Medicine (St Vincent's) - Research Publications
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ItemA systematic review of the epidemiology, disease characteristics and management of systemic sclerosis in Australian adults(WILEY, 2017-11)OBJECTIVE: Australia has one of the highest prevalence rates of systemic sclerosis (SSc) worldwide. In order to highlight management deficiencies and key areas for further research, it is essential to understand its local epidemiological patterns, natural history, prognosis and mortality trends over time. METHODS: To identify Australian SSc-specific information through a systematic review focusing on areas of epidemiology, disease characteristics, treatment, functional ability, disease burden and health-related quality of life (HRQoL). RESULTS: MEDLINE, EMBASE and the Cochrane Library were searched on 14 September, 2016. All original full text articles on SSc in Australia were included. Of the 54 articles included in this review, the majority of studies recruited from South Australia, Victoria and New South Wales. The prevalence of SSc in Australia is increasing and is similar among the general population and the Aboriginal population. Despite improvements in care over the last three decades, morbidity and mortality remain high, with an overall standardized mortality ratio of 3.4 and a 10-year survival of 84% in a newly diagnosed patient. Cardiorespiratory manifestations are the leading cause of SSc-related death. Malignancy is the leading cause of non-SSc-related death. The role of autoantibodies in predicting disease subtype, visceral involvement and their use as a prognostic marker is becoming increasingly recognized. CONCLUSION: Information on SSc in Australia, particularly unmet healthcare needs, HRQoL and economic burden, is limited. As a heterogenous condition, SSc requires a multi-disciplinary approach to care. Research aimed at quantifying HRQoL and burden of disease in Australia is essential for advocacy and resource allocation.
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ItemEVOLVE: The Australian Rheumatology Association's "top five' list of investigations and interventions doctors and patients should question(WILEY, 2018-02)BACKGROUND: The EVOLVE (evaluating evidence, enhancing efficiencies) initiative aims to drive safer, higher-quality patient care through identifying and reducing low-value practices. AIMS: To determine the Australian Rheumatology Association's (ARA) 'top five' list of low-value practices. METHODS: A working group comprising 19 rheumatologists and three trainees compiled a preliminary list. Items were retained if there was strong evidence of low value and there was high or increasing clinical use and/or increasing cost. All ARA members (356 rheumatologists and 72 trainees) were invited to indicate their 'top five' list from a list of 12-items through SurveyMonkey in December 2015 (reminder February 2016). RESULTS: A total of 179 rheumatologists (50.3%) and 19 trainees (26.4%) responded. The top five list (percentage of rheumatologists, including item in their top five list) was: Do not perform arthroscopy with lavage and/or debridement for symptomatic osteoarthritis of the knee nor partial meniscectomy for a degenerate meniscal tear (73.2%); Do not order anti-nuclear antibody (ANA) testing without symptoms and/or signs suggestive of a systemic rheumatic disease (56.4%); Do not undertake imaging for low back pain for patients without indications of an underlying serious condition (50.8%); Do not use ultrasound guidance to perform injections into the subacromial space as it provides no additional benefit in comparison to landmark-guided injection (50.3%) and Do not order anti-double-stranded DNA antibodies in ANA negative patients unless the clinical suspicion of systemic lupus erythematosus remains high (45.3%). CONCLUSIONS: This list is intended to increase awareness among rheumatologists, other clinicians and patients about commonly used low-value practices that should be questioned.
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ItemDigital ulcers in systemic sclerosis: their epidemiology, clinical characteristics, and associated clinical and economic burden(BMC, 2019-12-23)BACKGROUND: To determine the frequency and clinical characteristics of systemic sclerosis-related digital ulcers, and associated direct health care costs, quality of life, and survival. METHODS: Digital ulcers (DUs) were defined as an area with a visually discernible depth and a loss of continuity of epithelial coverage. DU severity was calculated based on the physician reported highest number of new DUs at clinical review (mild = 1-5 DUs, moderate 6-10 DUs, severe > 10 DUs). Healthcare use was captured through data linkage, wherein SSc clinical data captured prospectively in a dedicated clinical database were linked with health services databases to capture hospital admissions, emergency department (ED) presentations and ambulatory care (MBS) utilization and cost for the period 2008-2015. Healthcare cost determinants were estimated using logistic regression. RESULTS: Among 1085 SSc patients, 48.6% experienced a DU over a mean follow-up of 5.2 ± 2.5 years. Those who developed DUs were more likely to have diffuse disease subtype (34.9% vs 18.2%, p < 0.001), anti-Scl-70 antibody (18.9% vs 9.3%, p < 0.001), and a younger age at SSc onset (43.6 ± 13.9 vs 48.8 ± 14.0 years, p < 0.001) in addition to reduced health-related quality of life (HRQoL) measured by the SF-36 but without a significant impact on survival. SSc patients with a history of a DU utilized significantly more healthcare resources per annum than those without a DU, including hospitalizations, ED presentation, and ambulatory care services. Total healthcare services, excluding medications, were associated with an annual excess cost per DU patient of AUD$12,474 (8574-25,677), p < 0.001, driven by hospital admission and ED presentation costs. CONCLUSION: DUs place a large burden on the patient and healthcare system through reduced HRQoL and increased healthcare resource utilization and associated cost.
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ItemThe economic burden of systemic sclerosis related pulmonary arterial hypertension in Australia(BMC, 2019-11-27)BACKGROUND: To quantify the financial cost of pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc). METHODS: Healthcare use was captured through data linkage, wherein clinical data for SSc patients enrolled in the Australian Scleroderma Cohort Study were linked with hospital, emergency department (ED) and ambulatory care databases (MBS) for the period 2008-2015. PAH was diagnosed on right heart catheter according to international criteria. Determinants of healthcare cost were estimated using logistic regression. RESULTS: Total median (25th-75th) healthcare cost per patient (including hospital, ED and MBS cost but excluding medication cost) for our cohort during 2008-2015 was AUD$37,685 (18,144-78,811) with an annual per patient healthcare cost of AUD$7506 (5273-10,654). Total healthcare cost was higher for SSc-PAH patients compared with those without PAH with a total cost per patient of AUD$70,034 (37,222-110,814) vs AUD$34,325 (16,093 - 69,957), p < 0.001 respectively with an annual excess healthcare cost per PAH patient of AUD$2463 (1973-1885), p < 0.001. The cost of SSc-PAH occurs early post PAH diagnosis with 89.4% utilizing a healthcare service within the first 12 months post PAH diagnosis with an associated cost per patient of AUD$4125 (0-15,666). PAH severity was the main significant determinant of increased healthcare cost (OR 2.5, p = 0.03) in our PAH cohort. CONCLUSIONS: Despite SSc-PAH being a low prevalence disease, it is associated with significant healthcare resource utilization and associated economic burden, predominantly driven by the severity of PAH.
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ItemThe Australian Scleroderma Interest Group and database: 10 years of screening to save lives(AUSTRALASIAN MED PUBL CO LTD, 2017-03-20)
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ItemSurvival and quality of life in incident systemic sclerosis-related pulmonary arterial hypertension(BMC, 2017-06-02)BACKGROUND: Pulmonary arterial hypertension (PAH) is a leading cause of mortality in systemic sclerosis (SSc). We sought to determine survival, predictors of mortality, and health-related quality of life (HRQoL) related to PAH in a large SSc cohort with PAH. METHODS: We studied consecutive SSc patients with newly diagnosed (incident) World Health Organization (WHO) Group 1 PAH enrolled in a prospective cohort between 2009 and 2015. Survival methods were used to determine age and sex-adjusted standardised mortality ratio (SMR) and years of life lost (YLL), and to identify predictors of mortality. HRQoL was measured using the Short form 36 (SF-36) instrument. RESULTS: Among 132 SSc-PAH patients (112 female (85%); mean age 62 ± 11 years), 60 (45.5%) died, with a median (±IQR) survival time from PAH diagnosis of 4.0 (2.2-6.2) years. Median (±IQR) follow up from study enrolment was 3.8 (1.6-5.8) years. The SMR for patients with SSc-PAH was 5.8 (95% CI 4.3-7.8), with YLL of 15.2 years (95% CI 12.3-18.1). Combination PAH therapy had a survival advantage (p < 0.001) compared with monotherapy, as did anticoagulation compared with no anticoagulation (p < 0.003). Furthermore, combination PAH therapy together with anticoagulation had a survival benefit compared with monotherapy with or without anticoagulation and combination therapy without anticoagulation (hazard ratio 0.28, 95% CI 0.1-0.7). Older age at PAH diagnosis (p = 0.03), mild co-existent interstitial lung disease (ILD) (p = 0.01), worse WHO functional class (p = 0.03) and higher mean pulmonary arterial pressure at PAH diagnosis (p = 0.001), and digital ulcers (p = 0.01) were independent predictors of mortality. CONCLUSIONS: Despite the significant benefits conferred by advanced PAH therapies suggested in this study, the median survival in SSc PAH remains short at only 4 years.
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ItemDeterminants of health-related quality of life in a multinational systemic sclerosis inception cohort.( 2018)OBJECTIVES: To evaluate health-related quality of life (HRQoL) and its determinants in a systemic sclerosis (SSc) multinational inception cohort. We performed a meta-analysis of data from individual countries, and compared the meta-analysis to individual country results by pooling data from each of the countries. METHODS: SSc patients within 2 years of disease onset were recruited from 5 countries participating in the International Systemic Sclerosis Inception Cohort (INSYNC). Data from each country's database were exported for analysis using a harmonised platform. HRQoL was assessed using the Medical Outcomes Short Form-36 (SF-36). Multivariate linear regression assessed associations between HRQoL and predictors in cohorts separately and meta-analyzed to generate pooled estimates. The analyses were repeated using individual patient data. RESULTS: Of the 637 SSc patients recruited, the majority was female (80.2%-83.3%), aged between 52.4-56.7 years with limited cutaneous disease subtype (48.6%-66.7%). HRQoL scores were lower for SSc patients than the general population (SF-36 physical component summary (PCS) score (36.4-39.6), mental component summary (MCS) score (41.0-46.4)). Determinants of SF-36 PCS by meta-analysis included increasing age (β=-0.1, 95%CI -0.2, -0.01), diffuse cutaneous disease subtype (β=-8.4, 95%CI -10.6, -6.3), and pulmonary arterial hypertension (β=-10.9, 95%CI -16.6, -5.3). Increasing age (β=0.09, 95%CI 0.0, 0.18) was the only variable associated with SF-36 MCS. Analyses using individual patient data revealed similar results to those of the meta-analysis of cohort data. CONCLUSIONS: Our study provides estimates of HRQoL in a large inception SSc cohort and provides evidence that individual patient data analysis is valid in the INSYNC dataset.
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ItemA COMPARISON OF THE PREDICTIVE ACCURACY OF THREE SCREENING MODELS (DETECT V. ESC/ERS V. ASIG) FOR PULMONARY ARTERIAL HYPERTENSION IN SYSTEMIC SCLEROSIS(WILEY-BLACKWELL, 2014-05)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.
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ItemQuantifying the direct public health care cost of systemic sclerosis A comprehensive data linkage study(LIPPINCOTT WILLIAMS & WILKINS, 2017-12)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.
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ItemRisk factors for development of pulmonary arterial hypertension in Australian systemic sclerosis patients: results from a large multicenter cohort study(BMC, 2016-09-27)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-serologic risk factors for PAH differ based on disease subtype. In both subtypes, mild ILD is associated with PAH, suggesting the possibility of common pathogenic mechanisms underlying both of these disease manifestations. This model identifies a subset of patients at an appreciably higher risk of developing PAH, who should be screened and would in future, benefit from preventative therapies.