Health care supply, payment system and medical practice : evidence from obstetric practice

ABSTRACTA significant share of deliveries are performed by Cesarian section (C-section) in Europe and in many developed and developing countries. The aims of this thesis are to highlight the non medical, especially economic and financial, incentives that explain the use of C-section, as well as the medical consequences of C-section on women's health, in regard with other factors of ob¬stetrical care quality such as hospital concentration. Those diagnoses enable us to exhibit ways of improvement of obstetrical care quality in France. Our analysis focus on two countries, France and Switzerland. In the first part of the thesis, we show the influence of two non medical factors on the C-section use, namely the hospital payment system on the one hand and the obstetricians behaviour, especially their demand for leisure, on the other hand. With French data on the year 2003, we show firstly that the fee-for-service payment system of private for profit hospitals induces a higher probability of using C-section. Obstetricians play also a preeminent role in the decision to use a C-section, as the probability of a C-section rises with the number of obstetricians. We then focus on a French reform introduced in 2004, to investigate the impact of Prospective Payment System on obstetric practise. We show that the rise of C-section rate between 2003 and 2006 is mainly caused by changes in hospitals and patients features. Obstetricians practises do not vary a lot for patients with the same risk code. In the mean time however, the number of women coded with a high risk rises. This can be caused by improvements in the quality of coding, obstetricians chosing codes that match better the real health state of their patients. Yet, it can also show that obstetricians change their coding practises to justify the use of certain practises, such as C-section, with no regard to the health state of patients. Financial factors are not the only non medical fac¬tors that can influence the resort to C-section. Using Shelton Brown ΠΙ identification strategy, we focus on the potential impact of obstetricians leisure preference on the use of C-section. We use the distributions of days and hours of delivering and the types of C-section - planned or emergency C-sections - to show that the obstetricians demand for leisure has a significant impact on the resort to C-section, but only in emergency situations. The second part of the thesis deals with some ways to improve obstetric care quality. We use on the one hand swiss and french data to study the impact of C-section on the patients' probability of having an obstetric complication and on the other hand the influence of hospital concentration on the quality of obstetric care. We find the same results as former medical studies about the risks entailed by C-section on obstetric complications.These results prove women ought to be better informed of the medical consequences of C-section and that the slowing of C-section use should be a priority of public health policy. We finally focus on another way to improve obstetric care quality, that is hospital lmarket concentration. We investigate the impact of hospital concentration by integrating the Herfindahl-Hirschman index in our model, on health care quality, measured by the HCUP indicator. We find that hospital concentration has a negative impact on obstetric care quality, which undermines today's policy of hospital closings in France.JEL classification: 112; 118Keywords: Hospital; C-section; Payment System; Counterfactual Estimation; Quality of Care.RÉSUMÉUne part importante des accouchements sont réalisés par césarienne en Europe et dans de nom¬breux pays développés ou en développement. Les objectifs de cette thèse sont de mettre en évidence les déterminants non médicaux, notamment économiques et financiers, expliquant le développe¬ment de cette pratique, ainsi que ses conséquences sur la santé des femmes après Γ accouchement, en lien avec d'autres facteurs comme la concentration locale des structures hospitalières. Les résul¬tats exposés dans cette thèse éclairent les perspectives et voies d'amélioration de la qualité des soins en obstétriques.Notre analyse se concentre sur deux pays : la France et la Suisse. Dans la première partie de la thèse, nous mettons en évidence l'influence de deux déterminants non médicaux sur l'emploi de la césarienne : le système de paiement des hôpitaux d'une part, et le comportement des médecins obstétriciens d'autre part. En étudiant des données françaises de 2003, nous montrons d'abord que le financement à l'acte des établissements privés engendre une hausse de la proba¬bilité de pratiquer une césarienne. Le rôle de l'obstrétricien paraît également déterminant dans la décision d'opérer une césarienne, la probabilité d'employer cette technique augmentant avec le nombre d'obstétriciens. Nous nous intéressons ensuite à l'impact de la mise en place en 2004 du système de paiement prospectif sur l'évolution des pratiques obstétricales entre 2003 et 2006 en France. La hausse du taux de recours à la césarienne entre 2004 et 2006 peut ainsi être principa¬lement imputée aux évolutions des caractéristiques des hôpitaux et des patients, les pratiques des obstétriciens, pour un même codage de la situation du patient, variant peu. Dans le même temps cependant, les pratiques de codage des patients parles obstétriciens évoluent fortement, les femmes étant de plus en plus nombreuses à porter des codes correspondant à des situations à risques. Cette évolution peut indiquer que la qualité du codage en 2006 s'est améliorée par rapport à 2004, le codage correspondant de plus en plus à la situation réelle des patientes. H peut aussi indiquer que les pratiques de codage évoluent pour justifier un recours accru à la césarienne, sans lien avec l'état réel des patientes. Les facteurs financiers ne sont pas les seuls facteurs non médicaux à pouvoir expliquer le recours à la césarienne : nous nous intéressons, en suivant la stratégie d'identifica¬tion de Shelton Brown m, à l'impact potentiel de la demande de loisir des médecins obstétriciens sur la pratique de la césarienne. En utilisant la distribution des jours et heures d'accouchement, et en distinguant les césariennes planifiées de celles effectuées en urgence, nous constatons que la demande de loisir des obstétriciens influence significativement le recours à la césarienne, mais uni¬quement pour les interventions d'urgence. La deuxième partie de la thèse est consacrée à l'étude de la qualité des soins en obstétriques. Nous utilisons des données suisses et françaises pour analyser d'une part l'impact de la césarienne sur la survenue de complications obstétricales et d'autre part l'impact de la concentration des soins sur la qualité des soins en obstétrique. Nons confirmons les résultats antérieurs de la littérature médicale sur la dangerosité de la césarienne comme facteur de complications obstétricales. Ces conclusions montrent que les femmes ont besoin d'être informées des conséquences de la césarienne sur leur santé et que le ralentissement de l'augmentation de la pratique de la césarienne devrait être un objectif de la politique publique de santé. Nous nous in¬téressons à un autre facteur d'amélioration des soins en obstrétique, l'organisation des hôpitaux et particulièrement leur concentration. Nous estimons ainsi l'effet de la concentration sur la qualité des soins obstétriques en intégrant l'indice de Herfindahl-Hirschman dans notre modèle, la qualité des soins étant mesurée à l'aide de l'indicateur HCUP. Nous constatons que la concentration des naissances a un impact négatif sur la qualité des soins en obstétrique, résultat qui va dans le sens contraire des politiques de fermeture d'hôpitaux menées actuellement en France. JEL classification : 112 ; 118Mots-clés : Hôpital ; Césarienne ; Système de paiement ; Contrefactuels ; Qualité des soins, sur la qualité des soins en obstétrique.

Les préférences alimentaires sont-elles influencées par l'index de masse corporelle, l'âge, le sexe ou le tabac [Are food preferences affected by body mass index, age, sex or tobacco?].

In recent decades the percentage of energy derived from dietary fat has increased. The aim of this study was to explore the relationship between food taste preferences, BMI, age, gender and smoking habits. A computerized questionnaire using a hedonic scale (range 0 to 8) to quantify the liking for sweet and savoury, lean and fat foods, was filled by 233 adults: 171 normal weight (131 women, 40 men) and 62 overweight subjects (BMI > 25 kg/m2 42 women, 20 men). The majority of the subjects had a general preference for savoury lean food irrespective of their BMI or gender. Similarly, preference for sweet lean food was not influenced by the magnitude of the BMI. In contrast, overweight subjects had a preference for sweet fat food (p = 0.05) as well as for savoury fat food (p < 0.05). At any age or BMI, men preferred sweet fat food (p < 0.01). This was not the case for women. Overweight men over forty preferred savoury fat food, in contrast to overweight women of the same age (p < 0.01). The same difference existed between normal weight smokers and non-smokers. This study demonstrates that fat food preference plays a potential role in the development of obesity.

Colonoscopy is the preferred colorectal cancer screening method in a population-based program.

BACKGROUND AND STUDY AIMS: Various screening methods for colorectal cancer (CRC) are promoted by professional societies; however, few data are available about the factors that determine patient participation in screening, which is crucial to the success of population-based programs. This study aimed (i) to identify factors that determine acceptance of screening and preference of screening method, and (ii) to evaluate procedure success, detection of colorectal neoplasia, and patient satisfaction with screening colonoscopy. PATIENTS AND METHODS: Following a public awareness campaign, the population aged 50 - 80 years was offered CRC screening in the form of annual fecal occult blood tests, flexible sigmoidoscopy, a combination of both, or colonoscopy. RESULTS: 2731 asymptomatic persons (12.0 % of the target population) registered with and were eligible to take part in the screening program. Access to information and a positive attitude to screening were major determinants of participation. Colonoscopy was the method preferred by 74.8 % of participants. Advanced colorectal neoplasia was present in 8.5 %; its prevalence was higher in males and increased with age. Significant complications occurred in 0.5 % of those undergoing colonoscopy and were associated with polypectomy or sedation. Most patients were satisfied with colonoscopy and over 90 % would choose it again for CRC screening. CONCLUSIONS: In this population-based study, only a small proportion of the target population underwent CRC screening despite an extensive information campaign. Colonoscopy was the preferred method and was safe. The determinants of participation in screening and preference of screening method, together with the distribution of colorectal neoplasia in different demographic categories, provide a rationale for improving screening procedures.

Differential species-specific ectoparasitic mite intensities in two intimately coexisting sibling bat species: resource-mediated host attractiveness or parasite specialization?

1. The mechanisms underlying host choice strategies by parasites remain poorly understood. We address two main questions: (i) do parasites prefer vulnerable or well-fed hosts, and (ii) to what extent is a parasite species specialized towards a given host species? 2. To answer these questions, we investigated, both in the field and in the lab, a host-parasite system comprising one ectoparasitic mite (Spinturnix myoti) and its major hosts, two sibling species of bats (Myotis myotis and M blythii), which coexist intimately in colonial nursery roosts. We exploited the close physical associations between host species in colonial roosts as well as naturally occurring annual variation in food abundance to investigate the relationships between parasite intensities and (i) host species and (ii) individual nutritional status. 3. Although horizontal transmission of parasites was facilitated by the intimate aggregation of bats within their colonial clusters, we found significant interspecific differences in degree of infestation throughout the 6 years of the study, with M. myotis always more heavily parasitized than M. blythii. This pattern was replicated in a laboratory experiment in which any species-specific resistance induced by exploitation of different trophic niches in nature was removed. 4. Within both host species, S. myoti showed a clear preference for individuals with higher nutritional status. In years with high resource abundance, both bat hosts harboured more parasites than in low-resource years, although the relative difference in parasite burden across species was maintained. This pattern of host choice was also replicated in the laboratory. When offered a choice, parasites always colonized better-fed individuals. 5. These results show first that host specialization in our study system occurred. Second, immediate parasite choice clearly operated towards the selection of hosts in good nutritional state.

Evaluation of oral versus intravenous dose of vinorelbine to achieve equivalent blood exposures in patients with solid tumours.

Patient's preference is for oral chemotherapy when both oral and i.v. are available, provided that efficacy is equivalent. Reliable switch from oral to i.v. is possible if correspondence between respective doses has been established. Vinorelbine oral was developed as a line extension of VRL i.v. on the basis that similar AUCs result in similar activities. From a first crossover study on 24 patients receiving VRL 25 mg/m2 i.v. and 80 mg/m2 oral data extrapolation concluded on AUCs bioequivalence between Vinorelbine 30 mg/m2 i.v. and 80 mg/m2 oral. A new trial was performed to support this calculation. In a crossover design study on patients (PS 0-1) with advanced solid tumours (44% breast carcinoma), VRL was administered (30 mg/m2 i.v., 80 mg/m2 oral) with a standard meal and 5-HT3 antagonists, at 2 weeks interval. Pharmacokinetics was performed over 168 h and VRL was measured by LC-MS/MS. Statistics included bioequivalence tests. Forty-eight patients were evaluable for PK: median age 58 years (25-71), PS0/PS1: 20/28, M/F: 11/37. Mean AUCs were 1,230 +/- 290 and 1,216 +/- 521 ng/ml for i.v. and oral, respectively. The confidence interval of the AUC ratio (0.83-1.03) was within the required regulatory range (0.8-1.25) and proved the bioequivalence between the two doses. The absolute bioavailability was 37.8 +/- 16.0%, and close to the value from the first study (40%). Patient tolerability was globally comparable between both forms with no significant difference on either haematological or non-haematological toxicities (grade 3-4). This new study, conducted on a larger population, confirmed the reliable dose correspondence previously established between vinorelbine 80 mg/m2 oral and 30 mg/m2 i.v.

DNA binding specificity of different STAT proteins. Comparison of in vitro specificity with natural target sites.

STAT transcription factors are expressed in many cell types and bind to similar sequences. However, different STAT gene knock-outs show very distinct phenotypes. To determine whether differences between the binding specificities of STAT proteins account for these effects, we compared the sequences bound by STAT1, STAT5A, STAT5B, and STAT6. One sequence set was selected from random oligonucleotides by recombinant STAT1, STAT5A, or STAT6. For another set including many weak binding sites, we quantified the relative affinities to STAT1, STAT5A, STAT5B, and STAT6. We compared the results to the binding sites in natural STAT target genes identified by others. The experiments confirmed the similar specificity of different STAT proteins. Detailed analysis indicated that STAT5A specificity is more similar to that of STAT6 than that of STAT1, as expected from the evolutionary relationships. The preference of STAT6 for sites in which the half-palindromes (TTC) are separated by four nucleotides (N(4)) was confirmed, but analysis of weak binding sites showed that STAT6 binds fairly well to N(3) sites. As previously reported, STAT1 and STAT5 prefer N(3) sites; however, STAT5A, but not STAT1, weakly binds N(4) sites. None of the STATs bound to half-palindromes. There were no specificity differences between STAT5A and STAT5B.

Pro-opiomelanocortin gene and melanin-based colour polymorphism in a reptile

Colour polymorphism is widespread among vertebrates and plays important roles in prey-predator interactions, thermoregulation, social competition, and sexual selection. However, the genetic mechanisms involved in colour variation have been studied mainly in domestic mammals and birds, whereas information on wild animals remains scarce. Interestingly, the pro-opiomelanocortin gene (POMC) gives rise to melanocortin hormones that trigger melanogenesis (by binding the melanocortin-1-receptor; Mc1r) and other physiological and behavioural functions (by binding the melanocortin receptors Mc1-5rs). Owing to its pleiotropic effect, the POMC gene could therefore account for the numerous covariations between pigmentation and other phenotypic traits. We screened the POMC and Mc1r genes in 107 wild asp vipers (Vipera aspis) that can exhibit four discrete colour morphs (two unpatterned morphs: concolor or melanistic; two patterned morphs: blotched or lined) in a single population. Our study revealed a correlation between a single nucleotide polymorphism situated within the 3-untranslated region of the POMC gene and colour variation, whereas Mc1r was not found to be polymorphic. To the best of our knowledge, we disclose for the first time a relationship between a mutation at the POMC gene and coloration in a wild animal, as well as a correlation between a genetic marker and coloration in a snake species. Interestingly, similar mutations within the POMC 3-untranslated region are linked to human obesity and alcohol and drug dependence. Combined with our results, this suggests that the 3-untranslated region of the POMC gene may play a role in its regulation in distant vertebrates.

Guidelines for the clinical management of atrial fibrillation: a practical perspective.

Since the management of atrial fibrillation may be difficult in the individual patient, our purpose was to develop simple clinical recommendations to help the general internist manage this common clinical problem. Systematic review of the literature with evaluation of data-related evidence and framing of graded recommendations. Atrial fibrillation affects some 1% of the population in Western countries and is linked to a significant increase in morbidity and mortality. The management of atrial fibrillation requires individualised evaluation of the risks and benefits of therapeutic modalities, relying whenever possible on simple and validated tools. The two main points requiring a decision in clinical management are 1) whether or not to implement thromboembolic prevention therapy, and 2) whether preference should be given to a "rate control" or "rhythm control" strategy. Thromboembolic prophylaxis should be prescribed after individualised risk assessment: for patients at risk, oral anticoagulation with warfarin decreases the rate of embolic complications by 60% and aspirin by 20%, at the expense of an increased incidence of haemorrhagic complications. "Rate control" and "rhythm control" strategies are probably equivalent, and the choice should also be made on an individualised basis. To assist the physician in making his choices for the care of an atrial fibrillation patient we propose specific tables and algorithms, with graded recommendations. On the evidence of data from the literature we propose simple algorithms and tables for the clinical management of atrial fibrillation in the individual patient.

Role of the hypocretin system in cocaine- and alcohol-related behaviors : evidence from hypocretin-deficient mice

RésuméL'addiction aux drogues est une maladie multifactorieile affectant toutes les strates de notre société. Cependant, la vulnérabilité à développer une addiction dépend de facteurs environnementaux, génétiques et psychosociaux. L'addiction aux drogues est décrite comme étant une maladie chronique avec un taux élevé de rechutes. Elle se caractérise par un besoin irrépressible de consommer une drogue et une augmentation progressive de la consommation en dépit des conséquences néfastes. Les mécanismes cérébraux responsables des dépendances aux drogues ne sont que partiellement élucidés, malgré une accumulation croissante d'évidences démontrant des adaptations au niveau moléculaire et cellulaire au sein des systèmes dopaminergique et glutamatergique. L'identification de nouveaux facteurs neurobiologiques responsables de la vulnérabilité aux substances d'abus est cruciale pour le développement de nouveaux traitements thérapeutiques capables d'atténuer et de soulager les symptômes liés à la dépendance aux drogues.Au cours des dernières années, de nombreuses études ont démontré qu'un nouveau circuit cérébral, le système hypocrétinergique, était impliqué dans plusieurs fonctions physiologiques, tel que l'éveil, le métabolisme énergétique, la motivation, le stress et les comportements liés aux phénomènes de récompense. Le système hypocrétinergique est composé d'environ 3000-4000 neurones issus de l'hypothalamus latéral projetant dans tout ie cerveau. Des souris transgéniques pour le gène des hypocrétines ont été générées et leur phénotype correspond à celui des animaux sauvages, excepté le fait qu'elles soient atteintes d'attaques de sommeil similaires à celles observées chez les patients narcoleptiques. H semblerait que les hypocrétines soient requises pour l'acquisition et l'expression de la dépendance aux drogues. Cependant, le mécanisme précis reste encore à être élucidé. Dans ce rapport, nous rendons compte des comportements liés aux phénomènes de récompense liés à l'alcool et à la cocaine chez les souris knock-out (KO), hétérozygotes (HET) et sauvages (WT).Nous avons, dans un premier temps, évalué l'impact d'injections répétées de cocaïne (15 mg/kg, ip) sur la sensibilisation locomotrice et sur le conditionnement place préférence. Nous avons pu observer que les souris WT, HET et KO exprimaient une sensibilisation locomotrice induite par une administration chronique de cocaïne, cependant les souris déficientes en hypocrétines démontraient une sensibilisation retardée et atténuée. Π est intéressant de mentionner que les mâles HET exprimaient une sensibilisation comportementale intermédiaire. Après normalisation des données, toutes les souris exprimaient une amplitude de sensibilisation similaire, excepté les souris mâles KO qui affichaient, le premier jour de traitement, une sensibilisation locomotrice réduite et retardée, reflétant un phénotype hypoactif plutôt qu'une altération de la réponse aux traitements chroniques de cocaïne. Contre toute attente, toutes les souris femelles exprimaient un pattern similaire de sensibilisation locomotrice à la cocaïne. Nous avons ensuite évalué l'effet d'un conditionnement comportemental à un environnement associé à des injections répétées de cocaine (15 mg / kg ip). Toutes les souris, quelque soit leur sexe ou leur génotype, ont manifesté une préférence marquée pour l'environnement apparié à la cocaïne. Après deux semaines d'abstinence à la cocaïne, les mâles et les femelles déficientes en hypocrétines n'exprimaient plus aucune préférence pour le compartiment précédemment associé à la cocaïne. Alors que les souris WT et HET maintenaient leur préférence pour le compartiment associé à la cocaïne. Pour finir, à l'aide d'un nouveau paradigme appelé IntelliCage®, nous avons pu évaluer la consommation de liquide chez les femelles WT, HET et KO. Lorsqu'il n'y avait que de l'eau disponible, nous avons observé que les femelles KO avaient tendance à moins explorer les quatre coins de la cage. Lorsque les souris étaient exposées à quatre types de solutions différentes (eau, ImM quinine ou 0.2% saccharine, alcool 8% et alcool 16%), les souris KO avaient tendance à moins consommer l'eau sucrée et les solutions alcoolisées. Cependant, après normalisation des données, aucune différence significative n'a pu être observée entre les différents génotypes, suggérant que la consommation réduite d'eau sucrée ou d'alcool peut être incombée à l'hypoactivité des souris KO.Ces résultats confirment que le comportement observé chez les souris KO serait dû à des compensations développementales, puisque la sensibilisation locomotrice et le conditionnement comportemental à la cocaïne étaient similaires aux souris HET et WT. En ce qui concerne la consommation de liquide, les souris KO avaient tendance à consommer moins d'eau sucrée et de solutions alcoolisées. Le phénotype hypoactif des souris déficientes en hypocrétine est probablement responsable de leur tendance à moins explorer leur environnement. Il reste encore à déterminer si l'expression de ce phénotype est la conséquence d'un état de vigilance amoindri ou d'une motivation diminuée à la recherche de récompense. Nos résultats suggèrent que les souris déficientes en hypocrétine affichent une motivation certaine à la recherche de récompense lorsqu'elles sont exposées à des environnements où peu d'efforts sont à fournir afin d'obtenir une récompense.AbstractDrug addiction is a multifactorial disorder affecting human beings regardless their education level, their economic status, their origin or even their gender, but the vulnerability to develop addiction depends on environmental, genetic and psychosocial dispositions. Drug addiction is defined as a chronic relapsing disorder characterized by compulsive drug seeking, with loss of control over drug intake and persistent maladaptive decision making in spite of adverse consequences. The brain mechanisms responsible for drug abuse remain partially unknown despite accumulating evidence delineating molecular and cellular adaptations within the glutamatergic and the dopaminergic systems. However, these adaptations do not fully explain the complex brain disease of drug addiction. The identification of other neurobiological factors responsible for the vulnerability to substance abuse is crucial for the development of promising therapeutic treatments able to alleviate signs of drug dependence.For the past few years, growing evidence demonstrated that a recently discovered brain circuit, the hypocretinergic system, is implicated in many physiological functions, including arousal, energy metabolism, motivation, stress and reward-related behaviors. The hypocretin system is composed of a few thousands neurons arising from the lateral hypothalamus and projecting to the entire brain. Hypocretin- deficient mice have been generated, and unexpectedly, their phenotype resembles that of wild type mice excepting sleep attacks strikingly similar to those of human narcolepsy patients. Evidence suggesting that hypocretins are required for the acquisition and the expression of drug addiction has also been reported; however the precise mechanism by which hypocretins modulate drug seeking behaviors remains a matter of debate. Here, we report alcohol and cocaine reward-related behaviors in hypocretin-deficient mice (KO), as well as heterozygous (HET) and wild type (WT) littermates.We first evaluated the impact of repeated cocaine injections (15 mg/kg, ip) on locomotor sensitization and conditioned place preference. We observed that WT, HET and KO mice exhibited behavioral sensitization following repeated cocaine administrations, but hypocretin deficient males displayed a delayed and attenuated response to chronic cocaine administrations. Interestingly, HET males exhibited an intermediate pattern of behavioral sensitization. However, after standardization of the post-injection data versus the period of habituation prior to cocaine injections, all mice displayed similar amplitudes of behavioral sensitization, except a reduced response in KO males on the first day, suggesting that the delayed and reduced cocaine-induced locomotor sensitization may reflect a hypoactive phenotype and probably not an altered response to repeated cocaine administrations. Unexpectedly, all female mice exhibited similar patterns of cocaine-induced behavioral sensitization. We then assessed the behavioral conditioning for an environment repeatedly paired with cocaine injections (15 mg/kg ip). All mice, whatever their gender or genotype, exhibited a robust preference for the environment previously paired with cocaine administrations. Noteworthy, following two weeks of cocaine abstinence, hypocretin-deficient males and females no longer exhibited any preference for the compartment previously paired with cocaine rewards whereas both WT and HET mice continued manifesting a robust preference. We finally assessed drinking behaviors in WT, HET and KO female mice using a novel paradigm, the IntelliCages®. We report here that KO females tended to less explore the four cage comers where water was easily available. When exposed to four different kinds of liquid solutions (water, ImM quinine or saccharine 0.2%, alcohol 8% and alcohol 16%), KO mice tended to less consume the sweet and the alcoholic beverages. However, after data standardization, no significant differences were noticed between genotypes suggesting that the hypoactive phenotype is most likely accountable for the trend regarding the reduced sweet or alcohol intake in KO.Taken together, the present findings confirm that the behavior seen in Hcrt KO mice likely reflects developmental compensations since only a slightly altered cocaine-induced behavioral sensitization and a normal behavioral conditioning with cocaine were observed in these mice compared to HET and WT littermates. With regards to drinking behaviors, KO mice barely displayed any behavioral changes but a trend for reducing sweet and alcoholic beverages. Overall, the most striking observation is the constant hypoactive phenotype seen in the hypocretin-deficient mice that most likely is accountable for their reduced tendency to explore the environment. Whether this hypoactive phenotype is due to a reduced alertness or reduced motivation for reward seeking remains debatable, but our findings suggest that the hypocretin-deficient mice barely display any altered motivation for reward seeking in environments where low efforts are required to access to a reward.

Frequency and determinants of unprotected sex among HIV-infected persons: the Swiss HIV cohort study.

BACKGROUND: Access to antiretroviral therapy may have changed condom use behavior. In January 2008, recommendations on condom use for human immunodeficiency virus (HIV)-positive persons were published in Switzerland, which allowed for unprotected sex under well-defined circumstances ("Swiss statement"). We studied the frequency, changes over time, and determinants of unprotected sex among HIV-positive persons. METHODS: Self-reported information on sexual preference, sexual partners, and condom use was collected at semi-annual visits in all participants of the prospective Swiss HIV Cohort Study from April 2007 through March 2009. Multivariable logistic regression models were fit using generalized estimating equations to investigate associations between characteristics of cohort participants and condom use. FINDINGS: A total of 7309 participants contributed to 21,978 visits. A total of 4291 persons (80%) reported sexual contacts with stable partners, 1646 (30%) with occasional partners, and 557 (10%) with stable and occasional partners. Of the study participants, 5838 (79.9%) of 7309 were receiving antiretroviral therapy, and of these, 4816 patients (82%) had a suppressed viral load. Condom use varied widely and differed by type of partner (visits with stable partners, 10,368 [80%] of 12,983; visits with occasional partners, 4300 [88%] of 4880) and by serostatus of stable partner (visits with HIV-negative partners, 7105 [89%] of 8174; visits with HIV-positive partners, 1453 [48%] of 2999). Participants were more likely to report unprotected sex with stable partners if they were receiving antiretroviral therapy, if HIV replication was suppressed, and after the publication of the "Swiss statement." Noninjection drug use and moderate or severe alcohol use were associated with unprotected sex. CONCLUSIONS: Antiretroviral treatment and plasma HIV RNA titers influence sexual behavior of HIV-positive persons. Noninjection illicit drug and alcohol use are important risk factors for unprotected sexual contacts.