Nava Ferdowsi

Description:To define the frequency and associations of opioid use in SSc. Australian Scleroderma Cohort Study participants meeting ACR/EULAR criteria for SSc were included. Current or previous opioid use was recorded at each visit, with long-term use defined as use on two or more consecutive visits. Groups were compared using two-sample t-test, Wilcoxon rank sum test or chi-squared test. Generalised estimating equations were used to model longitudinal data. Of 1951 participants with a mean age of 46.7 years (s.d. 14.4), 88% were female and 12% had ever received any opioids since SSc onset. Of these, 46% recorded opioid use across multiple consecutive study visits. Digital ulcers (63% vs 52%), synovitis (57% vs 38%), interstitial lung disease (37% vs 27%), gastrointestinal (GI) symptoms (upper 97% vs 88%, lower 90% vs 80%) and immunosuppression (59% vs 46%) were all more frequent in opioid-exposed groups (P < 0.05). In multivariable modelling, current opioid use at each study visit was associated with digital ulcers [odds ratio (OR) 1.5 (95% CI 1.1, 2.0), P = 0.01], synovitis [OR 1.5 (95% CI 1.1, 2.1), P = 0.02], lower GI symptoms [OR 1.8 (95% CI 1.3, 2.6), P < 0.01] and poorer physical [OR 1.8 (95% CI 1.3, 2.4), P < 0.01] and mental [OR 1.8 (95% CI 1.1, 3.0), P = 0.02] quality of life (QoL). Current opioid use was associated with worse fatigue [regression coefficient (RC) 3.0 units (95% CI 1.2, 4.8), P < 0.01], functional disability [RC 0.2 (95% CI 0.2, 0.3), P < 0.01], dyspnoea [RC 2.0 (95% CI 0.8, 3.1), P < 0.01], depression [RC 2.5 (95% CI 0.9, 4.0), P < 0.01] and anxiety [RC 2.5 (95% CI 0.9, 4.0), P < 0.01]. Opioid use in SSc was associated with musculoskeletal, GI and lung involvement. Opioid prescription was associated with poorer QoL and physical function.

Description:Objective: Physician global assessments (PhyGAs) are variably applied in systemic sclerosis (SSc) clinical trials. The comparability of different PhyGA results is unknown. We sought to assess the comparability of results from three different PhyGA instruments simultaneously applied in the Australian Scleroderma Cohort Study (ASCS). Methods: Using data from 1,965 ASCS participants, we assessed the correlation between results of three PhyGA assessments: (1) overall health, (2) activity, and (3) damage. We evaluated the concordance of change in each PhyGA between study visits. Ordered logistic regression analysis was used to evaluate the clinical associations of each PhyGA. Results: The absolute scores of each PhyGA were strongly correlated at individual study visits. Concordant changes of the PhyGA scores occurred between 50% of study visits. Only patient-reported breathlessness was associated with all three PhyGA scores (overall health: odds ratio [OR] 1.67, P < 0.01; activity: OR 1.44, P < 0.01; damage: OR 1.32, P < 0.01). Changes in physician-assessed activity scores were also associated with patient-reported worsening skin disease (OR 1.25, P = 0.03) and fecal incontinence (OR 1.23, P = 0.01), whereas damage scores were associated with respiratory disease (pulmonary arterial hypertension: OR 1.25, P = 0.03; chronic obstructive pulmonary disease: OR 1.37, P = 0.04), as well as skin scores (OR 1.02, P < 0.01) and fecal incontinence (OR 1.21, P = 0.02). Conclusions: PhyGAs of overall health, activity, and damage are each associated with different SSc features, and changes in different PhyGA scores are discordant 50% of the time. Our findings suggest results of variably worded PhyGAs are not directly interchangeable and support the development of a standardized PhyGA.

Description:Scleroderma renal crisis (SRC) is associated with high morbidity and mortality and there remain unmet needs regarding early identification and treatment. We aimed to assess risk factors for and the outcomes of SRC at a large Australian tertiary hospital. Seventeen incident SRC cases were diagnosed between 2012 and 2022. Demographic, SSc manifestations and treatment data were extracted. Using data from the Australian Scleroderma Cohort Study (n = 483), logistic regression analysis was performed to identify risk factors for SRC. The prevalence of SRC was 3.52%. The median SSc disease duration at SRC onset was 2 years [interquartile range (IQR) 1-4]. Peak creatinine occurred at a median of 11 days (IQR 5-14) post-SRC diagnosis, with a median peak creatinine of 144 µmol/l (IQR 86-306). Nine (52.94%) SRC patients had evidence of acute neurologic and/or cardiac complications. Acute haemofiltration was required in 3 (17.65%) patients. Over the follow-up period, 7 (41.18%) SRC patients died 2.75 years (IQR 0.74-7.25) after SRC onset. Patients with SRC were more likely to be male [odds ratio (OR) 9.73 (95% CI 3.57, 26.56)], have diffuse disease [OR 23.16 (95% CI 5.22, 102.80)] and have antibodies to Scl70 [OR 3.34 (95% CI 1.24, 9.04)] or RNA polymerase III (RNAPIII) [OR 5.15 (95% CI 1.91, 13.89)]. SRC is an uncommon manifestation, but outcomes remain poor. A significant proportion of patients presenting with SRC in Australia are positive for Scl70 or RNAPIII antibody. Despite relatively low peak serum creatinine and rates of renal replacement therapy, SRC was still associated with significant mortality.

Description:Objective: The aim of this study was to determine the impact of season, temperature and humidity on the severity of Raynaud phenomenon (RP) in systemic sclerosis. Methods: Data from the Australian Scleroderma Cohort Study were used to assess associations of patient-reported worsened RP in the month preceding each study visit. Mean monthly weather data were obtained from the closest weather station to the patient's address. We evaluated the relationship between worsened RP and health-related quality of life (HRQoL) measured using the Short Form 36 instrument. Results: Among 1,972 patients with systemic sclerosis, RP was a near-universal finding, and worsened RP in the preceding month was reported in 26.7% of 9,175 visits. "Worsened RP" showed significant environmental variability. On multivariable analysis, worsened RP was associated with low mean maximum temperatures (odds ratio [OR] 0.91, 95% confidence interval [95% CI] 0.90-0.92, P < 0.001), high relative humidity (OR 1.05, 95% CI 1.04-1.05, P < 0.001) and lower mean daily evaporation (OR 0.77, 95% CI 0.73-0.81, P < 0.001). Worsened RP was strongly associated with telangiectasia, calcinosis, and digital ulceration, as well as demonstrating an association with anticentromere antibody and gastroesophageal reflux disease and a negative correlation with diffuse disease. Worsened RP was also strongly associated with worse HRQoL. Conclusions: Lower environmental temperature and higher relative humidity had significant associations with worsened RP in this systemic sclerosis cohort, suggesting an important role for dry warmth in managing this condition.

Description:Background: To determine the relationship between gastroesophageal reflux disease (GORD) and its treatment and interstitial lung disease in patients with systemic sclerosis (SSc). Methods: SSc patients from the Australian Scleroderma Cohort Study (ASCS) were included. GORD was defined as self-reported GORD symptoms, therapy with a proton pump inhibitor (PPI) or histamine 2 receptor antagonist (H2RA) and/or the presence of reflux oesophagitis diagnosed endoscopically. The impact of GORD and its treatment on ILD features (including severity and time to ILD development) and survival was evaluated. Results: GORD was a common manifestation affecting 1539/1632 (94%) of SSc patients. GORD affected 450/469 (96%) of those with SSc-ILD cohort. In SSc-ILD, there was no relationship between the presence of GORD or its treatment and time to ILD development or ILD severity. However, GORD treatment was associated with improved survival in those with ILD (p = 0.002). Combination therapy with both a PPI and a H2RA was associated with a greater survival benefit than single agent therapy with PPI alone (HR 0.3 vs 0.5 p < 0.050 respectively). Conclusions: GORD is a common SSc disease manifestation. While the presence or treatment of GORD does not influence the development or severity of ILD, aggressive GORD treatment, in particular with a combination of PPI and H2RA, is associated with improved survival in those with SSc-ILD.