Da dependência à independência: o papel da família no processo de reinserção do toxicodependente e alcoólico

Dissertação de mestrado em Sociologia (área de especialização em Desenvolvimento e Políticas Sociais)

Velhas e novas drogas: impactos da toxicodependência: estudo de caso na cidade de Braga

Dissertação de mestrado em Sociologia (área de especialização em Organizações e Trabalho)

Biomedical risk assessment as an aid for smoking cessation.

BACKGROUND: A possible strategy for increasing smoking cessation rates could be to provide smokers who have contact with healthcare systems with feedback on the biomedical or potential future effects of smoking, e.g. measurement of exhaled carbon monoxide (CO), lung function, or genetic susceptibility to lung cancer. OBJECTIVES: To determine the efficacy of biomedical risk assessment provided in addition to various levels of counselling, as a contributing aid to smoking cessation. SEARCH STRATEGY: We systematically searched the Cochrane Collaboration Tobacco Addiction Group Specialized Register, Cochrane Central Register of Controlled Trials 2008 Issue 4, MEDLINE (1966 to January 2009), and EMBASE (1980 to January 2009). We combined methodological terms with terms related to smoking cessation counselling and biomedical measurements. SELECTION CRITERIA: Inclusion criteria were: a randomized controlled trial design; subjects participating in smoking cessation interventions; interventions based on a biomedical test to increase motivation to quit; control groups receiving all other components of intervention; an outcome of smoking cessation rate at least six months after the start of the intervention. DATA COLLECTION AND ANALYSIS: Two assessors independently conducted data extraction on each paper, with disagreements resolved by consensus. Results were expressed as a relative risk (RR) for smoking cessation with 95% confidence intervals (CI). Where appropriate a pooled effect was estimated using a Mantel-Haenszel fixed effect method. MAIN RESULTS: We included eleven trials using a variety of biomedical tests. Two pairs of trials had sufficiently similar recruitment, setting and interventions to calculate a pooled effect; there was no evidence that CO measurement in primary care (RR 1.06, 95% CI 0.85 to 1.32) or spirometry in primary care (RR 1.18, 95% CI 0.77 to 1.81) increased cessation rates. We did not pool the other seven trials. One trial in primary care detected a significant benefit of lung age feedback after spirometry (RR 2.12; 95% CI 1.24 to 3.62). One trial that used ultrasonography of carotid and femoral arteries and photographs of plaques detected a benefit (RR 2.77; 95% CI 1.04 to 7.41) but enrolled a population of light smokers. Five trials failed to detect evidence of a significant effect. One of these tested CO feedback alone and CO + genetic susceptibility as two different intervention; none of the three possible comparisons detected significant effects. Three others used a combination of CO and spirometry feedback in different settings, and one tested for a genetic marker. AUTHORS' CONCLUSIONS: There is little evidence about the effects of most types of biomedical tests for risk assessment. Spirometry combined with an interpretation of the results in terms of 'lung age' had a significant effect in a single good quality trial. Mixed quality evidence does not support the hypothesis that other types of biomedical risk assessment increase smoking cessation in comparison to standard treatment. Only two pairs of studies were similar enough in term of recruitment, setting, and intervention to allow meta-analysis.

D-amphetamine fails to increase extracellular dopamine levels in mice lacking alpha 1b-adrenergic receptors: relationship between functional and nonfunctional dopamine release.

It was found recently that locomotor and rewarding effects of psychostimulants and opiates were dramatically decreased or suppressed in mice lacking alpha1b-adrenergic receptors [alpha1b-adrenergic receptor knock-outs (alpha1bAR-KOs)] (Drouin et al., 2002). Here we show that blunted locomotor responses induced by 3 and 6 mg/kg d-amphetamine in alpha1bAR-KO mice [-84 and -74%, respectively, when compared with wild-type (WT) mice] are correlated with an absence of d-amphetamine-induced increase in extracellular dopamine (DA) levels in the nucleus accumbens of alpha1bAR-KO mice. Moreover, basal extracellular DA levels in the nucleus accumbens are lower in alpha1bAR-KO than in WT littermates (-28%; p < 0.001). In rats however, prazosin, an alpha1-adrenergic antagonist, decreases d-amphetamine-induced locomotor hyperactivity without affecting extracellular DA levels in the nucleus accumbens, a finding related to the presence of an important nonfunctional release of DA (Darracq et al., 1998). We show here that local d-amphetamine releases nonfunctional DA with the same affinity but a more than threefold lower amplitude in C57BL6/J mice than in Sprague Dawley rats. Altogether, this suggests that a trans-synaptic mechanism amplifies functional DA into nonfunctional DA release. Our data confirm the presence of a powerful coupling between noradrenergic and dopaminergic neurons through the stimulation of alpha1b-adrenergic receptors and indicate that nonfunctional DA release is critical in the interpretation of changes in extracellular DA levels. These results suggest that alpha1b-adrenergic receptors may be important therapeutic pharmacological targets not only in addiction but also in psychosis because most neuroleptics possess anti-alpha1-adrenergic properties.

Systematic identification of genomic markers of drug sensitivity in cancer cells.

Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

When to Quit Under Uncertainty? A real options approach to smoking cessation

This paper models the decision to quit smoking like an investment decision where the quitter incurs a sunk withdrawal cost today and forgoes their consumer surplus from cigarettes (invests) and hopes to reap an uncertain reward of better health and therefore higher utility in the future (return). We show that a risk-averse mature smoker who expects to benefit from quitting may still rationally choose to delay quitting until they are more confident that quitting is the right decision for them. Such a decision by the smoker is due to the value associated with keeping their option of whether or not to quit open as they learn more about the damage that smoking will have on their future utility. Policies which reduce a smoker’s uncertainty about the damage that smoking with have on their future utility is likely to make them quit earlier.

Obesity and smoking: can we catch two birds with one tax?

The debate on tobacco and fat taxes often treats smoking and eating as independent behaviors. However, the available evidence shows that they are interdependent, which implies that policies against smoking or obesity may have larger scope than expected. To address this issue, we propose a dynamic rational model where eating and smoking are simultaneous choices that jointly affect body weight and addiction to smoking. Focusing on direct and cross-price effects, we compare tobacco taxes and food taxes and we show that a single policy tool can reduce both smoking and body weight. In particular, food taxes can be more effective than tobacco taxes at simultaneously fighting obesity and smoking.

Aspects génétiques de la consommation de tabac et prise en charge clinique [Genetic aspects of smoking and impact on clinical care]

Tobacco smoking is a major public health issue and a better understanding of tobacco addiction represents an important challenge. Many factors are involved in tobacco addiction, including genetic factors. Taking them into account in smoking cessation programs would allow to better adapt these programs to individual characteristics and improve their rate of success. Given enzymatic induction by tobacco smoke, smoking cessation can nevertheless have important consequences on the metabolism of some drugs, that have to be taken into consideration. Here we present different clinical and genetic aspects of smoking and of smoking cessation. A dose adjustment of drugs influenced by tobacco smoke is proposed when quitting smoking.

Analyse des données migrants du Monitorage suisse des addictions

L'office fédéral de la santé publique (OFSP) a lancé le Monitorage suisse des addictions en 2011 (en anglais : Addiction Monitoring in Switzerland- AMIS). A intervalles réguliers, des données représentatives de la population suisse sont recensées, notamment en ce qui concerne la consommation d'alcool, de tabac, de drogues illégales et de médicaments ainsi que les risques qui lui sont liés. A cet effet, 11'000 personnes âgées de 15 ans et plus sont contactées annuellement pour répondre à un questionnaire. A ce jour, les données de 2011 et 2012 sont disponibles. Dans le cadre du Programme national migration et santé (2008-2013), l'OFSP désire compléter les données disponibles sur la santé des migrants. Ce rapport présente une analyse secondaire des données portant sur les migrants dans le cadre de l'enquête téléphonique continue mentionnée ci-dessus qui a été effectuée auprès de plus de 22'000 personnes de 15 ans et plus, résidant en Suisse en 2011 et 2012.

Gambling among youths in Switzerland and its association with other addictive behaviours: a population-based study.

OBJECTIVE: To assess the prevalence of problem gambling in a population of youths in Switzerland and to determine its association with other potentially addictive behaviours. METHODS: Cross-sectional survey including 1,102 participants in the first and second year of post-compulsory education, reporting gambling, socio-demographics, internet use and substance use. For three categories of gambling (nongambler; nonproblem gambler and at-risk/problem gambler). socio-demographic and addiction data were compared using a bivariate analysis. All significant variables were included in a multinominal logistic regression using nongamblers as the reference category. RESULTS: The prevalence of gamblers was 37.48% (n = 413), with nonproblem gamblers being 31.94% (n = 352) and at-risk/problem gamblers 5.54% (n = 61). At the bivariate level, severity of gambling increased among adults (over 18 years) and among males, vocational students, participants not living with both parents and youths having a low socio-economic status. Gambling was also associated to the four addictive behaviours studied. At the multivariate level, risk of nonproblem gambling was increased in males, older youths, vocational students, participants of Swiss origin and alcohol misusers. Risk of at-risk/problem gambling was higher for males, older youths, alcohol misusers, participants not living with both parents and problem internet users. CONCLUSIONS: One-third of youths in our sample had gambled in the previous year and gambling is associated with other addictive behaviours. Clinicians should screen their adolescent patients for gambling habits, especially if other addictive behaviours are present. Additionally, gambling should be included in prevention campaigns together with other addictive behaviours.

Validació i adaptació de l'EuropASI a la població penitenciària catalana (Índex europeu de la severitat de l'addicció)

Aquest treball d'investigació fa una anàlisi de les possibilitats de l’escala EuropASI. Aquest instrument, adaptació europea de l'Addiction Severity Index (ASI), ha demostrat la seva utilitat com a instrument que permet avaluar diferents àrees, assignar als usuaris un tractament i avaluar els canvis produïts per un tractament. També s'han administrat altres proves, com ara la CMR-versió presó i la TECVASP, i s'han recollit diferents variables penitenciàries. En aquesta investigació s'ha fet una revisió dels principals treballs relacionats amb aquest instrument i s'ha utilitzat una mostra de 49 interns dels DAE del Centre Penitenciari Quatre Camins i del Centre Penitenciari Brians 2. Després d'analitzar les dades obtingudes, s'han observat algunes diferències significatives entre els interns del dos DAE que l'EuropASI és capaç de detectar. Les correlacions entre les escales de l'EuropASI indiquen una coherència interna en relació amb les mostres observades. Algunes escales, com ara les d'estat psiquiàtric, relacions familiars i socials i consum d'alcohol i drogues són les que aporten major informació en el global de l'escala. La inclusió de l'escala de l'ASI Criminalitat aporta informació especifica que complementa la resta de les escales. Al treball també s'emfatitzen alguns aspectes relacionats amb l'aplicació i amb la recomanació que les persones que utilitzin aquest instrument tinguin algun tipus de formació, així com algunes propostes relacionades amb l'escala.

Dimensionality of drinking consequences - cross-cultural comparability and stability over time

Despite the long tradition for asking about the negative social and health consequences of alcohol consumption in surveys, little is known about the dimensionality of these consequences. Analysing cross-sectional and longitudinal data from the Nordic Taxation Study collected for Sweden, Finland, and Denmark in two waves in 2003 and 2004 by means of an explorative principal component analysis for categorical data (CATPCA), it is tested whether consequences have a single underlying dimension across cultures. It further tests the reliability, replicability, concurrent and predictive validity of the consequence scales. A one-dimensional solution was commonly preferable. Whereas the two-dimensional solution was unable to distinguish clearly between different concepts of consequences, the one-dimensional solution resulted in interpretable, generally very stable scales within countries across different samples and time.

Avaluació de la capacitat de segrest de carboni d'un sòl restaurat amb fangs de depuradora: estabilitat de la matèria orgànica

L’avaluació de la capacitat de segrest de carboni d’un sòl denudat per l’extracció de calcàries i la seva posterior restauració amb fangs de depuradora s’ha realitzat mitjançant l’anàlisi de l’estabilitat de la matèria orgànica del sòl (MOS) en funció de la dosi de fangs aplicada. Els resultats d’aquest treball demostren dos fets fonamentals per a l’estudi de la capacitat de segrest de carboni, els qual són: la conservació del contingut total de MOS i l’augment de la seva estabilitat fins a nivells més alts que els de la MOS de les parcel·les de control. Aquests resultats són explicables per (i) la conservació i augment de la MOS recalcitrant, i (ii) la protecció d’una porció més o menys rellevant de la MO làbil continguda amb els fangs gràcies a l’acció simultània dels mecanismes d’estabilització de la MOS, com són: l’estabilització bioquímica (humificació), química, física, a més de la pròpia hidrofobicitat de la MOS, aquests dos últims potenciats per l’addicció del fangs de depuradora.

Prevalence of and potential influencing factors for alcohol dependence in europe.

Alcohol use disorders (AUDs), and alcohol dependence (AD) in particular, are prevalent and associated with a large burden of disability and mortality. The aim of this study was to estimate prevalence of AD in the European Union (EU), Iceland, Norway, and Switzerland for the year 2010, and to investigate potential influencing factors. The 1-year prevalence of AD in the EU was estimated at 3.4% among people 18-64 years of age in Europe (women 1.7%, men 5.2%), resulting in close to 11 million affected people. Taking into account all people of all ages, AD, abuse and harmful use resulted in an estimate of 23 million affected people. Prevalence of AD varied widely between European countries, and was significantly impacted by drinking cultures and social norms. Correlations with level of drinking and other drinking variables and with major known outcomes of heavy drinking, such as liver cirrhosis or injury, were moderate. These results suggest a need to rethink the definition of AUDs.

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.