Effectiveness of a health professional training program for treatment of tobacco addiction.

INTRODUCTION: Advice can have a small but clinically important effect in promoting smoking cessation. Where studied, the rate of delivery has been found to be low. Training has been found to increases this rates, but there is little research on effectiveness in terms of smoking cessation rates. This study aimed to assess the effectiveness and cost-effectiveness of an health professionals educational program to increase long-term rates of nicotine abstinence in smoking outpatients. METHODS: We conducted a pragmatic cluster-randomized, controlled trial in 35 primary health care centers in Spain. Participants were all 830 health professionals who attended 5,970 smokers during recruiting period. After that we measured continuous abstinence 6 months after the intervention and biochemically validated (saliva cotinine test) 1 year following intervention. Cost-effectiveness was measured in terms of cost per life year gained. RESULTS: After 6 months, the rate of continuous abstinence was significantly higher in the intervention group (2.1% vs. 0.3%, p > .0001) with an odds ratio of 6.5 (95% CI = 3.3-12.7). After 1 year, biochemical validation was performed on 31 of the 67 patients previously registered as abstinent. All of them were abstinent and belonged to intervention group. The incremental cost per life year gained after 6 months was €969. CONCLUSIONS: A primary care training program on smoking cessation based on scientific evidence, behavioral theory, and active learning methods increases long-term continuous nicotine abstinence rate among outpatients in a significant way. These may be relevant for planning training of professionals, clinical assistance, and public health programs.

[10 years of innovation in the treatment of latent tuberculosis infection: a comparison between standard and short course therapies in directly observed therapy]. / 10 años innovando en el tratamiento de la infección tuberculosa latente: comparación entre pautas estándar y pautas cortas en tratamiento directamente observado.

OBJECTIVES: The main aim of the study is to compare the acceptance, adherence, tolerance and safety of short course therapies in comparison to a standard 9 month treatment for latent tuberculosis infection (LTBI) in directly observed therapy (DOT) and contrast this with previous results from a standard therapy in patient self-administered treatment. MATERIALS AND METHODS: Retrospective longitudinal study carried out at a medium sized prison. Period of inclusion covers 10 years, from January 2000 to December 2009. The Centers for Disease Control and Prevention (CDC) inclusion and exclusion criteria were used, as well as the ones included in the Program for Tuberculosis Prevention and Control in the Prison Environment. 4 LTBI therapies according to the preference of the patient and possible interactions with other treatments were utilised. Therapy I consisted of isoniazid (H) in doses of 300 mg/day for 9 months (9H), therapy II with rifampicin for 2 months, twice a week, (2R2Z2) therapy III with rifampicin and isoniazid for 3 months (3RH) and therapy IV with rifampicin for four months (4R). Treatment was administered under strict DOT conditions by nursing staff. RESULTS: 902 patients were included, of which 810 accepted the treatment (89.90%), distributed as follows: 400 in the 9H therapy, and 410 with short course therapies (316 in the 2R2Z2, 82 in the 3RH therapy and 12 in the 4R therapy). 92 patients (10.20%) did not accept LTBI therapy, 271 patients (67.75%) concluded the LTBI treatment with 9H, and 314 (76.60%) with short courses. 232 patients (73.42%) concluded the 2R2Z2, 85.40% with the 3RH 70 therapy and 12 (100%) with the 4R treatment. 129 patients (32.25%) did not complete the LTBI 9H therapy (63 due to voluntary withdrawal, 35 due to adverse reactions, 26 for release or transfer, 2 for unknown reasons, 1 due to tuberculosis in a HIV-patient and 1 due to suicide). 96 patients (23.41%) did not conclude the short course therapies (36 due to voluntary withdrawal, 54 due to adverse reactions, 1 due to release or transfer, 3 for unknown reasons, 1 due to a psychotic episode, and 1 due to hepatitis of unknown aetiology). Significant differences could be discerned in the LTBI therapy conclusion rates when comparing the standard 9H and short course therapies. A greater, statistically significant, probability is observed with the short course therapies: p: 0.006; Odds Ration: 1.56 (LC95%: 1.14-2.12). This difference is a result of the 9H therapy presenting a greater number of voluntary withdrawals for no apparent reason (p: 0.002; OR: 2.03 [1.30-3.15]) and a greater number of withdrawals as a result of transfers to another prison or release (p<0.0001; OR 30.22 [4.07-224.29]), with no significant differences being found in withdrawals for adverse reactions between the 9H therapy and the short course treatments as a whole. The 2R2Z2 therapy shows a higher probability of withdrawals for adverse reactions (p: 0.006; OR: 1.87 [(1.21-2.88]) than the other therapies. CONCLUSION: Greater acceptance of initiating therapy was observed in all the DOT therapies. The 3RH, 2R2Z2 and 4R short course therapies favoured better adherence, with significantly lower ratios of withdrawal than the 9H therapy for the treatment of latent tuberculosis infection. Tolerance and safety of the short course therapies was very similar to the standard 9H treatment, with a significantly higher percentage of adverse reactions in the 2R2Z2 therapy in comparison to others. Our data backs up the safety and adherence of a short course 3RH therapy in DOT for treating latent tuberculosis infection and its preferential use in the prison environment in comparison to isoniazid due to the greater number of patients concluding treatment. The administration of LBTI therapy in DOT achieves a high percentage of acceptance and conclusion of treatments in prison, significantly improving on the previous results in a cross-sectional study of the prison environment and others obtained at our centre in self-administered treatment.

10 Años innovando en el tratamiento de la infección tuberculosa latente: comparación entre pautas estándar y pautas cortas en tratamiento directamente observado / 10 Years of innovation in the treatment of latent tuberculosis infection: a comparison between standard and short course therapies in directly observed therapy

Objetivos: El objetivo principal del estudio fue comparar la aceptación, adherencia, tolerancia y seguridad de varias pautas cortas para el tratamiento de la infección tuberculosa latente (TIT), frente a una estándar de 9 meses, en tratamiento directamente observado (TDO) y confrontarlas con resultados previos de una pauta estándar en tratamiento autoadministrado por el paciente. Pacientes y métodos: Estudio longitudinal retrospectivo realizado en un centro penitenciario de tamaño medio. El período de inclusión abarcó 10 años, de enero de 2000 a diciembre de 2009. Se utilizaron los criterios de inclusión y exclusión de los Centers for Disease Control and Prevention (CDC) y los recogidos en el Programa de Prevención y Control de la Tuberculosis en el Medio Penitenciario. Se utilizaron 4 pautas de TIT según la preferencia del paciente y posibles interacciones con otros tratamientos. La pauta incluía isoniazida (H) en dosis de 300 mg/dia 9 meses (9H), la pauta II rifampicina más pirazinamida durante 2 meses 2 veces por semana, (2R2Z2) la pauta III rifampicina más isoniazida durante 3 meses (3RH) y la pauta IV rifampicina durante 4 meses (4R). Se administró el tratamiento de forma estricta en TDO por el personal de enfermería. Resultados: Se incluyen 902 pacientes, aceptando el tratamiento 810 (89,80%), distribuidos de la siguiente forma: 400 en la pauta 9H, y 410 con las pautas cortas (316 en la pauta 2R2Z2, 82 en la pauta 3RH y 12 en la pauta 4R. No aceptaron el TIT 92 (10,20%) pacientes. Finalizaron el TIT 271 (67,75%) con 9H, y 314 (76,60%) con las pautas cortas. Finalizaron con 2R2Z2, 232 pacientes (73,42%), con 3RH 70 (85,40%) y 12 (100%) con 4R. No finalizan el TIT con la pauta 9H 129 (32,25%) pacientes por los siguientes motivos (63 por abandono voluntario, 35 por reacciones adversas, 26 por libertad o traslado, 2 por causa desconocida, 1 por enfermedad tuberculosa en un paciente VIH- y 1 por suicidio). No finalizan el TIT con las pautas cortas 96 (23,41%) pacientes, por los siguientes motivos (36 por abandono voluntario, 54 por reacciones adversas, 1 por libertad o traslado, 3 por causa desconocida, 1 por brote psicótico en enfermo psiquiátrico y 1 por hepatitis aguda no filiada). Se aprecian diferencias significativas en las tasas de finalización del TIT al comparar la pauta estándar 9H y las pautas cortas. Se observa una mayor probabilidad de finalización, estadísticamente significativa, con las pautas cortas: p: 0,006; Odds Ratio: 1.56 (LC95%: 1.14-2.12). Este diferencia en la finalización se debe a que la pauta 9H presenta un mayor número de abandonos voluntarios sin motivo aparente (p: 0.002; OR: 2.03 [1.30-3.15]) y un mayor número de abandonos por conducción a otro centro o libertad (p<0,0001; OR 30.22 [4.07-224.29]), sin encontrarse diferencias significativas en los abandonos por reacciones adversas entre la pauta 9H y el conjunto de pautas cortas. ...(AU)

Objectives: The main aim of the study is to compare the acceptance, adherence, tolerance and safety of short course therapies in comparison to a standard 9 month treatment for latent tuberculosis infection (LTBI) in directly observed therapy (DOT) and contrast this with previous results from a standard therapy in patient self-administered treatment. Materials and methods: Retrospective longitudinal study carried out at a medium sized prison. Period of inclusion covers 10 years, from January 2000 to December 2009. The Centers for Disease Control and Prevention (CDC) inclusion and exclusion criteria were used, as well as the ones included in the Program for Tuberculosis Prevention and Control in the Prison Environment. 4 LTBI therapies according to the preference of the patient and possible interactions with other treatments were utilised. Therapy I consisted of isoniazid (H) in doses of 300 mg/day for 9 months (9H), therapy II with rifampicin for 2 months, twice a week, (2R2Z2) therapy III with rifampicin and isoniazid for 3 months (3RH) and therapy IV with rifampicin for four months (4R). Treatment was administered under strict DOT conditions by nursing staff. Results: 902 patients were included, of which 810 accepted the treatment (89.90%), distributed as follows: 400 in the 9H therapy, and 410 with short course therapies (316 in the 2R2Z2, 82 in the 3RH therapy and 12 in the 4R therapy). 92 patients (10.20%) did not accept LTBI therapy, 271 patients (67.75%) concluded the LTBI treatment with 9H, and 314 (76.60%) with short courses. 232 patients (73.42%) concluded the 2R2Z2, 85.40% with the 3RH 70 therapy and 12 (100%) with the 4R treatment. 129 patients (32.25%) did not complete the LTBI 9H therapy (63 due to voluntary withdrawal, 35 due to adverse reactions, 26 for release or transfer, 2 for unknown reasons, 1 due to tuberculosis in a HIV- patient and 1 due to suicide). 96 patients (23.41%) did not conclude the short course therapies (36 due to voluntary withdrawal, 54 due to adverse reactions, 1 due to release or transfer, 3 for unknown reasons, 1 due to a psychotic episode, and 1 due to hepatitis of unknown aetiology). Significant differences could be discerned in the LTBI therapy conclusion rates when comparing the standard 9H and short course therapies. A greater, statistically significant, probability is observed with the short course therapies: p: 0.006; Odds Ration: 1.56 (LC95%: 1.14-2.12). ...(AU)

Tabaquismo pasivo: importancia / Passive smoking: importance

RESUMEN. Objetivo. Se denomina tabaquismo pasivo al hecho involuntario de respirar aire contaminado por el humo de tabaco. A lo largo de los últimos años se ha ido acumulando evidencia científica acerca de las consecuencias sobre la salud de quienes se ven expuestos involuntariamente al humo ambiental del tabaco. Material y métodos. Se ha revisado la relación entre el tabaquismo pasivo y la morbimortalidad que se presenta en niños y adultos expuestos a este riesgo. Resultados. Actualmente se sabe que el tabaquismo pasivo es causa de morbilidad y de mortalidad prematura, tanto en niños como en adultos. En adultos la exposición al humo ambiental de tabaco aumenta el riesgo tanto de morbimortalidad coronaria, así como de padecer cáncer de pulmón. La exposición de niños al humo ambiental del tabaco es causa de muerte súbita del lactante, infecciones respiratorias agudas, y problemas del oído medio; así mismo, agrava el asma, ocasiona síntomas respiratorios y enlentece el desarrollo pulmonar. Conclusiones. No ha sido posible detectar la existencia de un umbral de exposición por debajo del cual no se aprecien riesgos para los fumadores pasivos. Los estudios muestran que la única manera real de proteger a la población de este riesgo es la restricción del consumo de tabaco en los espacios cerrados (AU)

Abstract. Objective. Involuntary exposure to environmental tobacco smoke (ETS), i.e., breathing other people’s smoke is called passive or secondhand smoking. Scientific evidence about the toxicity of ETS on the health of passive smokers is overwhelming. Material and methods. A bibliographic revision on the relationship between passive smoking and morbid- mortality in children and adults exposed was performed. Results. ETS exposure cause premature death and disease both in adults and in children who do not smoke. Adults exposed to ETS are at a higher risk of dying of coronary heart disease and lung cancer. In children, exposure to ETS increase the risk of sudden infant death syndrome (SIDS), acute respiratory infections, and middle ear problems; additionally, it aggravates asthma, causes respiratory symptoms and slows lung growth. Conclusions. The scientific evidence indicates that there is no risk-free level of exposure to ETS. It has not been possible to determine the presence of a threshold under which exposure to ETS does not cause any deleterious effect on passive smokers. Eliminating smoking in indoor spaces protects nonsmokers from exposure to ETS. In fact, it is the only way to fully protect them (AU)

Control del tabaquismo. Perspectivas futuras / Tobacco control policies. Future perspectives

Objetivo: Mostrar la importancia del control del tabaquismo para abordar lo que es un problema de salud pública. Discutir los posibles nuevos avances que se van a producir en este campo. Material y métodos: Se revisan las políticas de control del tabaquismo y las terapias en fase de experimentación. Resultados: Las políticas más eficaces para el control del tabaquismo son: el aumento del precio, la restricción de la promoción, la creación de lugares libres de humo de tabaco y el tratamiento de los fumadores. Entre los posibles avances terapéuticos se encuentran: combinaciones de fármacos ya existentes, nuevos antidepresivos y, quizá, el desarrollo de vacunas. Conclusiones: Llevadas a cabo, las políticas de control de tabaquismo reducen la prevalencia de consumo de la población. Habitualmente falta la decisión política de llevarlas a cabo. Es previsible que haya avances sustanciales en el tratamiento del tabaquismo en los próximos años (AU)

El tabaquismo como trastorno adictivo / Smoking as an addictive disorder

Objetivo: Determinar la importancia de considerar el tabaquismo como una conducta adictiva. Material y métodos: Se lleva a cabo una revisión del consumo de tabaco como una conducta adictiva. Resultados: Considerar el tabaquismo como un trastorno adictivo lleva a considerarlo como un trastorno crónico, en el que la recaída es parte del proceso, en el que deben tenerse en cuenta los estímulos asociados al consumo, qué aporta la conducta adictiva y qué recursos presenta el paciente para realizar el cambio conductual. Conclusiones: Para tratar eficazmente el tabaquismo, éste debe ser considerado un trastorno adictivo. Lo contrario disminuye notablemente las tasas de cesación del tabaquismo a medio-largo plazo. La eficacia de un tratamiento depende fundamentalmente de las herramientas psicológicas empleadas. (AU)

Regulation of mu-opioid receptors, G-protein-coupled receptor kinases and beta-arrestin 2 in the rat brain after chronic opioid receptor antagonism.

The aim of this study was to analyse the biochemical and behavioural consequences of chronic treatment with opioid receptor antagonists in rats. We have evaluated the respiratory depressant and antinociceptive effects of the mu-opioid agonist sufentanil, the density of brain mu-opioid receptors, and the expression of G-protein-coupled receptor kinases and beta-arrestin 2 in cerebral cortex and striatum, following sustained opioid receptor blockade. Our results demonstrate that 24 h after interruption of 7 days chronic infusion of naltrexone (120 microg/h), the respiratory depressant potency of the mu-opioid receptor agonist sufentanil was increased to a similar extent as the antinociceptive potency (about three-fold). This was accompanied by mu-opioid receptor up-regulation in several areas of the rat brain associated with opioid control of pain perception and breathing. Moreover, chronic treatment with either naltrexone (120 microg/h) or naloxone (120 microg/h) caused significant increases in the expression levels of G-protein-coupled receptor kinases types 2, 3, and 6, and of beta-arrestin 2 in brain cortex and striatum. Together our data suggest an increased constitutive receptor activity secondary to mu-opioid receptor up-regulation following chronic antagonist treatment.

Paradoxical effect of chronic fentanyl treatment on naltrexone-induced supersensitivity and upregulation.

The present study sought to evaluate the influence of chronic opioid antagonist treatment upon the discriminative stimulus and analgesic effects of the opioid receptor agonist fentanyl. Male Wistar rats were trained to discriminate fentanyl (0.04 mg/kg) from saline in a two-lever food reinforced paradigm. After acquisition of the discrimination, they were implanted with osmotic minipumps which delivered either naltrexone (0.07 mg/h) or distilled water, and the sensitivity of discrimination was assessed at various times after pump removal. The influence of chronic naltrexone treatment upon the antinociceptive effects of fentanyl was assessed in drug-naive (control) rats and in rats which had received fentanyl in the same dosage schedule as those in drug discrimination experiments. Chronic infusion of naltrexone for 7 days did not modify the dose-response curve for the fentanyl vs. saline discrimination. Algesiometric tests revealed a significant increase in the antinociceptive effect of fentanyl in control rats after naltrexone treatment. In contrast, such supersensitivity was not observed in rats which had previously received fentanyl injections. Autoradiographic data revealed a naltrexone-induced upregulation of mu opioid receptors in control animals. Paradoxically, this effect was significantly increased in fentanyl-pretreated rats. These data suggest that prior drug experience can affect the development of antagonist-induced supersensitivity to the behavioral actions of opioid agonists. Furthermore, it would appear that after chronic agonist treatment the phenomena of opioid receptor upregulation and functional supersensitivity are dissociated.

Tolerance to the respiratory actions of opiates: withdrawal tolerance and asymmetrical cross-tolerance.

Cross-tolerance to the respiratory depression induced by i.c.v. [D-Ala2,D-Leu5]enkephalin (DADLE) and by s.c., i.c.v. and i.v. morphine was studied in anesthetized rats that had been rendered tolerant to s.c. sufentanil (4 micrograms/h per 7 days). Tolerance induced by i.c.v. sufentanil was also compared during withdrawal and its absence. Tolerance was evaluated by estimation of the changes in both the maximum attained reduction of respiratory frequency (Emax) and the area under the time-course curve for the effects (AUC). In contrast to the failure to develop tolerance, as estimated with the Emax, after i.c.v. sufentanil in the absence of abstinence (tolerance index: 1.1), rats displayed significant degrees of cross-tolerance to i.c.v. morphine (3.6), i.c.v. DADLE (4.3) and s.c. morphine (6.6). No tolerance, however, was obtained to i.v. morphine. Tolerance to i.c.v. sufentanil in non-abstinent rats was not present when the Emax was considered but was when AUC was considered. During withdrawal animals showed tolerance as estimated with both the Emax and AUC. These results complement previous findings and show that the appearance of dissimilar degrees of cross-tolerance to different agonists depends not only on their intrinsic activities but also on their pharmacokinetic properties. These observations, along with the critical influence of withdrawal upon the manifestation of tolerance, support the need to distinguish between the development of the tolerance state and the degree of tolerance that can be expressed under specific conditions.

Peripheral but not intracerebroventricular corticotropin-releasing hormone (CRH) produces antinociception which is not opioid mediated.

Corticotropin-releasing hormone and endogenous opioid peptide systems are both activated during stress. An elevation of the pain threshold also occurs under conditions of stress. In the present study the effects of CRH antinociception were examined. Rats were treated with CRH either centrally (i.c.v.) or peripherally (intracardially; i.c.) and their tail-flick latencies were measured. Central application of CRH (0-30 micrograms) was without effect on the analgesic test, while after peripheral application (0-32 micrograms) CRH produced a dose-dependent increase in tail-flick latencies. In a subsequent experiment we examined the possible involvement of endogenous opioids in the peripheral CRH-induced antinociceptive effects. To this end, two approaches were used: animals were either acutely treated with the opioid antagonist naloxone (3 or 6 mg/kg), or they were rendered tolerant to morphine, and then tested with CRH. In both cases, CRH effects on the tail-flick latencies were not modified. Our findings suggest that: (a) CRH may modulate pain sensitivity during stress; (b) opioids do not mediate this effect; and (c) brain CRH receptors are probably not involved in these processes.

Tolerance to respiratory actions of sufentanil: functional tolerance and route-dependent differential tolerance.

The work was aimed at 1) characterizing the development of chronic tolerance to the respiratory effects of sufentanil in anesthetized and awake rats and 2) analyzing the influence that routes of administration of opiates can exert on tolerance development and expression. Tolerance was developed by infusing sufentanil s.c. with osmotic minipumps for 7 days; it was evaluated by injecting acute sufentanil while the minipumps were still maintained. When maximal depression attained was considered, dose-response curves were displaced to the right, the tolerance indexes being 7.3 and 2.6 in awake and anesthetized rats, respectively. No displacement was observed when acute sufentanil was injected i.c.v. and i.v., indicating lack of tolerance. However, several signs of tolerance were detected when the areas under the time-course curve of the effects were considered: faster and more complete recovery of the depression and flattening of the slope of the dose-area under the curve responses, even after i.c.v. and i.v. administration. The results indicate the need for distinguishing between development and expression of tolerance. Differential tolerance can be explained by considering tolerance expression as a deferred phenomenon. In addition, functional compensation stands as a factor of tolerance and as a mechanism responsible for dose-response curve flattening in tolerant subjects.

Tolerance and selective cross-tolerance to the motivational effects of opioids.

The issue of whether tolerance develops to the motivational effects of opioids was addressed by use of an unbiased place preference conditioning procedure. Administration of the mu-opioid agonists morphine or fentanyl produced dose-related preferences for the drug-associated place in control rats. In contrast, the kappa-opioid agonist, U-69593 produced conditioned place aversions. Non-contingent administration of morphine (5.0 mg/kg/12 h) for 4 days prior to conditioning resulted in tolerance to its reinforcing effects, and cross-tolerance to the effects of fentanyl. No cross-tolerance to the motivational effects of the psychostimulant d-amphetamine or the kappa-opioid agonist U-69593 was observed. Chronic administration of U-69593 prior to conditioning produced tolerance to its aversive effects. This treatment did not, however, modify the reinforcement produced by morphine. These data demonstrate that tolerance develops to both the reinforcing and aversive properties of opioids and suggest that differential cross-tolerance may provide a useful method for determining the pharmacological basis underlying drug-induced motivational effects.