Association of pharmacogenetic markers with premature discontinuation of first-line anti-HIV therapy: an observational cohort study.

BACKGROUND: Poor tolerance and adverse drug reactions are main reasons for discontinuation of antiretroviral therapy (ART). Identifying predictors of ART discontinuation is a priority in HIV care. METHODS: A genetic association study in an observational cohort to evaluate the association of pharmacogenetic markers with time to treatment discontinuation during the first year of ART. Analysis included 577 treatment-naive individuals initiating tenofovir (n = 500) or abacavir (n = 77), with efavirenz (n = 272), lopinavir/ritonavir (n = 184), or atazanavir/ritonavir (n = 121). Genotyping included 23 genetic markers in 15 genes associated with toxicity or pharmacokinetics of the study medication. Rates of ART discontinuation between groups with and without genetic risk markers were assessed by survival analysis using Cox regression models. RESULTS: During the first year of ART, 190 individuals (33%) stopped 1 or more drugs. For efavirenz and atazanavir, individuals with genetic risk markers experienced higher discontinuation rates than individuals without (71.15% vs 28.10%, and 62.5% vs 14.6%, respectively). The efavirenz discontinuation hazard ratio (HR) was 3.14 (95% confidence interval (CI): 1.35-7.33, P = .008). The atazanavir discontinuation HR was 9.13 (95% CI: 3.38-24.69, P < .0001). CONCLUSIONS: Several pharmacogenetic markers identify individuals at risk for early treatment discontinuation. These markers should be considered for validation in the clinical setting.

Conviction Statistics as an Indicator of Crime Trends in Europe from 1990 to 2006

Convictions statistics were the first criminal statistics available in Europe during the nineteenth century. Their main weaknesses as crime measures and for comparative purposes were identified by Alphonse de Candolle in the 1830s. Currently, they are seldom used by comparative criminologists, although they provide a less valid but more reliable measure of crime and formal social control than police statistics. This article uses conviction statistics, compiled from the four editions of the European Sourcebook of Crime and Criminal Justice Statistics, to study the evolution of persons convicted in European countries from 1990 to 2006. Trends in persons convicted for six offences -intentional homicide, assault, rape, robbery, theft, and drug offences- and up to 26 European countries are analysed. These trends are established for the whole of Europe as well as for a cluster of Western European countries and a cluster of Central and Eastern European countries. The analyses show similarities between both regions of Europe at the beginning and at the end of the period under study. After a general increase of the rate of persons convicted in the early 1990s in the whole of Europe, trends followed different directions in Western and in Central and Eastern Europe. However, during the 2000s, it can be observed, throughout Europe, a certain stability of the rates of persons convicted for intentional homicides, accompanied by a general decrease of the rate of persons convicted for property offences, and an increase of the rate of those convicted for drug offences. The latter goes together with an increase of the rate of persons convicted for non lethal violent offences, which only reached some stability at the end of the time series. These trends show that there is no general crime drop in Europe. After a discussion of possible theoretical explanations, a multifactor model, inspired by opportunity-based theories, is proposed to explain the trends observed.

Socio-demographic and behavioural determinants of weight gain in the Swiss population.

BackgroundIn Switzerland, socio-demographic and behavioural factors are associated with obesity, but no study ever assessed their impact on weight gain using prospective data.MethodsData from 4,469 participants (53.0% women), aged 35 to 75 years at baseline and followed for 5.5 years. Weight gain was considered as a rate (kg/year) or as gaining ¿5 kg during the study period.ResultsRate of weight gain was lower among participants who were older (mean¿±¿standard deviation: 0.46¿±¿0.92, 0.33¿±¿0.88, 0.21¿±¿0.86 and 0.06¿±¿0.74 kg/year in participants aged [35-45[, [45-55[, [55¿65[and [65+ years, respectively, P<0.001); physically active (0.27¿±¿0.82 vs. 0.35¿±¿0.95 kg/year for sedentary, P¿<¿0.005) or living in a couple (0.29¿±¿0.84 vs. 0.35¿±¿0.96 kg/year for living single, P¿<¿0.05), and higher among current smokers (0.41¿±¿0.97, 0.26¿±¿0.84 and 0.29±0.85 kg/year for current, former and never smokers, respectively, p<0.001). These findings were further confirmed by multivariable analysis. Multivariable logistic regression showed that receiving social help, being a current smoker or obese increased the likelihood of gaining ¿5Kg: Odds ratio (OR) and 95% confidence interval (CI) 1.43 (1.16-1.77); 1.63 (1.35-1.95) and 1.95 (1.57-2.43), respectively, while living in couple or being physically active decreased the risk: 0.73 (0.62-0.86) and 0.72 (0.62-0.83), respectively. No association was found between weight gain and gender, being born in Switzerland or education.ConclusionsIn Switzerland, financial difficulties (indicated by receiving social help) and current smoking were associated with increases in body weight over a 5 years follow-up. Living in couple, being older or physically active were protective against weight gain.

Interruptions de grossesse dans le canton de Vaud en 2007

En 2007, un total de 1439 interruptions de grossesse ont été pratiquées dans le canton de Vaud, dont 89% concernaient des femmes domiciliées dans le canton. Rapporté à la population féminine en âge de procréer (15-49 ans), le taux d'interruption de grossesse est estimé à 7,6 pour mille (15-44 ans : 9,4 pour mille). Le taux d'interruptions de grossesses pour 1000 résidentes âgée de 15 à 49 ans marque une légère progression, passant de 6,8 pour mille en 2004 à 7,6 pour mille en 2007. Un écart important se maintient entre les femmes de nationalité étrangère (2007 : 13,1pour mille) et les Suissesses (4,6 pour mille). Dans les deux groupes, néanmoins, l'augmentation des interruptions de grossesse parmi les adolescentes (15-19 ans), observée au cours des trois dernières années, s'est interrompue en 2007. Le ratio des interruptions de grossesse par rapport aux nombre de naissances vivantes (exprimé en %) marque une très légère progression depuis 2003, passant de 15.2 à 16.7. Comme lors des années précédentes, on n'observe pas d'évolution particulière au niveau de l'âge gestationnel au moment de l'interruption. Dans leur très grande majorité, les interruptions de grossesse sont pratiquées avant la douzième semaine suivant l'arrêt des règles. En outre, l'âge gestationnel ne varie quasiment pas selon l'âge et la nationalité. Le pourcentage d'interruptions de grossesse par voie médicamenteuse continue d'augmenter. Il est passé de 31% en 2005 à 41% en 2007. Cette valeur reste encore nettement inférieure à la moyenne suisse (56%). Le recours à la méthode médicamenteuse demeure fortement associé au niveau de formation de la patiente (formation supérieure) et au type d'établissement dans lequel l'intervention est pratiquée. La probabilité d'une intervention médicamenteuse est ainsi trois fois plus élevée dans un hôpital régional qu'au CHUV. On observe peu d'évolution au niveau des caractéristiques sociodémographiques et des caractéristiques de la carrière reproductive. Le pourcentage de femmes ayant déjà interrompu une grossesse par le passé demeure élevé (31 %) en particulier dans certains groupes de nationalité (Afrique, Amérique du Sud). On note également, parmi les femmes ayant déjà eu un/des enfant/s, qu'un laps de temps relativement court sépare l'interruption de grossesse du dernier accouchement : 20% ont recouru à l'interruption de grossesse dans l'année ou dans l'année précédant l'interruption de grossesse.

Risk of falls and major bleeds in patients on oral anticoagulation therapy.

BACKGROUND: The risk of falls is the most commonly cited reason for not providing oral anticoagulation, although the risk of bleeding associated with falls on oral anticoagulants is still debated. We aimed to evaluate whether patients on oral anticoagulation with high falls risk have an increased risk of major bleeding. METHODS: We prospectively studied consecutive adult medical patients who were discharged on oral anticoagulants. The outcome was the time to a first major bleed within a 12-month follow-up period adjusted for age, sex, alcohol abuse, number of drugs, concomitant treatment with antiplatelet agents, and history of stroke or transient ischemic attack. RESULTS: Among the 515 enrolled patients, 35 patients had a first major bleed during follow-up (incidence rate: 7.5 per 100 patient-years). Overall, 308 patients (59.8%) were at high risk of falls, and these patients had a nonsignificantly higher crude incidence rate of major bleeding than patients at low risk of falls (8.0 vs 6.8 per 100 patient-years, P=.64). In multivariate analysis, a high falls risk was not statistically significantly associated with the risk of a major bleed (hazard ratio 1.09; 95% confidence interval, 0.54-2.21). Overall, only 3 major bleeds occurred directly after a fall (incidence rate: 0.6 per 100 patient-years). CONCLUSIONS: In this prospective cohort, patients on oral anticoagulants at high risk of falls did not have a significantly increased risk of major bleeds. These findings suggest that being at risk of falls is not a valid reason to avoid oral anticoagulants in medical patients.

Clinical characteristics and outcome of inpatients versus outpatients with venous thromboembolism: findings from the RIETE Registry.

BACKGROUND: Patients with venous thromboembolism (VTE) treated with anticoagulants are at risk of death from pulmonary embolism (PE) and/or bleeding. However, whether patients who develop VTE in hospital have a higher complication rate than those who develop VTE in an outpatient setting is unclear. PATIENTS AND METHODS: RIETE is an ongoing, prospective registry of consecutive patients with acute, objectively confirmed, symptomatic VTE. We compared the 3-month incidence of fatal PE and fatal bleeding in patients in whom the VTE had developed while in hospital for another medical condition (inpatients) with those who presented to the emergency ward because of VTE (outpatients). RESULTS: Up to April 2008, 22,133 patients with acute VTE were enrolled: 10,461 (47%) presented with PE, 11,672 with deep vein thrombosis. Overall, 6445 (29%) were inpatients. During the study period, those who developed VTE as inpatients had a significantly higher incidence of fatal PE (2.1% vs. 1.5%; odds ratio: 1.4; 95% CI: 1.1-1.7), overall death (7.0% vs. 5.4%; odds ratio: 1.3; 95% CI: 1.2-1.5), and major bleeding (2.9% vs. 2.1%; odds ratio: 1.4; 95% CI: 1.1-1.6) than outpatients. The incidence of fatal bleeding was not significantly increased (0.7% vs. 0.5%; odds ratio: 1.2; 95% CI: 0.9-1.8). In multivariable analysis, inpatient status was significantly associated with a higher risk for fatal PE (odds ratio: 1.3; 95% CI: 1.1-1.7). CONCLUSIONS: VTE occurring in hospitalized patients carries a significantly higher risk for death of PE than in outpatients, underscoring the importance of VTE prevention strategies in the hospital setting.

Prevalence and management of cardiovascular risk factors in Portuguese residents and Portuguese who migrated to Switzerland

Background: there is little information regarding the health status of migrants compared to subjects who remained in their country of origin. The aim was to compare Portuguese living in Porto (Portugal) with Portuguese migrants living in Lausanne (Switzerland). Design: cross-sectional studies conducted in Porto (EpiPorto, n=1150) and Lausanne (CoLaus, n=388) among Portuguese subjects aged between 35 and 65 years. Methods: body mass index, blood pressure, cholesterol and glucose levels were assessed using standardized procedures. Educational level, antihypertensive, hypocholesterolemic and antidiabetic treatments were collected using questionnaires. Results: Portuguese living in Lausanne were younger, more frequently male and had a lower education than Portuguese living in Porto. After multivariate adjustment, Portuguese living in Porto had a higher likelihood of being obese [Odds ratio and 95% confidence interval: 1.40 (1.01-1.94)] or abdominal obese [OR: 1.40 (1.02-1.93)] than Portuguese living in Lausanne. Portuguese living in Porto had a higher likelihood of being hypertensive than Portuguese living in Lausanne [OR: 1.38 (1.01-1.90)], while no differences were found regarding hypertension management and control. Portuguese living in Porto had a higher likelihood of being hypercholesterolemic [OR: 1.40 (1.06-1.85)] and were less likely to be treated [OR: 0.47 (0.27-0.83)] and controlled [OR: 0.47 (0.27-0.83)] than Portuguese living in Lausanne. Finally, no differences were found regarding smoking, prevalence and management of diabetes. Conclusion: Portuguese living in Lausanne, Switzerland, present a better cardiovascular risk profile and tend to be better managed regarding their cardiovascular risk factors than Portuguese living in Porto, Portugal.

Impact of job insecurity on sexual desire: an exploratory analysis.

To explore, for the first time, the impact of job insecurity on sexual desire. Cross-sectional analysis of a nationally representative sample of 7247 individuals aged 20-64 years working as full or part-time employees in Switzerland. The logistic regression analysis showed that workers aged 20-49 years perceiving high levels of job insecurity are exposed to a significantly higher risk of decrease of sexual desire compared to the reference group. The risk is 53% higher among men (OR 1.53; 95% CI 1.16-2.01) and 47% for woman (OR 1.47; 1.13-1.91). No increased risk was found for employees aged 50-64 years old. An increasing fear of job loss is associated with a deterioration in sexual desire. These first preliminary findings should promote further epidemiological and clinical prospective studies on the impact of job insecurity on intimate relationships and sexual dysfunction.

Estimation of the correlation structure of crustal velocity heterogeneity from seismic reflection data

Numerous sources of evidence point to the fact that heterogeneity within the Earth's deep crystalline crust is complex and hence may be best described through stochastic rather than deterministic approaches. As seismic reflection imaging arguably offers the best means of sampling deep crustal rocks in situ, much interest has been expressed in using such data to characterize the stochastic nature of crustal heterogeneity. Previous work on this problem has shown that the spatial statistics of seismic reflection data are indeed related to those of the underlying heterogeneous seismic velocity distribution. As of yet, however, the nature of this relationship has remained elusive due to the fact that most of the work was either strictly empirical or based on incorrect methodological approaches. Here, we introduce a conceptual model, based on the assumption of weak scattering, that allows us to quantitatively link the second-order statistics of a 2-D seismic velocity distribution with those of the corresponding processed and depth-migrated seismic reflection image. We then perform a sensitivity study in order to investigate what information regarding the stochastic model parameters describing crustal velocity heterogeneity might potentially be recovered from the statistics of a seismic reflection image using this model. Finally, we present a Monte Carlo inversion strategy to estimate these parameters and we show examples of its application at two different source frequencies and using two different sets of prior information. Our results indicate that the inverse problem is inherently non-unique and that many different combinations of the vertical and lateral correlation lengths describing the velocity heterogeneity can yield seismic images with the same 2-D autocorrelation structure. The ratio of all of these possible combinations of vertical and lateral correlation lengths, however, remains roughly constant which indicates that, without additional prior information, the aspect ratio is the only parameter describing the stochastic seismic velocity structure that can be reliably recovered.

Measuring alcohol-related consequences in school surveys: alcohol-attributable consequences or consequences with students' alcohol attribution.

In alcohol epidemiology surveys, there is a tradition of measuring alcohol-related consequences using respondents' attribution of alcohol as the cause. The authors aimed to compare the prevalence and frequency of self-attributed consequences to consequences without self-attribution using alcohol-attributable fractions (AAF). In 2007, a total of 7,174 Swiss school students aged 13-16 years reported the numbers of 6 alcohol-related adverse consequences (e.g., fights, injuries) they had incurred in the past 12 months. Consequences were measured with and without attribution of alcohol as the cause. The alcohol-use measures were frequency and volume of drinking in the past 12 months and number of risky single-occasion (> or =5 drinks) drinking episodes in the past 30 days. Attributable fractions were derived from logistic (> or =1 incident) and Poisson (number of incidents) regression analyses. Although relative risk estimates were higher when alcohol-attributed consequences were compared with nonattributed consequences, the use of AAFs resulted in more alcohol-related consequences (10,422 self-attributed consequences vs. 24,520 nonattributed consequences determined by means of AAFs). The likelihood of underreporting was higher among drinkers with intermediate frequencies than among either rare drinkers or frequent drinkers. Therefore, the extent of alcohol-related adverse consequences among adolescents may be underestimated when using self-attributed consequences, because of differential attribution processes, especially among infrequent drinkers.

Combination of carbon isotope ratio with hydrogen isotope ratio determinations in sports drug testing.

Carbon isotope ratio (CIR) analysis has been routinely and successfully applied to doping control analysis for many years to uncover the misuse of endogenous steroids such as testosterone. Over the years, several challenges and limitations of this approach became apparent, e.g., the influence of inadequate chromatographic separation on CIR values or the emergence of steroid preparations comprising identical CIRs as endogenous steroids. While the latter has been addressed recently by the implementation of hydrogen isotope ratios (HIR), an improved sample preparation for CIR avoiding co-eluting compounds is presented herein together with newly established reference values of those endogenous steroids being relevant for doping controls. From the fraction of glucuronidated steroids 5β-pregnane-3α,20α-diol, 5α-androst-16-en-3α-ol, 3α-Hydroxy-5β-androstane-11,17-dione, 3α-hydroxy-5α-androstan-17-one (ANDRO), 3α-hydroxy-5β-androstan-17-one (ETIO), 3β-hydroxy-androst-5-en-17-one (DHEA), 5α- and 5β-androstane-3α,17β-diol (5aDIOL and 5bDIOL), 17β-hydroxy-androst-4-en-3-one and 17α-hydroxy-androst-4-en-3-one were included. In addition, sulfate conjugates of ANDRO, ETIO, DHEA, 3β-hydroxy-5α-androstan-17-one plus 17α- and androst-5-ene-3β,17β-diol were considered and analyzed after acidic solvolysis. The results obtained for the reference population encompassing n = 67 males and females confirmed earlier findings regarding factors influencing endogenous CIR. Variations in sample preparation influenced CIR measurements especially for 5aDIOL and 5bDIOL, the most valuable steroidal analytes for the detection of testosterone misuse. Earlier investigations on the HIR of the same reference population enabled the evaluation of combined measurements of CIR and HIR and its usefulness regarding both steroid metabolism studies and doping control analysis. The combination of both stable isotopes would allow for lower reference limits providing the same statistical power and certainty to distinguish between the endo- or exogenous origin of a urinary steroid.