Smoking and life expectancy among HIV-infected individuals on antiretroviral therapy in Europe and North America.

BACKGROUND: Cardiovascular disease and non-AIDS malignancies have become major causes of death among HIV-infected individuals. The relative impact of lifestyle and HIV-related factors are debated. METHODS: We estimated associations of smoking with mortality more than 1 year after antiretroviral therapy (ART) initiation among HIV-infected individuals enrolled in European and North American cohorts. IDUs were excluded. Causes of death were assigned using standardized procedures. We used abridged life tables to estimate life expectancies. Life-years lost to HIV were estimated by comparison with the French background population. RESULTS: Among 17 995 HIV-infected individuals followed for 79 760 person-years, the proportion of smokers was 60%. The mortality rate ratio (MRR) comparing smokers with nonsmokers was 1.94 [95% confidence interval (95% CI) 1.56-2.41]. The MRRs comparing current and previous smokers with never smokers were 1.70 (95% CI 1.23-2.34) and 0.92 (95% CI 0.64-1.34), respectively. Smokers had substantially higher mortality from cardiovascular disease, non-AIDS malignancies than nonsmokers [MRR 6.28 (95% CI 2.19-18.0) and 2.67 (95% CI 1.60-4.46), respectively]. Among 35-year-old HIV-infected men, the loss of life-years associated with smoking and HIV was 7.9 (95% CI 7.1-8.7) and 5.9 (95% CI 4.9-6.9), respectively. The life expectancy of virally suppressed, never-smokers was 43.5 years (95% CI 41.7-45.3), compared with 44.4 years among 35-year-old men in the background population. Excess MRRs/1000 person-years associated with smoking increased from 0.6 (95% CI -1.3 to 2.6) at age 35 to 43.6 (95% CI 37.9-49.3) at age at least 65 years. CONCLUSION: Well treated HIV-infected individuals may lose more life years through smoking than through HIV. Excess mortality associated with smoking increases markedly with age. Therefore, increases in smoking-related mortality can be expected as the treated HIV-infected population ages. Interventions for smoking cessation should be prioritized.

Traitement pharmacologique de la schizophrénie : évaluation comparative de la qualité des recommandations de pratique clinique = Comparative evaluation of clinical practice guidelines for the treatment of schizophrenia

De nombreuses recommandations de pratique clinique (RPC) ont été publiées, en réponse au développement du concept de la médecine fondée sur les preuves et comme solution à la difficulté de synthétiser et trier l'abondante littérature médicale. Pour faire un choix parmi le foisonnement de nouvelles RPC, il est primordial d'évaluer leur qualité. Récemment, le premier instrument d'évaluation standardisée de la qualité des RPC, appelé " AGREE " pour appraisal of guidelines for research and evaluation, a été validé. Nous avons comparé - avec l'aide de la grille " AGREE " - les six principales RPC publiées depuis une dizaine d'années sur le traitement de la schizophrénie : (1) les Recommandations de l'Agence nationale pour le développement de l'évaluation médicale (ANDEM) ; (2) The American Psychiatric Association (APA) practice guideline for the treatment of patients with schizophrenia ; (3) The quick reference guide of APA practice guideline for the treatment of patients with schizophrenia [APA - guide rapide de référence] ; (4) The schizophrenia patient outcomes research team (PORT) treatment recommandations ; (5) The Texas medication algorithm project " T-MAP " ; (6) The expert consensus guideline for the treatment of schizophrenia. Les résultats de notre étude ont ensuite été comparés avec ceux d'une étude similaire publiée en 2005 par Gæbel et al. portant sur 24 RPC abordant le traitement de la schizophrénie, réalisée également avec l'aide de la grille " AGREE " et deux évaluateurs [Br J Psychiatry 187 (2005) 248-255]. De manière générale, les scores des deux études ne sont pas trop éloignés et les deux évaluations globales des RPC convergent : chacune des six RPC est perfectible et présente différemment des points faibles et des points forts. La rigueur d'élaboration des six RPC est dans l'ensemble très moyenne, la prise en compte de l'opinion des utilisateurs potentiels est lacunaire et un effort sur la présentation des recommandations faciliterait leur utilisation clinique. L'applicabilité des recommandations est également peu considérée par les auteurs. Globalement, deux RPC se distinguent et peuvent être fortement recommandées selon les critères de la grille " AGREE " : " l'APA - guide rapide de référence " et le " T-MAP ".

Rauchentwohnung-- die zentrale Rolle der Arztinnen und Arzte [Smoking cessation--a central role for physicians]

Physicians are in a unique position to advice smokers to quit by the ability to integrate the various aspects of nicotine dependence. This review provides an overview of intervention with smokers presenting in a primary care setting. Strategies used for smoking cessation counseling differed according to patient's readiness to quit. For smokers who do not intend to quit smoking, physicians should inform and sensitize patients about tobacco use and cessation, especially by personalizing benefits to quit and challenging smokers 'beliefs. For smokers who are dissonant, physicians should use motivational strategies, such as discussing barriers to cessation and their solutions. For smokers ready to quit, the physician should show strong support, help set a quit date, prescribe pharmaceutical therapies for nicotine dependence, such as replacement therapy and/or bupropion, with instructions for use, and suggest behavioral strategies to prevent relapse.

Glutathione deficit in schizophrenia: strategies to increase glutathione levels in " in vitro " and clinical studies

Summary: Decrease in glutathione (GSH) levels was observed in cerebrospinal fluid, prefrontal cortex and post-mortem striatum of schizophrenia patients. Evidences suggest a defect in GSH synthesis at the levels of the rate-limiting synthesizing enzyme, glutamate cysteine ligase (GCL). Indeed, polymorphisms in the gene of the modifier subunit of GCL (GCLM) was shown to be associated with the disease in three different populations, GCLM gene expression is decreaséd in fibroblasts from patients and the increase in GCL activity induced by an oxidative stress is lower in patients' fibroblasts compared to controls. GSH being a major antioxydant and redox regulator, its presence is of high importance for protecting cells against oxidative stress. The aim of the present work was to use various substances to increase GSH levels by diverse strategies. Since the synthesizing enzyme GCL is defective, bypassing this enzyme was the first strategy we used. GSH ethyl ester (GSHEE), a membrane permeable analog of GSH, succeeded in replenishing GSH levels in cultured neurons and astrocytes previously depleted in GSH by L-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of GCL. GSHEE also abolished dopamine-induced decrease of NMDA-mediated calcium response observed in BSO-treated neurons. y-Glutamylcysteine ethyl ester (GCSE), a membrane permeable analog of the product of GCL, increased GSH levels only in astrocytes. The second strategy was to boost the defective enzyme GCL. While quercetin (flavonoid) could increase GSH levels only in astrocytes, curcumin (polyphenol) and tertbutylhydroquinone (quinone) were successful in both neurons and astrocytes, via an increase in the gene expression of the two subunits of GCL and, consequently, an increase in the activity of the enzyme. However, FK506, an immunosupressant, was unefficient. Treating astrocytes from GCLM KO mice showed that the modulatory subunit is necessary for the action of the substances. Finally, since cysteine is the limiting precursor in the synthesis of GSH, we hypothesized that we could increase GSH levels by providing more of this precursor. N-acetyl-cysteine (NAC), a cysteine donor, was administered to schizophrenia patients, using adouble-blind and cross-over protocol. NAC significantly improved the mismatch negativity (MMN), a component of the auditory evoked potentials, thought to reflect selective current flowing through open, unblocked NMDA channels. Considering that NMDA function is reduced when GSH levels are low, increasing these levels with NAC could improve NMDA function as reflected by the improvement in the generation of the MMN. Résumé: Les taux de glutathion (GSH) dans le liquide céphalo-rachidien, le cortex préfrontal ainsi que le striatum post-mortem de patients schizophrènes, sont diminués. L'enzyme limitante dans la synthèse du GSH, la glutamyl-cysteine ligase (GCL), est défectueuse. En effet, des polymorphismes dans le gène de la sous-unité modulatrice de GCL (GCLM) sont associés à la maladie, l'expression du gène GCLM est diminuée dans les fibroblastes de patients et, lors d'un stress oxidative, l'augmentation de l'activité de GCL est plus faible chez les patients que chez les contrôles. Le GSH étant un important antioxydant et régulateur du status redox, sa présence est primordiale afin de protéger les cellules contre les stress oxydatifs. Au cours du présent travail, une variété de substances ont été utilisées dans le but d'augmenter les taux de GSH. Passer outre l'enzyme de synthèse GCL qui est défectueuse fut la première stratégie utilisée. L'éthylester de GSH (GSHEE), un analogue du GSH qui pénètre la membrane cellulaire, a augmenté les taux de GSH dans des neurones et des astrocytes déficitaires en GSH dû au L-buthionine-(S,R)-sulfoximine (BSO), un inhibiteur du GCL. Dans ces neurones, le GSHEE a aussi aboli la diminution de la réponse NMDA, induite parla dopamine. L'éthyl-ester de y-glutamylcysteine (GCEE), un analogue du produit de la GCL qui pénètre la membrane cellulaire, a augmenté les taux de GSH seulement dans les astrocytes. La seconde stratégie était d'augmenter l'activité de l'enzyme GCL. Tandis que la quercétine (flavonoïde) n'a pu augmenter les taux de GSH que dans les astrocytes, la curcumin (polyphénol) et le tert-butylhydroquinone (quinone) furent efficaces dans les deux types de cellules, via une augmentation de l'expression des gènes des deux sous-unités de GCL et de l'activité de l'enzyme. Le FK506 (immunosupresseur) n' a démontré aucune efficacité. Traiter des astrocytes provenant de souris GCLM KO a permis d'observer que la sous-unité modulatoire est nécessaire à l'action des substances. Enfin, puisque la cysteine est le substrat limitant dans la synthèse du GSH, fournir plus de ce présurseur pourrait augmenter les taux de GSH. Nacétyl-cystéine (NAC), un donneur de cystéine, a été administrée à des schizophrènes, lors d'une étude en double-aveugle et cross-over. NAC a amélioré le mismatch negativity (MMN), un composant des potentials évoqués auditifs, qui reflète le courant circulant via les canaux NMDA. Puisque la fonctionnalité des R-NMDA est diminuée lorsque les taux de GSH sont bas, augmenter ces taux avec NAC pourrait améliorer la fonction des R-NMDA, réflété par une augmentation de l'amplitude du MMN.

The role of smoking in changes in the survival curve: an empirical study in 10 European countries.

PURPOSE: We examined the role of smoking in the two dimensions behind the time trends in adult mortality in European countries, that is, rectangularization of the survival curve (mortality compression) and longevity extension (increase in the age-at-death). METHODS: Using data on national sex-specific populations aged 50 years and older from Denmark, Finland, France, West Germany, Italy, the Netherlands, Norway, Sweden, Switzerland, and the United Kingdom, we studied trends in life expectancy, rectangularity, and longevity from 1950 to 2009 for both all-cause and nonsmoking-related mortality and correlated them with trends in lifetime smoking prevalence. RESULTS: For all-cause mortality, rectangularization accelerated around 1980 among men in all the countries studied, and more recently among women in Denmark and the United Kingdom. Trends in lifetime smoking prevalence correlated negatively with both rectangularization and longevity extension, but more negatively with rectangularization. For nonsmoking-related mortality, rectangularization among men did not accelerate around 1980. Among women, the differences between all-cause mortality and nonsmoking-related mortality were small, but larger for rectangularization than for longevity extension. Rectangularization contributed less to the increase in life expectancy than longevity extension, especially for nonsmoking-related mortality among men. CONCLUSIONS: Smoking affects rectangularization more than longevity extension, both among men and women.

Tobacco control policies in hospitals before and after the implementation of a national smoking ban in Catalonia, Spain

Background: Diverse projects and guidelines to assist hospitals towards the attainment of comprehensive smoke-free policies have been developed. In 2006, Spain government passed a new smoking ban that reinforce tobacco control policies and banned completely smoking in hospitals. This study assesses the progression of tobacco control policies in the Catalan Network of Smokefree Hospitals before and after a comprehensive national smoking ban. Methods: We used the Self-Audit Questionnaire of the European Network for Smoke-free Hospitals to score the compliance of 9 policy standards (global score = 102). We used two crosssectional surveys to evaluate tobacco control policies before (2005) and after the implementation of a national smoking ban (2007) in 32 hospitals of Catalonia, Spain. We compared the means of the overall score in 2005 and 2007 according to the type of hospital, the number of beds, the prevalence of tobacco consumption, and the number of years as a smoke-free hospital. Results: The mean of the implementation score of tobacco control policies was 52.4 (95% CI:45.4-59.5) in 2005 and 71.6 (95% CI: 67.0-76.2) in 2007 with an increase of 36.7% (p < 0.01). The hospitals with greater improvement were general hospitals (48% increase; p < 0.01), hospitals with > 300 beds (41.1% increase; p < 0.01), hospitals with employees' tobacco consumption prevalence 35-39% (72.2% increase; p < 0.05) and hospitals that had recently implemented smoke-free policies (74.2% increase; p < 0.01). Conclusion: The national smoking ban appears to increase tobacco control activities in hospitals combined with other non-bylaw initiatives such as the Smoke-free Hospital Network.

Tobacco control policies in hospitals before and after the implementation of a national smoking ban in Catalonia, Spain

Background: Diverse projects and guidelines to assist hospitals towards the attainment of comprehensive smoke-free policies have been developed. In 2006, Spain government passed a new smoking ban that reinforce tobacco control policies and banned completely smoking in hospitals. This study assesses the progression of tobacco control policies in the Catalan Network of Smokefree Hospitals before and after a comprehensive national smoking ban. Methods: We used the Self-Audit Questionnaire of the European Network for Smoke-free Hospitals to score the compliance of 9 policy standards (global score = 102). We used two crosssectional surveys to evaluate tobacco control policies before (2005) and after the implementation of a national smoking ban (2007) in 32 hospitals of Catalonia, Spain. We compared the means of the overall score in 2005 and 2007 according to the type of hospital, the number of beds, the prevalence of tobacco consumption, and the number of years as a smoke-free hospital. Results: The mean of the implementation score of tobacco control policies was 52.4 (95% CI:45.4-59.5) in 2005 and 71.6 (95% CI: 67.0-76.2) in 2007 with an increase of 36.7% (p < 0.01). The hospitals with greater improvement were general hospitals (48% increase; p < 0.01), hospitals with > 300 beds (41.1% increase; p < 0.01), hospitals with employees' tobacco consumption prevalence 35-39% (72.2% increase; p < 0.05) and hospitals that had recently implemented smoke-free policies (74.2% increase; p < 0.01). Conclusion: The national smoking ban appears to increase tobacco control activities in hospitals combined with other non-bylaw initiatives such as the Smoke-free Hospital Network.

Targeting Oxidative Stress and Aberrant Critical Period Plasticity in the Developmental Trajectory to Schizophrenia.

Schizophrenia is a neurodevelopmental disorder reflecting a convergence of genetic risk and early life stress. The slow progression to first psychotic episode represents both a window of vulnerability as well as opportunity for therapeutic intervention. Here, we consider recent neurobiological insight into the cellular and molecular components of developmental critical periods and their vulnerability to redox dysregulation. In particular, the consistent loss of parvalbumin-positive interneuron (PVI) function and their surrounding perineuronal nets (PNNs) as well as myelination in patient brains is consistent with a delayed or extended period of circuit instability. This linkage to critical period triggers (PVI) and brakes (PNN, myelin) implicates mistimed trajectories of brain development in mental illness. Strategically introduced antioxidant treatment or later reinforcement of molecular brakes may then offer a novel prophylactic psychiatry.

Compliance of hospitality premises to the ban on smoking in all enclosed public places in the Seychelles

In Seychelles, comprehensive tobacco control legislation enacted in 2009, and subsequent regulations, ban smoking in all enclosed places (defined as any area under a fixed or transient roof). A survey in October-November 2014 assessed i) the compliance to the Act and these regulations in 63 restaurants, bars or discotheques and ii) knowledge of the Tobacco control Act and these regulations of supervisors and managers of these hospitality premises; (47 agreed to answer). No person was found smoking in 92% of all premises. However, "no smoking" signs did not conform to regulations in >70% of premises, and ashtrays were seen in 17% of enclosed premises. All supervisors and managers (100%) knew that smoking is banned in enclosed premises but <15% knew the fines liable to persons, respective owners of enclosed places, when a person smokes in an enclosed premise. Furthermore, 60% of supervisors were not aware that no smoking signs must comply with a specific regulation and 40% were not aware that ashtrays are not permitted in enclosed premises. In conclusion, the positive finding is that few persons smoke in restaurants, bars and discotheques, but the survey also showed that several aspects of regulations for tobacco control in enclosed premises are not well implemented. This calls for further information campaigns targeting both the public and the managers of hospitality premises, but also for strengthening enforcement measures, including fines for offenses. Scaling up comprehensive tobacco control measures, including full enforcement of clean air policy, is of paramount importance to meet the national target of 30% reduction of the smoking prevalence between 2010 and 2025.

Heavier smoking may lead to a relative increase in waist circumference: evidence for a causal relationship from a Mendelian randomisation meta-analysis. The CARTA consortium.

OBJECTIVES: To investigate, using a Mendelian randomisation approach, whether heavier smoking is associated with a range of regional adiposity phenotypes, in particular those related to abdominal adiposity. DESIGN: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730 in the CHRNA5-CHRNA3-CHRNB4 gene region) as a proxy for smoking heaviness, of the associations of smoking heaviness with a range of adiposity phenotypes. PARTICIPANTS: 148 731 current, former and never-smokers of European ancestry aged ≥16 years from 29 studies in the consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA). PRIMARY OUTCOME MEASURES: Waist and hip circumferences, and waist-hip ratio. RESULTS: The data included up to 66 809 never-smokers, 43 009 former smokers and 38 913 current daily cigarette smokers. Among current smokers, for each extra minor allele, the geometric mean was lower for waist circumference by -0.40% (95% CI -0.57% to -0.22%), with effects on hip circumference, waist-hip ratio and body mass index (BMI) being -0.31% (95% CI -0.42% to -0.19), -0.08% (-0.19% to 0.03%) and -0.74% (-0.96% to -0.51%), respectively. In contrast, among never-smokers, these effects were higher by 0.23% (0.09% to 0.36%), 0.17% (0.08% to 0.26%), 0.07% (-0.01% to 0.15%) and 0.35% (0.18% to 0.52%), respectively. When adjusting the three central adiposity measures for BMI, the effects among current smokers changed direction and were higher by 0.14% (0.05% to 0.22%) for waist circumference, 0.02% (-0.05% to 0.08%) for hip circumference and 0.10% (0.02% to 0.19%) for waist-hip ratio, for each extra minor allele. CONCLUSIONS: For a given BMI, a gene variant associated with increased cigarette consumption was associated with increased waist circumference. Smoking in an effort to control weight may lead to accumulation of central adiposity.