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Background Corticosteroid injection for knee osteoarthritis is limited by its modest duration of treatment effect. The liposome formulation of dexamethasone sodium phosphate (TLC599) was developed for the sustained relief of osteoarthritis pain. This clinical study was conducted to evaluate the efficacy and safety of TLC599 at two dose levels in patients with knee osteoarthritis. Methods A randomized, double-blinded, placebo-controlled study was conducted in 75 patients with osteoarthritis of the knee from 13 study centers. Patients were randomized and administered a single intra-articular injection of TLC599 or placebo and assessed for efficacy and safety for 24 weeks. Patient-reported outcomes included the Western Ontario and McMaster Universities Arthritis (WOMAC) Index for pain and function and visual analog scale for pain. Results TLC599 at 12 mg demonstrated significantly greater reduction in WOMAC pain through 12 weeks (least squares (LS) mean difference = − 0.37, p = 0.0027) and through 24 weeks (LS mean difference = − 0.35, p = 0.0037) when compared to placebo. TLC599 12 mg also exhibited significantly greater improvement in function when compared to placebo at 24 weeks (LS mean difference = − 0.26, p = 0.0457). TLC599 18 mg did not significantly improve pain or function in comparison with placebo. The use of acetaminophen during the study was less in both TLC599 groups in comparison with placebo. No major or unexpected safety issues were reported. Conclusions In participants with symptomatic knee osteoarthritis, TLC599 is a well-tolerated treatment that reduces pain and improves function for up to 24 weeks, a longer duration than that reported for existing IA treatments. Trial registration ClinicalTrials.gov , NCT03005873 . Registered on 29 December 2016

Introduction Uric acid was proposed to have anti-oxidant property and possible neuroprotective effects. We examined the association between gout and dementia with population database. Methods The study utilized the claims data from the nationwide representative sample of Taiwan National Health Insurance Research Database (NHIRD). We ascertained patients with gout and dementia covering vascular and non-vascular (including Alzheimer’s) subtypes using International Classification of Diseases Ninth Revision, Clinical Modification (ICD9-CM) codes. A control group matched on sex, age, and index date of gout patients was randomly sampled with a ratio of 1:4 from the same database for comparison. Results From 2002 to 2008, 28,769 gout patients who were older than 50 years old were identified, and 114,742 control patients was matched into the study. During follow-up, 7,119 patients developed dementia (1,214 with gout, and 5,905 without gout). After adjusting for age, sex, and relevant comorbidities, a Cox regression analysis showed that gout patients had a lower risk of developing non-vascular dementia (hazard ratio (HR): 0.77; 95% confidence interval (CI): 0.72 - 0.83; p < 0.001) and vascular dementia (HR: 0.76; 95% CI: 0.65 - 0.88; p < 0.001). Conclusions Patients with gout have a lower risk of developing dementia. This phenomenon exists for both non-vascular and vascular types of dementia.

An increased risk of mortality in patients with hyperuricemia has been reported. We examined (1) the risk of all-cause and cardiovascular disease (CVD) mortality in untreated hyperuricemic patients who did not receive urate-lowering therapy (ULT), and (2) the impact of ULT on mortality risk in patients with hyperuricemia. In this retrospective case-matched cohort study during a mean follow-up of 6.4 years, 40,118 Taiwanese individuals aged ≥17 years who had never used ULT and who had never had gout were examined. The mortality rate was compared between 3,088 hyperuricemic patients who did not receive ULT and reference subjects (no hyperuricemia, no gout, no ULT) matched for age and sex (1:3 hyperuricemic patients/reference subjects), and between 1,024 hyperuricemic patients who received ULT and 1,024 hyperuricemic patients who did not receive ULT (matched 1:1 based on their propensity score and the index date of ULT prescription). Cox proportional hazard modeling was used to estimate the respective risk of all-cause and CVD (ICD-9 code 390-459) mortality. After adjustment, hyperuricemic patients who did not receive ULT had increased risks of all-cause (hazard ratio, 1.24; 95% confidence interval, 0.97-1.59) and CVD (2.13; 1.34-3.39) mortality relative to the matched reference subjects. Hyperuricemic patients treated with ULT had a lower risk of all-cause death (0.60; 0.41-0.88) relative to hyperuricemic patients who did not receive ULT. Under-treatment of hyperuricemia has serious negative consequences. Hyperuricemic patients who received ULT had potentially better survival than patients who did not.

The in vivo activity of a monoclonal antibody that targets the CD4 binding site on T cells and blocks HIV-1 binding was assessed. In this study of antiretroviral treatment interruption involving persons with HIV-1 infection, activity of UB-421 was shown.

This paper discusses the interaction between students (humans) and an interaction response system (IRS) app (machine) in the teaching context and explores the interface usability and interactive experience design through the experimental method. The experiment mainly explored the differences in the use of the IRS app by learners with different learning styles. A total of 72 subjects were recruited for the experiment, of which the four learning styles (diverger, assimilator, converger, and accommodator) and the two kinds of information architecture (deep/shallow) are discussed respectively. With operating time performance and use experience as dependent variables, the relationship between variables was explored. The results of this study are as follows: in the learning style factor, subjects of the reflection and observation type responded faster to vibration; in the information architecture factor, with the deep information architecture, it took longer for page switching as more pages needed to be switched, and thus the operation performance was poor. According to the results of the two-stage experiment, the following design suggestions are proposed. It is expected that the research results can contribute to the fields of interactive experience design and teaching technology.

Background. Immunosuppressants can induce hepatitis B virus (HBV) reactivation; however, informative data about the risk of different immunosuppressive regimens, including biologics, on HBV reactivation (HBVr) among patients with rheumatoid arthritis (RA) are incomplete. Methods. Among 2334 RA patients who had available hepatitis B surface antigen (HBsAg) data, 123 patients positive for HBsAg who were not receiving anti-HBV prophylaxis were enrolled. These patients were undergoing varied mono or combination immunosuppressive therapy, including 36 who were receiving biological disease-modifying antirheumatic drugs (bDMARDs). Results. During 3459 person-months of follow-up, 30 (24.4%) patients developed HBVr. The multivariate Cox proportional hazard models showed that glucocorticoid significantly increased the risk of HBVr. Among all kinds of immunosuppressive treatments, glucocorticoid in combination with bDMARDs and synthetic disease-modifying antirheumatic drugs (sDMARDs) had the highest risk of HBVr (adjusted hazard ratio [HR] = 5.14; 95% confidence interval [CI] = 1.77–14.92; P = .003). Rituximab had the greatest risk for HBVr (adjusted HR = 16.51; 95% CI = 1.82–149.67; P = .01) among the patients who received bDMARDs. Conclusions. Glucocorticoid has a detrimental effect on HBVr in RA patients. Antiviral prophylactic strategies should be justified according to the risk of HBVr under different combinations of immunosuppressive therapy in rheumatic patients.

Objective This study assessed the efficacy and safety of canakinumab, a fully human anti-interleukin 1β monoclonal antibody, for prophylaxis against acute gouty arthritis flares in patients initiating urate-lowering treatment. Methods In this double-blind, double-dummy, dose-ranging study, 432 patients with gouty arthritis initiating allopurinol treatment were randomised 1:1:1:1:1:1:2 to receive: a single dose of canakinumab, 25, 50, 100, 200, or 300 mg subcutaneously; 4×4-weekly doses of canakinumab (50+50+25+25 mg subcutaneously); or daily colchicine 0.5 mg orally for 16 weeks. Patients recorded details of flares in diaries. The study aimed to determine the canakinumab dose having equivalent efficacy to colchicine 0.5 mg at 16 weeks. Results A dose-response for canakinumab was not apparent with any of the four predefined dose-response models. The estimated canakinumab dose with equivalent efficacy to colchicine was below the range of doses tested. At 16 weeks, there was a 62% to 72% reduction in the mean number of flares per patient for canakinumab doses ≥50 mg versus colchicine based on a negative binomial model (rate ratio: 0.28–0.38, p≤0.0083), and the percentage of patients experiencing ≥1 flare was significantly lower for all canakinumab doses (15% to 27%) versus colchicine (44%, p<0.05). There was a 64% to 72% reduction in the risk of experiencing ≥1 flare for canakinumab doses ≥50 mg versus colchicine at 16 weeks (hazard ratio (HR): 0.28–0.36, p≤0.05). The incidence of adverse events was similar across treatment groups. Conclusions Single canakinumab doses ≥50 mg or four 4-weekly doses provided superior prophylaxis against flares compared with daily colchicine 0.5 mg.

Other exploratory endpoints included ACR50, ACR70 and disease activity score 28 (DAS28) at week 12 and 24, tender/swollen joint counts, pain, Health Assessment Questionnaire-Disability Index, erythrocyte sedimentation rate, and C-reactive protein level. In the previous phase I/II trials, opinercept has been demonstrated to have acceptable safety and tolerability and improved clinical responses in patients with RA,14,15 warranting a corroborative phase III study. [...]in this study, we aimed to evaluate the efficacy and safety profile of opinercept for RA patients undergoing DMARDs therapy. Participants were screened for eligibility within 14±7 days before randomization. Besides granting consent and being competent to comply with study procedures, other inclusion criteria were: (i) age >20 years with RA functional class I-III by American College of Rheumatology (ACR) criteria for >6 months; (ii) currently active disease with at least six tender joints and swollen joints; (iii) erythrocyte sedimentation rate (ESR) >28 mm/hour and/or C-reactive protein (CRP) >10 mg/L; (iv) >8 weeks of prior treatment with stable doses of methotrexate, hydroxychloroquine, sulfasalazine, leflunomide, or azathioprine preenrollment. Efficacy assessments were conducted based on rates of improvement by 20%, 50% and 70% according to ACR criteria (ACR20/50/70), and changes from baseline in: disease activity score-28 (DAS28), ACR 66/68 count for tender and swollen joints, pain visual analog scale (VAS), patient and physician global assessments, Health Assessment Questionnaire-Disability Index (HAQ-DI), and levels of ESR and CRP.

The treatment landscape for psoriatic arthritis (PsA) has evolved significantly with the introduction of biologic therapies, such as adalimumab, which effectively inhibits tumor necrosis factor-alpha (TNF-α) activity. However, despite their efficacy in controlling inflammation, biologic therapies are associated with heightened risks of infectious complications and malignancies. We present a case of a 66-year-old female with PsA treated with adalimumab who presented with recurrent systemic bacterial infections. Despite attempts to adjust dosing intervals to minimize infection risks, the patient experienced severe complications, including urosepsis, endocarditis, and liver abscesses. The dilemma arises in balancing PsA control with anti-TNFα therapy while minimizing infection risks. Current evidence supporting prophylactic antibiotics in such cases is limited, and determining the next steps for treatment involves challenging decisions such as withholding TNF inhibitors or switching to alternative immunomodulators. This case underscores the need for further research into prophylactic treatment and monitoring protocols to manage recurrent infections during anti-TNF-α therapy effectively.

Background: Use of selective cyclooxygenase (COX)-2 inhibitors is associated with a better gastrointestinal (GI) safety profile than use of other NSAIDs. However, the risk factors for clinical upper GI events (symptomatic ulcers and ulcer complications) in COX-2 inhibitor users have been rarely evaluated in the past. Objective: The aim of this study was to assess the annual incidence of and identify the risk factors for clinical upper GI events in chronic COX-2 inhibitor (celecoxib and etoricoxib) users. Methods: A prospective, hospital-based, observational cohort study was conducted in patients taking COX-2 inhibitors (celecoxib or etoricoxib) without comorbidity. COX-2 inhibitor prescription was conducted according to the guidelines issued by the Taiwan National Health Insurance and was identified by the computerized prescribing system of the Taipei Veterans General Hospital, Taipei, Taiwan. Patients with cardiovascular disease, pulmonary, hepatic or renal insufficiency, or malignancy were excluded. Patients received regular follow-up once a month. Between visits, patients were asked to report to the outpatient clinic if they had persistent ulcer or GI symptoms (dyspepsia, vomiting, nausea, heartburn, or acid regurgitation) not relieved by antacids for 1 week, or to the emergency department if they had evidence of GI bleeding or ulcer complications (melena, hematemesis, hematochezia, or sudden onset of severe epigastric pain). Endoscopy was performed to document any gastroduodenal ulcers with or without ulcer complications. The primary end point was the annual incidence and the significant risk factors for clinical upper GI events (symptomatic ulcers and ulcer complications). Results: A total of 1158 COX-2 inhibitor users were identified; 96 refused to participate and 129 were excluded. The mean (SD) age of the remaining 933 COX-2 inhibitor users was 69 (15) years with 528 women (56.6%) and 405 men (43.4%). Mean time of follow-up was 12.4 months. The annual incidence of clinical upper GI events in these patients taking COX-2 inhibitors was 4.6% (44 events/959 patient-years), with symptomatic ulcers in 3.6% and ulcer complications in 1.0%. Multivariate logistic regression analysis found that a history of peptic ulcer disease (PUD) (odds ratio [OR = 4.61; 95% CI, 1.86–11.40; P = 0.001), concomitant use of steroids (OR = 2.99; 95% CI, 1.39–6.46; P = 0.005), aspirin (OR = 13.47; 95% CI, 5.89–30.82; P < 0.001), and other NSAIDs (OR = 60.49; 95% CI, 11.93–306.64; P < 0.001) were significant independent risk factors for clinical upper GI events in these patients taking COX-2 in-hibitors. Age >60 years was not found to be a risk factor. Conclusions: The annual incidence of clinical upper GI events was 4.6% in these Taiwanese patients without comorbidity taking COX-2 inhibitors. A history of PUD and concomitant use of steroids, aspirin, or other NSAIDs, were found to be significant risk factors for clinical upper GI events in these patients.