Abstinencia a corto plazo y seguridad de citisina. Un estudio multicéntrico y observacional en España / [Short-term withdrawal and safety of cytisine. A multicenter and observational study in Spain]

Introducción y objetivos. Citisina es un fármaco empleado para la cesación tabáquica recientemente comercializado en nuestro país. El objetivo de este estudio es analizar la abstinencia a corto plazo y la seguridad en la práctica clínica diaria en población sana y con comorbilidades. Material y métodos . Estudio observacional, descriptivo y multicéntrico realizado en un centro de saludde Atención Primaria y dos Unidades de Tabaquismo de hospitales de tercer nivel. Se realiza una búsqueda en la base de datos de Tabaquismo para identificar pacientes fumadores tratados con citisina. Se analizan las características basales de los fumadores, la abstinencia mantenida al mes y a los 3 meses, así como el porcentaje de eventos adversos y el tipo de los mismos. Resultados. Un 81,5% de los pacientes se mantienen sin fumar durante el primer mes desde el inicio del tratamiento y un 61% a los 3 meses. En los pacientes con comorbilidades significativas, los porcentajes de abstinencia al mes y a los 3 meses son los siguientes: en EPOC 73% y 56,6% respectivamente, en enfermedad cardiovascular 63,5% y 42,1%, en enfermedad psiquiátrica 71% y 57,1%, y en neoplasias 66% y 55%. Solo un 7,7% presentaban efectos adversos al fármaco. Conclusiones. Citisina es una opción terapéutica efectiva a corto plazo y segura. (AU)

Introduction and objectives. Cytisine is a drug used for smoking cessation recently marketed in our country. The aim of this study is to analyze short-term abstinence and safety in daily clinical practice in healthy population and with comorbidities. Material and methods. Observational, descriptive and multicenter study carried out in a primary care health center and two smoking cessation units of third level hospitals. A search was performed in the Smoking database to identify smoking patients treated with cytisine. We analyzed the baseline characteristics of the smokers, the abstinence maintained at 1 and 3 months, as well as the percentage of adverse events and their type. Results. 81.5% of patients remained smoke-free during the first month after starting treatment and 61% at 3 months. In patients with significant comorbidities, the abstinence percentages at 1 month and 3 months were as follows: In COPD 73% and 56.6% respectively, in cardiovascular disease 63.5% and 42.1%, in psychiatric disease 71% and 57.1% and in neoplasms 66% and 55%. Only 7.7% presented adverse effects to the drug. Conclusions. Cytisine is an effective short-term and safe therapeutic option. (AU)

Evaluation of two commercial nucleic acid amplification kits for detecting Mycobacterium tuberculosis in saliva samples.

OBJECTIVE: The objective of this study was to evaluate the efficacy of two commercial nucleic acid amplification techniques to identify Mycobacterium tuberculosis in saliva. SUBJECTS AND METHODS: Fifty-two participants were recruited, 32 patients with a clinical and microbiological diagnosis of pulmonary tuberculosis and 20 healthy volunteers as controls. Three sputum samples were collected from each participant and were examined by direct bacilloscopy, cultured in liquid and solid media, and processed using the Mycobacterium tuberculosis direct (MTD) test for rRNA detection. One saliva sample was collected from each participant using conventional methods and was examined by direct bacilloscopy, cultured, and processed using the MTD test for rRNA detection and the FluoroType Mycobacterium tuberculosis assay for DNA detection. RESULTS: In saliva samples, the sensitivity, specificity, and positive and negative predictive values of the MTD test were 71.8%, 95%, 95.8%, and 67.8%, respectively. The values obtained with the FluoroType assay were 56.2%, 90%, 90%, and 56.2%, respectively. CONCLUSIONS: Our results indicate that when a sufficient volume of sputum cannot be obtained, saliva could be an alternative biological sample for the rapid diagnosis of pulmonary tuberculosis using commercial nucleic acid amplification techniques.

N-acetyltransferase 2 polymorphisms and risk of anti-tuberculosis drug-induced hepatotoxicity in Caucasians.

OBJECTIVE: To analyse slow-acetylation N-acetyltransferase 2 (NAT2) polymorphisms for their association with the risk of anti-tuberculosis drug-induced hepatotoxicity (ATDH). DESIGN: A case-control study including Caucasian patients with tuberculosis (TB) treated with isoniazid, rifampicin and pyrazinamide. NAT2 genotype results were compared between ATDH cases and controls and with a healthy Spanish control population of Caucasian origin. RESULTS: Fifty cases and 67 controls were included in the study. Slow, intermediate and rapid NAT2 genotypes were found in respectively 72%, 18% and 10% of cases compared with 65.7%, 25.4% and 9% of controls (P> 0.05). On comparing NAT2 genotypes among cases with those among healthy controls (n = 1312), we found more slow NAT2 genotypes and fewer intermediate genotypes among cases (respectively 72% and 18% in cases vs. 54.8% and 38.1% in controls; OR 2.07, 95%CI 1.12-2.79, P = 0.016 and OR 0.37, 95%CI 0.18-0.75, P = 0.003). CONCLUSIONS: We could not demonstrate an increased risk of ATDH related to the presence of slow NAT2 polymorphisms among this Caucasian TB cohort. However, we found a significantly greater frequency of slow and a significantly lower frequency of intermediate NAT2 genotypes among the ATDH cases compared with the healthy control population.

Multidrug-resistant tuberculosis in a low-incidence region shows a high rate of transmission.

OBJECTIVE: To describe the characteristics of patients with multidrug-resistant tuberculosis (MDR-TB), a descriptive prospective study was carried out applying a combination of exhaustive conventional epidemiology with molecular genotyping. SETTING: All patients diagnosed with MDR-TB in Galicia, Spain, between 1998 and 2004 were included in the study. DESIGN: Of 9895 diagnosed cases of TB, 58 were MDR-TB (0.59%). The site of disease was pulmonary in 56 cases and 46 were smear-positive. Only two cases were co-infected with the human immunodeficiency virus (HIV) and seven were immigrants. Twenty-five (43%) had received previous TB treatment. These cases presented more risk factors for treatment default and a lower frequency of contact with cases of MDR-TB. RESULTS: Genotyping analysis was performed in 57 patients, showing evidence of four clusters (30 patients, 52.6%), each with identical genetic patterns. The patients included in the clusters were younger, and most had primary forms or had had contact with another case of MDR-TB, especially in hospital. Neither the Beijing/W nor the B strain was identified. CONCLUSION: There is a low prevalence of MDR-TB in Galicia. Unlike previous studies, there was a high rate of transmissibility, including nosocomial transmission. Transmission is not associated with HIV or previously reported strains with a high capacity for transmission.

[The tuberculin skin test in a healthy child program: should we change our practice]. / La prueba de tuberculina en los controles del niño sano. 'debemos cambiar nuestra práctica?

BACKGROUND: The Healthy Child Program and the Preventive Activities and Health Promotion Program involve systematic tuberculin skin testing at distinct ages according to different programs, with variable evaluation of its effectiveness. OBJECTIVE: To evaluate the tuberculin skin test performed in healthy children within the ongoing basic health program in order to determine whether our activity is effective in detecting latent tuberculin infection. MATERIAL AND METHODS: A prospective observational study was performed. POPULATION: Mantoux test performed in children aged 15 months to 14 years during regular health examinations in 22 primary care pediatric clinics over a 12-month period in southern Pontevedra in Spain (catchment population 300,613 inhabitants according to the official census data in January 2003, with 472,444 health cards). Descriptive study and univariate analysis were carried out. RESULTS: We studied 2,530 children with a mean age of 51.25 months (95 % CI: 49.38-53.13). Eight positive Mantoux tests were registered (0.36 %). There were three positive results in children aged less than 3 years, two positive results in children aged between 4 and 9 years old (all were immigrants) and the remaining positive results were registered in children between 10 and 14 years of age. CONCLUSIONS: Given that the tuberculin skin test is a good screening test despite its limitations in the control of latent tuberculin infection in children, its indications should be adjusted to ever-changing epidemiological characteristics. According to the results obtained in this study and considering the prevalence of tuberculosis in our environment, we propose that the systematic application of the Mantoux test be discontinued except in children from countries with a high incidence of this disease or risk factors. However, we also recommend that systematic Mantoux testing in adolescence (12-14 years of age) be maintained, when vaccination and various medical examinations are carried out. Epidemiological studies in this age group should simultaneously be performed.

La prueba de tuberculina en los controles del niño sano. ¿Debemos cambiar nuestra práctica? / The tuberculin skin test in a healthy child program: should we change our practice?

Antecedentes El programa del niño sano y el PAPPS (Programa de Actividades Preventivas y Promoción de la Salud) incluyen la realización de pruebas de tuberculina sistemáticas a diferentes edades según los diferentes programas con una variable evaluación de su efectividad. Objetivo Nos planteamos la posibilidad de evaluar la prueba de la tuberculina que se realizaba en el niño sano sin ningún tipo de patología dentro del programa de salud para ver si nuestra actividad era eficaz para la detección de la infección tuberculosa. Material y métodos Estudio observacional prospectivo, descriptivo. Población. Prueba de tuberculina realizados en niños de 15 meses a 14 años en la consulta del niño sano en 22 consultas de pediatría de atención primaria de la zona sur de Pontevedra (población de referencia 300.613 habitantes según el padrón del 1-01-2003 con 472.444 TIS); durante un período de 12 meses. Análisis univariante. Resultados Se estudiaron 2.530 niños con edad media 51,25 meses (IC 95 %: 49,38-53,13). Se registraron 8 pruebas de tuberculina positivas (0,36 %). En los menores de 3 años, hubo dos resultados positivos; tres resultados positivos en los niños menores de 9 años, todos ellos inmigrantes; el resto se dieron en niños de 10 a 14 años. Conclusiones Considerando la prueba de tuberculina como una buena prueba de cribado, a pesar de sus limitaciones para el control de la infección tuberculosa en niños, su indicación, debe ajustarse a las características epidemiológicas siempre cambiantes. Basados en nuestros resultados y considerando la prevalencia de la tuberculosis en nuestro medio, proponemos dejar la prueba de tuberculina sistemática para niños que provengan de países de alta incidencia de tuberculosis o con factores de riesgo; manteniendo la realización sistemática de una prueba de tuberculina en una edad cercana a la adolescencia como pueden ser a los 12-14 años, edades en que se realiza una revisión vacunación incluida, momento idóneo para la realización de la prueba y de manera simultánea realizar estudios epidemiológicos a esa edad

Background The Healthy Child Program and the Preventive Activities and Health Promotion Program involve systematic tuberculin skin testing at distinct ages according to different programs, with variable evaluation of its effectiveness. Objective To evaluate the tuberculin skin test performed in healthy children within the ongoing basic health program in order to determine whether our activity is effective in detecting latent tuberculin infection. Material and methods A prospective observational study was performed. Population: Mantoux test performed in children aged 15 months to 14 years during regular health examinations in 22 primary care pediatric clinics over a 12-month period in southern Pontevedra in Spain (catchment population 300,613 inhabitants according to the official census data in January 2003, with 472,444 health cards). Descriptive study and univariate analysis were carried out. Results We studied 2,530 children with a mean age of 51.25 months (95 % CI: 49.38-53.13). Eight positive Mantoux tests were registered (0.36 %). There were three positive results in children aged less than 3 years, two positive results in children aged between 4 and 9 years old (all were immigrants) and the remaining positive results were registered in children between 10 and 14 years of age. Conclusions Given that the tuberculin skin test is a good screening test despite its limitations in the control of latent tuberculin infection in children, its indications should be adjusted to ever-changing epidemiological characteristics. According to the results obtained in this study and considering the prevalence of tuberculosis in our environment, we propose that the systematic application of the Mantoux test be discontinued except in children from countries with a high incidence of this disease or risk factors. However, we also recommend that systematic Mantoux testing in adolescence (12-14 years of age) be maintained, when vaccination and various medical examinations are carried out. Epidemiological studies in this age group should simultaneously be performed

Study of Mycobacterium tuberculosis drug resistance in the region of Galicia, Spain.

FRAMEWORK: Galicia, a region in north-east Spain with its own government and health system and a population of 2 695 880. OBJECTIVE: To study the epidemiology of resistant tuberculosis (TB). DESIGN: A prospective, descriptive, and observational study of all Mycobacterium tuberculosis isolates processed by each of the laboratories in Galicia that perform mycobacterial cultures. The study followed the methodology recommended by the World Health Organization and the International Union Against Tuberculosis and Lung Disease, and included isolates processed between 1 November 2001 and 1 June 2002. FINDINGS: Of 400 strains analysed, 360 corresponded to previously untreated cases and 40 to previously treated cases. Of the previously untreated cases, 88.3% contained strains susceptible to isoniazid, rifampicin, streptomycin and ethambutol, while 4.4% were resistant to isoniazid. The rate of susceptibility to the four drugs was 77.5% in the previously treated cases. Multidrug-resistant TB was detected in 1.4% of the previously untreated cases and in 7.5% of the previously treated cases. CONCLUSION: Although Galicia has a high incidence of TB (49.4 cases per 100 000 population in 2001), the resistance levels detected by the study do not currently pose a serious problem for the region.

The influence of risk factors on the severity of anti-tuberculosis drug-induced hepatotoxicity.

BACKGROUND: Hepatotoxicity is one of the most serious adverse effects of anti-tuberculosis drugs (ATD). Although many risk factors have been associated with ATD-induced hepatotoxicity, their influence on hepatitis severity has not been studied systematically. OBJECTIVES: To evaluate whether the presence of hepatotoxicity risk factors (advanced age, chronic liver disease, abuse of alcohol or other drugs or malnutrition) influences the severity of ATD-induced hepatotoxicity. DESIGN: A prospective cohort study of 471 active tuberculosis patients treated with isoniazid, rifampicin and pyrazinamide and followed in a tuberculosis clinic between January 1998 and July 2002. Incidence of hepatotoxicity and its severity according to the presence or absence of ATD-induced hepatitis risk factors was evaluated. RESULTS: The incidence of ATD-induced hepatotoxicity (serum transaminase > 3 x the upper limit of normal [ULN]) was 18.2% (42/231 patients) in the risk factor group and 5.8% (14/240 patients) in the non-risk factor group (OR 3.5; 95% CI 1.9-6.7; P < 0.001). Severe hepatotoxicity (transaminase > 10 x ULN) occurred in 6.9% (16/231) of the risk factor group and in 0.4% (1/240) (OR 17.7; 95% CI 2.3-135; P < 0.001) of the group without risk factors. CONCLUSIONS: ATD-induced hepatitis is significantly more frequent and more severe in patients with hepatotoxicity risk factors.

[Incidence of childhood tuberculosis in southern Pontevedra (Spain)]. / Incidencia de la enfermedad tuberculosa en el área sur de la provincia de Pontevedra.

Background Epidemiological pattern of tuberculosis in Galicia is closer to that in developing countries than to that in Europe.ObjectivesThe aim of the present study was to determine the incidence and development of childhood tuberculosis, to analyze its clinical presentation and to quantify accurate diagnoses of pulmonary tuberculosis.MethodsObservational descriptive retrospective study in children aged 0-14 years old admitted to the Tuberculosis Unit of Vigo from 1 January 1995 to 31 December 1999.ResultsA total of 146 patients were included; 144 initial cases (98.63 %), one relapse (0.68 %), one withdrawal/recovery (0.68 %) and none with chronic disease or treatment failure. The incidence rate of tuberculosis showed no significant variations, changing from 46.08 x 5 in 1995 to 24.81 x 5 in 1998. The incidence rate was higher in younger children and was 111.38 x 5 in 1995 in children aged 0-4 years old. There were 78 boys (54.42 %) and 68 girls (46.75 %). A total of 51.36 % of the patients were from urban areas and 48.68 % were from rural areas. The most common location was the lung, with 132 cases (83.54 %). The diagnosis of pulmonary tuberculosis was accurate in 59 % of the patients and this percentage rose to 90.3 % in the group of patients aged 0-2 years old.ConclusionsIncidence of childhood tuberculous disease is high, especially in children aged 0-4 years old. A high percentage of diagnoses of pulmonary tuberculosis were accurate.

[Epidemiology of tuberculosis in Galicia]. / Epidemiología de la tuberculosis en Galicia.

BACKGROUND: To know the real incidence of tuberculosis in Galicia and its epidemiological characteristics. METHODS: Study of data recorded in the "Galician Programme for Tuberculosis Control and Prevention", where an active epidemiological survey of every diagnosis of tuberculosis is carried out in every part of Galicia. RESULTS: 1995 cases were included in this study, with an incidence of 72.7/100,000 inhabitants. 58% of the cases were detected by the epidemiological survey. 92% of the cases were newly diagnosed cases, being the remain relapses. The highest incidence were localized in the areas of A Coruña and Vigo. The mean age was 40.5 years with 57% being between 15 and 44 years. Male incidence was 92.8/100,000 and female incidence was 54.0/100,000 (RR = 1.72; CI 95%: 1.57-1.88). 18.1% of the patients had at least one of the following risk factors associated: HIV infection (9.1%), alcoholism (8.4%) or injecting drug use (7.3%). Other risk factors for tuberculosis were very unusual. Pulmonary localization was the most frequent form with 1389 cases (incidence: 50.6/100,000). 742 patients were considered to be bacilliferous (incidence: 27/100,000). CONCLUSIONS: The incidence of tuberculosis in Galicia is high. Its epidemiological characteristics suggest a historical lack of measures of tuberculosis control.

Epidemiología de la tuberculosis en Galicia / Epidemiology of tuberculosis in Galicia

Objetivo: Conocer la incidencia real de la tuberculosis en Galicia y sus características epidemiológicas. Método: Estudio de los datos recogidos durante 1996 en el "Programa Gallego de Prevención y Control de la Tuberculosis" en el cual se realiza un sistema de vigilancia activa epidemiológica de los casos de tuberculosis diagnosticados en la totalidad de la comunidad autónoma de Galicia. Resultados: Se incluyeron en el estudio 1995 casos de tuberculosis que suponen una incidencia de 72,7 por cien mil habitantes. Un 58% de los casos fueron detectados mediante el sistema de vigilancia activa epidemiológica. El 92%de los casos fueron iniciales, siendo el resto recidivas. Las mayores tasas de incidencia se dieron en las áreas de influencia de A Coruña y de Vigo. La edad media fue de 40,5 años, con el 57% de los pacientes entre los 15 y 44 años. La incidencia específica en varones fue de 92,8 por cien mil y en mujeres de 54,0 por cien mil (RR=1,72; IC95%: 1,57-1,88). Un 18,1% de los pacientes presentaron al menos uno de los siguientes factores de riesgo: anticuerpos frente al virus de la inmunodeficiencia humana (9,1%), alcoholismo (8,4%) o adicción a drogas por vía parenteral (7,3%). La presencia de otros factores de riesgo fue muy escasa. La localización pulmonar fue la forma más frecuente con 1389 casos (incidencia: 50,6 por cien mil); con 742 pacientes bacilíferos (incidencia: 27,0 por cien mil). Conclusiones: Galicia presenta una elevada incidencia de tuberculosis con unas características epidemiológicas que sugieren un déficit histórico en las medidas de control de la enfermedad (AU)

[A retrospective study on tuberculin in children under 19]. / Estudio retrospectivo sobre la tuberculina en niños menores de 19 años.

The objective of this study was to describe the tuberculin test (TT) in children younger than 19 years of age, including the analysis of the utility of a negative TT and to verify the effect of age and BCG vaccination on the TT. To this end, we reviewed the results of the TTs performed during the last 9 years. We classified the TT according to age, BCG vaccination and the reason why the TT was performed. We made graphics of the TT results (GT) and extracted graphics of the TT in children infected with Mycobacterium tuberculosis (CTI) from the GT. We then calculated the probability of a child being infected and having a negative TT (BCG vaccinated: < 15 mm., non BCG vaccinated: < 5 mm). We compared the GT of children 1 year old and children 2 to 18 years of age. We also compared the GT of BCG vaccinated children with the GT of non-vaccinated children. Variance homogeneity tests were used to make comparisons. The results were the following: TT: 20,555. GT (1 year): The number of TT descends, while the induration size augments. GT (2 to 18 years) The number of TT descends while the induration size augments until reaching a size when the frequency of TT begins to increase again, with a maximum of 15 mm. The frequency then decreases again. CTI (2 to 18 years): mean: 15 mm with a standard deviation of +/- 4.8 mm for BCG vaccinated children and +/- 5.2 mm for non-vaccinated children. With these figures, we calculated that 50% of BCG vaccinated infected children and 3% of non-vaccinated infected children have a negative T test. The GT of children 1 year of age were different from the GT of children 2 to 18 years old (p < 0.001). The GT of non-vaccinated children younger than 14 years of age was different from the GT of non-vaccinated children (p < 0.001). we conclude that there is a difference between T tests in children 1 year of age in comparison to those between 2 and 18 years of age. In BCG vaccinated children, 2 to 18 years old, a negative T test did not identify 50% of infected children. BCG vaccination influences T tests in children younger than 14 years of age.