Diseño de una intervención farmacéutica en farmacia comunitaria para mejorar la adherencia del paciente al tratamiento antibiótico / Design of a pharmaceutical intervention in community pharmacy to improve patient adherence to antibiotic therapy

JUSTIFICACIÓN: el buen uso de los antibióticos ha demostrado ser una de las medidas más efectivas para detener el incremento de las resistencias bacterianas. La farmacia comunitaria, por su proximidad y conocimiento del paciente, es un espacio ideal para la promoción de medidas para atajar este grave problema.OBJETIVOS: estudiar el efecto de la intervención del farmacéutico comunitario en el cumplimiento de los tratamientos antibióticos e identificar posibles factores asociados al uso incorrecto de los mismos.MATERIAL Y MÉTODOS: estudio cuasiexperimental prospectivo a realizar en 4 farmacias comunitarias (3 rurales y 1 urbana) aprobado por el CEIm (Tesis Doctoral).Sujetos del estudio: pacientes y cuidadores mayores de 18 años que acudan a las farmacias demandando antibiótico vía oral y deseen participar voluntariamente en el estudio. Tamaño muestral: para este estudio, en el que se compara un grupo control con un grupo intervención y variables mayoritariamente categóricas, se ha utilizado la fórmula de comparación de dos proporciones, siendo el tamaño muestral total de 72 participantes en cada uno de los grupos. Cuaderno de recogida de datos: incluye características de los participantes, prescripción médica, prescriptor del antibiótico y localización de infección así como los conocimientos del paciente-cuidador sobre antibióticos. Análisis del cumplimiento: se realizará el test de Morisky- Green-Levine y recuento de comprimidos.RESULTADOS ESPERADOS: la hipótesis que barajamos es que el refuerzo por parte del farmacéutico hará que los pacientes, mayoritariamente personas mayores en el caso de las farmacias rurales, mejoren su adherencia y por tanto completen adecuadamente el tratamiento. (AU)

Seguimiento farmacoterapéutico y sistemas personalizados de dosificación como herramientas para optimizar farmacoterapia y adherencia: caso clínico en prácticas tuteladas / Pharmacotherapeutic monitoring and personalised dosing systems as tools to optimise pharmacotherapy and adherence: a clinical case in supervised internships

PRESENTACIÓN DEL CASO: varón, 88 años, refiere episodios de tos crónica e irritación de garganta que le preocupan e incapacitan. Últimamente se encuentra asténico. Se le ofrece SFT y acepta. Problemas de salud actuales: HTA, hiperlipidemia, ERGE, tos, anemia, disuria, astenia.T ratamiento actual: enalapril 10 mg + nitrendipino 20 mg (1/0/0), simvastatina 20 mg (0/0/1), omeprazol 20 mg (1-0-0, incumple), carbocisteina 50 mg/ml (10/10/10), paracetamol 1 g (si dolor), sulfato ferroso 325 mg (1-0-0, incumple). Otros datos de interés PA: 119/52. Resto de parámetros bioquímicos dentro de la normalidad.EVALUACIÓN: se detectan los siguientes PRMs y RNMs: 1.- Enalapril/nitrendipino. Sospecha de PRM: reacción adversa, posible causa de tos. RNM: inseguridad no cuantitativa 2.- Omeprazol. PRM: incumplimiento terapéutico, posible causa de tos por ERGE no controlado. RNM: inefectividad cuantitativa3.- Carbocisteína. PRM: medicamento no necesario, no existe indicación. RNM: efecto de medicamento innecesario4.- Hierro. PRM: incumplimiento terapéutico, posible causa de anemia. RNM: inefectividad cuantitativa 5.- Disuria. PRM: problema de salud no tratado, el paciente refiere dificultad al miccionar. RNM: problema de salud no tratado.INTERVENCIONES: a.- Emitimos informe al MAP proponiendo valorar tratamiento antihipertensivo (enalapril) como causa de tos, poniéndole también en antecedentes del incumplimiento terapéutico de hierro y omeprazol e informándole de la astenia y la disuria. b.- Se retira carbocisteina, medicamento no sujeto a prescripción médica y, por tanto, susceptible de indicación farmacéutica. Se plantea sustitución por comprimidos para chupar como tratamiento sintomático alternativo. c.- Para mejorar la adherencia terapéutica del paciente a su farmacoterapia se le oferta el servicio de SPD, que acepta. Resultados1. (AU)

Servicio de indicación farmacéutica protocolizado INDICA+PRO y plataforma SEFAC e_XPERT: curso dirigido a estudiantes de farmacia. Diseño y valoración / INDICA+PRO protocolised pharmaceutical indication service and SEFAC e_XPERT platform: course aimed at pharmacy students. Design and assessment

JUSTIFICACIÓN: desde un enfoque eminentemente práctico, del que pueden beneficiarse alumnos de los últimos cursos del Grado en Farmacia, abordamos el diseño de una acción formativa específica sobre aspectos de la indicación farmacéutica: conocimiento de guías de síntomas menores, protocolos consensuados, requisitos, procedimientos de prestación y habilidades de comunicación necesarias para su correcto desarrollo.OBJETIVOS: diseñar el curso “Servicio de Indicación Farmacéutica protocolizado: implantación en la práctica habitual de la farmacia comunitaria”. El diseño se ha dirigido a estudiantes de 4º y 5º del Grado de Farmacia. Evaluar la formación a través de una encuesta de satisfacción.MATERIAL Y MÉTODOS: estructura del curso. 1.- Módulo teórico. 2.- Módulos prácticos: a) registro plataforma SEFAC e_XPERT (manejo y registro de casos reales) y b) sesiones de role- playing (simulación de casos propuestos).Instalaciones propias de la Facultad de Farmacia: salón de grados, aula de informática, aula simulada y anexo con circuito cerrado de TV y sonido. Ponentes: farmacéuticos comunitarios en activo, con experiencia en el Proyecto Indica+PRO® (autores del trabajo).Encuesta de satisfacción (escalas tipo Likert): valora contenido, duración, metodología, organización, profesorado, utilidad formativa percibida y valoración global del curso. Se incluyó pregunta abierta donde proponer aspectos para mejorar la calidad.RESULTADOS: el curso tuvo una duración de 20 horas lectivas y su realización supuso 1 crédito de libre configuración al alumnado. Temario. SPFA: definición y clasificación. Indicación farmacéutica. Técnicas de comunicación y fuentes de información en indicación. Actualización en medicamentos susceptibles de indicación. Síntomas menores: guías, consensos y criterios de derivación. Indica+PRO: protocolo y resultados. Plataforma SEFAC e_XPERT: registro de casos reales. (AU)

Disección bilateral de carótida tras traumatismo craneocervical de baja energía con excelente respuesta tras tratamiento endovascular precoz / Bilateral carotid dissection secondary to low-energy craniocervical trauma, with an excellent response following early endovascular treatment

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Burrowing behaviour of robotic bivalves with synthetic morphologies.

Several bivalve species burrow into sandy sediments to reach their living position. There are many hypotheses concerning the functional morphology of the bivalve shell for burrowing. Observational studies are limited and often qualitative and should be complemented by a synthetic approach mimicking the burrowing process using a robotic emulation. In this paper we present a simple mechatronic set-up to mimic the burrowing behaviour of bivalves. As environment we used water and quartz sand contained in a glass tank. Bivalve shells were mathematically modelled on the computer and then materialized using a 3D printer. The burrowing motion of the shells was induced by two external linear motors. Preliminary experiments did not expose any artefacts introduced to the burrowing process by the set-up. We tested effects of shell size, shape and surface sculpturing on the burrowing performance. Neither the typical bivalve shape nor surface sculpture did have a clear positive effect on burrowing depth in the performed experiments. We argue that the presented method is a valid and promising approach to investigate the functional morphology of bivalve shells and should be improved and extended in future studies. In contrast to the observation of living bivalves, our approach offers complete control over the parameters defining shell morphology and motion pattern. The technical set-up allows the systematic variation of all parameters to quantify their effects. The major drawback of the built set-up was that the reliability and significance of the results was limited by the lack of an optimal technique to standardize the sediment state before experiments.

Minimum inhibitory concentrations of medicinal plants used in Northern Peru as antibacterial remedies.

AIM: The plant species reported here are traditionally used in Northern Peru to treat bacterial infections, often addressed by the local healers as "inflammation". The aim of this study was to evaluate the minimum inhibitory concentration (MIC) of their antibacterial properties against gram-positive and gram-negative bacteria. MATERIALS AND METHODS: The antimicrobial activity of ethanolic and water extracts of 141 plant species was determined using a deep-well broth microdilution method on commercially available bacterial strains. RESULTS: The ethanolic extracts of 51 species inhibited Escherichia coli, and 114 ethanolic extracts inhibited Staphylococcus aureus. In contrast, only 30 aqueous extracts showed activity against Escherichia coli and 38 extracts against Staphylococcus aureus. The MIC concentrations were mostly very high and ranged from 0.008 to 256 mg/ml, with only 36 species showing inhibitory concentrations of <4 mg/ml. The ethanolic extracts exhibited stronger activity and a much broader spectrum of action than the aqueous extracts. Hypericum laricifolium, Hura crepitans, Caesalpinia paipai, Cassia fistula, Hyptis sidifolia, Salvia sp., Banisteriopsis caapi, Miconia salicifolia and Polygonum hydropiperoides showed the lowest MIC values and would be interesting candidates for future research. CONCLUSIONS: The presence of antibacterial activity could be confirmed in most species used in traditional medicine in Peru which were assayed in this study. However, the MIC for the species employed showed a very large range, and were mostly very high. Nevertheless, traditional knowledge might provide some leads to elucidate potential candidates for future development of new antibiotic agents.

A multicentre report from the Mexican Retinoblastoma Group.

BACKGROUND: Retinoblastoma (RB) is a relatively uncommon tumour in childhood. The incidence of retinoblastoma in Mexico is probably higher than the incidence reported worldwide, however there is not enough information about the characteristics of this illness in Mexico. This report aims to present the results of a multicentre clinical survey of RB in Mexico. METHODS: A retrospective study was carried out on all RB cases treated in 16 institutions during the last six years. The variables analysed were age at diagnosis, sex, affected eyes, treatment modalities, and pathological staging. Overall survival was obtained. RESULTS: The authors analysed 500 cases; age range was 0-182 months. There were 364 unilateral cases (72.8%). Enucleation was performed in 84.9% of the patients. The St Jude's staging was: 7.4% stage I, 52.8% stage II, 18.0% stage III, 11.4% stage IV, 7.2% not evaluated, and 3.2% missing data. Chemotherapy was used in 74.4% of the patients. Disease free survival was 89% at 73 months follow up. CONCLUSIONS: The paper presents a great number of cases and pioneers multicentre studies in paediatric ophthalmology and oncology in this country. Given the great number of patients in advanced stages and the variability on treatment schemes, it is evident that it is mandatory to work in a cooperative group and develop a national early detection programme as well as a treatment protocol which include all specialists involved in the care of patients with RB.

ROCK mediates thrombin's endothelial barrier dysfunction.

Thrombin-induced endothelial monolayer hyperpermeability is thought to result from increased F-actin stress fiber-related contractile tension, a process regulated by the small GTP-binding protein Rho. We tested whether this process was dependent on the Rho-associated protein kinase, ROCK, using a specific ROCK inhibitor, Y-27632. The effects of Y-27632 on thrombin-induced myosin light chain phosphorylation (MLCP) and tyrosine phosphorylation of p125 focal adhesion kinase (p125(FAK)) and paxillin were measured by Western blotting. F-actin organization and content were analyzed by digital imaging, and endothelial monolayer permeability was measured in bovine pulmonary artery endothelial cell (EC) monolayers using a size-selective permeability assay. Y-27632 enhanced EC monolayer barrier function due to a decline in small-pore number that was associated with increased EC surface area, reduced F-actin content, and reorganization of F-actin to beta-catenin-containing cell-cell adherens junctions. Although Y-27632 prevented thrombin-induced MLCP, stress fiber formation, and the increased phosphotyrosine content of paxillin and p125(FAK), it attenuated but did not prevent the thrombin-induced formation of large paracellular holes. These data indicate that thrombin-induced stress fiber formation is ROCK dependent. In contrast, thrombin-induced paracellular hole formation occurs in a ROCK-independent manner, whereas thrombin-induced monolayer hyperpermeability appears to be partially ROCK dependent.

RhoA inactivation enhances endothelial barrier function.

The modulation of endothelial barrier function is thought to be a function of contractile tension mediated by the cell cytoskeleton, which consists of actomyosin stress fibers (SF) linked to focal adhesions (FA). We tested this hypothesis by dissociating SF/FA with Clostridium botulinum exoenzyme C3 transferase (C3), an inhibitor of the small GTP-binding protein RhoA. Bovine pulmonary artery endothelial cell (EC) monolayers given C3, C3 + thrombin, thrombin, or no treatment were examined using a size-selective permeability assay and quantitative digital imaging measurements of SF/FA. C3 treatment disassembled SF/FA, stimulated diffuse myosin II immunostaining, and reduced the phosphotyrosine (PY) content of paxillin and 130- to 140-kDa proteins that included p125(FAK). C3-treated monolayers displayed a 60-85% decline in F-actin content and a 170-300% increase in EC surface area with enhanced endothelial barrier function. This activity correlated with reorganization of F-actin and PY protein(s) to beta-catenin-containing cell-cell junctions. Because C3 prevented the thrombin-induced formation of myosin ribbons, SF/FA, and the increased PY content of proteins, these characteristics were Rho dependent. Our data show that C3 inhibition of Rho proteins leads to cAMP-like characteristics of reduced SF/FA and enhanced endothelial barrier function.

VEGF stimulates tyrosine phosphorylation of beta-catenin and small-pore endothelial barrier dysfunction.

The purpose of this study was to test the hypothesis that tyrosine phosphorylation signaling events and protein kinase C (PKC) activation mediate vascular endothelial growth factor-A(165) (VEGF)-induced endothelial cell (EC) proliferation and barrier dysfunction in bovine pulmonary artery EC monolayers. A size-selective permeability assay showed that VEGF stimulated a delayed, prolonged (6-45 h), concentration-dependent (50-200 ng/ml, approximately 1-4 nM) increase in the number of predominantly small-"pore" transport pathways (<60 A) across EC monolayers. The tyrosine kinase inhibitor herbimycin A (HA) and the selective PKC inhibitor bisindolylmaleimide (BIM) prevented this phenomenon. After 6-24 h, VEGF-treated monolayers displayed an HA- and BIM-sensitive reorganization of beta-catenin adherens junctions with fingerlike projections and the loss of beta-catenin at sites of small paracellular hole formation. HA and BIM prevented the VEGF-induced increase in EC growth. HA blocked the VEGF-induced rapid and prolonged (10 min-45 h) increases in the phosphotyrosine (PY) contents of VEGF receptor 2, phospholipase C-gamma1, paxillin, and beta-catenin as well as approximately 140- and 128- to 117-kDa proteins, whereas BIM inhibited only the tyrosine phosphorylation of beta-catenin. These data suggest that VEGF initiates increased EC growth and chronic, small-pore endothelial barrier dysfunction by PY signaling through beta-catenin that depends on PKC.

The glomerular barrier fits a two-pore-and-fiber-matrix model: derivation and physiologic test.

Failure of the glomerular barrier causing proteinuria has been modeled chiefly by Chang, Deen, and Brenner. They have refined models from an isoporous filter to a mostly isoporous membrane, which during proteinuric disease opens up nondiscriminating shunts. This report extends these concepts by measuring a larger distribution of macromolecular tracer sizes and bringing in a fiber matrix. By clearance methods, glomerular sieving curves of relatively neutral tetramethyl rhodamine aminodextran from radii of 15 to over 80 A were obtained and fitted to theory. Two pores filled with matrix fit all data without exception, and no other model did. Five parameters described the curve in control rats and in proteinuric rats made so by albumin injections. From highest to lowest degree of confidence, these were small and large pore radii ros = 42.7 +/- 0.9 SEM A and rol = 926 +/- 156 A; small to large pore density ns/nl = 3859 +/- 942; mean fiber radius rf = 20.3 +/- 1. 1 A; and fiber void volume ratio epsilon = 0.52 +/- 0.05. In proteinuria, ros rose 13% (P = 0.002), nl increased 150% (P = 0.04), and there was a compensatory rise in rf of 26% (P = 0.002). The consideration of basement membrane and glycocalyx remain to be incorporated into the model. Moreover, the closeness of rf to ros indicates that fiber matrix theory may need modification for a complete description.

Soluble-protein and antigenic heterogeneity in axenic Blastocystis hominis isolates: pathogenic implications.

The protein profile and the antigenic cross-reactivity of 18 axenic isolates of Blastocystis hominis obtained from symptomatic patients with chronic diarrhea (14 isolates) showing no evidence of parasitic etiology and from patients with acute diarrhea attributable in 2 cases to Salmonella spp. were analyzed. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of soluble proteins showed the existence of a common profile composed of 31 bands, with molecular weights ranging between 24 and >200 kDa, and minor differences in the proteins of 149, 118, 106, 50, 48, 47, and 30 kDa. These differences allowed us to classify the strains into three related patterns (I-III). In an indirect immunofluorescence assay, all strains were serologically identical, but two related antigenic groups (1 and 2) were found in double-immunodiffusion and Western-blot studies. The isolates of protein patterns I and II belonging to antigenic group 1 were isolated from patients with chronic diarrhea, whereas the four isolates from patients with acute diarrhea were clustered in protein pattern III and in antigenic group 2. These results confirm the protein and antigenic heterogeneity of B. hominis and the existence of demes with different pathogenic roles.

H2O2 and genistein differentially modulate protein tyrosine phosphorylation, endothelial morphology, and monolayer barrier function.

The effects of hydrogen peroxide (H2O2) and the protein tyrosine kinase (PTK) inhibitor, genistein, to modulate protein tyrosine phosphorylation (PTP) and endothelial barrier function were examined in bovine pulmonary artery endothelial cell (EC) monolayers. H2O2 stimulated a concentration (100-800 microM) and time-dependent increase in the phosphotyrosine (PY) content of multiple (56-72, 93-97, 113-142, and 161-183 kDa) EC proteins. A size-selected solute permeability assay of EC monolayer barrier function showed that (200 microM) H2O2 elevated EC monolayer permeability to large solutes. This effect was associated with paracellular hole formation and a loss of beta-catenin immunostaining at these sites. In contrast, genistein (100 microM, 1 h) reduced basal PY protein content and reorganized F-actin to beta-catenin containing cell-cell junctions, enhancing endothelial monolayer barrier function. In addition, genistein prevented the H2O2-induced increases in tyrosine phosphorylation, monolayer permeability, and paracellular hole formation. These data suggest that H2O2 and genistein differentially regulate PTP, endothelial morphology, and monolayer barrier function.

In vitro encystation of Blastocystis hominis: a kinetics and cytochemistry study.

The kinetics of in vitro encystation of Blastocystis hominis was studied over 9 days. The differentiation between trophic (TF) and cyst forms (CF) was determined by differential counts before and after treatment with distilled water. A cytochemistry study using acridine orange and Calcofluor white wet-mount preparations of CF was carried out. The growth curves of TF and CF were related because the decrease in TF was followed by an increase in CF, and vice versa. The maximum of CF counts was obtained on the 6th or 7th day. Using the differential acridine orange stain, two subpopulations of CF, yellow-orange fluorescent cells or precysts and green fluorescent cells or cysts, were detected and their curves were also related. CF was stained by Calcofluor white, which suggested the existence of beta-(1-4)-glycosyl residues in the wall cysts of B. hominis.

Karyotypic diversity among Blastocystis hominis isolates.

Fifteen Blastocystis hominis strains, 13 axenic and 2 monoxenic, have been included in the present study. The chromosomal pattern was analyzed by the contour-clamped homogeneous electric-field (CHEF) system. The number of chromosomes detected ranged between 9 and 13, with sizes from 2200 kbp to 260 kbp. Eleven karyotypic profiles, with a common pattern constituted by 8 chromosomes of 2200, 1280, 890, 840, 700, 650, 540 and 260 kbp, were observed. The Jaccard index demonstrated that the similarity between isolates ranged from 0.5714 to 1. The different isolates were clustered in 3 karyotypes (A: 8 isolates; B: 6 isolates and C: 1 isolate). All isolates grouped in karyotype A presented a characteristic band of 730 kbp, whereas in the isolate of karyotype C the 810-kbp band was not observed.

[Clinical significance of Blastocystis hominis infection: epidemiologic study]. / Significación clínica de la infección por Blastocystis hominis: estudio epidemiológico.

BACKGROUND: To evaluate the frequency of Blastocystis hominis parasitation and to ascertain its role as an intestinal a prospective study during 18 months pathogen has been carried out. SUBJECTS AND METHODS: The study included 2,039 patients, which were classified in three groups (asymptomatic [group A], with suspicion of parasitosis [group B], with diarrhoea [group C]). In all cases a coproparasitological study was performed. In the group C the presence of non-parasitic enteropathogens was also investigated. In patients with B. hominis in the absence of other pathogens clinical and epidemiological characteristics were evaluated. Also, its was determined the morphology and quantification of parasites. RESULTS: Parasites were identified in 26.2% of population. B. hominis was identified in 336 patients (16.5%). The frequency of parasitation was superior in adults (p < 0.0001), with a slight predominance in the female sex. The rate of asymptomatic carriers was 3.3%. In 21 patients B. hominis (group C) was observed in absence of other enteropathogens. Statistical significant association was found between B. hominis, in absence of other pathogens and the presence of clinical manifestations (p < 0.0001), the most common of which were diarrhoea and abdominal pain. We did not find a statistically significant association between the number of B. hominis present and stool characteristics. The vacuolar form was the predominant morphological type. The ameboid form was observed only in diarrhoeal stools. CONCLUSIONS: B. hominis is the most frequent parasite found in faecal parasitological investigation. In absence of other causes, B. hominis must be considered as a pathogen.

Description of an improved method for Blastocystis hominis culture and axenization.

An improved method for Blastocystis hominis culture and axenization was developed in the present study. Stool samples were cultured in prereduced Boeck-Drbohlav NHI modified medium (with several modifications) supplemented with antibiotics (0.4% ampicillin, 0.1% streptomycin, 0.0006% amphotericin B). Axenization was performed by the combination of partial purification of B. hominis by Ficoll-metrizoic acid gradient and inoculation in fresh medium containing active antibiotics against remaining bacteria. A total of 25 strains were obtained by this procedure. The time required for axenization ranged between 3 and 5 weeks. The generation time of axenic strains ranged from 6.6 to 12.1 h (mean +/- SD 110.0 +/- 1.8 h) and the mean number of generations was 2.5 +/- 0.6 h per 24 h. The size of vacuolar and ameboid forms found in stools and in culture was similar. The special formulation of the medium used reduced the generation time and did not modify the cellular size as compared with fecal forms.