Improved survival in limited scleroderma-related pulmonary artery hypertension

Reportedly, patients with scleroderma-related pulmonary hypertension (SSc-PAH) respond poorly to new vasoactive drugs (NVD). Forty-nine SSc-PAH patients underwent right heart catheterization (RHC) and, according to NVD availability, divided as follows: Group 1 (n = 23, from 1999 to 2004, poor availability), and Group 2 (n = 26, from 2005 to 2010, good availability). Before diagnostic RHC, NVD had been given to 30 % of the patients in Group 1, and 58 % of those in Group 2 (p = 0.049). At diagnosis, patients in Group 1 had greater heart dilatation (p < 0.01), higher mean pulmonary artery pressure (p < 0.05), lower pulmonary artery capacitance (p < 0.05), and lower carbon monoxide lung diffusing capacity (DLco, p < 0.05) than those in Group 2. At a median follow-up time of 15.5 months, DLco further decreased in Group 1 (p < 0.05), whereas cardiac index increased in Group 2 (p < 0.05). At 36 months of follow-up, 72.4 % of the patients in Group 2 were still alive as opposed to 30.4 % in Group 1 (p = 0.02). In multivariate analysis, DLco and mixed venous oxygen saturation (SvO₂) were independent predictors of survival. A value of DLco <7.2 mL/mmHg/min was associated with a hazard ratio (HR) of 5.3 (p < 0.001); for SvO₂ <63.8 %, the HR was 3.7 (p < 0.01).NVD have beneficial effects in patients with SSc-PAH. Both DLco and SvO₂ are predictors of survival and may assist in planning treatment.     

Contribution of a new, rapid, quantitative and automated method for D-dimer measurement to exclude deep vein thrombosis in symptomatic outpatients.

Ninety-nine consecutive outpatients with symptoms suggestive of deep vein thrombosis (DVT) were tested for the presence of D-dimer using a new, rapid method (BC D-Dimer) based on the agglutination principle and performed on a BCT analyzer. Dimertest Gold EIA and VIDAS D-Dimer devices were used as comparative methods. Venography was performed in all patients, with DVT diagnosed in 39 of them (34 proximal). The BC D-Dimer test proved to be rapid, automated and well suited for individual tests with a good reproducibility (coefficient of variation % 1.5-5.3). Its performance was comparable with that of the other methods, as indicated by the areas under the receiver operating characteristic curves (Gold EIA 0.95; VIDAS 0.95; BC D-Dimer 0.91) and the coefficients of correlation (Pearson's coefficients from 0.832 to 0.876). On the basis of the Kappa coefficients, there was quite a good concordance between the three tests. At the cut-off levels that provided the highest sensitivity (97.4%, for all the tests), the negative predictive values were similar for all methods, at over 95%. The corresponding specificity ranged from 62.7 to 81.7%. In conclusion, this study shows that the new method can be included in prospective clinical trials to test the utility of D-dimer measurement in combination with other non-invasive diagnostic procedures in the management of the diagnosis of DVT.     

Immunomodulatory effects of statins and autoimmune rheumatic diseases: novel intracellular mechanism involved

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, known as statins, are the most commonly prescribed agents for the treatment of hypercholesterolemia. However, the effects of statins may extend beyond their influences on serum cholesterol levels resulting in cholesterol-independent or pleiotropic effects. Clinical, animal and in vitro studies suggest that statins have additional clinical uses because of their anti-inflammatory and immunomodulatory effects, in part due to their capacity to interfere with the mevalonate pathway and inhibit prenylation of Rho family GTPases. This review focuses on the molecular mechanisms of the anti-inflammatory and immunomodulatory effects of statins. In base to all these information, we suggest that statins could have similar inhibitory effects on MAPKs pathways in cells from RA patients, including osteoclasts and fibroblasts.     

Risk of venous thromboembolism recurrence: high negative predictive value of D-dimer performed after oral anticoagulation is stopped

In some patients with previous venous thromboembolism (VTE) D-dimer levels (D-Dimer) tend to increase after oral anticoagulant therapy (OAT) is stopped. The aim of our study was to evaluate the predictive value of D-Dimer for the risk of VTE recurrence after OAT withdrawal. After a first episode of deep vein thrombosis (DVT) of the lower limbs and/or pulmonary embolism (PE), 396 patients (median age 67 years, 198 males) were followed from the day of OAT discontinuation for 21 months. D-dimer was measured on the day of OAT withdrawal (T1), 3-4 weeks (T2) and 3 months (+/- 10 days, T3) thereafter. The main outcome events of the study were: objectively documented recurrent DVT and/or PE. D-dimer was found to be increased in 15.5%, 40.3% and 46.2% of the patients at T1, T2 and T3, respectively. In 199 (50.2%) patients, D-dimer levels were elevated in at least one measurement. During a follow-up of 628.4 years, 40 recurrences were recorded (10.1% of patients; 6.4% patient-years of follow-up). D-dimer was increased in at least one measurement in 28 of these cases, but remained normal in 11 subjects (three of whom had recurrent events triggered by circumstantial factors, three with malignancy-associated factors) (in one subject D-dimer was not measured). The negative predictive value (NPV) of D-dimer was 95.6% (95% CI 91.6-98.1) at T3 and was even higher (96.7%; 95% CI 92.9-98.8) after exclusion of the six recurrences due to circumstantial factors. Only five idiopathic recurrences occurred in the 186 patients with consistently normal D-dimer. In conclusion, D-dimer has a high NPV for VTE recurrence when performed after OAT discontinuation.     

The Po River Delta epidemiological study: use of medicines in a general population sample of north Italy

Purpose —To provide information on the actual use of medicines in a general population sample. Methods —Information was collected in a general population sample of North Italy (1946 subjects; 938 males, 1008 females) by an interviewer‐administered questionnaire. Results —Of the subjects 25.9% took habitually at least one medicine, whereas 11.1% used medicaments only occasionally. The use of medicines was significantly higher in females than in males (p < 0.001), but only in 15–44‐year‐old females, because of the use of oral contraceptives. The use of medicines increased with ageing (OR=1.80, p < 0.001). The highest use of habitual medicaments was found in subjects of 55+ years of both sexes. In both sexes, the medicines classified in the cardiovascular therapeutic group were the most frequently used. The use of gastrointestinal and cardiovascular medicines was significantly higher in males than in females (p < 0.001). In males, the use of habitual medicines was significantly (p < 0.001) higher in current smokers and ex‐smokers than in never smokers. Only 23% of allergic subjects used antiallergic medicines, and only 35% of subjects with respiratory symptoms/diseases used medicines classified into the bronchopulmonary therapeutic group. The percentage of subjects who reported cardiovascular symptoms/diseases and used medicines classified in the cardiovascular therapeutic group was greater (62%). Conclusions —We stress the importance of data collection in general population samples by questionnaires to investigate the actual use of medicines. This may give a more accurate estimate of medicine use than is possible from pharmacy sales or hospital records. Copyright © 2000 John Wiley & Sons, Ltd.