Liberal alcohol legislation: does it amplify the effects among Swiss men of person-related risk factors on heavy alcohol use?

AIM: To estimate the statistical interactions between alcohol policy strength and the person-related risk factors of sensation-seeking, antisocial personality disorder and attention-deficit/hyperactivity disorder related to heavy alcohol use. DESIGN: Cross-sectional survey. SETTING: Young Swiss men living within 21 jurisdictions across Switzerland. PARTICIPANTS: A total of 5701 Swiss men (mean age 20 years) participating in the Cohort Study on Substance Use Risk Factors (C-SURF). MEASUREMENTS: Outcome measures were alcohol use disorder (AUD) as defined in the DSM-5 and risky single-occasion drinking (RSOD). Independent variables were sensation-seeking, antisocial personality disorder (ASPD), attention-deficit/hyperactivity disorder (ADHD) and an index of alcohol policy strength. FINDINGS: Alcohol policy strength was protective against RSOD [odds ratio (OR) = 0.91 (0.84-0.99)], while sensation-seeking and ASPD were risk factors for both RSOD [OR = 1.90 (1.77-2.04); OR = 1.69 (1.44-1.97)] and AUD [OR = 1.58 (1.47-1.71); OR = 2.69 (2.30-3.14)] and ADHD was a risk factor for AUD [OR = 1.08 (1.06-1.10)]. Significant interactions between alcohol policy strength and sensation-seeking were identified for RSOD [OR = 1.06 (1.01-1.12)] and AUD [OR = 1.06 (1.01-1.12)], as well as between alcohol policy strength and ASPD for both RSOD [OR = 1.17 (1.03-1.31)] and AUD [OR = 1.15 (1.02-1.29)]. These interactions indicated that the protective effects of alcohol policy strength on RSOD and AUD were lost in men with high levels of sensation-seeking or an ASPD. No interactions were detected between alcohol policy strength and ADHD. CONCLUSION: Stronger alcohol legislation protects against heavy alcohol use in young Swiss men, but this protective effect is lost in individuals with high levels of sensation-seeking or having an antisocial personality disorder.

Morbidity and aging in HIV-infected persons: the Swiss HIV cohort study.

BACKGROUND: Patterns of morbidity and mortality among human immunodeficiency virus (HIV)-infected individuals taking antiretroviral therapy are changing as a result of immune reconstitution and improved survival. We studied the influence of aging on the epidemiology of non-AIDS diseases in the Swiss HIV Cohort Study. METHODS: The Swiss HIV Cohort Study is a prospective observational cohort established in 1988 with continuous enrollment. We determined the incidence of clinical events (per 1000 person-years) from January 2008 (when a new questionnaire on non-AIDS-related morbidity was introduced) through December 2010. Differences across age groups were analyzed using Cox regression, adjusted for CD4 cell count, viral load, sex, injection drug use, smoking, and years of HIV infection. RESULTS: Overall, 8444 (96%) of 8848 participants contributed data from 40,720 semiannual visits; 2233 individuals (26.4%) were aged 50-64 years, and 450 (5.3%) were aged ≥65 years. The median duration of HIV infection was 15.4 years (95% confidence interval [CI], 9.59-22.0 years); 23.2% had prior clinical AIDS. We observed 994 incident non-AIDS events in the reference period: 201 cases of bacterial pneumonia, 55 myocardial infarctions, 39 strokes, 70 cases of diabetes mellitus, 123 trauma-associated fractures, 37 fractures without adequate trauma, and 115 non-AIDS malignancies. Multivariable hazard ratios for stroke (17.7; CI, 7.06-44.5), myocardial infarction (5.89; 95% CI, 2.17-16.0), diabetes mellitus (3.75; 95% CI, 1.80-7.85), bone fractures without adequate trauma (10.5; 95% CI, 3.58-30.5), osteoporosis (9.13; 95% CI, 4.10-20.3), and non-AIDS-defining malignancies (6.88; 95% CI, 3.89-12.2) were elevated for persons aged ≥65 years. CONCLUSIONS: Comorbidity and multimorbidity because of non-AIDS diseases, particularly diabetes mellitus, cardiovascular disease, non-AIDS-defining malignancies, and osteoporosis, become more important in care of HIV-infected persons and increase with older age.

Les temporalités des médicaments : trajectoires en soins palliatifs à l'hôpital

A partir d'un terrain ethnographique réalisé au sein d'une équipe mobile de soins palliatifs d'un hôpital universitaire, cette thèse de doctorat porte sur les médicaments dans le contexte de la fin de vie. Au carrefour d'une socio-anthropologie de la maladie grave, du mourir et des médicaments, elle interroge les rapports à la morphine, ainsi qu'à certains psychotropes et sédatifs utilisés en soins palliatifs. Entre temporalité vécue et temporalité institutionnelle, les manières d'investir le temps lorsqu'il est compté, y sont centrales. Dans une dimension microsociale, les résultats montrent que l'introduction de certains médicaments comme la morphine et l'entrée en scène d'une équipe mobile de soins palliatifs sont des points de repère et peuvent sonner comme une annonce, sorte de sanction, dans la trajectoire incertaine de la personne malade. En outre, les médicaments permettent d'agir sur « le temps qui reste » en plus de soulager les symptômes lorsque la maladie grave bascule en maladie incurable. Ils font l'objet d'usages détournés du but initial de soulagement des symptômes pour repousser, altérer ou accélérer la mort dans une perspective de maîtrise de sa fin de vie. Dans une dimension mésosociale, ce travail considère les médicaments à la base d'échanges entre groupements professionnels sur fond d'institutionnalisation des soins palliatifs par rapport à d'autres segments de la médecine actifs dans la gestion de la fin de vie. Dans une médecine caractérisée par l'incertitude et les décisions -avec une teinte toute particulière en Suisse où le suicide assisté est toléré - les médicaments en soins palliatifs peuvent être considérés comme des instruments de mort, qu'ils soient redoutés ou recherchés. Interrogeant les risques de reproduire un certain nombre d'inégalités de traitements à l'approche de la mort, qui s'accentuent dans un contexte de plus en plus favorable aux pratiques euthanasiques, ce travail se propose, en définitive, de discuter le temps contraint de la mort dans les institutions hospitalo-universitaires, entre acharnement et abstention thérapeutique.¦-¦Based on ethnographie fieldwork conducted within a palliative care mobile team in an academic hospital, this doctoral thesis focuses on medicines used in end of life contexts. At the intersection of a socio-anthropology of illness, dying and pharmaceuticals, the relations to morphine, as well as to some psychotropic and sedative drugs used in palliative care are questioned. Between "lived" experiences of temporality and institutional temporality, the ways by which actors invest time when it is counted, appeared to be central. In a microsocial dimension, the results showed that introducing drugs such as morphine, as well as the arrival of a palliative care mobile team, are landmarks and sound like an announcement, a sort of sanction, during the uncertain trajectory of the ill person. In addition, medicines can act on "the remaining time" when severe illness shifts into incurable illness. Indeed, medicines are being diverted from the initial aim of symptom relief in order to defer, alter or hasten death in a perspective of control over one's death. In a mesosocial dimension, pharmaceuticals are seen as core to professional exchanges and to palliative care institutionalisation compared to other active medical segments in end of life care. In a medical context characterised by uncertainty and decision-taking-with a special shade in Switzerland where assisted suicide is tolerated - palliative medicines can be seen as instruments of death, whether sought or feared. Questioning the risks of reproducing treatment inequalities at the approach of death, which are accentuated in a context increasingly favorable to euthanasia practices, this study aims, ultimately, at discussing death's constrained time in academic hospitals, between therapeutic intervention and abstention.

Four-month-olds make triangular bids to father and mother during trilogue play with still-face

(from the journal abstract) A new observational procedure, Trilogue Play with Still-face, revealed 4-month-olds' capacities to address both their fathers and mothers, by rapidly shifting gaze and affect between them. Infants were observed in four interactive contexts: (1) '3-together' play with both parents; (2) '2 + 1' play with one parent engaging and the other as third party; (3) the same, with one parent posing a still-face; (4) '3-together' play. Infants were able to discriminate between the four contexts. They coordinated three social poles of attention in each one. Their affect configurations were context sensitive. These findings demonstrate the infant's social capacities for triangular, three-person interactions, in addition to dyadic, two-person, and triadic, two-person plus object, ones. They support a view of intersubjectivity as primary and point to a promising field of investigation for the study of family process. (PsycINFO Database Record (c) 2005 APA, all rights reserved)

New roles for community pharmacists in modern health care systems: a challenge for pharmacy education and research.

The academic activities led by the Unit of Community Pharmacy can be classified as translational. Our group is interested in person-centered pharmaceutical services aimed at a more responsible use of drugs (effectiveness, safety, efficiency) in collaboration with physicians and other health care professionals in a primary care setting. The following domains of education and research are high priorities for our group: medication therapy management, medication adherence, integrated care, individualization of therapies, care management for the elderly and e-health.

Il desiderio materno nei casi di maltrattamento infantile

The work of this thesis would like to investigate two particular questions about the care of underage: on the one hand, the maltreatment, and the mother's desire on the other hand. About the first, this proposal try to underscore the elaborate irregularity and disparity related to this phenomenon and his historical evolution. The objective's thesis propose to underline that the abuse crosses the crisis of educational dimension inside and outside the family. We are talking about a type of crisi that places at the origin of a specific clinic and that it is about the maltreatment designated, at the same time, to cope with the educational void and with the ill-treated under age's hardships. The so-called clinic of the maltreatment horns, therefore, with the purpose to join and to set in order the normative and educational aspects. However, the prescriptive requirement is intended to measure against the same one crisis in a paradoxical way; the laws and the juveniles court must make up for the lack absence of the rules that characterized the maltreatment, getting around to use the typical reference that traditionally were been at the base of the educational way's construction. The same crimes on underage often found in the father the responsibility. The requirements and the therapeutic needs has utilized the theoretical construct of the trauma as the key line of clinical practice. On the one hand, the trauma was been paired controversially to the psychoanalytical concepts as the notion of the phantom, in the same manner that the objective truth is been opposed to the notion of the imagination and fantasy; on the other hand, the trauma was gotten to be the mark and the characteristic that defined the individual identity of the mistreated persons, regardless of the person's clinical structure or, generally, regardless of the their individual position. Both the normative demand and therapeutic converge on the idealization of the imaginary figure that is able to supply to every type of maltreatment: the mother. This position is connected on theoretical construct well-established in the mythology, that associated the mother figure to a natural dimension; this is related to the second point at issue: the mother's desire. The awareness of the mother figure in natural and idealized terms describes accusingly and negatively the trauma, without seeing the difference between trauma that helps to give a structure to the individual position from the trauma solely devastating. The mother's mythology, therefore, is in an evident antagonism with the female figure and woman's sexuality. In these way the maltreatment's clinic suggests that a woman is able to be a mother only when she doesn't appreciate the rule of female. This situation preclusives a comparison with own sexuality and gives to the women a complex of castration. The clinic cases reported highlight as these difficulties are the expression of the familiarity's heredity that wasn't been sufficiently elaborated. This condition (into the relation between mother and his child) turn the infant in the incapacity to symbolized and it doesn't help him to accede to the positive trauma, to the language and to the edipic rule; this is the reason why the child toils difficulties to approach to own personality and to orient himself in the relation with his body, with the body of the adults and the same age children.

I want to quit education: a longitudinal study of stress and optimism as predictors of school dropout intention

Prior research on school dropout has often focused on stable person- and institution-level variables. In this research, we investigate longitudinally perceived stress and optimism as predictors of dropout intentions over a period of four years, and distinguish between stable and temporary predictors of dropout intentions. Findings based on a nationally representative sample of 16e20 year-olds in Switzerland (N ¼ 4312) show that both average levels of stress and optimism as well as annually varying levels of stress and optimism affect dropout intentions. Additionally, results show that optimism buffers the negative impact of annually varying stress (i.e., years with more stress than usual), but not of stable levels of stress (i.e., stress over four years). The implications of the results are discussed according to a dynamic and preventive approach of school dropout.

Integrated care organizations in Switzerland.

INTRODUCTION: The Swiss health care system is characterized by its decentralized structure and high degree of local autonomy. Ambulatory care is provided by physicians working mainly independently in individual private practices. However, a growing part of primary care is provided by networks of physicians and health maintenance organizations (HMOs) acting on the principles of gatekeeping. TOWARDS INTEGRATED CARE IN SWITZERLAND: The share of insured choosing an alternative (managed care) type of basic health insurance and therefore restrict their choice of doctors in return for lower premiums increased continuously since 1990. To date, an average of one out of eight insured person in Switzerland, and one out of three in the regions in north-eastern Switzerland, opted for the provision of care by general practitioners in one of the 86 physician networks or HMOs. About 50% of all general practitioners and more than 400 other specialists have joined a physician networks. Seventy-three of the 86 networks (84%) have contracts with the healthcare insurance companies in which they agree to assume budgetary co-responsibility, i.e., to adhere to set cost targets for particular groups of patients. Within and outside the physician networks, at regional and/or cantonal levels, several initiatives targeting chronic diseases have been developed, such as clinical pathways for heart failure and breast cancer patients or chronic disease management programs for patients with diabetes. CONCLUSION AND IMPLICATIONS: Swiss physician networks and HMOs were all established solely by initiatives of physicians and health insurance companies on the sole basis of a healthcare legislation (Swiss Health Insurance Law, KVG) which allows for such initiatives and developments. The relevance of these developments towards more integration of healthcare as well as their implications for the future are discussed.

Disseminated M. avium complex infection in the Swiss HIV Cohort Study: declining incidence, improved prognosis and discontinuation of maintenance therapy.

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.

Clinical and pharmacogenetic study on smoking and smoking cessation

Currently, smoking cessation represents one of the main strategies to reduce the incidence of tobacco-related diseases in the population. Smoking can also influence pharmacotherapy through several pharmacokinetic or pharmacodynamic interactions. Some of the most concerned drugs are those metabolized by the cytochrome P450 (CYP) 1A2 enzyme (e.g. caffeine, theophylline, clozapine, olanzapine, duloxetine), whose activity is induced by the polycyclic aromatic hydrocarbons found in tobacco smoke. This can result in a clinically significant decrease in the pharmacological effect of the drugs and the need of higher doses in smokers. Conversely, upon smoking cessation, toxic plasma levels of the drugs can be reached. The main objective of this thesis was to study the interindividual variability in CYP1A2 induction in a large cohort of smokers, by measuring CYP1A2 activity before smoking cessation and one month later in continuously abstinent subjects. For this purpose, a clinical study was conducted, including 194 smokers from the general population who wished to participate in a smoking cessation program and therefore received medical counseling and substitution therapy (nicotine or varenicline). An analytical method for the simultaneous quantification of nicotine, its metabolites and varenicline in plasma was developed and validated using ultra performance liquid chromatography coupled with tandem mass spectrometry. This method was used to confirm abstinence at different time points during the follow-up. Moreover, it was used to determine plasma levels of the smoking cessation drugs, to be used in the study of their pharmacogenetics, which was the secondary objective of this thesis. High interindividual variability in CYP1A2 induction by smoking was observed, ranging from no change to approximately 7 times decreased CYP1A2 activity after smoking cessation. Several clinical and genetic factors were investigated in an attempt to explain this variability. Firstly, a significant influence of CYP1A2*1F and *1D alleles, of contraceptive use and of the number of cigarettes smoked per day on CYP1A2 induced activity was observed, and of CYP1A2*1F and the use of contraceptives on the basal activity. But no influence of these factors was found on CYP1A2 inducibility. Given that known genetic polymorphisms in CYP1A2 gene were shown to explain only poorly the observed variations in activity, additional genetic factors were studied. SNPs in the CYP oxidoreductase (POR) gene were found to influence CYP1A2 basal activity, but not the induction. Finally, a pathway-based approach allowed to identify SNPs in genes coding for nuclear receptors (CAR, RXRa, VDR, PXR) and induction-mediating receptors (AhR), which significantly influenced CYP1A2 inducibility and basal activity (SNPs in the gene coding for CAR and RXRa). As secondary objective of the study, the pharmacogenetics of nicotine and varenicline is being investigated. Therefore, the nicotine metabolite ratio is used in the attempt to better explain nicotine dependence and the failure/success of quitting smoking. A population pharmacokinetic model is being developed for varenicline, integrating clinical and genetic factors (genes coding for its metabolizing enzymes and transporters), with the purpose of trying to predict efficacy and side effects. These findings suggest that the influence of smoking on pharmacotherapy could be better managed by including clinical and possibly in the future genetic factors, in the assessment of the adaptations needed when a person starts or stops smoking.  - L'arrêt du tabac représente une des principales stratégies pour diminuer l'incidence des maladies causées par celui-ci. Le tabagisme peut influencer la thérapie médicamenteuse par des interactions pharmacocinétiques ou pharmacodynamiques. Parmi les médicaments concernés, il y a ceux métabolisés par le cytochrome P450 (CYP) 1A2 (caféine, théophylline, clozapine, olanzapine, duloxétine, etc), dont l'activité enzymatique est induite par les hydrocarbures aromatiques polycycliques présents dans la fumée de cigarette. Ceci peut se traduire par une diminution de l'effet pharmacologique du traitement et la nécessité d'augmenter les doses d'entretien chez les fumeurs. Au contraire, à l'arrêt de la cigarette, les taux plasmatiques des médicaments peuvent devenir toxiques. L'objectif principal de cette thèse était d'étudier la variabilité interindividuelle dans l'induction du CYP1A2 dans une large cohorte de fumeurs, par la mesure de l'activité du CYP1A2 avant l'arrêt de la cigarette, ainsi qu'un mois après chez les sujets abstinents. Pour ce faire, une étude clinique a été conduite, incluant 194 fumeurs de la population générale dans un programme d'arrêt du tabac offrant des consultations spécifiques et un traitement pharmacologique (nicotine ou varénicline). Une méthode analytique pour la quantification simultanée de la nicotine, ses métabolites et la varénicline dans le plasma par chromatographie liquide couplée à la spectrométrie de masse en tandem à été développée et validée. Cette méthode a été utilisée pour confirmer l'abstinence pendant l'étude et déterminer les taux plasmatiques des médicaments, dans le but d'étudier leur pharmacogénétique. Une grande variabilité interindividuelle dans l'induction du CYP1A2 par la fumée a été observée, parfois sans changement et pouvant aller jusqu'à une diminution d'environ 7 fois l'activité du CYP1A2 après l'arrêt de la cigarette. Plusieurs facteurs cliniques et génétiques ont été étudiés pour essayer d'expliquer cette variabilité. Tout d'abord, on a observé une influence significative: des allèles CYP1A2*1F et *1D, des contraceptifs et du nombre de cigarettes fumées par jour sur l'activité induite du CYP1A2, ainsi que l'influence de l'allèle *1F et des contraceptifs sur l'activité basale. Cependant, aucune influence de ces facteurs n'a été démontrée sur l'inductibilité du CYP1A2. Étant donné que les polymorphismes génétiques du CYP1A2 apportent peu de renseignements sur la variabilité de son activité, des facteurs génétiques supplémentaires ont été étudiés. Des polymorphismes dans le gène POR (CYP oxidoreductase) ont été associés à l'activité basale du CYP1A2, mais pas à l'induction. Finalement, une approche basée sur la voie de signalisation du CYP1A2 a permis d'identifier des polymorphismes dans des gènes codant pour des récepteurs nucléaires (CAR, RXRa, VDR, PXR) et d'autres liés à l'induction (AhR) qui influencent significativement l'inductibilité et l'activité basale (les SNPs du CAR et RXRa). L'objectif secondaire de cette étude était d'investiguer la pharmacogénétique de la nicotine et de la varénicline. Le ratio métabolique de la nicotine est utilisé pour mieux expliquer la dépendance à la nicotine et le succès/échec de l'arrêt de la cigarette. Un modèle pharmacocinétique de population est en cours de développement pour la varénicline, intégrant des facteurs cliniques et génétiques (gènes codant pour ses enzymes de métabolisme et transporteurs), pour tenter de prédire son efficacité et ses effets secondaires. Les résultats de cette thèse suggèrent que l'influence du tabagisme sur la pharmacothérapie serait mieux gérée par l'inclusion des facteurs cliniques et peut-être, dans le futur, génétiques, dans l'évaluation des adaptations nécessaires lorsqu'une personne fume ou arrête de fumer.  - l'arrêt du tabac représente une des principales stratégies pour diminuer l'incidence des maladies causées par celui-ci dans la population. Le tabagisme peut influencer les traitements médicamenteux, soit en modifiant leur élimination par l'organisme, soit en agissant sur leur mode d'action. Parmi les médicaments les plus concernés, on retrouve par exemple: la caféine, la théophylline, la clozapine, l'olanzapine, la duloxétine, dont l'élimination est accélérée par la fumée de cigarette (induction enzymatique). Ceci peut se traduire par une diminution de l'effet du traitement et la nécessité d'en augmenter les doses chez les fumeurs. Au contraire, à l'arrêt de la cigarette, on observe un ralentissement de la fonction enzymatique, qui a pour conséquence une augmentation du taux de médicament dans le sang, pouvant devenir toxique. L'objectif principal de cette thèse était d'étudier comment cette induction par le tabac varie dans une population de fumeurs, par la mesure de l'activité de l'enzyme avant l'arrêt de la cigarette, ainsi qu'un mois après chez les sujets abstinents. Pour ce faire, une étude clinique a été conduite, incluant 194 fumeurs de la population générale dans un programme d'arrêt du tabac offrant des consultations spécifiques et un traitement médicamenteux (nicotine ou varénicline). Une méthode analytique a été mise au point pour mesurer la quantité de nicotine, de ses produits de dégradation et de la varénicline dans le sang des participants à l'étude. De plus, cette méthode a été utilisée pour confirmer l'abstinence pendant l'étude. Une grande variabilité interindividuelle a été observée dans l'induction de l'enzyme par la fumée; il en résulte aucun changement d'activité chez certains sujets après l'arrêt de la cigarette, alors que pour d'autres elle peut être diminuée jusqu'à 7 fois. Plusieurs facteurs cliniques et génétiques ont été étudiés pour essayer d'expliquer cette variabilité. Premièrement, une influence sur l'activité de l'enzyme a été observée pour les contraceptifs hormonaux et le nombre de cigarettes fumées par jour, ainsi que pour certaines variations génétiques dans le gène codant pour l'enzyme d'intérêt, mais il η y a pas eu d'influence sur l'induction. Par la suite, des variations génétiques dans d'autres gènes influençant le fonctionnement de l'enzyme ont été associées soit avec son activité, soit avec son induction par le tabac. Finalement, l'étude propose également d'investiguer si le métabolisme de la nicotine a une influence sur la dépendance, les symptômes de sevrage et le succès/échec de l'arrêt de la cigarette. Des variations génétiques dans les gènes du métabolisme de la varénicline sont également étudiées en lien avec les quantités de varénicline mesurées dans le sang ainsi que les effets du médicament. Ceci permettra peut-être de prédire son efficacité et ses effets secondaires. Les résultats de cette thèse suggèrent que l'influence du tabagisme sur la thérapie médicamenteuse serait mieux gérée en tenant compte des facteurs cliniques et peut-être, dans le futur, de la génétique dans l'adaptation des traitements, que la personne soit fumeuse ou en phase d'arrêt.

Improved virological outcome in White patients infected with HIV-1 non-B subtypes compared to subtype B.

BACKGROUND: Antiretroviral compounds have been predominantly studied in human immunodeficiency virus type 1 (HIV-1) subtype B, but only ~10% of infections worldwide are caused by this subtype. The analysis of the impact of different HIV subtypes on treatment outcome is important. METHODS: The effect of HIV-1 subtype B and non-B on the time to virological failure while taking combination antiretroviral therapy (cART) was analyzed. Other studies that have addressed this question were limited by the strong correlation between subtype and ethnicity. Our analysis was restricted to white patients from the Swiss HIV Cohort Study who started cART between 1996 and 2009. Cox regression models were performed; adjusted for age, sex, transmission category, first cART, baseline CD4 cell counts, and HIV RNA levels; and stratified for previous mono/dual nucleoside reverse-transcriptase inhibitor treatment. RESULTS: Included in our study were 4729 patients infected with subtype B and 539 with non-B subtypes. The most prevalent non-B subtypes were CRF02_AG (23.8%), A (23.4%), C (12.8%), and CRF01_AE (12.6%). The incidence of virological failure was higher in patients with subtype B (4.3 failures/100 person-years; 95% confidence interval [CI], 4.0-4.5]) compared with non-B (1.8 failures/100 person-years; 95% CI, 1.4-2.4). Cox regression models confirmed that patients infected with non-B subtypes had a lower risk of virological failure than those infected with subtype B (univariable hazard ratio [HR], 0.39 [95% CI, .30-.52; P < .001]; multivariable HR, 0.68 [95% CI, .51-.91; P = .009]). In particular, subtypes A and CRF02_AG revealed improved outcomes (multivariable HR, 0.54 [95% CI, .29-.98] and 0.39 [95% CI, .19-.79], respectively). CONCLUSIONS: Improved virological outcomes among patients infected with non-B subtypes invalidate concerns that these individuals are at a disadvantage because drugs have been designed primarily for subtype B infections.

Efficacité du counseling d'orientation: impacts de l'alliance de travail et du contexte psychosocial

La problématique centrale de cette thèse de doctorat est l'efficacité de l'accompagnement à l'orientation. Elle renvoie en particulier à la multiplicité des types d'interventions ainsi qu'aux tensions entre les finalités de l'orientation qui rendent improbable une mesure univoque et objective de l'efficacité des pratiques. Le «mythe » de l'efficacité trouve notamment sa source dans le persistent monopole du modèle de l'appariement qui a largement influencé le développement de la discipline. Le manuscrit est basé sur deux études empiriques. Premièrement, « voies professionnelles » est une étude longitudinale visant l'évaluation de l'efficacité d'un service de counseling d'orientation au travers de mesures intraindividuelles. Les résultats immédiats (pre-post) indiquent une forte diminution de l'indécision vocationnelle des consultants ainsi qu'une augmentation de leur bien-être. Les résultats longitudinaux sur un an indiquent une évolution positive des difficultés plus ancrées ainsi qu'un fort taux d'implémentation des projets professionnels. La qualité de l'alliance de travail démontre un impact positif sur l'efficacité de la démarche. Deuxièmement, l'étude « orientation et genre » a permis de mettre en évidence un effet d'interaction entre le sexe et le niveau scolaire d'élèves en fin de scolarité sur leurs profils d'intérêts professionnels. Ce résultat affecte en particulier les jeunes filles dans une filière à exigences élémentaires car ces deux identités psychosociales semblent restreindre doublement les options professionnelles envisageables. Les deux études ont permis de soulever cinq implications centrales : (1) La distinction entre les aspects cognitifs et émotionnels de l'indécision vocationnelle est importante. En particulier, la préparation au choix est un construit qui nécessite clarification ; (2) Les processus de transitions professionnelles ainsi que leur accompagnement doivent être considérés dans leur dimension temporelle ; (3) L'interconnexion des différentes sphères de vie est centrale dans les processus d'orientation et leur accompagnement ; (4) L'efficacité du conseil en orientation est affectée par la qualité des aspects relationnels ; (5) La complexité des pratiques et de leurs finalités confronte l'orientation à son rôle envers des identités psychosociales fragilisées. - The central issue of this doctoral thesis is the effectiveness of career counseling and guidance. In particular, this refers to the many types of career interventions as well as the tensions between their objectives. Those aspects make it unlikely to get an unambiguous and objective measure of the effectiveness of career practices. The "myth of efficiency" is particularly rooted in the persistent monopoly of person-environment fit models, which greatly influenced the development of the discipline. This manuscript is based on two empirical studies. First, "career paths" is a longitudinal study looking at the effectiveness of a career counseling service through intraindividual measures. Pre-post impacts showed a significant decrease in clients' vocational indecision as well as a moderate increase in their well-being. The one year-longitudinal results highlighted significant decreases in more constant decision-making difficulties with a high proportion of clients having implemented their professional projects. The quality of the working alliance had a positive impact on the effectiveness of the intervention. The second study, "vocational development and gender" highlighted an interaction effect between late schoolchildren's gender and school level on their professional interests profile. This result particularly affected girls at a low school level, because these psychosocial identities were a double restraint in restricting career options. The two studies raised five central implications: (1) The distinction between cognitive and emotional aspects of vocational indecision is important. In particular, readiness to make a choice is a construct that requires clarification; (2) career transitions processes as well as supporting these transitions, should be considered in their temporal dimension (3) the interconnection of different spheres of life is central to vocational development and career guidance and counseling; (4) the effectiveness of career counseling is affected by the quality of the relational aspects in the intervention; (5) and the complexity of career interventions and their objectives forces practitioners to consider their role and responsibilities towards clients with marginalized psychosocial identities.

Prenatal diagnosis of facial clefts : evaluation of a specialised counseling

Résumé: Questions étudiées / principes: Le diagnostic prénatal des fentes faciales et palatines a soulevé maintes questions concernant la meilleure manière d'informer les parents et d'offrir une aide appropriée durant les semaines de grossesse restant, afin de faire de la naissance une expérience positive. Le conseil prénatal diffère selon la personne qui en est responsable et ses connaissances concernant les aspects pratiques des soins ainsi que l'impact de cette malformation sur la qualité de vie de l'enfant. Le but de cette étude est d'évaluer nos techniques actuelles et de les modifier de façon appropriée. Méthodes: 29 couples ayant bénéficié d'un diagnostic prénatal ont été priés de répondre rétrospectivement à un questionnaire. L'histoire obstétrique personnelle ainsi que l'histoire familiale, le déroulement des évènements, la qualité de l'information fournie et leurs impressions à la naissance ont été considérées. Résultats: Les parents utilisent de multiples sources d'information: l'obstétricien, le conseil du chirurgien pédiatrique au sein de I « équipe fente », les groupes de soutien de parents et Internet. 93% des parents se sont sentis bien préparés à la naissance de leur enfant, autant psychologiquement que concernant les aspects pratiques des soins. 54% ont été soulagés de voir leur enfant moins affecté qu'ils ne l'imaginaient. Finalement, 96% considèrent que le diagnostic prénatal est un bénéfice. Conclusion: Une information de base devrait être apportée rapidement après l'ultrason confirmant le diagnostic, suivie de discussions techniques progressivement plus détaillées durant le temps de grossesse restant. Summary: Questions under study / principles: Prenatal diagnosis of cleft lip and palate has raised many questions concerning the best way to inform the parents and offer appropriate support during the remaining pregnancy to help prepare a positive birth experience. Prenatal counseling differs according to whose is responsible and that person's knowledge of practical aspects of care and the impact of the malformation on the child's quality of life. The aim of the study was to evaluate our current techniques and modify them when appropriate. Methods: 29 couples having experienced prenatal diagnosis were asked to respond retrospectively to a questionnaire. Personal obstetric and family history, timing and quality of information provided and their impressions at birth were considered. Results: The parents used several sources of information: the obstetrician, the counsel by the cleft team surgeon, the parents support groups and Internet. 93% of the parents felt well prepared for the birth of their child psychologically and concerning practical aspects of care. 54% felt relieved that their child was less affected than imagined. 96% considered prenatal diagnosis a benefit. Conclusion: Basic information should be provided soon after ultrasound confirmation, followed by progressively more detailed technical discussions over the remaining pregnancy.

Severe traumatic brain injury in Switzerland - feasibility and first results of a cohort study.

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.

Sudden cardiac death in the young (5-39 years) in the canton of Vaud, Switzerland.

BACKGROUND: Sudden cardiac death (SCD) among the young is a rare and devastating event, but its exact incidence in many countries remains unknown. An autopsy is recommended in every case because some of the cardiac pathologies may have a genetic origin, which can have an impact on the living family members. The aims of this retrospective study completed in the canton of Vaud, Switzerland were to determine both the incidence of SCD and the autopsy rate for individuals from 5 to 39 years of age. METHODS: The study was conducted from 2000 to 2007 on the basis of official statistics and analysis of the International Classification of Diseases codes for potential SCDs and other deaths that might have been due to cardiac disease. RESULTS: During the 8 year study period there was an average of 292'546 persons aged 5-39 and there were a total of 1122 deaths, certified as potential SCDs in 3.6% of cases. The calculated incidence is 1.71/100'000 person-years (2.73 for men and 0.69 for women). If all possible cases of SCD (unexplained deaths, drowning, traffic accidents, etc.) are included, the incidence increases to 13.67/100'000 person-years. However, the quality of the officially available data was insufficient to provide an accurate incidence of SCD as well as autopsy rates. The presumed autopsy rate of sudden deaths classified as diseases of the circulatory system is 47.5%. For deaths of unknown cause (11.1% of the deaths), the autopsy was conducted in 13.7% of the cases according to codified data. CONCLUSIONS: The incidence of presumed SCD in the canton of Vaud, Switzerland, is comparable to the data published in the literature for other geographic regions but may be underestimated as it does not take into account other potential SCDs, as unexplained deaths. Increasing the autopsy rate of SCD in the young, better management of information obtained from autopsies as well developing of structured registry could improve the reliability of the statistical data, optimize the diagnostic procedures, and the preventive measures for the family members.