Free software to analyse the clinical relevance of drug interactions with antiretroviral agents (SIMARV®) in patients with HIV/AIDS.

BACKGROUND: Highly active antiretroviral therapy has extended the expected lifespan of patients with HIV/AIDS. However, the therapeutic benefits of some drugs used simultaneously with highly active antiretroviral therapy may be adversely affected by drug interactions. OBJECTIVE: The goal was to design and develop a free software to facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. METHODS: A comprehensive Medline/PubMed database search of drug interactions was performed. Articles that recognized any drug interactions in HIV disease were selected. The publications accessed were limited to human studies in English or Spanish, with full texts retrieved. Drug interactions were analyzed, assessed, and grouped into four levels of clinical relevance according to gravity and probability. Software to systematize the information regarding drug interactions and their clinical relevance was designed and developed. RESULTS: Overall, 952 different references were retrieved and 446 selected; in addition, 67 articles were selected from the citation lists of identified articles. A total of 2119 pairs of drug interactions were identified; of this group, 2006 (94.7%) were drug-drug interactions, 1982 (93.5%) had an identified pharmacokinetic mechanism, and 1409 (66.5%) were mediated by enzyme inhibition. In terms of clinical relevance, 1285 (60.6%) drug interactions were clinically significant in patients with HIV (levels 1 and 2). With this information, a software program that facilitates identification and assessment of the clinical relevance of antiretroviral drug interactions (SIMARV®) was developed. CONCLUSIONS: A free software package with information on 2119 pairs of antiretroviral drug interactions was designed and developed that could facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS.

Enfermedades crónicas de alta prevalencia en una población asistida por la Seguridad Social / Highly prevalent chronic diseases in a population with Social Security coverage

Objetivo: Una de las prioridades sanitarias de las políticas europeas es la obtención de información sobre enfermedades crónicas y de alta prevalencia; ésta se encuentra limitada por la calidad de los datos disponibles. El objetivo del estudio fue describir el comportamiento de las enfermedades crónicas más prevalentes a través de bases de datos de gestión administrativa. Método: Estudio transversal retrospectivo sobre medicamentos fabricados industrialmente, dispensados y financiados total o parcialmente con fondos públicos por el Servicio de Salud deCastilla-La Mancha, a través de farmacias. El estudio se realizó durante 2003 y 2004 en el área de salud de Albacete y en él se aplicó la metodología recomendada por la Organización Mundial de la Salud para los estudios de utilización de medicamentos. El valor de la dosis diaria definida permitió conocer el número que contenía cada envase y el utilizado por 1.000 usuarios y por día, variable cuantitativa asimilable al concepto de tasa poblacional. Mediante la variable cualitativa, principio activo identificado por su código ATC, se agruparon medicamentos por indicación principal y se relacionaron con la variable cuantitativa. Resultados: La mayor prevalencia se observó en la hipertensión (27,3%: 24,2-36,7), las alteraciones del metabolismo lipídico (7,4%: 5,9-10,7) y la diabetes (6,8%: 5,9-9,7); se constató un incremento en todos los casos (del 8,9, el 27,5 y el 9,2%, respectivamente). Ambas situaciones destacan en los distritos dela sierra. Conclusiones: Es posible conocer cuál es la situación de las enfermedades crónicas de alta prevalencia, con bases de datos de gestión, mediante estudios de utilización de medicamentos. Su aplicación a ámbitos y periodos diferentes requiere la adopción de criterios metodológicos similares (AU)

Objective: One of the sanitary priorities in Europe is the obtaining of information about the high prevalence and chronic diseases, which is limited by the quality of the available information. The aim of the present study was to describe the behavior of the most prevalent chronic diseases using databases of administrative management. Method: We performed a retrospective, cross-sectional study of drugs made industrially, dispensation and financed, whole or partially with public funds, by the Health Service of Castilla-La Mancha, through pharmacies. The study was conducted between the years 2003 and 2004 in the health area of Albacete; in the study the methodology recommended by the World Health Organization WHO for conducting drug utilization studies was applied. The value of the defined daily dose allowed knowing the number contained in each package and the number of them used per thousand users and per day, quantitative assimilable variability to the population rate concept. Through the qualitative variable, active drug substance identified by ATC code, drugs with the same composition and principal indication were grouped, and they were related to the quantitative variable. Results: The greater prevalence was seen in hypertension(27.3%: 24.2-36.7), lipid metabolism alterations (7.4%: 5.9-10.7) and diabetes (6.8%: 5.9-9.7); an increase was established in all the cases (of 8.9%, of 27.5% and of 9.2%, respectively). Both situations stand out in the districts of the mountain range. Conclusions: It is possible to know the status of chronic diseases and high prevalence, with management databases, by means of studies of medication use. Its application to different areas and periods requires the adoption of similar methodological criteria (AU)

El seguimiento farmacoterapéutico: un componente de la calidad en la atención al paciente / Pharmacotherapy follow-up: as a quality component in patient care

La gestión de la Calidad Total busca la satisfacción del usuario, la implicación activa de los profesionales responsables de su salud y la incorporación de estrategias para la mejora continua de las actividades clínicas, incorporando la búsqueda de la seguridad del paciente como componente principal. La gestión de la seguridad del paciente minimiza las lesiones no intencionadas atribuibles a procesos de la atención sanitaria, incluido el uso de medicamentos. Los principios de seguridad del paciente se aplican en ambos niveles asistenciales y a todos los profesionales sanitarios. Gestionar el riesgo es cuidar al paciente. La Seguridad del paciente pretende resolver problemas y prevenir errores. La aportación del farmacéutico a la seguridad del paciente se realiza con la Atención Farmacéutica y en concreto con el Seguimiento Farmacoterapéutico (SFT) que previene, detecta y resuelve Problemas Relacionados con los Medicamentos (PRM). Uno de los principales problemas para avanzar, es la dificultad para homogeneizar resultados; existen diferencias en las definiciones, al igual que ocurre en el ámbito del medicamento, donde se mezcla permanentemente proceso y resultado: Efecto adverso, Acontecimiento no deseado, Errores de medicación, PRM, etc. Se ha de homogenizar la taxonomia; disponer de una información común permitiría conocer mejor la prevalencia, sus tipos, sus causas, su gravedad así como sus consecuencias. Se quiere caminar hacia la seguridad del paciente evaluando tecnologías su efectividad y su seguridad, acreditando establecimientos y acreditando competencia profesional. Este es el camino también para el SFT que comparte los principios básicos de calidad de la seguridad del paciente. El farmacéutico tiene la responsabilidad profesional y ética de poner a disposición de los pacientes el conocimiento, la experiencia y el método, igual que las acciones emprendidas por los sistemas sanitarios. Existe la oportunidad de estar, de ser los responsables de esta aportación, porque la seguridad del paciente, en general, y en relación al uso de los medicamentos en particular, va a desarrollarse

The principal aim of management of the Quality of Care is to assure patient satisfaction, through the active involvement of health care staff and the incorporation of strategies, whose main aim is to achieve continuous improvement in clinical activities and to incorporate patient safety as one of its principle components. The management of patient safety is a means to minimizing any possible harm to patients in care processes, including the use of medicines. The principles of patient safety can be applied to both levels of patient care and involve all health care professionals. The risk management is an integral part of patient care. Patient safety depends on the solution of problems and the prevention of errors. The pharmacist’s role in patient safety is carried out through Pharmaceutical Care processes and especially through Pharmacotherapy follow-up (PF), which aims to prevent, detect and resolve Drug Therapy Problems (DTP). One of the main difficulties associated with this field is the lack of uniformity of the results obtained throughout the different studies carried out, where differences in definitions occur, as in the classification of drug problems themselves, where process and result are constantly intermingled: Adverse effect, undesirable events, medication errors, DTP, etc. The criteria for classifying such aspects should be uniform, so as to make common information available, which will enable pharmacists to obtain greater knowledge on prevalence, their types, causes, severity and consequences. There is a general desire to improve upon patient safety, to assess the technological processes involved in evaluating effectiveness and safety, and to certify the establishments and health care professionals responsible for such processes. This same approach should also be applied to PF, which is subject to the same basic safety principles. As in the case of all work carried out within the health system, the work of the pharmacist involves the professional and ethical responsibility of making his knowledge, experience and methodology available to his patients. Pharmacists now have the opportunity of making a significant contribution to patient safety, both in general terms and more specifically in the use of medicines, in a field which is currently set for future development

Validación de un cuestionario para laidentificación de problemas relacionados con losmedicamentos en usuarios de un serviciode urgencias hospitalario / The validation of a questionnaire for the identification of problems arising from the use of medicines by patients at a hospital emergency ward

Los problemas relacionados con los medicamentos (PRM) son problemas de salud asociados al uso de medicamentos. Son muchos los PRM que podemos encontrar si analizamos la medicación que toman los pacientes y los problemas de salud que refieren y muy variadas las causas que los ocasionan. La entrevista con el paciente constituye un instrumento imprescindible para la obtención de información sobre qué medicamentos toma, como los toma y sobre la experiencia que de ellos tiene. Los servicios de urgencias hospitalarios constituyen cada día más una puerta de entrada al sistema sanitario para los ciudadanos, de forma que constituye un escenario adecuado para conocer la prevalencia de PRM, sin embargo las características propias de un servicio de urgencias de hospital requiere la adaptación de la entrevista con el usuario. Objetivo: El presente trabajo pretende diseñar y validar un cuestionario como instrumento para la obtención de información suficiente para la evaluación e identificación de PRM en los usuarios de un servicio de urgencias hospitalario. Metodología: Se procederá al diseño de un cuestionario con la intervención de expertos en Seguimiento Farmacoterapéutico, igualmente se procederá a la validación del mismo pilotandolo sobre una muestra de 222 pacientes usuarios de un servicio de urgencias hospitalario. Resultado: Tras el pilotaje el cuestionario fue validado (AU)

Programa Dáder de Seguimiento del TratamientoFarmacológico. Resultados de la fase piloto / Pilot phase results of the Dáder programme for drug therapy follow up

La Atención Farmacéutica (Pharmaceutical Care) o el Seguimiento del Tratamiento Farmacológico requiere de una formación de pregrado, pero también de postgrado, continuada y reglada. En ese intento de proporcionar formación continuada, se creó el Programa Dáder de Seguimiento del Tratamiento Farmacológico. Objetivo. El presente trabajo analiza los resultados de la fase piloto de la metodología Dáder para el Seguimiento Farmacoterapéutico, durante los meses de enero a marzo del 2000.Resultados. En 24 farmacias con 48 farmacéuticos comunitarios se realizó Seguimiento Farmacoterapéutico a 174 pacientes. Se intervino en 194 PRM, de los que se resolvieron 167. La distribución de tipos de PRM fue de 31 por ciento de necesidad, 32,9 por ciento de efectividad y 36,1 por ciento de seguridad. Hubo de comunicarse con el médico en el 68 por ciento de las ocasiones, resolviéndose el 81 por ciento de estos, y el 92 por ciento de los que se comunicó sólo con el paciente. Conclusiones: La metodología Dáder para el Seguimiento Farmacoterapéutico es útil para identificar y resolver problemas relacionados con medicamentos (AU)

Antihepatotoxic activity of Rosmarinus tomentosus in a model of acute hepatic damage induced by thioacetamide.

R. tomentosus is a vegetal species closely related to the culinary rosemary (R. officinalis), a plant reported to contain antihepatotoxic agents. A dried ethanol extract of the aerial parts of Rosmarinus tomentosus (Lamiaceae) and its major fraction separated by column chromatography (fraction F19) were evaluated for antihepatotoxic activity in rats with acute liver damage induced by a single oral dose of thioacetamide. Silymarin was used as a reference antihepatotoxic substance. Pre-treatment with R. tomentosus ethanol extract, fraction F19 or silymarin significantly reduced the impact of thioacetamide toxicity on plasma protein and urea levels as well as on plasma aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and gamma-glutamyl transpeptidase activities compared with thioacetamide-treated animals (group T). Pre-treatment with R. tomentosus ethanol extract significantly reduced the impact of thioacetamide damage on alkaline phosphatase and gamma-glutamyl transpeptidase activities compared with group T. Silymarin administration significantly reduced alkaline phosphatase and gamma-glutamyl transpeptidase activities compared with group T. Fraction F19 administration reduced only alkaline phosphatase activity compared with group T. According to these data, R. tomentosus extract shows promising antihepatotoxic activity, suggesting the need to isolate the chemical principles responsible for this activity and to study this activity in a model of thioacetamide-induced cirrhosis.

Atención Farmacéutica como respuestaa una necesidad social / Pharmaceutical Care as a response to social need

La utilización masiva de medicamentos es una de las causas del aumento de la esperanza de vida en los países desarrollados, pero conlleva riesgos colaterales. La mayoría de los fallos de la farmacoterapia se pueden atribuir a una mala utilización de los medicamentos por parte de los pacientes. La solución para este importante problema es la implementación de la Atención Farmacéutica, con objeto de asegurar una farmacoterapia efectiva y segura para todos los pacientes. La Atención Farmacéutica es la respuesta sanitaria a la necesidad social de ayudar a los pacientes para obtener el máximo beneficio de sus medicamentos (AU)

Addition of vitamin E to long-chain polyunsaturated fatty acid-enriched diets protects neonatal tissue lipids against peroxidation in rats.

BACKGROUND: Tissue 10:4(n-6) and 22:6(n-3) status have been correlated with neonatal development and growth. Artificial formulas for neonates have been supplemented with long chain polyunsaturated fatty acids (LCP) from animal and marine sources which may enhance sensitivity of cellular membranes to oxidative damage. Diet-derived antioxidants like vitamin E play a key role in the protection of tissue lipids against oxidation. AIM OF THE STUDY: We seek to determine the influence of dietary vitamin E on tissue sensitivity to oxidative stress in rats fed for 4 weeks on diets enriched in (n-3) and (n-6) long-chain polyunsaturated fatty acids. METHODS: Weanling rats received 10% fat diets that provided 18:1(n-9), 18:2(n-6) and 18:3(n-3) in a similar ratio to that of rat milk (group A), supplemented with fish oil (groups B and B+E) and supplemented with (n-6) and (n-3) LCP from an animal phospholipid concentrate (groups C and C+E). Vitamin E (500 mg vitamin E/kg fat) was added to diets B+E and C+E. Tissue fatty acid content and the activities of catalase, superoxide dismutase, glutathione transferase und glutathione peroxidase in liver and brain were measured. Glutathione status, vitamin E and the production of thiobarbituric acid reactive substances (TBARs) after incubation of erythrocyte, liver and brain lipids with inducers of enzymatic or non-enzymatic lipid peroxidation was measured. RESULTS: Group B registered significantly lower total superoxide dismutase activity than group B+. Catalase activity was significantly higher in group C than in group C+E. Hepatic total and reduced glutathione levels were decreased in vitamin E supplemented groups compared to unsupplemented ones. TBARs production in erythrocyte lipids was significantly higher in groups B and C compared to vitamin E supplemented groups B+E and C+E. CONCLUSIONS: This study shows that the addition of vitamin E protected erythrocyte and liver microsome lipids enriched in (n-3) and (n-6) LCP from lipid peroxidation during the postnatal development of rats. The protection was more effectively in group C+E than in group B+E.

Dietary long-chain polyunsaturated fatty acids influence tissue fatty acid composition in rats at weaning.

We studied the fatty acid composition of plasma, plasma phospholipids, erythrocyte membrane lipids, liver microsomal phospholipids and brain lipids in rats fed three different diets varying in their (n-3) and (n-6) long-chain polyunsaturated fatty acid (LCP) concentrations for 0, 2 and 4 wk after weaning. The three diets contained 10% fat; diet HO had a high-oleic acid proportion; diet FO was enriched in n-3 LCP provided by fish oil; and diet FO + BPL contained n-3 and n-6 LCP supplied by fish oil and a brain phospholipid concentrate. At 2 and 4 wk after weaning the proportions of oleic acid in all tissues, except in liver microsomes of the FO + BPL group, were significantly higher than in weanling rats. The absence of (n-3) LCP intake resulted in significantly lower levels of docosapentaenoic [20:5(n-3)] and 22:6(n-3) acids in plasma, plasma phospholipids, erythrocyte membrane lipids and liver microsomal phospholipids but not in brain lipids compared with rats at weaning. Dietary supplementation with (n-3) LCP (FO and FO + BPL groups) for 4 wk led to higher levels of 22:6(n-3) in all tissues compared with rats fed the HO fat. The proportions of 20:4(n-6) and total (n-6) LCP were significantly lower in all tissues from rats fed the FO diet than in rats at weaning and rats fed the HO diet. After 2 and 4 wk, rats fed the FO + BPL diet had significantly higher levels of 20:4(n-6) and total (n-6) LCP in plasma, plasma phospholipids, erythrocyte lipids and liver microsomal phospholipids; the brain also showed a higher content of those fatty acids after 4 wk. Our results suggest that dietary supplementation with 20:4(n-6) and 22:6(n-3) influences the concentration of 20:4-(n-6) and 22:6(n-3) in body tissues of rats after weaning.

[The effect of dietary supplementation with long-chain polyunsaturated fatty acids of the n-3 and n-6 series and with vitamin E on the plasma fatty acid profile]. / Efecto de la suplementación a la dieta de ácidos grasos poliinsaturados de cadena larga de las series n-3 y n-6 y de vitamina E sobre el perfil de ácidos grasos del plasma.

Dietary supplement with long-chain polyunsaturated fatty acids from the series n-3 and n-5 appears to be advisable in the nutritional repletion of a variety of conditions. It must be associated with the addition of a sufficient amount of an anti-oxidant to prevent the oxidative degradation of such fatty acids. The purpose of this study was to appraise the effect of the dietary addition of long-chain polyunsaturated fatty acids from the series n-3 and n-5 and of Vitamin E on the fatty acid profile of the plasma, and its lipidic fractions. Five groups of weaning rats were fed for a month as follows: Group A, a semipurified diet with 10% of fat [18:1(n-9) 40%; 18:2(n-6) 12%; 18:3(n-3) 1.2%]; Groups B and C, a semipurified diet with 7% of fat A and 3% of a marine oil concentrate; Groups D and E, a semipurified diet with 7% of fat A, 1.5% of a marine oil concentrate and 1.5% of a phospholipid concentrate of animal origin. Groups B and D were supplemented with 0.5 g of Vitamin E per kilogram of fat. The results obtained suggest that dietary supplement is necessary with long-chain polyunsaturated fatty acids from both the n-3 and n-5 series in order to maintain plasmatic levels of 20:4(n-6) and of 22:6(n-3) in the face of the tissular inability to produce them from their dietary precursors [18:2(n-6) and 18:3)], along with Vitamin E to prevent the oxidative malnutrition of these fatty acids.

Influences of postnatal age and dietary nucleotides on plasma fatty acids in the weanling rat.

Dietary nucleotides seem to play a number of physiologic roles during early life. They are improved in the maintenance of the immune system, intestinal maturation, and lipid metabolism. Nucleotides affect the conversion of essential fatty acids into their long-chain polyunsaturated (PUFA) derivatives in both preterm and at-term newborn infants. This work examines the effect of postnatal age and dietary nucleotides on the fatty acid composition of total plasma lipids and lipid fractions in the rat. Weanling rats (21 days old) were divided into three groups. The first group was killed, and the other two groups were fed a standard semipurified diet, and the same diet supplemented with 250 mg each of CMP, UMP, AMP, GMP, and IMP per 100 g of diet for 4 weeks. Advancing postnatal age led to an increase of total plasma fatty acids, especially saturated, and PUFA of the n-6 series, whereas PUFA of the n-3 series decreased. The fatty acid profile of plasma phospholipids (PL) exhibited minor changes, although there was a tendency to show lower levels of saturates and PUFA of the n-3 series and increased levels of PUFA of the n-6 series. Cholesteryl esters showed a response similar to that of PL, although the increase in arachidonic acid (20:4n-6) was significant. For triglycerides, linoleic acid (18:2n-6) and monounsaturates increased their levels, whereas saturates decreased. Dietary nucleotides mediated a significant increase in total plasma fatty acids, namely monounsaturated fatty acids and PUFA of both n-6 and n-3 series as compared with the control group. The relative fatty acid composition of PL and cholesteryl esters was mostly unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of long-term feeding olive and sunflower oils on fatty acid composition and desaturation activities of liver microsomes.

Changes in microsomal fatty acid composition, delta 9- and delta 6-desaturase activities and cholesterol and phosphorus liver content were studied in dogs fed olive and sunflower oil diets. No changes were observed in the saturated fatty acids between dietary groups. The level of monounsaturated fatty acids was more elevated in animals fed the OO diet, because of its high relative content in this diet although the in vitro delta 9-desaturase activity was similar in microsomes from the two groups. The proportion of arachidonic acid was similar in SO and OO fed animals. This similar level occurred despite a significant increase in the level of linoleic acid in membrane lipids as a result of feeding the SO supplement. The in vitro delta 6-desaturase activity in liver microsomes showed no differences between dogs fed the two diets. Thus, the higher desaturation presented in vivo by microsomes from OO group may be related to the inhibition by linoleic acid of delta 6-desaturase in dogs fed the SO diet. The polyunsaturated fatty acids (PUFA) from the n-3 series were higher in microsomal phosphatidylcholine and phosphatidylethanolamine from animals fed the OO supplemented diet. The cholesterol/phosphorus molar ratio was higher in the SO group in which the unsaturation index was only slightly affected in phospholipids.

Influences of diet and postnatal age on the lipid composition of red blood cell membrane in newborn infants.

The fatty acid and cholesterol contents of tissue membranes are determinants of their stability and functionality. This study was designed to evaluate the influences of diet and postnatal age on the polyunsaturated fatty acid (PUFA) composition of erythrocyte membrane phospholipid fractions and on the red blood cell membrane cholesterol and phosphorus contents in newborn infants during the 1st month of life. A group of infants was fed on human milk and another group on adapted milk formula. Blood samples were obtained at birth, from cord blood, and at 7 and 30 days of age. Long-chain w6 PUFA declined with advancing age in all membrane phosphoglycerides and sphingomyelin (SM) in those infants fed formula. w6 PUFA also decreased in phosphatidylcholine (PC) and phosphatidylserine (PS) in infants fed human milk and were maintained constant in phosphatidylethanolamine (PE) and SM. w3 PUFA were less affected by postnatal age. PE and SM showed significantly higher percentages of w6 and w3 long-chain PUFA in infants fed human milk than in those fed formula. Membrane cholesterol content increased in all infants from birth to 1 month of life but phosphorus levels were unaffected by diet and postnatal age. These results suggest that diets with a low content of long-chain PUFA, such as adapted cow's milk formulas, may induce changes in membrane functionality and that incorporation of PUFA to the diet in amounts similar to those found in human milk should be considered at least in early life.

[Free amino acid content of human milk in Spain]. / Contenido de aminoácidos libres en leche humana espanñola.

The concentrations of free amino-acids have been determined in 54 samples of human milk: 18 in colostrum, 18 in transition milk and 18 in mature milk, all of them taken from women in the Eastern part of Andalucía. The amino-acids have been determined through high pressure ion-exchange chromatography and fluorimetric detection. Glutamic acid is the major free amino-acid, representing 21-52% of the total amount of these components in human milk. Its level increase significantly with advancing lactation. Taurine represents 14-19 of total free amino-acids in human milk, remaining its levels practically unchanged during the whole lactation. The fact that the major content of essential free amino-acids in present in human colostrum could suppose a contribution of these substances which are directly absorbable during a period of life when the nutritional requirements of the neonate are incremented.