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1.
Arthritis Res Ther ; 21(1): 299, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31870459

RESUMO

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.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31740961

RESUMO

OBJECTIVE: To quantify the burden of interstitial lung disease (ILD) in SSc. METHODS: Clinical data for SSc patients enrolled in the Australian Scleroderma Cohort Study were linked with healthcare databases for the period 2008-2015. ILD was defined by characteristic fibrotic changes on high-resolution CT (HRCT) lung, while severity was defined by the extent lung involvement on HRCT (mild <10%, moderate 10-30%, severe >30%). Determinants of healthcare cost were estimated using logistic regression. RESULTS: SSc-ILD patients utilized more healthcare resources, including hospitalization, emergency department presentation and ambulatory care services, than those without ILD with a total cost per patient of AUD$48 368 (26 230-93 615) vs AUD$33 657 (15 144-66 905), P<0.001) between 2008-2015. Healthcare utilization was associated with an annual median (25th-75th) excess cost per SSc-ILD patient compared with those without ILD of AUD$1192 (807-1212), P<0.001. Increasing ILD severity was associated with significantly more healthcare utilization and costs with an annual excess cost per patient with severe ILD compared with mild ILD of AUD$2321 (645-1846), P<0.001. ILD severity and the presence of coexistent PAH were the main determinants of overall healthcare cost above median for this SSc-ILD cohort (OR 5.1, P<0.001, and OR 2.6, P=0.01, respectively). Furthermore, SSc-ILD patients reported worse physical HRQoL compared with those without ILD [34.3 (10.5) vs 39.1 (10.8), P<0.001], with a progressive decline with increasing ILD severity (P=0.002). CONCLUSION: SSc-ILD places a large burden on the healthcare system and the patient through poor HRQoL in addition to incremental healthcare resource utilization and associated direct cost.

3.
BMC Pulm Med ; 19(1): 226, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775705

RESUMO

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.

4.
Nat Commun ; 10(1): 4955, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672989

RESUMO

Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.

5.
Sci Rep ; 9(1): 14834, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619697

RESUMO

Fibrosis across different organs and tissues is likely to share common pathophysiological mechanisms and pathways. Recently, a polymorphism (rs12979860) near the interferon lambda gene (IFNL3) was shown to be associated with fibrosis in liver across multiple disease etiologies. We determined whether this variant is a risk factor for pulmonary fibrosis (PF) and worsening cutaneous fibrosis in systemic sclerosis (SSc). Caucasian patients with SSc (n = 733) were genotyped to test for association with the presence of PF and worsening of skin fibrosis. Serum IFN-λ3 levels from 200 SSc cases were evaluated. An association of the IFNL3 polymorphism with PF was demonstrated (OR: 1.66 (95% CI: 1.142-2.416, p = 0.008). The IFNL3 variant was not a risk factor for worsening of skin fibrosis. Functionally, IFN-λ3 serum levels were higher among subjects with PF compared to those unaffected (P < 0.0001). In conclusion, IFNL3 serum levels and the genetic variant known to be associated with liver fibrosis are similarly linked to PF, but not to worsening of skin fibrosis in SSc. These data highlight both common fibrosis pathways operating between organs, as well as differential effects within the same disease.

6.
Australas J Dermatol ; 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31612996

RESUMO

Hydroxychloroquine is an age-old drug whose use as an immunomodulatory agent with a low side-effect profile continues to expand. We present a review of this drug including recently updated prescribing recommendations and a summary of its clinical application in dermatology. A maximum daily dose of 5.0 mg/kg based on actual body weight and no greater than 400 mg is advised in order to reduce the risk of retinopathy, which is potentially permanent and has an estimated prevalence of 7.5% at 5 years on standard dosing. Baseline ophthalmologic assessment followed by annual screening after 5 years is recommended; however, closer monitoring should be considered in the setting of existing retinopathy, a cumulative dose > 1000 g or renal dysfunction. Hydroxychloroquine is now considered to be safe in pregnancy, and routine glucose-6-phosphate dehydrogenase (G6PD) deficiency testing is not required. Smoking can significantly decrease its efficacy although the reason is still uncertain. Hydroxychloroquine appears to also demonstrate antineoplastic and cardioprotective benefits.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31539207

RESUMO

OBJECTIVE: To quantify the burden of cancer in systemic sclerosis (SSc). METHODS: Standardized incidence ratios (SIR) and mortality ratios (SMR) relative to the general Australian population were derived. Cox proportional hazards regression was used to estimate survival in SSc patients with cancer compared to those without. Determinants of cancer were identified using logistic regression. Healthcare cost was quantified through cross-jurisicational data linkage. RESULTS: This SSc cohort of 1,727 had cancer incidence of 1.3% per annum and prevalence of 14.2%, with SIR of 2.15 (93%CI 1.84-2.49). The most common cancers were breast, melanoma, hematological and lung. RNAP III antibody was associated with increased risk of cancer (OR 2.9. p=0.044), diagnosed within five years of SSc disease onset. Calcium channel blockers were associated with a higher risk of overall cancer (OR 1.47,p=0.016), breast cancer (OR 1.61, p=0.051) and melanoma (OR 2.01, p=0.042). Interstitial lung disease (ILD) was associated with lung cancer (OR 2.83, p=0.031). Incident SSc cancer patients had more than a two-fold increased mortality compared to SSc patients without cancer [HR 2.85 (95%CI 1.51-5.37), p=0.001). SSc cancer patients utilized more healthcare than those without cancer with an excess annual healthcare cost of AUD$1,496 (p<0.001). CONCLUSION: SSc carries an increased risk of developing cancer, particularly lung cancer associated with ILD, and breast cancer and melanoma occurring close to SSc disease onset in association with RNAP III antibodies. Compared to those without cancer, SSc cancer patients had higher mortality and increased healthcare cost with an annual excess per patient cost of AUD$1,496 (p<0.001).

9.
Artigo em Inglês | MEDLINE | ID: mdl-31421031

RESUMO

OBJECTIVE: To evaluate the association between patient-reported symptoms and changes in disease activity over time in systemic sclerosis (SSc). METHODS: Using data from 1,636 patients enrolled in the Australian Scleroderma Cohort Study, we used generalised estimating equations to determine the relationship between patient-reported worsening of Raynaud phenomenon (RP), skin involvement and breathlessness in the month preceding each study visit and features of disease activity in the corresponding organ systems. The associations between the following parameters were analysed: patient-reported worsening RP and the presence of new-onset digital pitting and digital ulcers; patient-reported worsening skin involvement and increasing modified Rodnan skin score (mRSS), new areas of skin involvement and new-onset joint contractures; patient-reported worsening breathlessness and deteriorating respiratory functions tests (RFTs), indicated by 10% decrease in forced vital capacity (FVC) and 15% decrease in diffusing capacity of carbon monoxide (DLCO), new-onset interstitial lung disease (ILD) and new-onset pulmonary arterial hypertension (PAH). RESULTS: We found a significant association between patient-reported worsening RP and the presence of digital ulcers (OR 1.53; 95%CI:0.60-0.93); patient-reported worsening skin involvement and increasing mRSS (OR 2.10; 95%CI:1.54-2.86); and worsening patient breathlessness and deteriorating RFTs (FVC OR 2.12; 95%CI:1.70-2.65; DLCO OR 1.97; 95%CI:1.34-2.02), new-onset ILD (OR 1.91; 95%CI:1.40-2.61) and new-onset PAH (OR 5.08; 95%CI:3.59-7.19). CONCLUSION: These results demonstrate that patient-reported symptoms are associated with clinically meaningful changes in disease activity in SSc patients. This suggests that when objective measures of change in disease status are unavailable, patient-reported symptoms could be used to indicate a change in SSc-disease activity.

10.
BMJ Open ; 9(7): e029406, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31272981

RESUMO

OBJECTIVE: To measure the trade-off between risk of complications versus patient improvement in pain and function in orthopaedic surgeons' decisions about whether to undertake total knee arthroplasty (TKA). METHODS: A discrete choice experiment asking surgeons to make choices between experimentally-designed scenarios describing different levels of operative risk and dimensions of pain and physical function. Variation in preferences and trade-offs according to surgeon-specific characteristics were also examined. RESULTS: The experiment was completed by a representative sample of 333 orthopaedic surgeons (n=333): median age 52 years, 94% male, 91% fully qualified. Orthopaedic surgeons were willing to accept substantial increases in absolute risk associated with TKA surgery for greater improvements in a patient's pain and function. The maximum risk surgeons were willing to accept was 40% for reoperation and 102% for the need to seek further treatment from a general practitioner or specialist in return for a change from postoperative severe night-time pain at baseline to no night-time pain at 12 months. With a few exceptions, surgeon-specific characteristics were not associated with how much risk a surgeon is willing to accept in a patient undergoing TKA. CONCLUSION: This is the first study to quantify risk-benefit trade-offs among orthopaedic surgeons performing TKA, using a discrete choice experiment. This study provides insight into the risk tolerance of surgeons.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31282076

RESUMO

OBJECTIVE: Treat to target endpoints for Systemic Lupus Erythematosus (SLE) have been assessed for impact on damage accrual and flare, but whether they impact on the high healthcare utilization and costs in SLE has not been studied. We hypothesized that the recently described lupus low disease activity state (LLDAS) would be associated with reduced healthcare cost. METHODS: Data from a single tertiary hospital longitudinal SLE cohort were assessed. Baseline demographics, disease activity (SLE Disease Activity Index (SLEDAI)-2K; physician global assessment, PGA; and, flare index) and medication use were evaluated, and direct healthcare utilization and cost data were obtained from hospital information systems. LLDAS was defined as previously published: briefly, SLEDAI-2K ≤ 4 with no new activity, PGA ≤ 1, prednisolone ≤7.5mg/day, and optimal standard immunosuppressive agents. Analysis was performed using multivariable linear regression. RESULTS: Two hundred SLE patients, contributing 357.8 person-years observation, were included. A history of lupus nephritis was present in 42%, and damage (SLICC-ACR damage index >0) was present at study commencement in 57.3%. The mean (±standard deviation) annual direct medical cost per patient was US$7,413 (±US$13,133)/year. In multivariable analysis, increased cost was associated with the presence of baseline organ damage (41.7% increase, P=0.009), and corticosteroid use (>7.5-15 mg/day, 55.7% increase, P=0.02; > 15 mg/day, 202% increase, P<0.001). In contrast, spending ≥50% of the observation period in LLDAS was associated with a 25.9% reduction in annual direct medical cost (p=0.04). CONCLUSION: Greater time spent in LLDAS was associated with significantly reduced direct hospital healthcare costs among patients with SLE. This article is protected by copyright. All rights reserved.

14.
Intern Med J ; 49(6): 781-785, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31185523

RESUMO

Pulmonary arterial hypertension is an important cause of death and disability in patients with systemic sclerosis (SSc). Yearly screening of all SSc patients with transthoracic echocardiography (TTE) is recommended in international guidelines and currently utilised by the Australian Scleroderma Interest Group (ASIGSTANDARD ). Owing to the limitations of TTE, the ASIG developed a new screening algorithm (ASIGPROPOSED ) utilising a serum biomarker, NT-proBNP, in place of TTE, which has been shown to be equally accurate as the current algorithm. The aim of this study was to compare the cost of these two algorithms using different scenarios. The new algorithm resulted in significant yearly cost savings of between AU$42 913.35 and AU$84 570 in screening and diagnosis of an Australian cohort which, if extrapolated to the Australian population, would result in a yearly cost saving of between AU$367 066 and AU$725 564. There was no scenario in which the proposed algorithm did not result in a cost saving.

15.
J Rheumatol ; 46(6): 548-549, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31154442
18.
Ann Rheum Dis ; 78(6): 807-816, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30928903

RESUMO

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.

19.
J Scleroderma Relat Disord ; 4(1): 17-27, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30906878

RESUMO

The Scleroderma Clinical Trials Consortium (SCTC) represents many of the clinical researchers in the world who are interested in improving the efficiency of clinical trials in Systemic Sclerosis (SSc). The SCTC has established 11 working groups (WGs) to develop and validate better ways of measuring and recording multiple aspects of this heterogeneous disease. These include groups working on arthritis, disease damage, disease activity, cardiac disease, juvenile SSc, the gastrointestinal tract, vascular component, calcinosis, scleroderma renal crisis, interstitial lung disease, and skin measurement. Members of the SCTC may join any one or more of these groups. Some of the WGs have only recently started their work, some are nearing completion of their mandated tasks and others are in the midst of their projects. All these projects, which are described in this paper, will help to improve clinical trials and observational studies by improving or developing better, more sensitive ways of measuring various aspects of the disease. As Lord Kelvin stated, "To measure is to know. If you cannot measure it you cannot improve it." The SCTC is dedicated to improving the lives of patients with SSc and it is our hope that the contributions of the WGs will be one important step in this process.

20.
Arthritis Res Ther ; 21(1): 57, 2019 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-30764870

RESUMO

BACKGROUND: Up to 12% of patients with systemic sclerosis (SSc) have anti-neutrophil cytoplasmic antibodies (ANCA). However, the majority of these patients do not manifest ANCA-associated vasculitis (AAV) and the significance of ANCA in these patients is unclear. The aim of this study is to determine the prevalence of ANCA in a well-characterised SSc cohort and to examine the association between ANCA and SSc clinical characteristics, other autoantibodies, treatments and mortality. METHODS: Clinical data were obtained from 5 centres in the Australian Scleroderma Cohort Study (ASCS). ANCA positive was defined as the presence of any one or combination of cytoplasmic ANCA (c-ANCA), perinuclear ANCA (p-ANCA), atypical ANCA, anti-myeloperoxidase (anti-MPO) or anti-proteinase-3 (anti-PR3). Associations of demographic and clinical features with ANCA were investigated by logistic or linear regression. Survival analysis was performed using Kaplan-Meyer curves and Cox regression models. RESULTS: Of 1303 patients, 116 (8.9%) were ANCA positive. Anti-PR3 was more common than anti-MPO (13.8% and 11.2% of ANCA-positive patients, respectively). Only 3 ANCA-positive patients had AAV. Anti-Scl-70 was more common in ANCA positive vs ANCA negative (25% vs 12.8%, p < 0.001), anti-MPO positive vs anti-MPO negative (38.5% vs 13.6%, p = 0.006) and anti-PR3 positive vs anti-PR3 negative patients (44.4% vs 13.4%, p < 0.001). A higher prevalence of interstitial lung disease (ILD) was found in the ANCA positive (44.8% vs 21.8%, p < 0.001) and the anti-PR3 positive groups (50.0% vs 23.4%, p = 0.009). In multivariable analysis, ANCA-positive status remained associated with ILD after adjusting for anti-Scl-70 antibodies. Pulmonary embolism (PE) was more common in ANCA-positive patients (8.6% vs 3.0%, p = 0.002) and anti-PR3-positive patients (16.7% vs 3.3%, p = 0.022). ANCA-positive status remained associated with PE in a multivariable analysis adjusting for anti-phospholipid antibodies. Kaplan-Meier analysis revealed increased mortality in ANCA-positive patients (p = 0.006). In Cox regression analysis, ANCA was associated with increased mortality, after adjusting for age and sex. CONCLUSIONS: ANCA is associated with increased prevalence of ILD and PE in SSc. ANCA should be tested in SSc, as it identifies individuals with worse prognosis who require close monitoring for adverse outcomes.

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