Abortion trends 1990-1999 in a Swiss region and determinants of abortion recurrence.

OBJECTIVE: To assess age- and nationality-specific trends in abortion rates over the last decade, and to describe women's characteristics, identifying risk factors for repeated abortion. METHODS: From 1990-1999, the Health Department of Canton Vaud (Switzerland) received 13'857 abortion requests from residents aged 14-49. Population data were obtained to compute rates. RESULTS: Both the number of abortions (1400 annually) as well as their rate (8.9 per thousand women [95% confidence interval (CI) 7.3-10.5]) were stable over the decade in question. The rate of abortion for foreign women, especially from ex-Yugoslavia and Africa, was twice that for Swiss women. Half of the requests came from single women, 43% had a low education level, and half were childless. The main reason for requesting termination of pregnancy was psychosocial (93%). The mean gestational age was 7.7 weeks (SD +/- 2.3), but 96% of requests were submitted before 12 weeks. Sixty-three percent of women reported that they had used no contraception, 36% the condom and 17% the pill. Among requests, the adjusted risk of repeated abortion (22% of abortion candidates) was greater among divorced/separated/widowed women (odds ratio [OR] 1.9 [95% CI 1.5-2.4]), unemployed women (OR 1.8 [95% CI 1.5-2.1]), and those who had not attended university (OR 1.6 [95% CI 1.1-2.2]). CONCLUSIONS: Although Swiss law only permitted abortion under strict conditions, this procedure was widely available in Vaud, which nevertheless has one of the lowest rates worldwide. Efforts must be intensified to ensure universal access to family planning services, especially for foreign women and adolescents. Professionals should also target "repeaters" to provide personalised counselling.

Effects of recommended levels of physical activity on pregnancy outcomes.

OBJECTIVE: We sought to examine the relation between recommended levels of physical activity during pregnancy and pregnancy outcomes. STUDY DESIGN: We conducted an observational study with energy expenditure, aerobic fitness, and sleeping heart rate measured in 44 healthy women in late pregnancy. Medical records were examined for pregnancy outcome. RESULTS: Active women, who engaged in > or = 30 minutes of moderate physical activity per day, had significantly better fitness and lower sleeping heart rate compared to the inactive. Duration of second stage of labor was 88 and 146 minutes in the active vs inactive women, respectively (P = .05). Crude odds ratio of operative delivery in the inactive vs the active was 3.7 (95% confidence interval, 0.87-16.08). Birthweight, maternal weight gain, and parity adjusted odds ratio was 7.6 (95% confidence interval, 1.23-45.8). Neonatal condition and other obstetric outcomes were similar between groups. CONCLUSION: Active women have better aerobic fitness as compared to inactive women. The risk for operative delivery is lower in active women compared to inactive, when controlled for birthweight, maternal weight gain, and parity. Further studies with larger sample size are required to confirm the association between physical activity and pregnancy outcomes.

Perception of damaging effects of smoking, and brief cessation counselling by doctors : a comparison between native Swiss and immigrants

Résumé Une étude prospective ouverte a été menée parmi les patients venant pour la première fois, sans rendez-vous et en urgence, dans une policlinique urbaine (où plus de la moitié des patients sont d'origine étrangère) pour déterminer si les connaissances sur les méfaits du tabac sont identiques chez les immigrés et les Suisses, si le niveau d'intégration influence les connaissances et si les médecins du service donnent des conseils aussi souvent aux fumeurs Suisses qu'aux fumeurs étrangers. 226 fumeurs ont participé à l'étude, 105 Suisses (46.5%) et 121 étrangers (53,5%). 32.2% (95% IC [24.4%; 41.1%]) des migrants et 9.6% [5.3% ; 16.8%] des Suisses ne pouvaient pas mentionner un effet nocif du tabac. Après ajustement pour l'âge, l'analyse multivariée montre que le risque d'ignorer les méfaits du tabac est plus élevé pour les personnes ne maîtrisant pas la langue locale que pour celles la maîtrisant (odds ratio (OR)=7.5 [3.6; 15.8], p<0,001), et est plus élevé pour les hommes que pour les femmes (OR=4.3 [1.9 10.0], p<0.001). Un conseil pour arrêter de fumer a été donné avec une égale fréquence aux immigrants (31.9% [24.2% ; 40.1%]) et aux Suisses (29% [21.0% ; 38.5%]). Les patients ne maîtrisant pas la langue locale n'ont pas reçu moins de conseil que ceux la maîtrisant (0R-1.1 [0.6 ; 2.1], p=0.812). En conclusion, le niveau de connaissances des méfaits du tabac est moins bon chez les hommes immigrés non intégrés ou qui ne maîtrisent pas la langue locale. Un conseil sur l'arrêt du tabac n'est donné qu'à une minorité, mais à égale fréquence à tous les patients du service, quelle que soit leur nationalité. Abstract An open prospective study was conducted among the patients visiting an urban medical policlinic for the first time without an appointment to assess whether the immigrants (who represent more than half of our patients) are aware of the health effects of smoking, whether the level of acculturation influences knowledge, and whether doctors give similar advice to Swiss and foreign smokers. 226 smokers, 105 Swiss (46.5%), and 121 foreign-born (53.5%), participated in the study. 32.2% (95% CI [24.4%; 41.1%]) of migrants and 9.6% [5.3%; 16.8%] of Swiss patients were not aware of negative effects of smoking. After adjustment for age, the multivariate model showed that the estimated odds of "ignorance of health effects of smoking" was higher for people lacking mastery of the local language compared with those mastering it (odds ratio (OR) = 7.5 [3.6; 15.8], p <0.001), and higher for men (OR 4.3 [1.9; 10.0], p <0.001). Advice to stop smoking was given with similar frequency to immigrants (31.9% [24.2%; 40.8%] and Swiss patients (29.0% [21.0%; 38.5%]). Non-integrated patients did not appear to receive less counselling than integrated patients (OR = 1.1 [0.6; 2.1], p 0.812). We conclude that the level of knowledge among male immigrants not integrated or unable to speak the local language is lower than among integrated foreign-born and Swiss patients. Smoking cessation counselling by a doctor was only given to a minority of patients, but such counselling seemed irrespective of nationality.

Association of smoking and nicotine dependence with pre-diabetes in young and healthy adults.

INTRODUCTION: Several studies have shown an increased risk of type 2 diabetes among smokers. Therefore, the aim of this analysis was to assess the relationship between smoking, cumulative smoking exposure and nicotine dependence with pre-diabetes. METHODS: We performed a cross-sectional analysis of healthy adults aged 25-41 in the Principality of Liechtenstein. Individuals with known diabetes, Body Mass Index (BMI) >35 kg/m² and prevalent cardiovascular disease were excluded. Smoking behaviour was assessed by self-report. Pre-diabetes was defined as glycosylated haemoglobin between 5.7% and 6.4%. Multivariable logistic regression models were done. RESULTS: Of the 2142 participants (median age 37 years), 499 (23.3%) had pre-diabetes. There were 1,168 (55%) never smokers, 503 (23%) past smokers and 471 (22%) current smokers, with a prevalence of pre-diabetes of 21.2%, 20.9% and 31.2%, respectively (p <0.0001). In multivariable regression models, current smokers had an odds ratio (OR) of pre-diabetes of 1.82 (95% confidential interval (CI) 1.39; 2.38, p <0.0001). Individuals with a smoking exposure of <5, 5-10 and >10 pack-years had an OR (95% CI) for pre-diabetes of 1.34 (0.90; 2.00), 1.80 (1.07; 3.01) and 2.51 (1.80; 3.59) (p linear trend <0.0001) compared with never smokers. A Fagerström score of 2, 3-5 and >5 among current smokers was associated with an OR (95% CI) for pre-diabetes of 1.27 (0.89; 1.82), 2.15 (1.48; 3.13) and 3.35 (1.73; 6.48) (p linear trend <0.0001). DISCUSSION: Smoking is strongly associated with pre-diabetes in young adults with a low burden of smoking exposure. Nicotine dependence could be a potential mechanism of this relationship.

A mixed approach for proving non-inferiority in clinical trials with binary endpoints

When a new treatment is compared to an established one in a randomized clinical trial, it is standard practice to statistically test for non-inferiority rather than for superiority. When the endpoint is binary, one usually compares two treatments using either an odds-ratio or a difference of proportions. In this paper, we propose a mixed approach which uses both concepts. One first defines the non-inferiority margin using an odds-ratio and one ultimately proves non-inferiority statistically using a difference of proportions. The mixed approach is shown to be more powerful than the conventional odds-ratio approach when the efficacy of the established treatment is known (with good precision) and high (e.g. with more than 56% of success). The gain of power achieved may lead in turn to a substantial reduction in the sample size needed to prove non-inferiority. The mixed approach can be generalized to ordinal endpoints.

Laparoscope use and surgical site infections in digestive surgery

Rapport de synthèse : But: comparer les taux d'infections du site chirurgical (ISC) en fonction de la voie d'abord, ouverte ou laparoscopique, pour 3 procédures : l'appendicectomie, la cholécystectomie et la colectomie. Evaluer l'effet de la laparoscopie sur l'ISC pour ces trois interventions. Contexte : la laparoscopie est associée à de nombreux avantages par rapport à la chirurgie ouverte. Parmi ceux-ci, des taux inférieurs d'ISC ont été rapportés lors de laparoscopie. Ceci a été décrit en particulier lors de cholécystectomie. Mais des biais tels que le manque de suivi après la sortie de l'hôpital, et certains facteurs confondants, auraient pu contribuer à l'observation de différences entre ces deux techniques. Méthode : étude descriptive basée sur des données collectées entre mars 1998 et décembre 2004 de manière prospective dans le cadre d'un programme de surveillance des ISC dans 8 hôpitaux suisses. Ce programme comportait un suivi standardisé après le départ de l'hôpital. Les taux d'ISC ont été comparés après interventions faites par laparoscopie et chirurgie ouverte. Différents paramètres pouvant influencer la survenue d'une infection ont été identifiés en utilisant des modèles de régression logistiques. Résultats : les taux d'ISC après interventions par laparoscopie et par voie ouverte ont été respectivement de 59/1051 (5.6%) versus 117/1417 (8.3%) après appendicectomie (p = 0.01), 46/2606 (1.7%) versus 35/144 (7.9%) après cholécystectomie (p < 0.0001), et 35/311 (11.3%) versus 400/1781 (22.5%) après colectomie (p < 0,0001). Après ajustement, les interventions par laparoscopie étaient associées à un taux inférieur d'ISC : odds ratio = 0.61 (IC 95% : 0.43 - 0.87) pour l'appendicectomie, 0.27 (0.16 - 0.43) pour la cholécystectomie et 0.43 (0.29 - 0.63) pour la colectomie. Discussion et conclusion : bien que les patients aient quitté plus tôt l'hôpital après une intervention laparoscopique, leur suivi à un mois a été identique, ce qui a permis d'éviter une sous-estimation des ISC après chirurgie laparoscopique. De plus, l'analyse multivariée a inclus de nombreux facteurs potentiellement confondants, et l'utilisation de la laparoscopie était indépendamment et significativement liée à un effet protecteur à l'égard de l'ISC. La laparoscopie lors d'appendicectomie, cholécystectomie et colectomie semble diminuer le taux d'ISC en comparaison à la même chirurgie pratiquée par voie ouverte. Lorsqu'elle est faisable, cette voie d'abord minimalement invasive devrait être préférée à la chirurgie ouverte.

Tools in pharmacovigilance in psychiatry: therapeutic drug monitoring, pharmacogenetic tests and drug-drug interactions databases

SUMMARYIn order to increase drug safety we must better understand how medication interacts with the body of our patients and this knowledge should be made easily available for the clinicians prescribing the medication. This thesis contributes to how the knowledge of some drug properties can increase and how to make information readily accessible for the medical professionals. Furthermore it investigates the use of Therapeutic drug monitoring, drug interaction databases and pharmacogenetic tests in pharmacovigilance.Two pharmacogenetic studies in the naturalistic setting of psychiatric in-patients clinics have been performed; one with the antidepressant mirtazapine, the other with the antipsychotic clozapine. Forty-five depressed patients have been treated with mirtazapine and were followed for 8 weeks. The therapeutic effect was as seen in other previous studies. Enantioselective analyses could confirm an influence of age, gender and smoking in the pharmacokinetics of mirtazapine; it showed a significant influence of the CYP2D6 genotype on the antidepressant effective S-enantiomer, and for the first time an influence of the CYP2B6 genotype on the plasma concentrations of the 8-OH metabolite was found. The CYP2B6*/*6 genotype was associated to better treatment response. A detailed hypothesis of the metabolic pathways of mirtazapine is proposed. In the second pharmacogenetic study, analyses of 75 schizophrenic patients treated with clozapine showed the influence of CYP450 and ABCB1 genotypes on its pharmacokinetics. For the first time we could demonstrate an in vivo effect of the CYP2C19 genotype and an influence of P-glycoprotein on the plasma concentrations of clozapine. Further we confirmed in vivo the prominent role of CYP1A2 in the metabolism of clozapine.Identifying risk factors for the occurrence of serious adverse drug reactions (SADR) would allow a more individualized and safer drug therapy. SADR are rare events and therefore difficult to study. We tested the feasibility of a nested matched case-control study to examine the influence of high drug plasma levels and CYP2D6 genotypes on the risk to experience an SADR. In our sample we compared 62 SADR cases with 82 controls; both groups were psychiatric patients from the in-patient clinic Königsfelden. Drug plasma levels of >120% of the upper recommended references could be identified as a risk factor with a statistically significant odds ratio of 3.5, a similar trend could be seen for CYP2D6 poor metaboliser. Although a matched case-control design seems a valid method, 100% matching is not easy to perform in a relative small cohort of one in-patient clinic. However, a nested case-control study is feasible.On the base of the experience gained in the AMSP+ study and the fact that we have today only sparse data indicating that routine drug plasma concentration monitoring and/or pharmacogenetic testing in psychiatry are justified to minimize the risk for ADR, we developed a test algorithm named "TDM plus" (TDM plus interaction checks plus pharmacogenetic testing).Pharmacovigilance programs such as the AMSP project (AMSP = Arzneimittelsicherheit in der Psychiatrie) survey psychiatric in-patients in order to collect SADR and to detect new safety signals. Case reports of such SADR are, although anecdotal, valuable to illustrate rare clinical events and sometimes confirm theoretical assumptions of e.g. drug interactions. Seven pharmacovigilance case reports are summarized in this thesis.To provide clinicians with meaningful information on the risk of drug combinations, during the course of this thesis the internet based drug interaction program mediQ.ch (in German) has been developed. Risk estimation is based on published clinical and pharmacological information of single drugs and alimentary products, including adverse drug reaction profiles. Information on risk factors such as renal and hepatic insufficiency and specific genotypes are given. More than 20'000 drug pairs have been described in detail. Over 2000 substances with their metabolic and transport pathways are included and all information is referenced with links to the published scientific literature or other information sources. Medical professionals of more than 100 hospitals and 300 individual practitioners do consult mediQ.ch regularly. Validations with comparisons to other drug interaction programs show good results.Finally, therapeutic drug monitoring, drug interaction programs and pharmacogenetic tests are helpful tools in pharmacovigilance and should, in absence of sufficient routine tests supporting data, be used as proposed in our TDM plus algorithm.RESUMEPour améliorer la sécurité d'emploi des médicaments il est important de mieux comprendre leurs interactions dans le corps des patients. Ensuite le clinicien qui prescrit une pharmacothérapie doit avoir un accès simple à ces informations. Entre autres, cette thèse contribue à mieux connaître les caractéristiques pharmacocinétiques de deux médicaments. Elle examine aussi l'utilisation de trois outils en pharmacovigilance : le monitorage thérapeutique des taux plasmatiques des médicaments (« therapeutic drug monitoring »), un programme informatisé d'estimation du risque de combinaisons médicamenteuses, et enfin des tests pharmacogénétiques.Deux études cliniques pharmacogénétiques ont été conduites dans le cadre habituel de clinique psychiatrique : l'une avec la mirtazapine (antidépresseur), l'autre avec la clozapine (antipsychotique). On a traité 45 patients dépressifs avec de la mirtazapine pendant 8 semaines. L'effet thérapeutique était semblable à celui des études précédentes. Nous avons confirmé l'influence de l'âge et du sexe sur la pharmacocinétique de la mirtazapine et la différence dans les concentrations plasmatiques entre fumeurs et non-fumeurs. Au moyen d'analyses énantiomères sélectives, nous avons pu montrer une influence significative du génotype CYP2D6 sur l'énantiomère S+, principalement responsable de l'effet antidépresseur. Pour la première fois, nous avons trouvé une influence du génotype CYP2B6 sur les taux plasmatiques de la 8-OH-mirtazapine. Par ailleurs, le génotype CYP2B6*6/*6 était associé à une meilleure réponse thérapeutique. Une hypothèse sur les voies métaboliques détaillées de la mirtazapine est proposée. Dans la deuxième étude, 75 patients schizophrènes traités avec de la clozapine ont été examinés pour étudier l'influence des génotypes des iso-enzymes CYP450 et de la protéine de transport ABCB1 sur la pharmacocinétique de cet antipsychotique. Pour la première fois, on a montré in vivo un effet des génotypes CYP2C19 et ABCB1 sur les taux plasmatiques de la clozapine. L'importance du CYP1A2 dans le métabolisme de la clozapine a été confirmée.L'identification de facteurs de risques dans la survenue d'effets secondaire graves permettrait une thérapie plus individualisée et plus sûre. Les effets secondaires graves sont rares. Dans une étude de faisabilité (« nested matched case-control design » = étude avec appariement) nous avons comparé des patients avec effets secondaires graves à des patients-contrôles prenant le même type de médicaments mais sans effets secondaires graves. Des taux plasmatiques supérieurs à 120% de la valeur de référence haute sont associés à un risque avec « odds ratio » significatif de 3.5. Une tendance similaire est apparue pour le génotype du CYP2D6. Le « nested matched case-control design » semble une méthode valide qui présente cependant une difficulté : trouver des patients-contrôles dans le cadre d'une seule clinique psychiatrique. Par contre la conduite d'une « nested case-control study » sans appariement est recommandable.Sur la base de notre expérience de l'étude AMSP+ et le fait que nous disposons que de peux de données justifiant des monitorings de taux plasmatiques et/ou de tests pharmacogénétiques de routine, nous avons développé un test algorithme nommé « TDMplus » (TDM + vérification d'interactions médicamenteuses + tests pharmacogénétique).Des programmes de pharmacovigilances comme celui de l'AMSP (Arzneimittelsicherheit in der Psychiatrie = pharmacovigilance en psychiatrie) collectent les effets secondaires graves chez les patients psychiatriques hospitalisés pour identifier des signaux d'alertes. La publication de certains de ces cas même anecdotiques est précieuse. Elle décrit des événements rares et quelques fois une hypothèse sur le potentiel d'une interaction médicamenteuse peut ainsi être confirmée. Sept publications de cas sont résumées ici.Dans le cadre de cette thèse, on a développé un programme informatisé sur internet (en allemand) - mediQ.ch - pour estimer le potentiel de risques d'une interaction médicamenteuse afin d'offrir en ligne ces informations utiles aux cliniciens. Les estimations de risques sont fondées sur des informations cliniques (y compris les profils d'effets secondaires) et pharmacologiques pour chaque médicament ou substance combinés. Le programme donne aussi des informations sur les facteurs de risques comme l'insuffisance rénale et hépatique et certains génotypes. Actuellement il décrit en détail les interactions potentielles de plus de 20'000 paires de médicaments, et celles de 2000 substances actives avec leurs voies de métabolisation et de transport. Chaque information mentionne sa source d'origine; un lien hypertexte permet d'y accéder. Le programme mediQ.ch est régulièrement consulté par les cliniciens de 100 hôpitaux et par 300 praticiens indépendants. Les premières validations et comparaisons avec d'autres programmes sur les interactions médicamenteuses montrent de bons résultats.En conclusion : le monitorage thérapeutique des médicaments, les programmes informatisés contenant l'information sur le potentiel d'interaction médicamenteuse et les tests pharmacogénétiques sont de précieux outils en pharmacovigilance. Nous proposons de les utiliser en respectant l'algorithme « TDM plus » que nous avons développé.

Intrauterine exposure to carbamazepine and specific congenital malformations: systematic review and case-control study.

OBJECTIVE: To identify specific major congenital malformations associated with use of carbamazepine in the first trimester of pregnancy. DESIGN: A review of all published cohort studies to identify key indications and a population based case-control study to test these indications. SETTING: Review of PubMed, Web of Science, and Embase for papers about carbamazepine exposure in the first trimester of pregnancy and specific malformations, and the EUROCAT Antiepileptic Study Database, including data from 19 European population based congenital anomaly registries, 1995-2005. PARTICIPANTS: The literature review covered eight cohort studies of 2680 pregnancies with carbamazepine monotherapy exposure, and the EUROCAT dataset included 98 075 registrations of malformations covering over 3.8 million births. MAIN OUTCOME MEASURES: Overall prevalence for a major congenital malformation after exposure to carbamazepine monotherapy in the first trimester. Odds ratios for malformations with exposure to carbamazepine among cases (five types of malformation identified in the literature review) compared with two groups of controls: other non-chromosomal registrations of malformations and chromosomal syndromes. RESULTS: The literature review yielded an overall prevalence for a major congenital malformation of 3.3% (95% confidence interval 2.7 to 4.2) after exposure to carbamazepine monotherapy in the first trimester. In 131 registrations of malformations, the fetus had been exposed to carbamazepine monotherapy. Spina bifida was the only specific major congenital malformation significantly associated with exposure to carbamazepine monotherapy (odds ratio 2.6 (95% confidence interval 1.2 to 5.3) compared with no antiepileptic drug), but the risk was smaller for carbamazepine than for valproic acid (0.2, 0.1 to 0.6). There was no evidence for an association with total anomalous pulmonary venous return (no cases with carbamazepine exposure), cleft lip (with or without palate) (0.2, 0.0 to 1.3), diaphragmatic hernia (0.9, 0.1 to 6.6), or hypospadias (0.7, 0.3 to 1.6) compared with no exposure to antiepileptic drugs. Further exploratory analysis suggested a higher risk of single ventricle and atrioventricular septal defect. CONCLUSION: Carbamazepine teratogenicity is relatively specific to spina bifida, though the risk is less than with valproic acid. Despite the large dataset, there was not enough power to detect moderate risks for some rare major congenital malformations.

Quels sont les facteurs de risque d'une bactériémie à Stenotrophomonas maltophilia chez les patients nonatteints de mucoviscidose ?

Problématique : Stenotrophomonas maltophilia est une bactérie Gram négatif présente dans¦l'environnement mais également responsable de nombreuses infections nosocomiales. Le but de cette¦étude a été de trouver quels étaient les facteurs de risques des patients non atteints de mucoviscidose¦ayant eu une bactériémie à S. maltophilia.¦Méthode : Il s'agit d'une étude cas-témoin. La population étudiée était les patients du CHUV de plus¦de 18 ans avec une ou plus paire(s) d'hémoculture positive pour S. maltophilia entre 2000-2010, en¦excluant tout patient atteint de mucoviscidose. Les variables binaires ont été analysées par le test de¦McNemar. Les variables continues ont été comparées avec le Wilcoxon Rank-Sum test. L'analyse¦multivariée des facteurs de risque indépendants a été effectuée par une régression logistique¦conditionnelle.¦Résultats : 46 épisodes d'hémocultures positives ont été identifiés. L'insuffisance rénale, une maladie¦oncologique et l'agranulocytose ont été identifiés comme des facteurs de risques significatifs.¦L'analyse multivariée a montré les facteurs suivants sont associés indépendamment à une bactériémie :¦1) l'agranulocytose (odds ratio, 7.0 ; 95% intervalle de confiance, 1.5 - 32.2 ; p= 0.012) 2) le cancer¦(odds ratio, 4.9 ; 95% intervalle de confiance, 1.7 - 14.2 ; p= 0.003) 3)l'insuffisance rénale (odds¦ratio, 5.2 ; 95% intervalle de confiance, 1.5 - 17.4 ; p= 0.008)¦Conclusions : L'insuffisance rénale, la maladie oncologique et l'agranulocytose sont des facteurs de¦risque indépendants pour une bactériémie à S. maltophilia. Les patients présentant ces critères de¦vulnérabilité doivent donc être particulièrement surveillés.

IL28B alleles associated with poor hepatitis C virus (HCV) clearance protect against inflammation and fibrosis in patients infected with non-1 HCV genotypes.

Genetic polymorphisms near IL28B are associated with spontaneous and treatment-induced clearance of hepatitis C virus (HCV), two processes that require the appropriate activation of the host immune responses. Intrahepatic inflammation is believed to mirror such activation, but its relationship with IL28B polymorphisms has yet to be fully appreciated. We analyzed the association of IL28B polymorphisms with histological and follow-up features in 2335 chronically HCV-infected Caucasian patients. Assessable phenotypes before any antiviral treatment included necroinflammatory activity (n = 1,098), fibrosis (n = 1,527), fibrosis progression rate (n = 1,312), and hepatocellular carcinoma development (n = 1,915). Associations of alleles with the phenotypes were evaluated by univariate analysis and multivariate logistic regression, accounting for all relevant covariates. The rare G allele at IL28B marker rs8099917-previously shown to be at risk of treatment failure-was associated with lower activity (P = 0.04), lower fibrosis (P = 0.02) with a trend toward lower fibrosis progression rate (P = 0.06). When stratified according to HCV genotype, most significant associations were observed in patients infected with non-1 genotypes (P = 0.003 for activity, P = 0.001 for fibrosis, and P = 0.02 for fibrosis progression rate), where the odds ratio of having necroinflammation or rapid fibrosis progression for patients with IL28B genotypes TG or GG versus TT were 0.48 (95% confidence intervals 0.30-0.78) and 0.56 (0.35-0.92), respectively. IL28B polymorphisms were not predictive of the development of hepatocellular carcinoma. CONCLUSION: In chronic hepatitis C, IL28B variants associated with poor response to interferon therapy may predict slower fibrosis progression, especially in patients infected with non-1 HCV genotypes.

Health behaviours, socioeconomic status, and mortality: further analyses of the British Whitehall II and the French GAZEL prospective cohorts

BACKGROUND: Differences in morbidity and mortality between socioeconomic groups constitute one of the most consistent findings of epidemiologic research. However, research on social inequalities in health has yet to provide a comprehensive understanding of the mechanisms underlying this association. In recent analysis, we showed health behaviours, assessed longitudinally over the follow-up, to explain a major proportion of the association of socioeconomic status (SES) with mortality in the British Whitehall II study. However, whether health behaviours are equally important mediators of the SES-mortality association in different cultural settings remains unknown. In the present paper, we examine this issue in Whitehall II and another prospective European cohort, the French GAZEL study. METHODS AND FINDINGS: We included 9,771 participants from the Whitehall II study and 17,760 from the GAZEL study. Over the follow-up (mean 19.5 y in Whitehall II and 16.5 y in GAZEL), health behaviours (smoking, alcohol consumption, diet, and physical activity), were assessed longitudinally. Occupation (in the main analysis), education, and income (supplementary analysis) were the markers of SES. The socioeconomic gradient in smoking was greater (p<0.001) in Whitehall II (odds ratio [OR] = 3.68, 95% confidence interval [CI] 3.11-4.36) than in GAZEL (OR = 1.33, 95% CI 1.18-1.49); this was also true for unhealthy diet (OR = 7.42, 95% CI 5.19-10.60 in Whitehall II and OR = 1.31, 95% CI 1.15-1.49 in GAZEL, p<0.001). Socioeconomic differences in mortality were similar in the two cohorts, a hazard ratio of 1.62 (95% CI 1.28-2.05) in Whitehall II and 1.94 in GAZEL (95% CI 1.58-2.39) for lowest versus highest occupational position. Health behaviours attenuated the association of SES with mortality by 75% (95% CI 44%-149%) in Whitehall II but only by 19% (95% CI 13%-29%) in GAZEL. Analysis using education and income yielded similar results. CONCLUSIONS: Health behaviours were strong predictors of mortality in both cohorts but their association with SES was remarkably different. Thus, health behaviours are likely to be major contributors of socioeconomic differences in health only in contexts with a marked social characterisation of health behaviours. Please see later in the article for the Editors' Summary.

Diagnostic Accuracy of (18)F-FDG-PET and PET/CT in the Differential Diagnosis between Malignant and Benign Pleural Lesions: A Systematic Review and Meta-Analysis.

RATIONALE AND OBJECTIVES: To systematically review and meta-analyze published data about the diagnostic accuracy of fluorine-18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (CT) in the differential diagnosis between malignant and benign pleural lesions. METHODS AND MATERIALS: A comprehensive literature search of studies published through June 2013 regarding the diagnostic performance of (18)F-FDG-PET and PET/CT in the differential diagnosis of pleural lesions was carried out. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic odds ratio (DOR) of (18)F-FDG-PET or PET/CT in the differential diagnosis of pleural lesions on a per-patient-based analysis were calculated. The area under the summary receiver operating characteristic curve (AUC) was calculated to measure the accuracy of these methods. Subanalyses considering device used (PET or PET/CT) were performed. RESULTS: Sixteen studies including 745 patients were included in the systematic review. The meta-analysis of 11 selected studies provided the following results: sensitivity 95% (95% confidence interval [95%CI]: 92-97%), specificity 82% (95%CI: 76-88%), LR+ 5.3 (95%CI: 2.4-11.8), LR- 0.09 (95%CI: 0.05-0.14), DOR 74 (95%CI: 34-161). The AUC was 0.95. No significant improvement of the diagnostic accuracy considering PET/CT studies only was found. CONCLUSIONS: (18)F-FDG-PET and PET/CT demonstrated to be accurate diagnostic imaging methods in the differential diagnosis between malignant and benign pleural lesions; nevertheless, possible sources of false-negative and false-positive results should be kept in mind.

Fried potatoes and human cancer.

A considerable public concern about cancer risk from acrylamide-rich foods followed the announcement that high concentrations of acrylamide are found in fried potatoes and potato chips and, more generally, in starch-containing foods cooked at high temperatures. From a series of hospital-based case-control studies conducted in Italy and Switzerland between 1991 and 2000, we have analyzed the relation between intake of fried/baked potatoes and cancer risk. The cancer sites considered were oral cavity and pharynx (749 cases, 1772 controls), esophagus (395 cases, 1066 controls), larynx (527 cases, 1297 controls), large bowel (1225 colon and 728 rectum cases, 4154 controls), breast (2569 cases, 2588 controls) and ovary (1031 cases, 2411 controls). All cancer cases were incident and histologically confirmed. Controls were subjects admitted to the same network of hospitals of cases for acute, non-neoplastic conditions. All the odds ratios (OR) for the highest vs. the lowest tertile of intake ranged between 0.8-1.1. We found no evidence of interaction with age, gender, alcohol and tobacco use. Our data provide reassuring evidence for the lack of an important association between consumption of fried/baked potatoes and cancer risk.

Acidentes ocupacionais por exposição a material biológico entre a equipe multiprofissional do atendimento pré-hospitalar

Estudo transversal, tipo survey, realizado com a equipe multiprofissional de Atendimento Pré-hospitalar (APh) de Belo Horizonte, entre junho e dezembro de 2006. Objetivou-se determinar a incidência dos acidentes ocupacionais por exposição a material biológico, condutas pós-acidente, e fatores demográficos determinantes. Utilizou-se questionário estruturado, análise descritiva, cálculo de incidências e regressão logística. A incidência de acidentes com material biológico foi de 20,6%: 40,8% por pérfuro-cortantes e 49,0% por fluidos corporais; 35,3% entre médicos e 24,0% entre enfermeiros. Condutas pós-acidente: sem avaliação médica, 63,3%; subnotificação, 81,6%; nenhuma conduta, 55,0%; e, sem acompanhamento sorológico, 61,2%. Estiveram associados ao acidente: tempo na instituição (Odds ratio-OR 2,84; Intervalo de confiança-IC 95% 1,22-6,62), lotação na Unidade de Suporte Avançado (OR 4,18; IC 95% 1,64-10,64); interação: tempo na instituição e lotação na Unidade de Suporte Básico (OR 0,27; IC 95% 0,07-1,00). Sugere-se a implantação de protocolos pós-acidentes, visando a sua redução; a subnotificação e o aumento do acompanhamento pós-acidente.

Age above 60 years is not a negative predictive factor for combined antiviral therapy with pegylated interferon alpha and ribavirin in hepatitis C patients

Background: Age is frequently discussed as negative host factor to achieve a sustained virological response (SVR) to antiviral hepatitis C therapy. However, elderly patients often show relevant fibrosis or cirrhosis which is a known negative predictive factor, making it difficult to interpret age as an independent predictive factor. Methods: From the framework of the Swiss hepatitis C cohort (SCCS), we collected data from 545 antiviral hepatitis C therapies, including data from 67 hepatitis C patients ≥ 60 y who had been treated with PEG-interferon and ribavirin. We analyzed host factors (age, gender, fibrosis, haemoglobin, depression, earlier hepatitis C treatment), viral factors (genotype, viral load) and treatment course (early virological response, end of treatment response, SVR). Generalised estimating equations (GEE) regression modelling was used for the primary end point (SVR), with age ≥ 60 y and < 60 y as independent variable and gender, presence of cirrhosis, genotype, earlier treatment and viral load as confounders. SVR was analysed in young and elderly patients after matching for these confounders. Additionally, classification tree analysis was done in elderly patients using these confounders. Results: SVR analyzed in 545 patients was 55%. In genotype 1/4, SVR was 42.9% in 259 patients < 60 y and 26.1% in 46 patients ≥ 60 y. In genotype 2/3, SVR was 74.4% in 215 patients < 60 y and 84% in 25 patients ≥ 60 y. However, GEE model showed that age had no influence on achieving SVR (Odds ratio 0.91). Confounders influenced SVR as known from previous studies (cirrhosis, genotype 1/4, previous treatment and viral load >600'000 IE/ml as negative predictive factors). When young and elderly patients were matched (analysis in 59 elderly patients), SVR was not different in these patient groups (54.2% and 55.9%, resp.; p=0.795 in binomial test). The classification tree-derived best criterion for SVR in elderly patients was genotype, with no further criteria relevant for predicting SVR in genotype 2/3. In patients with genotype 1/4, further criteria were presence of cirrhosis and low viral load <600'000 IE/ml in non-cirrhotic patients. Conclusions: Age is not a relevant predictive factor for achieving SVR, when confounders were taken into account. In terms of effectiveness of antiviral therapy, age does not play a major role and should not be regarded as relevant negative predictive factor. Since life expectancy in Switzerland at age 60 is more than 22 y, hepatitis C therapy is reasonable in elderly patients with known relevant fibrosis or cirrhosis, because interferon-based hepatitis C therapy improves survival and reduces carcinogenesis.