Teresa Rodrigo

Tuberculosis treatment adherence and fatality in Spain.

BackgroundThe adherence to long tuberculosis (TB) treatment is a key factor in TB control programs. Always some patients abandon the treatment or die. The objective of this study is to identify factors associated with defaulting from or dying during antituberculosis treatment.MethodsProspective study of a large cohort of TB cases diagnosed during 2006-2007 by 61 members of the Spanish Society of Pneumology and Thoracic Surgery (SEPAR). Predictive factors of completion outcome (cured plus completed treatment vs. defaulters plus lost to follow-up) and fatality (died vs. the rest of patients) were based on logistic regression, calculating odds ratios (OR) and 95% confidence intervals (CI).ResultsOf the 1490 patients included, 29.7% were foreign-born. The treatment outcomes were: cured 792 (53.2%), completed treatment 540 (36.2%), failure 2 (0.1%), transfer-out 33 (2.2%), default 27 (1.8%), death 27 (1.8%), lost to follow-up 65 (4.4%), other 4 (0.3%). Completion outcome reached 93.5% and poor adherence was associated with: being an immigrant (OR = 2.03; CI:1.06-3.88), living alone (OR = 2.35; CI:1.05-5.26), residents of confined institutions (OR = 4.79; CI:1.74-13.14), previous treatment (OR = 2.93; CI:1.44-5.98), being an injecting drug user (IDU) (OR = 9.51; CI:2.70-33.47) and treatment comprehension difficulties (OR = 2.93; CI:1.44-5.98). Case fatality was 1.8% and it was associated with the following variables: age 50 or over (OR = 10.88; CI:1.12-105.01), retired (OR = 12.26;CI:1.74-86.04), HIV-infected (OR = 9.93; CI:1.48-66.34), comprehension difficulties (OR = 4.07; CI:1.24-13.29), IDU (OR = 23.59; CI:2.46-225.99) and Directly Observed Therapy (DOT) (OR = 3.54; CI:1.07-11.77).ConclusionImmigrants, those living alone, residents of confined institutions, patients treated previously, those with treatment comprehension difficulties, and IDU patients have poor adherence and should be targeted for DOT. To reduce fatality rates, stricter monitoring is required for patients who are retired, HIV-infected, IDU, and those with treatment comprehension difficulties.

Memantine is a useful drug to prevent the spatial and non-spatial memory deficits induced by methamphetamine in rats

Methamphetamine (METH) is a street drug that is abused by young people. In previous studies, we demonstrated the effectiveness of alpha-7 nicotinic receptor antagonists in preventing the neurotoxicity induced by this amphetamine derivative. The present study seeks to determine whether pre-treatment with memantine (MEM) (an antagonist of both NMDA and alpha-7 nicotinic receptors) counteracts the memory impairment induced by METH administration in male Long Evans rats. Non-spatial memory was tested in the object recognition test and spatial learning memory was tested in the Morris water maze. In our experimental conditions, rats that received the MEM (5 mg/kg, intraperitoneally) pre-treatment recovered the ability to discriminate between a familiar and a novel object. This ability had been abolished by METH (10 mg/kg, subcutaneously) at 72 h and 1 week after treatment. Moreover, MEM pre-treatment also inhibited the thigmotaxis behaviour induced by METH. Rats treated with METH showed impaired learning in the Morris water maze. The results of the probe trial demonstrated that METH-treated rats did not remember the location of the platform, but this memory impairment was also prevented by MEM pre-treatment. Moreover, MEM by itself improved the learning of the task. Finally, MEM significantly improved the learning and memory impairment induced by METH. Therefore, MEM constitutes the first successful approach to prevent the cognitive deficits induced by amphetamine derivatives which are frequently abused in western countries.

Memantine prevents the cognitive impairment induced by 3,4-methylenedioxymethamphetamine in rats

Amphetamine abuse is an important risk factor for the development of cognitive impairment involving learning and memory. Since in previous studies we have demonstrated the effectiveness of alpha-7 nicotinic receptor antagonists in preventing the neurotoxicity induced by amphetamine derivatives, the present paper seeks to determine whether pre-treatment with memantine (MEM) (an antagonist of both nicotinic and NMDA receptors) counteracts the memory impairment induced by 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) administration in male Long Evans rats. In mice, MDMA and MEM induced a locomotor stimulant response but with a different profile. Moreover, MEM inhibited the rearing and thygmotaxis behaviour induced by MDMA. Non-spatial memory was tested in the object recognition test and the spatial learning and memory was tested in the Morris water maze. In our experimental conditions, rats receiving MEM pre-treatment recovered the ability to discriminate between the familiar and the novel object that had been abolished by MDMA treatment. Animals treated with MDMA showed impaired learning in the Morris water maze. Results of the probe trial demonstrated that MDMA-treated rats did not remember the location of the platform, but this memory impairment was also prevented by the MEM pre-treatment. Moreover, MEM alone improved the learning task. No differences were observed between the different groups as regards swim speed. In conclusion, MEM significantly improved the learning and memory impairment induced by MDMA and constitutes the first approach to the treatment of the long-term cognitive deficits found in ecstasy users.

Social, Clinical and Microbiological Differential Characteristics of Tuberculosis among Immigrants in Spain

Background To identify the differential tuberculosis (TB) characteristics within the immigrant population with respect to natives in Spain. Methodology/Principal Findings A prospective cohort study design was implemented to examine the TB cases diagnosed and starting standard antituberculous treatment in Spain, between January 1st 2006 and March 31st 2007. A logistic regression analysis was performed to determine differential characteristics. 1,490 patients were included in the study population, 1,048 natives and 442 (29.7%) immigrants. According to the multivariate analysis, the following variables were significantly associated with immigrant TB cases: younger age (OR = 3.79; CI:2.16–6.62), living in group situation (OR = 7.61; CI:3.38–12.12), lower frequency of disabled (OR:0.08; CI:0.02–0.26) and retired (OR:0.21; CI:0.09–0.48) employment status, lower frequency of pulmonary disease presentation (OR = 0.47; CI:0.24–0.92), primary or emergency care admission (OR = 1.80; CI:1.05–3.06 and OR = 2.16; CI:1.36–3.45), drug resistance (OR = 1.86; CI:1.01–3.46), treatment default (OR:2.12; CI:1.18–3.81), lower frequency of alcohol and cigarette consumption (OR = 2.10; CI:1.42–3.11 and OR = 2.85; CI:2.10–3.87 respectively), more directly observed treatment (OR = 1.68; CI:1.04–2.69), and poor understanding of TB disease and its treatment (OR = 3.11; CI:1.86–5.20). The low percentage of primary MDR-TB in the native population (0.1% vs. 2.2% of immigrants) should be noted. Conclusions/Significance The differences show the need to introduce specific strategies in the management of TB within the immigrant population, including the improvement of social and work conditions.

Neuronal changes and oxidative stress in adolescent rats after repeated exposure to mephedrone

Mephedrone is a new designer drug of abuse. We have investigated the neurochemical/enzymatic changes after mephedrone administration to adolescent rats (3×25 mg/kg, s.c. in a day, with a 2 h interval between doses, for two days) at high ambient temperature (26±2 °C), a schedule that intends to model human recreational abuse. In addition, we have studied the effect of mephedrone in spatial learning and memory. The drug caused a transient decrease in weight gain. After the first dose, animals showed hypothermia but, after the subsequent doses, temperature raised over the values of saline-treated group. We observed the development of tolerance to these thermoregulatory effects of mephedrone. Mephedrone induced a reduction of the densities of dopamine (30% in the frontal cortex) and serotonin (40% in the frontal cortex and the hippocampus and 48% in the striatum) transporters without microgliosis. These deficits were also accompanied by a parallel decrease in the expression of tyrosine hydroxylase and tryptophan hydroxylase 2. These changes matched with a down-regulation of D2 dopamine receptors in the striatum. Mephedrone also induced an oxidative stress evidenced by an increase of lipid peroxidation in the frontal cortex, and accompanied by a rise in glutathione peroxidase levels in all studied brain areas. Drug-treated animals displayed an impairment of the reference memory in the Morris water maze one week beyond the cessation of drug exposure, while the spatial learning process seems to be preserved. These findings raise concerns about the neuronal long-term effects of mephedrone.

Registros de enfermedades respiratorias en España:: fundamentos y organización

This present paper describes the general characteristics, objectives and organizational aspects of the respiratory disease registries in Spain with the aim to report their activities and increase their diffusion. The document compiles information on the following registries: the Spanish Registry of Patients with Alpha-1 Antitrypsin Deficiency, Spanish Registry of Bronchiectasis, International Registry of Thromboembolic Disease, Spanish Registry of Occupational Diseases, Spanish Registry of Pulmonary Artery Hypertension, Registry of Pleural Mesothelioma, Spanish Registry of Tuberculosis and Spanish Multi-center Study of Neuroendocrine Pulmonary Tumors. Our paper provides information on each of the registries cited. Each registry has compiled specific clinical information providing data in real situations, and completes the results obtained from clinical assays. Said information has been published both in national as well as international publications and has lead to the creation of various guidelines. Therefore, the activities of the professionals involved in the registries have spread the knowledge about the diseases studied, promoting the exchange of information among workgroups.

Resistencia a fármacos antituberculosos de primera línea en España durante 2010-2011. Estudio RETUBES

INTRODUCTION The magnitude of current resistance to antituberculosis drugs in Spain is unknown. The objective of this study is to describe resistance to first-line antituberculosis drugs and determine the associated factors. METHODS Prospective multicenter study of adult tuberculosis patients with positive Mycobacterium tuberculosis culture and antibiogram including first-line drugs in 32 hospitals and one out-patient center of the Spanish Health System between 2010 and 2011. RESULTS A total of 519 patients, 342 Spanish nationals and 177 (34.1%) foreigners were studied. Drug resistance was found in 48 (9.2%), of which 35 (6.7%) were isoniazid-resistant. There were 10 (1.9%) multiresistant cases and no strain was extremely resistant. Initial isoniazid resistance was detected in 28 of the 487 (5.7%) antituberulosis-naïve patients, most of whom were foreigners (P<.01). Acquired resistance was seen in 7 (22.6%) previously treated cases. Multiresistance was initial in 6 cases (1.2%) and acquired in another 4 (12.9%). Factors associated with initial isoniazid resistance were immigrant status and group cohabitation OR=2.3; 95%CI: .98-5.67 and OR=2.2; 95%CI: 1.05-7.07 respectively). The factor associated with acquired resistance to isoniazid was age below 50 years (P=.03). CONCLUSIONS The rate of initial isoniazid resistance is greater than estimated, probably due to the increase in immigration during recent years, suggesting that systematic national monitoring is required. Immigrants and those who cohabit in groups have a higher risk of isoniazid resistance.

A predictive scoring instrument for tuberculosis lost to follow-up outcome

BackgroundAdherence to tuberculosis (TB) treatment is troublesome, due to long therapy duration, quick therapeutic response which allows the patient to disregard about the rest of their treatment and the lack of motivation on behalf of the patient for improved. The objective of this study was to develop and validate a scoring system to predict the probability of lost to follow-up outcome in TB patients as a way to identify patients suitable for directly observed treatments (DOT) and other interventions to improve adherence.MethodsTwo prospective cohorts, were used to develop and validate a logistic regression model. A scoring system was constructed, based on the coefficients of factors associated with a lost to follow-up outcome. The probability of lost to follow-up outcome associated with each score was calculated. Predictions in both cohorts were tested using receiver operating characteristic curves (ROC).ResultsThe best model to predict lost to follow-up outcome included the following characteristics: immigration (1 point value), living alone (1 point) or in an institution (2 points), previous anti-TB treatment (2 points), poor patient understanding (2 points), intravenous drugs use (IDU) (4 points) or unknown IDU status (1 point). Scores of 0, 1, 2, 3, 4 and 5 points were associated with a lost to follow-up probability of 2,2% 5,4% 9,9%, 16,4%, 15%, and 28%, respectively. The ROC curve for the validation group demonstrated a good fit (AUC: 0,67 [95% CI; 0,65-0,70]).ConclusionThis model has a good capacity to predict a lost to follow-up outcome. Its use could help TB Programs to determine which patients are good candidates for DOT and other strategies to improve TB treatment adherence.

Memory impairment induced by amphetamine derivatives in laboratory animals and in humans: a review.

Abstract The 20th century brought with it the so-called club drugs (the most notorious being amphetamine derivatives), which are used by young adults at all-night dance parties. Methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) are synthetic drugs with stimulant and psychoactive properties that belong to the amphetamine family. Here, we have reviewed the literature about the cognitive impairment induced by these two amphetamine derivatives and the preclinical and clinical outcomes. Although there is controversial evidence about the effect of methamphetamine and MDMA on learning and memory in laboratory animals, results from published papers demonstrate that amphetamines cause long-term impairment of cognitive functions. A large number of pharmacological receptors have been studied and screened as targets of amphetamine-induced cognitive dysfunction, and extensive research efforts have been invested to provide evidence about the molecular mechanisms behind these cognitive deficits. In humans, there is a considerable body of evidence indicating that methamphetamine and MDMA seriously disrupt memory and learning processes. Although an association between the impairments of memory performance and a history of recreational amphetamine ingestion has also been corroborated, a number of methodological difficulties continue to hamper research in this field, the most important being the concomitant use of other illicit drugs.

Tuberculosis costs in Spain and related factors

Objective: To analyse direct and indirect costs of tuberculosis (TB) diagnosis and treatment and factors associated with those costs. Methods: All TB patients diagnosed and registered in a database at national level within the Integrated Research Project on Tuberculosis of the Spanish Society of Pneumology and Thoracic Surgery between September 2014 and September 2015 were included. We calculated direct costs (hospital stays, visits, diagnostic tests, treatment), and the resulting indirect costs of absenteeism and lost of productivity, contact tracing and rehabilitation measures. All costs were compared according to the following variables: age, gender, immigration, microbiological results, treatment, directed observed therapy (DOT), place where the process started (inpatient or outpatient) and days of absenteeism. For the statistical analysis, chi square test and logistic regression analysis were used. Results: 319 patients were included with a mean age of 56.72 ± 20.79 years. The average cost per patient was 10.262,62 ± 14,961,66 €., and increased significantly in the presence of hospital admission, thoracic CT, pleural biopsy, drug treatment extended over nine months, DOT and absenteeism. In multivariate analysis hospitalization: OR= 9,68 (CI 2,9-47,2) p Conclusion: Tuberculosis carries significant health spending, and it would be advisable to prevent the disease and to reduce hospitalizations trying to reduce costs. Supported by Grant SEPAR 136/2013.