IRM cardiaque en évolution: de grandes études multicentriques en 2012 [Cardiac MR in development: the large multicenter CMR studies in 2012].

The results of several large multicenter CMR studies were reported in 2012, thus, constantly corroborating the evidence on CMR performance. In this review, we present results of the MR-IMPACT programme and the CE-MARC study, which demonstrated the superiority of perfusion-CMR over gated SPECT for the workup of suspected CAD, the currently available data from the European CMR registry, comprising almost 30,000 patients from 57 participating centers in 15 European countries, and finally, the results of the Advisa-MRI study, which documented the safety of a MRI-compatible pacemaker system. These large trials and others set the basis for the recommendations in the new European guidelines on heart failure to use CMR as a first line method if echocardiographic quality is inadequate or the etiology of heart failure is unclear.

Rheumatic fever: a multicenter study in the State of São Paulo

Rheumatic fever is still the most commonly seen rheumatic disease in Brazilian pediatric rheumatology clinics. It remains a significant health problem since subsequent cardiac sequelae represent one of the most important causes of chronic heart disease in children. We reviewed the clinical manifestations of rheumatic fever in 786 patients, followed at seven pediatric rheumatology clinics in the state of São Paulo, Brazil. All patients were diagnosed according to revised Jones' criteria. Regarding major criteria, 396 (50.4%) children exhibited carditis, 453 (57.6%) polyarthritis, 274 (34.8%) chorea, 13 (1.6%) erythema marginatum, and 12 (1.5%) subcutaneous nodules. Valvular lesions documented by echocardiography in the absence of accompanying auscultatory findings were found in 144 (18.3%) patients. Migratory polyarthritis was observed in 290 (64.0%) patients with articular involvement. Documented previous streptococcal infection assessed by serum antistreptolysin (ASO) titers occurred in 531 (67.5%) patients. Even though prophylaxis with benzathine penicillin was recommended to all patients, recurrent attacks were observed in 147 (18.7%). We emphasize the high frequency of chorea, silent carditis and recurrences in our series as well as the variable clinical presentation of arthritis in rheumatic fever. Multicenter studies should be encouraged to improve our understanding of the clinical features of rheumatic diseases in children and adolescents.

Graph based study of allergen cross-reactivity of plant lipid transfer proteins (LTPs) using microarray in a multicenter study.

The study of cross-reactivity in allergy is key to both understanding. the allergic response of many patients and providing them with a rational treatment In the present study, protein microarrays and a co-sensitization graph approach were used in conjunction with an allergen microarray immunoassay. This enabled us to include a wide number of proteins and a large number of patients, and to study sensitization profiles among members of the LTP family. Fourteen LTPs from the most frequent plant food-induced allergies in the geographical area studied were printed into a microarray specifically designed for this research. 212 patients with fruit allergy and 117 food-tolerant pollen allergic subjects were recruited from seven regions of Spain with different pollen profiles, and their sera were tested with allergen microarray. This approach has proven itself to be a good tool to study cross-reactivity between members of LTP family, and could become a useful strategy to analyze other families of allergens.

Response to methylphenidate by adult and pediatric patients with attention-deficit/hyperactivity disorder: the Spanish multicenter DIHANA study.

BACKGROUND The purpose of this multicenter Spanish study was to evaluate the response to immediate-release methylphenidate by children and adults diagnosed with attention-deficit/hyperactivity disorder (ADHD), as well as to obtain information on current therapy patterns and safety characteristics. METHODS This multicenter, observational, retrospective, noninterventional study included 730 patients aged 4-65 years with a diagnosis of ADHD. Information was obtained based on a review of medical records for the years 2002-2006 in sequential order. RESULTS The ADHD predominantly inattentive subtype affected 29.7% of patients, ADHD predominantly hyperactive-impulsive was found in 5.2%, and the combined subtype in 65.1%. Overall, a significant lower Clinical Global Impression (CGI) score and mean number of DSM-IV TR (Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision) symptoms by subtype were found after one year of treatment with immediate-release methylphenidate; CGI decreased from 4.51 to 1.69, symptoms of inattention from 7.90 to 4.34, symptoms of hyperactivity from 6.73 to 3.39, and combined subtype symptoms from 14.62 to 7.7. Satisfaction with immediate-release methylphenidate after one year was evaluated as "very satisfied" or "satisfied" by 86.90% of the sample; 25.75% of all patients reported at least one adverse effect. At the end of the study, 41.47% of all the patients treated with immediate-release methylphenidate were still receiving it, with a mean time of 3.80 years on therapy. CONCLUSION Good efficacy and safety results were found for immediate-release methylphenidate in patients with ADHD.

Neurological complications of infective endocarditis: risk factors, outcome, and impact of cardiac surgery: a multicenter observational study.

BACKGROUND The purpose of this study was to assess the incidence of neurological complications in patients with infective endocarditis, the risk factors for their development, their influence on the clinical outcome, and the impact of cardiac surgery. METHODS AND RESULTS This was a retrospective analysis of prospectively collected data on a multicenter cohort of 1345 consecutive episodes of left-sided infective endocarditis from 8 centers in Spain. Cox regression models were developed to analyze variables predictive of neurological complications and associated mortality. Three hundred forty patients (25%) experienced such complications: 192 patients (14%) had ischemic events, 86 (6%) had encephalopathy/meningitis, 60 (4%) had hemorrhages, and 2 (1%) had brain abscesses. Independent risk factors associated with all neurological complications were vegetation size ≥3 cm (hazard ratio [HR] 1.91), Staphylococcus aureus as a cause (HR 2.47), mitral valve involvement (HR 1.29), and anticoagulant therapy (HR 1.31). This last variable was particularly related to a greater incidence of hemorrhagic events (HR 2.71). Overall mortality was 30%, and neurological complications had a negative impact on outcome (45% of deaths versus 24% in patients without these complications; P<0.01), although only moderate to severe ischemic stroke (HR 1.63) and brain hemorrhage (HR 1.73) were significantly associated with a poorer prognosis. Antimicrobial treatment reduced (by 33% to 75%) the risk of neurological complications. In patients with hemorrhage, mortality was higher when surgery was performed within 4 weeks of the hemorrhagic event (75% versus 40% in later surgery). CONCLUSIONS Moderate to severe ischemic stroke and brain hemorrhage were found to have a significant negative impact on the outcome of infective endocarditis. Early appropriate antimicrobial treatment is critical, and transitory discontinuation of anticoagulant therapy should be considered.

Rationale and design of a randomized, double-blind, placebo controlled multicenter trial to study efficacy, security, and long term effects of intermittent repeated levosimendan administration in patients with advanced heart failure: LAICA study.

BACKGROUND Advanced heart failure (HF) is associated with high morbidity and mortality; it represents a major burden for the health system. Episodes of acute decompensation requiring frequent and prolonged hospitalizations account for most HF-related expenditure. Inotropic drugs are frequently used during hospitalization, but rarely in out-patients. The LAICA clinical trial aims to evaluate the effectiveness and safety of monthly levosimendan infusion in patients with advanced HF to reduce the incidence of hospital admissions for acute HF decompensation. METHODS The LAICA study is a multicenter, prospective, randomized, double-blind, placebo-controlled, parallel group trial. It aims to recruit 213 out-patients, randomized to receive either a 24-h infusion of levosimendan at 0.1 μg/kg/min dose, without a loading dose, every 30 days, or placebo. RESULTS The main objective is to assess the incidence of admission for acute HF worsening during 12 months. Secondarily, the trial will assess the effect of intermittent levosimendan on other variables, including the time in days from randomization to first admission for acute HF worsening, mortality and serious adverse events. CONCLUSIONS The LAICA trial results could allow confirmation of the usefulness of intermittent levosimendan infusion in reducing the rate of hospitalization for HF worsening in advanced HF outpatients.

Traitement de la dépression résistante par l'association citalopram-lithium. Méthodologie d'une étude multicentrique en double aveugle et résultats préliminaires [Treatment of resistant depression with the citalopram-lithium combination. Methodology of a double-blind multicenter study and preliminary results].

Citalopram, a new bicyclic antidepressant, is the most selective serotonin reuptake inhibitor. In a number of double-blind controlled studies, citalopram was compared to placebo and to known tricyclic antidepressants. These studies have shown their efficacy and good safety. The inefficacy of a psychotropic treatment in at least 20% of depressives has led a number of authors to propose original drug combinations and associations, like antidepressant/lithium (Li), antidepressant/sleep deprivation (agrypnia), antidepressant/ECT, or antidepressant/LT3. The aim of this investigation is to evaluate the clinical effectiveness and safety of a combined citalopram/lithium treatment in therapy-resistant patients, taking account of serotonergic functions, as tested by the fenfluramine/prolactin test, and of drug pharmacokinetics and pharmacogenetics of metabolism. DESIGN OF THE STUDY: A washout period of 3 days before initiating the treatment is included. After an open treatment phase of 28 days (D) with citalopram (20 mg D1-D3; 40 mg D4-D14; 40 or 60 mg D15-D28; concomitant medication allowed: chloral, chlorazepate), the nonresponding patients [less than 50% improvement in the total score on the 21 item-Hamilton Depression Rating Scale (HDRS)] are selected and treated with or without Li (randomized in double-blind conditions: citalopram/Li or citalopram/placebo) during the treatment (D29-D35). Thereafter, all patients included in the double-blind phase subsequently receive an open treatment with citalopram/Li for 7 days (D36-D42). The hypothesis of a relationship between serotoninergic functions in patients using the fenfluramine/prolactin test (D1) and the clinical response to citalopram (and Li) is assessed. Moreover, it is evaluated whether the pharmacogenetic status of the patients, as determined by the mephenytoin/dextromethorphan test (D0-D28), is related to the metabolism of fenfluramine and citalopram, and also to the clinical response. CLINICAL ASSESSMENT: Patients with a diagnosis of major depressive disorders according to DSM III are submitted to a clinical assessment of D1, D7, D14, D28, D35, D42: HDRS, CGI (clinical global impression), VAS (visual analog scales for self-rating of depression), HDRS (Hamilton depression rating scale, 21 items), UKU (side effects scale), and to clinical laboratory examens, as well as ECG, control of weight, pulse, blood pressure at D1, D28, D35. Fenfluramine/prolactin test: A butterfly needle is inserted in a forearm vein at 7 h 45 and is kept patent with liquemine. Samples for plasma prolactin, and d- and l-fenfluramine determinations are drawn at 8 h 15 (base line). Patients are given 60 mg fenfluramine (as a racemate) at 8 h 30. Kinetic points are determined at 9 h 30, 10 h 30, 11 h 30, 12 h 30, 13 h 30. Plasma levels of d- and l-fenfluramine are determined by gas chromatography and prolactin by IRNA. Mephenytoin/dextromethorphan test: Patients empty their bladders before the test; they are then given 25 mg dextropethorphan and 100 mg mephenytoin (as a racemate) at 8 h 00. They collect all urines during the following 8 hours. The metabolic ratio is determined by gas chromatography (metabolic ratio dextromethorphan/dextrorphan greater than 0.3 = PM (poor metabolizer); mephenytoin/4-OH-mephenytoin greater than 5.6, or mephenytoin S/R greater than 0.8 = PM). Citalopram plasma levels: Plasma levels of citalopram, desmethylcitalopram and didesmethylcitalopram are determined by gas chromatography--mass spectrometry. RESULTS OF THE PILOT STUDY. The investigation has been preceded by a pilot study including 14 patients, using the abovementioned protocol, except that all nonresponders were medicated with citalopram/Li on D28 to D42. The mean total score (n = 14) on the 21 item Hamilton scale was significantly reduced after the treatment, ie from 26.93 +/- 5.80 on D1 to 8.57 +/- 6.90 on D35 (p less than 0.001). A similar patCitalopram, a new bicyclic antidepressant, is the most selective serotonin reu

Epidemiological studies in the information and genomics era: experience of the Clinical Genome of Cancer Project in São Paulo, Brazil

Genomics is expanding the horizons of epidemiology, providing a new dimension for classical epidemiological studies and inspiring the development of large-scale multicenter studies with the statistical power necessary for the assessment of gene-gene and gene-environment interactions in cancer etiology and prognosis. This paper describes the methodology of the Clinical Genome of Cancer Project in São Paulo, Brazil (CGCP), which includes patients with nine types of tumors and controls. Three major epidemiological designs were used to reach specific objectives: cross-sectional studies to examine gene expression, case-control studies to evaluate etiological factors, and follow-up studies to analyze genetic profiles in prognosis. The clinical groups included patients' data in the electronic database through the Internet. Two approaches were used for data quality control: continuous data evaluation and data entry consistency. A total of 1749 cases and 1509 controls were entered into the CGCP database from the first trimester of 2002 to the end of 2004. Continuous evaluation showed that, for all tumors taken together, only 0.5% of the general form fields still included potential inconsistencies by the end of 2004. Regarding data entry consistency, the highest percentage of errors (11.8%) was observed for the follow-up form, followed by 6.7% for the clinical form, 4.0% for the general form, and only 1.1% for the pathology form. Good data quality is required for their transformation into useful information for clinical application and for preventive measures. The use of the Internet for communication among researchers and for data entry is perhaps the most innovative feature of the CGCP. The monitoring of patients' data guaranteed their quality.

Nosocomial infection: A risk factor for a complicated course in children with respiratory syncytial virus infection - Results from a prospective multicenter German surveillance study

BACKGROUND: Nosocomially acquired respiratory syncytial virus infections (RSV-NI) may cause serious problems in hospitalized paediatric patients. Hitherto, prospectively collected representative data on RSV-NI from multicenter studies in Germany are limited. METHODS: The DMS RSV Ped database was designed for the prospective multicenter documentation and analysis of clinically relevant aspects of the management of inpatients with RSV-infection. The study covered six consecutive seasons (1999-2005); the surveillance took place in 14 paediatric hospitals in Germany. RESULTS: Of the 1568 prospectively documented RSV-infections, 6% (n=90) were NI and 94% (n=1478) were community acquired (CA). A significantly higher proportion in the NI group displayed additional risk factors like prematurity, chronic lung disease, mechanical ventilation (med. history), congenital heart disease, and neuromuscular impairment. Of all NI, 55% occurred in preterms (30.6% of all RSV-infections in preterms with severe chronic lung disease of prematurity were NI). Illness severity as well as the total mortality, but not the attributable mortality was significantly higher in the NI group. In the multivariate analysis, NI was significantly associated with the combined outcome 'complicated course of disease'. CONCLUSION: This is the first prospective multicenter study from Germany, which confirms the increased risk of a severe clinical course in nosocomially acquired RSV-infection. Of great concern is the high rate of (preventable) NI in preterms, in particular in those with severe chronic lung disease or with mechanical ventilation due to other reasons.

Key Issues In Inhibitor Management In Patients With Haemophilia.

12 Suppl 1

Interaction between Tobacco and Alcohol Use and the Risk of Head and Neck Cancer: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium

Background: The magnitude of risk conferred by the interaction between tobacco and alcohol use on the risk of head and neck cancers is not clear because studies have used various methods to quantify the excess head and neck cancer burden. Methods: We analyzed individual-level pooled data from 17 European and American case-control studies (11,221 cases and 16,168 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We estimated the multiplicative interaction parameter (psi) and population attributable risks (PAR). Results: A greater than multiplicative joint effect between ever tobacco and alcohol use was observed for head and neck cancer risk (psi = 2.15; 95% confidence interval, 1.53-3.04). The PAR for tobacco or alcohol was 72% (95% confidence interval, 61-79%) for head and neck cancer, of which 4% was due to alcohol alone, 33% was due to tobacco alone, and 35% was due to tobacco and alcohol combined. The total PAR differed by subsite (64% for oral cavity cancer, 72% for pharyngeal cancer, 89% for laryngeal cancer), by sex (74% for men, 57% for women), by age (33% for cases < 45 years, 73% for cases > 60 years), and by region (84% in Europe, 51% in North America, 83% in Latin America). Conclusions: Our results confirm that the joint effect between tobacco and alcohol use is greater than multiplicative on head and neck cancer risk. However, a substantial proportion of head and neck cancers cannot be attributed to tobacco or alcohol use, particularly for oral cavity cancer and for head and neck cancer among women and among young-onset cases. (Cancer Epidemiol Biomarkers Prev 2009;18(2):541-50)

The Use of Statins in People at Risk of Developing Diabetes Mellitus: Evidence and Guidance for Clinical Practice

Reducing low-density lipoprotein cholesterol (LDL-C) levels using statins is associated with significant reductions in cardiovascular (CV) events in a wide range of patient populations. Although statins are generally considered to be safe, recent studies suggest they are associated with an increased risk of developing Type 2 diabetes (T2D). This led the US Food and Drug Administration (FDA) to change their labelling requirements for statins to include a warning about the possibility of increased blood sugar and HbA1c levels and the European Medicines Agency (EMA) to issue guidance on a small increased risk of T2D with the statin class. This review examines the evidence leading to these claims and provides practical guidance for primary care physicians on the use of statins in people with or at risk of developing T2D. Overall, evidence suggests that the benefits of statins for the reduction of CV risk far outweigh the risk of developing T2D, especially in individuals with higher CV risk. To reduce the risk of developing T2D, physicians should assess all patients for T2D risk prior to starting statin therapy, educate patients about their risks, and encourage risk-reduction through lifestyle changes. Whether some statins are more diabetogenic than others requires further study. Statin-treated patients at high risk of developing T2D should regularly be monitored for changes in blood glucose or HbA1c levels, and the risk of conversion from pre-diabetes to T2D should be reduced by intensifying lifestyle changes. Should a patient develop T2D during statin treatment, physicians should continue with statin therapy and manage T2D in accordance with relevant national guidelines.

Reversibility of ventricular dysfunction: clinical experience in a medical office

OBJECTIVE - To describe clinical observations of marked improvement in ventricular dysfunction in a medical office environment under circumstances differing from those in study protocols and multicenter studies performed in hospital or with outpatient cohorts. METHODS - Eleven cardiac failure patients with marked ventricular dysfunction receiving treatment at a doctors office between 1994 and 1999 were studied. Their ages ranged from 20 and 66 years (mean 39.42±14.05 years); 7 patients were men, 4 were women. Cardiopathic etiologies were arterial hypertension in 5 patients, peripartum cardiomyopathy in 2, nondefined myocarditis in 2, and alcoholic cardiomyopathy in 4. Initial echocardiograms revealed left ventricular dilatation (average diastolic diameter, 69.45±8.15mm), reduced left ventricular ejection fraction (0.38±0.08) and left atrial dilatation (43.36±5.16mm). The therapeutic approach followed consisted of patient orientation, elimination of etiological or causal factors of cardiac failure, and prescription of digitalis, diuretics, and angiotensinconverting enzyme inhibitors. RESULTS - Following treatment, left ventricular ejection fraction changed to 0.63±0.09; left ventricular diameters changed to 57.18±8.13mm, and left atrium diameters changed to 37.27±8.05mm. Maximum improvement was noted after 16.9±8.63 (6 to 36) months. CONCLUSION - Patients with serious cardiac failure and ventricular dysfunction caused by hypertension, alcoholism, or myocarditis can experience marked improvement in ventricular dysfunction after undergoing appropriate therapy within the venue of the doctor's office.

Reproducibility of Left Ventricular Mass by Echocardiogram in the ELSA-Brasil

Background: Echocardiography, though non-invasive and having relatively low-cost, presents issues of variability which can limit its use in epidemiological studies. Objective: To evaluate left ventricular mass reproducibility when assessed at acquisition (online) compared to when assessed at a reading center after electronic transmission (offline) and also when assessed by different readers at the reading center. Methods: Echocardiographers from the 6 ELSA-Brasil study investigation centers measured the left ventricular mass online during the acquisition from 124 studies before transmitting to the reading center, where studies were read according to the study protocol. Half of these studies were blindly read by a second reader in the reading center. Results: From the 124 echocardiograms, 5 (4%) were considered not measurable. Among the remaining 119, 72 (61%) were women, mean age was 50.2 ± 7.0 years and 2 had structural myocardial abnormalities. Images were considered to be optimal/ good by the reading center for 110 (92.4%) cases. No significant difference existed between online and offline measurements (1,29 g, CI 95% −3.60-6.19), and the intraclass correlation coefficient between them was 0.79 (CI 95% 0.71-0.85). For images read by two readers, the intraclass correlation coefficient was 0.86 (CI 95% 0.78-0.91). Conclusion: There were no significant drifts between online and offline left ventricular mass measurements, and reproducibility was similar to that described in previous studies. Central quantitative assessment of echocardiographic studies in reading centers, as performed in the ELSA-Brasil study, is feasible and useful in clinical and epidemiological studies performed in our setting.