Denosumab use reduces risk of rheumatoid arthritis in patients with osteoporosis.

OBJECTIVES: To investigate the protective effect of osteoporosis medications on the risk of developing rheumatoid arthritis (RA) in patients with osteoporosis. METHODS: We conducted a retrospective cohort study from 1 January, 2011 to 31 March, 2023. There was a total of 971901 patients from a hospital-based population in Taiwan. In this cohort, there was a total of 17065 osteoporosis patients with or without pathological fracture. In these patients, 7180 patients were osteoporosis medication users, and 9605 patients were non-osteoporosis medication users, after exclusion of previous RA. The risk of RA in the patients with osteoporosis medications was assessed, and stratified by sex and different medications, including bisphosphonates, denosumab, raloxifene and teriparatide. RESULTS: Patients with osteoporosis medication use had a reduced risk of RA compared with non-osteoporosis medication users [adjusted hazard ratio (aHR)=0.484, 95%CI: 0.270-0.867, p<0.05), after adjusting for age, comorbidites and medications. Specifically, patients with ever use of bisphosphonates (n=2069) or denosumab (n=4510) had a reduced risk of RA (aHR=0.405, 95%CI: 0.173-0.951, p<0.05, and aHR=0.394, 95%CI: 0.192-0.809, p<0.05, respectively). Notably, patients that only used denosumab (n=2938) had a further reduced risk of RA (aHR=0.32, 95%CI: 0.12-0.83, p<0.05), particularly in female patients (aHR=0.26, 95%CI: 0.09-0.74, p<0.05). Patients taking raloxifene or teriparatide did not have a significantly reduced risk of RA. CONCLUSIONS: Denosumab use reduces the risk of RA in patients with osteoporosis. Receptor activator of nuclear factor kappa B ligand (RANKL) mediated osteoclast joint damage may be involved in the pathogenesis of RA during the preclinical stage.

Hydroxychloroquine exposure reduces the risk of cardiovasular disease events in patients with hypertension or diabetes mellitus.

OBJECTIVES: To investigate the association of hydroxychloroquine (HCQ) with the risk of cardiovascular disease (CVD) events in patients with traditional risk factors, hypertension (HTN) or diabetes mellitus (DM). METHODS: We conducted a retrospective cohort study from 1 January, 2010 to 30 September, 2022. There was a total of 1007585 patients from a hospital-based population. In this cohort, 146862 patients had newly diagnosed HTN or DM. Among these patients, 1903 patients had HCQ exposure and 136396 patients had no HCQ exposure after exclusion of previous CVD events or invasive cardiovascular procedures. The risk of developing CVD events, a composite of acute myocardial infarction (AMI) and ischaemic stroke was evaluated. RESULTS: The patients with HCQ exposure had reduced risk of CVD events [HR (hazard ratio)=0.67 95%CI: 0.55-0.83], AMI (HR=0.61, 95%CI: 0.41-0.90) and ischaemic stroke (HR=0.74, 95%CI:0.59-0.93), when compared with non-HCQ exposure, after adjusting for age, sex, rheumatic diseases, comorbidities and medications. Specifically, reduced risk for CVD events (HR=0.67, 95%CI: 0.54-0.83), including AMI (HR=0.67, 95%CI: 0.44-1.00) and ischaemic stroke (HR=0.71, 95%CI: 0.55-0.90) were observed in older patients (age ≥50 yrs) with HCQ exposure, and reduced risk for AMI also observed in younger patients (age <50 yrs) (HR=0.28, 95%CI: 0.08-0.97). Reduced risk for CVD events (HR=0.63, 95%CI: 0.48-0.82) and ischaemic stroke (HR=0.63, 95%CI: 0.47-0.85) were observed particularly in female patients with HCQ exposure. Reduced risk for AMI was observed particularly in male patients with HCQ exposure (HR=0.44, 95%CI: 0.22-0.87). CONCLUSIONS: HCQ has protective effect on CVD events, including both AMI and ischaemic stroke in the patients with traditional risk factors. The protective effect of HCQ on CVD events is prominent in older patients.

Recommendations for psoriatic arthritis management: A joint position paper of the Taiwan Rheumatology Association and the Taiwanese Association for Psoriasis and Skin Immunology.

In Taiwan, the incidence and prevalence of psoriatic arthritis (PsA) have risen significantly in recent years. Moreover, data from the Taiwan National Health Insurance Research Database (NHIRD) show that more than 85% of PsA patients are treated with just non-steroidal anti-inflammatory drugs (NSAIDs) and/or conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Taiwanese clinicians have also expressed concerns regarding uncertainties in the diagnosis of PsA and the delayed, interrupted, and/or tapered use of biologics, as well as differences in therapeutic preferences between and within dermatologists and rheumatologists. To address these issues, the Taiwan Rheumatology Association and the Taiwanese Association for Psoriasis and Skin Immunology jointly convened a committee of 28 clinicians from the fields of rheumatology, dermatology, orthopedics, and rehabilitation, to develop evidence-based consensus recommendations for the practical management of PsA in Taiwan. A total of six overarching principles and 13 recommendations were developed and approved, as well as a treatment algorithm with four separate tracks for axial PsA, peripheral PsA, enthesitis, and dactylitis. Psoriasis (PsO) management was not discussed here, as the Taiwanese Dermatological Association has recently published a comprehensive consensus statement on the management of PsO. Together, these recommendations provide an up-to-date, evidence-based framework for PsA care in Taiwan.

Long-term renal prognosis among patients with primary Sjögren's syndrome and renal involvement: A nationwide matched cohort study.

BACKGROUND: The long-term renal outcome in patients with primary Sjögren's syndrome (pSS) remains uncertain. We aimed to determine the absolute incidence and relative risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in patients with pSS at the general population level. METHODS: We performed a retrospective cohort study using a national health insurance database in Taiwan from 2000 to 2013. We calculated the cumulative incidence of CKD and ESRD in our pSS and age-, sex- and entry time-matched control cohorts. Cox regression analyses were used to estimate adjusted hazard ratios (aHRs) after adjusting for comorbidities and medications. RESULTS: Among 17 505 patients with incident pSS, 1008 (5.8%) developed CKD and 38 (0.22%) developed ESRD. Of the 87 525 non-pSS controls, 3173 (3.6%) developed CKD and 256 (0.29%) developed ESRD. The risk of CKD was higher in patients with pSS than in the non-pSS controls (adjusted hazard ratio [HR] 1.49, 95% confidence interval [95% CI] 1.38-1.59). Notably, the risk of ESRD was similar in both pSS and non-pSS cohorts (aHR 0.82, 95% CI 0.58-1.16). CONCLUSIONS: Renal prognosis among patients with pSS and renal involvement is good. Although the risk of ESRD did not increase in patients with pSS, a significantly increased risk of CKD was observed in these patients, indicating the need for increased vigilance in regular monitoring for renal complications in patients with pSS.

Janus kinase-1 and 3 in ankylosing spondylitis.

BACKGROUND/PURPOSE: To investigate the Janus kinase-1 and 3 (JAK-1 and 3) expression in peripheral blood mononuclear cells (PBMCs) in ankylosing spondylitis (AS). METHODS: The levels of JAK-1 and JAK-3 mRNA in PBMCs, CD3+ T cells and CD14+ monocytes were measured by RT-PCR in 52 AS patients and 31 healthy controls (HCs). The demographic features, BASDAI, BASFI, HLA-B27, ESR, CRP and serum immunoglobulin A (IgA) level were recorded and correlated with the JAK-1 & JAK-3 transcripts in patients and HCs as appropriate. RESULTS: JAK-1 and JAK-3 expression in PB CD3+ T cells plus CD14+ monocytes was significantly higher in AS patients than in HCs (p < 0.05). There is a positive correlation between JAK-1 expression in CD3+ T cells plus CD14+ monocytes and ESR, CRP, IgA, HLA-B27, peripheral arthritis, enthesitis and uveitis (all p < 0.05), respectively. JAK-1 transcript was also increased in CD14+ monocytes from patients and correlated well with ESR and CRP as the disease deteriorated. Conversely, JAK-1 was negatively correlated to chest expansion. Area under the curve of standard receiver operating characteristic suggested that JAK-1 transcript in CD3+ T cells plus CD14+ monocytes is better to predict the higher BASDAI (>4) and BASFI (>4) than ESR or CRP in AS patients. CONCLUSION: In AS, JAK-1 expression in PB cells rather than ESR or CRP might be regarded as a bio-marker for monitoring disease activity and functional index in AS. These findings have also suggested that JAK-1 and JAK-3 expression may play a role in the inflammatory processes in patients with AS.

Suppressors of cytokine signalling in ankylosing spondylitis and their associations with disease severity, acute-phase reactants and serum cytokines.

OBJECTIVES: To investigate the suppressors of cytokine signalling (SOCS1 and SOCS3) expression in peripheral blood cells in ankylosing spondylitis (AS), and their associations with clinical and laboratory manifestations. METHODS: The levels of SOCS1 and SOCS3 mRNA in peripheral blood mononuclear cells (PBMCs), T cells and monocytes were measured by RT-PCR in 53 AS patients and 31 healthy controls. Patient's serum IL-6, IL-10 and IL-17A levels were determined by ELISA. We evaluated patient's disease activity, functional ability and global assessment, and tested their ESR, CRP and IgA levels. RESULTS: Cellular SOCS1 expression did not show significant differences between AS patients and controls. However, T cells SOCS1 decreased significantly in the AS subgroup with lower ESR than controls (p=0.013). PBMCs (p=0.047) and T cells (p=0.035) SOCS1 decreased significantly in the AS subgroup with lower CRP than controls. Importantly, SOCS3 expression increased significantly in AS patients compared to the controls in PBMCs (p=0.025), T cells (p=0.003) and monocytes (p=0.009). Moreover, PBMCs SOCS3 correlated with ESR (r=0.297, p=0.031) and CRP (r=0.320, p=0.019). T cells SOCS3 correlated with BASFI (r=0.337, p=0.015), ESR (r=0.435, p=0.001) and CRP (r=0.300, p=0.029). Monocytes SOCS3 correlated with ESR (r=0.281, p=0.041) and IgA (r=0.426, p=0.006). Furthermore, T cells SOCS1 (r=-0.454, p=0.023) and T cells SOCS3 (r=-0.405, p=0.045) negatively correlated with serum IL-17A. Monocytes SOCS3 negatively correlated with serum IL-6 (r=-0.584, p=0.002). CONCLUSIONS: The decreased SOCS1 and increased SOCS3 expression in AS PBMCs and T cells, and their correlation with patient's functional ability, acute-phase reactants and serum pro-inflammatory cytokines suggested that SOCS may participate in the pathogenesis of AS.

The clinical usefulness of ESR, CRP, and disease duration in ankylosing spondylitis: the product of these acute-phase reactants and disease duration is associated with patient's poor physical mobility.

We evaluated the clinical usefulness of ESR, CRP, and disease duration in ankylosing spondylitis (AS) disease severity. There were 156 Chinese AS patients included in Taiwan. Patients completed the questionnaires, containing demographic data, disease activity (BASDAI), functional status (BASFI), and patient's global assessment (BASG). Meanwhile, patient's physical mobility (BASMI) and acute-phase reactants, including ESR and CRP levels were measured. Receiver operating characteristic (ROC) plot analysis was used to evaluate the performance of ESR, CRP, and disease duration in the AS patients. ESR mildly correlated with BASFI (r = 0.176, p = 0.028) and disease duration (r = 0.214, p = 0.008), and moderately correlated with BASMI (r = 0.427, p < 0.001). CRP moderately correlated with BASMI (r = 0.410, p < 0.001). By using ROC plot analysis, ESR, CRP, and disease duration showed the best and significant "area under the curve (AUC)", in distinguishing the AS patients with poor physical mobility (BASMI ≥ 3.6, the Median) (AUC = 0.748, 0.751 and 0.738, respectively, all p < 0.001), as compared to BASDAI, BASFI, and BASG. ESR × disease duration (AUC = 0.801, p < 0.001) and CRP × disease duration (AUC = 0.821, p < 0.001) showed higher AUC values than ESR or CRP alone in indicating poor physical mobility. For detecting poor physical mobility (BASMI ≥ 3.6) in the AS patients: ESR × disease duration (≥60.0 mm/h × year): sensitivity = 72.7 % and specificity = 72.8 %; CRP × disease duration (≥8.3 mg/dl × year): sensitivity = 72.7 % and specificity = 74.6 %. ESR, CRP, and disease duration are particularly related to AS patient's poor physical mobility. Combining the usefulness of acute-phase reactants and disease duration, the values of ESR × disease duration and CRP × disease duration demonstrate better association with poor physical mobility in AS patients.

Upregulation of BMP-2 expression in peripheral blood mononuclear cells by proinflammatory cytokines and radiographic progression in ankylosing spondylitis.

OBJECTIVES: To investigate the effect of inflammation on expressions of bone morphogenetic proteins (BMPs) in peripheral blood mononuclear cells (PBMCs) and its association with individual radiographic changes in patients with ankylosing spondylitis (AS). METHODS: The changes in BMP-2, -4, and -7 gene expressions in PBMCs were measured after stimulation by tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß). The correlation of increase in gene expression with clinical and radiographic findings in patients with AS were analyzed. RESULTS: Both TNF-α and IL-1ß could enhance BMP-2 expression in PBMCs from AS patients. Increases in BMP-2, -4, and -7 expressions in PBMCs positively correlated with total modified Stoke Ankylosing Spondylitis Spinal Score (all p < 0.05). Moreover, increases in BMP-2, -4, and -7 gene expressions after TNF-α and IL-1ß stimulation were greater among AS patients with versus without severe sacroiliitis (all p < 0.05). Increases in BMP-2 and -7 expressions were greater in PBMCs from 4 patients with total (cervical, thoracic, and lumbar) spinal ankylosis than in the 8 patients who did not have total spinal ankylosis (all p < 0.05). CONCLUSIONS: In AS, inflammation upregulates the expression of BMPs in PBMCs which may lead to the radiographic progression with new bone formation.

The impact of comorbidity on survival after hemorrhagic stroke among dialysis patients: a nationwide population-based study.

BACKGROUND: This study was aimed at determining the outcome and examining the association between comorbidities and mortality after intracerebral hemorrhage in chronic dialysis patients. METHODS: We used the Taiwan National Health Insurance Research Database and enrolled patients who underwent maintenance dialysis between 2000 and 2007. Annual incidence of intracerebral hemorrhage in patients receiving dialysis from 2000 to 2007 was determined. To identify predictors of hemorrhagic stroke, we used logistic regression model to estimate the relative ratio of factors for intracerebral hemorrhage in the most recent cohort (2007). The cumulative survival rate and comorbid conditions associated with mortality after intracerebral hemorrhage among all dialysis patients between 2000 and 2007 was calculated using the Kaplan-Meier method and Cox regression analysis. RESULTS: We identified 57,261 patients on maintenance dialysis in the cohort of 2007, and 340 patients had history of intracerebral hemorrhage among them. Hypertension was the most common comorbidity of dialysis patients. The incidence rate of intracerebral hemorrhage among dialysis patients was about 0.6%. Adjusted logistic regression model showed that male gender, middle age (45-64 years), hypertension, and previous history of stroke were the independent predictors for the occurrence of intracerebral hemorrhage among chronic dialysis patients. 1,939 dialysis patients with development of intracerebral hemorrhage in the analysis period from 2000 to 2007 were identified. In-hospital mortality was high (36.15%) following intracerebral hemorrhage. They were followed up after intracerebral hemorrhage for a mean time of 41.56 months. Adjusted Cox regression analyses demonstrated that the factors independently associated with mortality after intracerebral hemorrhage among dialysis patients included diabetes mellitus, malignancy and a history of prior stroke. CONCLUSIONS: Dialysis patients who have history of prior stroke, diabetes and malignancy have worse survival than patients without these comorbidities. Attention must focus on providing optimal medical care after hemorrhagic stroke for these target groups to reduce mortality.

Engineering H2O2 Self-Supplying Platform for Xdynamic Therapies via Ru-Cu Peroxide Nanocarrier: Tumor Microenvironment-Mediated Synergistic Therapy.

Of the most common, hypoxia, overexpressed glutathione (GSH), and insufficient H2O2 concentration in the tumor microenvironment (TME) are the main barriers to the advancment of reactive oxygen species (ROS) mediated Xdynamic therapies (X = photo, chemodynamic, chemo). Maximizing Fenton catalytic efficiency is crucial in chemodynamic therapy (CDT), yet endogenous H2O2 levels are not sufficient to attain better anticancer efficacy. Specifically, there is a need to amplify Fenton reactivity within tumors, leveraging the unique attributes of the TME. Herein, for the first time, we design RuxCu1-xO2-Ce6/CPT (RCpCCPT) anticancer nanoagent for TME-mediated synergistic therapy based on heterogeneous Ru-Cu peroxide nanodots (RuxCu1-xO2 NDs) and chlorine e6 (Ce6), loaded with ROS-responsive thioketal (TK) linked-camptothecin (CPT). The Ru-Cu peroxide NDs (RCp NDs, x = 0.50) possess the highest oxygen vacancy (OV) density, which grants them the potential to form massive Lewis's acid sites for peroxide adsorption, while the dispersibility and targetability of the NDs were improved via surface modification using hyaluronic acid (HA). In TME, RCpCCPT degrades, releasing H2O2, Ru2+/3+, and Cu+/2+ ions, which cooperatively facilitate hydroxyl radical (•OH) formation and deactivate antioxidant GSH enzymes through a cocatalytic loop, resulting in excellent tumor therapeutic efficacy. Furthermore, when combined with laser treatment, RCpCCPT produces singlet oxygen (1O2) for PDT, which induces cell apoptosis at tumor sites. Following ROS generation, the TK linkage is disrupted, releasing up to 92% of the CPT within 48 h. In vitro investigations showed that laser-treated RCpCCPT caused 81.5% cell death from PDT/CDT and chemotherapy (CT). RCpCCPT in cancer cells produces red-blue emission in images of cells taking them in, which allows for fluorescence image-guided Xdynamic treatment. The overall results show that RCp NDs and RCpCCPT are more biocompatible and have excellent Xdynamic therapeutic effectiveness in vitro and in vivo.

Increased risk of mortality among haemodialysis patients with or without prior stroke: a nationwide population-based study in Taiwan.

BACKGROUND & OBJECTIVES: Patients with prior stroke (PS) undergoing chronic dialysis are at a high risk of mortality. However, little is known about the cumulative risk and survival rate of dialysis patients with long-term follow up. The aim of this study was to assess risks for mortality between patients with and without PS undergoing chronic haemodialysis (HD). METHODS: The Taiwan National Health Insurance Research Database (NHRI-NHIRD-99182) was used and all adult patients (≥18 yr) with end stage renal disease (ESRD) who started maintenance HD between January 1, 1999, and December 31, 1999, were selected. The patients were followed from the first reported date of HD to the date of death, end of dialysis or December 31, 2008. A Cox's proportional hazard model was applied to identify the risk factors for all-cause mortality. RESULTS: Among 5672 HD patients, 650 patients (11.5%) had PS. A higher proportion of stroke history at baseline was found in men (52.8%) and those aged ≥ 55 yr (80.9%). After adjusting for age, sex and other covariates, the patients with PS were found to have a 36 per cent increased risk of mortality compared to those without PS (HR 1.36, 95% CI: 1.22-1.52). The cumulative survival rates among HD patients without PS were 96.0 per cent at the first year, 68.4 per cent at the fifth year, and 46.7 per cent at the ninth year, and 92.9, 47.3 and 23.6 per cent, respectively, in those with PS (log-rank: P<0.001). INTERPRETATION & CONCLUSIONS: Our findings showed that PS was an important predictor for all-cause mortality and poor outcome in patients undergoing chronic HD.

Association of Systemic Sclerosis With Incident Clinically Evident Heart Failure.

OBJECTIVE: Primary myocardial involvement is an important cause of death in systemic sclerosis (SSc). Subclinical diastolic/systolic heart dysfunction is recognized; however, whether this indicates a subsequent increased risk of clinically overt heart failure (HF) remains largely unknown. We aimed to investigate the risk of clinically overt HF in a large, unselected SSc cohort. METHODS: This matched, retrospective cohort study was conducted using a nationwide insurance database in Taiwan. Incident SSc patients with no history of HF were identified, and non-SSc comparison groups were selected and matched to the SSc groups by age, sex, and cohort entry time. The cumulative HF incidence was estimated using the Kaplan-Meier method. Multivariable Cox proportional hazards regression was used to calculate adjusted hazard ratios (HRs) for HF hospitalization. RESULTS: A total of 1,830 SSc patients and 27,981 controls were identified. The cumulative incidence of hospitalized HF at 3, 5, and 10 years among patients with SSc were 3.5%, 5.3%, and 9.7%, respectively. Compared with non-SSc individuals, SSc patients had an increased risk of HF (adjusted HR 3.26 [95% confidence interval (95% CI) 2.49-4.28]). Subgroup analyses revealed that the impact of SSc on the occurrence of HF was greater among patients ages <50 years than those ages ≥50 years (HR 7.8 [95% CI 4.03-15.1] versus HR 2.78 [95% CI 2.06-3.76]). CONCLUSION: SSc is associated with a markedly higher risk of clinically evident HF and not asymptomatic ventricular dysfunction alone. These findings provide real-world evidence suggesting the use of appropriate screening strategies to detect these lethal complications early in SSc.

Long-term survival and predictors for mortality among dialysis patients in an endemic area for chronic liver disease: a national cohort study in Taiwan.

BACKGROUND: Patients with end-stage renal disease (ESRD) are at a higher risk for chronic hepatitis, liver cirrhosis (LC) and mortality than the general population. Optimal modalities of renal replacement therapy for ESRD patients with concomitant end-stage liver disease remain controversial. We investigated the long-term outcome for chronic liver disease among dialysis patients in an endemic area. METHODS: Using Taiwan's National Health Insurance claim data (NHRI-NHIRD-99182), We performed a longitudinal cohort study to investigate the impact of comorbidities on mortality in dialysis patients. We followed up 11293 incident hemodialysis (HD) and 761 peritoneal dialysis (PD) patients from the start of dialysis until the date of death or the end of database period (December 31, 2008). A Cox proportional hazards model was used to identify the risk factors for all-cause mortality. RESULTS: Patients receiving PD tended to be younger and less likely to have comorbidities than those receiving HD. At the beginning of dialysis, a high prevalence rate (6.16 %) of LC was found. Other than well-known risk factors, LC (hazard ratio [HR] 1.473, 95 % CI: 1.329-1.634) and dementia (HR 1.376, 95 % CI: 1.083-1.750) were also independent predictors of mortality. Hypertension and mortality were inversely associated. Dialysis modality and three individual comorbidities (diabetes mellitus, chronic lung disease, and dementia) interacted significantly on mortality risk. CONCLUSIONS: LC is an important predictor of mortality; however, the effect on mortality was not different between HD and PD patients.

Association of blood pressure and hypertension with radiographic damage among the patients with ankyloing spondylitis.

To investigate the association of blood pressure and hypertension with disease severity among the patients with ankyloing spondylitis (AS). There were 167 AS patients enrolled in the cross-sectional study. Blood pressure was measured and the presence of hypertension was recorded. Patient's disease severity, including disease activity, functional ability, patient's global assessments, physical mobility and radiographic damage were evaluated. ESR and CRP levels were tested. We recorded patient's medication use of NSAIDs, DMARDs and TNF-α blockers. Smoking, exercise habit, diabetes mellitus, hypercholesterolemia and obesity indices were assessed. Multivariate linear regression showed that systolic blood pressure was associated with TNF-α blocker [standard coefficient (ß) = 0.194, P = .007], DMARDs (ß = 0.142, P = .046), age (ß = 0.211, P = .003), male gender (ß = 0.242, P = .001) and body mass index (BMI) (ß = 0.245, P = .001). Diastolic blood pressure was associated with cervical rotation (ß = -0.174, P = .037), lateral lumbar flexion (ß = -0.178, P = .019), m-SASSS (ß = 0.198, P = .038) and BMI (ß = 0.248, P = .003). Notably, multivariate logistic regression showed that hypertension was associated with m-SASSS (OR = 1.033, P = .033), age (OR = 1.098, P = .0010) and BMI (OR = 1.210, P = .003). Using ROC cure analyses, age, BASMI, BASRI-Total, m-SASSS, waist circumference, BMI and waist-to-height ratio were useful in predicting hypertension, and m-SASSS is the best (AUC = 0.784, P < .001). Advanced radiographic damage is an independent risk factor of hypertension in AS, and m-SASSS is the most useful disease severity parameter in predicting the presence of hypertension. Advanced radiographic damage, poor cervical rotation, lateral lumbar flexion, older age, male gender, TNF-α blocker, DMARDs use and obesity are associated with increased blood pressure.

Increased risk of type 2 diabetes in patients with systemic lupus erythematosus: A nationwide cohort study in Taiwan.

Data on the risk of developing diabetes in patients with systemic lupus erythematosus (SLE) are limited and have yielded mixed results. We conducted a nationwide cohort study to investigate the risk of subsequent type 2 diabetes in patients with SLE compared with matched non-SLE controls. Data were collected from the Taiwan National Health Insurance Research Database. Adult patients newly diagnosed with SLE between 2003 to 2010 were identified as the study cohort. The non-SLE group was matched for age, gender, and date of initial diagnosis as the comparison cohort. A total of 6159 SLE patients (87.90% female, mean age 38.79 years) were identified during this period. Of these, 206 (3.34%) developed type 2 diabetes. The 3-year incidence of type 2 diabetes was significantly higher in the SLE cohort than in the control group (130.26 vs 101.18 cases per 10,000 person-years), with an adjusted hazard ratio of 1.22 (95% confidence interval [CI] 1.04-1.44), after adjusting for age, gender, underlying comorbidities, and monthly income. Stratified analyses showed that women with SLE and low-income SLE patients (monthly income < 20,000 New Taiwan Dollar) had a higher risk of type 2 diabetes than non-SLE controls, with adjusted hazard ratios of 1.21 (95% CI 1.01-1.45) and 1.36 (95% CI 1.10-1.69), respectively. Patients with newly diagnosed SLE had a 22% increased risk of developing type 2 diabetes during the 3-year follow-up period compared with matched controls.

Association of primary Sjögren's syndrome with incident heart failure: a secondary analysis of health claims data in Taiwan.

OBJECTIVE: Mounting evidence has demonstrated that various chronic inflammatory diseases are associated with incident heart failure (HF). However, there is scarce evidence about the association between primary Sjögren's syndrome (pSS) and HF. We aimed to explore this association using a nationwide database in Taiwan. METHODS: We selected patients with incident pSS and no history of HF. Using propensity score matching based on age, sex, cohort entry time, comorbidities, and concomitant medications, cohorts of patients with and without pSS (as controls) were created in a 1:1 ratio and the groups were compared. The cumulative incidence of HF was calculated using Kaplan-Meier estimation. Cox proportional hazard regression analysis was used to measure the hazard ratio (HR) of HF-related hospitalization for the pSS cohort compared with the comparison group. RESULTS: A total of 16,466 pairs of patients with pSS and those without pSS were identified. The cumulative incidence of HF-related hospitalization at 3, 5, and 10 years in patients with pSS was 1.05%, 1.89%, and 4.33%, respectively. The risk of HF-related hospitalization was not higher in patients with pSS than in the general population (HR: 0.98, 95% confidence interval [CI]: 0.84-1.14). There was no difference in survival probability after the first episode of HF-related hospitalization between pSS and non-pSS groups. CONCLUSION: Our results suggest that distinct inflammatory spectrums in each chronic inflammatory disease might have differential impacts on cardiac function and subsequent risk of HF. Future studies are needed to elucidate the complex and diverse mechanisms of HF in various chronic autoimmune diseases.

Time-Dependent Analysis of Risk of New-Onset Heart Failure Among Patients With Polymyositis and Dermatomyositis.

OBJECTIVE: To determine the risk and time trends of heart failure (HF) leading to hospitalization in individuals newly diagnosed as having polymyositis/dermatomyositis (PM/DM) relative to non-PM/DM controls at the general population level. METHODS: A retrospective cohort study was conducted using data from a nationwide insurance database in Taiwan. Patients with incident PM/DM and without a history of HF were selected between 2000 and 2013. Unmatched and propensity score-matched cohorts were established separately. A multivariable Cox proportional hazards regression model was used to estimate the adjusted hazard ratio (HR) for the risk of HF in the unmatched cohort. In the propensity score-matched cohort, general population controls were selected and matched at a 1:1 ratio to the patients with PM/DM based on propensity scores, which accounted for the confounding factors of age, sex, index date (year) of first diagnosis, comorbidities, and medication usage. The cumulative incidence of HF was estimated using the Kaplan-Meier method. A stratified Cox proportional hazards model was used to calculate the HR for the risk of HF events at different follow-up time points among patients with PM/DM compared with non-PM/DM controls in the propensity score-matched cohort. RESULTS: In the unmatched cohort, the study assessed 2,025 patients with PM/DM and 196,109 general population controls. Results of multivariable Cox regression analysis, adjusted for age, sex, comorbidities, and medication usage, revealed a greater risk of HF leading to hospitalization in the PM/DM group than in the control group (adjusted HR 3.29, 95% confidence interval [95% CI] 2.60-4.18). After matching based on propensity score, a total of 1,997 pairs of PM/DM patients and general population controls were identified. In this propensity score-matched cohort, the cumulative incidence of HF in patients with PM/DM at 3 years, 5 years, and 10 years was 3.3%, 4.4%, and 7.4%, respectively. The absolute difference in HF risk in the PM/DM group compared with the control group was 1.8% at 3 years, 2.1% at 5 years, and 3.0% at 10 years. Compared with general population controls, patients with PM/DM exhibited an augmented risk of HF (HR 2.06, 95% CI 1.36-3.12). Analyses stratified according to follow-up time point revealed that the increased risk of HF persisted for up to 10 years after the PM/DM diagnosis. CONCLUSION: These results indicate that the risk of HF leading to hospitalization was increased in patients with PM/DM throughout the study period, supporting the need for greater vigilance in the monitoring of patients with PM/DM for the development of this potentially lethal complication.

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.

Consensus recommendations on managing the selected comorbidities including cardiovascular disease, osteoporosis, and interstitial lung disease in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA)-related comorbidities, including cardiovascular disease (CVD), osteoporosis (OP), and interstitial lung disease (ILD), are sub-optimally managed. RA-related comorbidities affect disease control and lead to impairment in quality of life. We aimed to develop consensus recommendations for managing RA-related comorbidities. METHODS: The consensus statements were formulated based on emerging evidence during a face-to-face meeting of Taiwan rheumatology experts and modified through three-round Delphi exercises. The quality of evidence and strength of recommendation of each statement were graded after a literature review, followed by voting for agreement. Through a review of English-language literature, we focused on the existing evidence of management of RA-related comorbidities. RESULTS: Based on experts' consensus, eleven recommendations were developed. CVD risk should be assessed in patients at RA diagnosis, once every 5 years, and at changes in DMARDs therapy. Considering the detrimental effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids on CVD risks, we recommend using the lowest possible dose of corticosteroids and prescribing NSAIDs cautiously. The OP/fragility fracture risk assessment includes dual-energy X-ray absorptiometry and fracture risk assessment (FRAX) in RA. The FRAX-based approach with intervention threshold is a useful strategy for managing OP. RA-ILD assessment includes risk factors, pulmonary function tests, HRCT imaging and a multidisciplinary decision approach to determine RA-ILD severity. A treat-to-target strategy would limit RA-related comorbidities. CONCLUSIONS: These consensus statements emphasize that adequate control of disease activity and the risk factors are needed for managing RA-related comorbidities, and may provide useful recommendations for rheumatologists on managing RA-related comorbidities.

Association of sleep disturbance with calcitonin, disease severity and health index among patients with ankylosing spondylitis.

ABSTRACT: To investigate the association of sleep disturbance with calcium regulatory hormones, disease severity and health index among the patients with ankylosing spondylitis (AS).There were 104 AS patients enrolled in the cross-sectional study, and their sleep quality was recorded. Serum levels of calcium, parathyroid hormone, vitamin D3 and calcitonin were measured. We evaluated patient's disease activity, functional ability, patient's global assessment, physical mobility, radiographic damage and health index. Blood ESR and CRP levels were tested.Sleep quality was positively correlated with serum calcitonin levels (r = 0.260, P = .008). Bad sleep and advanced radiographic damage were found among the AS patients with detectable serum calcitonin levels (P < .05). Sleep quality was significantly correlated with disease duration, CRP, BASDAI, ASDAS-ESR, ASDAS-CRP, BASFI, BAS-G, BASMI and ASAS-HI among the AS patients (all P < .05). Female gender, longer disease duration, higher ASDAS-CRP and serum calcitonin levels (OR [95% CI] = 3.210 [1.012-10.181], P = .048) were independent factors associated with bad sleep. Inflammation, disease activity, functional ability, patient's global assessment and cervical rotation were useful in predicting bad sleep among the AS patients, and ASDAS-CRP was the best predictor (AUC = 0.772, P < .001).Serum calcitonin levels was elevated in the AS patients with bad sleep, and may participate in the pathophysiology of sleep disturbance. Bad sleep was associated with female gender, longer disease duration, higher inflammation, disease activity, functional impairment, mobility restriction, poor patient's global assessment and health index in AS. ASDAS-CRP was best in predicting bad sleep.