Effect of Anti-CD4 Antibody UB-421 on HIV-1 Rebound after Treatment Interruption.

BACKGROUND: Administration of a single broadly neutralizing human immunodeficiency virus (HIV)-specific antibody to HIV-infected persons leads to the development of antibody-resistant virus in the absence of antiretroviral therapy (ART). It is possible that monotherapy with UB-421, an antibody that blocks the virus-binding site on human CD4+ T cells, could induce sustained virologic suppression without induction of resistance in HIV-infected persons after analytic treatment interruption. METHODS: We conducted a nonrandomized, open-label, phase 2 clinical study evaluating the safety, pharmacokinetics, and antiviral activity of UB-421 monotherapy in HIV-infected persons undergoing analytic treatment interruption. All the participants had undetectable plasma viremia (<20 copies of HIV RNA per milliliter) at the screening visit. After discontinuation of ART, participants received eight intravenous infusions of UB-421, at a dose of either 10 mg per kilogram of body weight every week (Cohort 1) or 25 mg per kilogram every 2 weeks (Cohort 2). The primary outcome was the time to viral rebound (≥400 copies per milliliter). RESULTS: A total of 29 participants were enrolled, 14 in Cohort 1 and 15 in Cohort 2. Administration of UB-421 maintained virologic suppression (<20 copies per milliliter) in all the participants (94.5% of measurements at study visits 2 through 9) during analytic treatment interruption, with intermittent viral blips (range, 21 to 142 copies per milliliter) observed in 8 participants (28%). No study participants had plasma viral rebound to more than 400 copies per milliliter. CD4+ T-cell counts remained stable throughout the duration of the study. Rash, mostly of grade 1, was a common and transient adverse event; one participant discontinued the study drug owing to a rash. A decrease in the population of CD4+ regulatory T cells was observed during UB-421 monotherapy. CONCLUSIONS: UB-421 maintained virologic suppression (during the 8 to 16 weeks of study) in participants in the absence of ART. One participant discontinued therapy owing to a rash. (Funded by United Biomedical and others; ClinicalTrials.gov number, NCT02369146.).

Hepatitis B Virus Reactivation in Rheumatoid Arthritis Patients Undergoing Biologics Treatment.

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.

Risk of hemophagocytic lymphohistiocytosis in adults with fevers of unknown origin: the clinical utility of a new scoring system on early detection.

The diagnosis of hemophagocytic lymphohistiocytosis (HLH) is delayed by most physicians. This study aimed to identify early parameters and suitable scoring systems for the risk of HLH. Clinical and laboratory data collected ≤3 days after admission were defined as early parameters and used to calculate the number of HLH-2004 criteria met and bone marrow (BM) score. Between January 2006 and February 2016, 233 immunocompetent adults with naïve fever of unknown origin who underwent a BM study were enrolled to mimic patients at risk of HLH and randomly assigned into the developmental or validation cohort. Hemophagocytic lymphohistiocytosis was finally diagnosed in 47 patients, with non-Hodgkin lymphoma as the major etiology (51.1%). Upon admission, four-fifths of patients who developed subsequent HLH fulfilled ≤3 of 8 HLH-2004 criteria, and 6 early parameters were independent predictors of HLH: anemia (hemoglobin < 10 g/dL), thrombocytopenia (platelet count < 100 × 103 /µL), leukoerythroblastosis, hyperbilirubinemia (total bilirubin > 2 × upper normal limit), hyperferritinemia (ferritin > 1000 ng/mL), and splenomegaly. Compared with the HLH criteria met upon admission, the BM score was an independent predictor (odds ratio = 1.621; 95% confidence interval, 1.355-1.940) with excellent discrimination (area under the receiver operating characteristic curve = 0.920; 95% confidence interval, 0.883-0.958). The sensitivity and specificity for a BM score cutoff of 10 points were 95% and 75%, respectively. When approaching immunocompetent adults with a continuously high fever, the BM score at initial admission assists with early identification of patients at risk of HLH.

Short-term effect of ultrasound-guided low-molecular-weight hyaluronic acid injection on clinical outcomes and imaging changes in patients with rheumatoid arthritis of the ankle and foot joints. A randomized controlled pilot trial.

To determine whether hyaluronic acid (HA) injection into rheumatoid arthritis ankles and feet can achieve improvement in foot function and reduce synovial hyper-vascularization. Forty-four patients with RA having unilateral or bilateral painful ankle and foot involvement (N = 75) were studied. All the patients were randomized to receive HA (N = 40) or lidocaine (LI) (N = 35) injection at 2-week intervals; Clinical assessments were performed using a visual analog scale (VAS) and foot function index (FFItotal) including subscales of pain (FFIpain) before injection at baseline, 4 weeks (first evaluation) and 12 weeks (secondary evaluation). Imaging evaluation based on color Doppler ultrasound (CDUS) and synovitis scores was performed simultaneously. HA injection improved the VAS score (p = .009), FFIpain (p = .041), and FFItotal (p = .032) considerably more than LI injections did at the first evaluation. The CDUS values at first evaluation (p = .005) and secondary evaluation (p < .001) decreased significantly compared with the base line values. HA injections reduced the CDUS values of more than half of the joints (54%, p = .042) while the control group exhibited no change (20%, p = .56). However, HA injection did not reduce the CDUS values more than LI injection did. Regarding the evaluation of synovial hypertrophy, no significant difference was observed between or within the groups in the synovitis scores. HA injection improved short-term foot function and pain reduction. HA injection may have a modest effect in reducing synovial hyper-vascularization. Further large-scale study is warranted to confirm this result.

Decoy receptor 3 suppresses B cell functions and has a negative correlation with disease activity in rheumatoid arthritis.

OBJECTIVES: The decoy receptor 3 (DcR3) is a member of the tumour necrosis factor (TNF) receptor superfamily and may regulate inflammation. The aim of this study was to investigate the role of DcR3 in B cell functions and its correlation to disease activity in patients with rheumatoid arthritis (RA). METHODS: The concentrations of DcR3 and TNF-α were measured by ELISA. B cell proliferation was assessed by quantification of 3H-thymidine uptake. Staphylococcus aureus Cowan (SAC) strain were used to stimulate B cell proliferation and TNF-α production. RESULTS: Compared to the osteoarthritis (OA) patients, the RA group had higher synovial DcR3 levels (3273.6±1623.2 vs. 1594.8±1190.0 pg/ml, p=0.003), which were negatively correlated with the serum erythrocyte sedimentation rate and Disease Activity Score using 28 joint counts (DAS28) scores (r=-0.560, p=0.002; r=-0.579, p<0.001, respectively). Although the RA B cells have more active characteristics, B cell proliferation induced by SAC was successfully suppressed by recombinant DcR3.Fc fusion protein with an average inhibition of 44.8%. Moreover, DcR3.Fc fusion protein was found to suppress SAC-induced TNF-α production by B cells in 8 RA patients (average inhibition 47.0%). CONCLUSIONS: The results of our study indicated that the inhibition of B cell functions by DcR3 may partially explain the negative correlation between DcR3 level and disease activity in RA patients. Our findings imply that DcR3 may be used as a biomarker for disease activity and a potential therapeutic agent in the treatment of RA.

Disease activity affects all domains of quality of life in patients with rheumatoid arthritis and is modified by disease duration.

OBJECTIVES: This study was conducted to determine how disease activity affects quality of life (QOL) and its interaction with functional impairments, and disease duration in patients with rheumatoid arthritis (RA). METHODS: This cross-sectional study enrolled 230 patients with RA from a rheumatology clinic in Taiwan and 227 healthy controls matched according to age, sex, marital status, and education. QOL was measured using the Taiwan version of the short form of the World Health Organisation Quality of Life (WHOQOL-BREF) questionnaire. Activity of RA was assessed by the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28). Functional disability was assessed by the Health Assessment Questionnaire (HAQ). Multiple regression analyses were performed to explore independent effects and interactions among DAS28, HAQ, and duration after controlling demographic factors. RESULTS: A higher HAQ score, longer duration of disease, and higher DAS28 score were independently associated with lower QOL scores. DAS28 score affected most items in all physical, psychological, environment, and social domains after controlling other factors. Besides, patients with longer disease duration showed aggravated scores on many facets of the physical and psychological domains, if their disease activity was elevated. CONCLUSIONS: Disease activity affects QOL of RA patients in all domains. It also aggravates scores in physical and physiological domains among those with a longer duration.

The Dilemma of Balancing Anti-Tumor Necrosis Factor-Alpha (Anti-TNF-α) Biologics for Psoriatic Arthritis Control With the Risk of Severe Systemic Infection.

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.

DR-70 immunoassay for the surveillance of hepatocellular carcinoma.

BACKGROUND AND AIM: Although alpha-fetoprotein (AFP) is a widely used serological marker for hepatocellular carcinoma (HCC), its utility is limited due to its unsatisfactory sensitivity. Meanwhile, a newly developed immunoassay-DR-70-has been reported to have a good sensitivity for HCC in a small-scale study. The aim of this study was to determine the clinical value of DR-70 for the surveillance of HCC. METHODS: Serum levels of DR-70 and AFP were measured in 103 patients with HCC, 50 healthy volunteers, and 33 patients with chronic liver disease. In addition, we investigated the prognostic value of DR-70 in patients with HCC correlating with the clinical staging-Cancer of the Liver Italian Program (CLIP) score and Barcelona Clinic Liver Cancer (BCLC) classification. RESULTS: Based on the receiver operating characteristic curve with area under the curve of 0.836, the DR-70 cut-off value for detecting HCC was determined to be 0.75 µg/mL. DR-70 provided a sensitivity of 81.6% and a specificity of 77.1%, and correlated well with the CLIP score and BCLC classification. The combination of DR-70 and AFP increased the sensitivity to 91.2%. The prognosis for patients with HCC with DR-70 level > 0.75 µg/mL was worse than that for those with DR-70 ≤ 0.75 µg/mL. Among the patients with early stage HCC (CLIP score 0-2), DR-70 > 0.75 µg/mL independently predicted a poor survival. CONCLUSIONS: DR-70 immunoassay is complementary to AFP for the detection of HCC and has a good correlation with clinical staging and prognosis.

TLC599 in patients with osteoarthritis of the knee: a phase IIa, randomized, placebo-controlled, dose-finding study.

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.

Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double-blind, randomised study.

OBJECTIVE: This study assessed the efficacy and safety of canakinumab, a fully human anti-interleukin 1ß 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.

Thrombotic microangiopathy in systemic lupus erythematosus: a cohort study in North Taiwan.

OBJECTIVES: Thrombotic microangiopathy (TMA) co-existing with SLE is rarely reported. This study aimed to investigate the triggering factors, clinical features and outcomes of SLE patients with TMA in Northern Taiwan. METHODS: Twenty-five TMA cases out of 2461 SLE patients admitted to Taipei Veterans General Hospital, between 2000 and 2010, were enrolled. RESULTS: When TMA occurred, 16 (64.0%) patients had infection; 22 (88.0%) were in an active disease state with a SLEDAI score >10. Among the infection group, 13 (81.3%) had an increase in the SLEDAI score of ≥ 4. We found that older age (≥ 50 years), low platelets (≤ 20,000/nm(3)), presence of infection, acute renal failure (ARF) or four or more TMA features were independent risk factors for persistent haematological abnormalities (P < 0.05); older age (≥ 50 years) and a high reticulocyte index (>2%) were the risk factors for persistent renal function impairment (P < 0.05). The overall mortality rate was 52.0% (13 out of 25); older age (≥ 40 years), low complement value, presence of infection (P < 0.001), two or more infection sources, ARF and four or more TMA features were the statistically significant factors contributing to a higher mortality rate. Patients receiving plasma exchange seven times or more had a significantly higher rate of improvement in renal function and haematological abnormalities. CONCLUSIONS: Our study showed that infection was one of the major triggers for the flare-up of SLE disease activity and occurrence of TMA in SLE. Infection is also a strong risk factor for outcome in SLE patients with TMA. Plasma exchange can be considered as an adjuvant treatment modality.

Rheumatoid arthritis management in the APLAR region: Perspectives from an expert panel of rheumatologists, patients and community oriented program for control of rheumatic diseases.

Rheumatoid arthritis (RA) is a major health burden in Asia Pacific affecting the quality of life of patients and consuming healthcare resources. According to recent estimates from the World Health Organization-International League Against Rheumatism-Community Oriented Program for Control of Rheumatic Diseases, prevalence is around 0.3%-0.5%. Management guidelines have helped to improve treatment across this diverse region. To gain better insight into current real-world management applications in view of these guidelines, virtual meetings were conducted in mid-2020 to explore perspectives of rheumatologists and patients, as well as discuss the impact of coronavirus disease 2019 on RA management. Patients and rheumatologists from Hong Kong, Malaysia, Singapore, the Philippines, Thailand, India, Pakistan, and Taiwan were included, representing a diverse mix of healthcare systems, wealth, ethnicity and culture. Despite many countries having prospered in recent years, similar challenges in RA diagnosis and treatment were identified. The daily impact and patient experience of RA were also similar across countries, marked by "silent" pain and disability, and universal misunderstanding of the disease. Late diagnosis and treatment, and barriers to access to appropriate treatment, remain problematic. The experience shared by Taiwan offers a glimmer of hope, however, wherein patient advocacy groups have succeeded in being included in policy-making decisions and securing access to advanced treatment. Real-world solutions that pay heed to the unique local needs and diversity of Asia Pacific are required to improve RA management, which will take time. In the interim, help can be sought from the trained, non-rheumatologist community to reduce some of the disease burden.

Efficacy and Safety of Opinercept Tumor Necrosis Factor Inhibitor Therapy for Drug-Refractory Rheumatoid Arthritis: A Randomized Clinical Trial.

OBJECTIVES: This study aims to evaluate the efficacy and safety profile of opinercept for rheumatoid arthritis (RA) patients undergoing disease- modifying anti-rheumatic drugs (DMARDs) therapy. PATIENTS AND METHODS: A total of 98 patients with active RA (17 males, 81 females; mean age 58.6±12.2 years; range, 24.3 to 85.3 years) were randomized into opinercept plus DMARDs (OD group) or placebo plus DMARDs (PD group), in a 24-week treatment period. Primary outcome was American College of Rheumatology score (ACR20) at week 24. 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. Incidence of adverse events (AEs), vital signs and physical findings, and laboratory test results were also evaluated. RESULTS: Patients in OD group showed significantly higher achievement percentage of ACR20 at week 24 than the PD group (76.6% vs. 30.3%, p<0.001). The evaluation of DAS28 was significantly improved in OD patients compared to PD patients at weeks 12 and 24. Most of the occurred AEs were mild or moderate and considered unrelated to study treatments. CONCLUSION: Opinercept concurrent with DMARDs was superior to DMARDs alone in slowing RA progression and ameliorating symptoms, with well- tolerated and acceptable safety profile.

Neuromagnetic Amygdala Response to Pain-Related Fear as a Brain Signature of Fibromyalgia.

INTRODUCTION: Fibromyalgia (FM) is a chronic pain condition characterized by impaired emotional regulation. This study explored the brain response to pain-related fear as a potential brain signature of FM. METHODS: We used a conditioned fear task and magnetoencephalography to record pain-related fear responses in patients with FM. Two blocks of 30 fear responses were collected to compute the response strength in the first block and the strength difference between the first and second blocks (fear habituation). These measurements were investigated for their clinical relevance and compared with measurements obtained from healthy controls and patients with chronic migraine (CM), a different chronic pain condition often comorbid with FM. RESULTS: Pain-related fear clearly activated the bilateral amygdala and anterior insula in patients with FM (n = 52), patients with CM (n = 50), and the controls (n = 30); the response strength in the first block was consistent across groups. However, fear habituation in the right amygdala decreased in the FM group (vs. CM and control groups, both p ≤ 0.001, no difference between CM and control groups). At the 3-month follow-up, the patients with FM reporting < 30% improvement in pain severity (n = 15) after pregabalin treatment exhibited lower fear habituation in the left amygdala at baseline (vs. ≥ 30% improvement, n = 22, p = 0.019). Receiver operating characteristic analysis confirmed that amygdala fear habituation is a suitable predictor of diagnosis and treatment outcomes of FM (area under the curve > 0.7). CONCLUSIONS: Amygdala activation to pain-related fear is maladaptive and linked to treatment outcomes in patients with FM. Because the aberrant amygdala response was not observed in the CM group, this response is a potential brain signature of FM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT02747940.

Erratum to development and formulation of the classification criteria for osteoarthritis.

[This corrects the article DOI: 10.21037/atm-20-4673.].

Guidelines for the diagnosis and treatment of osteoarthritis in China (2019 edition).

Osteoarthritis (OA) is a degenerative disease of middle-aged and elderly people, contributed a higher burden of disease in China and the world. In 2017, under the support of the Rheumatology and Immunology Expert Committee of the Cross-Strait Medical and Health Exchange Association. The objective was to develop an evidence-based diagnosis and treatment guideline for OA in China based on emerging new evidence. The guideline was registered at International Practice Guidelines Registry Platform (IPGRP-2018CN028). The grading of recommendations assessment, development and evaluation (GRADE) approach was used to rate the quality of evidence and the strength of recommendations, and the RIGHT (Reporting Items for Practice Guidelines in Healthcare) checklist was followed to report the guideline. The guideline provides recommendations for the OA diagnosis, disease risks monitoring and evaluate, treatment purpose and physical, medical and surgical interventions. This guideline is intended to serve as a tool for Chinese clinicians for the best decisions-making on diagnosis and treatment of OA.

Development and formulation of the classification criteria for osteoarthritis.

BACKGROUND: The classification criteria of osteoarthritis (OA) is lack of the support of relevant research evidence and there is no standardized protocol for detailed steps of the development or clinical verification of classification criteria has yet been established. This study aims to describe the development process of the Categorization of Osteoarthritis CHecklist (COACH), which is designed to choose the precise treatment option for patients with OA. METHODS: A multidisciplinary panel was established to gather opinions. We conducted questionnaire survey and literature review to generate and COACH Panel members were invited to review the drafted classification criteria and optimize classification criteria. The final list of items was discussed and reached the agreement by the core group of the panel. RESULTS: Thirty-six experts participated in COACH Panel including rheumatologist (80.6%; 29/36), orthopedist (13.9%; 5/36), methodologist (2.8%; 1/36) and rehabilitation physician (2.8%; 1/36) for classification factors generating and optimizing. The main body of the final classification criteria consists of six types of OA pathogenesis, eight types of medical findings (which can be grouped into two categories), and six types of the location. The final criteria include load-based type, structure-based type, inflammation-based type, metabolic-based type, systemic factor based type and mixed type. CONCLUSIONS: COACH can better help clinicians quickly classify OA patients and help to choose the best treatment option from the aspects of types, findings and locations. What's more, the classification criteria are also helpful to promote the basic medical research and targeted prevention of OA.

Gastric mucosal injury in systemic lupus erythematosus patients receiving pulse methylprednisolone therapy.

AIMS: Whether glucocorticoids induce gastric mucosal injury remains uncertain. We investigated whether very high-dose steroids caused gastric mucosal injury in systemic lupus erythematous (SLE) patients and evaluated the possible risk factors for mucosal injury. METHODS: In this prospective paired study, 67 SLE patients who had received pulse methylprednisolone therapy were enrolled. Each patient underwent endoscopic examination and tissue and blood sampling before and after pulse steroid therapy. Mucosal injury was diagnosed if the follow-up injury scale was higher than the initial scale. Examined parameters included Helicobacter pylori infection, cyclooxygenase (COX)-1 and COX-2 activity, and current nonsteroidal anti-inflammatory drug (NSAID) usage including aspirin. RESULTS: Eleven (16.4%) of 67 cases who developed gastric mucosal injury after pulse therapy had significantly higher rates of peptic ulcer history, NSAID/aspirin use, lower gastric thromboxane B(2) and prostaglandin E(2) levels when compared with cases without gastric mucosal injury (P < 0.05). Infection by H. pylori was not a risk factor for gastric mucosal injury. Multivariate logistic regression analysis showed that NSAID/aspirin use was the only risk factor for gastric mucosal injury in these patients (odds ratio 26.99, 95% confidence interval 4.91, 148.57, P < 0.0001). Pulse steroid therapy alone did not induce gastric mucosal injury in fifty SLE patients without taking any NSAID/aspirin. CONCLUSIONS: Use of NSAIDs/aspirin, but not H. pylori infection, increases gastric mucosal injury in SLE patients receiving pulse methylprednisolone therapy. Very high-dose steroids de novo seem not to induce gastric mucosal injury in these patients. A larger case-controlled study enrolling a heterogeneous population is needed to clarify the role of glucocorticoids in gastric mucosal injury.

Disability and pain management methods of Taiwanese arthritic older patients.

AIM: This study aims to investigate the prevalence of disability, factors influencing disability and pain self-management techniques employed by older arthritis patients in Taiwan. BACKGROUND: Arthritis is the most common chronic disease in older people. It may result in pain, stiffness and joint deformity, which ultimately lead to disability. Understanding the factors influencing disability is needed to help arthritis sufferers to achieve optimal health status. DESIGN: A cross-sectional design was employed for this study. METHODS: One hundred and fifty-one older persons diagnosed with either rheumatoid arthritis or osteoarthritis were interviewed in the rheumatology clinics located in two medical centres in northern Taiwan. Six questionnaires were administered: Barthel Index, Instrumental Activity of Daily Living, Rapid Assessment of Disease Activity in Rheumatology, the Chinese version of Pain Management Inventory, Geriatric Depression Scale and Life Satisfaction Index. RESULTS: Disability was found in 11% of Taiwanese individuals diagnosed with either rheumatoid arthritis or osteoarthritis. Those in disability reported more severe disease activity, pain, depression and lower life satisfaction. Hierarchical multiple regression analysis revealed that 31-46% of the total variance of disability could be explained by age, gender, marriage, joint pain score, diagnosis, disease activity, depression and pain management. Patients with rheumatoid arthritis had significantly higher levels of disability, disease activity during the preceding six months, more depression and less life satisfaction than patients with osteoarthritis. CONCLUSION: Higher disability was explained by older age, female, unmarried, diagnosed with rheumatoid arthritis, more joint pain, more disease severity, more depression and more use of pain management strategies in arthritis patients. RELEVANCE TO CLINICAL PRACTICE: Nurses are urged to recognise the individual differences among the factors that are thought to contribute most to disability. An individualised, multidimensional and comprehensive treatment plan with informational support is essential to maximise pain management skills of arthritic older people to achieve improvement in pain, level of disability and mental health.

Omeprazole promotes gastric epithelial cell migration.

Proton pump inhibitors (PPIs) are effective at preventing non-steroidal anti-inflammatory drug (NSAID)-induced gastric ulcers. They are also superior to histamine H(2)-receptor antagonists and misoprostol in treating NSAID-induced gastric ulcer healing. This study explored whether omeprazole, a PPI, can modulate ulcer healing through epithelial cell proliferation and/or cell migration using a rat normal gastric epithelial cell line (RGM-1). Flow cytometry was used to determine cell proliferation and an artificial wound model was used to measure cell migration. Western blot analysis was performed to evaluate the possible mechanisms of action. Omeprazole treatment (10(-8), 10(-6) and 10(-4)M) for 12 and 24 h did not promote cell proliferation. However, similar doses of the drug (10(-6) and 10(-4)M) incubated for 24-48 h significantly promoted the basal cell migration of gastric epithelial cells. Further, the higher concentration of omeprazole (10(-4)M) reversed the inhibitory action of indometacin (10(-5)) on cell migration. Western blot results showed that omeprazole did not increase cyclooxygenase-2 expression and did not activate signal transduction pathways, including extracellular signal-regulated kinase (ERK1/ERK2), P38 mitogenic-activated protein kinase, and phosphatidyl inositol 3-kinase. The results suggest that omeprazole is beneficial in basal ulcer healing and it reversed the adverse action of indometacin on ulcer repair under acid-independent conditions. These actions are likely to be mediated through the promotion of gastric epithelial cell migration but not cell proliferation.