[Prospective study in 2 hospitals]. / Estudio prospectivo en dos hospitales.

OBJECTIVES: The purpose of this study is to know the incidence rate of medication reconciliation at admission and discharge in patients of La Rioja and to improve the patient safety on medication reconciliation. MATERIAL AND METHODS: An observational prospective study, part of the Joint Action PaSQ, Work Package 5, European Union Network for Patient Safety and Quality of Care. The study has taken into account the definitions of the Institute for Safe Medication Practices. Any unintended discrepancy in medication between chronic treatment and the treatment prescribed in the hospital was considered as a reconciliation error. RESULTS: A total of 750 patients were included, 9 (1.2%) of whom showed at least one discrepancy. The patients had a total of 3,156 mediations registered: 2,313 prescriptions (73.4%) showed no differences, while 821 prescriptions (26%) were intended discrepancies and 21 prescriptions (0.6%) unintended discrepancies were considered by the physician as reconciliation errors. A percentage of 1.2 of the patients, which represents 0.6% of the medicines (one in 166 medications registered) had reconciliation errors during their hospital stay. CONCLUSIONS: A proceeding has been implemented by means of the physician doing the medication reconciliation and reviewing it with the help of a medication reconciliation form. The medication reconciliation is a priority strategic objective to improve the safety of patients.

Safety and antitumor effect of oncolytic and helper-dependent adenoviruses expressing interleukin-12 variants in a hamster pancreatic cancer model.

Gene transfer of potent immunostimulatory cytokines such as interleukin-12 (IL-12) is a potential treatment for advanced cancer. Different vectors and IL-12 modifications have been developed to avoid side effects associated with high serum levels of the cytokine, while preserving its antitumor properties. Here we have evaluated two alternative strategies using the Syrian hamster as a model for pancreatic cancer metastatic to the liver. Local administration of an oncolytic adenovirus (OAV) expressing a single-chain version of IL-12 caused transient, very intense elevations of IL-12 in serum, resulting in severe toxicity at sub-therapeutic doses. Anchoring IL-12 to the membrane of infected cells by fusion with the transmembrane domain of CD4 reduced systemic exposure to IL-12 and increased the tolerance to the OAV. However, only a modest increase in the therapeutic range was achieved because antitumor potency was also reduced. In contrast, systemic administration of a helper-dependent adenoviral vector (HDAd) equipped with a Mifepristone-inducible expression system allowed sustained and controlled IL-12 production from the liver. This treatment was well tolerated and inhibited the progression of hepatic metastases. We conclude that HDAds are safer than OAVs for the delivery of IL-12, and are promising vectors for immunogene therapy approaches against pancreatic cancer.

Self-inactivating helper virus for the production of high-capacity adenoviral vectors.

Standard methods for producing high-capacity adenoviral vectors (HC-Ads) are based on co-infection with a helper adenovirus (HV). To avoid HV encapsidation, its packaging signal (Ψ) is flanked by recognition sequences for recombinases expressed in the producing cells. However, accumulation of HV and low yield of HC-Ad are frequently observed, due in part to insufficient recombinase expression. We describe here a novel HV (AdTetCre) in which Ψ is flanked by loxP sites that can be excised by a chimeric MerCreMer recombinase encoded in the same viral genome. Efficient modulation of cleavage was obtained by simultaneous control of MerCreMer expression using a tet-on inducible system, and translocation to the nucleus by 4-hydroxytamoxifen (TAM). Encapsidation of AdTetCre was strongly inhibited by TAM plus doxycicline. Using AdTetCre and 293Cre4 cells for the production of HC-Ads, we found that cellular and virus-encoded recombinases cooperate to minimize HV contamination. The method was highly reproducible and allowed the routine production of different HC-Ads in a medium-scale laboratory setting in adherent cells, with titers >10¹° infectious units and <0.1% HV contamination. The residual HVs lacked Ψ and were highly attenuated. We conclude that self-inactivating HVs based on virally encoded recombinases are promising tools for the production of HC-Ads.

Deletion of the E3-6.7K/gp19K region reduces the persistence of wild-type adenovirus in a permissive tumor model in Syrian hamsters.

A partial deletion of the adenovirus E3 region, comprising the overlapping 6.7K/gp19K genes, has been described for the incorporation of therapeutic genes in 'armed' oncolytic adenoviruses. This deletion allows the insertion of up to 2.5 kb genetic material into the virus and ensures strong expression of transgenes without reducing the replication and cytolytic potency of viruses in vitro. E3-gp19K and 6.7K proteins are involved in avoiding recognition and elimination of infected cells by the host immune system. Therefore, we have studied the effect of this deletion on the replication and transgene expression of the virus in immunocompetent models based on Syrian hamsters. Tumors were established by intrahepatic injection of pancreatic cancer cells with moderate (HaP-T1, HP-1) or low (H2T) permissivity for adenovirus replication. The wild-type human adenovirus 5 (Ad5) or a modified version containing the luciferase gene in the E3-6.7K/gp19K locus (Ad-WTLuc) were injected intratumorally. We found that elimination of Ad-WTLuc was faster than Ad5 in HaP-T1 and HP-1 tumors. In contrast, no differences were observed when the same tumor was established in severely immunocompromised NOD-scid IL2Rgamma(null) mice. In addition, virus-mediated luciferase expression was more stable in these animals. These results suggest that the lack of E3-6.7K/gp19K genes may accelerate the clearance of oncolytic adenoviruses in some immunocompetent tumor models.

[Effect of birth cohort, period of diagnosis and age on cancer incidence in Navarra, 1973-1997]. / Efecto de la cohorte de nacimiento, período de diagnóstico y de la edad en la incidencia de cáncer en Navarra, 1973-1997.

BACKGROUND: Population-based registers are one source of information about cancer incidence. Systematic study of its incidence in a specific population is a fundamental tool for estimating the present-day and future magnitude of cancer and provides elements for taking decisions with regard to the allocation of health resources. The aim of this article was to investigate the time trend in the incidence pattern of cancer in Navarre during the period 1973-1997, and to identify the components of age, diagnosis period and birth cohort as determinants of the time trend of cancer incidence. METHODS: Descriptive study of cancer incidence through age-period-cohort models. Monitoring of dynamic cohort over 25 years. Classical incidence summarizing indicators were analysed. Log-linear Poisson models were developed to quantify cancer risk and the relative annual trend. Age-period-cohort models were adjusted in order to ascertain the effect on the time trend exerted by the respective age, diagnosis period and birth cohort components. RESULTS: The age-standardized rate incidence for all sites -except non melanoma skin tumours- is maximum in the five-year period 1993-1997, in men: 304,1 new cases per 100,000 person-years, and in women: 190,6 new cases per 100,000 person-years. The average incidence changes for each of the 25 years of monitoring of the set data studied is 1.88% (95% CI 1.69 to 2.07) in men and 1.32% (95% CI 1.09 to 1.54) in women. The cancer increase in women is more pronounced from 35 to 64 years, a fact which should alert health authorities about the future evolution of cancer incidence in women. In the analysis of the trend components sharp increases are observed for the consecutive generations of males born in Navarre since 1900. In women, the risk associated with the year of birth increases markedly in the generations born after 1930-1940. CONCLUSIONS: There was an important increase in cancer incidence in Navarre from 1973 to 1997, in men and women. The cancer incidence pattern in Navarre does not yet show signs of stabilization.

[International classification of functioning, disability and health (ICF) 2001]. / La clasificación internacional del funcionamiento de la discapacidad y de la salud (CIF) 2001.

The approach which had been being employed to date for dealing with and classifying those aspects related to health and disability have been revised and updated thanks to the World Health Organization (WHO) having drafted the International Classification of Functioning, Disability and Health, which has now been accepted 191 countries after revamping the prior model and reaching a consensus regarding a new international model for describing and measuring health and disability. As background information, it must be recalled that the Classification of Impairments, Disabilities and Handicaps (CIDH) previously in effect was first published by the WHO in 1980. The process of revising this classification has resulted in some changes of far-reaching importance. The change in the name has been aimed at reflecting the wish to replace the negative perspective of impairments, disabilities and handicaps for a more neutral view of structure and function, considering the positive perspectives of activities and of participation. Another new aspect has been that of including a section related to environmental factors in recognition of their importance, given that by interacting with the health condition they may give rise to a disability, or, at the opposite end of the scale, may restore functioning. The data available has enabled the WHO make estimates including that of some 500 million years of life being lost annually due to disabilities related to health problems, which totals over one half of the years lost annually due to premature deaths. The main objective of this new classification is that of providing the conceptual framework by means of unified, standardized language with a view to of the underlying challenges, setting out a valuable instrument of practical use in public health.

[Changes in epidemiological pattern of methicillin-resistant Staphylococcus aureus infections in a tertiary hospital. Experience of 5 years]. / Cambios en los patrones epidemiológicos de la infección por Staphylococcus aureus resistente a la meticilina en un hospital de tercer nivel. Experiencia de 5 años.

OBJECTIVE: To describe the demographic pattern and tendency of the infections by MRSA between 1992 and 1997. DESIGN AND METHODS: Descriptive study of the infections by MRSA in a tertiary-care hospital. RESULTS: 267 MRSA infections, 131 infections were included within 58 buds and 136 cases isolated form. The more affected services were Internal Medicine, Urology, Neurology, Vascular surgery and intensive care unit. A tendency was observed to the increase in > 65 years cases and in medical services. CONCLUSIONS: The increase of elderly cases in medical services and > 65 years carriers in their nose could translate the existent situation in the community.