Persistence in the Methadone Maintenance Program and Its Relationship with the Medication Regimen Complexity Index in Opioid-Dependent Patients.

It has been shown that the Medication Regimen Complexity Index (MRCI) is a useful and reliable tool for calculating the complexity of the pharmacotherapeutic regimen (CPR). Furthermore, a high MRCI is associated with lower adherence. However, the MRCI of opioid-dependent patients (ODP) has not been studied. The aim of this study is to calculate the Methadone Maintenance Program (MMP) persistence and the MRCI score in a ODP cohort. Second, to analyze its relationship and association with other variables. To accomplish this research, an observational study including adults with a confirmed diagnosis of opiate-dependency according to the DSM-5 in a MMP center was carried out. To define MMP-persistence, a group was created by the researchers who defined five weighted items according to their agreed importance. Our first contribution was to create a new definition of MMP-persistence. This study also identified age, comorbidities, and received methadone maintenance doses as successful predictors for MMP-persistence. We have also shown that the MRCI does not seem to be a useful tool to determine MMP-persistence, probably because there are multiple factors that influence it in addition to the CPR. It is necessary to continue searching for more precise selection and stratification tools for ODP to improve their persistence.

Physicochemical and Microbiological Stability of Two Oral Solutions of Methadone Hydrochloride 10 mg/mL.

In this article, we studied physicochemical and microbiological stability and determined the beyond-use date of two oral solutions of methadone in three storage conditions. For this, two oral solutions of methadone (10 mg/mL) were prepared, with and without parabens, as preservatives. They were packed in amber glass vials kept unopened until the day of the test, and in a multi-dose umber glass bottle opened daily. They were stored at 5 ± 3 °C, 25 ± 2 °C and 40 ± 2 °C. pH, clarity, and organoleptic characteristics were obtained. A stability-indicating high-performance liquid chromatography method was used to determine methadone. Microbiological quality was studied and antimicrobial effectiveness testing was also determined following European Pharmacopoeia guidelines. Samples were analyzed at days 0, 7, 14, 21, 28, 42, 56, 70, and 91 in triplicate. After 91 days of storage, pH remained stable at about 6.5-7 in the two solutions, ensuring no risk of methadone precipitation. The organoleptic characteristics remained stable (colorless, odorless, and bitter taste). The absence of particles was confirmed. No differences were found with the use of preservatives. Methadone concentration remained within 95-105% in all samples. No microbial growth was observed. Hence, the two oral methadone solutions were physically and microbiologically stable at 5 ± 3 °C, 25 ± 2 °C, and 40 ± 2 °C for 91 days in closed and opened amber glass bottles.

Development and validation of a HPLC-UV method for methadone hydrochloride quantification in a new oral solution with preservatives to be implemented in physicochemical stability studies.

PURPOSE: The Pharmacy Service of the Infanta Leonor University Hospital acquires, compounds, distributes and dispenses more than 3000 L of methadone oral solution to Drug Addiction Patients Centers per year. Our purpose is to develop and validate an improved high performance liquid chromatography (HPLC) method to quantify methadone hydrochloride in a new oral solution with methylhydroxybenzoate (methylparaben) and propylhydroxybenzoate (propylparaben) to be implemented in physicochemical stability studies that allow to provide more information and even to increase the beyond-use date. METHODS: A HPLC-Agilent® 1100 equipment, comprising a quaternary pump and an ultraviolet diode-array-detector (DAD) was used. An analytical method development and validation was completed. The curve was constructed from methadone working concentrations of 75-125% (7.5, 9.0, 10.0, 11.0 and 12.5 mg/mL) to assess the linear relationship between the concentration of the analyte and the obtained areas. Precision and accuracy were calculated. Detection and quantification limit (LD, LQ) were estimated using the EURACHEM method. Forced-degradation studies were also performed. RESULTS: Chromatographic conditions were: flow rate 1.6 mL/min; mobile phase 55% acetonitrile and 45% sodium phosphate 25 mM (pH = 10); injection volume was 5 µL. The column was a Waters-XTerra™ RP18, maintained at 40 °C. DAD was λ = 254 nm. Retention times for methadone, methylparaben and propylparaben were 4.34, 0.70 and 0.88 min respectively. The method was linear (y = 284.3x - 97.8, r = 0.996). Instrumental precision was 0.33% for standards (n = 10); intra-assay precision 0.53% (n = 6) and inter-assay precision 1.95% (n = 12). The relative standard deviation percentage for accuracy was 1.28%. The recovery percentage was 101.5 ± 1.5%. LQ and LD were 2.18 µg/mL and 2.0 µg/mL respectively. The most destabilizing conditions were oxidizing and alkaline. The chromatograms confirmed no interference with the methadone signal. CONCLUSIONS: The HPLC method has proved to be valid and reproducible for methadone quantification in a new oral solution with methylparaben and propylparaben. This assay is a rapid, simple and reliable technique that can be used in daily analysis and physicochemical stability studies.

Centralización del plan de mantenimiento con metadona en un servicio de farmacia hospitalaria en la Comunidad de Madrid / Centralization of the methadone maintenance plan in a hospital pharmacy department in the Community of Madrid

En febrero de 2018 se publicó en la Comunidad de Madrid la Resolución 189/2018 con el objetivo de centralizar el procedimiento de adquisición, elaboración, distribución y dispensación de metadona a los Centros de Atención Integral a Drogodependientes del Servicio Madrileño de Salud bajo la responsabilidad de un servicio de farmacia hospitalaria. El servicio de farmacia hospitalaria inició esta actividad en marzo de 2018, siendo la primera vez que se centraliza en un servicio de farmacia hospitalaria la gestión integral del plan de mantenimiento con metadona para la atención de pacientes drogodependientes en la Comunidad de Madrid. Al inicio del proyecto se analizó el circuito anterior, se adaptó el laboratorio de farmacotecnia y se diseñó el procedimiento de adquisición de metadona. Se implementó una vía de comunicación con los Centros de Atención Integral a Drogodependientes, diseñándose formularios de so-licitud y se establecieron los correspondientes procedimientos de control derivados de su naturaleza estupefaciente. Se han diseñado y adjudicado, cumpliendo la Ley de Contratos de la Administración Pública, procedimientos normalizados para la adquisición de metadona, envases para la dosificación personalizada en los Centros de Atención Integral a Drogodependientes y rutas de transporte. Asimismo, se ha adjudicado un concurso para la implementación de un sistema informático de gestión y sistemas automatizados de dispensación, actualmente en vías de instalación. También se está actualizando el protocolo farmacoterapéutico del Plan de mantenimiento con metadona de la Comunidad de Madrid. En año y medio se han elaborado 5.300 litros de metadona solución y se han dispensado 2.844 prescripciones individualizadas. Disponemos de resultados de calidad percibida por los profesionales de los Centros de Atención Integral a Drogodependientes mediante una encuesta de satisfacción. La tasa de respuesta fue del 92%. El grado de satisfacción global fue: 91% muy satisfecho/bastante satisfecho y 9% satisfecho. Destaca el alto grado de satisfacción (bastante o muy satisfecho) del 81,8% con la eficacia y rapidez de la resolución de incidencias por parte de los profesionales del servicio de farmacia. Este proceso permite incorporar el conocimiento y experiencia de los farmacéuticos especialistas a este ámbito asistencial, así como aprovechar recursos, instalaciones y procedimientos ya existentes. Todo ello redunda en un abordaje eficiente, eficaz y seguro de esta actividad clínico-asistencial y posibilitar un cambio de modelo de asistencia farmacoterapéutica de los pacientes dependientes de opiáceos

In February 2018, Resolution 189/2018 was published in the Autonomous Community of Madrid with the objective of centralizing the procedure for the acquisition, preparation, distribution, and dispensing of methadone to Centres for the Comprehensive Care of Drug Addiction Patients within the Madrid Health Service under the responsibility of a Hospital Pharmacy Service. The Hospital Pharmacy Service began this activity in March 2018. This is the first time that the comprehensive management of a methadone maintenance plan has been centralized in an Hospital Pharmacy Service for the care of drug-dependent patients in the Autonomous Community of Madrid. At the beginning of the Project, the previous workflow was analysed, the pharmaceutical laboratory was adapted, and the methadone acquisition procedure was designed. A communication channel with the Centres for the Comprehensive Care of Drug Addiction Patients was implemented and application forms were designed. Corresponding control procedures were established given that the medication under consideration was a narcotic. Standard procedures for the acquisition of methadone, of containers for personalized dosing in Centres for the Comprehensive Care of Drug Addiction Patients, and transport routes were designed and contracted out through public tender in compliance with the Public Administration Contract Law. A tender has also been awarded for the implementation of a computerized management system and automated dispensing systems, which are currently undergoing installation. The pharmacotherapeutic protocol of the Methadone Maintenance Plan of the Autonomous Community of Madrid is also being updated. Over 18 months, 5,300 L of methadone solution have been prepared and 2,844 individual prescriptions have been dispensed. High levels of perceived satisfaction were reported via a questionnaire administered to the Centre for the Comprehensive Care of Drug Addiction Patients staff. The response rate was 92%. Overall satisfaction was very satisfied/quite satisfied (91%) and satisfied (9%). These results highlight the high level of satisfaction (quite satisfied or very satisfied: 81.8%) with the effectiveness and speed of resolution of incidents by the Hospital Pharma-cy Service staff. This process incorporates the knowledge and experience of hospital pharmacists into this healthcare field, as well as taking advantage of existing resources, facilities, and procedures. All these aspects lead to an efficient, effective, and safe approach to this clinical-care activity and enable a change in the pharmacotherapeutic health care model for opioid-dependent patients

Centralization of the methadone maintenance plan in a hospital pharmacy department in the Community of Madrid.

In February 2018, Resolution 189/2018 was published in the Autonomous Community of Madrid with the objective of centralizing the  procedure for the acquisition, preparation, distribution, and dispensing of methadone to Centres for the Comprehensive Care of Drug Addiction Patients  within the Madrid Health Service under the responsibility of a Hospital Pharmacy  Service. The Hospital Pharmacy Service began this activity in March 2018. This is the first time that the comprehensive management of a methadone  maintenance plan has been centralized in an Hospital Pharmacy Service for the care of drug-dependent patients in the Autonomous Community of Madrid. At the beginning of the Project, the previous workflow was analysed, the pharmaceutical laboratory was adapted, and the methadone acquisition procedure was designed. A communication channel with the Centres  for the Comprehensive Care of Drug Addiction Patients was implemented and application forms were designed. Corresponding control procedures were established given that the medication under consideration was a narcotic. Standard procedures for the acquisition of methadone, of containers for personalized dosing in Centres for the Comprehensive Care of Drug Addiction  Patients, and transport routes were designed and contracted out through public  tender in compliance with the Public Administration Contract Law. A tender has  also been awarded for the implementation of a computerized management  system and automated dispensing systems, which are currently undergoing  installation. The pharmacotherapeutic protocol of the Methadone Maintenance Plan of the Autonomous Community of Madrid is also being updated. Over 18  months, 5,300 L of methadone solution have been prepared and 2,844 individual prescriptions have been dispensed. High levels of perceived satisfaction were  reported via a questionnaire administered to the Centre for the Comprehensive  Care of Drug Addiction Patients staff. The response rate was 92%. Overall  satisfaction was very satisfied/quite satisfied (91%) and satisfied (9%). These  results highlight the high level of satisfaction (quite satisfied or very satisfied:  81.8%) with the effectiveness and speed of resolution of incidents by the  Hospital Pharmacy Service staff. This process incorporates the knowledge and  experience of hospital pharmacists into this healthcare field, as well as taking  advantage of existing resources, facilities, and procedures. All these aspects lead to an efficient, effective, and safe approach to this clinical-care activity and  enable a change in the pharmacotherapeutic health care model for opioid- dependent patients.

En febrero de 2018 se publicó en la Comunidad de Madrid la Resolución 189/2018 con el objetivo de centralizar el procedimiento de  adquisición, elaboración, distribución y dispensación de metadona a los Centros de Atención Integral a Drogodependientes del Servicio Madrileño de Salud bajo la responsabilidad de un servicio de farmacia hospitalaria. El  servicio de farmacia hospitalaria inició esta actividad en marzo de 2018, siendo  la primera vez que se centraliza en un servicio de farmacia hospitalaria la  gestión integral del plan de mantenimiento con metadona para la atención de  pacientes drogodependientes en la Comunidad de Madrid. Al inicio del proyecto  se analizó el circuito anterior, se adaptó el laboratorio de farmacotecnia y se  diseñó el procedimiento de adquisición de metadona. Se implementó una vía de  comunicación con los Centros de Atención Integral a Drogodependientes,  diseñándose formularios de solicitud y se establecieron los correspondientes  procedimientos de control derivados de su naturaleza estupefaciente. Se han  diseñado y adjudicado, cumpliendo la Ley de Contratos de la Administración  Pública, procedimientos normalizados para la adquisición de metadona, envases  para la dosificación personalizada en los Centros de Atención Integral a  Drogodependientes y rutas de transporte. Asimismo, se ha adjudicado un  concurso para la implementación de un sistema informático de gestión y  sistemas automatizados de dispensación, actualmente en vías de instalación. También se está actualizando el protocolo farmacoterapéutico del Plan de  mantenimiento con metadona de la Comunidad de Madrid. En año y medio se  han elaborado 5.300 litros de metadona solución y se han dispensado 2.844  prescripciones individualizadas. Disponemos de resultados de calidad percibida  por los profesionales de los Centros de Atención Integral a Drogodependientes  mediante una encuesta de satisfacción. La tasa de respuesta fue del 92%. El  grado de satisfacción global fue: 91% muy satisfecho/bastante satisfecho y 9%  satisfecho. Destaca el alto grado de satisfacción (bastante o muy satisfecho) del  81,8% con la eficacia y rapidez de la resolución de incidencias por parte de los  profesionales del servicio de farmacia. Este proceso permite incorporar el  conocimiento y experiencia de los farmacéuticos especialistas a este ámbito  asistencial, así como aprovechar recursos, instalaciones y procedimientos ya  existentes. Todo ello redunda en un abordaje eficiente, eficaz y seguro de esta  actividad clínico-asistencial y posibilitar un cambio de modelo de asistencia  farmacoterapéutica de los pacientes dependientes de opiáceos.

Transferability of PCR-based diagnostic protocols: An international collaborative case study assessing protocols targeting the quarantine pine pathogen Fusarium circinatum.

Fusarium circinatum is a harmful pathogenic fungus mostly attacking Pinus species and also Pseudotsuga menziesii, causing cankers in trees of all ages, damping-off in seedlings, and mortality in cuttings and mother plants for clonal production. This fungus is listed as a quarantine pest in several parts of the world and the trade of potentially contaminated pine material such as cuttings, seedlings or seeds is restricted in order to prevent its spread to disease-free areas. Inspection of plant material often relies on DNA testing and several conventional or real-time PCR based tests targeting F. circinatum are available in the literature. In this work, an international collaborative study joined 23 partners to assess the transferability and the performance of nine molecular protocols, using a wide panel of DNA from 71 representative strains of F. circinatum and related Fusarium species. Diagnostic sensitivity, specificity and accuracy of the nine protocols all reached values >80%, and the diagnostic specificity was the only parameter differing significantly between protocols. The rates of false positives and of false negatives were computed and only the false positive rates differed significantly, ranging from 3.0% to 17.3%. The difference between protocols for some of the performance values were mainly due to cross-reactions with DNA from non-target species, which were either not tested or documented in the original articles. Considering that participating laboratories were free to use their own reagents and equipment, this study demonstrated that the diagnostic protocols for F. circinatum were not easily transferable to end-users. More generally, our results suggest that the use of protocols using conventional or real-time PCR outside their initial development and validation conditions should require careful characterization of the performance data prior to use under modified conditions (i.e. reagents and equipment). Suggestions to improve the transfer are proposed.

Muscular contraction frequency does not affect plasma homocysteine concentration in response to energy expenditure- and intensity-matched acute exercise in sedentary males.

Acute exercise seems to increase total plasma homocysteine (tHcy); since this variable associated with cardiovascular risk, it is important to understand the determinants of its response to all types of exercise. The aim of this study was to examine the impact of cycling at 2 different rates of muscle contraction on the complete tHcy kinetics. Eight young sedentary males were required to complete 2 isocaloric (400 kcal) acute exercise trials at 50% peak oxygen uptake on separate occasions at 50 or 80 rpm. Blood samples were drawn at different points before (4 h before exercise and immediately before exercise), during (10, 20, 30, 45, and 60 min during exercise), and after exercise (immediately and 19 h after exercise). Dietary and lifestyle factors were controlled during the research. Maximum tHcy occurred during exercise for both conditions (50 rpm: 11.4 ± 2.7 µmol·L-1; 80 rpm: 10.8 ± 3.2 µmol·L-1). From this point onwards tHcy declined until the cessation of exercise and continued descending below pre-exercise values at 19 h postexercise (p < 0.05). No hyperhomocysteinemia were observed at any sampling point in both trials. In conclusion, the different muscular contraction frequency during exercise has no impact on tHcy during an acute bout of exercise in sedentary individuals, when at least 400 kcal are spent during exercise and the nutritional status for folate, B12, and B6 is adequate. This information is relevant to further inform healthy exercise prescription, not only in terms of duration and intensity of exercise, but also taking into account frequency of contraction.

Exploring drug solubility in fasted human intestinal fluid aspirates: Impact of inter-individual variability, sampling site and dilution.

One of the main factors defining intestinal drug absorption is the solubility of the compound in the gastrointestinal environment. This study reports the solubility of a series of 27 commonly used acidic, neutral and basic drugs in human intestinal fluid samples collected from the duodenum or jejunum of healthy volunteers under fasted state conditions. The interindividual variability as well as the impact of factors such as pH, sampling site and bile salts on the solubility in human intestinal fluids was investigated. The solubility measurements were evaluated using a statistical experimental design. Variability in solubility across volunteers and sampling sites was highly compound-specific and appeared to be substantial for weak acids and bases and for lipophilic drugs. Both pH of the samples and the abundance of amphiphilic components were responsible for the variability observed in the solubility values obtained. The results confirm strong interindividual differences in intraluminal solubility, especially for compounds with high lipophilicity and/or compounds with a pKa value within the physiological pH range. It is important to recognize this variability in intestinal drug solubility as it may considerably influence the therapeutic outcome among patients.

Estudio de 5 compuestos orgánicos volátiles en aire exhalado en la enfermedad pulmonar obstructiva crónica / Study of 5 Volatile Organic Compounds in Exhaled Breath in Chronic Obstructive Pulmonary Disease

Introducción: Un factor de riesgo importante para el desarrollo de la enfermedad pulmonar obstructiva crónica (EPOC) es el humo del tabaco, que genera estrés oxidativo en las vías respiratorias, dando lugar a la producción de compuestos orgánicos volátiles (VOC). El objetivo del trabajo es su identificación en el aire exhalado y su posible utilidad como biomarcadores de la enfermedad. Método: Se analizó el aire exhalado de 100 voluntarios sanos, clasificados en 3 grupos (no fumadores, exfumadores y fumadores activos) y un grupo de 57 pacientes con EPOC. La muestra de aire exhalado se recogió mediante BioVOC® y se traspasó a tubos de desorción para su posterior análisis por cromatografía de gases y espectrometría de masas. Los VOC analizados fueron aldehídos lineales y ácidos carboxílicos. Resultados: Hexanal mostró diferencias estadísticamente significativas entre el grupo EPOC y los controles sanos (no fumadores y exfumadores), y nonanal entre el grupo control no fumador y el grupo EPOC. Conclusiones: Hexanal discrimina entre pacientes con EPOC y controles sanos no fumadores y exfumadores. Nonanal diferencia entre fumadores y exfumadores (con o sin EPOC) frente a controles no fumadores

Introduction: A major risk factor for chronic obstructive pulmonary disease (COPD) is tobacco smoke, which generates oxidative stress in airways, resulting in the production of volatile organic compounds (VOC). The purpose of this study was to identify VOCs in exhaled breath and to determine their possible use as disease biomarkers. Method: Exhaled breath from 100 healthy volunteers, divided into 3 groups (never smokers, former smokers and active smokers) and exhaled breath from 57 COPD patients were analyzed. Samples were collected using BioVOC® devices and transferred to universal desorption tubes. Compounds were analyzed by thermal desorption, gas chromatography and mass spectrometry. VOCs analyzed were linear aldehydesand carboxylic acids. Results: The COPD group and healthy controls (never smokers and former smokers) showed statistically significant differences in hexanal concentrations, and never smokers and the COPD group showed statistically significant differences in nonanal concentrations. Conclusions: Hexanal discriminates between COPD patients and healthy non-smoking controls. Nonanal discriminates between smokers and former smokers (with and without COPD) and never smokers

Study of 5 Volatile Organic Compounds in Exhaled Breath in Chronic Obstructive Pulmonary Disease. / Estudio de 5 compuestos orgánicos volátiles en aire exhalado en la enfermedad pulmonar obstructiva crónica.

INTRODUCTION: A major risk factor for chronic obstructive pulmonary disease (COPD) is tobacco smoke, which generates oxidative stress in airways, resulting in the production of volatile organic compounds (VOC). The purpose of this study was to identify VOCs in exhaled breath and to determine their possible use as disease biomarkers. METHOD: Exhaled breath from 100 healthy volunteers, divided into 3groups (never smokers, former smokers and active smokers) and exhaled breath from 57 COPD patients were analyzed. Samples were collected using BioVOC® devices and transferred to universal desorption tubes. Compounds were analyzed by thermal desorption, gas chromatography and mass spectrometry. VOCs analyzed were linear aldehydesand carboxylic acids. RESULTS: The COPD group and healthy controls (never smokers and former smokers) showed statistically significant differences in hexanal concentrations, and never smokers and the COPD group showed statistically significant differences in nonanal concentrations. CONCLUSIONS: Hexanal discriminates between COPD patients and healthy non-smoking controls. Nonanal discriminates between smokers and former smokers (with and without COPD) and never smokers.

Fungal endophytic communities on twigs of fast and slow growing Scots pine (Pinus sylvestris L.) in northern Spain.

Most plant species harbour a diverse community of endophytic, but their role is still unknown in most cases, including ecologically and economically important tree species. This study describes the culturable fungal endophytic community of Pinus sylvestris L. twigs in northern Spain and its relationship with diametric growth of the host. In all, 360 twig samples were collected from 30 Scots pines in fifteen stands. Isolates were obtained from all twig samples and 43 fungal taxa were identified by morphogrouping and subsequent ITS rDNA sequencing. All isolates were Ascomycetes, being Dothideomycetes and Sordariomycetes the most abundant classes. Half of the species were host generalists while the others were conifer or pine specialists. We found three new endophytic species for the Pinaceae: Biscogniauxia mediterranea, Phaeomoniella effusa and Plectania milleri, and additional six new species for P. sylvestris: Daldinia fissa, Hypocrea viridescens, Nigrospora oryzae, Ophiostoma nigrocarpum, Penicillium melinii and Penicillium polonicum. The endophytic community of fast and slow growing trees showed differences in species composition, abundance and evenness, but not in diversity. Phoma herbarum was associated to fast growing trees and Hypocrea lixii to those growing slow. Our results support the hypothesis that some endophytic species may affect growth of P. sylvestris.

Cost-constrained optimal sampling for system identification in pharmacokinetics applications with population priors and nuisance parameters.

Pharmacokinetics (PK) applications can be seen as a special case of nonlinear, causal systems with memory. There are cases in which prior knowledge exists about the distribution of the system parameters in a population. However, for a specific patient in a clinical setting, we need to determine her system parameters so that the therapy can be personalized. This system identification is performed many times by measuring drug concentrations in plasma. The objective of this work is to provide an irregular sampling strategy that minimizes the uncertainty about the system parameters with a fixed amount of samples (cost constrained). We use Monte Carlo simulations to estimate the average Fisher's information matrix associated to the PK problem, and then estimate the sampling points that minimize the maximum uncertainty associated to system parameters (a minimax criterion). The minimization is performed employing a genetic algorithm. We show that such a sampling scheme can be designed in a way that is adapted to a particular patient and that it can accommodate any dosing regimen as well as it allows flexible therapeutic strategies.

Best estimation of spectrum profiles for diagnosing femoral prostheses loosening.

For the past few years, some authors have proposed several vibration analysis techniques to detect the prosthetic femoral stem loosening, having found some differences in the frequency response between secure and loose stems. Classical methods like periodogram have been used in most studies for the spectral estimation, and their conclusions have been reached only by visual inspection. A new metric called Non-linear Logarithmic Weighted Distance (NLWD), based on log-spectral distance is presented. As its name suggests, the spectral power is weighted in order to highlight discriminatory patterns of the spectral profiles. A Generalized Discriminant Ratio (GDR) based on NLWD metric has been also defined. In this study, experiments on a cadaveric dried bone with two kinds of fixation, Loose Stem class (LS) and Secure Stem class (SS), have been analyzed. To select the most discriminating approach to spectral estimation, five well known algorithms (Welch's, Burg's Auto-Regressive (AR), Auto-Regressive Moving Average (ARMA), Multiple Signal Classification (MUSIC) and Thomson's Multi-taper (MTM)) have been compared by using GDR. Finally, the use of the MTM method is proposed for the analysis of bone-stem interface vibratory signals, since it yields the most discriminatory profiles.

Estudio de compuestos orgánicos volátiles en aire exhalado en una población clínicamente sana: efecto del tabaquismo / Volatile Organic Compounds in Exhaled Breath in a Healthy Population: Effect of Tobacco Smoking

Introducción: El humo del tabaco es una fuente de radicales libres y especies reactivas de oxígeno y de nitrógeno, principales causantes de estrés oxidativo. El análisis de compuestos orgánicos volátiles (VOC) en aire exhalado es un método indirecto de medir el nivel de estrés oxidativo que se produce en las vías aéreas. El objetivo de este trabajo es conocer la influencia del tabaco en la producción de VOC en una población clínicamente sana. Métodos: Se analizó el aire exhalado de 89 voluntarios sanos, clasificados en 3 grupos: no fumadores, exfumadores y fumadores activos. La muestra de aire exhalado se recogió mediante Bio-VOC®, y se traspasó a tubos de desorción. La técnica analítica utilizada fue: desorción térmica, cromatografía de gases y espectrometría de masas. Los VOC analizados fueron hexanal, heptanal, octanal, nonanal, ácido propanoico y ácido nonanoico, cuya identificación se realizó mediante su tiempo de retención y espectro de masas referenciado en la biblioteca NIST 08, confirmándolo mediante el uso de estándares cromatográficos. Resultados: La mayoría de los VOC analizados se encuentran a concentraciones muy bajas. Únicamente el nonanal muestra diferencia estadísticamente significativa entre los grupos de estudio, depende exclusivamente del hábito de fumar, y es independiente de la cantidad de tabaco consumido, edad y género. Conclusiones: El hallazgo de nonanal se asocia al consumo de tabaco, actual o previo. Al ser un producto secundario de la destrucción de la membrana celular, su hallazgo probablemente muestra daño celular en personas fumadoras y permanece una vez cesado el hábito (AU)

Introduction: Tobacco smoke is a source of free radicals and reactive oxygen and nitrogen species, which are the main causes of oxidative stress. The analysis of volatile organic compounds (VOC) in exhaled breath is an indirect method of measuring the level of oxidative stress that occurs in the airways caused by tobacco consumption. The aim of this study was to determine whether smoking influences the production of VOC, in a clinically healthy population. Methods: Exhaled breath from 89 healthy volunteers, divided into three groups (non-smokers, ex-smokers and smokers), was analyzed. Samples were collected using Bio-VOC® devices and transferred to universal desorption tubes. Chemical compounds were analyzed by thermal desorption, gas chromatography and mass spectrometry. We analyzed hexanal, heptanal, octanal, nonanal, nonanoic acid and propanoic acid, and all were identified by retention time and mass spectra referenced in the NIST 08 mass spectral library; confirmation was carried out using reference standards of the pure chemical compound. Results: These VOC were found in very low concentrations. Only nonanal showed significant quantitative and qualitative statistical differences among the study groups. Nonanal concentration is dependent on smoking, but is independent of the amount of tobacco consumed, age and gender. Conclusions: Nonanal in exhaled breath is associated with tobacco consumption, current or previous. Nonanal is a sub-product of the destruction of the cell membrane, and its finding may be indicative of cell damage in smokers. This result appears in many farmers who smoke (AU)

Volatile organic compounds in exhaled breath in a healthy population: effect of tobacco smoking.

INTRODUCTION: Tobacco smoke is a source of free radicals and reactive oxygen and nitrogen species, which are the main causes of oxidative stress. The analysis of volatile organic compounds (VOC) in exhaled breath is an indirect method of measuring the level of oxidative stress that occurs in the airways caused by tobacco consumption. The aim of this study was to determine whether smoking influences the production of VOC, in a clinically healthy population. METHODS: Exhaled breath from 89 healthy volunteers, divided into three groups (non-smokers, ex-smokers and smokers) was analysed. Samples were collected using Bio-VOC® devices and transferred to universal desorption tubes. Chemical compounds were analysed by thermal desorption, gas chromatography and mass spectrometry. We analysed hexanal, heptanal, octanal, nonanal, nonanoic acid and propanoic acid, all identified by retention time and mass spectra referenced in the NIST 08 mass spectral library; confirmation was carried out using reference standards of the pure chemical compound. RESULTS: These VOC were found in very low concentrations. Only nonanal showed significant quantitative and qualitative statistical differences among the study groups. Nonanal concentration is dependent on smoking, but is independent of the amount of tobacco consumed, age and gender. CONCLUSIONS: Nonanal in exhaled breath is associated with tobacco consumption, current or previous. Nonanal is a sub-product of the destruction of the cell membrane, and its finding may be indicative of cell damage in smokers. This result appears in many farmers who smoke.

Biomechanical assays for the study of the effects of hip prostheses: application to the reconstruction of bone defects with femoral allografts.

There is a need to study and validate the mechanical behavior of the bone-implant total hip prosthesis and the treatment of its complications with experimental studies due to the limitations showed by numerical methods. Epoxy resin replicas of a femur (stereolithography) and a mechanical validation were performed. We studied three cases: intact femur (Case 1); non-defective femur with non-cemented LD primary stem (Case 2); and femur with a cavitary defect, short cemented stem over an impacted allograft (Case 3). The test pieces were connected to 7 strain gauges. Three assays per piece were carried out with a vertical and oblique load (load-unload curves after a sequence between 0 and 145.9 N). We measured the k coefficient (distance from the natural state of the strains) and stability of the stem (flexion-compression by strain gauges 1, 2, 5, and 7 and transversal lengthening by strain gauges 3, 4, and 6). Results of the strain gauge analysis revealed linearity of results in all cases, and more so in load than in unload. Gauge 7 (proximal) revealed shortening in all cases. Gauges 2 and 5 provided qualitatively similar data due to a significant increase in rigidity. K coefficients were obtained with a nonsignificant difference when each of the test pieces was compared with Case 2. The results were reproducible in all 7 gauges. Observation of the load-unload curves in all the test pieces assayed shows that there are no variations in the pattern of behavior (when comparing the stability of a primary stem and a stem in the simulated reconstructed femoral defect. If these reconstructions are considered theoretically appropriate for giving primary stability to the stem--a sine qua non for the success of replacement surgery--then our study is novel.

Changes in the mechanical properties of chemically treated bovine pericardium after a short uniaxial cyclic test.

The mechanical behavior of calf pericardium, a biomaterial utilized in the manufacture of cardiac bioprostheses, in response to a short tensile cyclic test has been evaluated. The trial involved 120 samples cut longitudinally or transversely, subjected to 10 cycles until a stress of between 1 and 3 MPa was reached. Tests of hardness and tear propagation were performed, and the results were compared with a control series. The energy loss was also computed, and it was approximately 10-fold greater in the first cycle than the loss in the subsequent nine cycles. Despite this singularity, they correlated very precisely. The effect of the direction in which the tissue is cut on energy loss was not significant nor the difference between hardness prior to and after testing. The results of the tear propagation tests gave no statistical differences prior to and after testing. From the obtained results, it seems that the test carried out does not affect significantly the mechanical properties of calf pericardium.

Fatigue behaviour of young ostrich pericardium.

Young ostrich pericardia (biomaterial under study for manufacturing cardiac valve leaflets), has been subjected to biaxial tension fatigue until breakage. Supraphysiological values of pressure (1 to 6 atm) have been employed to accelerate damage and, therefore, to reduce testing time but at physiological frequency in order to avoid viscoelastic behaviour changes. The lifetime fatigue curves have been obtained and large scatter has been observed in the results but this can be strongly reduced with adequate material selection. The thickness-based selection of samples has proved to be ineffective both in reducing scatter or improving strength, but the energy-based selection aided with statistical decision techniques has been shown to be very successful. The energy loss (energy under the hysteresis loop of each load and unload cycle) appears to be a very accurate predictor of the expected fatigue lifetime of the tissue.

Propagation of tears in pericardium from young bulls: influence of the suture.

The tearing of the collagen fibers of biological materials utilized in implants or bioprostheses is an important, and sometimes early cause of the failure of these devices. We studied the force necessary to propagate a tear in a biomaterial, pericardium from young bulls, and the influence of the suture. An Elmendorf pendulum capable of measuring the force necessary to tear a given length of tissue was employed. We analyzed 112 trials (70%) that proved valid after achieving the homogeneity of the samples according to their thickness, thus making the results comparable. Mean forces ranging between 19.87 and 150 N were required to propagate tears measuring from 0.25 to 2.0 cm. In the samples with a 1-cm-long suture, sewn using an edge-to-edge technique, the propagation of the tear required a mean force of 15.75 N when the suture was made of nylon and 28.73 N when Prolene was utilized. When these results were compared with the mean recorded in an unsutured control series (56.76 N), the loss of resistance was significant in both sutured series (P = 0.000 and P = 0.011, respectively). Finally, the equation that relates the force (y) with the length of the tear made in unsutured tissue (x) was also obtained: y = 58.14 + 9.62x(2) (R(2) = 0.924). The force necessary to produce a microtear, thus estimated, can be utilized as a parameter for comparison.

[Quality of observational post-authorization studies registered in Spain before their regulation]. / Calidad de los estudios postautorización de tipo observacional registrados en España antes de su regulación.

BACKGROUND AND OBJECTIVE: In July, 2002, observational post-authorization studies were subjected to regulation in Spain, giving rise to an uproar among sponsors and investigators. The aim of the present report was to assess the scientific and ethical quality of the studies presented during the year before the regulation came into force. In addition, we explored how many of them reached publication. MATERIAL AND METHOD: We extracted information relative to administrative procedures, methods, follow-up and ethical issues from the protocol of the studies presented to the Spanish Agency for Medicines and Healthcare Products (AEMPS) during 2001. RESULTS: A total of 162 studies intended to recruit 306,539 patients were registered as post-authorization studies in 2001. The most widely used design was the <> (122 studies; 75%). Physicians were the only source of information in 99% of the studies. In 43% of them, the sample size was neither specified nor justified. In 83% of the studies the observation period per patient was less than 12 months. An ethical review was requested for only 13% of the studies while a procedure to inform patients was planned in 44%. Eleven studies (10% of those finalized) had been published in scientific journals (1 of them international) and 13 (12% of those finalized) were reported as a communication to a national (11) or international (2) congress. CONCLUSIONS: Most post-authorization studies presented to the AEMPS in 2001 had poor methodological and ethical quality. Only a few became published, raising doubts about their scientific aims. These results give empirical support to the regulation adopted.