Outcomes of the PIRASOA programme, an antimicrobial stewardship programme implemented in hospitals of the Public Health System of Andalusia, Spain: an ecologic study of time-trend analysis.

OBJECTIVES: Inappropriate antimicrobial use favours the spread of resistance, and multidrug-resistant microorganisms (MDR) are currently of major concern. Antimicrobial stewardship programmes (ASPs) are essential for improving antibiotic use in hospitals. However, their impact on entire healthcare systems has not been thoroughly assessed. Our objective was to provide the results of an institutionally supported ASP involving 31 public hospitals in Andalusia, Spain. METHODS: We designed an ecologic time-series study from 1 January 2014 to 31 December 2017. Quarterly, data on indicators were collected prospectively, and feedback reports were provided. PIRASOA is an ongoing clinically based quality-improvement programme whose key intervention is the educational interview, regular peer-to-peer interventions between advisors and prescribers to reinforce the appropriate use of antibiotics. Seventy-two indicators were monitored to measure prescribing quality (inappropriate treatments), antimicrobial consumption (defined daily doses per 1000 occupied bed-days), incidence density of MDR per 1000 occupied bed-days and crude mortality rate associated with bloodstream infections. We used Joinpoint regression software to analyse the trends. RESULTS: The quality of antimicrobial prescribing improved markedly, and the inappropriate treatment rate was significantly lower, with quarterly percentage change (QPC) = -3.0%, p < 0.001. Total antimicrobial consumption decreased (QPC = -0.9%, p < 0.001), specifically carbapenems, amoxicillin/clavulanic acid, quinolones and antifungal agents, whereas antipseudomonal cephalosporin use increased. While the incidence of MDR showed a sustained decreasing trend (QPC = -1.8%; p 0.002), the mortality of patients with bloodstream infections remained stable (QPC = -0.2%, p 0.605). CONCLUSIONS: To date, the PIRASOA programme has succeeded in optimizing the use of antimicrobial agents and has had a positive ecologic result on bacterial resistance at level of an entire healthcare system.

Compliance with quality prescribing indicators linked to financial incentives: what about not incentivized indicators?: an observational study.

OBJECTIVE: The aims of this study were to investigate whether general practitioners (GPs) who complied with quality prescribing indicators included in the pay-for-performance programmes also complied with quality prescribing indicators which are not linked to incentives and to compare the prescribing behaviour between those GPs who showed compliance with quality prescribing indicators linked to financial incentives and those who did not. DESIGN AND METHODOLOGY: This was a descriptive cross-sectional study which was conducted in 2007 in the Aljarafe Primary Care Area (Andalusia, Spain) and involved 37 Health Care Centres and 176 GPs. The main outcome was the results of a comparison of six quality prescribing indicators linked to incentives and 14 quality prescribing indicators not linked to incentives. The chi-square test was used to compare qualitative variables. Quantitative variables were tested using Student's t test upon confirmation of normality. RESULTS: Those GPs showing compliance with the indicators included in the pay-for performance programme showed low levels of compliance with quality prescribing indicators that were unincentivised. With respect to compliance with the indicators not linked to financial incentives, we found no statistical difference between GPs who showed compliance with incentivised indicators (n = 57) and those showing non-compliance (n = 112) in terms of drug selection, with the exception of the selection of second- and third-line antibiotics and antihistamines, nor in terms of the appropriate use of drugs linked to patient's clinical conditions. CONCLUSIONS: The compliance of GPs showing compliance with quality prescribing indicators included in pay-for-performance programmes was not better than that of those who showed no compliance with other relevant quality prescribing indicators not linked to financial incentives.

Estatinas en pacientes sin enfermedad cardiovascular: una revisión crítica / Statins in patients without cardiovascular disease: a critical review

Se muestra una revisión crítica de los metaanálisis que evalúan la eficacia de las estatinas en la prevención primaria de la enfermedad cardiovascular. Se realizaron búsquedas en MEDLINE, EMBASE y Cochrane (período: enero 2005 a diciembre de 2011) de metaanálisis de en sayos clínicos dirigidos a estudiar el efecto de las estatinas en la prevención primaria de la enfermedad cardiovascular. Se utilizó el cuestionario PRISMA para evaluar la precisión y fiabilidad de los metaanálisis. Se seleccionaron un total de 9 metaanálisis (promedio de pacientes: 88.006). Cinco estudios encontraron beneficio en los eventos cardiovasculares mayores (rango del riesgo relativo [RR]: 0,69-0,85). Siete metaanálisis obtuvieron mejoras en los eventos coronarios mayores (rango RR: 0,61-0,77). No hubo concordancia en los resultados de mortalidad total, mortalidad coronaria y accidentes cerebrovasculares. Esta revisión crítica de los últimos metaanálisis sugiere un modesto beneficio de las estatinas en la prevención primaria de la enfermedad cardiovascular (AU)

It shows a critical review of meta-analysis assessing the efficacy of statins in primary prevention of cardiovascular disease. We searched MEDLINE, EMBASE and Cochrane (period: January 2000 to December 2011) for meta-analysis of randomized trials conducted to study the effect of statins in primary prevention of cardiovascular disease. We used PRISMA statement to evaluate accuracy and reliability ofmeta-analysis. We selected 9 meta-analysis (mean of patients: 88.006). Five studies found a benefit in mayor cardiovascular events (range of relative risk [RR]: 0.69-0.85). Seven meta-analysis obtained improvement in mayor coronary events (range of RR: 0.61-0.77). There was no agreement between the results of total mortality, coronary mortality and cerebrovascular events. This critical review of meta-analysis suggests a modest benefit of statins in a primary prevention set-up (AU)

Adecuación de la prescripción de beta-adrenérgicos de acción prolongada: resultados de una intervención en Atención Primaria / Quality prescribing of long-acting beta-agonists. Results of an intervention in Primary Care

Objetivo. Evaluar una intervención destinada a mejorar la adecuación de la prescripción de beta-adrenérgicos de acción larga (BAAL) en Atención Primaria. Material y métodos. Diseño: Estudio cuasi-experimental antes-después sin grupo control. Ámbito: Distrito de Atención Primaria (Servicio Andaluz de Salud). Sujetos: Médicos de familia con prescripciones de BAAL sin corticoides inhalados (CTi), que trabajaron más del 40% de los días hábiles del periodo estudiado. Unidad de estudio: Pacientes con prescripciones de BAAL sin CTi, seleccionados mediante muestreo aleatorio simple (fiabilidad 95%, precisión 5%). Intervenciones: Envío de carta y boletín con recomendaciones sobre uso adecuado de BAAL y la relación de pacientes con prescripciones inadecuadas. Variables: Adecuación de la prescripción de BAAL a las indicaciones autorizadas en fichas técnicas. En relación con los pacientes, se analizaron edad, sexo, tipo de BAAL y diagnóstico. Fuentes: Sistema de información de facturación de recetas e historia clínica informatizada. Resultados. Antes de la intervención, el porcentaje de inadecuación fue del 70,3%. Un 51,8% de los pacientes tenían una indicación de BAAL sin CTi no autorizada. El 18,5% no tenía registrado en su historia clínica diagnósticos relacionados con patologías respiratorias. Tras la intervención, el porcentaje de inadecuación pasó a ser del 4,5%, debido principalmente a la actualización de los tratamientos (retirada de BAAL o adición de CTi). Conclusiones. Existe un bajo grado de adecuación de la utilización de BAAL en Atención Primaria. El envío de material educativo con la relación de pacientes con prescripciones inadecuadas es una estrategia eficaz para mejorar los hábitos de prescripción en patologías respiratorias(AU)

Objective. To assess an intervention aimed to reduce inappropriate prescribing of long-acting beta-agonists (LABA) in Primary Care. Material and methods; Design Quasi-experimental pre/post study without control group. Setting: Aljarafe Primary Health Care Area (Seville, Spain). Participants: General practitioners with LABA prescriptions without inhaled corticosteroids (iCT), who worked more than 40% of working days in the study period. Study unit: Simple randomised sample of patients with LABA prescriptions without iCT. Interventions: Mailing educational material with recommendations on the appropriate use of LABA and a list of their patients with inappropriate prescriptions. Main measurement: Appropriateness of LABA prescriptions as indicated in the Product Summary Characteristics. Patient age, sex, type of LABA and diagnoses were analysed. Sources: An information system for billing computerized prescriptions and medical history. Results. Before intervention, prescriptions were inappropriate in 70.3% of patients, and 51.8% received LABA without iCT for unapproved conditions. A diagnosis associated with a respiratory condition was not recorded in the Computerised Medical Records of 18.5% of the patients. After intervention, the percentage of inappropriate prescriptions in the sample dropped to 4.5%, mainly due to a review of the treatment (LABA cessation or iCT addition). Conclusions. There is a high level of inappropriate use of LABA in Primary Health Care. Mailing educational materials combined with the list of patients with an inappropriate LABA prescription to general practitioners seems to be an effective strategy to improve quality prescribing in respiratory pathologies(AU)

[Quality prescribing of long-acting beta-agonists. Results of an intervention in Primary Care]. / Adecuación de la prescripción de beta-adrenérgicos de acción prolongada: resultados de una intervención en Atención Primaria.

OBJECTIVE: To assess an intervention aimed to reduce inappropriate prescribing of long-acting beta-agonists (LABA) in Primary Care. MATERIAL AND METHODS; DESIGN: Quasi-experimental pre/post study without control group. SETTING: Aljarafe Primary Health Care Area (Seville, Spain). PARTICIPANTS: General practitioners with LABA prescriptions without inhaled corticosteroids (iCT), who worked more than 40% of working days in the study period. Study unit: Simple randomised sample of patients with LABA prescriptions without iCT. INTERVENTIONS: Mailing educational material with recommendations on the appropriate use of LABA and a list of their patients with inappropriate prescriptions. MAIN MEASUREMENT: Appropriateness of LABA prescriptions as indicated in the Product Summary Characteristics. Patient age, sex, type of LABA and diagnoses were analysed. SOURCES: An information system for billing computerized prescriptions and medical history. RESULTS: Before intervention, prescriptions were inappropriate in 70.3% of patients, and 51.8% received LABA without iCT for unapproved conditions. A diagnosis associated with a respiratory condition was not recorded in the Computerised Medical Records of 18.5% of the patients. After intervention, the percentage of inappropriate prescriptions in the sample dropped to 4.5%, mainly due to a review of the treatment (LABA cessation or iCT addition). CONCLUSIONS: There is a high level of inappropriate use of LABA in Primary Health Care. Mailing educational materials combined with the list of patients with an inappropriate LABA prescription to general practitioners seems to be an effective strategy to improve quality prescribing in respiratory pathologies.

Acreditación de entrevistas individualizadas con los facultativos de Atención Primaria / Accreditation of individualized interviews for Primary Care professional

Una de las actividades realizadas por los farmacéuticos de Atención Primaria dirigidas a mejorar la calidad de la prescripción consiste en la entrevista cara a cara con los facultativos. La acreditación de estas entrevistas como actividad formativa aporta un valor añadido para el profesional entrevistado y para el farmacéutico, en cuanto a la incorporación de una metodología estructurada, el establecimiento de objetivos consensuados, el compromiso de colaboración mutua y el seguimiento periódico del perfil de prescripción. Esta metodología motiva al profesional a mejorar el perfil de prescripción ya que se enmarca en un contexto clínico y no puramente de gestión (AU)

One of the activities carried out by Primary Care pharmacists aimed at improving prescription quality is a face-to-face interview with the medical professionals. Accreditation of these interviews as a training activity provides added value for the professional interviewed and for the pharmacist, in regards to incorporation of a structured methodology, establishment of the objectives agreed on, commitment for mutual collaboration and periodic follow-up of the prescription profile. This methodology motivates the professional to improve the prescription profile since it puts it into a clinical context frame and not a purely management one (AU)

Sobre el cambio de atorvastatina por simvastatina. Respuesta / No disponible

No disponible

Development of controlled release formulations of alachlor in ethylcellulose.

The herbicide alachlor (2-chloro-N-(2,6-diethylphenyl)-N-(methoxymethyl)-acetamide) is frequently implicated in groundwater contamination. Microencapsulated alachlor should have reduced potential for leaching in the soil while maintaining effective biological activity. Microspheres of alachlor were prepared using ethylcellulose, according to the solvent evaporation method. The influence of formulation variables affecting the release rate of pesticide, such as the molecular weight of ethylcellulose, the amount of emulsifying agent, the pesticide/polymer ratio and the particle size, were investigated. The results showed that microspheres retarded the release of alachlor in different degrees. Pesticide/polymer ratio and particle size were the more important factors determining the alachlor release. Ethylcellulose microspheres may prove useful for the prolonged release of alachlor.

Enhancement of nasal absorption of insulin using chitosan nanoparticles.

PURPOSE: To investigate the potential of chitosan nanoparticles as a system for improving the systemic absorption of insulin following nasal instillation. METHODS: Insulin-loaded chitosan nanoparticles were prepared by ionotropic gelation of chitosan with tripolyphosphate anions. They were characterized for their size and zeta potential by photon correlation spectroscopy and laser Doppler anemometry, respectively. Insulin loading and release was determined by the microBCA protein assay. The ability of chitosan nanoparticles to enhance the nasal absorption of insulin was investigated in a conscious rabbit model by monitoring the plasma glucose levels. RESULTS: Chitosan nanoparticles had a size in the range of 300-400 nm, a positive surface charge and their insulin loading can be modulated reaching values up to 55% [insulin/nanoparticles (w/w): 55/100]. Insulin association was found to be highly mediated by an ionic interaction mechanism and its release in vitro occurred rapidly in sink conditions. Chitosan nanoparticles enhanced the nasal absorption of insulin to a greater extent than an aqueous solution of chitosan. The amount and molecular weight of chitosan did not have a significant effect on insulin response. CONCLUSIONS: Chitosan nanoparticles are efficient vehicles for the transport of insulin through the nasal mucosa.

Evaluation of hepatic antioxidant systems after intravenous administration of polymeric nanoparticles.

We have investigated the modifications of the levels of intracellular markers of the oxidative stress in hepatocytes, after single or repeated injections of poly(isobutyl cyanoacrylate) (PIBCA) and polystyrene (PS) nanoparticles. Nanoparticles were administered intravenously at single doses of 20 and 100 mg kg 1 for 14 days. Levels of reduced (GSH) and oxidized (GSSG) glutathione, superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CT) and the peroxidation of membrane lipids were measured. Single and repeated administration of PIBCA and PS nanoparticles induced a transient depletion of GSH and GSSG levels, a transient inhibition of SOD activity and a slight increase in CT activity. However, GPx activity was not modified and lipid peroxidation was not observed, suggesting that hepatocytes are not strongly affected by these modifications. Since nanoparticles do not distribute in hepatocytes, oxidative species could proceed from hepatic macrophages, activated after nanoparticle phagocytosis. It is unlikely that poly(alkyl cyanoacrylate) degradation products might be responsible for the oxidative attack because non-biodegradable PS nanoparticles induced the same effect. Uptake of polymeric nanoparticles by Kupffer cells in the liver induce modifications in hepatocyte antioxidant systems, probably due to the production of radical oxygen species. However, the depletion in glutathione was not great enough to initiate hepatocyte damage, since no changes in lipid peroxidation and reversible alterations were observed. This is an important factor to be considered in the use of polymeric nanoparticles as drug carriers.

Effect of polymeric nanoparticle administration on the clearance activity of the mononuclear phagocyte system in mice.

We investigated the consequences of acute and subacute administration of mice with polyisobutylcyanoacrylate (PIBCA), polyisohexylcyanoacrylate (PIHCA), poly(D,L-lactic) acid (PLA), and polystyrene (PS) nanoparticles on the mononuclear phagocyte system phagocytic function. This was done by measuring the clearance rate of colloidal carbon. Single administration of PIBCA and PIHCA (but not PLA and PS) nanoparticles reduced carbon clearance in both a time- and dose-dependent fashion. Since clearance of preopsonized carbon was normal, it was assumed that PIBCA and PIHCA nanoparticles deplete opsonins specific for carbon recognition. A decrease in plasma fibronectin levels resulting from nanoparticle administration suggested its implication in their removal from blood. However, fibronectin does not seem to be responsible for PIBCA and PIHCA blockade. Phagocytic function was preserved after repeated treatment with nanoparticles, probably as a result of increased Kupffer cell phagocytic activity and the contribution of spleen macrophages. Neither toxicity nor effects due to nanoparticle hepatic accumulation were observed.

Evaluation of liver toxicological effects induced by polyalkylcyanoacrylate nanoparticles.

Intravenous administration of drug-loaded polyalkylcyanoacrylate (PACA) nanoparticles is followed by a rapid uptake by the tissues of the reticuloendothelial system, mainly the liver. Nevertheless, it is so far unknown whether chronic administration of nanoparticles can lead to damage to the liver cells. We have studied the subacute toxicological effects of these drug carriers in a rat in vivo/ex vivo model. Nanoparticles were administered intravenously at a total dose of 200 mg/kg for 14 days (10 individual doses of 20 mg/kg). Hepatocytes were then isolated. Levels of alpha 1-acid glycoprotein secretion increased while albumin secretion decreased in hepatocytes from rats treated with PACA nanoparticles. In addition, glucose production due to the fructose metabolism was lowered. Treated rats induced a temporary increase and hyposialyation of serum alpha 1-acid glycoprotein. These effects were reversible 15 days after the treatment was concluded. Finally, the involvement of Kupffer cells and polymer degradation products was studied in vitro. Modifications of hepatocyte protein synthesis related to the treatments were only observed when direct contact between nanoparticles and hepatocytes existed. Kupffer cells and polymer degradation products did not mediate the hepatocyte response to nanoparticles in vitro. In conclusion, modifications in hepatic function after chronic administration of PACA nanoparticles have been detected by the use of very sensitive models for detecting hepatoxicity. These effects were, however, found to be reversible when the treatment was stopped.