess the association between a comprehensive list of morbidities and serious infection (SI) in patients with rheumatoid arthritis (RA). MethodsThis study evaluated SI risk associated with 55 comorbidities using a population-based inception cohort including all adult patients with incident RA from 1999 through 2014 with follow up through 2021. Morbidities and SI were ascertained using previously validated international classification of disease (ICD)-9 and ICD-10 codes. Conditional frailty models were utilized to analyze the association between each morbidity and SI: Model 1 adjusted for age, sex, and calendar year; Model 2 adjusted for factors in Model 1 and the Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) Risk Score of Infections; and Model 3 adjusted for factors in Model 1 and the Mayo SI Risk Score. Results911 patients (70 % female, mean age 56 years, 66 % seropositive) were included. There were 293 SI among 155 patients (17 %), corresponding to an incidence of 3.9 SI per 100 person-years. Eighteen SI were fatal. Risk of SI was significantly increased in 27 of 55 morbidities in Model 1, 11 morbidities in Model 2, and 23 morbidities in Model 3. Additionally, several morbidities included in the RABBIT and Mayo risk scores continued to have large effect sizes despite adjustment. Serious infection risk increased by 11–16 % per morbidity in the three models. ConclusionsSeveral morbidities are associated with an increased risk for SI. Future risk scores may include morbidities identified in this study for improved SI risk assessment.

Metabolic Syndrome Is Associated With an Increased Risk of Rheumatoid Arthritis: A Prospective Cohort Study Including 369,065 Participants.

To explore the associations between metabolic syndrome (MetS) and its individual components and the risk of rheumatoid arthritis (RA). A total of 369,065 individuals were included in the present study based on the UK Biobank. Multivariable Cox proportional hazards regression models were applied to estimate the associations between MetS and its individual components and the risk of RA. Mediation analysis was performed to further assess the potential mediating role of C-reactive protein (CRP) in the relationship between MetS and RA. During a median follow-up period of 12.04 years, a total of 4901 incident RA cases were documented. MetS (hazard ratio [HR] 1.22, 95% CI 1.14-1.30) and 4 of its 5 components (elevated waist circumference [WC; HR 1.21, 95% CI 1.12-1.32], elevated triglyceride [TG] level [HR 1.12, 95% CI 1.05-1.19], reduced high-density lipoprotein cholesterol [HDL-C] level [HR 1.31, 95% CI 1.23-1.39], and hyperglycemia [HR 1.15, 95% CI 1.05-1.25]) were associated with an increased risk of RA. In addition, the risk of RA increased as the number of diagnosed MetS components increased, with the highest risk in participants with all 5 components. Mediation analysis showed that CRP might mediate the association between MetS and RA, accounting for 9.27% of the total effect. These findings indicated positive associations between MetS and 4 of its components (WC, TG, HDL-C, and hyperglycemia) and the risk of RA, highlighting the importance of MetS management in the prevention of RA.

Molecular Dynamics Simulation of Various Bioactive Compounds of Red Betel (Piper crocatum) as Anti-Inflammatory Drug-Like Candidates in Rheumatoid Arthritis Treatment

Joint inflammation and damage can be caused by rheumatoid arthritis (RA), a systemic autoimmune disorder. Long-term RA affects the joints, causing pain, edema, and stiffness. Several studies have revealed that the exact origin of RA is still unidentified, but inherited disorder and external factors may contribute to the inflammatory condition. The incidence of RA is mostly caused by uncontrolled-production of pro-inflammatory cytokines under nuclear factor-kappa B (NF-κB) overexpression condition. The nuclear factor-kappa B plays an important role in inflammatory T cell activation, differentiation, and effector function. Therefore, the inhibition of NF-κB can be a strategy to reduce the adverse effects or incidence of RA. Red betel is a perennial herb native to Indonesia that is widely used by conventional healers. Many reports show that red betel leaf extracts contain several critical bioactive compounds such as Apigenin, Luteolin, Hydroxychavicol, Eugenol, and Chavibetol. This present study aims to evaluate and predict the therapeutic potential of those compounds as medication that reduce inflammation against RA by disturbing and inactivating the NF-κB molecular interaction. The LC-MS chromatography was used to evaluate the chemical contents of red betel leaves. Furthermore, in silico study, the 3D structure of the active compounds of red betel leaves is obtained from PubChem web server, while NF-κB is obtained from Protein Data Bank (PDB) website. Molecular docking was used to screen the potential compounds compared to aspirin as control. As a result, 2 compounds including Apigenin and Luteolin have smaller bond affinity values, −6.3 and −6.0 kcal/mol, respectively compared to aspirin. Based on molecular dynamics (MD) simulation, the root-mean-square deviation (RMSD) value of protein-ligand complexes have the similar pattern over 1000/ps except the NF-κB-Chavibetol complex which has an unstable pattern. On the other hand, the total energy of the protein-ligand complexes have similar average number of −1.69 kJ/mol. The simulation indicates the ligands have constant binding energy to the protein. Furthermore, numerous pharmacokinetic properties of compounds including absorption, distribution, metabolism, excretion and toxicity are exponentially greater than the control drugs. Finally, red betel active compounds can be used as alternative candidates of RA therapy medication. HIGHLIGHTS Rheumatoid arthritis, a systemic autoimmune condition, damages joints. Long-term RA causes joint discomfort, swelling, and stiffness. The identified flavonoids from red betel leaf extract include flavonone, isoflavone, auron, catechin, anthocyanidin, and chalcone. Apigenin, chavibetol, eugenol, hydroxychavicol, and luteolin, the active chemicals found in red betel, have the potential to serve as NF-B inhibitors, making them potentially useful in the treatment of rheumatoid arthritis. GRAPHICAL ABSTRACT

Relationship of weight change patterns from young to middle adulthood with incident rheumatoid arthritis and osteoarthritis: a retrospective cohort study.

The relationship between weight change patterns and arthritis onset, specifically rheumatoid arthritis (RA) and osteoarthritis (OA), is unclear. We examined the association between weight changes from young adulthood to midlife and arthritis onset. Using data from NHANES 1999-2018, participants with self-reported arthritis were selected. Age at diagnosis determined arthritis onset. Weight change patterns were based on BMI at age 25 and 10 years before the survey. Patterns were categorized as stable non-obese, non-obese to obese, obese to non-obese, and stable obese. Cox regression models and restricted cubic spline (RCS) analysis were employed, calculating hazard ratios (HRs) and 95% confidence intervals (CIs) considering covariates. Out of 20,859 participants (male 11,017, 52.82%), 4922 developed arthritis over a mean 8.66-year follow-up. Compared to stable non-obese individuals, the HRs for arthritis were 1.55 (95% CI=1.45 to 1.66, P < 0.0001) for non-obese to obese and 1.74 (95% CI=1.56 to 1.95, P < 0.0001) for stable obese. Those gaining 10-20kg had a HR of 1.33 (95% CI=1.22 to 1.46, P < 0.0001), and gains >20kg had a HR of 1.56 (95% CI=1.42 to 1.71, P < 0.0001), compared to stable weight (change within 2.5kg). Identical results observed for OA and RA. RCS showed a nonlinear relationship between weight change and arthritis (all P < 0.01). Stable obesity and weight gain during adulthood increase arthritis risk. Maintaining a non-obese weight throughout adult years might reduce arthritis risk in later life.

Antimalarial Adherence and Risk of Cardiovascular Events in Patients With Rheumatoid Arthritis and Systemic Lupus Erythematosus: A Population-Based Study.

We aimed to assess the association between antimalarial adherence and cardiovascular events between incident rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) population-based cohorts. All patients with incident RA/SLE and incident antimalarial use in British Columbia, Canada, between January 1997 and March 2015 were identified using provincial administrative databases. The outcomes were incident cardiovascular events, including myocardial infarction (MI), stroke, or venous thromboembolism (VTE). The exposure was antimalarial adherence with levels: discontinuation (proportion of days covered [PDC=0]), nonadherence (0 < PDC < 0.90), and adherence (PDC ≥ 0.90). We used marginal structural models to estimate the effect of antimalarial adherence on the rate of cardiovascular events, accounting for potential confounders. We identified 16,538 individuals with incident RA/SLE and incident antimalarial use without any cardiovascular event before the index date. Over nine years mean follow-up, 2,174 incident cardiovascular events (13.2%) were observed. The adjusted hazard ratio (aHR) for incident cardiovascular events for antimalarial adherence relative to discontinuation was 0.72 (95% confidence interval [CI] 0.64-0.81) and 1.01 (95% CI 0.90-1.14) for nonadherence. Additionally, the aHRs for all cardiovascular events, MI, stroke, and VTE for adherence relative to nonadherence was 0.71 (95% CI 0.61-0.82), 0.62 (95% CI 0.51-0.75), 0.45 (95% CI 0.36-0.58), and 0.65 (95% CI 0.46-0.93), respectively. We found older age modified the association between antimalarial adherence and cardiovascular events (P = 0.02). When people newly diagnosed with RA or SLE take their antimalarial regularly as prescribed (PDC ≥ 0.90), they have a 29% lower risk of sustaining a cardiovascular event than patients with a lower degree of adherence (PDC < 0.90) and a 28% lower risk than if they discontinue antimalarials.

A potential role for chlamydial infection in rheumatoid arthritis development

Abstract Objectives To assess the relationship between self-reported and serological evidence of prior chlamydial infection, rheumatoid arthritis (RA)-related autoantibodies and risk of RA development. Methods This is a nested study within a prospective Swiss-based cohort including all first-degree relatives of RA patients (RA-FDR) who answered a questionnaire on past chlamydial infections. Primary outcome was systemic autoimmunity associated with RA (RA autoimmunity) defined as positivity for anti-citrullinated peptide antibodies (ACPA) and/or rheumatoid factor (RF). Secondary outcomes were high levels of RA autoimmunity, RA-associated symptoms and RA autoimmunity, and subsequent seropositive RA diagnosis. We conducted a nested case–control analysis by measuring the serological status against the major outer membrane protein of Chlamydia trachomatis. We replicated our analysis in an independent USA-based RA-FDR cohort. Results Among 1231 RA-FDRs, 168 (13.6%) developed RA autoimmunity. Prevalence of self-reported chlamydial infection was significantly higher in individuals with RA autoimmunity compared with controls (17.9% vs 9.8%, odds ratio [OR] = 2.00; 95% CI: 1.27, 3.09; P &amp;lt; 0.01). This association remained significant after adjustments (OR = 1.91; 95% CI: 1.20, 2.95). Stronger effect sizes were observed in later stages of RA development. There was a similar trend between a positive C. trachomatis serology and high levels of RA autoimmunity (OR = 3.05; 95% CI: 1.10, 8.46; P = 0.032). In the replication cohort, there were significant associations between chlamydial infection and RF positivity and incident RA, but not anti-CCP positivity. Conclusion Self-reported chlamydial infections are associated with elevated RA autoimmunity in at-risk individuals. The differing association of chlamydial infections and ACPA/RF between cohorts will need to be explored in future studies, but is consistent with a role of mucosal origin of RA-related autoimmunity.

Decline in Incidence of Extra-Articular Manifestations of Rheumatoid Arthritis: A Population-Based Cohort Study.

The focus of this study was to assess changes in the cumulative incidence of extra-articular manifestations of rheumatoid arthritis (ExRAs) and associated mortality risk. This study evaluated trends in occurrence of ExRAs using a population-based inception cohort that included all adult patients with incident rheumatoid arthritis (RA) from 1985 through 2014 meeting the 1987 American College of Rheumatology criteria. Patients were divided into two cohorts based on the incidence date of RA, 1985 to 1999 and 2000 to 2014. The occurrence of ExRAs was determined by manual chart review, and the 10-year cumulative incidence was estimated for each ExRA in both cohorts. Cox proportional hazard models were used to determine associations between specific demographic and RA disease characteristics and ExRAs and between ExRAs and mortality. There were 907 patients included, 296 in the 1985 to 1999 cohort and 611 in the 2000 to 2014 cohort. The 10-year cumulative incidence of any ExRA decreased significantly between the earlier and later cohorts (45.1% vs 31.6%, P < 0.001). This was largely driven by significant declines in subcutaneous rheumatoid nodules (30.9% vs 15.8%, P < 0.001) and nonsevere ExRAs (41.4% vs 28.8%, P = 0.001). Identified risk factors for the development of any ExRAs include rheumatoid factor positivity (hazard ratio [HR] 2.02, 95% confidence interval [CI] 1.43-2.86) and current smoking (HR 1.61, 95% CI 1.10-2.34). Mortality was increased in patients with either nonsevere (HR 1.83, 95% CI 1.18-2.85) or severe ExRAs (HR 3.05, 95% CI 1.44-6.49). The incidence of ExRAs has decreased over time. Mortality remains increased in patients with ExRAs.

Large-scale genome-wide association study to identify causal relationships and potential mediators between education and autoimmune diseases.

Epidemiological studies suggested a potential connection between education and autoimmune disorders. This study investigated the possible cause-and-effect relationship using a Mendelian randomization approach. We explored the causality between four education traits (n = 257,841~1,131,881) and 22 autoimmune diseases. The mediating role of smoking (632,802 individuals), BMI (681,275 individuals), alcohol (335,394 individuals), and income (397,751 individuals) was also investigated. Transcriptome-wide association study (TWAS) and enriched signaling pathways analysis were used to investigate the underlying biological mechanisms. Especially, higher cognitive performance was protective for psoriasis (odds ratio (OR) = 0.69, 95% confidence interval (CI) = 0.60-0.79, p = 6.12×10-8), rheumatoid arthritis (RA) (OR = 0.75, 95% CI = 0.67-0.83, p = 4.62×10-6), and hypothyroidism (OR = 0.83, 95% CI = 0.77-0.90, p = 9.82×10-6). Higher levels of educational attainment decreased risks of psoriasis (OR = 0.61, 95% CI = 0.52-0.72, p = 1.12×10-9), RA (OR = 0.68, 95% CI = 0.59-0.79, p = 1.56×10-7), and hypothyroidism (OR = 0.80, 95% CI = 0.72-0.88, p = 5.00×10-6). The completion of highest-level math class genetically downregulates the incidence of psoriasis (OR = 0.66, 95% CI = 0.58-0.76, p = 2.47×10-9), RA (OR = 0.71, 95% CI = 0.63-0.81, p = 5.28×10-8), and hypothyroidism (OR = 0.85, 95% CI = 0.79-0.92, p = 8.88×10-5). Higher self-reported math ability showed protective effects on Crohn's disease (CD) (OR = 0.67, 95% CI = 0.55-0.81, p = 4.96×10-5), RA (OR = 0.76, 95% CI = 0.67-0.87, p = 5.21×10-5), and psoriasis (OR = 0.76, 95% CI = 0.65-0.88, p = 4.08×10-4). Protein modification and localization, response to arsenic-containing substances may participate in the genetic association of cognitive performance on UC, RA, psoriasis, and hypothyroidism. According to mediation analyses, BMI, smoking, and income served as significant mediators in the causal connection between educational traits and autoimmune diseases. Higher levels of education-related factors have a protective effect on the risk of several autoimmune disorders. Reducing smoking and BMI and promoting income equality can mitigate health risks associated with low education levels.

Mediterranean diet and incident rheumatoid arthritis: A nine-year cohort study among UK Biobank participants

Mediterranean diet and incident rheumatoid arthritis: A nine-year cohort study among UK Biobank participants