Functional disability and its predictors in systemic sclerosis: a study from the DeSScipher project within the EUSTAR group.

Objectives: The multisystem manifestations of SSc can greatly impact patients' quality of life. The aim of this study was to identify factors associated with disability in SSc. Methods: SSc patients from the prospective DeSScipher cohort who had completed the scleroderma health assessment questionnaire (SHAQ), a disability score that combines the health assessment questionnaire and five visual analogue scales, were included in this analysis. The effect of factors possibly associated with disability was analysed with multiple linear regressions. Results: The mean SHAQ and HAQ scores of the 944 patients included were 0.87 (s.d. = 0.66) and 0.92 (s.d. = 0.78); 59% of the patients were in the mild to moderate difficulty SHAQ category (0 ⩽ SHAQ < 1), 34% in the moderate to severe disability category (1 ⩽ SHAQ < 2) and 7% in the severe to very severe disability category (2 ⩽ SHAQ ⩽ 3). The means of the visual analogue scales scores were in order of magnitude: overall disease severity (37 mm), RP (31 mm), pulmonary symptoms (24 mm), gastrointestinal symptoms (20 mm) and digital ulcers (19 mm). In multiple regression, the main factors associated with high SHAQ scores were the presence of dyspnoea [modified New York Heart Association (NYHA) class IV (regression coefficient B = 0.62), modified NYHA class III (B = 0.53) and modified NYHA class II (B = 0.21; all vs modified NYHA class I)], FM (B = 0.37), muscle weakness (B = 0.27), digital ulcers (B = 0.20) and gastrointestinal symptoms (oesophageal symptoms, B = 0.16; stomach symptoms, B = 0.15; intestinal symptoms, B = 0.15). Conclusion: SSc patients perceive dyspnoea, pain, digital ulcers, muscle weakness and gastrointestinal symptoms as the main factors driving their level of disability, unlike physicians who emphasize objective measures of disability.

Mapping and predicting mortality from systemic sclerosis.

OBJECTIVES: To determine the causes of death and risk factors in systemic sclerosis (SSc). METHODS: Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation. RESULTS: We identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile. CONCLUSION: Combining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients' survival.

Is there a role for TNFα antagonists in the treatment of SSc? EUSTAR expert consensus development using the Delphi technique.

OBJECTIVES: To obtain experiences and expert opinion on treatment of SSc patients with TNF-α antagonists. METHODS: An investigation was carried out among the EUSTAR centres into their expertise on use of TNF-α antagonists. Assessment forms on the frequency of TNF-α inhibitor use were distributed to EULAR Scleroderma Trials and Research Group (EUSTAR) centres. Afterwards, a three round Delphi exercise was performed to obtain expert consensus on the use of TNF-α inhibitors in SSc. RESULTS: Seventy-nine centres returned information on use of TNF-α antagonists in SSc patients. A total of 65 patients were treated with TNF-α inhibitors in 14 different centres. Forty-eight of the 65 patients treated with TNF-α inhibitors improved. Improvement was mainly seen in patients with arthritis, whereas the effects on fibrosis varied. In the first round of the subsequent Delphi approach, 71 out of 79 experts stated that they would use TNF-α antagonists in SSc. Arthritis was suggested as an indication for TNF-α antagonists by 75% of the experts. However, after the third stage of the Delphi exercise, the acceptance for the off-label use of TNF-α antagonists decreased and 59% recommended that TNF-α antagonists should not be used or only used in clinical trials in SSc patients, while 38% of the experts suggested the use of TNF-α antagonists for arthritis associated with SSc. CONCLUSIONS: Most of the experts do not recommend the routine use of TNF-α antagonists in systemic sclerosis. Arthritis might be a potential indication in SSc, although controlled clinical trials with TNF-α antagonists are needed before general recommendations can be given.

[Antiphospholipid syndrome: from diagnosis to treatment]. / Antifosfolipidni sindrom: od dijagnoze do lijecenja.

Antiphospholipid syndrome (APS) is a prothrombotic disorder mediate with characteristic antiphospholipide antibodies (aPL). Patients with APS have got higher risk for arterial or venous thromboembolism. However, in spite of numerous studies the true association between aPL and first thromboembolism is still unknown. It is not clear whether the presence of aPL is a risk factor for thromboembolism or do they directly take a part in thrombogenesis. Many patients with aPL never experienced thromboembolic event. So far there is not any recommendation for primary prophylaxis of thromboembolic complications in such patients. Guidelines for secondary prevention recommended permanent anticoagulation. In this paper we offer a concise review of the vast body of published work and appropriateness of anticoagulation or antiplatelat therapy in various clinical subcategories of this syndrome.

Predictors of type and site of first acute myocardial infarction in men and women.

BACKGROUND: The importance of pathophysiological mechanisms involved in onset of acute myocardial infarction (AMI) differs with age, gender, and risk profiles. Diversity in the triggering of cardiovascular events has been observed, particularly between men and women. Therefore, we investigated the relationship between age, gender, and risk factors and location of AMI and the presence of Q waves in ECG. PATIENTS AND METHODS: Data was obtained from a chart review of 2958 patients with first AMI: 770 (26%) patients with non-Q-wave AMI and 2188 (74%) patients with Q-wave AMI. Four clinical groups were formed by predetermined criteria (anterior Q-wave, anterior non-Q-wave, inferior Q-wave, inferior non-Q-wave). A logistic regression was performed to assess independent predictors of AMI type and site. RESULTS: Key findings were: 1) inferior non-Q-wave AMI was more frequent in young women (P<0.001); 2) inferior Q-wave AMI was more common in young men (P<0.001); 3) anterior non-Q-wave AMI was more common in older men (P<0.001). Multivariate analysis revealed that independent predictors of anterior non-Q-wave AMI were age over 65 (P=0.002), male gender (P=0.04) and hypercholesterolemia (P=0.0003), and that predictors of inferior Q-wave AMI were male gender (P<0.0001), smoking (P=0.04) and diabetes (P=0.049). In the gender-subgroup analyses, age <45 years (P=0.04), hypecholesterolemia (P=0.02) and smoking (P=0.01) were independent predictors of inferior Q-wave AMI whereas age >65 years (P<0.0001) and smoking (P=0.0003) were predictors of anterior non-Q-wave AMI in men. In women, age <45 years (P<0.0001) and smoking (P=0.02) were independent predictors of non-Q-wave AMI and hypercholesterolemia (P=0.02) was a predictor of inferior Q-wave AMI. CONCLUSION: The link between particular types and the site of AMI and age, gender and risk factors suggest that the importance of pathophysiological mechanisms for onset of AMI differs according to sex and age subgroup.