Prospective Assessment of Bone Metabolism Biomarkers and Survival in Metastatic Castration-resistant Prostate Cancer Patients Treated with Radium-223: The PRORADIUM Study.

BACKGROUND: Radium-223 is an active therapy option for bone metastatic castration-resistant prostate cancer (mCRPC). The lack of adequate biomarkers for patient selection and response assessment are major drawbacks for its use. OBJECTIVE: To assess the prognostic value of bone metabolism biomarkers (BMBs) in ra-223-treated mCRPC patients. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of mCRPC patients treated with Ra-223 (PRORADIUM study: NCT02925702) was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The main objective of the study was to evaluate the association between high (≥median) baseline values in at least three bone formation (bone alkaline phosphatase [BAP] and C-terminal type-I collagen propeptide) and bone resorption (N-terminal telopeptide and pyridinoline) biomarkers, and survival. The independent prognostic value of each BMB was also assessed. The association with time to radiographic, clinical, and prostate-specific antigen (PSA) progression; time to skeletal-related events; and PSA response were secondary objectives. Multivariable (MV) Cox-regression models were evaluated. RESULTS AND LIMITATIONS: A total of 169 patients were included. Of the patients, 70.4% received Ra-223 in second/third line; 144 (85.2%) were Eastern Cooperative Oncology Group 0-1, 126 (74.6%) were in pain, and 80 (47.5%) had more than ten bone metastases. Sixty-seven (39.6%) patients had elevation in at least three BMBs. The median overall survival was 12.1 mo (95% confidence interval [CI]: 10-14.7). No association was observed with other treatment-related secondary outcome parameters. Patients with high values in three or more BMBs had significantly worse survival (9.9 vs 15.2 mo; hazard ratio [HR]: 1.8 [95% CI: 1.3-2.5]; p < 0.001) in the univariate analysis, but not independent in the MV analysis (HR: 1.33; 95% CI: 0.89-2; p = 0.181). High baseline BAP was the only biomarker associated with survival in the MV model (HR: 1.89; 95% CI: 1.28-2.79; p = 0.001). Addition of BAP to the MV clinical model increased the area under the receiver operating characteristic curve 2-yr value from 0.667 to 0.755 (p = 0.003). CONCLUSIONS: Biomarkers of bone formation, especially BAP, have prognostic value in mCRPC patients treated with radium-223. Its predictive value remains to be assessed, ideally in prospective, adequately powered, randomised clinical trials. PATIENT SUMMARY: In this study, we evaluate the role of bone metabolism biomarkers to help improve the use of radium-223 as therapy for advanced prostate cancer. We found that bone alkaline phosphatase may be a suitable tool.

Adjuvant dabrafenib and trametinib for patients with resected BRAF -mutated melanoma: DESCRIBE-AD real-world retrospective observational study.

BRAF and MEK inhibitor, dabrafenib plus trametinib, adjuvant therapy is effective for high-risk resected melanoma patients with BRAF - V600 mutations. However, real-world evidence is limited. We aimed to determine the feasibility of this therapy in routine clinical practice. DESCRIBE-AD, a retrospective observational study, collected real-world data from 25 hospitals in Spain. Histologically confirmed and resected BRAF -mutated melanoma patients aged ≥18 years who were previously treated with dabrafenib plus trametinib adjuvant therapy, were included. The primary objectives were treatment discontinuation rate and time to discontinuation. The secondary objectives included safety and efficacy. From October 2020 to March 2021, 65 patients were included. Dabrafenib and trametinib discontinuation rate due to treatment-related adverse events (TRAEs) of any grade was 9%. Other reasons for discontinuation included patients' decisions (6%), physician decisions (6%), unrelated adverse events (3%), disease progression (5%), and others (5%). The median time to treatment discontinuation was 9 months [95% confidence interval (CI), 5-11]. G3-4 TRAEs occurred in 21.5% of patients, the most common being pyrexia (3%), asthenia (3%), and diarrhoea (3%). Unscheduled hospitalisations and clinical tests occurred in 6 and 22% of patients, respectively. After 20-month median follow-up (95% CI, 18-22), 9% of patients had exitus due to disease progression, with a 12-month relapse-free survival and overall survival rates of 95.3% and 100%, respectively. Dabrafenib and trametinib adjuvant therapy proved effective for melanoma patients in a real-world setting, with a manageable toxicity profile. Toxicity frequencies were low leading to low incidence of unscheduled medical visits, tests, and treatment discontinuations.

Clinical Factors Associated With Long-Term Benefit in Patients With Metastatic Renal Cell Carcinoma Treated With Axitinib: Real-World AXILONG Study.

BACKGROUND: Axitinib monotherapy obtained approval in pre-treated mRCC patients and recently in combination with pembrolizumab or avelumab in the first-line setting. However, patient profiles that may obtain increased benefit from this drug and its combinations still need to be identified. PATIENTS AND METHODS: Retrospective multicentre analysis describing clinical characteristics associated with axitinib long-responder (LR) population by comparing two extreme-response sub-groups (progression-free survival [PFS] ≥9 months vs. disease progression/refractory patients [RP]). A multivariate logistic-regression model was used to analyse clinical factors. Efficacy and safety were also analysed. RESULTS: In total, 157 patients who received axitinib in second or subsequent line were evaluated (91 LR and 66 RP). Older age at start of axitinib and haemoglobin levels > LLN were independent predictive factors for LR in multivariate analyses. In LR patients, median (m) PFS was 18.1 months, median overall survival was 36.0 months and objective response rate (ORR) was 45.5%. In 59 LR patients receiving axitinib in second-line, mPFS was 18.7 months, mOS was 44.8 months and ORR was 43.9%. mOS was significantly longer in second line compared to subsequent lines (44.8 vs. 26.5 months; P = .009). In LR vs. RP, mPFS with sunitinib in first-line was correlated with mPFS with axitinib in second-line (27.2 vs. 10.9 months P < .001). The safety profile was manageable and consistent with known data. CONCLUSIONS: This study confirms the long-term benefits of axitinib in a selected population, helping clinicians to select the best sequential approach and patients who could obtain a greater benefit from axitinib.

Preferences for Renal Cell Carcinoma Pharmacological Treatment: A Discrete Choice Experiment in Patients and Oncologists.

INTRODUCTION: The purpose of this investigation was to explore patients' and oncologists' preferences for the characteristics of a pharmacological regimen for patients with advanced renal cell carcinoma (aRCC). MATERIAL AND METHODS: Cross-sectional observational study based on a discrete choice experiment (DCE) conducted in Spain. A literature review, a focus group with oncologists and interviews with patients informed the DCE design. Five attributes were included: progression survival gain, risk of serious adverse events (SAEs), health-related quality of life (HRQoL), administration mode, and treatment cost. Preferences were analyzed using a mixed-logit model to estimate relative importance (RI) of attributes (importance of an attribute in relation to all others), which was compared between aRCC patients and oncologists treating aRCC. Willingness to pay (WTP, payer: health system) for a benefit in survival or in risk reduction and maximum acceptable risk (MAR) in SAEs for improving survival were estimated from the DCE. Subgroup analyses were performed to identify factors that influence preference. RESULTS: A total of 105 patients with aRCC (77.1% male, mean age 65.9 years [SD: 10.4], mean time since RCC diagnosis 6.3 years [SD: 6.1]) and 67 oncologists (52.2% male, mean age 41.9 years [SD: 8.4], mean duration of experience in RCC 10.2 years [SD: 7.5]) participated in the study. The most important attribute for patients and oncologists was survival gain (RI: 43.6% vs. 54.7% respectively, p<0.05), followed by HRQoL (RI: 35.5% vs. 18.0%, respectively, p<0.05). MAR for SAEs was higher among oncologists than patients, while WTP (for the health system) was higher for patients. Differences in preferences were found according to time since diagnosis and education level (patients) or length of professional experience (oncologists). CONCLUSION: Patients' and oncologists' preferences for aRCC treatment are determined mainly by the efficacy (survival gain) but also by the HRQoL provided. The results of the study can help to inform decision-making in the selection of appropriate aRCC treatment.

Tipos de estudios más comunes en la residencia de higiene y epidemiología en la provincia Camagüey / Types of studies most common in the residence of hygiene and epidemiology in the Camagüey province

RESUMEN Fundamento: la higiene y epidemiología como especialidad juega un importante papel en la búsqueda de soluciones para los problemas emergentes de salud a través de la investigación, lo cual se refleja en las publicaciones periódicas de las revistas especializadas dedicadas al tema. Objetivo: informar sobre los diseños más utilizados en las investigaciones de terminación de residencia de higiene y epidemiología y hacia qué áreas de la especialidad tributaron. Métodos: se realizó un estudio descriptivo de corte transversal. Se revisaron 72 tesis de grado existentes en la biblioteca del Centro Provincial de Higiene Epidemiología y Microbiología de la provincia de Camagüey desde el curso 1989-90, fecha en que se integraron las dos especialidades en una sola y que incluyó los residentes de Ciego de Ávila y Las Tunas formados también en la institución. El eje de clasificación de las investigaciones propuestas se basó, a fin de unificar criterios, en la segunda edición de la segunda reimpresión corregida en inglés y traducida al español del libro Epidemiología Básica de Bonita R, Beaglehole R y Kjellstrӧm T (2008). Resultados: tanto en el área de epidemiología como en la de salud ambiental existe un predominio del diseño descriptivo sobre el resto de las modalidades. El área a la que mayor tributaron los trabajos investigativos fue la de epidemiología, a pesar de lo bien representada que está la salud ambiental (higiene) en el programa de estudios. Conclusiones: existe un predominio de los trabajos descriptivos sobre otros diseños investigativos. Los temas de tesis en su mayoría tributaron al área de la epidemiología a pesar de lo bien representada que está la salud ambiental en el plan de estudios de la residencia.

ABSTRACT Background: hygiene & epidemiology as a specialty plays an important role in the search of solutions for emerging health problems by means of research, as it is reflected in periodic publications in specialized journals devoted to the topic. Objective: to inform about the most common designs used in research for the termination of residency of hygiene & epidemiology and to what areas of the specialty they were devoted. Methods: a descriptive, cross-section study was carried out. 72 scientific thesis were studied at the library of the Provincial Center of Hygiene, Epidemiology and Microbiology of Camagüey since the academic year 1989-90, the period of integration of the former two specialties, including residents from Ciego de Avila and Las Tunas. In order to unify criteria, the axis of classification for the proposed researches was based on the 2nd edition translated into Spanish of the book Basic Epidemiology by Bonita R, Beaglehole R & Kjellstrӧm T (2008). Results: in both areas, epidemiology and environmental health, prevails the descriptive design over the rest of the models. The area with majority of research work was epidemiology in spite of the well represented that environmental health area is in the study program. Conclusions: there was a prevalence of the descriptive works over other investigative designs. Majority of thesis topics were related to epidemiology in spite of the well represented area of environmental health is in the residency program.

Tipos de estudios más comunes en la residencia de higiene y epidemiología en la provincia Camagüey / Types of studies most common in the residence of hygiene and epidemiology in the Camagüey province

Fundamento: la higiene y epidemiología como especialidad juega un importante papel en la búsqueda de soluciones para los problemas emergentes de salud a través de la investigación, lo cual se refleja en las publicaciones periódicas de las revistas especializadas dedicadas al tema. Objetivo: informar sobre los diseños más utilizados en las investigaciones de terminación de residencia de higiene y epidemiología y hacia qué áreas de la especialidad tributaron. Métodos: se realizó un estudio descriptivo de corte transversal. Se revisaron 72 tesis de grado existentes en la biblioteca del Centro Provincial de Higiene Epidemiología y Microbiología de la provincia de Camagüey desde el curso 1989-90, fecha en que se integraron las dos especialidades en una sola y que incluyó los residentes de Ciego de Ávila y Las Tunas formados también en la institución. El eje de clasificación de las investigaciones propuestas se basó, a fin de unificar criterios, en la segunda edición de la segunda reimpresión corregida en inglés y traducida al español del libro Epidemiología Básica de Bonita R, Beaglehole R y Kjellstrӧm T (2008). Resultados: tanto en el área de epidemiología como en la de salud ambiental existe un predominio del diseño descriptivo sobre el resto de las modalidades. El área a la que mayor tributaron los trabajos investigativos fue la de epidemiología, a pesar de lo bien representada que está la salud ambiental (higiene) en el programa de estudios. Conclusiones:existe un predominio de los trabajos descriptivos sobre otros diseños investigativos. Los temas de tesis en su mayoría tributaron al área de la epidemiología a pesar de lo bien representada que está la salud ambiental en el plan de estudios de la residencia(AU)

Background: hygiene & epidemiology as a specialty plays an important role in the search of solutions for emerging health problems by means of research, as it is reflected in periodic publications in specialized journals devoted to the topic. Objective: to inform about the most common designs used in research for the termination of residency of hygiene & epidemiology and to what areas of the specialty they were devoted. Methods: a descriptive, cross-section study was carried out. 72 scientific thesis were studied at the library of the Provincial Center of Hygiene, Epidemiology and Microbiology of Camagüey since the academic year 1989-90, the period of integration of the former two specialties, including residents from Ciego de Avila and Las Tunas. In order to unify criteria, the axis of classification for the proposed researches was based on the 2nd edition translated into Spanish of the book Basic Epidemiology by Bonita R, Beaglehole R & Kjellstrӧm T (2008). Results: in both areas, epidemiology and environmental health, prevails the descriptive design over the rest of the models. The area with majority of research work was epidemiology in spite of the well represented that environmental health area is in the study program. Conclusions: there was a prevalence of the descriptive works over other investigative designs. Majority of thesis topics were related to epidemiology in spite of the well represented area of environmental health is in the residency program(AU)

Dabrafenib plus trametinib for compassionate use in metastatic melanoma: A STROBE-compliant retrospective observational postauthorization study.

The main objective of the study was to evaluate the efficacy and safety of dabrafenib alone or combined with trametinib for compassionate use in patients with metastatic melanoma.This retrospective, observational study involved 135 patients with unresectable stage IIIC or stage IV melanoma from an expanded-access program at 30 Spanish centers.Forty-eight patients received dabrafenib monotherapy and 87 received combination dabrafenib and trametinib; 4.4% and 95.6% of the patients had stage IIIC and IV melanoma, respectively. All patients showed BRAF mutations in their primary or metastatic lesions; 3 were positive for V600K while the remainder had V600E or V600+. A positive response to treatment was reported in 89.3% of the patients. Overall survival rates at 12 and 24 months were 59.6% (95% confidence interval [CI], 52.5-68.9%) and 36.4% (95% CI, 27.8-45%), respectively. Progression-free survival rates at 12 and 24 months were 39.3% (95% CI, 31.1-47.5%) and 21.6% (95% CI, 14.5-28.7%), respectively. Fifty-seven patients (42.2%) reported cutaneous toxicity of any type, mainly hyperkeratosis (14.8%) and rash (11.9%). The most frequent adverse events were pyrexia (27.4%), asthenia (19.3%), arthralgia (16.9%), and diarrhoea (13.2%).Our results suggest that both dabrafenib alone or in combination with trametinib are effective for compassionate use in terms of response and/or survival rates. However, differences in patients' prognostic features ought to be considered. No new findings were revealed regarding the safety profiles of either regimen. This is the first study to evaluate the efficacy of these 2 selective BRAF and mitogen-activated extracellular signal-regulated kinase inhibitors in a real-world setting in Spain.

Impact on clinical practice of the implementation of guidelines for the toxicity management of targeted therapies in kidney cancer. The protect-2 study.

BACKGROUND: The impact of such recommendations after their implementation of guidelines has not usually been evaluated. Herein, we assessed the impact and compliance with the Spanish Oncology Genitourinary Group (SOGUG) Guidelines for toxicity management of targeted therapies in metastatic renal cell carcinoma (mRCC) in daily clinical practice. METHODS: Data on 407 mRCC patients who initiated first-line targeted therapy during the year before and the year after publication and implementation of the SOGUG guideline program were available from 34 Spanish Hospitals. Adherence to SOGUG Guidelines was assessed in every cycle. RESULTS: Adverse event (AE) management was consistent with the Guidelines as a whole for 28.7% out of 966 post-implementation cycles compared with 23.1% out of 892 pre-implementation cycles (p = 0.006). Analysis of adherence by AE in non-compliant cycles showed significant changes in appropriate management of hypertension (33% pre-implementation vs. 44.5% post-implementation cycles; p < 0.0001), diarrhea (74.0% vs. 80.5%; p = 0.011) and dyslipemia (25.0% vs. 44.6%; p < 0.001). CONCLUSIONS: Slight but significant improvements in AE management were detected following the implementation of SOGUG recommendations. However, room for improvement in the management of AEs due to targeted agents still remains and could be the focus for further programs in this direction.

Safety and effectiveness of vinflunine in patients with metastatic transitional cell carcinoma of the urothelial tract after failure of one platinum-based systemic therapy in clinical practice.

BACKGROUND: Patients with transitional cell carcinoma of the urothelial tract (TCCU) who fail initial platinum-based chemotherapy for advanced disease represent a challenge in daily clinical practice. Vinflunine is approved by the European Medicine Agency (EMA) but, up to now, limited experience has been reported outside clinical trials. METHODS: We assessed the efficacy and safety of vinflunine in an unselected group of 102 consecutive patients with metastatic TCCU. RESULTS: The median age was 67 years (range 45-83). Among the most common comorbidities that patients presented at baseline were hypertension (50.5%) and diabetes (20.7%).Distant metastases were present in retroperitoneal nodes (58%), lung (29.3%), and bone (20.2%). The ECOG 0, 1 and 2 performance status at the start of vinflunine were 31.3%, 60.6% and 8.1%, respectively. The most commonly reported adverse events of any grade were constipation 70.6% (5.9% grade 3-4), vomiting 49.1% (2% grade 3-4), neutropenia 48.1% (12.8% grade 3-4) and abdominal pain 34.3% (4.9% grade 3-4). A median of 4 cycles of vinflunine was administered per patient (range 1-18). Median progression free and overall survival for all patients (N = 102) were 3.9 months (2.3-5.5) and 10 months (7.3-12.8), respectively. Time to tumor progression was 4.3 months (2.6-5.9). Two patients (2%) achieved CR, 23 (22.5%) patients had PR, and 42 (41.2%) presented SD as best response. The clinical benefit rate with vinflunine was 65.7%. CONCLUSIONS: Our results show that the behavior of vinflunine in routine clinical practice resembles that of the pivotal phase III randomized study.

Metastatic castration-resistant prostate cancer: changing landscape with cabazitaxel.

Docetaxel is the standard first-line chemotherapy for men with metastatic castration-resistant prostate cancer. Until recently, there was no standard therapy after failure of docetaxel treatment. Cabazitaxel has been shown to improve overall survival in this setting. As a result, the treatment paradigm for mCRPC is changing rapidly. The improved survival shown with cabazitaxel provides an important new opportunity to treat men with mCRPC after docetaxel treatment. Despite the toxicity recorded in the pivotal study, subsequent trials have shown that cabazitaxel is a safe drug. Patient selection and the optimal interval between prior docetaxel treatment and cabazitaxel remain the critical issues. According to a subanalysis of the various studies discussed in this review, there is a patient profile that will probably benefit from use of cabazitaxel after docetaxel failure. Cabazitaxel represents a new treatment option for patients with prostate cancer.

Sunitinib: the first to arrive at first-line metastatic renal cell carcinoma.

Tyrosine kinase inhibitors (TKIs) are beneficial for the treatment of renal cell carcinoma (RCC), gastrointestinal stromal tumors (GIST), pancreatic neuroendocrine tumors (pNETs), and other tumors. The antitumor activity of sunitinib has been based on time-related parameters such as progression-free survival (PFS) and overall survival (OS). Advances in knowledge of the molecular mechanisms and oncogenic processes associated with RCC have enabled the availability of rational targets for pharmacotherapy. Although each small molecule is modeled to block the activity of selected kinase signaling enzymes, it is increasingly evident that many have nontargeted effects (on other kinases) that may cause unexpected complications. The recommended dose for sunitinib in patients with advanced RCC is a 50 mg oral daily dose, with or without food, on a 4/2 week schedule (4 weeks "on" vs. 2 weeks "off") until progression. An alternative continuous 37.5 mg/day dosing schedule has also been evaluated and appears to be well tolerated, allowing the maintenance of the dose density of sunitinib with a similar outcome. The continuous administration schedule provides a constant exposure to the drug, and may prevent potential tumor regrowth and angiogenesis recovery. Most side effects are reversible and should not result in sunitinib discontinuation. In this article, the body of evidence behind the use of sunitinib in metastatic RCC (mRCC) compared to other targeted agents that have recently come into the field is summarized, and the need for correct management of an adverse event profile in order to better optimize available treatment options is underlined.

Percepción de riesgo en desastres, un tema a priorizar en la educación médica / Risk Perception in Disasters, a Topic to Prioritize in Medical Education

Se realizó una breve introducción al tema de los desastres. Se enfatiza en la estrategia de las Naciones Unidas para su enfrentamiento, así como, el reto que plantean estos a los países pobres para mitigar sus efectos. Se presenta su definición, clasificación, y se esclarecen los términos riesgo, peligro o amenaza y vulnerabilidad. Finalmente, se expone con brevedad la metodología para el análisis y manejo tanto del riesgo como de su percepción(AU)...

A brief introduction to the theme of disasters was carried out. The United Nations Strategy for their confrontation and the challenge raised to these poor countries to mitigate the disasters effects was emphasized. The disasters definition and classification were also showed, as well as the explanation of terms: risk, danger or threat and vulnerability. Finally the methodology for the analysis and management of both risk and its perception was briefly outlined(AU)...

Desarrollo de la formación de técnicos y tecnólogos de la Salud en Cuba / Development of the formation of Health technicians and technologists in Cuba

Se caracterizan las etapas de la formación de técnicos medios y tecnólogos de la salud en Cuba, atendiendo a las peculiaridades en los currículos. Se aborda el actual modelo del licenciado en Tecnología de la Salud, con un ciclo básico fortalecido y la consiguiente reducción a ocho especialidades. Se muestra el impacto social de este nuevo modelo pedagógico, que ha dado respuesta a las exigencias de los servicios de salud cubanos y ha permitido cumplir las demandas de cooperación en otros países.

This paper describes the stages of the formation of Health technicians and technologists in Cuba, including the particularities of the syllabi. It deals with the current model of bachelor of Health Technology, which presents a ber basic cycle and eight specialties. It also includes the social impact of this new educational model, which responds to the demands of both Cuban health services and cooperation in other countries.

Insuficiencias con el manejo de epidemias en el Programa Integral de Salud nicaragüeño. Propuesta de guía práctica / Epidemics managing insufficiencies in the Nicaraguan Health Integrated Program. A practical guide proposal

Se presenta un estudio observacional descriptivo que identificó las insuficiencias en el manejo de epidemias en las regiones autónomas del Atlántico norte y sur y en los departamentos de Matagalpa y Río San Juan, donde miembros de la brigada médica cubana cooperan con la asistencia y la docencia. En estos territorios se forman especialistas en Medicina General Integral, quienes cumplen su servicio social como médicos generales nacionales. A cooperantes y nacionales se les aplicó una encuesta para evaluar su conocimiento sobre el manejo de epidemias a nivel de la Atención Primaria de Salud. La misma incluyó aspectos técnicos, metodológicos, organizativos y operacionales. Los resultados demostraron un bajo nivel de conocimientos. A partir de las insuficiencias detectadas se diseñó una guía práctica para mejorar la preparación del personal en el enfrentamiento de estos eventos adversos a la salud.

An observational descriptive study was carried out to identify inefficiencies in the management of epidemics, in the autonomous North and South Atlantic regions and the departments of Matagalpa and Río San Juan, where Cuban medical brigade members cooperate with the assistance and teaching of future specialists of Integrated General Medicine who discharge their social service as physicians. Both cooperationists and nationals were surveyed to assess their knowledge about the management of epidemics in primary health care, including the technical, methodological, organizational, and operational aspects. Results showed little knowledge. A practical guide was designed to improve personnel training in facing up health-endangering events.

Diseño de reportes técnicos para perfeccionar el Sistema de Vigilancia en Salud nicaragüense / Technical report designing to improve the Nicaraguan Health Surveillance System

Se realizó un estudio observacional descriptivo de las insuficiencias del Ministerio de Salud Pública nicaragüense en la notificación y el reporte de eventos adversos a la salud. Entre los factores identificados estaban la falta de personal calificado para asumir tareas a nivel de puestos y centros de salud, la carencia de medios de comunicación para transmitir la información recolectada en comunidades y unidades de salud, y la falta de disciplina informativa, de retroalimentación y uniformidad de los formatos para la recolección del dato primario, lo que dificultaba el procesamiento automatizado de la información y la calidad de los partes diarios y semanales. Se diseñaron e implementaron nuevos formatos que fueron validados y que mejoraron la calidad del sistema de vigilancia y la detección oportuna de los problemas que afectaban la salud de la población.

An observational descriptive study was carried out to detect insufficiencies of the Nicaraguan Ministry of Health in notifying and reporting health-endangering events. Among the identified factors, there were lack of qualified personnel to assume responsibilities, lack of communication systems to transmit the information collected in communities and health units, and the inadequate informative discipline, feedback, and format inconsistency to collect of primary data, which attempted the information automatic processing, as well as the quality of daily and weekly reports. New formats were designed and implemented, which were later assessed as they improved the quality of the system of surveillance and detection of health-endangering problems.

Sistema de vigilancia en salud en la provincia Holguín. 1993-2007 / Health Surveillance System in Holguín Province. 1993-2007

Se realizó una investigación observacional descriptiva en la cual se abordan definiciones de los términos epidemiología, vigilancia epidemiológica y vigilancia en salud. La transición que se observa con mayor relevancia hacia las enfermedades no transmisibles, se acompaña de nuevos comportamientos en algunas enfermedades transmisibles ya controladas, así como, la aparición de nuevas emergencias como la epidemia de neuropatía en el país, y más recientemente, el síndrome de Guillan-Barré en la capital, por lo que se hace ostensible la necesidad de fortalecer y desarrollar el conocimiento y la práctica de la Epidemiología en todos los niveles del Sistema Nacional de Salud, al demostrase la existencia de brechas en los sistemas de vigilancia epidemiológica existentes...(AU)

An observational descriptive research was done in which epidemiological definitions, terms, surveillance and health surveillance were defined. The transition to non- transmissible illnesses was the one of highest incidence, new behaviors were observed in some transmissible illnesses already controlled such as the new epidemic of neuropathy in the country, and more recently Gillians syndrome. It demonstrated that it was necessary to foster epidemiological surveillance regarding the existing difficulties...(AU)

Comprehensive lung injury pathology induced by mTOR inhibitors.

Interstitial lung disease is a rare side effect of temsirolimus treatment in renal cancer patients. Pulmonary fibrosis is characterised by the accumulation of extracellular matrix collagen, fibroblast proliferation and migration, and loss of alveolar gas exchange units. Previous studies of pulmonary fibrosis have mainly focused on the fibroproliferative process in the lungs. However, the molecular mechanism by which sirolimus promotes lung fibrosis remains elusive. Here, we propose an overall cascade hypothesis of interstitial lung diseases that represents a common, partly underlying synergism among them as well as the lung pathogenesis side effects of mammalian target of rapamycin inhibitors.

La prevención de las ITS/ VIH/sida en jóvenes adolescentes / The Prevention of IST/HIV/AIDS in Adolescents

Se realizó un estudio de intervención educativa con adolescentes de la Secundaria Básica Carlos Manuel de Céspedes del municipio Holguín, en el periodo de enero a diciembre de 2008. La muestra estuvo constituida por 50 estudiantes, a los que se les aplicó un cuestionario para medir el nivel de conocimiento sobre las ITS/VIH/sida para determinar las necesidades de aprendizaje de acuerdo con las cuales se elaboró y aplicó un conjunto de actividades mediante el Servicio de Extensión Bibliotecaria que brinda el Centro Provincial de Información de Ciencias Médicas . Los datos fueron procesados con ayuda de una computadora Pentium 4 , calculadora con el método porcentual y fueron colocados en tablas según las variables expresadas en números y porcentajes. Se concluyó que la mayoría de los estudiantes, que cursaban el noveno grado y cuyas edades estaban comprendidas entre 13 y 15 años poseían mejores conocimientos sobre las infecciones de trasmisión sexual después de haber participado en las diferentes actividades organizadas con este fin...(AU)

An educative intervention study in adolescents from Carlos Manuel de Céspedes secondary school , from January to December 2008 was carried out. The sample was constituted by 50 students. This work was aimed at knowing the students knowledges on IST/HIV/AIDS. Different activities were planned in order to determine the students` needs on this topic. Data were processed in a computer and a calculator through porcentual method and were written on tables according to the variables that were studied. The results showed that most of adolescents between 13 and 15 years old had better knowledges on IST...(AU)

Production and composition of cider spirits distilled in "alquitara".

The capacity of alquitara (a traditional distillation system) to produce cider brandies is evaluated. To do so, the chemical composition of 12 fractions obtained during the distillation process and the cider brandies obtained from five ciders were analyzed (alcohol strength, methanol, volatile substances, furfural, and metals), taking into account European and Spanish legislation. During the course of distillation, an important increase in methanol, furfural, 2-phenylethanol, and metals in the last fractions was observed, while fusel oils were more abundant in the first fractions collected. Only acetaldehyde behaved differently, showing a minimum concentration in the middle fractions that might be explained by its formation on the surface of alquitara. On the other hand, the final distillates obtained by means of this method complied with the considered regulations. Worth highlighting in this regard are the low levels of a potential toxin such as methanol, as well as the detection of a constant ratio for methanol, ethanol, and fusel oil for the pairs of cider/spirits analyzed, which could be interpreted as an indication of good uniformity in the distillation system and method, thus guaranteeing product quality.

Dehydroepiandrosterone sulfate (DHEA-S) distribution in Spanish prepuberal children: relationship with fasting plasma insulin concentrations and insulin resistance.

BACKGROUND: The aim of this study was to analyze dehydroepiandrosterone sulfate (DHEA-S) levels in a population-based sample of Spanish prepuberal children and to investigate the relationship between DHEA-S and insulin. METHODS: 854 (440 boys and 414 girls) randomly selected prepuberal children were included in our study after a sampling. Children were 6 to 8 years old and were classified for the analysis in half-year intervals. DHEA-S and insulin levels were measured. RESULTS: DHEA-S levels increase significantly with age during prepuberty reaching the maximum level of DHEA-S for this period at 7.5 years old in girls and 8 years old in boys. Girls have significantly higher log DHEA-S levels than boys, except at the age of 8, where the levels are similar (median: 41.7 nmol/l girls and 41.1 nmol/l boys). DHEA-S correlates positively and significantly with weight, height, and BMI in all age intervals but the correlation between DHEA-S and insulin and HOMA is present only at the age of 6.5 in boys and 8 in girls. CONCLUSIONS: We report data about the distribution of DHEA-S in the Spanish prepuberal population. The maximum level of DHEA-S in this prepuberal period was reached before in girls than in boys, with girls having higher DHEA-S levels than boys until the end of this period. We found an important association between DHEA-S levels and weight, height and BMI but an inconsistent association of DHEA-S with insulin and HOMA.