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ID PMID Title PublicationDate abstract
35306043 Bioavailability, anti-inflammatory and anti-arthritic effect of Acetyl Keto Boswellic acid 2022 Jun 28 ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis is one of the most common disabling chronic progressive autoimmune diseases affecting the adult world population. Boswellia serrata has been a known anti-inflammatory agent since ancient times. Therefore, research on Boswellia extract based on Acetyl Keto Boswellic Acid (AKBA) content evaluating its efficacy and safety is necessary. The study aimed to find a suitable Boswellia extract rich in AKBA to evaluate its bioavailability, anti-inflammatory, and anti-arthritic effect. In addition, the synergistic action of AKBA extract with methotrexate (MTX) was also assessed on an animal model. MATERIALS AND METHODS: Oral bioavailability of AKBA and the anti-inflammatory activity of 10% AKBA (5, 10, 20, 40 mg/kg b.w) was assessed and compared with 2% AKBA (40 mg/kg) and diclofenac (10 mg/kg). The effect of 10% AKBA at 20 mg/kg and 40 mg/kg was evaluated in the FCA induced arthritis animal model alone and combined with methotrexate (MTX) at 2 mg/kg b.w. Subplantar injection of FCA produced edema within a few hours with progressive arthritis by the 9th day after injection. All the treatments were initiated from the 10th day until the 45th day. Oral administration of 10% AKBA was done daily and MTX by intraperitoneal route once a week from day 10 to day 45. Paw volume, erythrocyte sedimentation rate (ESR), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP), total bilirubin, oxidative markers (superoxide dismutase (SOD) levels, malondialdehyde (MDA), total proteins and liver histopathology were examined. RESULTS: 10% AKBA provided 8.48-fold, 24.22-fold, 47.36-fold, and 110.53-fold higher AUC (0-α) of AKBA at 5 mg/kg, 10 mg/kg, 20 mg/kg and 40 mg/kg, respectively compared to 2% AKBA at 40 mg/kg. Percentage paw edema inhibition of 10% AKBA at 20 mg/kg and 40 mg/kg were significantly higher than 2% regular AKBA (40 mg/kg) and diclofenac (10 mg/kg). 10% AKBA at a dose of 20 and 40 mg/kg significantly reduced ESR compared with FCA treated group. A combination of methotrexate with 10% AKBA showed the highest reduction in ESR. 10% AKBA at both dose levels significantly reduced hepatic marker enzymes and total bilirubin levels. Treatment with 10% AKBA showed a significant increase in total proteins, antioxidant enzymes and a decrease in malondialdehyde levels. Similarly, 10% AKBA protected the hepatocytes compared with the FCA and FCA + MTX treated group. 10% AKBA was capable of significantly minimizing FCA and FCA + MTX induced changes. CONCLUSION: Anti-inflammatory activity of AKBA due to inhibition of lipoxygenase (LOX) enzymes supports the use of AKBA in inflammatory disorders. Combination therapy of 10% AKBA with MTX is effective in inhibiting arthritis and circumventing hepatotoxicity produced by MTX in arthritic animals.
34313940 Predicting presenteeism using measures of health status. 2022 Feb OBJECTIVES: To identify whether it is feasible to develop a mapping algorithm to predict presenteeism using multiattribute measures of health status. METHODS: Data were collected using a bespoke online survey in a purposive sample (n = 472) of working individuals with a self-reported diagnosis of Rheumatoid arthritis (RA). Survey respondents were recruited using an online panel company (ResearchNow). This study used data captured using two multiattribute measures of health status (EQ5D-5 level; SF6D) and a measure of presenteeism (WPAI, Work Productivity Activity Index). Statistical correlation between the WPAI and the two measures of health status (EQ5D-5 level; SF6D) was assessed using Spearman's rank correlation. Five regression models were estimated to quantify the relationship between WPAI and predict presenteeism using health status. The models were specified based in index and domain scores and included covariates (age; gender). Estimated and observed presenteeism were compared using tenfold cross-validation and evaluated using Root mean square error (RMSE). RESULTS: A strong and negative correlation was found between WPAI and: EQ5D-5 level and WPAI (r = - 0.64); SF6D (r =- 0.60). Two models, using ordinary least squares regression were identified as the best performing models specifying health status using: SF6D domains with age interacted with gender (RMSE = 1.7858); EQ5D-5 Level domains and age interacted with gender (RMSE = 1.7859). CONCLUSIONS: This study provides indicative evidence that two existing measures of health status (SF6D and EQ5D-5L) have a quantifiable relationship with a measure of presenteeism (WPAI) for an exemplar application of working individuals with RA. A future study should assess the external validity of the proposed mapping algorithms.
35188715 IgG Anti-Citrullinated Protein Antibody Variable Domain Glycosylation Increases Before the 2022 Feb 21 OBJECTIVE: The autoimmune response in rheumatoid arthritis (RA) is marked by the presence of anti-citrullinated protein antibodies (ACPAs). A notable feature of IgG ACPA is the abundant expression of N-linked glycans in the variable domain. However, the presence of ACPA variable domain glycosylation (VDG) across disease stages, and its response to therapy, are poorly described. To understand its dynamics, we investigated the abundance of IgG ACPA VDG in 1,498 samples from individuals in different clinical stages. METHODS: Using liquid chromatography, we analyzed IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden. We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. Additionally, we measured VDG in 234 samples from patients with RA who did or did not achieve long-term drug-free remission (DFR) during up to 16 years follow-up. RESULTS: IgG ACPA VDG significantly increased (P < 0.0001) toward disease onset and was associated with ACPA levels and epitope spreading prior to diagnosis. A slight increase in VDG was observed in patients with established RA, with a moderate influence of treatment (P = 0.007). In patients in whom DFR was later achieved, IgG ACPA VDG was already reduced at the time of RA onset. CONCLUSION: The abundance of IgG ACPA VDG increases toward RA onset and correlates with maturation of the ACPA response. While IgG ACPA VDG levels are fairly stable in established disease, a lower degree of VDG at RA onset correlates with DFR. Although the underlying biologic mechanisms remain elusive, our data support the concept that VDG relates to an expansion of the ACPA response in the pre-disease phase and contributes to disease development.
34471964 Radiographic changes in the distal ulna in non-rheumatoid patients with extensor digitorum 2022 Feb INTRODUCTION: Osteoarthritis of the distal radioulnar joint (DRUJ) is relatively common in elderly people. Extensor digitorum communis (EDC) ruptures occasionally and occurs with or without prior signs in these people. The purpose of this study was to clarify the radiographic changes in the distal ulna associated with EDC rupture. MATERIALS AND METHODS: We analyzed plain radiographs of 71 patients with non-rheumatoid arthritis and 40 controls. Radiographic changes in the distal ulna were categorized into normal, osteoarthritic-change (OA-change), and taper. We measured the ulnar variance (UV) and ulnar bowing angle in the posteroanterior radiographs and the dorsal bowing angle (DBA) and dorsal protrusion (DP) in the lateral radiographs. The shape of the sigmoid notch (SN) was categorized into flat, radial inclination, and dimple. The primary outcome was a comparison of radiographic parameters between the patient and the control groups. The secondary outcome was an analysis of the type of SN to investigate factors affecting ulnar deformation. RESULTS: The ratio of the radiographic change in the ulna, UV, DBA, and DP was significantly larger in the patient group than in the control group. Patients with the radial inclination type of SN showed a greater UV than those with the dimple type. CONCLUSIONS: Deformation of the distal ulna, a large UV, dorsal penetration, and dorsal bowing was related to EDC rupture. Regarding the large UV, the lunate shaved the upper half of the distal ulna, whereas the DRUJ shaved the lower half. These processes formed a tapered ulna head. A large UV and an inclination of the DRUJ played a role in ulnar head deformation.
35325053 Soluble interleukin-2 receptor serum levels facilitate prediction of relapses in subgroups 2022 Mar 23 OBJECTIVES: Juvenile idiopathic arthritis (JIA) is characterised by a chronic disease course. Once patients achieve a state of inactive disease, there are no established biomarkers to predict the further course of inflammation for these patients. Therefore, the purpose of this study was to quantify serum biomarkers during quiescent disease to evaluate their use in identifying JIA-patients at risk for future disease flare. METHODS: Patients with non-systemic JIA reaching inactive disease status were divided into 2 groups: 92 patients with future active disease after a median period of 6 months (range 3-9) and 80 patients with persistent inactive disease for the following period (median 11 months, range 7-16) according to the juvenile arthritis disease activity score (JADAS). Clinical parameters and serum levels of various biomarkers were measured in the state of inactive disease using immunoassays in both groups and were analysed for their potential to predict the further course of disease. RESULTS: Soluble interleukin-2 receptor (sIL-2R) serum levels were significantly higher in patients with future active disease (p= 0.021), which especially applied to patients with rheumatoid factor (RF)-negative polyarticular and extended oligoarticular JIA (p< 0.001). Higher sIL-2R serum levels during inactive disease were associated with a greater number of active joints at future active disease. CONCLUSION: Patients without clinical signs of disease activity already presented with increased sIL-2R serum levels several months before disease relapses, whereas conventional inflammation parameters were not elevated. Determination of sIL-2R serum levels during inactive disease may facilitate identifying patients with subclinical disease activity at risk for future active disease.
30511559 Association between interleukin-10 polymorphisms and juvenile idiopathic arthritis: a meta 2022 Feb INTRODUCTION: The aim of this review is to investigate IL-10 polymorphisms (-1082 G/A, -819 C/T, and -592 C/A) and their association with susceptibility to JIA. EVIDENCE ACQUISITION: A meta-analysis was conducted after database search for relevant articles (MEDLINE and EMBASE). EVIDENCE SYNTHESIS: A total of seven studies involving 1495 patients and 1670 controls were considered in the meta-analysis. There was no association between the IL-10 -1082 G/A, -819 C/T, and -592 C/A polymorphisms and JIA in allele contrast and any of the genetic models (allele contrast: odds ratio [OR] 0.90, 95% confidence interval [CI] 0.79-1.02, P=0.09; OR=0.97, 95% CI 0.83-1.13, P=0.68; OR=0.92, 95% CI 0.81-1.06, P=0.24, respectively). In subgroup analysis, none of the subtypes of JIA including systemic, rheumatoid factor (RF)-positive polyarticular, RF-negative polyarticular, and oligoarticular was not significantly associated with IL-10 polymorphism. Meta-analysis of the IL-10 haplotype revealed no association between GCC, ACC, and ATA haplotypes and JIA. CONCLUSIONS: This meta-analysis showed that IL-10 polymorphisms were not associated with risk of JIA.
35456567 Mesenchymal Stem Cell-Derived Extracellular Vesicles as Non-Coding RNA Therapeutic Vehicle 2022 Mar 29 Autoimmune diseases (ADs) are characterized by the activation of the immune system against self-antigens. More common in women than in men and with an early onset, their incidence is increasing worldwide, and this, combined with their chronic nature, is contributing to an enlarged medical and economic burden. Conventional immunosuppressive agents are designed to alleviate symptoms but do not constitute an effective therapy, highlighting a need to develop new alternatives. In this regard, mesenchymal stem cells (MSCs) have demonstrated powerful immunosuppressive and regenerative effects. MSC-derived extracellular vesicles (MSC-EVs) have shown some advantages, such as less immunogenicity, and are proposed as novel therapies for ADs. In this review, we summarize current perspectives on therapeutic options for ADs based on MSCs and MSC-EVs, focusing particularly on their mechanism of action exerted through their non-coding RNA (ncRNA) cargo. A complete state-of-the-art review was performed, centralized on some of the most severe ADs (rheumatoid arthritis, autoimmune type 1 diabetes mellitus, and systemic lupus erythematosus), giving evidence that a promising field is evolving to overcome the current knowledge and provide new therapeutic possibilities centered on MSC-EVs and their role as ncRNA delivery vehicles for AD gene therapy.
35580335 The Potential Role of Protease Systems in Hemophilic Arthropathy. 2022 May 17 Haemophilic arthropathy is characterised by joint damage following recurrent joint bleeds frequently observed in patients affected by the clotting disorder haemophilia. Joint bleeds or haemarthroses trigger inflammation in the synovial tissue which promotes damage to the articular cartilage. The plasminogen activation system is integral to fibrinolysis, and urokinase plasminogen activator or uPA in particular is strongly upregulated following haemarthroses. uPA is a serine protease that catalyses the production of plasmin, a broad-spectrum protease that can degrade fibrin as well as proteins of the joint extracellular matrix and cartilage. Both uPA and plasmin are able to proteolytically generate active forms of matrix metalloproteinases (MMPs). The MMPs are a family of >20 proteases that are secreted as inactive proenzymes and are activated extracellularly. MMPs are involved in degradation of all types of collagen and proteoglycans that constitute the extracellular matrix, which provides structural support to articular cartilage. The MMPs have an established role in joint destruction following rheumatoid arthritis (RA). They degrade cartilage and bone, indirectly promoting angiogenesis. MMPs are also implicated in the pathology of osteoarthritis (OA) characterized by degradation of the cartilage matrix that precipitates joint damage and deformity. HA shares a number of overlapping pathological characteristics with RA and OA. Here we discuss how the plasminogen activation system and MMPs might exacerbate joint damage in HA, lending insight into novel possible therapeutic targets to reduce co-morbidity of haemophilia.
35098840 What might have happened: the impact of interrupting entry of innovative drugs on disease 2022 Feb 21 INTRODUCTION: The study estimated the extent to which drug innovations over the past 30 years may have improved outcomes for six diseases. AREAS COVERED: We analyzed six diseases (ischemic heart disease, lung cancer, breast cancer, human immunodeficiency virus [HIV] infection, type 2 diabetes mellitus, and rheumatoid arthritis [RA]) with significant mortality or morbidity for which there have been major drug innovations over the past 30 years. We used U.S. data from the Global Burden of Disease (GBD) database and a patient registry to perform counterfactual time-series analyses predicting the improved health outcomes that may have been associated with major drug innovations. For 5 conditions using data from the GBD study, years of life lost per individual with the condition could have been higher by 17.1% (breast cancer) to 660.6% (HIV infection) in 2017 had the major drug innovations not been introduced. For RA, using patient registry data, patients' functional status could have been 11.5% worse had biological therapies not been introduced. EXPERT OPINION: Policies targeting drug prices should be broadened to consider the price and value of all health-care services. The societal importance of the pharmaceutical industry's ability to respond rapidly to emerging diseases should be recognized.
34983161 A Case of IgG4-related Mesenteritis and Ankylosing Spondylitis. 2022 Jan Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory disease of unknown etiology and pathogenesis, which can affect all organs. The most commonly involved organs are the pancreas, hepatobiliary system, salivary glands, orbits and lymph nodes. Rarely, the thyroid, pituitary, aorta, lung and kidney may also be involved; mesenteric involvement is rare. The association of IgG4-RD with some rheumatological diseases is observed; while there are data in the literature about rheumatoid arthritis and Sjögren syndrome, but association with ankylosing spondylitis is rare. Anti-tumor necrosis factor alpha (anti-TNFα) treatment has been tried in refractory IgG4-RD cases; but this case is of great interest in terms of progressive presentation under treatment with etanercept, an anti-TNFα agent, which is also used for the treatment. But, IgG4-related mesenteritis with ankylosing spondylitis receiving anti-TNFα therapy, which has also been tried in the treatment of IgG4 disease, has not been reported in the literature. Key Words: IgG4-related disease, Mesenteritis, Ankylosing spondylitis.
34284592 Villous atrophy, an endoscopic and diagnostic challenge. 2022 Mar A 57-year-old female presented with a five-year history of non-bloody diarrhea, reaching 10 to 20 daily depositions without abdominal cramping and a weight loss of 25 kg. Past medical history was significant for rheumatoid arthritis treated with rituximab during the last six years. All her previous endoscopic and histological studies identified lymphocytic infiltration. Previously, she received treatment with rifaximin, cholestyramine, and loperamide without improvement.
35039664 The role of neutrophils in rheumatic disease-associated vascular inflammation. 2022 Mar Vascular pathologies underpin and intertwine autoimmune rheumatic diseases and cardiovascular conditions, and atherosclerosis is increasingly recognized as the leading cause of morbidity in conditions such as systemic lupus erythematosus (SLE), rheumatoid arthritis and antineutrophil cytoplasmic antibody-associated vasculitis. Neutrophils, important cells in the innate immune system, exert their functional effects in tissues via a variety of mechanisms, including the generation of neutrophil extracellular traps and the production of reactive oxygen species. Neutrophils have been implicated in the pathogenesis of several rheumatic diseases, and can also intimately interact with the vascular system, either through modulating endothelial barriers at the blood-vessel interface, or through associations with platelets. Emerging data suggest that neutrophils also have an important role maintaining homeostasis in individual organs and can protect the vascular system. Furthermore, studies using high-dimensional omics technologies have advanced our understanding of neutrophil diversity, and immature neutrophils are receiving new attention in rheumatic diseases including SLE and systemic vasculitis. Developments in genomic, imaging and organoid technologies are beginning to enable more in-depth investigations into the pathophysiology of vascular inflammation in rheumatic diseases, making now a good time to re-examine the full scope of roles of neutrophils in these processes.
35611846 Intra-arterial chemoradiotherapy for locally advanced buccal mucosal cancer in an elderly 2022 May 25 BACKGROUND: The management of locally advanced oral cavity squamous cell carcinoma (LA-OCScc) in elderly patients with multiple comorbidities is difficult. CASE: We report the case of an elderly patient with buccal mucosal squamous cell carcinoma as well as chronic renal dysfunction, hepatic cirrhosis, rheumatoid arthritis, and metachronous diffuse large B-cell lymphoma. We performed radiation therapy (a total dose of 70 Gy in 35 fractions) and six cycles of intra-arterial chemotherapy with 40 mg/m(2) cisplatin per week. After treatment, the tumor completely disappeared, and there was no recurrence or deterioration of comorbidities during the 12-month follow-up period. CONCLUSION: Intra-arterial chemoradiotherapy may be a good treatment option for LA-OCScc in elderly patients with multiple comorbidities.
35558547 Oral Complications in Cancer Patients-Medication-Related Osteonecrosis of the Jaw (MRONJ). 2022 Medication-Related Osteonecrosis of the Jaw (MRONJ) was first reported in 2003. Despite the progress in the understanding of this oral complication in cancer patients for the past 18 years, there is still discussion about the best way to define MRONJ, prevent the complication, how to diagnose, and the options of treatment available. The initial reports associated MRONJ to bisphosphonates and denosumab, medications that work as bone-modifying agents. Later, other agents such as the antiangiogenics, have also been reported to cause the oral complication, either alone or in combination with antiresorptives. Initially, these medications were prescribed to patients with osteoporosis and cancers patients with bone metastasis. Today, because of the effect of the medications in the bone remodeling system, patients with several other diseases such as giant cell tumors, rheumatoid arthritis, Paget's disease of bone, fibrous dysplasia, osteogenesis imperfecta, are managed with these medications, significantly increasing the population of individuals at risk for developing MRONJ. This mini review focused on the cancer patient. It updates the dental clinician on the recent scientific literature about MRONJ and provides information on how to diagnose and manage patients being treated with these medications, suggests protocols to prevent the development of MRONJ, and present ways to manage those patients who develop the oral complication.
35126992 Causal Biological Network Model for Inflammasome Signaling Applied for Interpreting Transc 2022 Virtually any stressor that alters the cellular homeostatic state may result in an inflammatory response. As a critical component of innate immunity, inflammasomes play a prominent role in the inflammatory response. The information on inflammasome biology is rapidly growing, thus creating the need for structuring it into a model that can help visualize and enhance the understanding of underlying biological processes. Causal biological network (CBN) models provide predictive power for novel disease mechanisms and treatment outcomes. We assembled the available literature information on inflammasome activation into the CBN model and scored it with publicly available transcriptomic datasets that address viral infection of the lungs, osteo- and rheumatoid arthritis, psoriasis, and aging. The scoring inferred pathway activation leading to NLRP3 inflammasome activation in these diverse conditions, demonstrating that the CBN model provides a platform for interpreting transcriptomic data in the context of inflammasome activation.
35607574 Multiple Sclerosis and Autoimmunity: A Veiled Relationship. 2022 Apr Multiple sclerosis (MS) is an autoimmune inflammatory illness that affects the central nervous system (CNS) when the body's immune system attacks its tissue. It is characterized by demyelination and varying degrees of axonal loss. This article has compiled various studies elaborating MS and other autoimmune diseases (ADs) co-occurrence. Several conditions that fall into this category, including type 1 diabetes (T1D), rheumatoid arthritis (RA), Guillain-Barre syndrome (GBS), myasthenia gravis (MG), and many others, are found in MS patients and their relatives, suggesting one or more common etiologic mechanisms, including genetic, environmental, and immunological factors, supporting the concept of a possible influence of poly-autoimmunity on MS and the rest of ADs, as well as providing a significant feature for early detection of the disease and also a potential treatment option by clinical neurologists.
35180488 Inflammation: Biochemistry, cellular targets, anti-inflammatory agents and challenges with 2022 Apr Keeping in view the involvement of inflammation in the pathogenesis of several diseases including cancer, diabetes, neurodegenerative disorders and rheumatoid arthritis, herein, we review the processes for the initiation of inflammation and the treatment measures. While focusing on the cyclooxygenase mediated arachidonic acid metabolic pathways, biochemistry of inflammatory prostaglandins is discussed. The data corresponding to efficacy, pharmacokinetic profile and the side effects of the available natural and synthetic anti-inflammatory drugs is reviewed. Moreover, the given information for the drug-based design of new anti-inflammatory agents may help in the development of more potent and safe molecules.
35535158 Clinical Efficacy of Acupuncture for the Treatment of Rheumatoid Arthritis: Meta-Analysis 2022 OBJECTIVE: Acupuncture has been used by rehabilitation specialists as an adjunctive treatment for the symptomatic treatment of rheumatoid arthritis (RA). This meta-analysis aims to evaluate the efficacy of acupuncture in treating patients with RA. METHODS: A comprehensive search was conducted in CBM, CNKI, PubMed, CENTRAL, Web of Science, and Embase from their inception up to March 2022. All randomized controlled trials (RCTs) without the language restriction, concerning the patients with RA treated with acupuncture, were included. Two reviewers independently assessed the risk of bias with the Cochrane Risk of Bias Assessment tool. Weight mean difference (MD) and 95% CI were calculated, and data were pooled with random effects model. RESULTS: A total of eleven RCTs involving 796 patients with RA met the established inclusion criteria. This systematic review indicated the efficacy of acupuncture as an adjunctive treatment for patients with RA. Invasive acupuncture could reduce significantly in pain (MD = -1.00, 95% CI: -1.96 to -0.05, P=0.040), health assessment questionnaire (HAQ, MD = -0.20, 95% CI: -0.30 to -0.11, P < 0.001), physician global assessment (PhGA, MD = -0.98, 95% CI: -1.23 to -0.72, P < 0.001), tender joint count (TJC, MD = -1.24, 95% CI: -2.11 to -0.37, P=0.005), C-reactive protein (CRP, MD = -1.81, 95% CI: -3.32 to -0.29, P=0.019), and erythrocyte sedimentation rate (ESR, MD = -3.03, 95% CI: -5.80 to -0.26, P=0.032), while compared to control group. Laser acupuncture could reduce HAQ (MD = -0.15, 95% CI: -0.28 to -0.01, P=0.034), the RA quality of life questionnaire (RAQoL, MD = -2.32, 95% CI: -4.40 to -0.25, P=0.028), CRP (MD = -35.24, 95% CI: -36.49 to -33.99, P < 0.001), and interleukin-6 (IL-6, MD = -29.63, 95% CI: -49.34 to -9.92, P=0.003), while compared to control group. No adverse events associated with acupuncture were reported. CONCLUSION: Available evidence suggests that acupuncture is beneficial for relieving pain and ameliorating quality of life and health index in patients with RA; thereby, it should be available as an adjunctive nonpharmacological treatment in rehabilitation programmes.
35582845 Using potential variable to study gene-gene and gene-environment interaction effects with 2022 May 18 One of the critical issues in genetic association studies is to evaluate the risk of a disease associated with gene-gene or gene-environment interactions. The commonly employed procedures are derived by assigning a particular set of scores to genotypes. However, the underlying genetic models of inheritance are rarely known in practice. Misspecifying a genetic model may result in power loss. By using some potential genetic variables to separate the genotype coding and genetic model parameter, we construct a model-embedded score test (MEST). Our test is free of assumption of gene-environment independence and allows for covariates in the model. An effective sequential optimization algorithm is developed. Extensive simulations show the proposed MEST is robust and powerful in most of scenarios. Finally, we apply the proposed method to rheumatoid arthritis data from the Genetic Analysis Workshop 16 to further investigate the potential interaction effects.
35233479 Factors associated with depressive symptoms in Japanese women with rheumatoid arthritis. 2022 OBJECTIVES: It has been suggested that patients with RA are more likely to suffer from depression. Therefore, this study identified the factors associated with depressive states in female RA patients to inform future patient care. METHODS: A self-assessment questionnaire was administered to 150 female RA patients aged ≥20 years regarding their satisfaction with disease activity, pain (measured using a visual analogue scale), self-rated depression scale (SDS), stress content (illness, work, family, difficulty in daily life, appearance, treatment and other), confidence in stress management and satisfaction (treatment effect, health status and relationships with health-care professionals). The factors related to depression and the presence of depressive tendencies were investigated. RESULTS: Data from 145 patients were analysed. Eighteen patients (12.4%) showed depressive tendencies according to their SDS scores. Among these patients, SDS scores were positively correlated with disease activity and with scores on the modified HAQ, visual analogue scale for pain, and stress content. The SDS score was also negatively correlated with patients' confidence in stress management and health status satisfaction. CONCLUSION: Female RA patients had family problems and various stressors in their daily lives. Nurses need to conduct regular mental health assessments to monitor their self-management status and support them to improve their confidence and satisfaction in coping. To achieve this, it is important for health-care teams involving various health-care professionals to collaborate and cooperate.