Reports of abnormal cervical cancer screening tests in systemic sclerosis.

OBJECTIVE: To assess the prevalence of abnormal cervical cancer screening (Pap tests) reported by women with SSc onset before the age of 50 yrs. METHODS: Female members of a Canadian multi-centre SSc cohort completed standardized assessments and were questioned regarding a history of an abnormal Pap test. Potential correlates examined included demographics, reproductive history, smoking, diffuse vs limited SSc type, immunosuppressant exposure and SSc duration. RESULTS: In the 320 women with SSc onset before the age of 50 yrs, the life-time prevalence of an abnormal Pap test (according to self-report) was 25.4% (95% CI CI 20.9, 30.4%). By comparison, self-reported prevalence of abnormal Pap tests among general population Canadian females was recently reported at 13.8% (95% CI 11.6, 16.4%). Women with diffuse SSc (n = 142), tended to have a higher prevalence of self-reported cervical dysplasia (31.7%) compared with those with limited disease (20.7%), but the CIs overlapped. A multivariate logistic regression found a significant positive association between self-reported abnormal Pap test and diffuse disease [odds ratio (OR) 1.87; 95% CI 1.01, 3.47]. An independent association of an abnormal Pap test with smoking (OR 2.43; 95% CI 1.23, 4.78) and with younger age at disease onset was also noted. CONCLUSIONS: We noted a high prevalence of abnormal Pap tests self-reported in our sample. Increased risk was seen among those with diffuse SSc, and also among smokers and those with a younger age at disease onset. Thus, it seems prudent to ensure that adequate attention is paid to cervical cancer screening for women with SSc.

A comparison of the frequency of antibodies to cyclic citrullinated peptides using a third generation anti-CCP assay (CCP3) in systemic sclerosis, primary biliary cirrhosis and rheumatoid arthritis.

The objective was to investigate the frequency of anti-cyclic citrullinated peptides (CCP) antibodies in systemic sclerosis (SSc) and primary biliary cirrhosis (PBC), utilizing a new "third generation" anti-CCP ELISA (anti-CCP3) kit and a conventional anti-CCP2 assay. Patients with PBC, SSc, RA, and normal controls were included in the study. Serum samples were screened for autoantibodies by indirect immunofluorescence (IIF), antibodies to CCP by a second- and third-generation ELISA, antibodies to "scleroderma" antigens (CENP B, Scl-70, PM/Scl and fibrillarin-Scl-34) by a line immunoassay (LIA), and IgM RF by ELISA. The frequency of anti-CCP2 antibodies in SSc and PBC samples was 14.8% (11/74) and 6.2% (5/80), respectively, and the frequency of anti-CCP3 antibodies in SSc was 13.5% (10/74) and in PBC was 3.7% (3/80). By comparison, in the RA group the frequency of anti-CCP3 and anti-CCP2 antibodies was 79.1% (38/48) and 77% (37/48), respectively. Anti-CCP3 ELISA had a sensitivity, specificity, and positive and negative likelihood ratios (LR) of 79% (95% confidence interval [CI] = 64-89%), 93% (95% CI = 88-96%), 11.8 (95% CI = 6.8-20.3), and 0.22 (95% CI = 0.12-0.38), respectively. By comparison, the anti-CCP2 assay had a sensitivity, specificity, and positive and negative LRs of 77% (95% CI = 62-87), 90% (95% CI = 85-94), 8.3 (95% CI = 5.2-13.2), and 0.25 (95% CI = 0.15-0.42), respectively. In patients with SSc, there was an association of anti-CCP2 antibodies with the presence of arthritis, but there was no association of anti-CCP2 or anti-CCP3 with anti-CENP B, anti-Scl 70, or RF. This study confirmed the high specificity and sensitivity of both anti-CCP assays for the diagnosis of RA. The presence of anti-CCP antibodies in SSc was only correlated with the presence of arthritis.

The relationship of dyspnoea to function and quality of life in systemic sclerosis.

AIM: Up to 50% of patients with systemic sclerosis (SSc) have complaints of dyspnoea. We evaluated the independent contributions of dyspnoea to function and health related quality of life (HRQoL) in SSc and also assessed the contributions of pulmonary hypertension, measured by the pulmonary artery systolic pressure (PASP), and interstitial lung disease, measured by the forced vital capacity (FVC), to dyspnoea. METHODS: We assessed dyspnoea, PASP, FVC, function and HRQoL in a cohort of unselected patients with SSc. Multiple linear regression was used to assess the independent contributions of dyspnoea, PASP and FVC to function and HRQoL, after controlling for possible confounding variables. RESULTS: A total of 194 patients with mean disease duration of 11.6 years were studied. Dyspnoea was a significant independent predictor of function and HRQoL. A model including age, gender, disease duration, disease severity and dyspnoea explained 33.3%, 10.6%, 39.2% and 29.4% of the variance of the Stanford Health Assessment Questionnaire, the Short-Form 36 (SF-36) mental component summary score, the SF-36 physical component summary score and the World Health Organization Disability Assessment Schedule II. PASP and FVC were significant independent predictors of dyspnoea but only 21.9% of the variance in dyspnoea was explained by age, gender, disease duration, FVC and PASP. The FVC was a significant independent predictor of function and HRQoL. CONCLUSION: In an unselected population of SSc patients, dyspnoea is a very important contributor to function and HRQoL. Interstitial lung disease, as measured by the FVC, contributes significantly to the sense of dyspnoea, function and HRQoL in SSc. Pulmonary hypertension, assessed echocardiographically by the PASP, predicts the degree of dyspnoea but not function and HRQoL in SSc.

Review of calls to NHS Direct related to attendance in the paediatric emergency department.

OBJECTIVE: To examine the outcomes of calls to NHS Direct (NHS-D) in relation to attendance at the accident and emergency (A&E) department. DESIGN: A prospective collection of data about consecutive calls to NHS-D North West Coast was matched with attendances at the A&E department over a period of 3 months. SETTING: NHS-D Regional Trust and a large urban paediatric A&E department. PATIENTS: Children and young adults aged <16 years living in local postal code areas. MAIN OUTCOME MEASURES: To examine (1) whether advice given by NHS-D was followed and (2) the differences in disease severity and necessity of attendance of patients referred by NHS-D and those referred by general practitioners and self-presenters. RESULTS: The relationship between the advice given and subsequent action is complex. Only 70% of calls advised to attend the A&E department did so. A further 1% (176) were advised not to attend the A&E department did in fact attend the department. Patients referred by NHS-D represented only 3.2% of department attendances. There was little difference in the triage categories of the presenting groups, but there were significantly less admissions (p<0.01) in the NHS-D group. CONCLUSIONS: Delivering telephone advice about illness severity in children is difficult as visual clues are so important. More collaborative prospective studies are needed, including with primary care, to understand families' choices, and to refine and assess NHS-D's ability to discriminate those requiring further clinical assessment.

A randomized, controlled trial of methotrexate versus placebo in early diffuse scleroderma.

OBJECTIVE: Early diffuse scleroderma (systemic sclerosis; SSc) has no proven treatment. This study was undertaken to examine the efficacy of methotrexate (MTX) in improving the skin and other disease parameters in early diffuse SSc. METHODS: Seventy-one patients with diffuse SSc of <3 years' duration were enrolled in a multicenter, randomized, placebo-controlled, double-blind trial. Thirty-five patients were treated with MTX and 36 with placebo. Treatment was administered for 12 months. The primary outcome measures were skin score (as determined with 2 different indices) and physician global assessment. RESULTS: At baseline, there were no statistically significant differences in skin scores, carbon monoxide diffusing capacity (DLco), physician global assessment, or other secondary outcome measurements between the 2 treatment groups. At study completion, results slightly favored the MTX group (mean +/- SEM modified Rodnan skin score 21.4+/-2.8 in the MTX group versus 26.3+/-2.1 in the placebo group [P < 0.17]; UCLA skin score 8.8+/-1.2 in the MTX group versus 11.0+/-0.9 in the placebo group [P < 0.15]; DLco in the MTX group 75.7+/-4.6 versus 61.8+/-3.4 in the placebo group [P < 0.2]). In addition, physician global assessment results favored MTX (P < 0.035), whereas patient global assessment did not differ significantly between groups. When between-group differences for changes in scores from baseline to 12 months were examined using intent-to-treat methodology, MTX appeared to have a favorable effect on skin scores (modified Rodnan score -4.3 in the MTX group versus 1.8 in the placebo group [P < 0.009]; UCLA score -1.2 in the MTX group versus 1.2 in the placebo group [P < 0.02]), but differences in the degree of change in the DLco and physician global assessment were not significant. For the UCLA skin score, these differences in results were not statistically significant after adjustment for baseline differences in sex distribution and steroid use. Dropout rates were similar in the 2 groups. CONCLUSION: Although results of this trial demonstrated a trend in favor of MTX versus placebo in the treatment of early diffuse SSc, the between-group differences were small and the power to rule out false-negative results was only 50%. Our findings do not provide evidence that MTX is significantly effective in the treatment of early diffuse SSc.