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Introduction: Systemic sclerosis (SSc) is an incurable multi-organ autoimmune disease with substantial morbidity and mortality. Due to varied clinical manifestations, patients with SSc are usually on multiple medications and require frequent hospitalization and consultation with specialists and allied health from a broad range of disciplines. We hypothesize that the cost of healthcare in SSc is substantial, and sought to quantify this health service utilization and associated cost among Australian SSc patients. Material(s) and Method(s): Health service use was captured by means of data linkage. Data for all Victorian SSc patients enrolled in the Australian Scleroderma Cohort Study (ASCS) (n=531) between 2011-2015 were linked with the Victorian hospital admissions and emergency presentations data sets and the Medicare Benefits Schedule (MBS), which contains all government subsidized ambulatory care services. Hospitalization cost was calculated based on the financial year of admission, admission diagnosis, length of stay and the corresponding value of each admission unit for that financial year. Ambulatory care cost was based on the MBS fee payable by the Australian government for each service, and medication cost was estimated from the Pharmaceutical Benefits Scheme (PBS). Cost was extrapolated to all Australian SSc patients based on SSc prevalence (21.1 per 100,000) and population data (Australian population 24,304,682 in 2015). Result(s): Total health service utilization cost to the Australian government extrapolated to all Australian SSc patients between 2011-2015 amounted to AUD$298,065,737.15 (USD$219,376,382.55), which is an average annual cost of AUD$59,613,147.43 (USD$43,875,276.51) and annual cost per patient of AUD$11,622.76 (USD$8,554.35). Hospital costs, including inpatient hospitalization and emergency department presentations, accounted for the majority (44.5%) of these costs, followed by medication cost (31.1%) and ambulatory care cost (24.4%). Determi

Objective: The role of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in the assessment of disease activity in systemic sclerosis (SSc) remains controversial. We sought to evaluate the relationship between clinical features of SSc and raised inflammatory markers and to determine if changes in ESR and CRP reflect changes in other disease features over time. Method(s): One thousand, five hundred and forty-five patients enrolled in the Australian Scleroderma Cohort Study were observed over a mean 3.52+/-2.91 years and assessed at 6,119 study visits. Generalised estimating equations were used to determine the relationship between ESR>=20mm/hr and CRP>=5mg/L and features of disease. The associations between change in inflammatory markers and change in skin scores and respiratory function tests were analysed. Result(s): Overall, there was a significant association between raised ESR and forced vital capacity (FVC)<80% predicted, diffusing capacity of the lung (DLCO)<80% predicted, pulmonary arterial hypertension (PAH), body mass index (BMI), proximal muscle strength, anaemia, and hypocomplementaemia (p<0.05). Raised CRP was significantly associated with modified Rodnan Skin Score>20, FVC<80%, DLCO<80%, PAH, digital ulcers, BMI, synovitis, tendon friction rub, anaemia, and hypocomplementaemia (p<0.05). A significant deterioration in respiratory function tests (RFTs) was associated with a 2-fold increase in both ESR and CRP (p<0.05). Conclusion(s): Raised inflammatory markers are associated with pulmonary, cutaneous and musculoskeletal manifestations of SSc. Rising inflammatory markers are correlated with declining respiratory function tests. This suggests inflammatory markers have a role in the assessment of SSc disease activity.Copyright © COPYRIGHT CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2018.

OBJECTIVE: We sought to develop the first Damage Index (DI) in systemic sclerosis (SSc). METHODS: The conceptual definition of 'damage' in SSc was determined through consensus by a working group of the Scleroderma Clinical Trials Consortium (SCTC). Systematic literature review and consultation with patient partners and non-rheumatologist experts produced a list of potential items for inclusion in the DI. These steps were used to reduce the items: (1) Expert members of the SCTC (n=331) were invited to rate the appropriateness of each item for inclusion, using a web-based survey. Items with >60% consensus were retained; (2) Using a prospectively acquired Australian cohort data set of 1568 patients, the univariable relationships between the remaining items and the endpoints of mortality and morbidity (Physical Component Summary score of the Short Form 36) were analysed, and items with p<0.10 were retained; (3) using multivariable regression analysis, coefficients were used to determine a weighted score for each item. The DI was externally validated in a Canadian cohort. RESULTS: Ninety-three (28.1%) complete survey responses were analysed; 58 of 83 items were retained. The univariable relationships with death and/or morbidity endpoints were statistically significant for 22 items, with one additional item forced into the multivariable model by experts due to clinical importance, to create a 23-item weighted SCTC DI (SCTC-DI). The SCTC-DI was predictive of morbidity and mortality in the external cohort. CONCLUSIONS: Through the combined use of consensus and data-driven methods, a 23-item SCTC-DI was developed and retrospectively validated.

Aims. The pathogenesis of systemic sclerosis (SSc) includes fibrosis, vas-culopathy and inflammation; hence the role of inflammatory markers in measurement of disease activity remains controversial. We evaluated the relationship between clinical features of SSc and raised erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to determine if increased inflammatory markers correlate with features of disease activity. Methods. Patients enrolled in the Australian Scleroderma Cohort Study who fulfilled 2013 ACR/EULAR criteria for diagnosis of SSc were included. Generalized estimating equations were used to determine the relationship between ESR>20mm/hr and CRP>5mg/L and clinical features of disease. Results. There were 1,545 patients included in this study who were followed for a mean (SD) 3.52+/-2.91 years and a total of 6,119 study visits. Approximately half of the patients recorded elevated inflammatory markers on at least one occasion. Multivariable analysis showed that raised ESR was associated with fibrotic lung disease, indicated by reduced forced vital capacity (FVC)<80% (OR 1.34 p=0.004), and pulmonary arterial hyper-tension (PAH), diagnosed on right heart catheter (OR 1.89 p=0.003) and diffusing capacity of the lung (DLCO)<80% (OR 1.53 p<0.001). Proximal muscle weakness was also correlated with raised ESR (OR 0.67 p<0.001). Multivariable analysis of the clinical associations with raised CRP showed that respiratory involvement indicated by FVC<80% (OR 1.42 p=0.001) and DLCO<80% (OR 1.38 p=0.001), as well as cutaneous and articular manifestations of disease (mRSS>20 OR 2.00 p<0.001, synovitis OR 1.22 p=0.045, tendon friction rub OR 2.13 p<0.001) were associated with raised CRP. Conclusion. Elevated ESR and CRP are associated with fibrotic and vas-culopathic as well as inflammatory manifestations of disease. The association of inflammatory markers with cutaneous, respiratory and musculoskeletal features suggests ESR and CRP have a role in the assessmen

Introduction: Work disability is a significant consequence of chronic rheumatic disorders, impacting both the society through indirect costs and the individual and their family through loss of income and social activities, and a negative influence on quality of life. We sought to assess employment status, risk factors for unemployment, and the associations of unemployment with patients' health related quality of life (HRQoL). Method(s): Patients enrolled in a SSc longitudinal observational cohort were included. All patients completed an employment questionnaire on enrollment. Clinical manifestations were defined as present if present at the time of enrollment. Pulmonary arterial hypertension (PAH) was diagnosed on right heart catheterization (mPAP >25 and PAWP <15 mmHg). Summary statistics, chi-square tests, univariate and multivariable logistic regression were used to determine the associations of different risk factors with employment. All statistical analysis were performed using STATA 14.0. Result(s): Among 1587 SSc patients, 160 (20%) were unemployed at the time of cohort enrolment. Of these 82.5% were female, 63% had limited disease subtype. Mean (+/- SD) age and disease duration at recruitment from first non-Raynaud's symptom were 51.9 (+/- 10.4) and 11.1 (+/- 10.9) years, respectively. Multivariable regression analysis revealed the presence of digital amputation (OR 3.9, 95% CI 1.7-9.1, p = 0.002) diffuse disease subtype (OR 2.2, 95% CI 1.3-3.5, p-value = 0.002), sicca symptoms (OR 2.7, 95% CI 1.6-4.4, p<0.001), physical job (OR 1.8, 95% CI 1.1-3.1, p = 0.03) and PAH (OR 2.2, 95% CI 1.1-4.5, p = 0.02) to be associated with unemployment. Unemployed patients had consistently poorer HRQoL scores in all domains (physical, emotional and mental health) of the SF-36 form than those who were employed. Conclusion(s): SSc is associated with substantial work disability and poor quality of life. Raising awareness, identifying modifiable risk factors and implementing emp

Aim: There is evidence that early screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) improves outcomes. We compared the predictive accuracy of two recently published screening algorithms (DETECT 2013 and Australian Scleroderma Interest Group - ASIG 2012) for SSc associated PAH (SSc-PAH) with the commonly used European Society of Cardiology / Respiratory Society (ESC/ERS 2009) guidelines. Method(s): We included 73 consecutive SSc patients with suspected PAH undergoing RHC. The predictive accuracy of the models was presented as sensitivity, specificity, positive (PPV) and negative predictive values (NPV). These properties were also evaluated in an 'alternate scenario analysis' where the prevalence of PAH was set at 10%. Result(s): RHC revealed PAH (WHO group 1 PH) in 27 (36.9%) patients and non-PH in 34 patients, while 12 patients hadWHO group 2 or 3 PH and were excluded from further analyses. TR jet was undetectable in 3 patients to whom the ESC/ERS guidelines could not be applied; none had PAH on RHC. Both DETECT and ASIG algorithms performed equally in predicting PAH with sensitivity and NPV of 100%. The ESC/ERS guidelines had sensitivity of 96.3% and NPV of 91%, missing one case of PAH. The ASIG algorithm had the highest specificity (54.5%) and PPV (60%). The DETECT algorithm and ESC/ERS guidelines had similar specificity (35.3% vs 32.3%) and PPV (55.1% vs 55.3%). With PAH prevalence set at 10%, the NPV of the models was unchanged, but the PPV dropped to less than 20%. Conclusion(s): In this cohort, the DETECT and ASIG algorithms outperform the ESC/ERS guidelines, detecting all patients with PAH. The specificity of all models is low, as expected in a screening test. The ESC/ERS guidelines have limitations in the absence of TR jet. Ultimately, the choice of SSc-PAH screening algorithm will also depend on cost and ease of application.

Aim: Hypocomplementemia constitutes one of the ten parameters needed to determine the European Scleroderma Study Group (EScSG) disease activity score. However few studies have investigated the clinical manifestations and relationship to disease activity of hypocomplementemia in systemic sclerosis (SSc).The objective of this study was therefore to determine the clinical features of hypocomplementemia in SSc and define its utility as a marker of disease activity. Method(s): 1140 patients from the Australian Scleroderma Cohort Study, comprising a total of 2867 visits were included. These patients fulfilled the 2013 ACR classification criteria for SSc. Demographic, serological and clinical data obtained through annual review were analysed using univariate methods. Linear and logistic regression, together with generalised estimating equations were used to determine the independent correlates of hypocomplementemia ever, and at each visit, respectively. Result(s): At least one episode of hypocomplementemia (low C3 and/or low C4) occurred in 24.1% of patients over a follow-up of 3.4 +/- 1.7 years, these patients were more likely to be seropositive for anti-ribonuclear protein (odds ratio [OR] = 3.8, p = 0.002), anti-Ro (OR = 2.2, p = 0.002), anti- Smith (OR = 6.3, p = 0.035) and anti-phospholipid antibodies (OR = 1.4, p = 0.021) and display features of mixed connective tissue disorder (OR = 1.5, p = 0.007), specifically polymyositis (OR = 16.0, p = 0.012). No association was found between hypocomplementemia and the EScSG disease activity score (calculated without hypocomplementemia to avoid over correlation) or any of its components (including ESR). Among patients with overlap disease features (n = 221), those who were hypocomplementemic were more likely to have a lower BMI (OR = 0.9, p < 0.0005), digital ulcers (OR = 1.6, p = 0.034), tendon friction rubs (OR = 2.4, p = 0.037) and a forced vital capacity <80% predicted (OR = 2.9, p = 0.008) at that visit. Conclusion(s): Hyp

Background: Pulmonary arterial hypertension (PAH) is the leading cause of death in systemic sclerosis (SSc). Annual screening with echocardiogram (ECHO) is recommended. We present the methodological aspects of a PAH screening programme in a large Australian SSc cohort, the epidemiology of SSc-PAH in this cohort, and an evaluation of factors influencing physician adherence to PAH screening guidelines. Method(s): Patient characteristics and results of PAH screening were determined in all patients enrolled in a SSc longitudinal cohort study. Adherence to PAH screening guidelines was assessed by a survey of Australian rheumatologists. Summary statistics, chi-square tests, univariate and multivariable logistic regression were used to determine the associations of risk factors with PAH. Result(s): Among 1636 patients with SSc, 194 (11.9%) had PAH proven by right-heart catheter. Of these, 160 were detected by screening. The annual incidence of PAH was 1.4%. Patients with PAH diagnosed on subsequent screens, compared with patients in whom PAH was diagnosed on first screen, were more likely to have diffuse SSc (p = 0.03), be in a better World Health Organisation (WHO) Functional Class at PAH diagnosis (p = 0.01) and have less advanced PAH evidenced by higher mean six-minute walk distance (p = 0.03), lower mean pulmonary arterial pressure (p = 0.009), lower mean pulmonary vascular resistance (p = 0.006) and fewer non-trivial pericardial effusions (p = 0.03). Adherence to annual PAH screening using an ECHO-based algorithm was poor among Australian rheumatologists, with less than half screening their patients with SSc of more than ten years disease duration. Conclusion(s): PAH is a common complication of SSc. Physician adherence to PAH screening recommendations remains poor. Identifying modifiable barriers to screening may improve adherence and ultimately patient outcomes.Copyright © 2017 The Author(s).

To quantify the direct healthcare cost of systemic sclerosis (SSc) and identify its determinants. Healthcare use was captured through data linkage, wherein clinical and medication data for SSc patients from the state of Victoria enrolled in the Australian Scleroderma Cohort Study were linked with the Victorian hospital admissions and emergency presentations data sets, and the Medicare Benefits Schedule which contains all government subsidized ambulatory care services, for the period 2011-2015. Medication cost was determined from the Pharmaceutical Benefits Scheme. Costs were extrapolated to all Australian SSc patients based on SSc prevalence of 21.1 per 100,000 and an Australian population of 24,304,682 in 2015. Determinants of healthcare cost were estimated using logistic regression. Total healthcare utilization cost to the Australian government extrapolated to all Australian SSc patients from 2011 to 2015 was Australian Dollar (AUD)$297,663,404.77, which is an average annual cost of AUD$59,532,680.95 (US Dollar [USD]$43,816,040.08) and annual cost per patient of AUD$11,607.07 (USD$8,542.80). Hospital costs, including inpatient hospitalization and emergency department presentations, accounted for the majority of these costs (44.4% of total), followed by medication cost (31.2%) and ambulatory care cost (24.4%). Pulmonary arterial hypertension (PAH) and gastrointestinal (GIT) involvement were the major determinants of healthcare cost (OR 2.3 and 1.8, P = .01 for hospitalizations; OR 2.8 and 2.0, P = .01 for ambulatory care; OR 7.8 and 1.6, P < .001 and P = .03 for medication cost, respectively). SSc is associated with substantial healthcare utilization and direct economic burden. The most costly aspects of SSc are PAH and GIT involvement.Copyright © 2017 the Author(s). Published by Wolters Kluwer Health, Inc.

To quantify the direct healthcare cost of systemic sclerosis (SSc) and identify its determinants. Healthcare use was captured through data linkage, wherein clinical and medication data for SSc patients from the state of Victoria enrolled in the Australian Scleroderma Cohort Study were linked with the Victorian hospital admissions and emergency presentations data sets, and the Medicare Benefits Schedule which contains all government subsidized ambulatory care services, for the period 2011-2015. Medication cost was determined from the Pharmaceutical Benefits Scheme. Costs were extrapolated to all Australian SSc patients based on SSc prevalence of 21.1 per 100,000 and an Australian population of 24,304,682 in 2015. Determinants of healthcare cost were estimated using logistic regression. Total healthcare utilization cost to the Australian government extrapolated to all Australian SSc patients from 2011 to 2015 was Australian Dollar (AUD)$297,663,404.77, which is an average annual cost of AUD$59,532,680.95 (US Dollar [USD]$43,816,040.08) and annual cost per patient of AUD$11,607.07 (USD$8,542.80). Hospital costs, including inpatient hospitalization and emergency department presentations, accounted for the majority of these costs (44.4% of total), followed by medication cost (31.2%) and ambulatory care cost (24.4%). Pulmonary arterial hypertension (PAH) and gastrointestinal (GIT) involvement were the major determinants of healthcare cost (OR 2.3 and 1.8, P = .01 for hospitalizations; OR 2.8 and 2.0, P = .01 for ambulatory care; OR 7.8 and 1.6, P < .001 and P = .03 for medication cost, respectively). SSc is associated with substantial healthcare utilization and direct economic burden. The most costly aspects of SSc are PAH and GIT involvement.

BACKGROUND: Pulmonary arterial hypertension (PAH) is the leading cause of death in systemic sclerosis (SSc). Annual screening with echocardiogram (ECHO) is recommended. We present the methodological aspects of a PAH screening programme in a large Australian SSc cohort, the epidemiology of SSc-PAH in this cohort, and an evaluation of factors influencing physician adherence to PAH screening guidelines. METHODS: Patient characteristics and results of PAH screening were determined in all patients enrolled in a SSc longitudinal cohort study. Adherence to PAH screening guidelines was assessed by a survey of Australian rheumatologists. Summary statistics, chi-square tests, univariate and multivariable logistic regression were used to determine the associations of risk factors with PAH. RESULTS: Among 1636 patients with SSc, 194 (11.9%) had PAH proven by right-heart catheter. Of these, 160 were detected by screening. The annual incidence of PAH was 1.4%. Patients with PAH diagnosed on subsequent screens, compared with patients in whom PAH was diagnosed on first screen, were more likely to have diffuse SSc (p = 0.03), be in a better World Health Organisation (WHO) Functional Class at PAH diagnosis (p = 0.01) and have less advanced PAH evidenced by higher mean six-minute walk distance (p = 0.03), lower mean pulmonary arterial pressure (p = 0.009), lower mean pulmonary vascular resistance (p = 0.006) and fewer non-trivial pericardial effusions (p = 0.03). Adherence to annual PAH screening using an ECHO-based algorithm was poor among Australian rheumatologists, with less than half screening their patients with SSc of more than ten years disease duration. CONCLUSION: PAH is a common complication of SSc. Physician adherence to PAH screening recommendations remains poor. Identifying modifiable barriers to screening may improve adherence and ultimately patient outcomes.

OBJECTIVE: To determine mortality and causes of death in a multinational inception cohort of subjects with systemic sclerosis (SSc). METHODS: We quantified mortality as standardized mortality ratio (SMR), years of life lost, and percentage mortality in the first decade of disease. The inception cohort comprised subjects recruited within 4 years of disease onset. For comparison, we used a prevalent cohort, which included all subjects irrespective of disease duration at recruitment. We determined a single primary cause of death (SSc related or non-SSc related) using a standardized case report form, and we evaluated predictors of mortality using multivariable Cox regression. RESULTS: In the inception cohort of 1,070 subjects, there were 140 deaths (13%) over a median follow-up of 3.0 years (interquartile range 1.0-5.1 years), with a pooled SMR of 4.06 (95% confidence interval [95% CI] 3.39-4.85), up to 22.4 years of life lost in women and up to 26.0 years of life lost in men, and mortality in the diffuse disease subtype of 24.2% at 8 years. In the prevalent cohort of 3,218 subjects, the pooled SMR was lower at 3.39 (95% CI 3.06-3.71). In the inception cohort, 62.1% of the primary causes of death were SSc related. Malignancy, sepsis, cerebrovascular disease, and ischemic heart disease were the most common non-SSc-related causes of death. Predictors of early mortality included male sex, older age at disease onset, diffuse disease subtype, pulmonary arterial hypertension, and renal crisis. CONCLUSION: Early mortality in SSc is substantial, and prevalent cohorts underestimate mortality in SSc by failing to capture early deaths, particularly in men and those with diffuse disease.

Objective. Asymmetric dimethylarginine (ADMA) is a novel biomarker of endothelial cell dysfunction. In this proof of concept study, we sought to evaluate the role of ADMA as a screening biomarker for incident systemic sclerosis-related pulmonary arterial hypertension (SSc-PAH). Methods. ADMA levels were measured using high performance liquid chromatography in 15 consecutive treatment-naive patients with newly-diagnosed SSc-PAH and compared with 30 SSc-controls without PAH. Logistic regression models were used to evaluate the independent association of ADMA with PAH. The optimal cut-point of ADMA for SSc-PAH screening was determined. NT-proBNP levels were previously measured in the same patients and the optimal cut-point of NT-proBNP of >210ng/mL was coupled with the optimal cut-point of ADMA to create a screening model that combined the two biomarkers. Results. The PAH group had significantly higher mean ADMA levels than the control group (0.76+/-0.14 muM versus 0.59+/-0.07 muM; p < 0.0001). ADMA levels remained significantly associated with PAH after the adjustment for specific disease characteristics, cardiovascular risk factors and other SSc-related vascular complications (all p < 0.01). An ADMA level >=0.7 muM had a sensitivity of 86.7%, specificity of 90.0% and AUC of 0.86 for diagnosing PAH. A screening model that combined an NT-proBNP >=210ng/mL and/or ADMA >=0.7 ng/mL resulted in a sensitivity of 100% and specificity of 90% for the detection of SSc-PAH. Conclusion. In this small study, use of ADMA in combination with NT-proBNP produced excellent sensitivity and specificity for the non-invasive identification of SSc-PAH. The role of ADMA as a screening biomarker for SSc-PAH merits further evaluation.

Objective. To report the efficacy and tolerability of mycophenolate mofetil (MMF) and azathioprine (AZA) in the management of systemic sclerosis-associated interstitial lung disease (SSc-ILD). Methods. Patients in the Australian Scleroderma Cohort Study treated with at least 3 months of MMF or AZA for SSc-ILD confirmed on high resolution computed tomography (HRCT) chest were identified and their pulmonary function tests (PFTs) retrieved. Individuals with available results for T-1 (12 months prior to treatment commencement), T0 (date of treatment commencement) and at least one subsequent time point were included in the drug efficacy analysis. The Wilcoxon signed-rank test was used to compare absolute FVC at T-1, T0, 12 months (T1), 24 months (T2) and 36 months (T3). Analysis of drug tolerability included all identified patients treated with MMF or AZA. Results. 18/22 patients treated with MMF and 29/49 treated with AZA had adequate PFTs for inclusion in the drug efficacy analysis. Median absolute FVC at T-1 for MMF treatment was 2.50L, declining to 2.12L at T0 (p=0.02). Following MMF therapy, FVC results were stable at T1 (2.13L, p=0.86), T2 (2.17L, p=0.65) and T3 (2.25L, p=0.78). In the AZA group, a statistically significant decline did not occur prior to treatment, however FVC results remained stable at T1, T2 and T3. Adverse events leading to early discontinuation ( < 12 months treatment) were less common in the MMF group (4/22 vs. 13/49). Gastrointestinal complications were the main cause of discontinuation in both groups. Conclusion. In patients with SSc-ILD with declining pulmonary function, MMF therapy was associated with stability for up to 36 months. Early adverse events leading to discontinuation occurred less frequently in patients treated with MMF than in AZA treated patients.

Background/Purpose: Pulmonary arterial hypertension (PAH) is the leading cause of systemic sclerosis (SSc) related mortality. We sought to determine survival, predictors of mortality, and health related quality of life (HRQoL) of PAH in a large SSc cohort followed from the time of PAH diagnosis in the modern era of PAH-specific vasodilator therapy. Method(s): Patients enrolled in a SSc longitudinal cohort between 2009 - 2015 were included. Group 1 PAH was diagnosed on right heart catheterization (RHC) (mPAP >=25 and PAWP <15 mmHg). Other causes of pulmonary hypertension were excluded. Summary statistics, chi-square tests and survival methods were used to determine survival rates and identify predictors of mortality. HRQoL was measured using the Medical Outcomes Study Short Form 36 (SF-36). Result(s): Among 132 SSc-PAH patients, 84.9% were female and 68.9% had limited disease subtype. The mean (+/-SD) age at diagnosis of PAH was 62.3 (+/-10.5) years and disease duration at PAH diagnosis was 14.1 (+/-11.9) years. Over a median (IQR) follow-up of 3.7 (1.6- 5.8) years, 60 (45.5%) patients died, with a median survival time from PAH diagnosis of 3.7 years. The standardized mortality ratio for patients with SSc-PAH compared with the general population was 5.8 (95%CI 4.3-7.8). The years of life lost with SSc-PAH was 15.22 years (95%CI 12.3-18.1). Kaplan-Meier survival curves (Figure 1) showed a survival advantage with combination PAH therapy and anticoagulation. Older age at PAH diagnosis (p=0.03), coexistence of mild ILD (p=0.01), worse WHO functional class (p=0.03), higher mean pulmonary arterial pressure at PAH diagnosis (p=0.001) and presence of digital ulcers (p=0.01) during follow-up were predictive of PAH mortality (Table 1). Combination therapy together with anticoagulation provided the most significant survival advantage, with a 72% reduction in mortality compared with pulmonary vasodilator monotherapy without anticoagulation (Figure 1). Patients with SSc-PAH had c

Background: In some rheumatic diseases such as systemic lupus erythematosus (SLE), low serum complement ('hypocomplementaemia') is a feature of active disease. However, the role of hypocomplementaemia in systemic sclerosis (SSc) is unknown. We sought to determine the frequency, clinical associations and relationship to disease activity of hypocomplementaemia in SSc. Method(s): The study included 1140 patients fulfilling the 2013 American College of Rheumatology criteria for SSc. Demographic, serological and clinical data, obtained prospectively through annual review, were analysed using univariable methods. Linear and logistic regression, together with generalised estimating equations, were used to determine the independent correlates of hypocomplementaemia ever, and at each visit, respectively. Result(s): At least one episode of hypocomplementaemia (low C3 and/or low C4) occurred in 24.1 % of patients over 1893 visits; these patients were more likely to be seropositive for anti-ribonucleoprotein (OR = 3.8, p = 0.002), anti-Ro (OR = 2.2, p = 0.002), anti-Smith (OR = 6.3, p = 0.035) and anti-phospholipid antibodies (OR = 1.4, p = 0.021) and were more likely to display features of overlap connective tissue disease, in particular polymyositis (OR = 16.0, p = 0.012). However, no association was found between hypocomplementaemia and either the European Scleroderma Study Group disease activity score or any of its component variables (including erythrocyte sedimentation rate) in univariate analysis. Among patients with SSc overlap disease features, those who were hypocomplementaemic were more likely to have digital ulcers (OR = 1.6, p = 0.034), tendon friction rubs (OR = 2.4, p = 0.037), forced vital capacity <80 % predicted (OR = 2.9, p = 0.008) and lower body mass index (BMI) (OR for BMI = 0.9, p < 0.0005) at that visit, all of which are features associated with SSc disease activity and/or severity. Conclusion(s): While hypocomplementaemia is not associated with disease

BACKGROUND: In some rheumatic diseases such as systemic lupus erythematosus (SLE), low serum complement ('hypocomplementaemia') is a feature of active disease. However, the role of hypocomplementaemia in systemic sclerosis (SSc) is unknown. We sought to determine the frequency, clinical associations and relationship to disease activity of hypocomplementaemia in SSc. METHODS: The study included 1140 patients fulfilling the 2013 American College of Rheumatology criteria for SSc. Demographic, serological and clinical data, obtained prospectively through annual review, were analysed using univariable methods. Linear and logistic regression, together with generalised estimating equations, were used to determine the independent correlates of hypocomplementaemia ever, and at each visit, respectively. RESULTS: At least one episode of hypocomplementaemia (low C3 and/or low C4) occurred in 24.1 % of patients over 1893 visits; these patients were more likely to be seropositive for anti-ribonucleoprotein (OR = 3.8, p = 0.002), anti-Ro (OR = 2.2, p = 0.002), anti-Smith (OR = 6.3, p = 0.035) and anti-phospholipid antibodies (OR = 1.4, p = 0.021) and were more likely to display features of overlap connective tissue disease, in particular polymyositis (OR = 16.0, p = 0.012). However, no association was found between hypocomplementaemia and either the European Scleroderma Study Group disease activity score or any of its component variables (including erythrocyte sedimentation rate) in univariate analysis. Among patients with SSc overlap disease features, those who were hypocomplementaemic were more likely to have digital ulcers (OR = 1.6, p = 0.034), tendon friction rubs (OR = 2.4, p = 0.037), forced vital capacity <80 % predicted (OR = 2.9, p = 0.008) and lower body mass index (BMI) (OR for BMI = 0.9, p < 0.0005) at that visit, all of which are features associated with SSc disease activity and/or severity. CONCLUSIONS: While hypocomplementaemia is not associated with disease activi

BACKGROUND: Pulmonary arterial hypertension (PAH) is the leading cause of mortality in patients with systemic sclerosis (SSc). We sought to determine the incidence, prevalence and risk factors for PAH development in a large Australian SSc cohort. METHODS: PAH was diagnosed on right heart catheterisation (mPAP >25 and PAWP <15 mmHg at rest). Patients with PH secondary to interstitial lung disease (ILD; defined as abnormal HRCT scan and FVC < 60 %) were excluded. Summary statistics, chi-square tests, univariate and multivariable logistic regression along with post-estimation diagnostics were used to determine the associations of different combinations of risk factors with PAH. RESULTS: Among 1579 SSc patients, 8.4 % (132 patients) were diagnosed with PAH over a mean (±SD) follow-up of 3.2 (±2.5) years. The incidence of PAH in this cohort was 0.7 % per annum. Of these, 68.9 % had limited disease subtype (lcSSc). In multivariable regression analysis, the presence of anti-centromere antibody (ACA) (OR 1.6, 95 % CI 1.1-2.5, p = 0.03), oesphageal stricture (OR 2.0, 95 % CI 1.2-3.3, p = 0.006), calcinosis (OR 1.9, 95 % CI 1.2-2.9, p = 0.003), sicca symptoms (OR 1.6, 95 % CI 1.1-2.5, p = 0.03), mild ILD (OR 2.3, 95 % CI 1.5-3.7, p < 0.001) and digital ulcers (OR 1.6, 95 % CI 1.0-2.4, p = 0.03) were predictive of PAH. This model had an area under the curve of 0.7 and concordance of 91.8 %. When analysed by disease subtype, the presence of calcinosis (OR 2.2, 95 % CI 1.4-3.7, p = 0.01), sicca symptoms (OR 2.6, 95 % CI 1.5-4.6, p = 0.001), mild ILD (OR 2.3, 95 % CI 1.4-3.8, p = 0.001) and digital ulcers (OR 1.9, 95 % CI 1.2-3.7, p = 0.01) were predictive of PAH in lcSSc; and oesophageal stricture (OR 4.4, 95 % CI 1.9-10.5, p = 0.001), mild ILD (OR 2.8, 95 % CI 1.2-6.8, p = 0.02) and ACA (OR 5.2, 95 % CI 1.8-14.8, p = 0.002) were predictive of PAH in dcSSc. CONCLUSIONS: The incidence and prevalence of PAH in this cohort are 0.7 % per annum and 8.4 %, respectively. The clinical-s

Introduction: There is evidence that early screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) improves outcomes. We compared the predictive accuracy of two recently published screening algorithms (DETECT 2013 and Australian Scleroderma Interest Group (ASIG) 2012) for SSc-associated PAH (SSc-PAH) with the commonly used European Society of Cardiology/European Respiratory Society (ESC/ERS 2009) guidelines. Method(s): We included 73 consecutive SSc patients with suspected PAH undergoing right heart catheterization (RHC). The three screening models were applied to each patient. For each model, contingency table analysis was used to determine sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values for PAH. These properties were also evaluated in an 'alternate scenario analysis' in which the prevalence of PAH was set at 10%. Result(s): RHC revealed PAH in 27 (36.9%) patients. DETECT and ASIG algorithms performed equally in predicting PAH with sensitivity and NPV of 100%. The ESC/ERS guidelines had sensitivity of 96.3% and NPV of only 91%, missing one case of PAH. these guidelines could not be applied to three patients who had absent tricuspid regurgitant (TR) jet. The ASIG algorithm had the highest specificity (54.5%). With PAH prevalence set at 10%, the NPV of the models was unchanged, but the PPV dropped to less than 20%. Conclusion(s): In this cohort, the DETECT and ASIG algorithms out-perform the ESC/ERS guidelines, detecting all patients with PAH. The ESC/ERS guidelines have limitations in the absence of a TR jet. Ultimately, the choice of SSc-PAH screening algorithm will also depend on cost and ease of application.Copyright © 2015 Hao et al.. licensee BioMed Central.

Background: Screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) is now standard care in this disease. The existing Australian Scleroderma Interest Group algorithm (ASIGSTANDARD) is based on transthoracic echocardiography (TTE) and pulmonary function tests (PFT). Recently, ASIG has derived and validated a new screening algorithm (ASIGPROPOSED) that incorporates N-terminal pro-B-type natriuretic peptide level together with PFT in order to decrease reliance on TTE, which has some limitations. Right heart catheterisation (RHC) remains the gold standard for the diagnosis of PAH in patients who screen 'positive'. Aim(s): To compare the cost of PAH screening in SSc with ASIGSTANDARD and ASIGPROPOSED algorithms. Method(s): We applied both ASIGSTANDARD and ASIGPROPOSED algorithms to 643 screen-naive SSc patients from the Australian Scleroderma Cohort Study (ASCS), assuming a PAH prevalence of 10%. We compared the costs of screening, the number of TTE required and both the total number of RHC required and the number of RHC needed to diagnose one case of PAH, and costs, according to each algorithm. We then extrapolated the costs to the estimated total Australian SSc population. Result(s): In screen-naive patients from the ASCS, ASIGPROPOSED resulted in 64% fewer TTE and 10% fewer RHC compared with ASIGSTANDARD, with $1936 (15%) saved for each case of PAH diagnosed. When the costs were extrapolated to the entire Australian SSc population, there was an estimated screening cost saving of $946000 per annum with ASIGPROPOSED, with a cost saving of $851400 in each subsequent year of screening. Conclusion(s): ASIGPROPOSED substantially reduces the number of TTE and RHC required and results in substantial cost savings in SSc-PAH screening compared with ASIGSTANDARD.Copyright © 2015 Royal Australasian College of Physicians.

Background and aim. Most screening models for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) use transthoracic echocardiography (TTE) as a 'first tier' test. TTE is costly, requires expertise, and is limited by the absence of a TR jet and inestimable sPAP in up to 30% of patients. We have recently derived and validated a novel screening algorithm for SSc-PAH, based on serum NT-proBNP measurement combined with pulmonary function testing (PFT), which is highly sensitive and easy to use. In this study, our objective was to compare the accuracy and cost of SSc-PAH screening using this new algorithm (ASIGnew), with an existing TTE-based algorithm (ASIGold). Methods. We included consecutive patients enrolled into the Australian Scleroderma Cohort Study who had undergone their first screening for pulmonary arterial hypertension using TTE and PFT between 2007 and 2012, and in whom serum had been collected for NT-proBNP measurement using the Elecsys immunoassay, at the time of screening or right heart catheterization (RHC). The existing Australian Scleroderma Interest Group SSc-PAH screening algorithm (ASIGold) recommends RHC for patients with sPAP >=40 mmHg on TTE or DLCO <=50% with FVC >85% predicted on PFT. In ASIGnew, patients screen positive if either DLCO <70% and FVC/DLCO >=1.8 on PFT, or NT-proBNP level is >=210 pg/ml. All patients who screen positive then undergo TTE followed by RHC. PAH was defined based on RHC as mPAP >25mmHg at rest and PCWP <15mmHg. The cost of the tests was obtained from the Australian medical benefits schedule. We compared ASIGold and ASIGnew in terms of (i) the number of TTE and RHC required to diagnose one case of PAH and (ii) the total cost of screening, and the cost of diagnosing one case of PAH. Results. The results of the application of the algorithms to 643 patients are presented in Table I. ASIGold missed 1 case of PAH detected by ASIGnew. ASIGnew resulted in 64% fewer TTE and 10% fewer RHC. ASIGnew resulted in a cos

Background and Aim. There is evidence that screening for Pulmonary Arterial Hypertension (PAH) in systemic sclerosis (SSc) improves outcomes. We compared the predictive accuracy of two recently published SSc-PAH screening algorithms (DETECT 2013 and Australian Scleroderma Interest Group - ASIG 2012) with the commonly used European Society of Cardiology/Respiratory Society (ESC/ERS 2009) guidelines. Method. We included 71 consecutive SSc patients with suspected PAH undergoing RHC. We excluded patients with FVC<40%. The three screening models were applied to each patient as follows: a positive screen in DETECT was a score of 300+ in 'step 1' (FVC/DLCO%, telangiectasia, anti-centromere antibody, NTproBNP, urate, ECG right axis deviation) together with a score of 35+ in 'step 2' (step 1 points, RA area, tricuspid regurgitant velocity [TRV]) calculated using a nomogram; a positive screen in the ASIG algorithm was DLCOCORR <70% and FVC/DLCOCORR>=1.8, or NT-proBNP>=210 pg/ml; a positive screen in the ESC/ERS guidelines was TRV >3.4 m/s, or TRV >2.8-<=3.4 and symptoms, or TRV <=2.8 m/s and symptoms and additional suggestive echo variables. PAH was defined as mPAP>25 and PCWP<=15 mmHg on RHC. For each model, contingency table analysis was used to determine sensitivity, specificity, positive (PPV) and negative predictive values (NPV) for PAH. These test properties were also evaluated in an 'alternate scenario analysis' where the prevalence of PAH was set at 10%. Results. RHC revealed PAH in 27 (38%) patients, while 10 patients had WHO group 2 and 3 PH and were excluded from further analyses. TR jet was undetectable in 3 patients to whom the ESC/ERS guidelines could not be applied; none had PAH on RHC. Test properties of the three models are summarized in Table I. Both DETECT and ASIG algorithms performed equally well with sensitivity and NPV of 100%. However, the ESC/ERS guidelines had NPV of only 90%, missing one case of PAH. All three models lacked specificity, ranging from

INTRODUCTION: There is evidence that early screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) improves outcomes. We compared the predictive accuracy of two recently published screening algorithms (DETECT 2013 and Australian Scleroderma Interest Group (ASIG) 2012) for SSc-associated PAH (SSc-PAH) with the commonly used European Society of Cardiology/European Respiratory Society (ESC/ERS 2009) guidelines. METHODS: We included 73 consecutive SSc patients with suspected PAH undergoing right heart catheterization (RHC). The three screening models were applied to each patient. For each model, contingency table analysis was used to determine sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values for PAH. These properties were also evaluated in an 'alternate scenario analysis' in which the prevalence of PAH was set at 10%. RESULTS: RHC revealed PAH in 27 (36.9%) patients. DETECT and ASIG algorithms performed equally in predicting PAH with sensitivity and NPV of 100%. The ESC/ERS guidelines had sensitivity of 96.3% and NPV of only 91%, missing one case of PAH; these guidelines could not be applied to three patients who had absent tricuspid regurgitant (TR) jet. The ASIG algorithm had the highest specificity (54.5%). With PAH prevalence set at 10%, the NPV of the models was unchanged, but the PPV dropped to less than 20%. CONCLUSIONS: In this cohort, the DETECT and ASIG algorithms out-perform the ESC/ERS guidelines, detecting all patients with PAH. The ESC/ERS guidelines have limitations in the absence of a TR jet. Ultimately, the choice of SSc-PAH screening algorithm will also depend on cost and ease of application.