Increased Circulating CD14+ Monocytes in Patients with Psoriatic Arthritis Presenting Impaired Apoptosis Activity.

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis primarily affecting peripheral and axial joints. The osteolytic effect in the damaged joint is mediated by osteoclast activation. We aimed to investigate differential gene expression in peripheral CD14+ monocytes between patients with psoriatic arthritis (n = 15) and healthy controls (HCs; n = 15). Circulating CD14+ monocytes were isolated from peripheral blood mononuclear cells using CD14+ magnetic beads. Cell apoptosis was measured via Annexin V using flow cytometry. The gene expression profiling was analyzed via microarray (available in the NCBI GEO database; accession number GSE261765), and the candidate genes were validated using PCR. The results showed a higher number of peripheral CD14+ monocytes in patients with PsA than in the HCs. By analyzing the microarray data, identifying the differentially expressed genes, and conducting pathway enrichment analysis, we found that the apoptosis signaling pathway in CD14+ cells was significantly impaired in patients with PsA compared to the HCs. Among the candidate genes in the apoptotic signaling pathway, the relative expression level of cathepsin L was confirmed to be significantly lower in the PsAs than in the HCs. We concluded that the numbers of peripheral CD14+ monocytes increased, and their apoptosis activity was impaired in patients with PsA, which could lead to enhanced macrophage maturation and osteoclast activation. The resistance of apoptotic death in peripheral CD14+ monocytes may contribute to active joint inflammation in PsA.

Development and Comparison of Treatment Decision Tools for Glucocorticoid-Induced Osteoporosis.

Long-term Glucocorticoid (GC) use results in compromised bone strength and fractures, and several treatment recommendations have been developed to prevent fractures, but none have been validated in a real-world setting. This study aims to create a treatment decision tool and compares this tool to the treatment suggestions from the American College of Rheumatology (ACR), International Osteoporosis Foundation and European Calcified Tissue Society (IOF-ECTS), and GC-adjusted Fracture Risk Assessment Tool (GC-FRAX), above the intervention threshold. We utilized registry data gathered at Chang Gung Memorial Hospital at Kaohsiung, Taiwan, between September 2014 and April 2021. This research is a single-center, observational, and case-controlled study. We recruited participants using prednisone for at least 2.5 mg/day or the equivalent dose for over 3 months, excluding those younger than 40, those with malignancies, or those currently undergoing anti-osteoporosis therapy. The primary endpoint was new fragility fractures within 3 years, including morphometric vertebral fractures detected at baseline and with a follow-up thoracic-lumbar spine X-ray. Participants were randomly allocated into derivation and validation sets. We developed the Steroid-Associated Fracture Evaluation (SAFE) tool in the derivation cohort by assessing the weights of exploratory variables via logistic regression. Prediction performance was compared in the validation set by the receiver operating characteristic (ROC) curve, the area under the curve (AUC), and sensitivity and specificity. A total of 424 treatment-naïve subjects were enrolled, and 83 (19.6%) experienced new fractures within 3 years. The final formula of the SAFE tool includes osteoporosis (1 point), an accumulated GC dose ≥ 750 mg within 6 months (or equivalent prednisolone of ≥4.5 mg/day for 6 months) (1 point), a BMI ≥ 23.5 (1 point), previous fractures (1 point), and elderliness of ≥70 years (2 points). In the validation set, a treatment decision based on the SAFE ≥ 2 points demonstrated an AUC of 0.65, with a sensitivity/specificity/accuracy of 75.9/54.0/58.9, with an ACR of 0.56 (100.0/11.0/31.0), IOF-ECTS 0.61 (75.9/46.0/52.7), and GC-FRAX 0.62 (82.8/42.0/51.2). Among current GIOP recommendations, the SAFE score serves as an appropriate treatment decision tool with increased accuracy and specificity.

Disease-modifying anti-rheumatic drugs associated with different diabetes risks in patients with rheumatoid arthritis.

OBJECTIVES: Patients with rheumatoid arthritis are prone to developing diabetes, which may lead to various sequelae and even cardiovascular diseases, the most common cause of death in such patients. Previous research has shown that some rheumatoid arthritis treatments may help prevent the development of diabetes. This study aimed to investigate whether patients using disease-modifying anti-rheumatic drugs (DMARDs) may have different levels of risk for diabetes and to analyse other risk factors for diabetes. METHODS: This cohort study used data from the Chang Gung Research Database. 5530 adults with rheumatoid arthritis but without diabetes were eligible for the analysis. The endpoint of this study was new-onset diabetes, defined as an HbA1c value ≥7% during follow-up. The entire follow-up period was divided into monthly subunits. These 1-month units were then divided into methotrexate (MTX) monotherapy, any biological DMARDs (bDMARDs), MTX combination, other conventional DMARDs (cDMARDs) and non-DMARDs. RESULTS: A total of 546 participants (9.87%) developed diabetes between 2001 and 2018. The risk of diabetes was significantly lower in the bDMARD periods (HR 0.51; 95% CI 0.32 to 0.83), MTX combination periods (HR 0.50; 95% CI 0.32 to 0.78) and other cDMARD periods (HR 0.56; 95% CI 0.37 to 0.84) than in the MTX monotherapy periods. Individual drug analysis showed that hydroxychloroquine (HR 0.52; 95% CI 0.42 to 0.65) reduced the risk of diabetes. Tumour necrosis factor-α inhibitors (HR 0.69; 95% CI 0.46 to 1.03) tended to be protective. CONCLUSION: Patients with rheumatoid arthritis may have different levels of risk of diabetes depending on the treatment options.

Factors associated with subclinical inflammation of wrist joints in rheumatoid arthritis patients with low or no disease activity- a RA ultrasound registry study.

BACKGROUND: To evaluate the factors to predict subclinical inflammation of wrist joints in patients with RA who are in clinical remission or low disease activity. METHODS: Gray scale and power Doppler ultrasound were performed on the dorsal radio-lunate of both wrists. The presence of synovitis, comorbidities, and use of disease modifying anti-rheumatic drugs were recorded. A Multivariable forward logistical regression model was used to identify factors associated with subclinical inflammation. RESULTS: There were 1248 patients (1010 females, 238 males; mean age: 60.0 ± 10.5 years ). 57.4% of patients in complete remission and low disease activity had sonographic inflammation. Multivariable forward logistic regression analysis indicated that male sex, smoking are positively associated with inflammation and that age, alcohol consumption, and use of methotrexate, glucocorticoid, or a biological therapy are negatively associated with inflammation. Use of biological agents decreased the risk of inflammation by 40.9%. CONCLUSIONS: There was evidence of subclinical inflammation in most patients who were in low or no disease activity, those with biological therapy had lower risk of subclinical inflammation.

Identify differential inflammatory cellular and serology pathways between children and adult patients in the lupus registry.

BACKGROUND: Age variances in systemic lupus erythematosus (SLE) may reflect different patterns and consequences. Monocyte differentiation is critical, and cytokine and chemokine milieu may be associated with long term outcome and treatment responses. This study aims to evaluate the inflammatory cellular and serology pathways associated with age in our lupus registry. METHODS: We included patients with SLE and divided them into 2 groups according to age, ≤18 or >18 years old. We performed flow cytometry analysis to define the peripheral blood monocyte differentiation pattern and phenotypes and used the multiplex method to detect cytokine and chemokine panels. The results were then compared between the 2 subgroups. RESULTS: In total, 47 SLE patients were included in this study. Of those, 23 patients were 18 years old or younger, and 24 patients were over the age of 18 years old. An increased distribution of circulating Type 2b macrophage (M2b) subsets was found in patients over 18 years old (P < 0.01), and we found the Type 1 macrophage (M1) to demonstrate a marked increase in those patients ≤18 years old (P = .05). Eotaxin values were significantly higher in patients >18 years old (P = .03), and Macrophage Inflammatory Protein (MIP)-1alpha, MIP-1beta, Interleukine (IL)-1Ra, Interferon (IFN)-alpha2, IL-12, IL-13, IL-17A, IL-1beta, IL-2, IL-4, IL-5, IL-7, IL-9, Monocyte Chemoattractant Protein (MCP)-3, Transforming Growth Factor (TGF)-alpha, and Tumor necrosis factor (TNF)-beta were significantly higher in patients ≤18 years old (all P < .05). CONCLUSIONS: We found significant M2b polarization in adult SLE patients, and several cytokines and chemokines were significantly higher in SLE patients ≤ 18 years old. Peripheral blood mononuclear cell differentiation and cytokine milieu could represent composite harm from both Type 2 helper T cells (Th2) and Type 17 helper T cells (Th17) pathways and may thus be a potential therapeutic target in younger SLE patients.

Time-dependent risk of mortality and end-stage kidney disease among patients with granulomatosis with polyangiitis.

Objective: To describe the time-dependent impact of granulomatosis with polyangiitis (GPA) on the risk of mortality and end-stage kidney disease (ESKD). The results would provide valuable insight regarding the most vulnerable period for patients with GPA. Methods: We conducted a retrospective cohort study using a nationally representative database in Taiwan. Patients with incident GPA without prior ESKD were identified, and non-GPA control cohorts were selected and matched to GPA cohorts based on sex, age, entry time and comorbidities in a 1:4 ratio. Cox regression model was used to estimate hazard ratios (HR) for mortality and ESKD stratified by the follow-up period. Results: We identified a total of 142 GPA patients and 568 matched controls. Of those, 52 GPA patients died during follow-up, 48.1% of whom did so within the first 6 months after diagnosis. The 1-, 3-, 5-, and 10-year survival rates of GPA were 78.2, 71.2, 62.6, and 54.7%, respectively. Patients with GPA exhibited the greatest risk of mortality within the first 6 months after follow-up compared with non-GPA cohorts (HR: 21.9, 95% CI: 8.41-57.5). The mortality risk diminished after 1 year and to a marginally significant level during the follow-up period of 5-10 years (HR: 2.71, 95% CI: 0.97-7.62). Ten (7.1%) of the GPA patients experienced ESKD, and these cases occurred exclusively in the first 3 years following diagnosis. Conclusion: Our findings suggest that physicians should closely monitor the treatment response and complications of patients with GPA in the first critical 6-month period after diagnosis to improve long-term survival outcome.

Gut microbiota differences between psoriatic arthritis and other undifferentiated arthritis: A pilot study.

BACKGROUND: Psoriatic arthritis (PSA) is a form of immune-mediated inflammatory arthritis that predominantly begins with enthesitis. Studying the gut microbiota of PSA patients may offer new insights into the pathogenesis of enthesitis, compared to other arthritis. We designed a prospective study to examine gut microbiome of patients with PSA, primarily with enthesitis and dactylitis, and compared the data with other undifferentiated types of arthritis (NO PSA) patients, without enthesitis or dactylitis. METHODS: We enrolled 9 PSA patients and 10 NO PSA patients in this study. We excluded rheumatoid arthritis, systemic lupus erythematosus, Sjogren syndrome, systemic sclerosis, mixed connective tissue disease, polymyositis, dermatomyositis, ANCA-associated vasculitis, and gouty arthritis patients. The fecal samples were investigated using 16S rRNA amplicon sequencing, followed by bioinformatics and statistical analyses. RESULTS: None of the available objective clinical laboratory data could differentiate PSA group from the NO PSA subgroup. The microbiota result shows that Family: XIII_AD3011 is significantly higher in NO PSA patients' than in PSA patients' stool samples (P = .039). Megasphaera elsdenii in the PSA group was 10,000 times higher than in the NO PSA group.Our results demonstrated high intragroup homogeneous and high intergroup heterogeneous microbiota. The clinical symptoms of either enthesitis or dactylitis are associated with higher presence of specific microbiota in the current study. The PSA and other undifferentiated arthritis could be differentiated with microbiota analysis. In the future, a larger cohort and thorough biochemical study are needed for confirmation.The microbiota is different between PSA and NO PSA patients, and the species could be used as a differential diagnostic tool between these 2 diseases. The clinically available serum markers may not be enough to reflect the details of patients with different patterns of arthritis. Megasphaera elsdenii species could be a link between gut flora and enthesitis and/or dactylitis clinically in PSA. We confirm the fact that the Bifidobacterium longum correlates negatively with eosinophils.

TNF-α Activating Osteoclasts in Patients with Psoriatic Arthritis Enhances the Recruitment of Osteoclast Precursors: A Plausible Role of WNT5A-MCP-1 in Osteoclast Engagement in Psoriatic Arthritis.

Psoriatic arthritis (PsA) results from joint destruction by osteoclasts. The promising efficacy of TNF-α blockage indicates its important role in osteoclastogenesis of PsA. WNT ligands actively regulate osteoclastogenesis. We investigated how WNT ligands activate osteoclasts amid the TNF-α milieu in PsA. We first profiled the expression of WNT ligands in CD14+ monocyte-derived osteoclasts (MDOC) from five PsA patients and five healthy controls (HC) and then validated the candidate WNT ligands in 32 PsA patients and 16 HC. Through RNA interference against WNT ligands in MDOC, we determined the mechanisms by which TNF-α exerts its effects on osteclastogenesis or chemotaxis. WNT5A was selectively upregulated by TNF-α in MDOC from PsA patients. The number of CD68+WNT5A+ osteoclasts increased in PsA joints. CXCL1, CXCL16, and MCP-1 was selectively increased in supernatants of MDOC from PsA patients. RNA interference against WNT5A abolished the increased MCP-1 from MDOC and THP-1-cell-derived osteoclasts. The increased migration of osteoclast precursors (OCP) induced by supernatant from PsA MDOC was abolished by the MCP-1 neutralizing antibody. WNT5A and MCP-1 expressions were decreased in MDOC from PsA patients treated by biologics against TNF-α but not IL-17. We conclude that TNF-α recruits OCP by increased MCP-1 production but does not directly activate osteoclastogenesis in PsA.

Different Effects of Biologics on Systemic Bone Loss Protection in Rheumatoid Arthritis: An Interim Analysis of a Three-Year Longitudinal Cohort Study.

Objective: To compare changes in bone mineral density (BMD) in rheumatoid arthritis (RA) patients receiving three-year conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD), tumor necrosis factor-α inhibitors (TNFi), and abatacept. Methods: Patients with RA were recruited from September 2014 to February 2021. Dual-energy X-ray absorptiometry was used to measure BMD at the femoral neck (FN), total hip (TH), and lumbar spine (L1-4) at enrollment and three years later. Changes in the BMD of each regimen group were analyzed. Multiple ordinary least squares regression was used with the dependent variables to develop a model to predict the change in BMD. Results: A total of 752 participants were enrolled and 485 completed the three-year follow-up period. Of these, 375 (Group I), 84 (Group II), and 26 (Group III) participants received csDMARDs, TNFi, and abatacept therapy, respectively. Considering both type of therapy and completion of the follow-up period, participants were divided into groups A (csDMARDs, n = 104), B (TNFi, n = 52), and C (abatacept, n = 26). Compared to baseline, BMD decreased significantly at FN (p = 0.003) and L1-4 (p = 0.002) in Group A and at L1-4 (p = 0.005) in Group B, but remained stable at all sites in Group C. In terms of regression-adjusted percent change in BMD, there was a significant difference seen at all measured sites between group C compared to both groups A and B (+0.8%, -2.7%, -1.8% at FN; +0.5%, -1.1%, -1.0% at TH; +0.8%, -2.0%, -3.5% at L1-4, respectively; all p < 0.05). Anti-osteoporosis therapy had a BMD-preserving effect in RA. Conclusion: Compared with csDMARDs and TNFi, abatacept may have a better BMD-preserving effect in RA. Anti-osteoporosis therapy can prevent systemic bone loss irrespective of RA therapy.

Upregulation of miR-941 in Circulating CD14+ Monocytes Enhances Osteoclast Activation via WNT16 Inhibition in Patients with Psoriatic Arthritis.

Psoriatic arthritis (PsA) is a destructive joint disease mediated by osteoclasts. MicroRNAs (miRNAs) regulate several important pathways in osteoclastogenesis. We profiled the expression of miRNAs in CD14+ monocytes from PsA patients and investigated how candidate microRNAs regulate the pathophysiology in osteoclastogenesis. The RNA from circulatory CD14+ monocytes was isolated from PsA patients, psoriasis patients without arthritis (PsO), and healthy controls (HCs). The miRNAs were initially profiled by next-generation sequencing (NGS). The candidate miRNAs revealed by NGS were validated by PCR in 40 PsA patients, 40 PsO patients, and 40 HCs. The osteoclast differentiation and its functional resorption activity were measured with or without RNA interference against the candidate miRNA. The microRNA-941 was selectively upregulated in CD14+ monocytes from PsA patients. Osteoclast development and resorption ability were increased in CD14+ monocytes from PsA patients. Inhibition of miR-941 abrogated the osteoclast development and function while increased the expression of WNT16. After successful treatment, the increased miR-941 expression in CD14+ monocytes from PsA patients was revoked. The expression of miR-941 in CD14+ monocytes is associated with PsA disease activity. MiR-941 enhances osteoclastogenesis in PsA via WNT16 repression. The miR-941 could be a potential biomarker and treatment target for PsA.

Adherence to anti-osteoporosis medication associated with lower mortality following hip fracture in older adults: a nationwide propensity score-matched cohort study.

BACKGROUND: We investigated the association of anti-osteoporosis medication with mortality risk in older adults with hip fractures and evaluated the influence of medication adherence on mortality. METHODS: We conducted a population-based cohort study and identified a total of 13,123 patients aged 65 years or older with hip fracture from the Taiwan National Health Insurance Database during the period 2001-2010. Individuals with (n = 2092) and without (n = 2092) receiving anti-osteoporosis medication were matched using propensity score matching (1:1 ratio). The 1-, 3- and 5-year survival rates after the index fracture were compared between patients with and without treatment. In the treated group, survival rate was compared between those with good and non-adherence. Good adherence was defined as the medication possession ratio of ≥80% and non-adherence as a ratio < 80%. RESULTS: The 1-, 3- and 5-year mortality rates were significantly lower in the treated vs. the non-treated group (all p < 0.0001). In the treated group, the estimated 1-, 3- and 5-year survival rates were higher in those with good adherence than in those with non-adherence (all p < 0.0001). Regarding all-cause mortality, the adjusted hazard ratio in the treated vs. the non-treated group was 0.63 (95% confidence interval 0.58-0.68, p < 0.0001). The good adherence subgroup showed a significantly lower mortality risk than that in the non-adherence subgroup (hazard ratio 0.41, 95% confidence interval 0.32-0.51, p < 0.0001). CONCLUSIONS: The 1-, 3- and 5-year survival rates were significantly higher in patients receiving anti-osteoporosis medication than in the untreated group. All-cause mortality rates were lower in patients with good adherence to anti-osteoporosis medication.

Anti-TNF-Alpha-Adalimumab Therapy Had Time Lag of Improvement in Synovial Hypertrophy Compared to Rapid Response in Power Doppler Synovial Vascularity.

OBJECTIVES: The quantification of synovitis is of great significance for follow-up in patients with rheumatoid arthritis (RA). This study aimed to validate the use of power Doppler ultrasonography (PDUS) for evaluating synovial vascularity and synovial hypertrophy for synovitis in patients with rheumatoid arthritis treated with adalimumab. MATERIALS AND METHODS: The synovial disease activity and vascularity of RA on both wrists (radio-carpal joint) were assessed using GS and PDUS to derive the composite US scores based on abnormal counts and severity. The relationship between each measure was determined. RESULTS: The 71 patients who received adalimumab therapy had significantly decreased DAS28, ESR, and CRP. After one month, PD score decreased and then remained low for 12 months. Synovial hypertrophy did not change until 3-6 months after, when it started to improve (p = 0.017). By multivariate analysis, sex, age, BMI, and DAS28 did not lead to any difference between synovial hypertrophy and PDUS changes (p = 0.498). DISCUSSION: Composite US markers of synovial hypertrophy correlate significantly to the DAS28 score and ESR/CRP in adult RA. The time needed for synovial hypertrophy to decrease may be up to 3-6 months after adalimumab therapy. Switching to biological therapy before 3-6 months is inappropriate and ineffective.

Delayed anti-TNF therapy increases the risk of total knee replacement in patients with severe rheumatoid arthritis.

BACKGROUND: This study evaluated the effect of early anti-tumor necrosis factor (TNF) therapy in patients with severe rheumatoid arthritis (RA) on the subsequent risk of total knee replacement (TKR) surgery. METHODS: This retrospective observational study included a hospital-based cohort of 200 patients diagnosed with severe RA who received treatment with anti-TNF therapy between 2003 and 2014. Clinical parameters including age, sex, body mass index, and the time from the diagnosis of RA to the initiation of anti-TNF therapy were analyzed. RESULTS: Of the 200 enrolled patients, 84 underwent an early intervention (≤3 years from the diagnosis of RA to the initiation of anti-TNF therapy), and 116 underwent a late intervention(>3 years from the diagnosis of RA to the initiation of anti-TNF therapy). Five (6.0%) patients in the early intervention group underwent TKR compared to 31 (26.7%) in the late intervention group (p = 0.023). After adjusting for confounding factors, the late intervention group still had a significantly higher risk of TKR (p = 0.004; odds ratio, 5.572; 95% confidence interval, 1.933-16.062). Those receiving treatment including methotrexate had a lower risk of TKR (p = 0.004; odds ratio, 0.287; 95% confidence interval, 0.122-0.672). CONCLUSIONS: Delayed initiation of anti-TNF therapy in the treatment of severe RA was associated with an increased risk of TKR surgery. Adding methotrexate treatment decreased the risk of future TKR.

Cumulative immunosuppressant exposure is associated with diversified cancer risk among 14 832 patients with systemic lupus erythematosus: a nested case-control study.

Objectives: Immunosuppressive therapy is necessary to alter the natural course of SLE. However, immunosuppressant-related cancer risk is a major concern. The aim of this study was to determine whether immunosuppressant use is associated with cancer risk in SLE. Methods: We designed a retrospective nested case-control study within an SLE population based on the National Health Insurance Research Database in Taiwan. We screened 14 842 patients with SLE from 2001 to 2013 and compared patients with SLE complicated by later cancer with patients with SLE but without cancer. The cumulative dose of immunosuppressants was calculated from the SLE diagnosis date to the occurrence of cancer. The immunosuppressants of interest were AZA, CYC, MTX, HCQ and systemic glucocorticoids. Adjusted odds ratios (ORs) for cancer were calculated in conditional Cox regression models after propensity score matching. Results: The top five types of cancers were breast (16.9%), haematological (11.7%), colorectal (11.0%), lung (10.6%) and hepatobiliary (10.4%) cancers. After matching, this study included 330 cancer patients and 1320 matched cancer-free patients. The adjusted analyses showed an association of a higher cumulative CYC dose (OR = 1.09, 95% CI: 1.04, 1.13) and lower HCQ dose (OR = 0.93, 95% CI: 0.90, 0.97) with cancer risk in comparison with the controls. Conclusion: Diverse cancer risks are associated with different immunosuppressants in patients with SLE. CYC increases the risk of cancer, and HCQ decreases this risk in SLE patients, both in a dose-dependent manner.

The Epstein-Barr virus-encoded microRNA MiR-BART9 promotes tumor metastasis by targeting E-cadherin in nasopharyngeal carcinoma.

MicroRNAs (miRNAs) are a family of small RNA molecules that negatively regulate the expression of protein-coding genes and play critical roles in orchestrating diverse cellular processes. This regulatory mechanism is also exploited by viruses to direct their life cycle and evade the host immune system. Epstein-Barr virus (EBV) is an oncogenic virus that is closely associated with multiple human diseases, including nasopharyngeal carcinoma (NPC), which is a highly metastatic type of tumor and is frequently reported in South Asia. Several viral proteins have been found to promote the migration and invasiveness of NPC cells. However, not all tumor tissues express these viral oncoproteins, suggesting that other mechanisms may contribute to the aggressive behavior of NPC tumor cells. A previous sequencing study by our group revealed that the EBV miRNA miR-BART9 was expressed at high levels in all EBV-positive NPC tissues. In the present study, we used gain- and loss-of-function approaches to investigate the effect of miR-BART9 in EBV-negative and EBV-positive NPC cells. We discovered that miR-BART9 promotes the migration and invasiveness of cultured NPC cells. The promigratory activity observed in vitro was manifested as an enhanced metastatic ability in vivo. Computational analysis revealed that miR-BART9 may target E-cadherin, a membrane protein that is pivotal in preserving cell-cell junctions and the epithelial phenotype. Through biochemical assays and functional rescue analysis, we confirmed that miR-BART9 specifically inhibits E-cadherin to induce a mesenchymal-like phenotype and promote the migration of NPC cells. These results indicated that miR-BART9 is a prometastatic viral miRNA and suggested that high levels of miR-BART9 in EBV-positive NPC cells may contribute to the aggressiveness of tumor cells.

Non-adherence to anti-osteoporotic medications in Taiwan: physician specialty makes a difference.

Adherence to anti-osteoporotic regimens gradually decreases over time. We hypothesized that the determinants of non-compliance or non-persistence at different times vary and identified these differences. We used an outpatient database to retrieve information on anti-osteoporotic medications prescribed by a medical centre in southern Taiwan during 2001-2007. Compliance was defined as a medication possession ratio (MPR) ≥80 %. Persistence was determined as continuous use, allowing for a refill gap of 30 days. A multivariate Cox regression model evaluated potential predictors of non-adherence. A total of 3589 patients were included. In the multivariate analyses, non-compliance for both year 1 and year 2 was more likely in patients with non-vertebral non-hip fractures, respiratory disorders, prescription of the first anti-osteoporotic regimen by an orthopedist; and less likely in patients with follow-up bone densitometry and switched regimens. Risks for non-persistence at year 1 and year 2 were generally similar to those for non-compliance; insurance coverage and malignancy were associated with a lower risk of non-persistence at year 1 and year 2, respectively. In the subgroup with an MPR ≥80 % at year 1, an index prescription by an orthopedist was the only independent predictor of non-compliance and non-persistence at year 2. In conclusion, the positive or negative determinants of non-adherence were different at year 1 and year 2, which indicated that clinicians might deliver effective interventions to improve adherence via different precautions annually. This study also provided evidence that physician specialty had a significant effect on adherence to osteoporosis care.

Overexpression of gelsolin in human cervical carcinoma and its clinicopathological significance.

OBJECTIVES: Cervical carcinoma is the second most common cause of death from gynecological cancers worldwide. Knowledge of the molecular mechanisms underlying the tumorigenesis of cervical cancer cell, except human papilloma virus infection, is limited. METHODS: A microarray was used to study the differential expression of genes in cancerous tissues to identify new molecular markers for diagnosis and prognosis. Their differential expression was confirmed with Western blotting and immunohistochemical analyses. The clinical correlations and prognostic significance of the aberrantly expressed proteins were evaluated to identify novel biomarkers of cervical cancer. RESULTS: The expression of gelsolin was significantly upregulated in 78% of patients with cervical cancer, and gelsolin was selected for further study. Gelsolin expression was stronger in cervical tumor tissues than in the surrounding noncancerous tissues (P<0.001). Gelsolin expression in the plasma of cervical cancer patients was increased 2.2-fold compared with that of healthy control subjects (P<0.001). The levels of plasma gelsolin in the early and late stages were significantly different (P=0.006). According to immunohistochemical analysis, increased gelsolin expression was associated with histological type and FIGO stage II. The 5-year overall survival and recurrence-free survival rates for the low-expression group (cut-off=115) were significantly higher than those of the high-expression group. Cancer cells with reduced gelsolin expression exhibited reduced migration and proliferation. CONCLUSIONS: These results provide strong evidence that gelsolin plays an important role in cellular proliferation and migration in cervical cancer and suggest that gelsolin is a promising marker for cervical cancer screening and prognosis.