Application of High-Z Gold Nanoparticles in Targeted Cancer Radiotherapy-Pharmacokinetic Modeling, Monte Carlo Simulation and Radiobiological Effect Modeling.

High-Z gold nanoparticles (AuNPs) conjugated to a targeting antibody can help to improve tumor control in radiotherapy while simultaneously minimizing radiotoxicity to adjacent healthy tissue. This paper summarizes the main findings of a joint research program which applied AuNP-conjugates in preclinical modeling of radiotherapy at the Klinikum rechts der Isar, Technical University of Munich and Helmholtz Zentrum München. A pharmacokinetic model of superparamagnetic iron oxide nanoparticles was developed in preparation for a model simulating the uptake and distribution of AuNPs in mice. Multi-scale Monte Carlo simulations were performed on a single AuNP and multiple AuNPs in tumor cells at cellular and molecular levels to determine enhancements in the radiation dose and generation of chemical radicals in close proximity to AuNPs. A biologically based mathematical model was developed to predict the biological response of AuNPs in radiation enhancement. Although simulations of a single AuNP demonstrated a clear dose enhancement, simulations relating to the generation of chemical radicals and the induction of DNA strand breaks induced by multiple AuNPs showed only a minor dose enhancement. The differences in the simulated enhancements at molecular and cellular levels indicate that further investigations are necessary to better understand the impact of the physical, chemical, and biological parameters in preclinical experimental settings prior to a translation of these AuNPs models into targeted cancer radiotherapy.

Sentinel lymph node mapping and intraoperative assessment in a prospective, international, multicentre, observational trial of patients with cervical cancer: The SENTIX trial.

BACKGROUND: SENTIX (ENGOT-CX2/CEEGOG-CX1) is an international, multicentre, prospective observational trial evaluating sentinel lymph node (SLN) biopsy without pelvic lymph node dissection in patients with early-stage cervical cancer. We report the final preplanned analysis of the secondary end-points: SLN mapping and outcomes of intraoperative SLN pathology. METHODS: Forty-seven sites (18 countries) with experience of SLN biopsy participated in SENTIX. We preregistered patients with stage IA1/lymphovascular space invasion-positive to IB2 (4 cm or smaller or 2 cm or smaller for fertility-sparing treatment) cervical cancer without suspicious lymph nodes on imaging before surgery. SLN frozen section assessment and pathological ultrastaging were mandatory. Patients were registered postoperatively if SLN were bilaterally detected in the pelvis, and frozen sections were negative. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02494063). RESULTS: We analysed data for 395 preregistered patients. Bilateral detection was achieved in 91% (355/395), and it was unaffected by tumour size, tumour stage or body mass index, but it was lower in older patients, in patients who underwent open surgery, and in sites with fewer cases. No SLN were found outside the seven anatomical pelvic regions. Most SLN and positive SLN were localised below the common iliac artery bifurcation. Single positive SLN above the iliac bifurcation were found in 2% of cases. Frozen sections failed to detect 54% of positive lymph nodes (pN1), including 28% of cases with macrometastases and 90% with micrometastases. INTERPRETATION: SLN biopsy can achieve high bilateral SLN detection in patients with tumours of 4 cm or smaller. At experienced centres, all SLN were found in the pelvis, and most were located below the iliac vessel bifurcation. SLN frozen section assessment is an unreliable tool for intraoperative triage because it only detects about half of N1 cases.

Cost-consequence analysis of fluticasone furoate/vilanterol 92/22 mcg for the management of COPD in the Spanish NHS.

OBJECTIVES: The Salford Lung Study in Chronic Obstructive Pulmonary Disease (SLS COPD) is a 12-month, open-label randomized clinical trial comparing clinical effectiveness and safety of initiating once-daily fluticasone furoate/vilanterol (FF/VI) 92/22 mcg with continuing usual care (UC) in patients with COPD followed in primary care in the UK. The objective of this analysis is to estimate the economic impact of these results when applied to Spain. MATERIALS AND METHODS: An Excel-based cost-consequence model with a one-year time horizon was populated with SLS COPD results, adopting the Spanish National Health System (NHS) perspective. Patients analyzed were diagnosed COPD patients ≥40 years old, currently managed with maintenance treatment and with a history of exacerbations (total number estimated from Spanish data). Mean least squares annual rates of moderate/severe exacerbations after 1 year for the intention-to-treat population from SLS COPD were included in the model (1.50 [FF/VI] and 1.64 [UC]); serious adverse events were excluded from the analysis as no differences between treatment arms were found. Medication and exacerbation management costs in euros were estimated from Spanish public sources for 2016. Model base-case analysis assumed an increased usage of FF/VI from 4% to 10% within 1 year, and a 100% proportion of days covered with study medications. Deterministic sensitivity analyses were performed for mitigating uncertainty. RESULTS: At base case, within 50,522 COPD patients analyzed, substitution of UC with FF/VI 92/22 mcg was associated with reduced medication and exacerbation management costs, leading to potential total annual savings of €353,623. Deterministic sensitivity results ranged from €218,333 up to €1,532,366 potential cost savings associated with FF/VI, showing the robustness of base-case results. CONCLUSION: The decreased rate of exacerbations with FF/VI 92/22 mcg compared with UC observed in SLS COPD could be translated into potential health care savings for the Spanish NHS. These results may be useful to inform decision-making processes.

[Bacteraemia at a second level hospital: epidemiological study, analysis of pronostic factors associated to mortality and economic cost estimation]. / Bacteriemias en un hospital de segundo nivel: estudio epidemiológico, análisis de factores pronósticos asociados a mortalidad y estimación de su coste económico.

INTRODUCTION: Bacteraemia (B) accounts for a considerable proportion (0.36%) of all hospital admissions due to infections diseases and it is associated to increased hospital costs. The aim of this study is to describe a cohort of patients with bacteraemia at a second level hospital, to analyze factors associated to mortality and its economical impact during hospital admission. PATIENTS AND METHODS: Observational study of a cohort of adult patients with bacteraemia admitted at a second level hospital during 2010. Data collection from clinical records has been done according to a standard protocol: epidemiological and clinical variables and factors associated to mortality were analysed. Total economical cost per patient was estimated. RESULTS: 148 patients were included: 80 community B (55.4%), 23 health care associated B (15.5%) and 45 nosocomial B (28.5%). The incidence was 9 cases 10.000 persons/year. Mean age was 69 years and the global mortality was 24%. In bivariate analysis smoking, diabetes mellitus, McCabe Jackson score type I-II, Pitt Index ≥ 3, APACHE ≥ 20, Glasgow ≤ 9, shock, respiratory distress, invasive procedures, nosocomial bacteraemia and inadequate empiric or definitive antibiotic treatment were associated to mortality (p<0.05). Factors associated to mortality in multivariate analysis included McCabe Jackson score type I-II (OR 4.95; 95% CI 1.095-22.38), haemodialysis during acute stage (OR 7.8; 95% CI 2.214-27.773) and inadequate empiric antibiotic treatment (OR 7.68; 95% CI 19.82-29.77). Admission economic cost per patient was 9,459 € for community acquired bacteriemia, 5,656 € for health care associated bacteraemia and 41,680€ for nosocomial bacteraemia. CONCLUSIONS: Comorbidity, inadequate empiric antibiotic treatment and haemodialysis during acute phase are statistically significantly in our cohort of patients with bacteraemia.

Evaluación de la calidad de atención pediátrica desde la perspectiva de género / Evaluation of the quality of pediatric care from a gender perspective / Avaliação da qualidade da atenção pediátrica na perspectiva de gênero

Objetivo: Evaluar la calidad de atención, desde una perspectiva de género por las y los usuarios y las y los proveedores de salud, en un hospital de tercer nivel que brinda atención pediátrica, para describir la situación que existe en las dimensiones de estructura, proceso y resultado. Método: Este estudio tiene un diseño transversal, no experimental. Su alcance es Descriptivo y Exploratorio, de enfoque Mixto. La variable medida fue Calidad de la atención pediátrica, en las dimensiones de: estructura, proceso y resultado; con las Categorías del modelo de Isabel Matamala (Enfoque de Género): Dignificación de usurarias/os, Conciencia y ejercicio de derechos humanos, Competencia técnica, vínculo interpersonal y comportamientos favorables. Universo: Personal de salud del servicio de urgencias en los diferentes turnos y las y los usuarios (padres, madres y tutores) de niñas y niños ingresados al servicio de urgencias (mayo 2010). La muestra: Para los proveedores se tomó el 100% del personal médico y de enfermería del servicio de urgencias (72 proveedores). La muestra de los usuarios se calculó con base en el número de ingresos otorgados en el mes anterior a la aplicación del instrumento. No. 1114, n167. Se realizaron 6 entrevistas a profundidad, 2 usuarias/os y 4 a proveedores. Para la recolección de datos: Se elaboraron 2 cuestionarios tipo Likert, uno para usuarias/os y otro para proveedores, en base a los indicadores del modelo y dos guías para entrevistas a profundidad. Las cuales fueron audio grabadoras y se realizó una nota de campo y se realizó una nota de campo, en este proceso se solicitó consentimiento informado verbal y escrito. Los cuestionarios tienen 3 apartados, el primero datos socio demográficos, el segundo un apartado de respuestas dicotómicas que miden calidad y el tercero afirmaciones con escala tipo Liker, sobre calidad de atención pediátrica, al último 2 respuestas abiertas. Los datos se procesaron en la base de datos SPSS versión 18. Ambos instrumentos arrojaron un alfa Cronbach de (0.8), en una prueba piloto con 30 sujetos por cada caso, en un hospital similar al del estudio en la ciudad de México. Resultados: Se destaca: Que en la calificación total de calidad de atención por parte de las usuarias y usuarios, se encontró una mínima de 78 y máxima de 129, siendo la calificación ideal de 130 puntos, con una media 118±16. En cambio para la calificación total de calidad en sus dimensiones de estructuran proceso y resultado se encontró una media de 109±15 con una calificación mínima de 87 y máxima de 138 con el ideal de 145 puntos. La calidad de los servicios de salud pediátrica de esta institución medida en las 5 categorías, se calificó como excelente en un 55%. Por parte de los padres, madres y tutores, se encontró que a mayor edad califican mejor la calidad de atención. En el caso de los padres menores de 25 años califican mejor la dimensión de resultado, lo que conlleva a declarar que se enfocan a la resolución de su problema de salud y no al proceso de cómo se brinda la atención. Por otro lado se encontró que existe un trato diferente entre proveedoras y proveedores, donde las médicas refieren sufrir algún tipo de discriminación y ser menos reconocidas que los médicos. El personal de enfermería, reiteró que existe inequidad en el trato entre proveedores de salud. Por otro lado el sexo femenino prevalece en la práctica pediátrica y las disparidades por razón de género están presentes.

Objective: To evaluate the quality of care, from a gender perspective by users and health providers, in a tertiary hospital that provides pediatric care, to describe the situation that exists in the dimensions of structure, process and result. Method: This study has a cross-sectional, non-experimental design. Its scope is descriptive and exploratory, with a mixed approach. The variable measured was Quality of pediatric care, in the dimensions of: structure, process and result; with the Isabel Matamala Model Categories (Gender Approach): Dignification of usurers, Awareness and exercise of human rights, Technical competence, interpersonal bond and favorable behaviors. Universe: Health personnel of the emergency service in the different shifts and the users (parents, mothers and guardians) of children admitted to the emergency service (May 2010). The sample: For the providers, 100% of the medical and nursing personnel of the emergency service were taken (72 providers). The sample of the users was calculated based on the number of income granted in the month prior to the application of the instrument. No. 1114, n167. Six in-depth interviews were conducted, 2 users and 4 providers. For data collection: 2 Likert questionnaires were created, one for users and one for providers, based on model indicators and two guides for in-depth interviews. Which were audio recorders and a field note was made and a field note was made, verbal and written informed consent was requested in this process. The questionnaires have 3 sections, the first socio-demographic data, the second a section of dichotomous answers that measure quality and the third Liker-type affirmations, on quality of pediatric care, to the last 2 open responses. The data were processed in the SPSS database, version 18. Both instruments yielded a Cronbach alpha of (0.8), in a pilot test with 30 subjects per case, in a hospital similar to that of the study in Mexico City. Results: It stands out: That in the total qualification of quality of attention by the users and users, a minimum of 78 and a maximum of 129 was found, with an ideal score of 130 points, with an average of 118 ± 16. On the other hand, for the total quality qualification in its dimensions of structure, process and result, an average of 109 ± 15 was found with a minimum score of 87 and a maximum of 138 with the ideal of 145 points. The quality of the pediatric health services of this institution, measured in the 5 categories, was rated as excellent by 55%. On the part of parents, mothers and guardians, it was found that at a higher age the quality of care is better qualified. In the case of parents under the age of 25, the result dimension is better qualified, which leads to the statement that they focus on the resolution of their health problem and not on the process of how care is provided. On the other hand, it was found that there is a different treatment between providers and providers, where the doctors refer to suffer some type of discrimination and be less recognized than the doctors. The nursing staff reiterated that there is inequity in the treatment of health providers. On the other hand, the female sex prevails in pediatric practice and disparities due to gender are present.

Objetivo: Avaliar a qualidade da assistência, na perspectiva de gênero, por usuários e profissionais de saúde, em um hospital terciário que oferece assistência pediátrica, para descrever a situação existente nas dimensões de estrutura, processo e resultado. Método: Este estudo possui delineamento transversal, não experimental. Seu escopo é descritivo e exploratório, com abordagem mista. A variável medida foi a qualidade da assistência pediátrica, nas dimensões de: estrutura, processo e resultado; com as Categorias de Modelo de Isabel Matamala (Abordagem de Gênero): Dignificação dos usuários, Conscientização e exercício dos direitos humanos, Competência técnica, vínculo interpessoal e comportamentos favoráveis. Universo: Pessoal de saúde do serviço de emergência nos diferentes turnos e os usuários (pais, mães e responsáveis) das crianças admitidas no serviço de emergência (maio de 2010). A amostra: Para os provedores, 100% do pessoal médico e de enfermagem do serviço de emergência foram atendidos (72 provedores). A amostra dos usuários foi calculada com base no número de receitas concedidas no mês anterior à aplicação do instrumento. No. 1114, n167. Seis entrevistas em profundidade foram realizadas, 2 usuários e 4 fornecedores. Para coleta de dados: foram criados 2 questionários tipo Likert, um para usuários e outro para provedores, baseado em indicadores de modelos e dois guias para entrevistas em profundidade. Que eram gravadores de áudio e uma anotação de campo foi feita e uma anotação de campo foi feita, consentimento informado verbal e por escrito foi solicitado neste processo. Os questionários possuem 3 seções, os primeiros dados sociodemográficos, a segunda uma seção de respostas dicotômicas que medem a qualidade e a terceira Afirmações do tipo Liker, sobre a qualidade da assistência pediátrica, às duas últimas respostas abertas. Os dados foram processados ​​no banco de dados SPSS versão 18. Ambos os instrumentos mostrou um alfa Cronbach de (0,8) em um teste piloto com 30 indivíduos em cada caso, em um hospital estudo semelhante na Cidade do México. Resultados: Destaca-se: Que a avaliação global da qualidade de atenção de usuários e usuários, um mínimo de 78 e máximo de 129 foi encontrada, sendo a pontuação ideal de 130 pontos, com média de 118 ± 16. Em contraste com a avaliação global da qualidade dimensionalmente eles estruturado processo e resultar em uma média de 109 ± 15 com uma pontuação mínima de 87 e máximo de 138 com o ideal de 145 pontos foi encontrado. A qualidade dos serviços de saúde pediátrica dessa instituição, medida nas 5 categorias, foi classificada como excelente por 55%. Por parte dos pais, mães e responsáveis, constatou-se que, em idade mais avançada, a qualidade do atendimento é mais qualificada. Para os pais com menos de 25 qualificar dimensão melhor resultado, levando a testemunhar que o foco em resolver seu problema de saúde e não o processo de como os cuidados são prestados. Por outro lado, verificou-se que existe um tratamento diferenciado entre prestadores e prestadores, onde os médicos referem sofrer algum tipo de discriminação e serem menos reconhecidos que os médicos. A equipe de enfermagem reiterou que há desigualdade no tratamento dos profissionais de saúde. Por outro lado, o sexo feminino prevalece na prática pediátrica e as disparidades por gênero estão presentes.