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Aims Ceramides exert several biological activities that may contribute to the pathophysiology of cardiovascular disease and heart failure (HF). The association between plasma levels of distinct ceramides (that have been previously associated with increased cardiovascular risk) and cardiovascular mortality in patients with chronic HF has received little attention. Methods and results In a post hoc ancillary analysis of the Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure (GISSI‐HF; NCT00336336) trial, we randomly selected a sample of 200 ambulatory patients with chronic HF who died due to cardiovascular causes and 200 patients who were alive at the end of the trial (after a median follow‐up period of 3.9 years). We measured baseline plasma concentrations of six previously identified high‐risk ceramide species [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), and Cer(d18:1/24:1) and their individual plasma ratios with Cer(d18:1/24:0)]. Patients who died due to cardiovascular causes had significantly (P

BackgroundThe long noncoding RNA LIPCAR (Long Intergenic noncoding RNA Predicting CARdiac remodeling) has emerged as a promising biomarker in cardiac disease and cardiac remodeling. To determine whether LIPCAR levels help for a molecular phenotyping of chronic heart failure (HF) patients, this study assessed the association of LIPCAR with severity of the disease and its progression, and with risk of death or hospitalization in HF patients.MethodsLIPCAR was measured in plasma of 967 HF patients with symptomatic heart failure participating in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca - Heart Failure (GISSI-HF) biohumoral sub-study.ResultsPlasma levels of LIPCAR were significantly associated with functional impairment as assessed by the New York Heart Association (NYHA) class, kidney function as reflected by estimated glomerular filtration rate, and creatinine, hemoglobin and mitral insufficiency. In females, these associations were more marked as compared to males. LIPCAR plasma levels were significantly related to the two cardiac markers, N-terminal pro-B type natriuretic peptide and high-sensitivity cardiac troponin T, but not to inflammatory markers such as high sensitivity C-reactive protein and pentraxin-3, nor to patient reported outcomes such as depression and quality of life. HF patients with high LIPCAR levels univariately showed significantly higher incidence of cardiovascular hospitalizations but not of death; after adjusting for covariates, no significant effects of LIPCAR were found for cardiovascular hospitalizations.ConclusionThe circulating long noncoding RNA LIPCAR was increased in HF patients with higher NYHA class, impaired kidney function, and lower hemoglobin, which are indicators of patients’ overall state.

Ceramides are sphingolipids that play roles as structural lipids and as second messengers in biological processes. Circulating ceramides are influenced by diet/food and predict major cardiovascular (CV) events, such as atrial fibrillation (AF). In 1227 patients with symptomatic chronic heart failure (HF), an association between diet and ceramides was found for coffee consumption of ≥3 cups and Cer(d18:1/24:0). Increased Cer(d18:1/24:0) was associated with lower incident AF (24.3% vs 15.4% tertile 1 vs 3, P = 0.016) and lower CV mortality (28.4% vs 12.0% tertile 1 vs 3, P < 0.0001). For coffee consumption, only an association with incident AF was found (24.5% never, 5.2% ≥3 cups). These inverse associations with AF were confirmed in survival analyses corrected for biomarkers (Cer(d18:1/24:0) HR: 0.79, P = 0.018; coffee consumption HR: 0.22, P = 0.001). In conclusion, higher coffee intake was associated with a lower risk of incident AF and with higher concentrations of Cer(d18:1/24:0). Cer(d18:1/24:0) was inversely associated to risk of AF.

Aims: A multicentre trial, ICOS-ONE, showed increases above the upper limit of normality of cardiac troponin (cTn) in 27% of patients within 12months after the end of cancer chemotherapy (CT) with anthracyclines, whether cardiac protection with enalapril was started at study entry in all (prevention arm) or only upon first occurrence on supra-normal cTn (troponin-triggered arm). The aims of the present post hoc analysis were (i) to assess whether anthracycline-based treatment could induce cardiotoxicity over 36month follow-up and (ii) to describe the time course of three cardiovascular biomarkers (i.e. troponin I cTnI-Ultra, B-type natriuretic peptide BNP, and pentraxin 3 PTX3) and of left ventricular (LV) function up to 36months. Methods and results: Eligible patients were those prescribed first-in-life CT, without evidence of cardiovascular disease, normal cTn, LV ejection fraction (EF) >50%, not on renin-angiotensin aldosterone system antagonists. Patients underwent echocardiography and blood sampling at 24 and 36months. No differences were observed in biomarker concentration between the two study arms, ‘prevention' vs. ‘troponin-triggered'. During additional follow-up 13 more deaths occurred, leading to a total of 23 (9.5%), all due to a non-cardiovascular cause. No new occurrences of LV-dysfunction were reported. Two additional patients were admitted to the hospital for cardiovascular causes, both for acute pulmonary embolism. No first onset of raised cTnI-Ultra was reported in the extended follow-up. BNP remained within normal range: at 36months was 23.4ng/L, higher (N.S.) than at baseline, 17.6ng/L. PTX3 peaked at 5.2ng/mL 1month after CT and returned to baseline values thereafter. cTnI-Ultra peaked at 26ng/L 1month after CT and returned to 3ng/L until the last measurement at 36months. All echocardiographic variables remained stable during follow-up with a median LVEF of 63% and left atrial volume index about 24mL/m2. Conclusions: First-in-life CT with median cumulative dose of anthracyclines of 180mg/m2 does not seem to cause clinically significant cardiac injury, as assessed by circulating biomarkers and echocardiography, in patients aged 51years (median), without pre-existing cardiac disease. This may suggest either a 100% efficacy of enalapril (given as preventive or troponin-triggered) or a reassuringly low absolute cardiovascular risk in this cohort of patients, which may not require intensive cardiologic follow-up.

Aims Although oral anticoagulants (OACs) are effective in preventing stroke in older people with atrial fibrillation (AF), they are often underused in this particularly high-risk population. The aim of the present study was to assess the appropriateness of OAC prescription and its associated factors in hospitalized patients aged 65 years or older. Methods Data were obtained from the retrospective phase of Simulation-based Technologies to Improve the Appropriate Use of Oral Anticoagulants in Hospitalized Elderly Patients With Atrial Fibrillation (SIM-AF) study, held in 32 Italian internal medicine and geriatric wards. The appropriateness of OAC prescription was assessed, grouping patients in those who were and were not prescribed OACs at hospital discharge. Multivariable logistic regression was used to establish factors independently associated with the appropriateness of OAC prescription. Results A total of 328 patients were included in the retrospective phase of the study. Of these, almost 44% (N = 143) were inappropriately prescribed OACs, being mainly underprescribed or prescribed an inappropriate antithrombotic drug (N = 88). Among the patients prescribed OACs (N = 221), errors in the prescribed doses were the most frequent cause of inappropriate use (N = 55). Factors associated with a higher degree of patient frailty were inversely associated with the appropriateness of OAC prescription. Conclusions In hospitalized older patients with AF, there is still a high prevalence of inappropriate OAC prescribing. Characteristics usually related to frailty are associated with the inappropriate prescribing. These findings point to the need for targeted interventions designed for internists and geriatricians, aimed at improving the appropriate prescribing of OACs in this complex and high-risk population.

The nature and the purpose of the ECRIN Data Centre Certification Programme are summarised, and a very brief description is given of the underlying standards (129 in total, divided into 19 separate lists). The certification activity performed so far is described. In a pilot phase 2 centres were certified in 2012. Calls in 2014 and 2015 resulted in a further 8 certified centres, with 2 certifications still in progress, and the 2016 call has generated several additional applications. The impact and benefits of the programme are listed, divided into a) the effects of the introduction of the standards, b) the effects of the certification programme in general, and c) the effects of the certification programme on individual units. The discussion emphasises the generally positive impact of the programme so far but stresses the need to better clarify the perspective and role of the programme.

Background Galectin-3 (Gal-3) is involved in collagen deposition and inflammation and is a prognostic biomarker in heart failure (HF).Methods and Results:Gal-3 and other markers of fibrosis or cardiac stress were measured serially in 413 patients with mild HF randomized to the mineralocorticoid receptor antagonist canrenone or placebo to evaluate treatment effect and association with clinical outcome. Gal-3 increased slightly over 6 months in both arms of the study and was associated with clinical endpoints. Conclusions Although Gal-3 showed prognostic value, the effect of canrenone on clinical outcomes was unaffected by baseline concentrations of biomarkers of fibrosis or cardiac stress.

Aims To assess the appropriateness of oral anticoagulant (OAC) prescription and its associated factors in acutely hospitalized elderly patients. Methods Data were obtained from the prospective phase of SIM-AF (SIMulation-based technologies to improve the appropriate use of oral anticoagulants in hospitalized elderly patients with Atrial Fibrillation) randomized controlled trial, aimed to test whether an educational intervention improved OAC prescription, compared to current clinical practice, in internal medicine wards. In this secondary analysis, appropriateness of OAC prescription was assessed at hospital admission and discharge. Results For 246 patients, no significant differences were found between arms (odds ratio 1.38, 95% confidence interval [CI] 0.84-2.28) in terms of appropriateness of OAC prescription. Globally, 92 patients (37.4%, 95% CI = 31.6-43.6%) were inappropriately prescribed or not prescribed at hospital discharge. Among 51 patients inappropriately prescribed, 82% showed errors on dosage, being mainly under-dosed (n = 29, 56.9%), and among 41 inappropriately not prescribed, 98% were taking an antiplatelet drug. Factors independently associated with a lower probability of appropriateness at discharge were those related to a higher risk of bleeding (older age, higher levels of aspartate aminotransferase, history of falls, alcohol consumption) and antiplatelet prescription at admission. The prescription of OACs at admission was the strongest predictor of appropriateness at discharge (odds ratio = 7.43, 95% CI = 4.04-13.73). Conclusions A high proportion of hospitalized older patients with AF remains inappropriately prescribed or nonprescribed with OACs. The management of these patients at hospital admission is the strongest predictor of prescription appropriateness at discharge.

Background The genetic structure of human populations is the outcome of the combined action of different processes such as demographic dynamics and natural selection. Several efforts toward the characterization of population genetic architectures and the identification of adaptation signatures were recently made. In this study, we provide a genome-wide depiction of the Italian population structure and the analysis of the major determinants of the current existing genetic variation. Results We defined and characterized 210 genomic loci associated with the first Principal Component calculated on the Italian genotypic data and correlated to the North–south genetic gradient. Using a gene-enrichment approach we identified the immune function as primarily involved in the Italian population differentiation and we described a locus on chromosome 13 showing combined evidence of North–south diversification in allele frequencies and signs of recent positive selection. In this region our bioinformatics analysis pinpointed an uncharacterized long intergenic non-coding (lincRNA), whose expression appeared specific for immune-related tissues suggesting its relevance for the immune function. Conclusions Our study, combining population genetic analyses with biological insights provides a description of the Italian genetic structure that in future could contribute to the evaluation of complex diseases risk in the population context. Electronic supplementary material The online version of this article (doi:10.1186/s12863-015-0293-x) contains supplementary material, which is available to authorized users.

Emotion may be defined as a special perception that informs us about current body status and its modification due to internal or external stimuli and feelings such as mental representations of bodily changes, including thoughts (Damasio, 2003). Emotions have been generally associated with products but there has been little published research on emotions related to food, and more specifically to wine. Every culture may describe its emotions in different ways and may have its own emotional lexicon, allowing feelings to be socially shared: the purpose of this research is to develop a list of emotional adjectives appropriate to the Italian culture to describe the feelings of wine consumers. By means of three studies, we selected 16 words which allow wine consumers to describe their feelings while consuming wine. The emotion terms selected could be divided into two categories: high/low arousal and high/low pleasantness. Unlike the general prevalence in the emotional lexicon of languages of words expressing unpleasant emotions, most of the 16 Italian terms focused on emotions elicited by wine consumption fall into the pleasure category.

Objectives: Adiponectin has insulin-sensitizing, anti-inflammatory and anti-atherogenic properties. There are few and controversial data on the role of ADIPOQ variants in heart failure (HF) pathogenesis. We planned this large association study to investigate the potential association of four selected ADIPOQ polymorphisms with HF in a population of Italian origin. Methods: We genotyped 1173 cases with symptomatic HF and 1136 controls for alleles rs17300539, rs266729, rs1501299 and rs2241766. Cases were patients enrolled in the GISSI-Heart Failure genetic sub-study, with a long-term follow up (median 3.9 years). Controls were blood donors with no history of diabetes or cardiovascular disease (CVD). Genotype and allele frequencies of the four single nucleotide polymorphisms (SNPs) were compared between the two groups. Results: Clinical characteristics were significantly different between HF patients and controls. No significant differences were reported in the allelic and genotypic distribution, with the exception of rs266729 G allele, which showed a significant association with an increased risk of HF [odds ratio (OR) = 1.26; 95% confidence interval (CI) = 1.07–1.48; p = 0.006). We divided the GISSI-HF population according to HF etiology (ischemic and nonischemic) and presence of diabetes. For rs266729 G allele, a significant association with HF was confirmed in both ischemic (OR = 1.29; 95% CI = 1.06–1.56; p = 0.009) and nonischemic patients (OR = 1.2; 95% CI = 1.02–1.42; p = 0.03) as well as in nondiabetic patients (OR = 1.25; 95% CI = 1.05–1.49; p = 0.012). rs2241766 G allele showed a significant reduction of risk of HF in nonischemic (OR = 0.77; 95% CI = 0.62–0.95; p = 0.02) and diabetic patients (OR = 0.62; 95% CI = 0.45–0.84; p = 0.0025). Conclusions: We confirm the association between rs266729 G allele and an increased risk of HF and between rs2241766 G allele and decreased risk of HF. Our study extends the knowledge on the influence of ADIPOQ variants on CVD.

The high ethanol level in wine has become an important issue for all the main wine producing countries. Several techniques are available to the wine industry to reduce the ethanol content; among them, the membrane contactors are certainly one of the newest. Very few studies on the effect of this practice on the wine quality and aroma profile and on the stable isotopes composition are available. A pilot and industrial plant equipped with the membrane contactor system were used in the study in the dealcoholisation on several white and red wines. Significant changes for several classes of aroma compounds in both pilot- and industrial-scale experiments were observed, even though these changes were not always in perfect agreement with the sensory evaluation carried out. Finally, modifications on the δ18O of up to 1 ‰ for 2 % v/v and of up to 4 ‰ for 8 % v/v ethanol removal were encountered. An increase of δ13C of ethanol of up to 1.1 ‰ for 2 % and of up to 2.3 ‰ for 4 % of dealcoholisation rate was also observed. Dealcoholisation via membrane contactor seemed to affect the overall wine composition (aroma and flavour), even though the main concern resided on the alteration of the isotopic composition which could be linked to product authenticity issues.

The Coordinating Centre (CC) of the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico (GISSI) used telecommunication technology to develop a computerized network system for the data management of the GISSI studies. Through a personal computer (PC), a communication program, a modem and a telephone line, the investigator in each participating centre can connect with a micro-computer at the CC, to recruit/randomize patients and download reports on the progress of the trial. In the first case, the investigator is required to answer a set of predefined questions, and thereby the system automatically checks eligibility criteria and randomly assigns the patient to a treatment arm. In the second case, once the investigator has made a choice from a list of standard reports and the relative query on CC central database, the generation, the formatting and the transfer of the selected report to the PC are executed automatically on line. The main advantages of this system are a reduction in number of mistakes in data completion and in the human and economic resources required, as well as the real time updating of participating centres. The system was successfully adopted in the GISSI-3 trial (200 Coronary Care Units and 19 394 patients enrolled), in the European arm of the CORE trial and it is currently being used in the GISSI-Prevenzione trial.

Background Patients with end-stage heart failure are often refractory to maximal oral therapy, and they have high mortality rates, poor quality of life, and frequent hospitalizations with elevated health care costs. Intermittent dobutamine therapy has been suggested as an additional option in this clinical setting. Methods and Results Thirty-eight patients clinically stable for at least 48 hours with standard treatment, New York Heart Association (NYHA) functional class III or IV, cardiac index ≤2.2 L/min/m 2 , and left ventricular ejection fraction ≤30% were randomly assigned to ambulatory intermittent dobutamine or optimal standard treatment. Dobutamine was infused at 2.5 μg/kg/min with a portable pump 48 hours/week for 6 months. The primary study end point was the reduction of hospitalizations for worsening of congestive heart failure (CHF); changes in NYHA functional class, 6-minute walking test, and mortality rates were secondary end points. During the 6-month follow-up, all patients in dobutamine and control groups underwent weekly clinical visits with serum sodium and potassium measurement. Baseline characteristics were age 65 ± 2 years, NYHA class III/IV 17/21, ejection fraction 22% ± 1%, and cardiac index 1.89 ± 0.1 L/min/m 2 , without differences between treatment groups. Hospitalizations for all causes over a 6-month period were 17 and 11 in control and dobutamine groups; 11 of 17 and 7 of 11 were for worsening CHF. Four control patients but none in the dobutamine group had 2 or more hospitalizations for worsening of CHF. There were no significant differences in NYHA functional class and in 6-minute walking test. Three patients in the control group died and 5 in the dobutamine group died. Two patients in the dobutamine group underwent heart transplantation. Protocol was discontinued in the dobutamine group for severe ventricular arrhythmias (1 patient), infusion system failure (1 patient), and consent withdrawal (1 patient). In 3 patients in the dobutamine group, drug dose was increased to 5 μg/kg/min because of CHF. Conclusions Six-month intermittent low-dose dobutamine administration was well tolerated by patients with severe CHF; it did not improve the functional status and did not significantly increase the mortality rate as found with higher dobutamine doses in other studies. Hospitalizations for all causes and for worsening of CHF tended to be fewer in the dobutamine group. (Am Heart J 1999;138:247-53.)

INTRODUCTION:Healthcare professionals need to continually update their knowledge to provide care based on scientific evidence. In some cases it can be difficult to gain access to the different sources of medical information. In an attempt to overcome these problems, a toll-free telephone medical information service (Doctorline) was established.OBJECTIVETo describe the development, aims, organization, and activities of this private service.METHODS:Doctorline is an independent, unbiased, toll-free medical information service that provides information on clinical, pharmacologic, and toxicologic issues; bibliographic searches; full-text articles; public and private clinics; details of forthcoming congresses; and legislative documentation. The service is available Monday through Friday, 1000 to 2000. Staff members are physicians trained in communication techniques, literature evaluation methodologies, and computerized database use. The main on-line facilities are MEDLINE, Micromedex-CCIS, and the Italian Formulary on CD-ROM. Books, bulletins, national and international drug formularies, and property files (i.e., directory of Italian public and private clinics) are also available.RESULTSIn 5 years, Doctorline has received 65 258 calls. Nearly 34% of the calls were made by general practitioners, followed by cardiologists (22%), orthopedists (15%), pharmacists (14%), gastroenterologists (13%), and urologists (10%). From 1991 to 1996, nearly 20% of the calls concerned pharmacologic issues, 43% nonpharmacologic issues, while the rest of the calls were for nonclinical requests. Approximately 21% of all questions received an answer during the same phone call (on-line answers); for the other answers (off-line answers) the mean ± SD waiting time was 7.8 ± 10.4 days. Although the nature of the questions has been recorded since 1991, data about the exact number of physicians who used the service are available only from 1994. Data from 1994 indicate that of the 52 181 physicians who could access the service, only 8817 (16.9%) called at least once, with a mean number of calls per physician of 3.9 (range 3.0–5.6).CONCLUSIONSThe future of Doctorline will depend on the quality and validity of the information provided (i.e., based exclusively on scientific evidence, independent of the source of funds), the promotion of the aims, organization, and clinical utility of the service (especially among physicians who made little or no use of the service), and differentiation of the service activities in relation to the physician's specific needs.OBJETIVOLos profesionales de la salud necesitan actualizar contínuamente sus conocimientos de manera que puedan prestar servicios de atención al paciente fundamentados en evidencia científica. Para algunos proveedoresk, puede resultar dificil obtener acceso a las diferentes fuentes de información médica. El objetivo de este artículo es describir el desarrollo, propósito, organización, y actividades de un servicio telefónico de información médica libre de costo al usario (Doctorline).MÉTODOSDoctorline es un servicio telefónico independiente (no afiliado a companias farmacéuticas) que ofrece información sobre asuntos clínicos, farmacológicos y toxicológicos, búsquedas bibliográficas, artículos, detalles sobre congresos profesionales, clínicas públicas y privadas, y documentación legislativa. El servicio está disponible de lunes a viernes, de 1000 a 2000. El servicio es ofrecido por médicos adiestrados en técnicas de comunicación, evaluación de la literatura, y uso de bases de datos en computadoras. Doctorline cuenta con acceso a MEDLINE, Micromedex-CCIS, y el Formulario Italiano en CD-ROM. También cuenta con libros, boletines, formularios nacionales e internacionales, e información propietaria (como, por ejemplo, el directorio de clínicas italians públicas y privadas).RESULTADOSEn 5 años, se han recibido 65 259 llamadas telefónicas en Doctorline. Casi 34% de las llamadas fueron realizadas por generalistas, seguido por cardiólogos (22%), ortopedas (15%), farmacéuticos (14%), y urólogos (10%). De 1991 a 1996, casi 20% de las llamadas estuvieron relacionadas con asuntos farmacológicos, 43% con asuntos no-farmacológicos, y el restante con consultas no-clínicas. Cerca del 21% de todas las preguntas fueron contestadas durante la misma llamada mientras que para las otras preguntas el tiempo promedio de espera fue 7.8 días (desviación estándar = 10.4 días). A pesar que la naturaleza de las preguntas ha sido recopilada desde 1991, los datos relacionados con el número exacto de médicos que han usado el servicio se tabula sólo desde 1994. Estos datos indican que de los 52 181 médicos que tuvieron acceso al servicio, sólo 8817 (16.9%) llamaron por lo menos una vez, con un promedio de llamadas por médico de 3.9 (margen = 3.0–5.6 llamadas).CONCLUSIONESEl futuro de Doctorline dependerá de la calidad y validez de la información que se provea (basada exclusivamente en evidencia científica e independiente de la fuentes de fondos), la diseminación del propósito, organización, y utilidad clínica del servicio (especialmente entre los médicos que no hacen uso del mismo), y la diferenciación de las actividades de servicio en relación a las necesidades específicas del médico.INTRODUCTIONLes professionnels de la santé ont besoin de mettre constamment à jour leurs connaissances pour être en mesure de fournir des soins qui so basent sur des évidences scientifiques. Dans certains cas, il peut être difficile d'accéder aux différentes sources d'information. À cause de ceci, un service téléphonique sans frais d'information médicale (Doctorline) fut mis sur pied.OBJECTIFSCet article décrit le développement, les buts, l'organisation, et les activités de ce service privé.MÉTHODESDoctorline est un service téléphonique sans frais d'information, indépendant et sans biais, qui fournit de l'information sur des sujets cliniques, pharmacologiques, toxicologiques, des recherches bibliographiques; des articles scientifiques; des cliniques publiques et privées; des détails sur des congrès à venir, et sur de la documentation législative. Le service est disponible du lundi au vendredi, de 1000 à 2000. Les employés sont des médecins ayant été formés en techniques de communication, en évaluation des méthodologies de la littérature, et en utilisation des banques de données informatisées. Les outils informatisés utilisés sont MEDLINE, Micromedex-CCIS, et le formulaire Italien sur CD-ROM. En plus, des livres, des bulletins, des formulaires nationaux et internationaux, des dossiers privés (i.e., annuaires de cliniques italiennes publiques et privées) sont aussi disponibles.RÉSULTATSLe service Doctorline a reçu 65 258 appels en 5 ans. Près de 34% les appels furent effectués par les omnipraticiens, suivis des cardiologues avec (22%), des orthopédistes avec (15%), des poharmaciens avec (14%), et des urologues avec (10%). Entre 1991 et 1996, près de 20% des appels portaient sur des problèmes pharmacologiques, 43% sur des problèmes non pharmacologiques et le reste des appels étaient des demandes non cliniques. Environ 21% des appels furent répondus sur le champ tandis que pour les autres, un délai moyen de 7.8 jours (10.4 SD) était nécessaire. Même si la nature des appels est répertoiriée depuis 1991, les données sur le nombre exact de médecins utilisant le service ne sont disponibles que depuis 1994. Les données de 1994 indiquent que sur les 52 181 médecins ayant accès au service, seulement 8817 (16.9%) l'ont utilisé au moins une fois avec une moyenne de 3.9 appels par médecins (intervalle entre 3.0–5.6).CONCLUSIONSLe futur de ce service dépendra de la qualité et de la validité des informations fournies (i.e., basées uniquement sur des évidences scientifiques et indépendantes des sources de financement), de la publicisation des buts, de l'organisation, et de l'utilité clinique (spécialement pour les médecins qui utilisant peu ou pas le service), et la différentiation des activités du service en relation avec les besoins spécifiques des médecins.

International audience; The pilot phase of the ECRIN (European Clinical Research Infrastructure Network) certification programme for European data centres, in late 2011, led to a substantial revision of the original ECRIN standards, completed by June 2012. The pilot phase, the conclusions drawn from it and the revised set of standards are described. Issues concerning the further development of standards and related material are discussed, as are the methods available to best support that development. A strategy is outlined based on short-lived specific task groups, established as necessary by a steering group drawn from ECRIN-ERIC. A final section discusses possible future developments.

In the last decade, several clinical trials in patients with, or recovering from, acute myocardial infarction (AMI) have evaluated the role of calcium antagonists in affecting patients' prognosis. Results have been disparate, with evidence of possible harm, no effect, or some benefit, depending on the agent used. We evaluated how the evidence from these trials has influenced the pattern of prescription of calcium antagonists and assessed the important determinants of use of these agents in patients after AMI. We analyzed retrospectively the prescription of calcium antagonists at discharge in all patients recovering from AMI enrolled in 3 large randomized clinical trials (Gruppo Italiano per lo Studio della Sopravvivenza nell' Infarto-1 [GISSI-1], GISSI-2, and GISSI-3) during the last 10 years. A progressive decrease in prescriptions for calcium antagonists was evident, from 47.2% in GISSI-1 to 35.1% in GISSI-2 to 19.0% in GISSI-3 (p0.001). The presence of post AMI angina, history of hypertension, and occurrence of reinfarction were associated with a higher usage of calcium antagonists, whereas the use of beta blockers at discharge was a major independent negative determinant. Use of calcium antagonists for secondary prevention after AMI (i.e., without specific clinical indications for their use) decreased by approximately 60% (from 26.1% to 10.3%). The data indicate that the usage of calcium antagonists in GISSI studies has been strongly affected by the results of other large multicenter trials evaluating calcium antagonists. These agents are now prescribed in patients after AMI almost exclusively in the presence of specific indications such as systemic hypertension or angina.

Treatment with long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) can improve clinical outcomes in patients with heart failure (HF). Circulating levels of n-3 PUFA, an objective estimation of exposure, have never been measured in a large cohort of patients with HF.We measured n-3 PUFA in plasma phospholipids at baseline and after 3 months in 1,203 patients with chronic HF enrolled in the GISSI-Heart Failure trial and randomized to n-3 PUFA 1 g/daily or placebo. N-3 PUFA levels were related to clinical characteristics, pharmacologic treatments, dietary habits, circulating biomarkers, and mortality.Baseline n-3 PUFA (5.1 ± 1.8 mol%) was associated with dietary fish intake, with an average difference of 43% between patients with the lowest and highest consumptions (P.0001). Baseline eicosapentaenoic acid (EPA) but not docosahexaenoic acid (DHA) was inversely related to C-reactive protein, pentraxin-3, adiponectin, natriuretic peptide, and troponin levels. Three-month treatment with n-3 PUFA raised their levels by 43%, independently of dietary fish consumption; increases in EPA levels were associated with decreased pentraxin-3. Low baseline levels of EPA but not DHA were no longer related to higher mortality after the addition of circulating biomarkers to multivariable models.Before supplementation, circulating n-3 PUFA levels in patients with chronic HF mainly depend on dietary fish consumption and are inversely related to inflammatory markers and disease severity. Three-month treatment with n-3 PUFA markedly enriched circulating EPA and DHA, independently of fish intake, and lowered pentraxin-3. Low EPA levels are inversely related to total mortality in patients with chronic HF.

PTX3 is a long pentraxin of the innate immune system produced by different cell types (mononuclear phagocytes, dendritic cells, fibroblasts and endothelial cells) at the inflammatory site. It appears to have a cardiovascular protective function by acting on the immune-inflammatory balance in the cardiovascular system. PTX3 plasma concentration is an independent predictor of mortality in patients with acute myocardial infarction (AMI) but the influence of PTX3 genetic variants on PTX3 plasma concentration has been investigated very little and there is no information on the association between PTX3 variations and AMI. Subjects of European origin (3245, 1751 AMI survivors and 1494 controls) were genotyped for three common PTX3 polymorphisms (SNPs) (rs2305619, rs3816527, rs1840680). Genotype and allele frequencies of the three SNPs and the haplotype frequencies were compared for the two groups. None of the genotypes, alleles or haplotypes were significantly associated with the risk of AMI. However, analysis adjusted for age and sex indicated that the three PTX3 SNPs and the corresponding haplotypes were significantly associated with different PTX3 plasma levels. There was also a significant association between PTX3 plasma concentrations and the risk of all-cause mortality at three years in AMI patients (OR 1.10, 95% CI: 1.01-1.20, p = 0.02). Our study showed that PTX3 plasma levels are influenced by three PTX3 polymorphisms. Genetically determined high PTX3 levels do not influence the risk of AMI, suggesting that the PTX3 concentration itself is unlikely to be even a modest causal factor for AMI. Analysis also confirmed that PTX3 is a prognostic marker after AMI.

The onset of acute myocardial infarction (AMI) is unevenly distributed over the 24 h and the week. While presence of a morning peak is generally agreed upon, contrasting results had been obtained regarding other periods of the day, probably due to differences of origin, size and composition of the populations. The 24 h and weekly distributions were studied within 6 h from the beginning of the symptoms in a population following a Latin life-style, who were enrolled in the GISSI 2 Study (n = 11472). Subgroups (smokers, the elderly (> 65 years), diabetics, hypertensives) were also considered. Six hour periods starting at midnight were tested for uniformity. Circadian non-uniformity was found. Events increased in the morning hours and reduced during the night regardless of the day of the week. The night and day difference was attenuated in smokers and diabetics. Non-uniformity of the events was also found among the days of the week. AMI significantly increased in non-smokers on Monday. We suggest that there is a night-day gradient (characterized by the short time interval between the two frequency extremes) in the time of onset of AMI. The different distribution in smokers stresses the possible unfavourable and masking effect of a heightened sympathetic tone during the day while the general protective role of the night hours is preserved. Moreover, the increased incidence of events on Monday may suggest the importance of the shift from a period of non-scheduled to scheduled activity.

Controversy exists with regard to the influence of APOE polymorphisms on coronary heart disease development and on the efficacy of statin treatment. we investigated the relationship between apoe, mortality and the response to treatment in Mediterranean myocardial infarction (mi) survivors.We analysed 3304 Italian patients with MI randomized to pravastatin or no treatment in the GISSI-Prevenzione study, with a mean follow-up time of 23.0 +/- 6.7 months (median 24.3 months). Mortality curves were calculated using Kaplan-Meier method, and differences in survival were tested using the log-rank test. There were 109 deaths during follow-up. Patients treated with pravastatin showed a significant decrease in mortality compared with non-treated patients (HR 0.67, 95% confidence interval 0.45-0.97, P = 0.038). Among the 3304 patients, 554 (16.8%) were epsilon4 carriers and 2750 (83.2%) were non-epsilon4 carriers. No significant difference in terms of mortality was observed between the epsilon4 and the non-epsilon4 carriers (3.61% vs. 3.24%, P = 0.67). However, although in non-epsilon4 carriers no significant difference in mortality was observed between patients treated with pravastatin and non-treated (2.81% vs. 3.67%, P = 0.21), among the epsilon4 carriers a significant reduction in mortality was observed in patients treated compared with non-treated (1.85% vs. 5.28%, P = 0.023).We found that epsilon4 allele is a determinant of pravastatin response in terms of survival. Though in the entire population investigated,we found a beneficial effect of pravastatin in terms of survival, only the epsilon4 carriers seemed to have gained a significant benefit from this treatment. We suggest that the effect of statins is of particular interest in this fraction of the population. Genetic markers can help in identifying patients that benefit more from statin treatment.

The serum concentration of lipoprotein Lp (a) is known to be highly heritable and associated with cardiovascular risk. A genome-wide variance component linkage analysis was performed to localise quantitative trait loci (QTLs) influencing Lp(a) levels in a large cohort collected in the PROCARDIS coronary heart disease study. Highly significant linkage was detected at the previously described LP(a) locus on chromosome 6q27 (LOD 108). Taking into account the effect of the locus detected on chromosome 6, a highly significant LOD score was detected on chromosome 13q22-31 (LOD 7.0). Another significant region of linkage was observed on chromosomes 11p14-15 (LOD 3.5). The significant peak at 13q22-31 shows an essential overlap with a locus modulating cholesterol in familial hypercholesterolemia. If the gene underlying these loci is the same, it will be a promising candidate target for manipulating LDL-cholesterol and Lp(a). We also detected linkage at a previously identified locus influencing Lp(a) on chromosome 1q23 (LOD 1.5). Our findings provide new and confirmatory information about genomic regions involved in the quantitative variation of Lp(a) and serve as a basis for further studies of candidate genes in these regions.

INTRODUCTION: The Internet and the World Wide Web have been recently introduced in the management of some aspects of large scale clinical trials. We have developed a model for a clinical trial Web site in order to enhance communication among people involved in a clinical trial, to disseminate clinical trials information, and to decentralise some trials activities. METHODS: One section of the Web site should include general medical information such as summary of the background, aim, design of the ongoing trial and results of similar trials. A directory of investigators, members committees, sponsors and monitors (with their e-mail address) could also help people in improving communication. Another section should include centre based summaries of the trial: randomised patients, follow-up schedule, patients lost to follow-up, outstanding case report forms and queries, and statistics on centres quality are some examples. An additional section should be dealing with the latest trial news: trial newsletter, planned meetings, congresses presentations, archive of frequently asked questions on the application of the trial protocol. Patient randomisation/registration and remote data entry are two additional components of a clinical data management system that could be included in the site. In this case database access rules and security should be implemented. Other Web based applications are related with the supply of study material (protocol, case report forms, informed consent), the management of mailing lists for the investigators, the publishing of sub-analyses results. DISCUSSION: Although some problems still exist (Internet connection limitations, security, lack of common standard for client software, personnel training), the Internet and the clinical trial Web sites could in the few years transform the way a clinical trial is conducted. []