Development of antibiotic loaded biodegradable matrices to prevent superficial infections associated to total knee arthroplasty.

Development of a pharmaceutical form for the superficial infections related with arthroplasties would be helpful for clinical practice. In this context, we set out to evaluate ciprofloxacin and gentamicin elution from systems based on chitosan. Films and semisolid hydrogels containing chitosan alone (2%) or in combination with gelatin (6%) or different proportions (from 12% to 36%) of tetrakis-(hydroxymethyl)-phosphonium-chloride (THPC) were tested as delivery systems. Different antibiotic doses were assayed (0.5 mg/cm2,1 mg/cm2 and 2 mg/cm2). Antibiotic release was studied for each formulation. In vitro cytocompatibility studies and a simulation exercise for bioactivity evaluation were performed. Samples containing chitosan or chitosan-gelatin released the antibiotics at very high rates. On the contrary, ciprofloxacin released was kept for 6 days from THPC-chitosan films and hydrogels. From hydrogel formulations release could be changed by varying the percentage of THPC. The system containing 12%-THPC-chitosan with 2 mg/cm2 of ciprofloxacin showed that 100% of patient would be covered during 72 h post-surgery. The concentration of 12%-THPC did not show cytotoxicity in NIH3T3 mouse fibroblasts after 48 h. THPC is suitable as crosslinker for chitosan when ciprofloxacin is incorporated showing a sustained release during 6 days.

Antibiotic-loaded Bone Cement as Prophylaxis in Total Joint Replacement.

One of its most serious complications associated with arthroplasty is the development of infections. Although its prevalence is only between 0.5% and 3%, in some cases it can lead to death. Therefore, an important challenge in joint surgery is the prevention of infections when an arthroplasty is performed. The use of antibiotic-loaded cements could be a suitable tool due to numerous advantages. The main advantage of the use of antibiotic loading into bone cement derives directly from antibiotic release in the effect site, allowing achievement of high concentrations at the site of action, and minimal or no systemic toxicity. This route of administration was first described by Buchholz and Engelbrecht. In the case of infection treatment, this is an established method and its good results have been confirmed. However, its role in infection prevention, and, therefore, the use of these systems in clinical practice, has proved controversial because of the uncertainty about the development of possible antibiotic resistance after prolonged exposure time, their effectiveness, the cost of the systems, toxicity and loosening of mechanical properties. This review discusses all these topics, focusing on effectiveness and safety, antibiotic decisions, cement type, mixing method, release kinetics and future perspectives. The final objective is to provide the orthopaedic surgeons the right information in their clinical practice based on current evidence.

Análisis de la calidad y seguridad de la información de aplicaciones móviles en prevención terciaria / Quality and security analysis of mobile applications in tertiary prevention

Objetivo: Analizar la calidad y seguridad de la información de las aplicaciones móviles en la App Store de Apple® destinadas a prevención terciaria. Material y métodos: Estudio observacional transversal de las aplicaciones móviles más populares en la categoría de medicina disponibles en Apple Store® a día de 21 de diciembre de 2014. Las aplicaciones fueron evaluadas con los criterios establecidos en el programa AppSaludable. Se seleccionaron aquellos criterios relacionados con la evaluación de la calidad y seguridad de la información. Resultados: De las 160 aplicaciones recogidas, sólo 12 aplicaciones estaban incluidas en la prevención terciaria. Todas las aplicaciones recuperadas estaban relacionadas con la adherencia, diabetes, hipertensión y alergia. Las aplicaciones desarrolladas por equipos multidisciplinares fueron las que presentaron mayor rigor en su información, Conclusiones: La presencia de un profesional sanitario como colaborador de la aplicación parece mejorar la calidad de la información (AU)

Objective: Analyze quality and information security of mobile applications in the Apple App Store® used for tertiary prevention. Methods: Cross-sectional study of the most popular mobile applications in the category of medicine available in Apple Store® to date of 21 December 2014. Criteria established in the AppSaludable program and related to quality and information security criteria were used for applications’ assessment. Results: Of the 160 applications found, only 12 applications were included in tertiary prevention. They were related to adherence, diabetes, hypertension and allergy. Applications developed by multidisciplinary teams showed more rigorous information. Conclusion: The presence of a health professional as a team member would improve information quality (AU)

Pirfenidone experience in mild-to-moderate Idiopathic Pulmonary Fibrosis in a General Hospital / Experiencia con pirfenidona en fibrosis pulmonar idiopática leve-moderada en un hospital general

This article present the experience and outcomes of patients treated with pirfenidone. FVC and DLCO parameters during 12 months were collected in patients treated with pirfenidone. Eight of the ten patients continued treatment until month 12. 7 patients presented at 12 months an adequate response treatment, 1 patient did not achieve therapeutic targets established (improvement or stability). At week 52, our patients had a mean of change in FVC(%) of -2.38±6.93%; patients of clinical trials showed -5.2% and -8.3% treated with pirfenidone and placebo respectively. Higher incidence of adverse effects was observed than clinical trials. Our results show that pirfenidone is a well-tolerated drug, whose toxicity can be controlled by dose adjustment, and it is effective in mild-moderate IPF. Due to no proven effectiveness and safety in medium / long term and the high economic impact, it is necessary to identify those patients who may get more clinical benefits (AU)

Este artículo presenta la experiencia y los resultados de pacientes tratados con pirfenidona. Se obtuvieron parámetros de FVC y DLCO durante 12 meses en pacientes tratados con pirfenidona. Ocho de los diez pacientes continuaron el tratamiento hasta el mes 12. 7 pacientes presentaron a los 12 meses un tratamiento de respuesta adecuada, 1 paciente no logró objetivos terapéuticos establecidos (mejoría o estabilidad). En la semana 52, nuestros pacientes tenían una media de cambio en FVC(%) de - 2.38±6.93%; los pacientes de los ensayos clínicos demostraron-5.2% y- 8.3% tratados con pirfenidona y placebo respectivamente. Se observó mayor incidencia de efectos adversos de los ensayos clínicos. Nuestros resultados muestran que pirfenidona es un fármaco bien tolerado, cuya toxicidad puede ser controlada mediante el ajuste de la dosis, y es eficaz en IPF de leve a moderada. Debido a la no probada eficacia y seguridad a medio/largo plazo y alto impacto económico, es necesario identificar a aquellos pacientes que pueden obtener mayores beneficios clínicos (AU)

Evaluación de la bioactividad de ciprofloxacino y vancomicina incorporados en cementos óseos poliacrílicos / Evaluation of ciprofloxacin and vancomycin bioactivity loaded in bone cements

La inclusión de antibióticos en el cemento óseo destinado a la fijación mecánica de las prótesis constituye un sistema de liberación local de antibiótico que permite minimizar la prevalencia y la gravedad de las reacciones adversas que pueden desencadenar los fármacos cuando éstos se administran por vía sistémica. El objetivo del trabajo es estudiar el mecanismo y cinética de liberación in vitro de ciprofloxacino y vancomicina incorporados en diferentes cementos óseos comerciales y evaluar la bioactividad mediante un ejercicio de simulación farmacocinética. Se prepararon mezclas de los cementos de estudio con ciprofloxacino clorhidrato y vancomicina (40:0,5:0,5). Los estudios de liberación se realizaron en agitación continua en solución salina de tampón fosfatos, pH = 7,4, durante dos meses a 37ºC. El análisis estadístico de las cantidades de antibiótico liberadas acumuladas y las velocidades de elución se realizó mediante ANOVA. Con el fin estudiar la bioactividad, se realizó una simulación de Monte Carlo. La cantidad total liberada de ciprofloxacino en un periodo de 8 semanas fue de 0,29 ± 0,06 mg desde los cementos Palacos(R), 0,44 ± 0,06mg LimaCMT1(R) y 0,18 ± 0,04 mg Simplex(R). La cantidad total de vancomicina liberada en 24 horas fue de 0,34 ± 0,17mg desde el cemento Palacos(R), 0,68 ± 0,16 mg LimaCMT1(R) y 0,17 ± 0,02 mg Simplex(R). Transcurrido este tiempo la liberación cesó. El estudio de simulación, muestra que durante las primeras 72 horas, la cobertura antibiótica dependería tanto del cemento elegido como de la sensibilidad del microorganismo y el tiempo postquirúrgico. En tiempos posteriores, es de prever que la bioactividad local aumente

Antibiotic loaded bone cement used in prosthesis fixing, is a local release form that minimizes the prevalence and the complications that the antibiotics would unleash when administered intravenously. The aim of this work is to study in vitro release kinetics of ciprofloxacin and vancomycin loaded in different commercial cements and evaluate the bioactivity through a simulation exercise pharmacokinetics. Samples were prepared with commercial bone cement and ciprofloxacin and vancomycin hydrochloride (40:0,5:0,5). Release study were carried out under stirring in phosphate buffer, pH=7,4, for two months at 37ºC. The antibiotic amount and elution rate, were compared using ANOVA. In order to study the bioactivity, Monte Carlo simulation was performed. The ciprofloxacin released from samples for 8 weeks was 0.29 ± 0.06 mg from the Palacos(R) cements, 0.44 ± 0.06 mg from LimaCMT1® and 0.18 ± 0.04 mg from Simplex(R). The vancomycin released for 24 hours was 0.34 ± 0.17 mg from Palacos(R) cement, 0.68 ± 0.16 mg from LimaCMT1(R) and 0.17 ± 0.02 mg from Simplex(R). After this time the release stopped. The simulation study shows that during the first 72 hours, the antibiotic coverage would depends on the bone cement, the sensitivity of the microorganism and postoperative day. At subsequence times, it is expected that local bioactivity increases

Study of the Influence of Bone Cement Type and Mixing Method on the Bioactivity and the Elution Kinetics of Ciprofloxacin.

The objectives of this study were to examine ciprofloxacin release from three trademarks of bone cements (Simplex®, Lima® and Palacos®) and its bioactivity using as variables, the mixing method, the chemical form of the antibiotic and the antibiotic combination. The antibiotic amount released in base form represents 35% of antibiotic amount released when hydrochloride form is incorporated. Moreover, the combination (vancomycin and ciprofloxacin) shows a stronger release (132%) than hydrochloride ciprofloxacin alone. Three cements show equal drug release profile (P > 0.05). A bioactivity simulation exercise showed that until 72 hours post-surgery, ciprofloxacin concentrations in the implant would be higher than 0.1 µg/mL in 100% of the patients. After drain removal, it is expected that bioactivity would increase since drug clearance from implant would decrease.