Peter Youssef

Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia

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Publications (9)20.16 Total impact

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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; · 2.66 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. · 4.27 Impact Factor
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    ABSTRACT: Rituximab is one of nine biologic agents approved for the treatment of rheumatoid arthritis (RA) in Australia. The primary study objective was to analyze the factors that lead to the therapeutic decision to use rituximab in RA. A cross-sectional, retrospective chart review was conducted to identify patients who were treated with rituximab and to evaluate their response to treatment. Factors influencing the prescription of rituximab were identified. The most commonly reported reason for prescribing rituximab was the presence of comorbidities and the presence of seropositive disease. Median rituximab treatment duration was 32.5 months and mean number of treatment cycles was 4.1. Disease activity scores showed significant improvement from baseline to most recent visit. Rituximab treatment was well-tolerated in this group of RA patients. Rituximab was effective in a refractory group of RA patients and appears to be safe in a population with a high prevalence of comorbidities, including malignancy and recurrent infections/bronchiectasis. This study may assist rheumatologists in selecting appropriately targeted therapy in RA.
    International Journal of Rheumatic Diseases 10/2013; · 1.65 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; · 4.24 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. · 4.27 Impact Factor
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    ABSTRACT: Background:  Pulmonary arterial hypertension (PAH) is an increasingly recognised serious illness with insidious onset, often delayed diagnosis, complex diagnostic algorithms and poor prognosis, but with recently available effective treatments. In order to efficiently diagnose and offer treatment for PAH, we established a multidisciplinary service in 2005, where patients attend a clinic staffed by specialists in cardiology, respiratory medicine, rheumatology and immunology in a tertiary referral hospital setting. Methods:  We studied the first 200patients referred. Serology, echocardiography, lung function tests, high resolution computerised tomography, World Health Organisation (WHO) Class determination and 6-min walk tests and/or right heart catheterisation (RHC) were performed, as clinically indicated. Results:  Of 200 patients seen, 66 had confirmed pulmonary hypertension (mean PAP >25mmHg) diagnosed on echocardiography ± RHC. Of these, 58 had catheter-proven PAH (mean PAP>25mmHg with mean wedge pressure < 15mmHg). Underlying diagnoses for the confirmed PAH patients were idiopathic (32), scleroderma-associated (14), other connective tissue disease (4), and those associated with congenital heart disease (8). Patients with confirmed PAH were commenced on PAH-specific therapy - initially Bosentan in the majority but Sildenafil, and Iloprostwere occasionally used initially for patient-specific reasons. Median time from when the patient first called the clinic to prescription of therapy was 16 days (IQR; 0-31 days). All surviving patients with PAH have attended for regular 6-monthly follow-up visits with a 100% retention rateup to 4 years. Conclusion:  A multidisciplinary clinic can provide efficient diagnosis and rapid triage to PAH-specific therapy, if appropriate. Retention rates remain high, at follow-up.
    Internal Medicine Journal 10/2011; · 1.82 Impact Factor
  • Heart Lung and Circulation - HEART LUNG CIRC. 01/2009; 18.
  • Heart Lung and Circulation - HEART LUNG CIRC. 01/2009; 18.
  • Heart Lung &amp Circulation 19:S2. · 1.25 Impact Factor