334 resultados para spanish cohort


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Introduction of potent antiretroviral combination therapy (ART) has reduced overall morbidity and mortality amongst HIV-infected adults. Some prophylactic regimes against opportunistic infections can be discontinued in patients under successful ART. (1) The influence of the availability of ART on incidence and mortality of disseminated M. avium Complex infection (MAC). (2) The safety of discontinuation of maintenance therapy against MAC in patients on ART. The Swiss HIV-Cohort Study, a prospective multicentre study of HIV-infected adults. Patients with a nadir CD4 count below 50 cells/mm3 were considered at risk for MAC and contributed to total follow-up time for calculating the incidence. Survival analysis was performed by using Kaplan Meier and Cox proportional hazards methods. Safety of discontinuation of maintenance therapy was evaluated by review of the medical notes. 398 patients were diagnosed with MAC from 1990 to 1999. 350 had a previous CD4 count below 50 cells/mm3. A total of 3208 patients had a nadir CD4 count of less than 50 cells/mm3 during the study period and contributed to a total follow-up of 6004 person-years. The incidence over the whole study period was 5.8 events per 100 person-years. In the time period of available ART the incidence of MAC was significantly reduced (1.4 versus 8.8 events per 100 person-years, p < 0.001). Being diagnosed after 1995 was the most powerful predictor of better survival (adjusted hazard ratio for death: 0.27; p < 0.001). None of 24 patients discontinuing maintenance therapy while on ART experienced recurrence of MAC during a total follow-up of 56.6 person-years (upper 95% confidence limit 5.3 per 100 person-years). Introducing ART has markedly reduced the risk of MAC for HIV-infected individuals with a history of very low CD4 counts. Survival after diagnosis of MAC has improved after ART became available. In patients responding to ART, discontinuation of maintenance therapy against M. avium may be safe.

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Ce projet de thèse consiste en deux travaux sur le thème commun des thromboses veineuses mésentériques. Dans le premier travail, préliminaire au deuxième, nous avons décrit les signes d'évolution chronique des thromboses veineuses mésentériques. Les signes aigus sont bien connus et bien décrits (défaut de remplissage intra-luminal) contrairement aux signes chroniques dont la description manquait dans la littérature. Nous avons de plus cherché quels étaient les facteurs prédicateurs pour une évolution chronique. Pour se faire, nous avons sélectionné un collectif de patients avec un diagnostic de thromboses veineuses mésentériques aiguës et avons revu tous les scanners abdominaux en phase veineuse de ces patients à la recherche des signes d'évolution des thromboses. Cette étude a permis de mettre en évidence que les signes d'évolution chronique des thromboses veineuses mésentériques sont la sténose ou l'obstruction complète de la veine thrombosée et le développement d'un réseau de collatérales permettant de contourner la veine thrombosée. D'autre part, nous avons mis en évidence que la plupart des cas de thrombose veineuse mésentérique présente une évolution chronique, indépendamment de si le patient a reçu un traitement anticoagulant. Les thromboses étendues, situées dans des veines de petit calibre, auquel s'associe une infiltration de la graisse mésentérique au moment du diagnostic sont des facteurs favorisants pour une évolution chronique. La seconde étude a été réalisée grâce et avec la collaboration de la « Swiss Inflammatory Bowel Disease Cohort study » (SIBDCS). Les patients atteints de maladie inflammatoire chronique de l'intestin (MICI) présentent un risque augmenté de complications thromboemboliques, principalement de thrombose veineuse périphérique et d'embolie pulmonaire mais également de thrombose veineuse mésentérique. La littérature à ce sujet est pauvre et la prévalence de cette complication n'est pas connue dans cette population. Les buts de cette étude étaient donc d'évaluer la prévalence des thromboses veineuses mésentériques chez les patients atteints de MICI et de corréler leur survenue avec l'évolution clinique des patients. Parmi les patients inclus dans la SIBDCS, suivis au CHUV, nous avons revu tous les scanners abdominaux réalisés en phase veineuse à la recherche de signes (aigus ou chroniques) de thrombose veineuse mésentérique. Nous avons ainsi créé deux groupes de patients : les patients avec ou sans thrombose veineuse mésentérique. Ces deux collectifs ont ensuite été corrélés à la présence de signes radiologiques d'activité de la maladie inflammatoire de l'intestin et à la survenue aux complications liées à la MICI. Ainsi, nous avons mis en évidence que les thromboses veineuses mésentériques sont fréquentes chez les patients atteints de MICI, soit près de 30% chez les patients atteints de maladie de Crohn et 20% chez les patients atteints de RCUH. D'autre part, dans le groupe de patients atteints de maladie de Crohn, nous avons trouvé une association entre la survenue de thrombose veineuse mésentérique et une évolution de la maladie de Crohn plus sévère (plus de signes d'activité radiologique) et plus compliquée (plus de sténose et de nécessité de recours à la chirurgie). Ces deux articles ont été publiés dans l'American Journal of Roentgenology au mois de juillet 2014 dans la rubrique Gastrointestinal imaging.

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We sought to provide a contemporary picture of the presentation, etiology, and outcome of infective endocarditis (IE) in a large patient cohort from multiple locations worldwide. Prospective cohort study of 2781 adults with definite IE who were admitted to 58 hospitals in 25 countries from June 1, 2000, through September 1, 2005. The median age of the cohort was 57.9 (interquartile range, 43.2-71.8) years, and 72.1% had native valve IE. Most patients (77.0%) presented early in the disease (<30 days) with few of the classic clinical hallmarks of IE. Recent health care exposure was found in one-quarter of patients. Staphylococcus aureus was the most common pathogen (31.2%). The mitral (41.1%) and aortic (37.6%) valves were infected most commonly. The following complications were common: stroke (16.9%), embolization other than stroke (22.6%), heart failure (32.3%), and intracardiac abscess (14.4%). Surgical therapy was common (48.2%), and in-hospital mortality remained high (17.7%). Prosthetic valve involvement (odds ratio, 1.47; 95% confidence interval, 1.13-1.90), increasing age (1.30; 1.17-1.46 per 10-year interval), pulmonary edema (1.79; 1.39-2.30), S aureus infection (1.54; 1.14-2.08), coagulase-negative staphylococcal infection (1.50; 1.07-2.10), mitral valve vegetation (1.34; 1.06-1.68), and paravalvular complications (2.25; 1.64-3.09) were associated with an increased risk of in-hospital death, whereas viridans streptococcal infection (0.52; 0.33-0.81) and surgery (0.61; 0.44-0.83) were associated with a decreased risk. In the early 21st century, IE is more often an acute disease, characterized by a high rate of S aureus infection. Mortality remains relatively high.

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BACKGROUND/AIMS: Prospective studies on factors associated with adverse kidney outcomes in European general populations are scant. Also, few studies consider the potential confounding effect of baseline kidney function. METHODS: We used baseline (2003-2006) and 5-year follow-up data of adults from the general population to evaluate the effect of baseline kidney function and proteinuria on the association of clinical, biological (e.g. uric acid, homocysteine, cytokines), and socioeconomic factors with change in kidney function, rapid decline in kidney function, and incidence of chronic kidney disease (CKD). Estimated glomerular filtration rate (eGFR) and urinary albuminuria-to-creatinine ratio (UACR) were collected. Kidney outcomes were modeled using multivariable regressions. RESULTS: A total of 4,441 subjects were included in the analysis. Among participants without CKD at baseline, 11.4% presented rapid decline in eGFR and/or incident CKD. After adjustment for baseline eGFR and log UACR, only age (Odds Ratio; 1.25 [95%CI 1.18-1.33]), diabetes (OR 1.48 [1.03-2.13]), education (OR middle vs. high 1.51 [1.08-2.11]) and log ultrasensitive CRP (OR 1.16 [1.05-1.22]) were associated with rapid decline in eGFR or incident CKD. Baseline log UACR (OR 1.18 [1.06-1.32]) but not eGFR was associated with rapid decline in eGFR and/or incident CKD. CONCLUSION: In addition to age and diabetes, education and CRP levels are associated with adverse kidney outcomes independently of baseline kidney function.

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Background: Despite their relevance to the prevention of sexually transmitted infections, there are few data on the frequency of recourse to prostitution in the male population in Switzerland. Using data gathered for the evaluation of the Swiss AIDS prevention strategy, we analysed net aggregate change and cohort-based change in lifetime prevalence of recourse to prostitution. Methods: Seven repeated cross-sectional telephone surveys of the general population aged 17-45 years (17-30 years only for the 1987 and 1988 surveys) were undertaken from 1987 to 2000 providing information on sexual behaviour including men's recourse to prostitution (total n¼9318). Age categories were: 17-20, 21-25, 26-30, 31-35, 36-40 and 41-45 years. Prevalence at 17-30 years was available in all surveys and prevalence at 41-45 was available for 1989-2000, though not for the same cohorts. Intra-cohort increase in prevalence over 10 years was analysed using truncated information for cohorts aged 21-25 and 26-30 years in 1987 and 1990. Population estimates were computed with 95% confidence intervals (CI). Results: No net change occurred in the 17-45 years male population prevalence between 1989 (17.6%, CI ¼ 15.4; 20.0) and 2000 (17.7%, CI ¼ 15.6; 20.0). The median starting prevalence of recourse to prostitution at age 17-20 was 4.8% (in 1989, CI ¼ 2.0; 9.7) and the range was from 1.8 (in 1994) to 10.4% (in 1990). The median ending prevalence at age 41-45 was 21.9% (in 1994, CI 16.7; 27.9) and the range was from 17.9 (in 2000) to 26.1% (in 1992). No clear trend was observed in either starting or ending prevalence. Intra-cohort evolution of the 1997 and 1990 cohorts was very similar. Conclusions: Based on available data, there was no net (aggregate) change in the prevalence of recourse to prostitution by males in Switzerland between 1989 and 2000. Within the time frame available, intra-cohort evolution was also very similar.

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OBJECTIVE: The aim of this study was to examine the effect of a smoking ban on lung function, fractional exhaled nitric oxide, and respiratory symptoms in nonsmoking hospitality workers. METHODS: Secondhand smoke exposure at the workplace, spirometry, and fractional exhaled nitric oxide were measured in 92 nonsmoking hospitality workers before as well as twice after a smoking ban. RESULTS: At baseline, secondhand smoke-exposed hospitality workers had lung function values significantly below the population average. After the smoking ban, the covariate-adjusted odds ratio for cough was 0.59 (95% confidence interval, 0.36 to 0.93) and for chronic bronchitis 0.75 (95% confidence interval, 0.55 to 1.02) compared with the preban period. CONCLUSIONS: The below-average lung function before the smoking ban indicates chronic damages from long-term exposure. Respiratory symptoms such as cough decreased within 12 months after the ban.

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OBJECTIVES: The aim of the study was to assess whether prospective follow-up data within the Swiss HIV Cohort Study can be used to predict patients who stop smoking; or among smokers who stop, those who start smoking again. METHODS: We built prediction models first using clinical reasoning ('clinical models') and then by selecting from numerous candidate predictors using advanced statistical methods ('statistical models'). Our clinical models were based on literature that suggests that motivation drives smoking cessation, while dependence drives relapse in those attempting to stop. Our statistical models were based on automatic variable selection using additive logistic regression with component-wise gradient boosting. RESULTS: Of 4833 smokers, 26% stopped smoking, at least temporarily; because among those who stopped, 48% started smoking again. The predictive performance of our clinical and statistical models was modest. A basic clinical model for cessation, with patients classified into three motivational groups, was nearly as discriminatory as a constrained statistical model with just the most important predictors (the ratio of nonsmoking visits to total visits, alcohol or drug dependence, psychiatric comorbidities, recent hospitalization and age). A basic clinical model for relapse, based on the maximum number of cigarettes per day prior to stopping, was not as discriminatory as a constrained statistical model with just the ratio of nonsmoking visits to total visits. CONCLUSIONS: Predicting smoking cessation and relapse is difficult, so that simple models are nearly as discriminatory as complex ones. Patients with a history of attempting to stop and those known to have stopped recently are the best candidates for an intervention.

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BACKGROUND: Superinfection with drug resistant HIV strains could potentially contribute to compromised therapy in patients initially infected with drug-sensitive virus and receiving antiretroviral therapy. To investigate the importance of this potential route to drug resistance, we developed a bioinformatics pipeline to detect superinfection from routinely collected genotyping data, and assessed whether superinfection contributed to increased drug resistance in a large European cohort of viremic, drug treated patients. METHODS: We used sequence data from routine genotypic tests spanning the protease and partial reverse transcriptase regions in the Virolab and EuResist databases that collated data from five European countries. Superinfection was indicated when sequences of a patient failed to cluster together in phylogenetic trees constructed with selected sets of control sequences. A subset of the indicated cases was validated by re-sequencing pol and env regions from the original samples. RESULTS: 4425 patients had at least two sequences in the database, with a total of 13816 distinct sequence entries (of which 86% belonged to subtype B). We identified 107 patients with phylogenetic evidence for superinfection. In 14 of these cases, we analyzed newly amplified sequences from the original samples for validation purposes: only 2 cases were verified as superinfections in the repeated analyses, the other 12 cases turned out to involve sample or sequence misidentification. Resistance to drugs used at the time of strain replacement did not change in these two patients. A third case could not be validated by re-sequencing, but was supported as superinfection by an intermediate sequence with high degenerate base pair count within the time frame of strain switching. Drug resistance increased in this single patient. CONCLUSIONS: Routine genotyping data are informative for the detection of HIV superinfection; however, most cases of non-monophyletic clustering in patient phylogenies arise from sample or sequence mix-up rather than from superinfection, which emphasizes the importance of validation. Non-transient superinfection was rare in our mainly treatment experienced cohort, and we found a single case of possible transmitted drug resistance by this route. We therefore conclude that in our large cohort, superinfection with drug resistant HIV did not compromise the efficiency of antiretroviral treatment.

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BACKGROUND: We aimed to study the incidence and outcome of severe traumatic brain injury (TBI) in Switzerland and to test the feasibility of a large cohort study with case identification in the first 24 hours and 6-month follow-up. METHODS: From January to June 2005, we consecutively enrolled and followed up all persons with severe TBI (Abbreviated Injury Score of the head region >3 and Glasgow Coma Scale <9) in the catchment areas of 3 Swiss medical centres with neurosurgical facilities. The primary outcome was the Extended Glasgow Outcome Scale (GOSE) after 6 months. Secondary outcomes included survival, Functional Independence Mea - sure (FIM), and health-related quality of life (SF-12) at defined time-points up to 6 months after injury. RESULTS: We recruited 101 participants from a source population of about 2.47 million (ie, about 33% of Swiss population). The incidence of severe TBI was 8.2 per 100,000 person-years. The overall case fatality was 70%: 41 of 101 persons (41%) died at the scene of the accident. 23 of 60 hospitalised participants (38%) died within 48 hours, and 31 (53%) within 6 months. In all hospitalised patients, the median GOSE was 1 (range 1-8) after 6 months, and was 6 (2-8) in 6-month survivors. The median total FIM score was 125 (range 18-126); median-SF-12 component mea - sures were 44 (25-55) for the physical scale and 52 (32-65) for the mental scale. CONCLUSIONS: Severe TBI was associated with high case fatality and considerable morbidity in survivors. We demonstrated the feasibility of a multicentre cohort study in Switzerland with the aim of identifying modifiable determinants of outcome and improving current trauma care.

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Background: A nti-TNF d rugs (Infliximab (IFX), Adalimumab (ADA), Certolizumab pegol (CZP)) are effective in inducing and maintaining response a nd remission in i nflammatory bowel disease (IBD). Insufficient response or side effects may lead to a switch o f the anti-TNF d rug. W e aimed to e valuate the frequency and reasons for anti-TNF switches. Methods: Analysis of data from the Swiss Inflammatory Bowel Disease Cohort (SIBDCS). Eighty percent of included patients were recruited in hospitals and 20% from private practice. Results: From 2,058 patients ( 1,172 with Crohn's disease (CD), 842 with ulcerative colitis (UC) and 44 with indeterminate colitis (IC)), 772 received at least one anti-TNF. Forty-eight % of patients w ith CD, 23% with U C, a nd 30% with IC w ere ever treated with an anti-TNF drug. There was no gender difference with respect to the frequency of a nti-TNF treatment. A total of 584 patients (76%) were treated with one, 142 (18%) with two, and 46 (6%) with three anti-TNF (of which 32 were female). A total of 89% patients were treated with IFX, 28% ADA and 13% with CZP. Overall response rate (defined as drop in CDAI >100 points) to anti-TNF was 50%, with best response rates for the first used anti-TNF. Reasons t o switch t he anti-TNF w ere in 11% a primary non-response, in 38% a loss of response and in 36% anti-TNF s ide effects o r intolerance ( reasons for 15% of treatment failures not documented). Conclusion: A nti-TNF d rugs were used in h alf of the CD patients a nd in o ne quarter of U C patients. Anti-TNF d rug switch d ue to insufficient response a nd/or side effects w as necessary in one quarter of IBD patients. IFX was mainly used as first-line therapy. Best response rates were observed for the first used anti-TNF. Following analyses will identify risk median treatment duration as well as risk factors for anti-TNF switch.

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Over the last decade, mortality from oral and pharyngeal cancer has been declining in most European countries, but it had been increasing substantially in Hungary, Slovakia and a few other countries of central Europe, reaching rates comparable to those of lung cancer in several western European countries in males. To update trends in oral cancer mortality and further analyse the recent epidemic in central Europe, official death certifications for oral and pharyngeal cancer for 37 European countries were derived over the period 1970-2007, and an age-period-cohort model was fitted for selected countries. Male oral cancer mortality continued to decline in most European countries, including the Russian Federation, and, more importantly, it also started to decline in some of the countries with the highest male rates, i.e. Hungary and Slovakia; persisting rises were, however, observed in Belarus, Bulgaria and Romania. Oral cancer mortality rates for women were lower than in men and showed no appreciable trend over recent periods in the EU overall. Estimates from the age-period-cohort analysis for most selected countries showed a fall in effects for the cohorts born after the 1950s. For the period effect displayed a rise for the earlier periods, an inversion in the 1990s and a continuous fall up to the last studied period. Only some former non-market economy countries, like Romania, Ukraine and Lithuania, had rising cohort effect trends up to most recent generations. The major finding of this updated analysis of oral cancer mortality is the leveling of the epidemic for men in most European countries, including Hungary and other central European countries, where mortality from this cancer was exceedingly high. These trends essentially reflect the changes in alcohol and tobacco consumption in various populations.

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Background. Des études précédentes ont démontré l'efficacité et la tolérance de l'adalimumab chez les patients avec maladie de Crohn modérée ou sévère. Les patients qu'on rencontre dans la pratique quotidienne peuvent être différents des patients rigoureusement sélectionnés dans les études contrôlées.But. Dans ce travail, nous résumons notre expérience avec l'adalimumab durant une période de 3 ans.Méthodes. Nous avons analysé rétrospectivement les dossiers de 55 patients atteints d'une maladie de Crohn modérée ou sévère et traités par adalimumab dans les hôpitaux universitaires de Bâle, Zurich, Genève et Lausanne, ainsi que dans un cabinet médical à Olten. Les informations collectées étaient les suivantes : données démographiques, localisation, phénotype et durée de la maladie, traitements chirurgicaux précédents, traitements précédents par anti-TNF alpha ou immunosuppresseur, le traitement concomitant et l'activité de la maladie à la « baseline » et durant le traitement. La sévérité de la maladie à l'inclusion a été établie en utilisant le score Harvey- Bradshaw Index (HBI). Durant le traitement, la rémission a été définie avec un HBI<4 et la réponse comme une réduction de l'HBI de plus de 3 points. L'analyse de régression logistique univariée a été utilisée pour déterminer si les variables étudiées étaient associées à la réponse ou à la rémission durant le traitement.Résultats. L'âge moyen des patients a été de 37.5 ± 11.4 ans et la durée moyenne de maladie à été de 12.7 ans. 29 des 55 patients étaient des fumeurs. Le traitement d'induction a été effectué chez 31 patients avec l'adalimumab en sous-cutané 160 mg à la semaine 0 et 80 mg à la semaine 2 et chez 24 patients avec 80 mg à la semaine 0 et 40 mg à la semaine 2. Le traitement d'entretien a été de 40 mg en sous-cutané toutes les 2 semaines. 13 patients (23.6%) ont nécessité l'augmentation de la dose d'adalimumab pour maintenir la rémission ou la réponse.Le taux de rémission et de réponse à la semaine 4-6 était de 52.7%, respectivement 83.6%. La rémission a été maintenue aux semaines 12, 24 et 52 chez 89.6%, 72.4%, respectivement 44.7% des patients. Le taux de rémission et de réponse n'a pas été influencé par le tabagisme, la location ou la durée de la maladie, la dose totale donnée durant le premier mois de traitement, la dose d'adalimumab par kilogramme-corps ou par le traitement précédent par infliximab. La rémission à la semaine 4-6 a été significativement plus élevée chez les patients intolérants à l'infliximab comparativement à ceux qui avaient perdu la réponse à l'infliximab (78.9% vs 42.1%, p=0.02). Le traitement par adalimumab a été bien toléré. Les effets secondaires les plus signalés ont été : la douleur au site d'injection (10.9%), l'asthénie (9%) et des infections (7.2%).Conclusions. L'adalimumab a démontré une bonne efficacité et tolérance dans la pratique quotidienne chez les patients avec une maladie de Crohn modérée ou sévère.

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RYR1 mutations are the most common cause of structural congenital myopathies and may exhibit both dominant and recessive inheritance. Histopathological findings are variable and include central cores, multi-minicores, type 1 predominance/ uniformity, fibre type disproportion, increased internal nucleation and fatty and connective tissue. Until recently, diagnostic RYR1 sequencing was limited to mutational hotspots due to the large size of the gene. Since the introduction of full RYR1 sequencing in 2007 we have detected pathogenic mutations in 77 families: 39 had dominant inheritance and 38 recessive inheritance. In some cases with presumably recessive inheritance, only one heterozygous mutation inherited from an asymptomatic parent was identified. Of 28 dominant mutations, 6 were novel; 37 of the 59 recessive mutations were also novel. Dominant mutations were more frequently in recognized hotspot regions, while recessive mutations were distributed throughout the coding sequence. Dominant mutations were predominantly missense, whereas recessive mutations included many nonsense and splice mutations expected to result in reduced RyR1 protein. There was wide clinical variability in patients with both dominant and recessive inheritance. As a group, those with dominant mutations were generally more mildly affected than those with recessive inheritance, who had earlier onset and were weaker with more functional limitations. Extraocular muscle involvement was almost exclusively observed in the recessive group. Bulbar involvement was also more prominent in this group, resulting in a larger number requiring gastrostomy insertion. In conclusion, genomic sequencing of the entire RYR1 leads to the detection of many novel mutations, but may miss large genetic rearrangements in some cases. Assigning pathogenicity to novel mutations is often difficult and interpretation of genetic results in the context of clinical, histological and, increasingly, muscle MRI findings is essential.

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BACKGROUND: Adherence to guidelines is associated with improved outcomes of patients with acute coronary syndrome (ACS). Clinical registries developed to assess quality of care at discharge often do not collect the reasons for non-prescription for proven efficacious preventive medication in Continental Europe. In a prospective cohort of patients hospitalized for an ACS, we aimed at measuring the rate of recommended treatment at discharge, using pre-specified quality indicators recommended in cardiologic guidelines and including systematic collection of reasons for non-prescription for preventive medications. METHODS: In a prospective cohort with 1260 patients hospitalized for ACS, we measured the rate of recommended treatment at discharge in 4 academic centers in Switzerland. Performance measures for medication at discharge were pre-specified according to guidelines, systematically collected for all patients and included in a centralized database. RESULTS: Six hundred and eighty eight patients(54.6%) were discharged with a main diagnosis of STEMI, 491(39%) of NSTEMI and 81(6.4%) of unstable angina. Mean age was 64 years and 21.3% were women. 94.6% were prescribed angiotensin converting enzyme inhibitors/angiotensin II receptor blockers at discharge when only considering raw prescription rates, but increased to 99.5% when including reasons non-prescription. For statins, rates increased from 98% to 98.6% when including reasons for non-prescription and for beta-blockers, from 82% to 93%. For aspirin, rates further increased from 99.4% to 100% and from to 99.8% to 100% for P2Y12 inhibitors. CONCLUSIONS: We found a very high adherence to ACS guidelines for drug prescriptions at discharge when including reasons for non-prescription to drug therapy. For beta-blockers, prescription rates were suboptimal, even after taking into account reason for non-prescription. In an era of improving quality of care to achieve 100% prescription rates at discharge unless contra-indicated, pre-specification of reasons for non-prescription for cardiovascular preventive medication permits to identify remaining gaps in quality of care at discharge. TRIAL REGISTRATION: ClinicalTrials.gov NCT01000701.