Medicine (St Vincent's) - Research Publications
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ItemNo Preview AvailablePrognostic and functional importance of both overt and subclinical left ventricular systolic dysfunction in systemic sclerosis.(Elsevier BV, 2024-06)OBJECTIVES: To quantify the frequency and clinical implications of systemic sclerosis (SSc)-associated left ventricular function (LV) impairment. METHODS: Australian Scleroderma Cohort Study participants meeting ACR/EULAR criteria for SSc with ≥1 echocardiographic LVEF measurement were included. Overt LV dysfunction was indicated by reduced LV ejection fraction (LVEF) and subclinical LV dysfunction was measured using impaired LV global longitudinal strain (LV-GLS>-16 %). Those with secondary causes of LV dysfunction (myocardial ischaemia, valvulopathy and pulmonary arterial hypertension) were excluded. Chi-squared tests, two-sample t-tests or Wilcoxon rank-sum tests were used for between-group comparison as appropriate. Generalised estimating equations(GEE) were used to model longitudinal data. Kaplan-Meier and Cox proportional hazard models were used for survival analyses. RESULTS: Of 1141 participants with no co-morbid cardiac disease, 2.4 % ever recorded a LVEF<50 %, while only 0.6 % ever recorded a LVEF≤40 %. LV-GLS data were available for 90 % of participants at one centre (n = 218). Impaired LV-GLS was detected in 21 % despite LVEF≥50 %. Those with a LVEF<50 % were more frequently male (p = 0.01) with dcSSc (p < 0.01), higher inflammatory markers (p < 0.02) and skeletal muscle disease (p < 0.05). In multivariable analyses, recording a LVEF<50 % was associated with increased mortality (HR2.3, 95 %CI1.0-4.8, p = 0.04). Impaired LV-GLS was also associated with poorer survival in univariable analyses (HR3.4, 95 %CI1.0-11.8, p = 0.05). Those with a LVEF<50 % more frequently recorded WHO Class III/IV dyspnoea (OR3.5, 95 %CI1.6-7.7, p < 0.01), with shorter six-minute walk distance (p = 0.01), higher Health Assessment Questionnaire-Disability Index scores (p < 0.01) and lower Short Form-36 Physical Component Summary scores (p = 0.02). Increased dyspnoea (WHO Class III/IV dyspnoea; OR3.6, 95 %CI1.4-9.2, p < 0.01) was also seen in those with impaired LV-GLS. CONCLUSIONS: Both overt and subclinical SSc-associated LV dysfunction are associated with worse survival and impaired physical function. The frequency of abnormal LV-GLS in those with consistently normal LVEF suggests an under-appreciated burden of subtle LV systolic dysfunction in SSc that has a significant impact on patient symptomatology.
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ItemNo Preview AvailableProximal weakness and creatine kinase elevation in systemic sclerosis: Clinical correlates, prognosis and functional implications(W B SAUNDERS CO-ELSEVIER INC, 2024-04)OBJECTIVES: To determine the frequency, clinical correlates and implications of clinical evidence of muscle disease in systemic sclerosis (SSc). METHODS: Australian Scleroderma Cohort Study participants with ≥1 creatine kinase (CK) and proximal power assessment were subdivided according to presence of proximal weakness (PW: proximal muscle power<5/5) and CK elevation(≥140IU/L). Participants were assigned to one of four groups: concurrent PW&CK elevation, PW alone, CK elevation alone or neither. Between-group comparisons were made with chi-squared, ANOVA or Kruskal-Wallis tests. Survival analysis was performed using time-varying-covariate Cox regression modelling. Longitudinal data were modelled using multinomial logistic and linear regression. RESULTS: Of 1786 participants, 4 % had concurrent PW&CK elevation, 15 % PW alone, 24 % CK elevation and 57 % neither. Participants with PW&CK elevation displayed a severe, inflammatory SSc phenotype, with more frequent dcSSc(p < 0.01), tendon friction rubs(p < 0.01), synovitis(p < 0.01) and digital ulceration(p = 0.03). Multimorbidity(p < 0.01) and cardiopulmonary disease, including ischaemic heart disease(p < 0.01) and pulmonary arterial hypertension(p < 0.01), were most common in those with PW, with and without CK elevation. Men with anti-Scl70 positivity most frequently had CK elevation alone, without other significant clinical differences. Multivariable modelling demonstrated 3.6-fold increased mortality in those with PW&CK elevation (95 %CI 1.9-6.6, p < 0.01) and 2.1-fold increased mortality in PW alone (95 %CI 1.4-3.0, p < 0.01) compared to those without PW or CK elevation. CK elevation alone conferred better survival (HR 0.7, 95 %CI 0.4-1.1, p = 0.09) compared to those with no PW or CK elevation. PW regardless of CK elevation was associated with impaired physical function, with reduced six-minute-walk-distance (p < 0.01), higher HAQ-DI scores (p < 0.01) and increased patient-reported dyspnoea (p = 0.04). CONCLUSION: Clinical features of myopathy are highly prevalent in SSc, affecting almost half of our study cohort. Detection of PW and elevated CK alone, even without imaging or histopathological identification of SSc-myopathy, identified important clinical associations and are associated with poorer function and overall prognosis.
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ItemWhat are the core recommendations for gout management in first line and specialist care? Systematic review of clinical practice guidelines(SPRINGERNATURE, 2023-06-15)BACKGROUND: Gout is the most common inflammatory arthritis, increasing in prevalence and burden. Of the rheumatic diseases, gout is the best-understood and potentially most manageable condition. However, it frequently remains untreated or poorly managed. The purpose of this systematic review is to identify Clinical Practice Guidelines (CPG) regarding gout management, evaluate their quality, and to provide a synthesis of consistent recommendations in the high-quality CPGs. METHODS: Gout management CPGs were eligible for inclusion if they were (1) written in English and published between January 2015-February 2022; focused on adults aged ≥ 18 years of age; and met the criteria of a CPG as defined by the Institute of Medicine; and (2) were rated as high quality on the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Gout CPGs were excluded if they required additional payment to access; only addressed recommendations for the system/organisation of care and did not include interventional management recommendations; and/or included other arthritic conditions. OvidSP MEDLINE, Cochrane, CINAHL, Embase and Physiotherapy Evidence Database (PEDro) and four online guideline repositories were searched. RESULTS: Six CPGs were appraised as high quality and included in the synthesis. Clinical practice guidelines consistently recommended education, commencement of non-steroidal anti-inflammatories, colchicine or corticosteroids (unless contraindicated), and assessment of cardiovascular risk factors, renal function, and co-morbid conditions for acute gout management. Consistent recommendations for chronic gout management were urate lowering therapy (ULT) and continued prophylaxis recommended based on individual patient characteristics. Clinical practice guideline recommendations were inconsistent on when to initiate ULT and length of ULT, vitamin C intake, and use of pegloticase, fenofibrate and losartan. CONCLUSION: Management of acute gout was consistent across CPGs. Management of chronic gout was mostly consistent although there were inconsistent recommendations regarding ULT and other pharmacological therapies. This synthesis provides clear guidance that can assist health professionals to provide standardised, evidence-based gout care. TRIAL REGISTRATION: The protocol for this review was registered with Open Science Framework (DOI https://doi.org/10.17605/OSF.IO/UB3Y7 ).
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ItemNo Preview AvailableEndobronchial obstruction in connective tissue diseases: an uncommon but life threatening complication: two case reports(BMC, 2023-08-02)BACKGROUND: Granulomatosis with polyangiitis and relapsing polychondritis are rare, multisystemic and potentially life-threatening connective tissue diseases. We present two cases of severe endobronchial obstruction in the aforementioned conditions and discuss difficulties with detection and treatment. Despite differing underlying pathophysiologies, endobronchial disease is a less frequently reported but serious complication of both conditions. CASE PRESENTATION: Case 1, a 31-year-old South Asian woman with relapsing polychondritis, required partial tracheal resection and reconstruction in combination with immunosuppressive therapy to achieve respiratory recovery following collapse of her right main bronchus and a stricture in her left main bronchus. Case 2, a 22-year-old Caucasian male with granulomatosis with polyangiitis, underwent surgical resection of an endobronchial growth causing occlusion of his right main bronchus. Although his respiratory status was initially stabilised with increased immunosuppression, he continues to have disease progression in spite of this. CONCLUSIONS: Our cases highlight the importance of a multidisciplinary approach combining immunosuppression with supportive care and judicious use of surgical interventions in select cases. A further review of the literature shows endobronchial obstruction is potentially under-reported due to overlap in connective tissue disease symptomatology and there is no consensus on best practice.
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ItemNo Preview AvailableProgressive pulmonary fibrosis and its impact on survival in systemic sclerosis-related interstitial lung disease(OXFORD UNIV PRESS, 2023-09-19)OBJECTIVE: To describe the frequency of progressive pulmonary fibrosis (PPF) in an incident cohort of systemic sclerosis (SSc) related interstitial lung disease (ILD) and its impact on survival. METHODS: Incident ILD was defined as the new development of characteristic fibrotic changes on chest HRCT scan. PPF was defined as per the 2022 American Thoracic Society. Determinants of PPF were identified using generalised estimating equations. Impact on survival was analysed using accelerated failure time regression modelling. RESULTS: Of our incident SSc-ILD cases, 38.8% (n = 180) experienced PPF within a 12-month period after ILD diagnosis. Determinants of PPF included older age (OR 1.02, 95%CI 1.00-1.03, p= 0.011), dcSSc (OR 1.54, 95% CI 1.06-2.25, p= 0.024) and SSc specific antibodies (anticentomere antibody OR 0.51, 95%CI 0.29-0.91, p= 0.021 and anti-Scl-70 antibody OR 1.46, 95%CI 1.01-2.09, p= 0.043). Raised CRP was numerically associated with PPF but did not reach statistical significance (OR 1.29, 95%CI 0.99-1.68, p= 0.064) nor did GORD or dysphagia (OR 1.18, 95%CI 0.57-2.42, p= 0.658 and OR 1.17, 95%CI 0.57-2.40, p= 0.664 respectively). The presence of PPF significantly impacted survival in SSc-ILD (hazard ratio 2.66, 95%CI 1.59-4.41, p< 0.001). CONCLUSIONS: PPF occurred in a third of our incident SSc-ILD cohort; however, its occurrence was significantly associated with mortality indicating an at-risk group who may be suitable for earlier introduction of immunosuppressive and/or antifibrotic therapy.
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ItemNo Preview AvailableSudden cardiac death, arrhythmias and abnormal electrocardiography in systemic sclerosis: A systematic review and meta-analysis(W B SAUNDERS CO-ELSEVIER INC, 2023-10)OBJECTIVE: To calculate the frequency of sudden cardiac death(SCD), arrhythmia and conduction defects in SSc. METHODS: MEDLINE/EMBASE were searched to January 2023. English-language studies reporting the incidence/frequency of SCD, arrhythmia and electrocardiography(ECG) abnormalities in SSc were included. Odds ratios(OR), estimations of annual incidence or pooled frequencies were calculated. RESULTS: Seventy-nine studies(n = 13,609 participants with SSc) were included in the meta-analysis. Methodology and outcomes were heterogeneous. Ten studies included cohorts with known/suspected SSc-associated heart involvement(SHI), generally defined as clinically-manifest cardiac disease/abnormal cardiac investigations. The incidence of SCD in SHI was estimated to be 3.3% annually(n = 4 studies, 301PY follow-up). On ambulatory ECG, 18% of SHI cohorts had non-sustained ventricular tachycardia(NSVT; n = 4, 95%CI3.2-39.3%), 70% frequent premature ventricular complexes (PVCs; n = 1, 95%CI34.8-93.3%), and 8% atrial fibrillation (AF; n = 1, 95%CI4.2-13.6%). Nineteen studies included participants without SHI, defined as normal cardiac investigations/absence of cardiac disease. The estimated incidence of SCD was approximately 2.9% annually (n = 1, 67.5PY). Compared to healthy controls, individuals without SHI demonstrated NSVT 13.3-times more frequently (n = 2, 95%CI2-102), and paroxysmal supraventricular tachycardia 7-times more frequently (n = 4, 95%CI3-15). Other ambulatory ECG abnormalities included NSVT in 9% (n = 7, 95%CI6-14%), >1000 PVCs/24 h in 6% (n = 2, 95%CI1-13%), and AF in 7% (n = 5, 0-21%). Fifty studies included general SSc cohorts unselected for cardiac disease. The incidence of SCD was estimated to be 2.0% annually(n = 4 studies, 1646PY). Unselected SSc cohorts were 10.5-times more likely to demonstrate frequent PVCs (n = 2, 95%CI 2-59) and 2.5-times more likely to have an abnormal electrocardiography (n = 2, 95%CI1-4). CONCLUSIONS: The incidence of SCD in SSc is estimated to be 1.0-3.3% annually, at least 10-fold higher than general population estimates. Arrhythmias including NSVT and frequent PVCs appear common, including amongst those without known/suspected SHI.
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ItemNo Preview AvailableSystemic sclerosis-associated interstitial lung disease: Diagnostic approaches and challenges(Elsevier BV, 2024-04-01)
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ItemPatterns of Medication Use in Systemic Lupus Erythematosus: A Multicenter Cohort Study(WILEY, 2022-12)OBJECTIVE: Evidence for the utility of medications in settings lacking randomized trial data can come from studies of treatment persistence. The present study was undertaken to examine patterns of medication use in systemic lupus erythematosus (SLE) using data from a large multicenter longitudinal cohort. METHODS: Prospectively collected data from the Asia Pacific Lupus Collaboration cohort including disease activity (SLE Disease Activity Index 2000 [SLEDAI-2K]) and medication details, captured at every visit from 2013-2018, were used. Medications were categorized as glucocorticoids (GCs), antimalarials (AM), and immunosuppressants (IS). Cox regression analyses were performed to determine the time-to-discontinuation of medications, stratified by SLE disease activity. RESULTS: Data from 19,804 visits of 2,860 patients were analyzed. Eight medication categories were observed: no treatment; GC, AM, or IS only; GC plus AM; GC plus IS; AM plus IS; and GC plus AM plus IS (triple therapy). Triple therapy was the most frequent pattern (31.4% of visits); single agents were used in 21% of visits, and biologics in only 3%. Time-to-discontinuation analysis indicated that medication persistence varied widely, with the highest treatment persistence for AM and lowest for IS. Patients with a time-adjusted mean SLEDAI-2K score of ≥10 had lower discontinuation of GCs and higher discontinuation of IS. CONCLUSION: Most patients received combination treatment. GC persistence was high, while IS persistence was low. Patients with high disease activity received more medication combinations but had reduced IS persistence, consistent with limited utility. These data confirm unmet need for improved SLE treatments.
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ItemMultidisciplinary team discussion: the emerging gold standard for management of cardiopulmonary complications of connective tissue disease(WILEY, 2023-10)Cardiopulmonary complications of connective tissue diseases (CTDs), particularly pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD), are major determinants of morbidity and mortality. Multidisciplinary meetings may improve diagnostic accuracy and optimise treatment. We review the literature regarding multidisciplinary meetings in CTD-ILD and PAH and describe our tertiary centre experience of the role of the multidisciplinary meeting in managing CTD-PAH.
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ItemThe Effect of Body Fat Distribution on Systemic Sclerosis(MDPI, 2022-10)Obesity contributes to a chronic proinflammatory state, which is a known risk factor to develop immune-mediated diseases. However, its role in systemic sclerosis (SSc) remains to be elucidated. Therefore, we conducted a two-sample mendelian randomization (2SMR) study to analyze the effect of three body fat distribution parameters in SSc. As instrumental variables, we used the allele effects described for single nucleotide polymorphisms (SNPs) in different genome-wide association studies (GWAS) for SSc, body mass index (BMI), waist-to-hip ratio (WHR) and WHR adjusted for BMI (WHRadjBMI). We performed local (pHESS) and genome-wide (LDSC) genetic correlation analyses between each of the traits and SSc and we applied several Mendelian randomization (MR) methods (i.e., random effects inverse-variance weight, MR-Egger regression, MR pleiotropy residual sum and outlier method and a multivariable model). Our results show no genetic correlation or causal relationship between any of these traits and SSc. Nevertheless, we observed a negative causal association between WHRadjBMI and SSc, which might be due to the effect of gastrointestinal complications suffered by the majority of SSc patients. In conclusion, reverse causality might be an especially difficult confounding factor to define the effect of obesity in the onset of SSc.
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