Beyond lecanemab: Examining Phase III potential in Alzheimer's therapeutics.

This review focuses on the development of therapeutic interventions for Alzheimer's dementia. While established treatments targeted acetylcholine and NMDA receptors, there is a growing demand for innovative therapies as the aging population increases. The paper highlights the US Food and Drug Administration's approval of aducanumab (Aduhelm) and lecanemab (Leqembi), emphasizing the developmental status of new treatments. Specifically, it covers seven principal drugs in Phase III trials, detailing their mechanisms of action, clinical trial specifics in the United States and Japan, and the current status of regulatory applications. The review focuses on amyloid removal (donanemab), tau protein mitigation (E2814), drug repositioning (Semaglutide, GV1001), and disease-modifying small molecules (fosgonimeton, hydralazine, masitinib). However, Gantenerumab and Solanezumab, unsuccessful in Phase III, are not covered. While the future approval status remains uncertain, we hope these drugs will offer beneficial therapeutic effects for potential dementia patients.

A preliminary survey of rheumatologists on the management of late-onset rheumatoid arthritis in Japan.

Objectives We investigated the current perspectives regarding the management of late-onset rheumatoid arthritis (LORA) among rheumatologists in clinical practice. Methods This study was performed in October 2021, and included 65 rheumatologists certified by the Japan College of Rheumatology, who were administered questionnaires (including multiple choice and descriptive formulae) regarding the management of LORA. We aggregated and analyzed the responses. Results All 65 rheumatologists responded to the survey; 47 (72%) answered that >50% of newly diagnosed patients were aged ≥65 years, 42 (65%) answered that achievement of remission or low disease activity was the treatment goal, and 40 (62%) considered patient safety to be the highest priority. Most rheumatologists are concerned about the management of conditions other than RA, such as comorbidities, financial constraints, and life circumstances that interfere with standard or recommended treatment implementation. Conclusion This preliminary survey highlighted various rheumatologists' perspectives regarding the management of LORA.

Safety and effectiveness of certolizumab pegol in Japanese patients with rheumatoid arthritis: Up to 3-year results from a postmarketing surveillance study.

OBJECTIVES: To report up to 3-year safety and effectiveness of certolizumab pegol (CZP) in Japanese patients with rheumatoid arthritis from a postmarketing surveillance study. METHODS: Patients enrolled previously completed 24 weeks of CZP in the 24-week postmarketing surveillance study. Adverse drug reactions (ADRs) were recorded for patients who received ≥1 CZP dose. Effectiveness outcomes were 28-joint Disease Activity Score with erythrocyte sedimentation rate and European Alliance of Associations for Rheumatology response. Week 24-156 safety and Week 0-52 effectiveness data are reported here. RESULTS: A total of 781 patients were enrolled, with 735 and 376 patients evaluated for safety and effectiveness, respectively. Within the safety set, 17.8% (131/735) of patients reported ADRs; 9.4% (69/735) reported serious ADRs. Among patients with history of respiratory, thoracic, and mediastinal disorders, 38.4% (28/73) reported ADRs. The most frequent ADRs were infections and infestations (11.8%; 87/735); skin and subcutaneous tissue disorders (1.9%; 14/735); respiratory, thoracic, and mediastinal disorders (1.6%; 12/735). Mean 28-joint Disease Activity Score with erythrocyte sedimentation rate reduced from 4.6 (Week 0) to 2.8 (Week 52). At Week 52, 51.8% (161/311) of patients achieved European Alliance of Associations for Rheumatology Good response. CONCLUSIONS: The long-term safety and effectiveness of CZP in the real-world setting in Japan were consistent with previously reported data; no new safety signals were identified.

Comparison of early clinical outcome in carpal tunnel release - mini-open technique with palmar incision vs. endoscopic technique with wrist crease incision.

BACKGROUND: The purpose of this study was to examine two techniques for Carpal Tunnel Syndrome, mini-Open Carpal Tunnel Release (mini-OCTR) and Endoscopic Carpal Tunnel Release (ECTR), to compare their therapeutic efficacy. METHODS: Sixteen patients who underwent mini-OCTR in palmar incision and 17 patients who underwent ECTR in the wrist crease incision were included in the study. All patients presented preoperatively and at 1, 3, and 6 months postoperatively and were assessed with the Visual Analogue Scale (VAS) and the Disabilities of Arm, Shoulder and Hand Score (DASH). We also assessed the pain and cosmetic VAS of the entire affected hand or surgical wound, and the patient's satisfaction with the surgery. RESULTS: In the objective evaluation, both surgical techniques showed improvement at 6 months postoperatively. The DASH score was significantly lower in the ECTR group (average = 3 months: 13.6, 6 months: 11.9) than in the mini-OCTR group (average = 3 months: 27.3, 6 months: 20.6) at 3 and 6 months postoperatively. Also, the pain VAS score was significantly lower in the ECTR group (average = 17.1) than in the mini-OCTR group (average = 36.6) at 3 months postoperatively. The cosmetic VAS was significantly lower in the ECTR group (average = 1 month: 15.3, 3 months: 12.2, 6 months: 5.41) than in the mini-OCTR group (average = 1 month: 33.3, 3 months: 31.2, 6 months: 24.8) at all time points postoperatively. Patient satisfaction scores tended to be higher in the ECTR group (average = 3.3) compared to the mini-OCTR group (average = 2.7). CONCLUSIONS: ECTR in wrist increase incision resulted in better pain and cosmetic recovery in an early postoperative phase compared with mini-OCTR in palmar incision. Our findings suggest that ECTR is an effective technique for patient satisfaction.

Consensus statement on the management of late-onset rheumatoid arthritis.

OBJECTIVES: Late-onset rheumatoid arthritis (LORA), which has been increasing in recent years, lacks evidence for initial treatment. Japanese rheumatology experts recognized this gap and addressed it by developing consensus statements on the first clinical application of LORA. METHODS: These statements were created following an introductory discussion about treatment fundamentals, which included a review of existing literature and cohort data. The steering committee created a draft, which was refined using a modified Delphi method that involved panel members reaching a consensus. The panel made decisions based on input from geriatric experts, clinical epidemiologists, guideline developers, patient groups, and the LORA Research Subcommittee of the Japan College of Rheumatology. RESULTS: The consensus identified four established facts, three basic approaches, and six expert opinions for managing LORA. Methotrexate was recommended as the primary treatment, with molecular-targeted agents being considered if treatment goals cannot be achieved. An emphasis was placed on assessing the lives of older patients due to challenges in risk management and methotrexate accessibility caused by comorbidities or cognitive decline. CONCLUSIONS: The experts substantiated and refined 13 statements for the initial treatment of LORA. To validate these claims, the next is to conduct a registry study focusing on new LORA cases.

High Fracture Rate of AVANTA Silicone Implant Following Arthroplasty of the Thumb MCP Joint of Rheumatoid Arthritis Patients with Boutonniere Deformities.

We retrospectively investigated the mid-term outcomes of arthroplasty using the AVANTA silicone implant for thumb metacarpophalangeal (MCP) joints with boutonniere deformity in patients with rheumatoid arthritis (RA). This study involved 36 thumbs of 33 RA patients with a mean follow-up period of 5.1 years (range, 2.0-13.3). Postoperatively, the mean extension was significantly increased and the mean flexion was significantly decreased (p<0.001, p<0.001, respectively), resulting in the mean arc of range of motion (ROM) shifting in the direction of extension after surgery. Implant fracture was observed in 10 thumbs (28%), and 4 of these (11%) underwent revision surgery. The survivorship with implant fracture and revision surgery as endpoints were 73.4% and 91.8% at 5 years, respectively. The preoperative arc of ROM and the postoperative flexion range of the implant-fracture group were significantly greater than those in the no-implant-fracture group (p=0.039, 0.034, respectively). These results suggest the importance of patient education and careful rehabilitation to prevent excessive flexion. Overall, the AVANTA silicone implant showed a relatively high rate of implant fracture at our institute.

Inhibitory Effect of a Tankyrase Inhibitor on Mechanical Stress-Induced Protease Expression in Human Articular Chondrocytes.

We investigated the effects of a Tankyrase (TNKS-1/2) inhibitor on mechanical stress-induced gene expression in human chondrocytes and examined TNKS-1/2 expression in human osteoarthritis (OA) cartilage. Cells were seeded onto stretch chambers and incubated with or without a TNKS-1/2 inhibitor (XAV939) for 12 h. Uni-axial cyclic tensile strain (CTS) (0.5 Hz, 8% elongation, 30 min) was applied and the gene expression of type II collagen a1 chain (COL2A1), aggrecan (ACAN), SRY-box9 (SOX9), TNKS-1/2, a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), and matrix metalloproteinase-13 (MMP-13) were examined by real-time PCR. The expression of ADAMTS-5, MMP-13, nuclear translocation of nuclear factor-κB (NF-κB), and ß-catenin were examined by immunocytochemistry and Western blotting. The concentration of IL-1ß in the supernatant was examined by enzyme-linked immunosorbent assay (ELISA). TNKS-1/2 expression was assessed by immunohistochemistry in human OA cartilage obtained at the total knee arthroplasty. TNKS-1/2 expression was increased after CTS. The expression of anabolic factors were decreased by CTS, however, these declines were abrogated by XAV939. XAV939 suppressed the CTS-induced expression of catabolic factors, the release of IL-1ß, as well as the nuclear translocation of NF-κB and ß-catenin. TNKS-1/2 expression increased in mild and moderate OA cartilage. Our results demonstrated that XAV939 suppressed mechanical stress-induced expression of catabolic proteases by the inhibition of NF-κB and activation of ß-catenin, indicating that TNKS-1/2 expression might be associated with OA pathogenesis.

Influence of Janus kinase inhibitors on early postoperative complications in patients with rheumatoid arthritis undergoing orthopaedic surgeries.

OBJECTIVE: We retrospectively reviewed the records of rheumatoid arthritis (RA) patients who underwent orthopaedic surgery to examine the influence of the perioperative use of Janus kinase (JAK) inhibitors on early postoperative complications. PATIENTS AND METHODS: Thirty-two patients with RA under disease control with JAK inhibitors who underwent 49 orthopaedic procedures were included in the study. Patient records after surgery were investigated for surgical site infection (SSI), delayed wound healing (DWH), a flare-up of the disease, preoperative and postoperative absolute lymphocyte counts (ALCs), venous thromboembolism, and other postoperative complications. RESULTS: JAK inhibitors were continued during the perioperative period in 31 procedures. In the remaining 18 procedures, JAK inhibitors were discontinued perioperatively with a mean discontinuation period of 2.4 days. No instances of SSI were identified in any patient during at least 90 days' follow-up, while DWH was seen in one patient. Disease flare-up was noted in two patients after 3 and 9 days of discontinuation of JAK inhibitors, respectively. The ALCs significantly decreased on postoperative Day 1 (P < .0001), and there was a significant correlation between pre- and post-one-day ALCs (r = 0.75, P < .0001). CONCLUSION: JAK inhibitors seem to be safe during the perioperative period of orthopaedic surgery.

The Effectiveness of Rehabilitation after Open Surgical Release for Trigger Finger: A Prospective, Randomized, Controlled Study.

BACKGROUND: It is not clear whether rehabilitation after surgery for trigger finger is effective. The aim of this study was to reveal its effectiveness for trigger finger. METHODS: This study was a randomized, controlled trial that included patients who underwent operations for trigger fingers. The patients in the rehabilitation group had postoperative occupational therapy (OT) for 3 months, while the patients in the control group were not referred for rehabilitation but received advice for a range of motion exercises. We evaluated the severity of trigger finger, Disability of Arm-Shoulder-Hand (DASH) score, pain-visual analogue scale (VAS), grip strength, whether they gained a full range of motion (ROM), and complications before and after surgery. RESULTS: Finally, 29 and 28 patients were included in the control and rehabilitation groups, respectively. At final follow-up, the DASH score, grip strength, and ROM were significantly improved in the rehabilitation group compared to that preoperatively. At final follow-up, pain was significantly improved in both groups from that preoperatively. There were no significant differences in the results, including the DASH score, grip strength, ROM and pain-VAS between the control and rehabilitation groups at the final follow-up. Subgroup analysis showed that there is a significant difference in the DASH score of patients doing housework or light work and those with a duration of symptoms >12 months between the control and rehabilitation groups at the final follow-up.

Wrist arthrodesis combined with a bulk bone allograft for implant loosening after total wrist arthroplasty: A case report.

Total wrist arthroplasty (TWA) is a challenging procedure for wrist joints severely destroyed by rheumatoid arthritis. The most common postoperative complication of TWAs is the loosening of the carpal component. Revision surgeries for failed TWAs can be complicated owing to severe bone loss and concomitant soft-tissue problems. Here, we report a case (68-year-old woman with a history of rheumatoid arthritis for 24 years) of severe aseptic loosening of semi-constrained TWA and its salvage surgery. During the primary arthroplasty procedure, severe instability at the second through fifth carpometacarpal joints was observed and arthrodesis of these joints was required. The radiographs obtained 9 months after surgery showed loosening of the carpal component. Subsequently, she suffered a stroke, resulting in a loss of follow-up, and higher stress was loaded on her upper extremities during standing and walking. In the radiograph taken at her revisit 25 months after the primary surgery, the subsidence of the carpal component progressed and loosening of the radial component was observed. Total wrist arthrodesis was performed using a bulk bone allograft of the femoral head, combined with a penetrating Wrist Fusion Rod®. Rapid bone union was achieved without soft-tissue irritation. We conclude that wrist arthrodesis with a bulk bone allograft combined with an intramedullary nail is a reasonable option for failed total wrist arthroplasty.

Effectiveness and Changes in Brain Functions by an Occupational Therapy Program Incorporating Mindfulness in Outpatients with Anxiety and Depression: A Randomized Controlled Trial.

INTRODUCTION: This study examined the efficacy of an 8-week occupational therapy program incorporating mindfulness (MOT) as a form of psychiatric rehabilitation to ameliorate residual social and occupational impairment in patients with anxiety disorders and depression. The objective was to evaluate the effects of MOT on their personal well-being and to assess the impact of MOT on brain function using quantitative electroencephalography (qEEG). METHODS: This study was a randomized, wait-list control trial with assessments performed at baseline, post-intervention (9 weeks), and follow-up (18 weeks) in outpatients with anxiety disorders and depression. The MOT was conducted in small groups, comprising eight weekly 1.5-h sessions. The primary outcome was the mean score change between the pre- and post-interventions with Questionnaire about the Process of Recovery (QPR) scale. Other clinical assessments and qEEG served as secondary and biological outcomes, respectively. RESULTS: A total of 25 patients (mean age: 44.1) were included in the analysis. The MOT group demonstrated a significantly improved QPR compared to the control group after adjusting for baseline covariates (p < 0.01). This improvement was sustained for 9 weeks after the 8-week intervention. In the qEEG analysis, a significant increase in current source density in the ß2 band of the left dorsolateral prefrontal cortex was observed in the MOT group compared to the control group (p < 0.02). CONCLUSION: This study demonstrates that MOT improves subjective well-being and potentially, global function. This suggests that MOT may serve as a viable option for those whose symptoms have abated but who still struggle with social and occupational functioning.

Association of phase angle with sarcopenia in chronic musculoskeletal pain patients: a retrospective study.

BACKGROUND: In chronic musculoskeletal pain patients, detection of sarcopenia is of significant clinical interest. Phase angle, which can be measured through bioelectrical impedance analysis (BIA), can detect sarcopenia; however, the evidence in chronic musculoskeletal pain patients is limited. This study aimed to assess the relationship between phase angle and sarcopenia in patients with chronic musculoskeletal pain. Our hypothesis was that phase angle would be a useful indicator to identify sarcopenia in patients with chronic musculoskeletal pain. METHODS: A total of 190 patients (51 men and 139 women) with chronic musculoskeletal pain were included in this retrospective cross-sectional study. Patient data of backgrounds, numeric rating scale score for pain, skeletal muscle index, and phase angle assessed using BIA were retrospectively reviewed. Sarcopenia was diagnosed using the Asian Working Group for Sarcopenia criteria 2019. RESULTS: A total of 51 patients (26.7%), including 10 men (19.6%) and 41 women (29.5%), were diagnosed with sarcopenia. Phase angle, sarcopenia-related factors, age, and body mass index (BMI) differed significantly in patients with and without sarcopenia. On multiple logistic regression analysis, the prevalence of sarcopenia was significantly correlated with phase angle and BMI. The areas under the curve exhibited high accuracy in discriminating sarcopenia in men and moderate accuracy in both sexes and in women. CONCLUSIONS: Phase angle may be a valid discriminator of sarcopenia in patients with chronic musculoskeletal pain.

Outcome of unlinked total elbow arthroplasty for rheumatoid arthritis in patients younger than 50 years old.

AIMS: There are concerns regarding complications and longevity of total elbow arthroplasty (TEA) in young patients, and the few previous publications are mainly limited to reports on linked elbow devices. We investigated the clinical outcome of unlinked TEA for patients aged less than 50 years with rheumatoid arthritis (RA). METHODS: We retrospectively reviewed the records of 26 elbows of 21 patients with RA who were aged less than 50 years who underwent primary TEA with an unlinked elbow prosthesis. The mean patient age was 46 years (35 to 49), and the mean follow-up period was 13.6 years (6 to 27). Outcome measures included pain, range of motion, Mayo Elbow Performance Score (MEPS), radiological evaluation for radiolucent line and loosening, complications, and revision surgery with or without implant removal. RESULTS: The mean MEPS significantly improved from 47 (15 to 70) points preoperatively to 95 (70 to 100) points at final follow-up (p < 0.001). Complications were noted in six elbows (23%) in six patients, and of these, four with an ulnar neuropathy and one elbow with postoperative traumatic fracture required additional surgeries. There was no revision with implant removal, and there was no radiological evidence of loosening around the components. With any revision surgery as the endpoint, the survival rates up to 25 years were 78.1% (95% confidence interval 52.8 to 90.6) as determined by Kaplan-Meier analysis. CONCLUSION: The clinical outcome of primary unlinked TEA for young patients with RA was satisfactory and comparable with that for elderly patients. A favourable survival rate without implant removal might support the use of unlinked devices for young patients with this disease entity, with a caution of a relatively high complication rate regarding ulnar neuropathy.Level of Evidence: Therapeutic Level IVCite this article: Bone Jt Open 2023;4(1):19-26.

Precise Discrimination for Multiple Etiologies of Dementia Cases Based on Deep Learning with Electroencephalography.

INTRODUCTION: It is critical to develop accurate and universally available biomarkers for dementia diseases to appropriately deal with the dementia problems under world-wide rapid increasing of patients with dementia. In this sense, electroencephalography (EEG) has been utilized as a promising examination to screen and assist in diagnosing dementia, with advantages of sensitiveness to neural functions, inexpensiveness, and high availability. Moreover, the algorithm-based deep learning can expand EEG applicability, yielding accurate and automatic classification easily applied even in general hospitals without any research specialist. METHODS: We utilized a novel deep neural network, with which high accuracy of discrimination was archived in neurological disorders in the previous study. Based on this network, we analyzed EEG data of healthy volunteers (HVs, N = 55), patients with Alzheimer's disease (AD, N = 101), dementia with Lewy bodies (DLB, N = 75), and idiopathic normal pressure hydrocephalus (iNPH, N = 60) to evaluate the discriminative accuracy of these diseases. RESULTS: High discriminative accuracies were archived between HV and patients with dementia, yielding 81.7% (vs. AD), 93.9% (vs. DLB), 93.1% (vs. iNPH), and 87.7% (vs. AD, DLB, and iNPH). CONCLUSION: This study revealed that the EEG data of patients with dementia were successfully discriminated from HVs based on a novel deep learning algorithm, which could be useful for automatic screening and assisting diagnosis of dementia diseases.

Non-drug and surgical treatment algorithm and recommendations for the 2020 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis-secondary publication.

OBJECTIVES: The aim of this study was to update the Japan College of Rheumatology (JCR) clinical practice guidelines (CPGs) for the management of rheumatoid arthritis (RA) and prepare an algorithm for non-drug and surgical treatments. This article is a digest version of the guidelines. METHODS: The Japanese Ministry of Health, Labour and Welfare's research group, in collaboration with the JCR, used the Grading of Recommendations, Assessment, Development, and Evaluation method to update the 2014 JCR CPG for RA. The consensus was formed by CPG panel members. RESULTS: We raised 19 clinical questions regarding non-drug and surgical treatments for RA and developed recommendations. The treatments included exercise therapy; occupational therapy; joint injection of corticosteroids; and orthopaedic surgeries including cervical spine surgery, wrist and foot arthroplasty, ankle arthrodesis, and replacement arthroplasty of the shoulder, elbow, finger, hip, knee, and ankle. Recommendations regarding the risks of surgery and perioperative discontinuation of medications have also been developed. Based on these recommendations, we created an original algorithm for the non-drug and surgical treatment of RA. CONCLUSIONS: These recommendations are expected to serve rheumatologists, health care professionals, and patients with RA as tools for shared decision-making to treat residual limb joint symptoms and functional impairment.

Drug treatment algorithm and recommendations from the 2020 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis-secondary publication.

OBJECTIVE: The aim of this study was to update the Japan College of Rheumatology (JCR) clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA; JCR CPG for RA) according to recent changes in the medical environment in Japan. This article is a digest version of the guidance. METHODS: We used the Grading of Recommendations, Assessment, Development, and Evaluation method to update the 2014 JCR CPG for RA. A consensus was formed by CPG panel members. RESULTS: We identified 36 important clinical questions regarding drug treatment and developed corresponding recommendations for RA. The recommendations included the following RA medications: non-steroidal anti-inflammatory drugs, corticosteroids, conventional synthetic disease-modifying antirheumatic drugs, biological disease-modifying antirheumatic drugs, anti-receptor activator for nuclear factor-κB ligand antibodies, and Janus kinase inhibitors, as well as the tapering and discontinuation of these medications. Recommendations regarding the efficacy and safety of treatments in the elderly and patients with comorbidities were also developed. Finally, we used these recommendations to create an original algorithm for drug treatment for RA based on the Treat-to-Target approach. CONCLUSION: The 2020 JCR CPG for RA provides a useful tool for rheumatologists, health care professionals, and patients with RA, enabling shared decision-making in a variety of clinical situations.

Safety and effectiveness of certolizumab pegol in Japanese patients with rheumatoid arthritis: Results from a 24-week post-marketing surveillance study.

OBJECTIVES: To report 24-week safety and effectiveness of certolizumab pegol (CZP) in Japanese patients with rheumatoid arthritis from a post-marketing surveillance study. METHODS: Enrolled patients were newly receiving CZP. All adverse events (AEs) and adverse drug reactions (ADRs) were recorded for patients who received ≥1 CZP dose. Effectiveness outcomes included: 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) and European Alliance of Associations for Rheumatology (EULAR) response. Missing data were imputed using the last observation carried forward. RESULTS: 3727 patients were enrolled; safety and effectiveness were evaluated in 3586 and 1794 patients, respectively. 24.9% of patients reported AEs (893/3586), 14.7% reported ADRs (528/3586), 8.3% (298/3586) reported serious AEs and 5.3% (190/3586) reported serious ADRs. Selected serious ADRs of interest: infections (110; 3.1%), tuberculosis (6; 0.2%), interstitial pneumonia (15; 0.4%), malignancy (8; 0.2%), and hepatic function disorder (7; 0.2%). No allergic reactions, autoimmune disease, cardiac failure, demyelinating diseases, or pancytopenia were reported. Mean DAS28-ESR reduced from 4.8 (baseline) to 3.4 (final evaluation). At final evaluation, 34.7% of patients achieved EULAR good response. CONCLUSIONS: These real-world safety and effectiveness results were consistent with previously reported data, with no new safety signals identified. Long-term, real-world CZP safety and effectiveness data are needed.

Late-onset rheumatoid arthritis registry study, LORIS study: study protocol and design.

BACKGROUND: Although drug treatment strategies for rheumatoid arthritis (RA) are relatively well established, there is a paucity of evidence on the treatment in older patients. The purpose of this study is to build a registry for late-onset RA (LORA), which is expected to increase rapidly worldwide. In addition, we aim to propose optimal treatment strategies according to the patient background including frailty, thereby contributing to improving the quality of treatment and daily living in patients with RA. METHODS/DESIGN: The LORIS (Late-onset Rheumatoid Arthritis Registry) Study is a prospective nation-wide multicenter observational study of patients with LORA. The inclusion criteria were patients aged ≥ 65 years at onset, meeting 2010 ACR/EULAR classification criteria for RA, and starting either any disease-modifying antirheumatic drugs (DMARDs) in a DMARD-naïve patient or the first biologic/targeted synthetic DMARDs during the study period. Enrollment was started on 11 January, 2022 and will be closed on 31 December, 2023. Patients will undergo a comprehensive baseline assessment including clinical data, medication, cognitive and physical function, psychosocial factors, and frailty. Data will be collected at baseline, Month 3, 6, 12, 18, 24, 36, and summarized descriptively. The factors associated with adverse events and achieving remission will be determined. DISCUSSION: A multi-disciplinary panel including patients, rheumatologists, and geriatric specialists will discuss the results and build a consensus regarding the treatment goals of LORA. We expect to provide a broad range of information for evidence-based shared decision making in the treatment of LORA. STUDY REGISTRATION: Registered at the UMIN registry (UMIN000046086) on 1 January 2022.

Factors influencing caregiver burden in chronic pain patients: A retrospective study.

Chronic pain coexists with disability, anxiety, depression, and sleep disturbances, which are factors of pain chronicity in the fear-avoidance model. Self-efficacy for managing pain plays a protective role against pain chronicity. For chronic pain sufferers, social support from caregivers is important. However, such caregivers face enormous physical and mental burdens. This study aimed to assess how self-efficacy and factors related to the fear-avoidance model affect caregiver burden. Participants were 135 chronic pain patients and their caregivers who visited our outpatient pain special clinic. In clinical assessments, numeric rating scale (NRS), pain catastrophizing scale (PCS), hospital anxiety and depression scale (HADS), Athens insomnia scale (AIS), pain disability assessment scale (PDAS), pain self-efficacy questionnaire (PSEQ) for the patients and Zarit Burden Interview (ZBI) for their caregivers were evaluated. Participants were divided into 2 groups (L group ZBI < 24 points and H group ZBI ≥ 24 points) and compared. Regression analyses were conducted to identify factors correlated with the ZBI scores. Compared to L group, H group showed significantly higher NRS and HADs depression scores, and lower PSEQ scores. In univariate regression analysis, ZBI scores were significantly correlated with NRS, PCS, HADS anxiety, HADS depression, PDAS and PSEQ. Multiple linear regression analysis revealed that ZBI scores were significantly correlated with PSEQ. The caregivers who perceived high caregiver burden had significantly higher patients' pain intensity, depression, and lower self-efficacy than those who perceived low caregiver burden. Caregiver burden correlated with the pain intensity, pain catastrophizing, anxiety, depression, disability, and self-efficacy of chronic pain patients. Among these factors, self-efficacy was the most negatively correlated with caregiver burden. Treatments focused on increasing self-efficacy for managing pain have the potential to reduce caregiver burden.