La cultura compasiva en el abordaje de la poliomielitis en entornos sanitarios. El caso español (1940-1970) / Compassionate culture in addressing polio in healthcare settings. The spanish case (1940-1970)

La presencia de brotes epidémicos de poliomielitis en las décadas iniciales y centrales del siglo pasado constituyó un importante problema de Salud Pública, debido a la ausencia de tratamientos eficaces, por afectar de forma preferente a edades infantiles, en entornos con niveles aceptables de salubridad y por las temibles secuelas paralíticas. En este trabajo se intentan reconstruir algunas de las respuestas que se dieron en el estado español, tanto en los ámbitos profesionales sanitarios como desde planteamientos hete-rodoxos alternativos como el método Kenny, tomando como eje de referencia la cultura compasiva que estuvo detrás del desarrollo de las medidas adoptadas, así como su análisis crítico, en el periodo anterior a la puesta en marcha de las vacunas antipoliomielíticas.(AU)

The presence of epidemic outbreaks of poliomyelitis in the initial and central decades of the last century constituted an important Public Health problem due to the absence of effective treatments because it preferentially affected children, in environments with acceptable levels of health, and the fear of the paralytic sequelae. This work attempted to reconstruct some of the responses that were given in the Spanish state, both in professional health settings and from alternative heterodox approaches such as the Kenny method, taking as a reference axis the compassionate culture that was behind the development of the measures. adopted and their critical analysis, in the period before the implementation of anti-polio vaccines.(AU)

[Compassionate culture in addressing polio in healthcare settings. The spanish case (1940-1970)]. / La cultura compasiva en el abordaje de la poliomielitis en entornos sanitarios. El caso español (1940-1970).

The presence of epidemic outbreaks of poliomyelitis in the initial and central decades of the last century constituted an important Public Health problem due to the absence of effective treatments because it preferentially affected children, in environments with acceptable levels of health, and the fear of the paralytic sequelae. This work attempted to reconstruct some of the responses that were given in the Spanish state, both in professional health settings and from alternative heterodox approaches such as the Kenny method, taking as a reference axis the compassionate culture that was behind the development of the measures. adopted and their critical analysis, in the period before the implementation of anti-polio vaccines.

La presencia de brotes epidémicos de poliomielitis en las décadas iniciales y centrales del siglo pasado constituyó un importante problema de Salud Pública, debido a la ausencia de tratamientos eficaces, por afectar de forma preferente a edades infantiles, en entornos con niveles aceptables de salubridad y por las temibles secuelas paralíticas. En este trabajo se intentan reconstruir algunas de las respuestas que se dieron en el estado español, tanto en los ámbitos profesionales sanitarios como desde planteamientos heterodoxos alternativos como el método Kenny, tomando como eje de referencia la cultura compasiva que estuvo detrás del desarrollo de las medidas adoptadas, así como su análisis crítico, en el periodo anterior a la puesta en marcha de las vacunas antipoliomielíticas.

Approach to the so-called "Invisible Dermatosis": When Subtle Histopathological Findings Guide Diagnosis.

ABSTRACT: Invisible dermatosis is a concept that can be applied either to clinical or histopathological findings. We will focus on the dermatopathological aspect of this invisible dermatosis that can be seen as dermatosis with subtle histopathological findings that are mandatory to known to stablish the diagnosis. With a proper approach facing in depth the different skin layers from stratum corneum to subcutaneous tissue combined with some especial stains, special investigations and mostly a proper clinicopathological correlation, the problem of missing out a diagnosis can be decreased. We will review the general aspects for diagnosis and the peculiar findings of an in-depth review of them because it is important to note that minor changes on a skin biopsy do not mean it is disease free. We will review classic clues, we will add some new useful ones, and we will also provide a guide on the special stains helpful, such as periodic acid-Schiff when facing fungi, orcein-Giemsa and van Gieson when altered elastic fibers are suspected, or Pearl and Masson Fontana when an altered skin pigmentation is suspected.

Evidence-based guidelines for hypofractionated radiation in breast cancer: conclusions of the Catalan expert working group

IntroductionDaily, moderate hypofractionation has become standard treatment for breast cancer following breast-conserving surgery, although substantial variation exists in its use. This paper describes the generation of consensus-based recommendations for the utilisation of this therapy at the healthcare system level and compares these to American Society for Radiation Oncology (ASTRO) guidelines.Materials and methodsConsensus-based guidelines were developed in three steps, including a systematic literature review and involvement of radiation oncologists specialising in breast cancer in Catalonia: (a) creation of a working group and evidence review; (b) consideration of the levels of evidence and agreement on the formulation of survey questions; and (c) performance of survey and development of consensus-based recommendations. Results were compared to the ASTRO recommendations.ResultsConsensus was above 80% for 10 of the 14 survey items. Experts supported hypofractionated radiotherapy for all breast cancer patients aged 40 years or more; with invasive carcinoma and breast-conserving surgery; without radiation of lymph nodes; and regardless of the tumour size, histological grade, molecular subtype, breast size, laterality, other treatment characteristics, or need for a boost. Over half favoured its use in all situations, even where available scientific evidence is insufficient. The resulting recommendations and the quality of the evidence are comparable to those from ASTRO, despite some differences in the degree of consensus.ConclusionSpecialists agree that hypofractionation is the standard treatment for breast cancer following breast-conserving surgery, but some specific areas require a higher level of evidence before unequivocally extending indications. (AU)

Evidence-based guidelines for hypofractionated radiation in breast cancer: conclusions of the Catalan expert working group.

INTRODUCTION: Daily, moderate hypofractionation has become standard treatment for breast cancer following breast-conserving surgery, although substantial variation exists in its use. This paper describes the generation of consensus-based recommendations for the utilisation of this therapy at the healthcare system level and compares these to American Society for Radiation Oncology (ASTRO) guidelines. MATERIALS AND METHODS: Consensus-based guidelines were developed in three steps, including a systematic literature review and involvement of radiation oncologists specialising in breast cancer in Catalonia: (a) creation of a working group and evidence review; (b) consideration of the levels of evidence and agreement on the formulation of survey questions; and (c) performance of survey and development of consensus-based recommendations. Results were compared to the ASTRO recommendations. RESULTS: Consensus was above 80% for 10 of the 14 survey items. Experts supported hypofractionated radiotherapy for all breast cancer patients aged 40 years or more; with invasive carcinoma and breast-conserving surgery; without radiation of lymph nodes; and regardless of the tumour size, histological grade, molecular subtype, breast size, laterality, other treatment characteristics, or need for a boost. Over half favoured its use in all situations, even where available scientific evidence is insufficient. The resulting recommendations and the quality of the evidence are comparable to those from ASTRO, despite some differences in the degree of consensus. CONCLUSION: Specialists agree that hypofractionation is the standard treatment for breast cancer following breast-conserving surgery, but some specific areas require a higher level of evidence before unequivocally extending indications.

Narrativas vacunales y políticas de vacunación contra la poliomielitis en el contexto de la provincia de Alicante (1963-1978) / Vaccine narratives and polio vaccination policies in the context of the province of Alicante (1963-1978)

El análisis a pequeña escala es una vía de abordaje historiográfico que abrió, en su momento, nuevos caminos en la investigación. La proximidad del objeto de estudio, permite profundizar en los determinantes propios y específicos y en las realidades y prácticas, por ejemplo, de las campañas de inmunización masiva contra la poliomielitis diseñada a nivel nacional pero implementadas localmente, como en el estudio de caso que abordamos. Utilizando como modelo el ámbito sanitario provincial de Alicante, el trabajo añade datos para completar la información de proximidad sobre estas campañas y de ese modo, completar una visión de conjunto y un análisis comparado tanto en un ámbito externo como en un ámbito interno interterritorial, nacional y provincial, así como el seguimiento de las directrices dadas por los organismos nacionales e internacionales. En segundo término, dotar de significado al conjunto de actividades llevadas a cabo por diferentes actores, instituciones y medios de comunicación, implicados en el proceso de implantación, cobertura y seguimiento de las campañas de vacunación contra la polio en el ámbito provincial alicantino. El uso de narrativas de personas afectadas por la enfermedad permite añadir elementos relevantes sobre experiencias personales en el contexto de las campañas vacunales

Small-scale analysis is a path of historiographical approach that opened, at the time, new paths in research. The proximity of the study object allows us to delve into our own and specific determinants and the realities and practices of, for example, mass immunization campaigns against polio, designed at the national level but implemented locally, as in the case study that we discuss. Using as a model the provincial sanitary area of Alicante, the work adds data to complete the proximity information on these campaigns and thus, complete an overview and a comparative analysis both in an external and in an internal interterritorial, national scope and provincial level as well as the follow-up of the guidelines given by the national and international organisms. Secondly, to give meaning to the set of activities carried out by different actors, institutions and media, involved in the process of implementation, coverage and follow-up of polio vaccination campaigns in the province of Alicante. The use of narratives of people affected by the disease allows to add relevant elements about personal experiences in the context of the vaccine campaigns

Breast Cancer Patient with Li-Fraumeni Syndrome: A Case Report Highlighting the Importance of Multidisciplinary Management.

Germline mutations in TP53, a tumor suppressor gene, are involved in the development of Li-Fraumeni syndrome, a rare disorder that predisposes carriers to multiple tumors. TP53 mutations have been associated with resistance to treatment and poor prognosis. A young female with the pathogenic germline TP53 mutation c.844C > T (p.R282W) was diagnosed with two metachronous breast tumors, one HER2-negative and the other HER2-positive. She was later diagnosed with synchronous glioblastoma, epidermal growth factor receptor-mutated lung adenocarcinoma, and HER2-negative breast cancer metastases. The patient was treated with local therapies, including brain surgery and radiotherapy, lung surgery, and a bilateral mastectomy, as well as with targeted systemic treatment. She proved to be highly sensitive to systemic therapy, and 13 years after the initial diagnosis of breast cancer and 6 years after the diagnosis of the two new primary tumors and recurrence of a prior cancer, she is alive with an excellent performance status. This surprising positive evolution may well be partly due to the pronged multidisciplinary approach to managing her disease and her extraordinary response to treatment: the lung adenocarcinoma showed excellent response to erlotinib; the breast cancer responded extremely well to eribulin and pegylated liposomal doxorubicin; and the glioblastoma has remained in response to surgery and radiotherapy. Despite harboring a TP53 mutation and having multiple tumors, this patient has shown an unexpectedly favorable evolution. The coordinated participation of a multidisciplinary team and the patient's own extraordinarily high sensitivity to systemic treatment played a major role in this evolution.

Chorioamnionitis due to Leptotrichia trevisanii.

Very long fusiform gram-negative bacilli were observed after Gram staining of amniotic fluid from a 36-year-old multigravida woman. At 24 hours, pure, abundant growth of smooth, gray, only slightly convex catalase-positive and oxidase-negative colonies measuring about 2 mm were observed. Growth was greater in anaerobic than in aerobic conditions. The bacterium was identified as Leptotrichia trevisanii by matrix-assisted laser desorption ionization time of flight mass spectrometry. Ampicillin and gentamicin were prescribed for chorioamnionitis, and vaginal prostaglandins were administered to terminate the pregnancy. The patient remained afebrile throughout 48 hours and was discharged. Microscopic examination of the placenta revealed severe acute chorioamnionitis with a maternal inflammatory response and abundant bacillary-shaped microorganisms. To our knowledge, this isolate constitutes the first reported case of chorioamnionitis caused by L. trevisanii.

Predictive and Prognostic Brain Metastases Assessment in Luminal Breast Cancer Patients: FN14 and GRP94 from Diagnosis to Prophylaxis.

FN14 has been implicated in many intracellular signaling pathways, and GRP94 is a well-known endoplasmic reticulum protein regulated by glucose. Recently, both have been associated with metastasis progression in breast cancer patients. We studied the usefulness of FN14 and GRP94 expression to stratify breast cancer patients according their risk of brain metastasis (BrM) progression. We analyzed FN14 and GRP94 by immunohistochemistry in a retrospective multicenter study using tissue microarrays from 208 patients with breast carcinomas, of whom 52 had developed BrM. Clinical and pathological characteristics and biomarkers expression in Luminal and non-Luminal patients were analyzed using a multivariate logistic regression model adjusted for covariates, and brain metastasis-free survival (BrMFS) was estimated using the Kaplan-Meier method and the Cox proportional hazards model. FN14 expression was associated with BrM progression mainly in Luminal breast cancer patients with a sensitivity (53.85%) and specificity (89.60%) similar to Her2 expression (46.15 and 89.84%, respectively). Moreover, the likelihood to develop BrM in FN14-positive Luminal carcinomas increased 36.70-fold (3.65-368.25, p = 0.002). Furthermore, the worst prognostic factor for BrMFS in patients with Luminal carcinomas was FN14 overexpression (HR = 8.25; 95% CI: 2.77-24.61; p = 0.00015). In these patients, GRP94 overexpression also increased the risk of BrM (HR = 3.58; 95% CI: 0.98-13.11; p = 0.054-Wald test). Therefore, FN14 expression in Luminal breast carcinomas is a predictive/prognostic biomarker of BrM, which combined with GRP94 predicts BrM progression in non-Luminal tumors 4.04-fold (1.19-8.22, p = 0.025), suggesting that both biomarkers are useful to stratify BrM risk at early diagnosis. We propose a new follow-up protocol for the early prevention of clinical BrM of breast cancer patients with BrM risk.

Saúde e educação no contexto escolar / Health and education in the school context

Higiene, saúde e educação têm estado estreitamente ligadas, embora sua relação tenha assumido diferentes formas e intensidades.Para remontar a história desse processo, contamos, em diversos países, com um grande número de fontes escritas entre 1850 e o primeiro tercil do século XX, que têm valor intestimável para a avaliação do aumento da inserção de temas da saúde na escola. Do mesmo modo que no período histórico de vigência da higiene escolar, analisado ao longo do capítulo, a educação para a saúde se constitui em um campo multidisciplinar que envolve profissionais de diversas áreas. Assim, a atual educação para a saúde no universo escolar herdou muitos aspectos da antiga higiene das escolas e dos escolares.

FN14 and GRP94 expression are prognostic/predictive biomarkers of brain metastasis outcome that open up new therapeutic strategies.

Brain metastasis is a devastating problem in patients with breast, lung and melanoma tumors. GRP94 and FN14 are predictive biomarkers over-expressed in primary breast carcinomas that metastasized in brain. To further validate these brain metastasis biomarkers, we performed a multicenter study including 318 patients with breast carcinomas. Among these patients, there were 138 patients with metastasis, of whom 84 had brain metastasis. The likelihood of developing brain metastasis increased by 5.24-fold (95%CI 2.83-9.71) and 2.55- (95%CI 1.52-4.3) in the presence of FN14 and GRP94, respectively. Moreover, FN14 was more sensitive than ErbB2 (38.27 vs. 24.68) with similar specificity (89.43 vs. 89.55) to predict brain metastasis and had identical prognostic value than triple negative patients (p < 0.0001). Furthermore, we used GRP94 and FN14 pathways and GUILD, a network-based disease-gene prioritization program, to pinpoint the genes likely to be therapeutic targets, which resulted in FN14 as the main modulator and thalidomide as the best scored drug. The treatment of mice with brain metastasis improves survival decreasing reactive astrocytes and angiogenesis, and down-regulate FN14 and its ligand TWEAK. In conclusion our results indicate that FN14 and GRP94 are prediction/prognosis markers which open up new possibilities for preventing/treating brain metastasis.

Local health policies under the microscope: consultants, experts, international missions and poliomyelitis in Spain, 1950-1975.

One of the main focuses of analysis of this paper concerns the missions of international health agency experts to Spain to report on the situation, the activities in the fight against physical disabilities in children and on the actions taken to cope with the problem. The Spain-23 Plan was the instrument used by WHO and other agencies to start the process of change in a country undergoing a period of transformation under the enduring Franco dictatorship. As key sources, the paper uses unpublished reports of WHO experts on the subject, which resulted from visits to the country between 1950 and 1975. The methodological approach consists of an analysis of discourses from primary sources within the historiographical framework.

Políticas sanitarias locales puestas a prueba: consultores, expertos, misiones internacionales y poliomielitis en España, 1950-1975 / Local health policies under the microscope: consultants, experts, international missions and poliomyelitis in Spain, 1950-1975

Este trabajo analisa las misiones de expertos de organismos sanitarios internacionales en España destinadas a informar sobre la situación, las actividades realizadas y las intervenciones necesarias en la lucha contra la discapacidad física de los niños. El Plan España-23 fue el instrumento utilizado por la OMS y otras agencias para poner en marcha el proceso de cambio en un país en transformación durante la larga etapa de vigencia de la dictadura franquista. El trabajo utiliza como fuentes informes inéditos de expertos de la OMS, que fueron resultado de visitas realizadas al país entre 1950 y 1975. El abordaje metodológico consistió en un análisis del discurso que se encuentra en las fuentes y su contextualización en los marcos historiográficos pertinentes.

One of the main focuses of analysis of this paper concerns the missions of international health agency experts to Spain to report on the situation, the activities in the fight against physical disabilities in children and on the actions taken to cope with the problem. The Spain-23 Plan was the instrument used by WHO and other agencies to start the process of change in a country undergoing a period of transformation under the enduring Franco dictatorship. As key sources, the paper uses unpublished reports of WHO experts on the subject, which resulted from visits to the country between 1950 and 1975. The methodological approach consists of an analysis of discourses from primary sources within the historiographical framework.

Mericitabine and ritonavir-boosted danoprevir with or without ribavirin in treatment-naive HCV genotype 1 patients: INFORM-SVR study.

BACKGROUND & AIMS: Safety and tolerability of peginterferon-based hepatitis C virus (HCV) infection therapy remains suboptimal, even when direct-acting antiviral agents are added. This study assessed the efficacy, safety and tolerability of mericitabine combined with ritonavir-boosted danoprevir (danoprevir/r) ± ribavirin for up to 24 weeks in treatment-naïve HCV genotype (G)1 infected patients. METHODS: Patients received twice daily mericitabine (1000 mg) and danoprevir/r (100 mg/100 mg) plus either ribavirin (1000/1200 mg/day; Arm A) or placebo (Arm B) for 12 or 24 weeks. Patients with HCV RNA <43 IU/ml between Weeks 2 and 8 and HCV RNA <15 IU/ml at Week 10 were rerandomized (1:1) at Week 12 to discontinue/continue assigned regimens until Week 24. Because of unacceptable relapse rates in both 12-week arms and in ribavirin-free Arm B, treatment was extended to 24 weeks and patients in Arm B received peginterferon alfa-2a/ribavirin. The primary outcome was sustained virological response 24 weeks after end of treatment (SVR24). RESULTS: In Arm A, the SVR24 rate in patients receiving 24 weeks of therapy was 37.9% (25/66); 63.6% (14/22) in G1b and 25.0% (11/44) in G1a patients. Virologic breakthrough and relapse were associated with danoprevir-resistant virus in most cases. The mericitabine-resistance mutation (NS5BS282T) was detected in two patients bearing dual resistant virus NS3 R155K/NS5B S282T and dual resistance mutation L159F/L320F in one patient. Treatment was safe and well tolerated. CONCLUSIONS: Mericitabine, danoprevir/r plus ribavirin for 24 weeks were safe and well tolerated. However, SVR rates were poor, achieving rates of only 25.0% in G1a and 63.6% in G1b patients.

Información, autoayuda y creación de identidades: las tecnologías de la información y la comunicación (TIC) y las asociaciones de discapacitados físicos. El ejemplo de la poliomielitis / Information, self-help and identity creation: information and communication technologies (ICTs) and associations for the physically disabled. The example of poliomyelitis

El objetivo del trabajo es estudiar la calidad de las páginas web de asociaciones de personas afectadas por poliomielitis y síndrome postpolio, como uno de los sistemas de intercambio de información y de visibilidad social de las personas con discapacidades físicas. Se realizó un estudio descriptivo de carácter transversal; fueron evaluadas 375 páginas web que cumplían los criterios de inclusión, encontradas a través del motor de búsqueda Google. La calidad fue estudiada a través de 22 variables, 8 de las cuales conforman el "Indicador de Credibilidad". Ninguna de las páginas cumplió con todos los criterios de calidad ni con los 8 puntos del Indicador de Credibilidad. Se observa una correlación positiva entre las variables de calidad y los criterios de credibilidad (r de Pearson = 0,81, p<0,001), por lo que se sugiere el Indicador de Credibilidad como una herramienta útil para determinar la calidad de las páginas web. Su uso debe complementarse con otro tipo de acercamientos cualitativos que exploren el contexto de las relaciones expertos-legos y las funciones que dichas páginas cumplen.

The aim of this paper is to study the quality of the websites of associations for people with polio and post-polio syndrome as an example of an important method for exchanging information and promoting the social visibility of physically disabled people. A descriptive cross-sectional study of 375 sites that met inclusion criteria, found using of the Google search engine, was carried out. The quality was studied through 22 variables, 8 of which make up the "Credibility Indicator". None of the websites met all the quality criteria nor all 8 items in the Credibility Index. A positive correlation between the variables of quality and credibility criteria (Pearson r = 0.81, p<0.001) was observed, therefore the Credibility Index is suggested as a useful tool for determining the quality of the websites. However, this tool must be supplemented with other qualitative approaches that explore both the contexts of lay-expert relationships and the function these sites serve.

Spain and the international scientific conferences on polio, 1940s-1960s.

The development of international health from a historical point of view has undergone major advances in recent times and constitutes a substantial part of the current agenda for historians of medicine. Within this framework, and focussing on a specific case study (international responses to poliomyelitis outbreaks in the 20th century), we explore the main actions and achievements of agencies such as the WHO and other private and international scientific organizations. Furthermore, this paper seeks to identify the Spanish presence and absence in these activities, their causes and consequences.

[The historical meaning of serological surveys as a laboratory technology applied to the immunization campaigns. The case of poliomyelitis in Spain]. / El significado histórico de las encuestas de seroprevalencia como tecnología de laboratorio aplicada a las campañas de inmunización. El caso de la poliomielitis en España.

The aim of the paper is to analyse the introduction, use and diffusion of the serological surveys, a public health technology on the borderline between epidemiology and laboratory, in connection with poliomyelitis in Spain during the Francoism period. Within the framework of the "new history" of medical technologies and innovations, the serological surveys played an important role both in the improvement of knowledge on socio-demographic distribution and the health politics arena.

El análisis modal de fallos y efectos (AMFE) ayuda a aumentar la seguridad en radioterapia / No disponible

Objetivos: A raíz de una incidencia de sobredosis detectada en el servicio de radioterapia, se puso en marcha un proyecto de análisis y eliminación de riesgos para aumentar la seguridad de los pacientes.Material y método: Se aplicó el análisis modal de fallos y efectos (AMFE), un instrumento analítico aplicado en varios hospitales de Estados Unidos. Como exige la metodología, se cuantificaron los riesgos de cada modo de fallo en una escala de 1:1.000 utilizando el índice NPR (número de priorización del riesgo). En una primera fase de mejora, se definió el nivel de actuación como NPR > 100. Se detectaron varios riesgos en los protocolos actuales y se eliminaron todos ellos mediante redefinición de circuitos, controles y verificaciones adicionales, listas de comprobación y auditorias internas, entre otros. Posteriormente, se introdujo un sistema de gestión de la calidad según ISO9001, se definió una serie de indicadores y la dirección se implicó realizando revisiones mensuales de los resultados. Resultados: Se implantaron 100 acciones de mejora. El índice de riesgo calculado después de haber tomado las acciones bajó significativamente y aumentó la seguridad. Las mejoras realizadas aseguran el mantenimiento del grado de seguridad logrado. Conclusiones: La experiencia muestra que se puede identificar objetivamente los riesgos de cada paso que damos y destinar los escasos recursos de que disponemos a los procesos o actividades donde el riesgo es mayor, mediante mejoras metodológicas de nuestros protocolos de trabajo

Objectives: As a result of an adverse event detected at the Radiotherapy Treatment Unit, a safety improvement project was undertaken to analyze and eliminate risks and thus increase patient safety. Material and method: Failure Mode and Effects Analysis (FMEA), ananalytical tool used in many US hospitals, was applied. As required by FMEA, risks of potential failure modes were quantified on a scale of 1 to 1000, using the Risk Priority Number (RPN). In the first improvement phase, an RPN value greater than 100 was consideredto be the limit above which corrective actions should be taken. Several potential failure modes were detected in existing treatment protocols and all the causes of potential failure modes were eliminatedthrough corrective actions that included redefinition of treatment protocols, the creation of new records for existing controls and the addition of new controls, checklists, and internal audits, amongother measures. Subsequently, a quality management system based on ISO9001 was introduced. Process indicators were defined to measure treatment quality, and the results were analyzed on a monthly basis with top management participation.Results: A total of 100 improvement actions were taken. The RPN values calculated after the implementation of the actions were significantly lower, increasing patient safety. The actions taken ensure the maintenance of the achieved safety levels. Conclusions: The experience shows that the risks present in all steps taken can be objectively identified. Through improved procedures, the limited resources available can be allocated to those processes or activities that pose maximum risk