Peter Nash

University of the Sunshine Coast, Gold Coast, Queensland, Australia

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Publications (66)405.44 Total impact

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    ABSTRACT: IntroductionThere 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.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, positive (PPV) and negative predictive values (NPV) for PAH. These properties were also evaluated in an `alternate scenario analysis¿ where the prevalence of PAH was set at 10%.ResultsRHC revealed PAH in 27 (36.9%) patients. 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 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 of 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.
    Arthritis Research & Therapy 01/2015; 17(1):7. DOI:10.1186/s13075-015-0517-5 · 4.12 Impact Factor
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    ABSTRACT: Axial involvement in patients with psoriatic arthritis (PsA) remains common and can be defined in terms of spinal disease alone or in combination with peripheral manifestations. Diagnosis is based upon inflammatory spinal symptoms or the presence of radiological sacroiliitis and other radiographic signs of spondylitis, or by criteria for axial spondyloarthritis (SpA) defined by ASAS (Assessment of SpondyloArthritis International Society). Although recent data are scarce for efficacy of traditional therapies for axial disease (e.g., nonsteroidal antiinflammatory drugs, methotrexate, etc.), limited data are available for targeted biologics and novel agents. We identify and evaluate the efficacy of therapeutic interventions for treatment of axial disease in PsA. This review is an update of the axial PsA section of the treatment recommendations project by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).
    The Journal of Rheumatology 11/2014; 41(11):2286-2289. DOI:10.3899/jrheum.140877 · 3.17 Impact Factor
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    ABSTRACT: IntroductionThe aim of the study was to interrogate the genetic architecture and autoimmune pleiotropy of scleroderma susceptibility in the Australian population.Methods We genotyped individuals from a well-characterized cohort of Australian scleroderma patients with the Immunochip, a custom array enriched for single nucleotide polymorphisms (SNPs) at immune loci. Controls were taken from the 1958 British Birth Cohort. After data cleaning and adjusting for population stratification the final dataset consisted of 486 cases, 4,458 controls and 146,525 SNPs. Association analyses were conducted using logistic regression in PLINK. A replication study was performed using 833 cases and 1938 controls.ResultsA total of 8 loci with suggestive association (P <10-4.5) were identified, of which 5 showed significant association in the replication cohort (HLA-DRB1, DNASE1L3, STAT4, TNP03-IRF5 and VCAM1). The most notable findings were at the DNASE1L3 locus, previously associated with systemic lupus erythematosus, and VCAM1, a locus not previously associated with human disease. This study identified a likely functional variant influencing scleroderma susceptibility at the DNASE1L3 locus; a missense polymorphism rs35677470 in DNASE1L3, with an odds ratio of 2.35 (P¿=¿2.3¿×¿10¿10) in anti-centromere antibody (ACA) positive cases.Conclusions This pilot study has confirmed previously reported scleroderma associations, revealed further genetic overlap between scleroderma and systemic lupus erythematosus, and identified a putative novel scleroderma susceptibility locus.
    Arthritis Research & Therapy 10/2014; 16(5):438. DOI:10.1186/s13075-014-0438-8 · 4.12 Impact Factor
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    ABSTRACT: Objective. Investigate the safety of long-term subcutaneous (SC) abatacept using integrated clinical trial data in patients with rheumatoid arthritis refractory to traditional disease-modifying antirheumatic drugs.Methods. Data from the double-blind and open-label periods of five SC abatacept clinical trials were pooled. Overall and 6-monthly incidence rates (IRs) were calculated as events/100 patient-years (pt-yrs) of exposure.Results. This analysis included 1879 patients with 4214.6 pt-yrs of SC abatacept exposure. Mean (standard deviation) exposure was 27.3 (9.1) months. Serious infections were reported at an IR (95% confidence interval) of 1.79 (1.42, 2.24); the most frequent being pneumonia (0.36 [0.22, 0.59]), urinary tract infection (0.14 [0.06, 0.32]), and gastroenteritis (0.10 [0.04, 0.25]). Tuberculosis occurred rarely (IR 0.09 [0.04, 0.25]). Malignancies were reported at an IR of 1.32 (1.01, 1.72), the most frequent being solid organ malignancy (IR 0.69 [0.46, 0.99]). Autoimmune events occurred at an IR of 1.37 (1.06, 1.78), the most frequent being psoriasis (IR 0.33 [0.20, 0.56]), and Sjögren's syndrome (IR 0.24 [0.13, 0.44]). Local injection-site reactions (ISRs) were reported at an IR of 1.72 (1.36, 2.17), primarily during the first 6 months; 69/70 were of mild or moderate intensity. IRs for serious infections, malignancies, autoimmune events, and ISRs did not increase over time.Conclusion. Long-term SC abatacept treatment was associated with low IRs of serious infections, malignancies and autoimmune events, and was well tolerated with infrequent ISRs. Findings are consistent with observations of intravenous abatacept. Long-term treatment did not lead to new safety signals over time. © 2014 American College of Rheumatology.
    08/2014; 66(8). DOI:10.1002/art.38687
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    ABSTRACT: Assess longterm tolerability, safety, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate-refractory patients with rheumatoid arthritis (RA). The phase III, multinational Abatacept Comparison of Sub[QU]cutaneous Versus Intravenous in Inadequate Responders to MethotrexatE (ACQUIRE) trial comprised a 6-month, randomized, double-blind (DB) period, in which patients received intravenous (IV) or SC ABA, plus MTX, followed by an open-label, longterm extension (LTE), in which patients received SC ABA, 125 mg/week. Safety and efficacy from the LTE (~3.5 yrs of exposure) are reported. Patients who completed the DB period (1372/1385, 99.1%) entered the LTE; 1134 patients (82.7%) kept taking the treatment at time of reporting. Mean (SD) was 31.9 months (6.8); median (range) exposure was 33.0 (8-44) months. Patients entering the LTE had longstanding, moderate-to-severe disease [mean 7.6 (7.9) yrs and DAS28 (C-reactive protein) 6.2 (0.9)]. Incidence rates (events/100 patient-yrs) were reported for serious adverse events (8.76, 95% CI 7.71, 9.95), infections (44.80, 95% CI 41.76, 48.01), serious infections (1.72, 95% CI 1.30, 2.27), malignancies (1.19, 95% CI 0.86, 1.66), and autoimmune events (1.31, 95% CI 0.95, 1.79). Twenty-seven patients (2%) experienced injection-site reactions; all except 1 were mild. American College of Rheumatology 20, 50, and 70 responses achieved during the DB period were maintained through the LTE, and on Day 981 were 80.2% (95% CI 77.2, 83.2), 63.5% (95% CI 58.2, 68.9), and 39.5% (95% CI 34.0, 44.9) for patients who kept taking SC ABA, and 80.0% (95% CI 77.0, 83.0), 63.2% (95% CI 57.8, 68.7), and 39.2% (95% CI 33.7, 44.7) for those who switched from IV to SC ABA. These findings support SC ABA as a well-tolerated and efficacious longterm treatment for patients with RA and inadequate response to MTX (ClinicalTrials.gov identifier NCT00559585).
    The Journal of Rheumatology 03/2014; 41(4). DOI:10.3899/jrheum.130112 · 3.17 Impact Factor
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    ABSTRACT: To determine the prevalence and correlates of antiphospholipid antibodies (APLA) in systemic sclerosis (SSc). Nine hundred and forty SSc patients were tested for APLA using an ELISA assay at recruitment. Clinical manifestations were defined as present, if ever present from SSc diagnosis. Logistic regression analysis was used to determine the associations of APLA. One or more types of APLA were present in 226 (24.0%) patients. Anticardiolipin (ACA) IgG (ACA-IgG) antibodies were associated with right heart catheter-diagnosed pulmonary arterial hypertension (PAH), with higher titres corresponding with a higher likelihood of PAH (moderate titre (20-39 U/ml) ACA-IgG odds ratio [OR] 1.70, 95% CI: 1.01-2.93, p=0.047; high titre (>40 U/ml) ACA-IgG OR 4.60, 95% CI:1.02-20.8, p=0.047). Both ACA-IgM (OR 2.04, 95% CI: 1.4-3.0, p<0.0001) and ACA-IgG (OR 1.84, 95% CI: 1.2-2.8, p=0.005) were associated with interstitial lung disease (ILD). Increasing ACA-IgM and IgG titres were associated with increased likelihood of ILD. ACA-IgG was a marker of coexistent pulmonary hypertension and ILD (ILD-PH) (OR 2.10, 95% CI: 1.1-4.2, p=0.036). We also found an association between ACA-IgG and digital ulcers (OR 1.76, 95% CI: 1.16-2.67, p=0.008) and ACA-IgM and Raynaud's phenomenon (OR 2.39, 95% CI: 1.08-5.27, p=0.031). There was no association between APLA and SSc disease subtype, peak skin score, presence of other autoantibodies, mortality or other disease manifestations. The association of APLA with PAH, ILD, ILD-PH, Raynaud's phenomenon and digital ulcers suggests that endothelial abnormalities and small vessel thrombosis may be important in the pathogenesis of these disease features.
    Clinical and experimental rheumatology 02/2014; · 2.97 Impact Factor
  • Annals of the Rheumatic Diseases 01/2014; 71(Suppl 3):670-670. DOI:10.1136/annrheumdis-2012-eular.567 · 9.27 Impact Factor
  • Annals of the Rheumatic Diseases 01/2014; 72(Suppl 3):A432-A432. DOI:10.1136/annrheumdis-2013-eular.1305 · 9.27 Impact Factor
  • Annals of the Rheumatic Diseases 01/2014; 71(Suppl 3):234-235. DOI:10.1136/annrheumdis-2012-eular.2200 · 9.27 Impact Factor
  • Annals of the Rheumatic Diseases 01/2014; 71(Suppl 3):155-155. DOI:10.1136/annrheumdis-2012-eular.1970 · 9.27 Impact Factor
  • Annals of the Rheumatic Diseases 01/2014; 72(Suppl 3):A886-A886. DOI:10.1136/annrheumdis-2013-eular.2645 · 9.27 Impact Factor
  • Peter Nash, Dave Nicholls
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    ABSTRACT: To improve treatment for rheumatoid arthritis (RA), rheumatologists have embraced patient-reported outcomes; however, limited data are available on patient perceptions of treatment. Our objective was to assess the use and perceptions of methotrexate (MTX) by patients with RA (primary objective) and their rheumatologists, patient-reported adverse events (AEs) related to MTX, and patient-reported use of alcohol, folic acid and biologic agents. Each rheumatologist completed a rheumatologist questionnaire and then asked patients with RA to complete a patient questionnaire. Questionnaires were completed by 46/50 rheumatologists and 1313/1313 patients. Patients (72% female, 38% > 10 years RA) took oral MTX regularly (72% never miss a dose) and at therapeutic doses. Most patients (79%) were currently taking MTX, but 36% of patients were on low doses (≤ 10 mg/week) and 8% intentionally and regularly did not take MTX. Most patients had a positive perception of MTX; 82% of patients considered MTX to be important; 60% preferred to continue taking MTX. Although AEs (generally mild and gastrointestinal) occurred regularly (38%) and in some patients continuously (13%), 41% of patients did not experience an AE. Patients abstained from alcohol (46%) and took folic acid (91%, but with variable dosage regimens and doses). There were 29% of patients taking biologic agent therapy; only 70% of these patients were also taking MTX. MTX was well used, well tolerated and well perceived. However, to ensure that MTX therapy is as effective as possible, rheumatologists should discuss MTX use with their patients and consider alternative strategies for some patients.
    International Journal of Rheumatic Diseases 12/2013; 16(6):652-61. DOI:10.1111/1756-185X.12183 · 1.65 Impact Factor
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    ABSTRACT: Pulmonary arterial hypertension (PAH) is a major cause of mortality in systemic sclerosis (SSc). Screening guidelines for PAH recommend multiple investigations, including annual echocardiography, which together have low specificity and may not be cost-effective. We sought to evaluate the predictive accuracy of serum N-Terminal pro-brain natriuretic peptide (NT-proBNP) in combination with pulmonary function tests (PFT) ('proposed' algorithm) in a screening algorithm for SSc-PAH. We evaluated our proposed algorithm (PFT with NTproBNP) on 49 consecutive SSc patients with suspected pulmonary hypertension undergoing right heart catherisation (RHC). The predictive accuracy of the proposed algorithm was compared with existing screening recommendations, and is presented as sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Overall, 27 patients were found to have pulmonary hypertension (PH) at RHC, while 22 had no PH. The sensitivity, specificity, PPV and NPV of the proposed algorithm for PAH was 94.1%, 54.5%, 61.5% and 92.3%, respectively; current European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines achieved a sensitivity, specificity, PPV and NPV of 94.1%, 31.8%, 51.6% and 87.5%, respectively. In an alternate case scenario analysis, estimating a PAH prevalence of 10%, the proposed algorithm achieved a sensitivity, specificity, PPV and NPV for PAH of 94.1%, 54.5%, 18.7% and 98.8% , respectively. The combination of NT-proBNP with PFT is a sensitive, yet simple and non-invasive screening strategy for SSc-PAH. Patients with a positive screening result can be referred for echocardiography, and further confirmatory testing for PAH. In this way, it may be possible to shift the burden of routine screening away from echocardiography. The findings of this study should be confirmed in larger studies.
    Arthritis research & therapy 11/2013; 15(6):R193. DOI:10.1186/ar4383 · 4.12 Impact Factor
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    ABSTRACT: Objective To assess 2-year golimumab efficacy/safety in patients with active rheumatoid arthritis (RA) who had never taken methotrexate (MTX). MethodsRA patients who had never taken MTX (n = 637) were randomized (1:1:1:1) to placebo + MTX (group 1), golimumab 100 mg + placebo (group 2), golimumab 50 mg + MTX (group 3), or golimumab 100 mg + MTX (group 4) every 4 weeks. Nonresponders based on week 28 swollen/tender joint counts changed treatment as follows: group 1 added golimumab 50 mg, group 2 added MTX, group 3 increased golimumab to 100 mg, and group 4 had no change. Most group 1 patients (85%) initiated golimumab 50 mg + MTX at week 28 or subsequently at week 52. After the last patient completed week 52 and blinding was broken, the investigator could escalate golimumab to 100 mg and/or adjust MTX. The co–primary end points (week 24 American College of Rheumatology criteria for 50% improvement [ACR50] response and week 52 change in Sharp/van der Heijde score [SHS]) have been published previously. We now detail week 52 major secondary end points (Health Assessment Questionnaire [HAQ] disability index [DI] scores and SHS among patients with a baseline C-reactive protein [CRP] level >1.0 mg/dl) and week 104 findings. ResultsAt week 52 for combined groups 3 and 4 versus group 1, the respective proportions of patients achieving ACR20 and ACR50 responses were 63.2% versus 51.9% (P = 0.017) and 45.3% versus 35.6% (P = 0.044). Respective week 52 mean HAQ DI improvements were 0.70 versus 0.58 (P = 0.053); mean SHS changes were 0.41 versus 1.37 (P = 0.006) among all patients and 0.74 versus 2.16 (P = 0.003) in patients with a CRP level >1.0 mg/dl. Improvements were maintained through week 104. Golimumab + MTX for 2 years yielded statistically less radiographic progression than initial MTX or golimumab 100 mg monotherapy. Golimumab safety profiles through weeks 24, 52, and 104 were generally consistent with those observed in other golimumab studies. Conclusion In RA patients who had never taken MTX, up to 2 years of golimumab + MTX yielded sustained improvements in clinical signs/symptoms, physical function, and radiographic progression.
    11/2013; 65(11). DOI:10.1002/acr.22072
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    ABSTRACT: Objective To evaluate the impact of concomitant methotrexate (MTX) on subcutaneous (SC) abatacept immunogenicity, and to assess safety and efficacy. Methods This phase III, open-label study had a 4-month short-term (ST) period and an ongoing long-term extension (LTE) period. Rheumatoid arthritis patients were stratified to receive SC abatacept (125 mg/week) with (combination) or without MTX (monotherapy), with no intravenous loading dose; patients receiving monotherapy could add MTX in the LTE period. Immunogenicity (percentage of anti-abatacept antibody–positive patients) was assessed. ST and LTE period data are reported, including efficacy through LTE month 14 and safety through LTE month 20. ResultsNinety-six of 100 enrolled patients completed the ST period; 3.9% (combination) and 4.1% of patients (monotherapy) developed transient immunogenicity, and no patients were antibody positive at month 4. Serious adverse events (SAEs) were reported in 3.9% (combination) and 6.1% of patients (monotherapy); 5.9% (combination) and 8.2% of patients (monotherapy) experienced SC injection reactions, and all were mild in intensity. Mean 28-joint Disease Activity Score (DAS28) changes were −1.67 (95% confidence interval [95% CI] −2.06, −1.28; combination) and −1.94 (95% CI −2.46, −1.42; monotherapy) at month 4. Ninety patients entered and were treated in the LTE period; 83.3% (75 of 90) remained ongoing at month 24. One LTE-treated patient (1.1%) developed immunogenicity, 14.4% of patients experienced SAEs, and no SC injection reactions were reported. For patients entering the LTE period, mean DAS28 changes from baseline were −1.84 (95% CI −2.23, −1.34; combination) and −2.86 (95% CI −3.46, −2.27; monotherapy) at month 18. ConclusionSC abatacept did not elicit immunogenicity associated with loss of safety or efficacy, either with or without MTX.
    05/2013; 65(5). DOI:10.1002/acr.21876
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    ABSTRACT: Objective The purpose of this 24-month phase III study was to examine structural preservation with tofacitinib in patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX). Data from a planned 12-month interim analysis are reported. Methods In this double-blind, parallel-group, placebo-controlled study, patients receiving background MTX were randomized 4:4:1:1 to tofacitinib at 5 mg twice daily, tofacitinib at 10 mg twice daily, placebo to tofacitinib at 5 mg twice daily, and placebo to tofacitinib at 10 mg twice daily. At month 3, nonresponder placebo-treated patients were advanced in a blinded manner to receive tofacitinib as indicated above; remaining placebo-treated patients were advanced at 6 months. Four primary efficacy end points were all analyzed in a step-down procedure. ResultsAt month 6, response rates according to the American College of Rheumatology 20% improvement criteria for tofacitinib at 5 mg and 10 mg twice daily were higher than those for placebo (51.5% and 61.8%, respectively, versus 25.3%; both P < 0.0001). At month 6, least squares mean (LSM) changes in total modified Sharp/van der Heijde score for tofacitinib at 5 mg and 10 mg twice daily were 0.12 and 0.06, respectively, versus 0.47 for placebo (P = 0.0792 and P ≤ 0.05, respectively). At month 3, LSM changes in the Health Assessment Questionnaire disability index score for tofacitinib at 5 mg and 10 mg twice daily were –0.40 (significance not declared due to step-down procedure) and –0.54 (P < 0.0001), respectively, versus –0.15 for placebo. At month 6, rates of remission (defined as a value
    Arthritis & Rheumatology 03/2013; 65(3). DOI:10.1002/art.37816 · 7.48 Impact Factor
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    ABSTRACT: BACKGROUND: Clinical remission and low disease activity are essential treatment targets in patients with rheumatoid arthritis. Although moderately active rheumatoid arthritis is common, treatment effects in moderate disease have not been well studied. Additionally, optimum use of biologics needs further investigation, including the use of induction, maintenance, and withdrawal treatment strategies. The aim of the PRESERVE trial was to assess whether low disease activity would be sustained with reduced doses or withdrawal of etanercept in patients with moderately active disease. METHODS: In a randomised controlled trial, patients aged between 18 and 70 years with moderately active rheumatoid arthritis (disease activity score in 28 joints [DAS28] >3·2 and ≤5·1) despite treatment with methotrexate were enrolled at 80 centres in Europe, Latin America, Asia, and Australia between March 6, 2008, and Sept 9, 2009. To be eligible, patients had to have been receiving 15-25 mg of methotrexate every week for at least 8 weeks. In an open-label period of 36 weeks, all patients were given 50 mg etanercept plus methotrexate every week. To be eligible for a subsequent double-blind period of 52 weeks, participants had to have achieved sustained low disease activity. These patients were randomly assigned (1:1:1) by an interactive voice-response system to one of three treatment groups: 50 mg etanercept plus methotrexate, 25 mg etanercept plus methotrexate, or placebo plus methotrexate. Patients were stratified in blocks of three by DAS28 response (low disease activity or remission) at week 36. Patients, investigators, data analysts, and study staff were all masked to treatment allocation. The primary endpoint was the proportion of patients with low disease activity at week 88 in the groups given 50 mg etanercept or placebo in the double-blind period. A conditional primary endpoint was the proportion of patients receiving 25 mg etanercept who achieved low disease activity. Modified intention-to-treat populations were used for analyses. This trial is registered with ClinicalTrials.gov, number NCT00565409. FINDINGS: 604 (72·4%) of 834 enrolled patients were eligible for the double-blind period, of whom 202 were assigned to 50 mg etanercept plus methotrexate, 202 to 25 mg etanercept plus methotrexate, and 200 to placebo plus methotrexate. At week 88, 166 (82·6%) of 201 patients who had received at least one dose of 50 mg etanercept and one or more DAS28 evaluations had low disease activity, compared with 84 (42·6%) of 197 who had received placebo (mean difference 40·8%, 95% CI 32·5-49·1%; p<0·0001). Additionally, 159 (79·1%) of 201 patients given 25 mg etanercept had low disease activity at week 88 (mean difference from placebo 35·9%, 27·0-44·8%; p<0·0001). INTERPRETATION: Conventional or reduced doses of etanercept with methotrexate in patients with moderately active rheumatoid arthritis more effectively maintain low disease activity than does methotrexate alone after withdrawal of etanercept. FUNDING: Pfizer.
    The Lancet 01/2013; DOI:10.1016/S0140-6736(12)61811-X · 39.21 Impact Factor
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    ABSTRACT: Objectives. In a multi-centre study, we sought to determine whether extent of disease on high-resolution CT (HRCT) lung, reported using a simple grading system, is predictive of decline and mortality in SSc-related interstitial lung disease (SSc-ILD), independently of pulmonary function tests (PFTs) and other prognostic variables.Methods. SSc patients with a baseline HRCT performed at the time of ILD diagnosis were identified. All HRCTs and PFTs performed during follow-up were retrieved. Demographic and disease-related data were prospectively collected. HRCTs were graded according to the percentage of lung disease: >20%: extensive; <20%: limited; unclear: indeterminate. Indeterminate HRCTs were converted to limited or extensive using a forced vital capacity threshold of 70%. The composite outcome variable was deterioration (need for home oxygen or lung transplantation), or death.Results. Among 172 patients followed for mean (s.d.) of 3.5 (2.9) years, there were 30 outcome events. In Weibull multivariable hazards regression modelling, baseline HRCT grade was independently predictive of outcome, with an adjusted hazard ratio (aHR) = 3.0, 95% CI 1.2, 7.5 and P = 0.02. In time-varying covariate models (based on 1309 serial PFTs and 353 serial HRCTs in 172 patients), serial diffusing capacity of the lung for carbon monoxide by alveolar volume ratio (ml/min/mmHg/l) (aHR = 0.4; 95% CI 0.3, 0.7; P = 0.001) and forced vital capacity (dl) (aHR = 0.9; 95% CI 0.8, 0.97; P = 0.008), were also strongly predictive of outcome.Conclusion. Extensive disease (>20%) on HRCT at baseline, reported using a semi-quantitative grading system, is associated with a three-fold increased risk of deterioration or death in SSc-ILD, compared with limited disease. Serial PFTs are informative in follow-up of patients.
    Rheumatology (Oxford, England) 10/2012; DOI:10.1093/rheumatology/kes289 · 4.44 Impact Factor
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    ABSTRACT: OBJECTIVE: To develop new composite disease activity indices for psoriatic arthritis (PsA). METHODS: Data from routine clinic visits at multiple centres were collected in a systematic manner. Data included all domains identified as important in randomised controlled trials in PsA. Decisions to change treatment were used as surrogates for high disease activity. New indices were developed by multiple linear regression (psoriatic arthritis disease activity score: PASDAS) and empirically, utilising physician-defined cut-offs for disease activity (arithmetic mean of desirability functions: AMDF). These were compared with existing composite measures: Composite Psoriatic arthritis Disease Activity Index (CPDAI), Disease Activity for PSoriatic Arthritis (DAPSA), and Disease Activity Score for rheumatoid arthritis (DAS28). RESULTS: 161/503 (32%) subjects had treatment changes. Although all measures performed well, compared with existing indices, PASDAS was better able to discriminate between high and low disease activity (area under receiver operating curves (ROC)) curve with 95% CI: PASDAS 0.773 (0.723, 0.822); AMDF 0.730 (0.680, 0.780); CPDAI 0.719 (0.668, 0.770); DAPSA 0.710 (0.654, 0.766); DAS28 0.736 (0.680, 0.792). All measures were able to discriminate between disease activity states in patients with oligoarthritis, although area under the receiver operating curves (AUC) were generally smaller. In patients with severe skin disease (psoriasis area and severity index >10) both nonparametric and AUC curve statistics were nonsignificant for all measures. CONCLUSIONS: Two new composite measures to assess disease activity in PsA have been developed. Further testing in other datasets, including comparison with existing measures, is required to validate these instruments.
    Annals of the rheumatic diseases 07/2012; DOI:10.1136/annrheumdis-2012-201341 · 9.27 Impact Factor
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    ABSTRACT: Pulmonary arterial hypertension is a major cause of mortality in systemic sclerosis. N-terminal pro-brain natriuretic peptide (NT-proBNP) has emerged as a candidate biomarker that may enable the early detection of systemic sclerosis-related pulmonary arterial hypertension (SSc-PAH). The objective of our study was to incorporate NT-proBNP into a screening algorithm for SSc-PAH that could potentially replace transthoracic echocardiography (TTE) as a more convenient and less costly "first tier" test. NT-proBNP levels were measured in patients from four clinical groups: a group with right heart catheter (RHC)-diagnosed SSc-PAH before commencement of therapy for PAH; a group at high risk of SSc-PAH based on TTE; a group with interstitial lung disease; and systemic sclerosis (SSc) controls with no cardiopulmonary complications. NT-proBNP levels were compared by using ANOVA and correlated with other clinical variables by using simple and multiple linear regression. ROC curve analyses were performed to determine the optimal cut point for NT-proBNP and other clinical variables in prediction of PAH. NT-proBNP was highest in the PAH group compared with other groups (P < 0.0001), and higher in the risk group compared with controls (P < 0.0001). NT-proBNP was positively correlated with systolic pulmonary artery pressure (PAP) on TTE (P < 0.0001), and mean PAP (P = 0.013), pulmonary vascular resistance (P = 0.005), and mean right atrial pressure (P = 0.006) on RHC. A composite model wherein patients screened positive if NT-proBNP was ≥ 209.8 pg/ml, and/or DLCOcorr was < 70.3% with FVC/DLCOcorr ≥ 1.82, had a sensitivity of 100% and specificity of 77.8% for SSc-PAH. We have proposed a screening algorithm for SSc-PAH, incorporating NT-proBNP level and PFTs. This model has high sensitivity and specificity for SSc-PAH and, if positive, should lead to TTE and confirmatory testing for PAH. This screening algorithm must be validated prospectively.
    Arthritis research & therapy 06/2012; 14(3):R143. DOI:10.1186/ar3876 · 4.12 Impact Factor

Publication Stats

2k Citations
405.44 Total Impact Points

Institutions

  • 2013
    • University of the Sunshine Coast
      Gold Coast, Queensland, Australia
  • 2008–2013
    • University of Queensland 
      • Department of Medicine
      Brisbane, Queensland, Australia
  • 2003–2013
    • Nambour General Hospital
      Намбор, Queensland, Australia
  • 2011
    • University of Melbourne
      • Department of Medicine
      Melbourne, Victoria, Australia
  • 2010
    • Université René Descartes - Paris 5
      Lutetia Parisorum, Île-de-France, France
    • University of California, Los Angeles
      • Division of Rheumatology
      Los Angeles, CA, United States
  • 2009
    • Medical University of Bialystok
      Belostok, Podlasie, Poland
  • 2007
    • German Rheumatism Research Centre
      Berlín, Berlin, Germany
  • 2005
    • University of Utah
      Salt Lake City, Utah, United States
    • Ruhr-Universität Bochum
      Bochum, North Rhine-Westphalia, Germany