La enfermedad por virus Zika en España. Resultados de la vigilancia y epidemiología de los casos notificados en 2015-2017 / Zika virus disease in Spain. Surveillance results and epidemiology on reported cases, 2015-2017

Introducción y objetivo: La enfermedad por virus Zika constituye un reto para la salud pública por su rápida expansión y sus potenciales complicaciones fetales. En España la enfermedad por virus Zika es importada, aunque la presencia de Aedes albopictus no descarta su transmisión autóctona. La enfermedad por virus Zika y los casos congénitos se vigilan desde 2016. El objetivo es conocer su epidemiología y el resultado de la gestación en las embarazadas. Material y métodos: Estudio descriptivo de casos notificados a la Red Nacional de Vigilancia Epidemiológica (RENAVE) entre el 30/11/2015 y el 31/12/2017. La definición de caso y la encuesta se recogen en los protocolos de la RENAVE. Las variables fueron: fecha, comunidad autónoma (CC.AA.), clasificación, modo y lugar de infección, variables sociodemográficas, clínicas, microbiológicas, embarazo y su evolución. Se realizó un análisis descriptivo de los casos y su distribución según el resto de variables. Resultados: Diecisiete CC.AA. notificaron 512 casos, de los cuales 507 fueron no congénitos: 327 (64,5%) eran mujeres (52,5% en edad fértil); 403 casos (79,5%) correspondieron a 2016 y 193 (38,1%) residían en CC.AA. colonizadas por A. albopictus entre mayo y octubre. El 96,1% de casos importados se infectaron en América y el 51,7% en visitas familiares. Se detectaron 3 casos de infección congénita en 77 embarazadas. Conclusiones: La evolución de notificaciones mostró paralelismo con la de la epidemia en América. El grupo más numeroso de viajeros fue el de mujeres jóvenes que fueron a Latinoamérica en visitas familiares. El seguimiento de las embarazadas permitió identificar complicaciones fetales

Introduction and objective: Zika virus disease is a challenge for public health due to its rapid spread and potential foetal complications. Although it is imported in Spain, there is a risk of autochthonous transmission due to Aedes albopictus presence. Zika disease and congenital cases have been under surveillance since 2016. The objective of this study is to explore the epidemiology of disease and pregnancies result. Material and methods: A descriptive study was carried out into cases reported to the National Surveillance Network (RENAVE) during the 30/11/2015 to 31/12/2017 period. The case definition and the survey are included in the RENAVE protocol. The variables were: date; notifying region (Autonomous Community (AC)); pregnancy and its evolution; case classification; mode of transmission; country or region of infection; socio-demographical, clinical and microbiological data. A descriptive analysis of the cases and their distribution according to the other variables was carried out. Results: A total of 512 cases were reported by 17 ACs. 507 were non-congenital, of which 327 (64.5%) were women (52.5% of childbearing age). 403 cases (79.5%) corresponded to 2016 and 193 (38.1%) resided in regions with A. albopictus presence between May and October. 96.1% of imported cases were infected in America (51.7% while visiting relatives). Three cases (3.9%) of congenital Zika virus infection were detected among 77 pregnant women. Conclusions: The evolution of reported cases was in accordance with that of the epidemic in America. The largest group of travellers was young women who travelled to Latin America on family visits. Pregnancy monitoring resulted in the identification of Zika related foetal complications

Zika virus disease in Spain. Surveillance results and epidemiology on reported cases, 2015-2017. / La enfermedad por virus Zika en España. Resultados de la vigilancia y epidemiología de los casos notificados en 2015-2017.

INTRODUCTION AND OBJECTIVE: Zika virus disease is a challenge for public health due to its rapid spread and potential foetal complications. Although it is imported in Spain, there is a risk of autochthonous transmission due to Aedes albopictus presence. Zika disease and congenital cases have been under surveillance since 2016. The objective of this study is to explore the epidemiology of disease and pregnancies result. MATERIAL AND METHODS: A descriptive study was carried out into cases reported to the National Surveillance Network (RENAVE) during the 30/11/2015 to 31/12/2017 period. The case definition and the survey are included in the RENAVE protocol. The variables were: date; notifying region (Autonomous Community (AC)); pregnancy and its evolution; case classification; mode of transmission; country or region of infection; socio-demographical, clinical and microbiological data. A descriptive analysis of the cases and their distribution according to the other variables was carried out. RESULTS: A total of 512 cases were reported by 17 ACs. 507 were non-congenital, of which 327 (64.5%) were women (52.5% of childbearing age). 403 cases (79.5%) corresponded to 2016 and 193 (38.1%) resided in regions with A. albopictus presence between May and October. 96.1% of imported cases were infected in America (51.7% while visiting relatives). Three cases (3.9%) of congenital Zika virus infection were detected among 77 pregnant women. CONCLUSIONS: The evolution of reported cases was in accordance with that of the epidemic in America. The largest group of travellers was young women who travelled to Latin America on family visits. Pregnancy monitoring resulted in the identification of Zika related foetal complications.

Climate induced human demographic and cultural change in northern Europe during the mid-Holocene.

The transition from hunter-gatherer-fisher groups to agrarian societies is arguably the most significant change in human prehistory. In the European plain there is evidence for fully developed agrarian societies by 7,500 cal. yr BP, yet a well-established agrarian society does not appear in the north until 6,000 cal. yr BP for unknown reasons. Here we show a sudden increase in summer temperature at 6,000 cal. yr BP in northern Europe using a well-dated, high resolution record of sea surface temperature (SST) from the Baltic Sea. This temperature rise resulted in hypoxic conditions across the entire Baltic sea as revealed by multiple sedimentary records and supported by marine ecosystem modeling. Comparison with summed probability distributions of radiocarbon dates from archaeological sites indicate that this temperature rise coincided with both the introduction of farming, and a dramatic population increase. The evidence supports the hypothesis that the boundary of farming rapidly extended north at 6,000 cal. yr BP because terrestrial conditions in a previously marginal region improved.

Association of BRCA1 germline mutations in young onset triple-negative breast cancer (TNBC)

BACKGROUND: BRCA1-associated breast cancers have been associated to a triple-negative phenotype. The prevalence of BRCA1 germline mutations in young onset TNBC based on informativeness of family history has not been reported. PATIENTS AND METHODS: From January 2008 to May 2009 were collected blood and tumor samples from patients with TNBC younger than 50 years and without a family history of breast and ovarian cancer in first- and second-degree relatives. Analysis of BRCA1 germline mutations was made. Age at diagnosis and informativeness of family history (presence of female in first- and second-degree relatives alive until age 45) was collected in all cases. Immunohistochemistry of basal-like features was performed centrally in all available tumors. RESULTS: Seven pathogenic mutations were detected in 92 patients (7.6 %), two of them in patients younger than 35 years (28.6 %) (Fisher's exact test, p = 0.631). Three non-classified variants were detected (3.2 %). Family history was informative in two patients with a pathogenic mutation (28.6 %) and not informative in five (71.4 %) (Fisher's exact test, p = 0.121). Of the seven patients with a pathogenic mutation, four had a basal-like phenotype. CONCLUSION: Patients with apparently sporadic TNBC younger than 50 years and a non-informative family history are candidates for germline genetic testing of BRCA1 (AU)

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Association of BRCA1 germline mutations in young onset triple-negative breast cancer (TNBC).

BACKGROUND: BRCA1-associated breast cancers have been associated to a triple-negative phenotype. The prevalence of BRCA1 germline mutations in young onset TNBC based on informativeness of family history has not been reported. PATIENTS AND METHODS: From January 2008 to May 2009 were collected blood and tumor samples from patients with TNBC younger than 50 years and without a family history of breast and ovarian cancer in first- and second-degree relatives. Analysis of BRCA1 germline mutations was made. Age at diagnosis and informativeness of family history (presence of female in first- and second-degree relatives alive until age 45) was collected in all cases. Immunohistochemistry of basal-like features was performed centrally in all available tumors. RESULTS: Seven pathogenic mutations were detected in 92 patients (7.6 %), two of them in patients younger than 35 years (28.6 %) (Fisher's exact test, p = 0.631). Three non-classified variants were detected (3.2 %). Family history was informative in two patients with a pathogenic mutation (28.6 %) and not informative in five (71.4 %) (Fisher's exact test, p = 0.121). Of the seven patients with a pathogenic mutation, four had a basal-like phenotype. CONCLUSION: Patients with apparently sporadic TNBC younger than 50 years and a non-informative family history are candidates for germline genetic testing of BRCA1.

The fate of nanocarriers as nanomedicines in vivo: important considerations and biological barriers to overcome.

Many pharmaceuticals on the market suffer from two significant limitations to their activity: lack of specificity toward the pathological site and poor aqueous solubility. Both factors therefore require the application of a large total dose of a drug to achieve high local concentration, causing numerous off-target toxic effects. Consequently, the grand aim of targeted drug delivery - the often-referred "magic bullet" - promises to improve drug concentration at the target site and maximize therapeutic response. Nanomaterial drug delivery systems have been explored extensively in the recent years for just this purpose. In the field of medicine, nanocarriers (NCs) have the potential to improve the biodistribution and pharmacokinetic characteristics of drugs, thereby reducing side effects while improving the therapeutic effect of drugs. Many nanomaterials are exquisitely designed and possess potent properties, yet it is extremely important to note that a general understanding of the interaction of nanomaterials with biological systems is essential for any such model properties to be effective in vivo, since the body presents a host of biological 'barriers' that will be encountered drug NCs. This review offers a general overview of the different biological obstacles that a NC must negotiate before it can carry out its desired role as a medicinal agent. From this standpoint we suggest aspects that should be considered for the rational design of novel nanomaterials possessing physicochemical properties that are appropriate for therapeutic or theragnostic applications.

Application of magnetically induced hyperthermia in the model protozoan Crithidia fasciculata as a potential therapy against parasitic infections.

BACKGROUND: Magnetic hyperthermia is currently a clinical therapy approved in the European Union for treatment of tumor cells, and uses magnetic nanoparticles (MNPs) under time-varying magnetic fields (TVMFs). The same basic principle seems promising against trypanosomatids causing Chagas disease and sleeping sickness, given that the therapeutic drugs available have severe side effects and that there are drug-resistant strains. However, no applications of this strategy against protozoan-induced diseases have been reported so far. In the present study, Crithidia fasciculata, a widely used model for therapeutic strategies against pathogenic trypanosomatids, was targeted with Fe(3)O(4) MNPs in order to provoke cell death remotely using TVMFs. METHODS: Iron oxide MNPs with average diameters of approximately 30 nm were synthesized by precipitation of FeSO(4) in basic medium. The MNPs were added to C. fasciculata choanomastigotes in the exponential phase and incubated overnight, removing excess MNPs using a DEAE-cellulose resin column. The amount of MNPs uploaded per cell was determined by magnetic measurement. The cells bearing MNPs were submitted to TVMFs using a homemade AC field applicator (f = 249 kHz, H = 13 kA/m), and the temperature variation during the experiments was measured. Scanning electron microscopy was used to assess morphological changes after the TVMF experiments. Cell viability was analyzed using an MTT colorimetric assay and flow cytometry. RESULTS: MNPs were incorporated into the cells, with no noticeable cytotoxicity. When a TVMF was applied to cells bearing MNPs, massive cell death was induced via a nonapoptotic mechanism. No effects were observed by applying TVMF to control cells not loaded with MNPs. No macroscopic rise in temperature was observed in the extracellular medium during the experiments. CONCLUSION: As a proof of principle, these data indicate that intracellular hyperthermia is a suitable technology to induce death of protozoan parasites bearing MNPs. These findings expand the possibilities for new therapeutic strategies combating parasitic infection.

Condiciones de transporte de medicamentos en misiones internacionales de las Fuerzas Armadas. Diseño de un estudio de estabilidad especifico para operaciones / Conditions of drugs transportation in international missions of the Armed Forces. Design of a specific stability study of operations

Introducción: El abastecimiento de los recursos sanitarios es una parte crítica del apoyo sanitario en las operaciones de nuestras Fuerzas Armadas. El transporte de medicamentos y productos sanitarios se realiza por vía aérea. La regulación del medicamento exige que las condiciones de almacenamiento y transporte se efectúen de modo que su calidad se mantenga íntegra durante el periodo de validez del mismo, por lo que un trasporte de calidad no debe generar riesgos sobre los medicamentos, derivados de exposiciones a elevados grados de calor, frío, humedad, otros factores negativos, microorganismos o plagas. Podremos caracterizar, por tanto, las condiciones ambientales asociadas a un transporte mediante la medición de la Temperatura y la Humedad Relativa. Objetivo: Cualificación del transporte de medicamentos. Diseño de un Estudio de Estabilidad específico para Operaciones (EEO). Material y métodos: Se efectúa una monitorización de los transportes efectuados al ROLE 2 E (Herat) durante un ciclo anual. Se utilizan Data logger: LOG 32 con rango de medición -40 a +70°C y 0 a 100% HR y programa para cálculo de los parámetros de cualificación de los envíos, para la cualificación y evaluación del transporte. Distintos aparatos de laboratorio y sus correspondientes métodos para el ensayo de estabilidad. Paquete estadístico SPSS versión 15 para el tratamiento de resultados Las temperaturas máximas y mínimas registradas en los 18 transportes monitorizados, a lo largo de 13 meses, muestran valores que no rebasan los límites establecidos en el ensayo de estabilidad propuesto. La HR media se mantuvo, de manera habitual, durante el periodo monitorizado, en valores inferiores al 50%. Los resultados analíticos de los medicamentos sometidos al ensayo de estabilidad, basado en la aplicación de oscilaciones térmicas en diferentes ciclos, arrojan valores que se sitúan dentro de las especificaciones del producto terminado, no apreciándose diferencias significativas entre los productos testigo y los sometidos a variaciones térmicas, demostrándose que las oscilaciones de temperatura entre 2ºC y 50ºC establecidas para el ensayo, durante un periodo de 7 días, no afectan a las características de los medicamentos seleccionados en este estudio. Conclusiones: Evaluadas las características ambientales del transporte durante un ciclo anual, no se aprecian diferencias estacionales destacables entre los diferentes envíos. Desde el punto de vista ambiental, el transporte de medicamentos a Role 2E (Herat), resulta cualificado, demostrándose la calidad del mismo. Todos los elaborados fabricados en el Centro Militar de Farmacia de la Defensa, seleccionados en este estudio y que han sido sometidos al nuevo ensayo de estabilidad, se mantienen dentro de las especificaciones, por lo que no se observa alteración en la calidad de los mismos. Para el control del transporte de medicamentos a las Misiones Internacionales, se considerarán condiciones seguras de transporte, oscilaciones térmicas comprendidas entre 2°C y 50°C durante al menos 7 días (AU)

Introduction: The supply of medical materiel and pharmaceuticals is a critical part of medical support in our military operations. The transport of medical materiel and drugs is provided by Air. The drug regulation requires performed storage and transportation conditions so that its quality are maintained during the whole period of drug validity, so a quality transportation should not generate risks to drugs derived from high temperature, cold, humidity or other negative factors, such as microorganisms or pests. We characterize, therefore, the environmental conditions associated to the transport with the measurement of the temperature and relative humidity. Objective: Qualification of drug transport. Design of a specific stability study to Operations (SSO). Materials and Methods: Monitoring is performed for the drugs transport ROLE 2 E (Herat) during an annual cycle. Data logger are used: LOG 32 with measurement range -40 to +70 °C and 0 to 100% RH and program for calculating the parameters of qualified shipments for the qualification and evaluation of transport. Different laboratory equipments and their corresponding methods for stability testing. SPSS version 15 for the treatment of results. Results: The maximum and minimum recorded temperatures in the 18 transports monitored, during 13 months, show values that not exceed the limits in the proposed test stability. Mean relative humidity was maintained on a regular basis during the period monitored, at values below 50%. The analytical results of the drugs tested against stability, based on the of fluctuations temperature application in different cycles, give values that are within the specifications of the finished product, without significant differences between control products and the products subjected to thermal variations, showing that the oscillations of 2 °C and 50 °C set for the trial, during a period of 7 days, do not affect the drugs characteristics selected in this study Conclusions: Have been evaluated environmental characteristics of transportation during an annual cycle, showing there are not remarkable seasonal differences between the various shipments. From the environmental standpoint, drugs transportation to Role 2(Herat) is qualified. All medicines produced by the Military Pharmacy Center of Defense, choosen in this study and which have been subjected on the new stability test, remain within specification, by what alteration is not observed in the quality of the same ones. In order to control the drugs transport to the International Mission, temperature fluctuations between 2 ºC and 50 °C during at least 7 days would be considered safe conditions (AU)

Functionalized Fe3O4@Au superparamagnetic nanoparticles: in vitro bioactivity.

The interaction of nanoparticles with cells has been a focus of interest during the past decade. We report the fabrication and characterization of hydrosoluble Fe3O4@Au nanoparticles functionalized with biocompatible and fluorescent molecules and their interaction with cell cultures by visualizing them with confocal microscopy. Gold covered iron oxide nanoparticles were synthesized by reducing metal salts in the presence of oleylamine and oleic acid. The functionalization of these particles with an amphiphilic polymer provides a water soluble corona as well as the possibility to incorporate different molecules relevant for bio-applications such as poly(ethylene glycol), glucose or a cadaverine derived dye. The particle size, and the presence of polymer layers and conjugated molecules were characterized and confirmed by transmission electron microscopy, thermogravimetric measurements and infrared spectroscopy. A complete magnetic study was performed, showing that gold provides an optimum coating, which enhances the superparamagnetic behaviour observed above 10-15 K in this kind of nanoparticle. The interaction with cells and the cytotoxicity of the Fe3O4@Au preparations were determined upon incubation with the HeLa cell line. These nanoparticles showed no cytotoxicity when evaluated by the MTT assay and it was demonstrated that nanoparticles clearly interacted with the cells, showing a higher level of accumulation in the cells for glucose conjugated nanoparticles.

Gestión del riesgo en la transferencia de procesos productivos. Aplicación a la fabricación de comprimidosde oseltamivir en la pandemia de gripe A / Risk management in the transfer of manufacturing processes. Application to the manufacturing of oseltamivir tablets in the swine flu pandemic

Introducción: La gestión de riesgos aplicada a la industria farmacéutica, a través de su identificación, valoración y control, es una herramienta útil para garantizar la calidad del medicamento. La declaración por la Organización Mundial de la Salud en el año 2.009, de la pandemia provocada por el virus de la influenza H1N1, origina la necesidad de transformar en medicamento parte de las reservas estratégicas de fosfato de oseltamivir, pertenecientes al Ministerio de Sanidad y Política Social y a las Comunidades Autónomas. Debido a esta circunstancia, se dibuja, un nuevo escenario de actuación de los Servicios Farmacéuticos de la Defensa, bajo la tutela de la Agencia Española de Medicamentos y Productos Sanitarios. Objetivo: La aplicación de los principios de gestión del riesgo, posibilitará una rápida adaptación de la tecnología necesaria para la fabricación de comprimidos de fosfato de oseltamivir. Se realiza la evaluación del riesgo asociado a las diversas fases del proceso y se establecen determinados parámetros de control sobre la calidad final del medicamento producido. Material y Método: Se aplica el Análisis modal de fallos modales y efectos y su criticidad para establecer y evaluar los posibles riesgos del proceso productivo y se efectúan las correspondientes determinaciones analíticas referidas a la calidad del producto obtenido. Resultados: Los riesgos asociados al proceso son establecidos y evaluados. La media del contenido de los comprimidos y del porcentaje de disolución de los mismos a los 20 minutos es de 101,9 % y 102,5% respectivamente, cumpliendo todos los lotes fabricados el ensayo de evaluación de la contaminación microbiológica. Los resultados obtenidos para los lotes en las variables objeto de validación del proceso (peso de los comprimidos y porcentajes de principio activo, de homogeneidad de la mezcla y de disolución) cumplen las especificaciones establecidas y no se aprecian diferencias significativas entre los diferentes lotes (p>0,05). Conclusiones: Los resultados obtenidos corroboran el éxito de la transferencia del proceso productivo de comprimidos de fosfato de oseltamivir a las instalaciones y equipos disponibles, así como la consecución de un proceso robusto y repetitivo, que proporciona un medicamento ajustado a las especificaciones de calidad establecidas (AU)

Introduction: Risks management applied to the pharmaceutical industry, through their identification, evaluation and control, is a useful tool to guarantee drug quality. The declaration of swine flu H1N1 pandemic in 2009 by the World Health Organization, resulted in the need to transform into tablets part of the strategic reserves of oseltamivir phosphate of the Ministry of Health and Social Policy and the Autonomous Communities. This situation led to a change in the activity of the Defense Pharmaceutical Service under the auspices of the Spanish Agency for Medicines and Health Products. Objective: Applying the principles of risk management makes possible a fast adaptation of the technology to manufacture the oseltamivir phosphate tablets. We evaluated the risk associated to the different stages of the process and established particular control parameters of the final quality of the product. Materials and Methods: We applied the modal analysis of failures and effects and their criticality to establish and evaluate possible risks of the manufacturing process and carried out the necessary lab tests to check the quality of the product. Results: The risks associated to the process are established and evaluated. The average tablet content and the dissolution percentage at 20 minutes is 101.9% and 102.5%, respectively. All batches passed the microbiological contamination control. The results obtained for all batches in the validating variables of the process (weight of the tablets, percentages of active principle, homogeneity of the mix and dissolution) fulfill the required specifications and there are not significant differences among the different batches (p>0,05). Conclusions: The results confirm the successful transfer of the manufacturing process of the oseltamivir phosphate tablets to the facilities and equipment available, as well as the achievement of a robust and repetitive process that provides a drug fulfilling the required quality specifications(AU)

Desarrollo de una nueva forma farmacéutica líquida necesaria en una situación de accidente nuclear / Development of a new liquid pharmaceutical form needed in a situation of a nuclear accident

Introducción: La administración de yodo estable, en forma de yoduro, es empleado como protector frente a los efectos nocivos de la radiación, esta pauta profiláctica también es asumida por la OTAN en su STANAG 2461 N BC/MED. E l dificultoso suministro a determinados grupos de población, con dificultades en la deglución, de formas orales sólidas de yodo estable, obliga a disponer de determinados preparados que soslayen los inconvenientes de estas formas farmacéuticas y faciliten la administración de este activo. Lugar de realización: Centro M ilitar de Farmacia de la D efensa. Objetivo: Diseñar y evaluar una preparación estable de yoduro potásico en solución, para administración oral, que complete la laguna existente en el arsenal terapéutico español y europeo. Producción y validación del proceso a escala industrial de una solución oral de yoduro potásico. D efinición de los parámetros indicativos de la calidad del producto. E valuación de la estabilidad del preparado. T ratamiento estadístico de los resultados obtenidos. Material y métodos: Componentes del producto fabricado. E quipos de proceso y control utilizados en la fabricación farmacéutica industrial de soluciones. D efinición de límites aplicados a especificaciones de producto. E studio de estabilidad según protocolo I CH 1QE para zonas climáticas III y IV sobre los lotes industriales fabricados. Paquete estadístico S PSS versión 15. Resultados: Los resultados corroboran la calidad y estabilidad de tres lotes industriales sometidos a estudio (Volumen envasado 18-22 ml; densidad: 1,100-1,300 g/ml; pH:5,5-6,5; contenido yoduro: 90%-110%, yodo molecular < 2%; aerobios totales a 37ºC y 25ºC<100 col/g; ausencia microorganismos patógenos ). E l nivel de significación obtenido en el análisis de varianza en la uniformidad de volumen, densidad, pH, contenido de yoduro y valoración de Yodo libre es superior a 0,05. Los lotes cumplen valores establecidos para todas las especificaciones durante 2 años. E n tercer y cuarto año se observa deterioro del envase y elevación de la concentración de la solución, sin ninguna otra alteración. Discusión: La ausencia de significación en la comparación de las medias, en las variables estudiadas en los tres lotes, muestra que el proceso es robusto y repetitivo. Los resultados de estabilidad permiten asignar un periodo de validez de al menos 2 años. E l mantenimiento de las especificaciones del producto, salvo la concentración de la solución, a pesar del deterioro observado en el envase, permite asegurar un elevado grado de estabilidad de la fórmula diseñada. Conclusiones: Se diseña y fabrica a escala industrial una solución estable de yoduro potásico. Los datos obtenidos, referentes a la calidad del producto fabricado, permiten asegurar la ausencia de variaciones significativas entre los diferentes lotes estudiados, demostrando el adecuado diseño del proceso. Los datos obtenidos permiten asegurar, igualmente, un comportamiento estable de la solución, tanto desde el punto de vista químico como microbiológico, al menos durante dos años

Introduction: T he administration of stable iodine in the form of iodide, is used as a buffer against the harmful effects of radiation, this prophylactic regimen is also assumed by NATO STANAG 2461 in N BC / MED . T he difficult delivery to specific population groups with difficulties in swallowing solid oral forms of stable iodine, requires the availability of certain preparations that would circumvent the disadvantages of these formulations and facilitate the management of this asset. Place: Center Pharmacy M ilitary D efense. Objective: D esign and to evaluate a stable preparation of potassium iodide in solution for oral administration to complete the gap in the S panish and E uropean therapeutic arsenal. Production and validation of industrialscale process of an oral solution of potassium iodide. D efining the parameters which determine the quality of the product. E valuation of the stability of the preparation. S tatistical treatment of results. Material and methods: Components manufactured product. Process and control equipment used in industrial pharmaceutical manufacturing solutions. D efinition of limits applied to product specifications. S tability study according to protocol 1QE I CH climatic zones III and IV on manufactured industrial lots. S PSS version 15. Results: T he results corroborate the quality and stability of three industrial lots under study (18-22 ml packed volume, density :1,100-1, 300 g / ml, pH :5,5-6, 5; iodide content: 90% -110%, molecular iodine <2% total aerobes at 37 ° C and 25 ° C <100 col / g; no pathogens). T he level of significance obtained from analysis of variance in the uniformity of size, density, pH, content of iodine and free iodine value is greater than 0.05. T he values set for lots meet all specifications for 2 years. T hird and fourth year there is damage to the packaging and elevated concentration of the solution, without any alteration. Discussion: T he absence of significance in the comparison of the means in the variables studied in the three lots, shows that the process is robust and repetitive. T he results of stability allow to assign a validity period of at least 2 years. T he upkeep specifications product, despite the deterioration observed in the package, ensures a high degree of stability of the scheme drawn up. Conclusions: A stable solution of potassium iodide has been designed and manufactured on an industrial scale. T he data obtained concerning the quality of the manufactured product helps to ensure the absence of significant variations between different batches studied, confirming that process design is the proper. T he data obtained allow us to ensure, also a stable behavior of the solution, both from the standpoint of chemical and biological

First autochthonous malaria case due to Plasmodium vivax since eradication, Spain, October 2010.

In October 2010, one case of autochthonous malaria due to Plasmodium vivax was diagnosed in Spain. The case occurred in Aragon, north-eastern Spain, where the vector Anopheles atroparvus is present. Although the source of infection could not be identified, this event highlights that sporadic autochthonous transmission of vector-borne diseases in continental Europe is possible and calls for enhanced surveillance and vector control measures.

Risk factors for disease severity among hospitalised patients with 2009 pandemic influenza A (H1N1) in Spain, April - December 2009.

We describe the clinical and epidemiological characteristics of patients hospitalised with confirmed 2009 pandemic influenza A(H1N1) in Spain from April to December 2009 and the risk factors associated with a worse outcome (admission to an intensive care unit or death) in adults. Case-based epidemiological information was collected as part of the national strategy for the surveillance of severe cases. Of 3,025 patients, 852 were admitted to an intensive care unit and overall, 200 died. The median patient age was 38 years (range: 0­94). A total of 662 (26%) patients had no underlying risk conditions. Antiviral therapy was initiated within 48 hours after symptom onset in only 35.2% (n=711); the median length of time before treatment was four days. In a multivariate analysis, the start of antiviral therapy more than 48 hours after symptom onset (odds ratio (OR) 2.39; 95% confidence interval (CI): 1.79 to 3.2), morbid obesity (OR: 2.01; 95% CI 1.38 to 2.94), cardiovascular disease (OR: 1.79; 95% CI: 1.2 to 2.67) and chronic obstructive pulmonary disease (OR: 1.51; 95% CI: 1.03 to 2.2) were significantly associated with a worse outcome in adults.

Actividades de vigilancia epidemiológica durante la pandemia de gripe (H1N1) 2009 en España. Reflexiones un años después / Epidemiological surveillance activities during the 2009 influenza pandemic in Spain. Lessons learnt one year after

En este artículo se revisan las actuaciones llevadas a cabo en España en materia de vigilancia epidemiológica durante la pandemia de gripe y las recomendaciones de ellas derivadas en los diferentes momentos de la evolución de la misma. El funcionamiento del Sub-comité de Vigilancia, contemplado en el Plan Nacional de Prepara-ción y Respuesta ante una pandemia de gripe, fue clave para la coor-dinación de estas actividades de vigilancia. Este Subcomité se activó de forma inmediata tras la declaración de la alerta y su papel también se describe en este trabajo. La existencia del Plan permitió una respuesta rápida y coordina-da tras la declaración de la alerta. La vigilancia epidemiológica y virológica de la gripe hubo de ir adaptándose a una situación cam-biante, y se pusieron en marcha sistemas adicionales a los de la vigi-lancia habitual de la gripe, tales como la vigilancia individualizada de casos en la comunidad y de casos graves y mortales. Entre las lecciones aprendidas destacan la necesidad de fortale-cer el análisis de los datos que se recogen durante una alerta, la nece-sidad de favorecer el intercambio de información entre los profesio-nales de salud pública y los asistenciales, y de reforzar la capacidad de respuesta para poder disponer de estructuras de salud pública fuertes y consolidadas ante futuras alertas sanitarias(AU)

In this article the actions taken in the area of epidemiological sur-veillance in Spain during the influenza pandemic and the recommen-dations drawn from them during the progression of the pandemic are reviewed. The performance of the Surveillance Subcommittee established in the National Influenza Preparedness and Response Plan was cen-tral to the coordination of these activities. The Surveillance Subcom-mittee was immediately activated when the alert was issued. Its role is also described in this review. The existence of a National Plan allowed a rapid and coordinated response after the alert declaration. The epidemiological and virolo-gical surveillance of the influenza pandemic was adapted to an evol-ving situation. In addition to routine influenza monitoring systems, new surveillance systems were put in place such as a case-based sur-veillance for community influenza cases and a case-based survei-llance for severe cases and deaths due to the pandemic. Among the lessons learned from this pandemic, we would high-light the need to strengthen the timely analysis of data collected during an alert, the need to promote the exchange of information among public health and health care professionals, and to strengthen the response capacity in order to have resilient and consolidated public health structures for future health alerts(AU)

Vigilancia individualizada de los casos iniciales de infección por gripe pandémica (H1N1) 2009 en España, abril-junio 2009 / Enhanced surveillance of initial cases of pandemic influenza (H1N1) 2009 infection in Spain, April-June 2009

Fundamentos: En abril de 2009 se inició en España una nueva estrategia de vigilancia con el objetivo de detectar los casos originados por el virus pandémico (H1N1) 2009 y de implementar las medidas de control adecuadas para contener su transmisión. Se describen las características clínicas y epidemiológicas de los casos confirmados en España notificados por la Red Nacional de Vigilancia Epidemiológica desde el 24 Abril al 30 Junio 2009. Métodos: Como parte de la respuesta inicial de vigilancia a la pandemia, a nivel nacional se recogió información clínica y epide-miológica individualizada de todos los casos en investigación de infección por virus pandémico (H1N1) 2009, así como de sus contactos. Resultados: De los 717 casos confirmados el 91% fueron notificados por 5 Comunidades Autónomas. A 15 de junio de 2009 el 49,1% de los casos pertenecían a brotes en centros educativos. No se detectaron brotes nosocomiales. La mediana de período de incubación fue de 3 días. El 88% de los casos tenía menos de 30 años y el 24,9% eran importados. Los síntomas más frecuentes fueron tos (92%) y fiebre (81,8%). La mediana de duración de síntomas fue de 5 días. Trece casos requirieron ingreso hospitalario y uno falleció. Conclusiones: Durante los primeros meses de pandemia los casos de gripe pandémica presentaron un cuadro leve similar al de la gripe estacional que afectó mayoritariamente a niños y adultos jóvenes. A finales de junio 2009 la aparición de brotes en diferentes colectivos reflejaba la penetración del virus pandémico en la comunidad y el inicio de su circulación(AU)

Background: In April 2009, a new surveillance strategy for the detection of cases of pandemic influenza (H1N1) 2009 infection and for the implementation of appropriate control measures to contain its transmission was initiated in Spain. We describe the clinical and epi-demiological characteristics of confirmed cases in Spain notified by the National Epidemiological Surveillance Network from April 24 to June 30, 2009. Methods: As part of the initial surveillance response to the pan-demic, case-based clinical and epidemiological information was co-llected nationwide on cases under investigation for pandemic virus (H1N1) 2009 infection and their contacts. Results: Of 717 confirmed cases, 91% were notified by 5 Auto-nomous Communities. As of June 15, 49.1% of cases belonged to school outbreaks. No nosocomial outbreaks were detected. The me-dian incubation period was 3 days. Eighty-eight percent of cases were under the age of 30 years, and 24.9% were imported. The most frequent symptoms were cough (92%) and fever (81.8%). The me-dian duration of symptoms was 5 days. Thirteen cases required hos-pitalization and one died. Conclusions: During the first months of the pandemic, pande-mic influenza cases experienced a mild illness similar to seasonal influenza, predominantly affecting children and young adults. By the end of June 2009, the detection of outbreaks in different settings indicated the diffusion of the pandemic virus into the community and the start of its circulation(AU)

Casos de infección por gripe pandémica (H1N1) 2009 hospitalizados en cuidados intensivos en España: factores asociados a riesgo de muerte, abril 2009-enero2010 / Critically ill patients with 2009 pandemic influenza A (H1N1) infection in Spain: factors associated with death, April 2009-January 2010

Fundamento: El análisis de los casos graves de gripe pandémica es necesario para identificar grupos de población vulnerables y adecuar las políticas de prevención y control. Se analizan las características clínicas y epidemiológicas así como los factores asociados a riesgo de muerte en los casos de infección por virus pandémico (H1N1) 2009 hospitalizados en unidades de cuidados intensivos (UCI) en España y notificados entre el 24 de abril de 2009 y el 31 de enero de 2010. Método:En el marco de la estrategia nacional de vigilancia de casos hospitalizados por gripe pandémica, se recogió a nivel nacional informa-ción clínica y epidemiológica individualizada de todos los casos hospitali-zados en UCI por infección por virus pandémico (H1N1) 2009. Resultados:De los 1.231 casos ingresados en una UCI fallecieron 271 (letalidad: 22%). La mediana de edad fue 40 años (rango: 0-90). Un total de 838 (76,3%) pacientes presentaban alguna patología subyacente, siendo la respiratoria la más frecuente (34,1%), seguida en adultos de la obesidad mórbida (18,8%). Un 93,1% recibió tratamiento antiviral y un 25,6% (n=231) lo recibió en 48 horas desde el inicio de síntomas. En el análisis multivariante el cáncer (OR 2,71; IC95% 1,44-5,1), las inmunodeficiencias (OR 2,25; IC95% 1,29-3,92) y la obesidad mórbida (OR 1,79; IC95% 1,13-2,85) estaban asociados significativamente a muerte en los adultos. Conclusión:La caracterización de los casos graves de gripe pandé-mica ha sido clave para identificar como factores de riesgo para sufrir complicaciones y muerte por gripe, la existencia de cáncer e inmunodefi-ciencias y, por primera vez, la obesidad mórbida en personas adultas(AU)

Background: It is necessary to analyse the severe cases of pandemic influenza infection in order to identify vulnerable populations and adapt prevention and control policies accordingly. We analysed the clinical and epidemiological characteristics and risk factors associated with death in patients with 2009 pandemic influenza A (H1N1) infection hospitalised in intensive care units (ICUs) in Spain and reported from 24 April 2009 to 31 January 2010. Methods: As part of the national strategy for surveillance of hospita-lized cases with pandemic influenza, cased-based clinical and epidemiolo-gical information on all cases admitted to an ICU with 2009 pandemic virus (H1N1) infection was collected nationwide. Results: Of 1,231 cases admitted to ICU, 271 died (case fatality ratio, 22%). The median age was 40 years (range: 0-90). A total of 838 (76.3%) patients had an underlying risk condition, being respiratory disease the most frequently reported (34.1%), followed by morbid obesity (18.8%), in adults. Antiviral treatment was given in 93.1% patients and in 25.6% (n = 231) it was initiated within 48 hours of symptoms onset. In a multivariate analysis, cancer (OR 2.71, 95%CI 1.44 to 5.1), immunodeficiency (OR 2.25, 95%CI 1.29 - 3.92) and morbid obesity (OR 1.79, 95%CI 1.13 to 2.85) were significantly associated with death in adults. Conclusions:The characterization of severe pandemic influenza cases has been crucial in identifying as risk factors of complications and death from influenza the presence of cancer and immunodeficiencies and for the first time, morbid obesity in adults(AU)

Brote de gripe pandémica (H1N1) 2009 en una academia militar: inicio de la circulación comunitaria en España / Pandemic influenza (H1N1) 2009 outbreak in a military academy: start of community circulation in Spain

Fundamento: El 19 de mayo de 2009 se declararon 21 casos de soldados con síntomas de infección respiratoria aguda en la Academia Militar de Ingenieros (ACING) en Hoyo de Manzanares, España. En el contexto de una alerta mundial por gripe A(H1N1) 2009, se decide investigar la posible aparición de un brote por este virus. El objetivo es describir un posible brote de gripe (H1N1) 2009 en un Centro de Formación Militar y describir las medidas adoptadas, en la fase de contención, para evitar su transmisión. Métodos: Se administró un cuestionario específico y se recogieron muestras biológicas a todos los casos en investigación. Se recomendaron aislamiento y cuarentena, respectivamente de los casos y contactos. Resultados: Se confirmaron 81 casos de infección por virus de la gripe A (H1N1)2009. De las 52 muestras procesadas 31 fueron positivas para virus influenza A/California/7/2009. La edad media de los casos fue 22,0 años (rango, 18-31). El 84% eran varones. Los síntomas más comunes fueron tos y fiebre. Todos los casos permanecieron aislados y fueron tratados con oseltamivir, con buena evolución. La tasa de ataque global fue 12,42%. Ningún caso tenía antecedentes de viaje a zonas de riesgo o vinculo epidemiológico con un caso diagnosticado previamente fuera de la ACING. Se identificaron 31 casos relacionados con este brote fuera de la ACING, 24 casos eran contactos familiares y amigos. Conclusiones: Este brote alertó del inicio de la circulación comunitaria del virus pandémico en España. La detección precoz del mismo favoreció la puesta en marcha de medidas para la contención de su trasmisión(AU)

Background: On May 19, 2009, 21 cases of influenza-like illness were reported among soldiers from an Engineering Military Academy (ACING) in Hoyo de Manzanares, Spain. In the context of an influenza A (H1N1)2009 global alert, it was decided to investigate a possible pandemic influenza outbreak. To describe a possible outbreak of influenza A (H1N1)2009 in a Military Training Centre and to describe the measures adopted for transmission control of this new infection. Methods: A specific questionnaire was administered and biological samples were collected from all cases under investigation. Isolation and quarantine were recommended for cases and contacts, respectively. Results: Eighty-one cases were confirmed. Among 52 samples tested, 31 were positive for influenza virus A/California/7/2009. The average age of the cases was 22.0 years (range 18-31 years) and 84% were men. Most common reported symptoms were cough and fever. All cases were isolated and treated with oseltamivir, with full recovery. The total attack rate was 12.42%. None of the cases had history of travel to risk areas or contact with previously diagnosed cases outside the academy. Thirty-one confirmed cases related to this outbreak were identified outside the academy, 24 cases were family contacts and friends. Conclusions: This outbreak was the first evidence of community transmission of pandemic influenza H1N1 in Spain. The rapid detection of this outbreak enhanced an early implementation of measures aiming at the containment of its transmission(AU)

Diseño de un sistema para obtención de agua, con garantías sanitarias adecuadas, destinada al consumo ndividual en condiciones de emergencia. Evaluación de su capacidad desinfectante y análisis de costes para su aplicación en las Fuerzas Armadas / Design of a system for water production with adequate medical guarantees for individual consumption in emergency conditions. Assessment of its disinfection capacity and cost analysis for its application in the Armed Forces

Introducción: La disponibilidad de agua, con las adecuadas garantías sanitarias, en situaciones de emergencia y durante cortos periodos de tiempo, se considera de suma importancia en el ámbito operativo de las Fuerzas Armadas. La existencia de sistemas que aseguren un suministro de agua de calidad aceptable y que no supongan riesgo para la salud del consumidor, en estas circunstancias, debe ser considerado de vital importancia, tanto desde el punto de vista sanitario como táctico. Lugar de realización: Centro Militar de Farmacia de la Defensa. Objetivo: Diseñar un sistema para depuración de agua, destinada al consumo individual en condiciones de emergencia, que satisfaga los diversos requisitos exigibles para su uso por miembros de las Fuerzas Armadas, tales como disminución de patógenos transmisibles por vía hídrica hasta niveles seguros, rápida purificación del agua, utilización sencilla o estable en condiciones de campaña. La eficacia de este sistema será evaluada mediante la aplicación de condiciones que reproduzcan las características de un agua natural. Conclusiones: Se desarrolla un sistema depurador, consistente en comprimidos de rápida disolución, cuyo componente activo es el agente clorógeno Dicloroisocianurato sódico - dihidrato (CAS 51580- 86-0), cuyo perfil de liberación de cloro resulta superior a otros agentes ensayados; demostrando, además, una adecuada eficacia bactericida en un medio de ensayo que emula las condiciones de un agua natural. La inclusión de este producto en la lista positiva de sustancias utilizables en el tratamiento de aguas destinadas al consumo y su menor coste, en comparación a otras moléculas activas, permite proponer su utilización como nuevo desinfectante, para tratamiento de aguas de consumo en situaciones de emergencia, utilizable por las Fuerzas Armadas (AU)

Introduction: water availability, in accordance with medical standards, in emergency situations and for shorts periods of time is considered of the highest importance in the military operational environment. Water production systems that ensure a supply of acceptable quality water that does not entail a health risk in these circumstances, must be considered of vital importance, from the medical and tactical viewpoints. Location of the tests: Military Center for Pharmacy. Objective: to design a system for water treatment for individual consumption in emergency conditions, complying with the diverse requirements for military utilization, such as reduction of waterborne pathogens to safe levels, rapid purification of the water, stable and easy use in field conditions. The efficacy of this system will be assessed applying conditions that simulate the characteristics of natural water. Conclusions: a purifying system based on fast dissolving tablets is developed. The active principle is sodium dichloroisocyanurate dihydrate (CAS 51580-86-0), whose chlorine release profile is superior to other tested agents. It also has demonstrated an acceptable bactericidal efficiency in an assay medium that simulates the natural water conditions. The inclusion of this product in the list of useful substances in the treatment of drinking water and its lower cost, in comparison with other active molecules, permits to propose its utilization for the military as a new disinfecting agent for drinking water treatment in emergency situations (AU)