Limitación de tratamientos de soporte vital en Unidades de Cuidados Intensivos españolas: análisis del estudio ETHICUS II / Limitation of life support treatments in Spanish Intensive Care Units: Analysis of the ETHICUS II study

Objetiv Describir los resultados obtenidos en UCI españolas en el estudio ETHICUS II. Diseño Subestudio planificado de pacientes del ETHICUS II. Ámbito 12 UCI españolas. Pacientes o participantes Pacientes que fallecieron o en los que se decidió una limitación de tratamiento de soporte vital (LTSV) durante un periodo de reclutamiento de 6 meses. Intervenciones Se realizó seguimiento hasta el alta de la UCI y 2 meses tras la decisión de LTSV o fallecimiento. Variables de interés principales Características demográficas, clínicas, tipo de decisión de LTSV. Se clasificaron en 4 categorías: omisión o retirada de tratamientos de soporte, acortar el proceso de morir, resucitación cardiopulmonar ineficaz y muerte cerebral. Resultados Un total de 12 UCI participaron en el ETHICUS II. Incluyeron 795 pacientes; 129 fallecieron tras realizarse RCP, 129 desarrollaron muerte encefálica. Se decidió LTSV en 537, fallecieron en UCI 485, el 90,3%. La edad media fue 66,19 años±14,36, el 63,8% fueron hombres. En un 41% se decidió retirada de tratamientos de soporte total y en un 59% se procedió a no iniciar medidas. Diecinueve pacientes (2,38%) disponían de documento de voluntades vitales anticipadas. Conclusiones El perfil clínico predominante cuando se estableció una LTSV fue el de pacientes varones mayores de 65 años con comorbilidad mayoritariamente cardiovascular. La supervivencia fue mayor en las decisiones de LTSV que comprendían la omisión de tratamientos respecto a aquellas en las que se decidió la retirada. España ha ocupado un papel destacado en este estudio multicéntrico de ámbito mundial. (AU)

Objective The aim of this study is to describe the results of Spanish ICUs in ETHICUS II study. Design Planned substudy of patients from ETHICUS II study. Setting 12 Spanish ICU. Patients or participants Patients admitted to Spanish ICU who died or in whom a limitation of life-sustaining treatment (LLST) was decided during a recruitment period of 6 months. Interventions Follow-up of patients was performed until discharge from the ICU and 2 months after the decision of LLST or death. Main variables of interest Demographic characteristics, clinical profile, type of decision of LLST, time and form in which it was adopted. Patients were classified into 4 categories according to the ETHICUS II study protocol: withholding or withdrawing life-sustaining therapy, active shortening of the dying process, failed cardiopulmonary resuscitation and patients with brain death. Results A total of 795 patients were analyzed; 129 patients died after CPR, 129 developed brain death. LLST was decided in 537 patients, 485 died in the ICU, 90.3%. The mean age was 66.19 years±14.36, 63.8% of male patients. In 221 (41%) it was decided to withdraw life-sustaining treatments and in 316(59%) withholding life-sustaining treatments. Nineteen patients (2.38%) had advance living directives. Conclusions The predominant clinical profile when LTSV was established was male patients over 65 years with mostly cardiovascular comorbidity. We observed that survival was higher in LLST decisions involving withholding of treatments compared to those in which withdrawal was decided. Spain has played a leading role in both patient and ICU recruitment participating in this worldwide multicenter study. (AU)

Limitation of life support treatments in Spanish Intensive Care Units: Analysis of the ETHICUS II study.

OBJECTIVE: The aim of this study is to describe the results of Spanish ICUs in ETHICUS II study. DESIGN: Planned substudy of patients from ETHICUS II study. SETTING: 12 Spanish ICU. PATIENTS OR PARTICIPANTS: Patients admitted to Spanish ICU who died or in whom a limitation of life-sustaining treatment (LLST) was decided during a recruitment period of 6 months. INTERVENTIONS: Follow-up of patients was performed until discharge from the ICU and 2 months after the decision of LLST or death. MAIN VARIABLES OF INTEREST: Demographic characteristics, clinical profile, type of decision of LLST, time and form in which it was adopted. Patients were classified into 4 categories according to the ETHICUS II study protocol: withholding or withdrawing life-sustaining therapy, active shortening of the dying process, failed cardiopulmonary resuscitation and patients with brain death. RESULTS: A total of 795 patients were analyzed; 129 patients died after CPR, 129 developed brain death. LLST was decided in 537 patients, 485 died in the ICU, 90.3%. The mean age was 66.19 years ± 14.36, 63.8% of male patients. In 221 (41%) it was decided to withdraw life-sustaining treatments and in 316 (59%) withholding life-sustaining treatments. Nineteen patients (2.38%) had advance living directives. CONCLUSIONS: The predominant clinical profile when LTSV was established was male patients over 65 years with mostly cardiovascular comorbidity. We observed that survival was higher in LLST decisions involving withholding of treatments compared to those in which withdrawal was decided. Spain has played a leading role in both patient and ICU recruitment participating in this worldwide multicenter study.

Controlled exchange of protein and nucleic acid signals from and between synthetic minimal cells.

Synthetic minimal cells are a class of bioreactors that have some, but not all, functions of live cells. Here, we report a critical step toward the development of a bottom-up minimal cell: cellular export of functional protein and RNA products. We used cell-penetrating peptide tags to translocate payloads across a synthetic cell vesicle membrane. We demonstrated efficient transport of active enzymes and transport of nucleic acid payloads by RNA-binding proteins. We investigated influence of a concentration gradient alongside other factors on the efficiency of the translocation, and we show a method to increase product accumulation in one location. We demonstrate the use of this technology to engineer molecular communication between different populations of synthetic cells, to exchange protein and nucleic acid signals. The synthetic minimal cell production and export of proteins or nucleic acids allows experimental designs that approach the complexity and relevancy of natural biological systems. A record of this paper's transparent peer review process is included in the supplemental information.

Eventos de vida estresantes y su efecto en la conducta suicida en mujeres durante la pandemia por Covid-19 en México.

OBJETIVO: Analizar la estructura factorial, la validez convergente y divergente de la Escala Columbia de Severidad Suicida (CSSRS) y el Cuestionario de Eventos de Vida Estresantes (EVE) y medir la asociación entre EVE y conducta suicida (CS) en mujeres mexicanas durante la pandemia por Covid-19. Material y métodos. Se usaron datos de 2 398 mujeres que participaron en un estudio multicéntrico, realizado en México entre mayo y octubre de 2021. La información se recolectó mediante un cuestionario en línea que incluyó la CSSRS y el EVE. Se hizo un análisis factorial confirmatorio para valorar el ajuste de los modelos. RESULTADOS: El modelo final mostró asociación entre los EVE y la CS, y tuvo a la violencia como variable central. Dicho modelo presentó un ajuste adecuado (CFI = 0.950, IFI = 0.950, MFI = 0.975, RMSEA = 0.031, CI RMSEA = 0.026-0.036). CONCLUSIONES: La pandemia por Covid-19 evidenció la necesidad de crear e implementar estrategias que promuevan el cuidado de la salud mental, reduzcan la exposición a la violencia y faciliten los procesos de duelo para prevenir la CS en mujeres mexicanas.

The Columbia-suicide severity rating scale: validity and psychometric properties of an online Spanish-language version in a Mexican population sample.

The aim of this study was to evaluate the validity and psychometric properties in a Mexican sample of a Spanish-language online version of the Columbia-Suicide Severity Rating Scale (C-SSRS). Data were collected between May and October 2021 from 3,645 participants aged 18 years and over, who agreed to complete the questionnaire. Reliability analysis, confirmatory factor analysis (CFA), and psychometric properties were calculated using a two-parameter model. The results showed a reasonable level of reliability with a Cronbach's alpha of 0.814, and evidence of unidimensionality, and construct validity for suicide risk at three risk levels: low, medium, and high. Analysis of the items suggests that they are consistent with the proposed theoretical model. Our results also demonstrate that the parameters are stable and able to efficiently discriminate individuals at high risk of suicide. We propose the use of this version of the C-SSRS in the Spanish-speaking population, since it is a multifactorial assessment of suicide risk and the inclusion of other clinical and risk factor assessments for a more comprehensive evaluation.

Violence against Women during the COVID-19 Pandemic in Mexico.

This study measured the prevalence of cases of domestic violence against women and some associated factors during the COVID-19 pandemic in Mexico. Data were collected through a remote survey during 2020. The sample included 47,819 women aged 15 years and older. Jointpoint regression and logistic regression models were used. The prevalence of violence was 11.5%, which decreased in July and subsequently increased. The associated factors were being unemployed (OR = 2.01; 95%CI 1.89-2.16); being partially and totally quarantined (OR = 1.58; 95%CI 1.43-1.75 and OR = 1.47; 95%CI 1.32-1.63); being a caregiver of children; being a caregiver of elderly and/or suffering from a chronic illness (OR = 1.27; 95%CI 1.19-1.36; OR = 1.42; 95%CI 1.33-1.53; OR = 1.59; 95%CI 1.47-1.73); losing a family member to COVID-19 (OR = 1.26; 95%CI 1.13-1.41); and binge drinking (OR = 1.94; 95%CI 1.78-2.12). The confinement measures increased gender inequalities, economic problems and workload which further evidenced violence against women.

Determinantes sociales asociados con ideación suicida durante la pandemia por Covid-19 en México.

OBJETIVO: Estimar la prevalencia de la ideación suicida (IS) y su asociación con los determinantes sociales (DS) en la pobla-ción mexicana durante la pandemia de Covid-19. Material y métodos. Datos de la encuesta de Atención Psicológica a Distancia para la Salud Mental debido a la Contingencia por Covid-19 obtenidos durante 2020. La muestra fue de 79 665. Se realizaron modelos de regresión logística obteniendo razones de momios (RM) con intervalos de confianza del 95% (IC95%). RESULTADOS: La prevalencia de IS fue de 17.1% (mujeres:18.8% y hombres: 14.4%). Principales DS asociados fueron: ser mujer (RM=1.11; IC95% 1.06,1.13), mujeres jóvenes (RM=1.30; IC95% 1.09,1.54), escolaridad (RM=1.89; IC95% 1.14,3.12), soltera(o) (RM= 1.31; IC95% 1.24,1.38), desempleo (RM= 2.33; IC95% 2.21,2.45), distanciamiento social (RM 1.81; IC95%1.68,1.96), vivir solo (RM 1.18; IC95% 1.10,1.27), pérdida de familiar por Covid-19 (RM= 1.41; IC95%1.30,1.54), tener un diagnóstico de depresión (RM= 5.72; IC95% 5.41,6.05), ser víctima de violencia física (RM=2.71; IC95% 2.49,2.95), consumo excesivo de alcohol (RM=1.68; IC95%1.58,1.79) y drogas (RM= 3.13; IC95% 2.88,3.41), y sospecha o diagnóstico de Covid-19 (RM=1.79; IC95% 1.67,1.89). CONCLUSIONES: La prevalencia de IS durante la pandemia por Covid-19 fue elevada; se discute la relevancia de los DS estructurales e intermedios que influyen en la IS.

Measurement invariance of the GAD-5 Generalized Anxiety Disorder Scale in a Mexican general population sample.

The primary objective of this study was to evaluate the measurement of invariance by sex, age, and educational level of an online version of the Generalized Anxiety Disorder Scale in a five-item version (GAD-5). Configural, metric, scalar, and strict invariance were evaluated using data from 79,473 respondents who answered a mental health questionnaire during the COVID-19 pandemic in Mexico. The sex variable was classified as male or female; age was categorized as minors, youth, young adults, adults, and older adults; and educational level was divided into basic, upper secondary, higher, and graduate education. To test for configural invariance, confirmatory factor models were constructed. For metric invariance, equality restrictions were established for the factor loadings between the construct and its items; for scalar invariance, equality restrictions were established between the intercepts; strict variance implied the additional restriction of the residuals. Statistical analysis was performed in R software with the lavaan package. The results show that with respect to sex, age, and educational level, configural and metric measurement invariance was confirmed (ΔCFI < 0.002; ΔRMSEA < 0.015). However, with respect to scalar and strict invariance, the results showed significant differences regarding the fit model (ΔCFI > 0.002; ΔRMSEA > 0.015). We conclude that the GAD-5 presents configural and metric invariance for sex, age, and educational level, and scalar invariance for sex and age groups. However, the scale does not demonstrate strict invariance. We discuss the implications and suggest that this result could be related to the evaluation of sociodemographic variables.

Programmable Fusion and Differentiation of Synthetic Minimal Cells.

Synthetic cells can mimic the intricate complexities of live cells, while mitigating the level of noise that is present natural systems; however, many crucial processes still need to be demonstrated in synthetic cells to use them to comprehensively study and engineer biology. Here we demonstrate key functionalities of synthetic cells previously available only to natural life: differentiation and mating. This work presents a toolset for engineering combinatorial genetic circuits in synthetic cells. We demonstrate how progenitor populations can differentiate into new lineages in response to small molecule stimuli or as a result of fusion, and we provide practical demonstration of utility for metabolic engineering. This work provides a tool for bioengineering and for natural pathway studies, as well as paving the way toward the construction of live artificial cells.

Serial prolactin sampling as a confirmatory test for true hyperprolactinemia / Curva de prolactina para la confirmación de hiperprolactinemia real

INTRODUCTION: Hyperprolactinemia may be due to physiological or pathological causes, and may be asymptomatic or induce hypogonadism, infertility, and/or galactorrhea. It is important to take prolactin samples while avoiding stress, as this may increase prolactin levels. Therefore, our aim was to assess the value of prolactin serial sampling after brachial vein cannulation. PATIENTS AND METHODS: Sixty-six patients (34.9±11.8 years of age, 92.4% female) with an initial elevated random prolactin level were included. A prolactin sample was drawn at baseline and after a 30min rest. RESULTS: The median referral prolactin level was 37.4ng/ml (interquartile range [IQR* 23.3), the baseline prolactin level at serial sampling was 19.5ng/ml (IQR 8), and the value after a 30min rest was 17.1ng/ml (IQR 7.9). Hyperprolactinemia was not confirmed by serial sampling in 45 patients (68.2%). There were no statistically significant differences in referral prolactin levels between patients with and without confirmed hyperprolactinemia (41.2ng/ml and 36.7ng/ml respectively, p = 0.3). Galactorrhea was found in 13.6% of patients, amenorrhea or oligomenorrhea in 28.8%, infertility in 7.6%, erectile dysfunction in 4.6%, and gynecomastia in 3%, while 45.5% were asymptomatic. There were no statistical differences regarding the presence or absence of any of these symptoms and subsequent confirmed hyperprolactinemia. Fifty-seven patients (86.4%) were discharged after the results of the prolactin serial sampling were obtained. CONCLUSIONS: Prolactin serial sampling may be a useful test to detect artefactual hyperprolactinemias, thus avoiding unnecessary additional tests and treatments

INTRODUCCIÓN: La hiperprolactinemia puede ser debida a causas fisiológicas o patológicas, y puede ser asintomática o inducir hipogonadismo, infertilidad y/o galactorrea. Es importante obtener las muestras de prolactina evitando situaciones de estrés, puesto que este puede incrementar sus niveles. Por tanto, nuestro objetivo era evaluar la utilidad de la realización de curvas de prolactina mediante canalización de la vena braquial. MATERIALES Y MÉTODOS: Se incluyeron 66 pacientes (edad: 34,9±11,8 años; 92,4% mujeres) con una prolactina aleatoria inicial elevada. Se obtuvieron una muestra de prolactina basal y otra tras un reposo de 30min. RESULTADOS: La prolactina mediana inicial fue 37,4ng/ml (IQR: 23,3), la prolactina basal de la curva 19,5ng/ml (IQR: 8), y tras 30min de reposo, 17,1ng/ml (IQR: 7,9). La curva descartó una hiperprolactinemia en 45 pacientes (68,2%) No hubo diferencias estadísticamente significativas en la prolactina de derivación entre aquellos pacientes en los que se confirmó una hiperprolactinemia y aquellos que no (41,2 vs. 36,7ng/ml; p = 0,3). Un 13,6% de los pacientes presentaron galactorrea, un 28,8% amenorrea u oligomenorrea, un 7,6% infertilidad, un 4,6% disfunción eréctil y un 3% ginecomastia. El 45,5% estaban asintomáticos. No hubo diferencias estadísticamente significativas entre la presencia o ausencia de ninguno de estos síntomas y una hiperprolactinemia confirmada posteriormente. Se pudo dar de alta a 57 pacientes (86,4%) tras la obtención de los resultados de la curva de prolactina. CONCLUSIONES: La curva de prolactina puede ser una prueba útil pata detectar falsas hiperprolactinemias, evitando la realización de pruebas complementarias y tratamientos adicionales innecesarios

Serial prolactin sampling as a confirmatory test for true hyperprolactinemia.

INTRODUCTION: Hyperprolactinemia may be due to physiological or pathological causes, and may be asymptomatic or induce hypogonadism, infertility, and/or galactorrhea. It is important to take prolactin samples while avoiding stress, as this may increase prolactin levels. Therefore, our aim was to assess the value of prolactin serial sampling after brachial vein cannulation. PATIENTS AND METHODS: Sixty-six patients (34.9±11.8 years of age, 92.4% female) with an initial elevated random prolactin level were included. A prolactin sample was drawn at baseline and after a 30min rest. RESULTS: The median referral prolactin level was 37.4ng/ml (interquartile range [IQR* 23.3), the baseline prolactin level at serial sampling was 19.5ng/ml (IQR 8), and the value after a 30min rest was 17.1ng/ml (IQR 7.9). Hyperprolactinemia was not confirmed by serial sampling in 45 patients (68.2%). There were no statistically significant differences in referral prolactin levels between patients with and without confirmed hyperprolactinemia (41.2ng/ml and 36.7ng/ml respectively, p=0.3). Galactorrhea was found in 13.6% of patients, amenorrhea or oligomenorrhea in 28.8%, infertility in 7.6%, erectile dysfunction in 4.6%, and gynecomastia in 3%, while 45.5% were asymptomatic. There were no statistical differences regarding the presence or absence of any of these symptoms and subsequent confirmed hyperprolactinemia. Fifty-seven patients (86.4%) were discharged after the results of the prolactin serial sampling were obtained. CONCLUSIONS: Prolactin serial sampling may be a useful test to detect artefactual hyperprolactinemias, thus avoiding unnecessary additional tests and treatments.

Personal Opinions Seem to be the Major Contributor to the Influenza Vaccination Disparity in Sneedville, TN.

Relevance Although the seasonal flu vaccine remains the most effective way to prevent the spread of influenza and reduce its associated mortalities, the proportion of individuals receiving the vaccine continues to be an issue in various communities across the United States. The attitudes of residents who live in Sneedville, a small town in a rural northeastern Tennessee, were surveyed. Objective(s) To determine the barriers to influenza vaccination in Sneedville, Tennessee and contribute to the literature on why some rural communities across the United States show low influenza vaccination rates. Materials and Methods Door-to-door convenience sampling was conducted in Sneedville, TN. Participants were asked to complete a survey consisting of --three yes or no demographic questions (one with an option to further elaborate) and nine opinion questions based on a five-point Likert scale (1 = strongly disagree, 2 = disagree, 3 = undecided, 4 = agree, 5 = strongly agree). Participants were not provided any additional details pertaining to the Likert scale questions and were given the option to skip the Likert scale questions. These questions were chosen to gauge the potential structural, socioeconomic, belief, and provider-related barriers to vaccination. Two-tailed independent t-tests were used to compare the Likert scale means for each of the nine opinion questions in those that received the influenza vaccine and those who did not. Univariate analysis was conducted to assess difference in the distribution of Likert responses in vaccinators compared to non-vaccinators. Results This project surveyed 172 residents of which 60.5% (104/172) indicated that they did not receive the influenza vaccine for the 2017-2018 flu season. Compared to individuals who vaccinate against the flu, individuals who do not vaccinate against the flu believe the flu shot is not worthwhile and believe the flu shot has a greater chance to make them sick.  Conclusions This study finds that structural, socioeconomic, and provider-related barriers are not the underlying cause of the low influenza vaccination rates in this rural area. Instead, public opinion on influenza vaccination seems to be the reason for the disparity.

Conocimientos, creencias y actitudes de la población gitana ante el cribado del cáncer colorrectal / Knowledge, beliefs and attitudes of the Roma population regarding colorectal cancer screening

Objetivo: Identificar los factores predisponentes, inhibidores y facilitadores que pueden afectar a la participación en los programas de cribado del cáncer colorrectal en la población gitana. Método: Estudio cualitativo exploratorio mediante técnica de grupo focal. Se realizaron tres grupos focales de hombres y tres de mujeres, con un total de 16 hombres y 18 mujeres participantes de población romaní, de 50-69 años de edad, de la provincia de Alicante. Se realizó un análisis del discurso con el modelo PRECEDE como marco de análisis. Resultados: Se identificaron diversas barreras a la participación, como la aversión de la población gitana a hablar de cáncer, el rechazo a anticipar un diagnóstico que puede provocar sufrimiento de la persona y su entorno familiar, escaso conocimiento de la enfermedad y del programa preventivo, rechazo hacia la recogida y manejo de las muestras, miedo y vergüenza ante la posible colonoscopia, aceptación de la voluntad divina, dificultades de comprensión y lectura, y percepción de estar discriminados por su etnia en el ámbito sanitario. Sin embargo, se identificaron factores predisponentes a la participación en el programa de cribado, como la predisposición favorable a recibir información pertinente a través de vías más apropiadas, así como su confianza en el consejo profesional. Conclusión: La predisposición a recibir la recomendación de participar en los programas de cribado colorrectal y una información comprensible de los profesionales sanitarios permiten entrever posibles estrategias de aproximación a este colectivo. Esto podría contribuir a la mejora de la participación de la población gitana en el programa de cribado de cáncer colorrectal y abrir nuevas vías para promover conductas preventivas (AU)

Objective: To identify predisposing, inhibitory and facilitating factors that may affect participation in colorectal cancer screening programs in the Roma population. Method: Qualitative and exploratory study by focus group technique. Three focus groups of men and three groups of women were carried out, with a total of 16 men and 18 women from the Roma population, aged 50-69 years, from the province of Alicante. A discourse analysis was performed with the PRECEDE model as an analysis framework. Results: Several barriers to participation were identified, such as the aversion of the Roma population to talk about cancer, refusal to anticipate a diagnosis that can cause suffering to the person and their family, poor knowledge of the disease and the preventive programmes, refusal to collect and handle samples, fear and shame about the colonoscopy, acceptance of divine will, difficulties in understanding and reading, and the perception of being discriminated by their ethnicity in the health sector. However, predisposing factors to participate in the screening programme also were identified, for example willingness to receive relevant information through more appropriate pathways, as well as their confidence in professional counselling. Conclusion: A willingness to receive the recommendation to participate and understanding information from health professionals have been identified. This will enable us to envisage potential strategies for approaching this population group. This could contribute to improved participation of the Roma population in colorectal cancer screening programmes and to open up new ways to promote preventive behaviours (AU)

[Knowledge, beliefs and attitudes of the Roma population regarding colorectal cancer screening]. / Conocimientos, creencias y actitudes de la población gitana ante el cribado del cáncer colorrectal.

OBJECTIVE: To identify predisposing, inhibitory and facilitating factors that may affect participation in colorectal cancer screening programs in the Roma population. METHOD: Qualitative and exploratory study by focus group technique. Three focus groups of men and three groups of women were carried out, with a total of 16 men and 18 women from the Roma population, aged 50-69 years, from the province of Alicante. A discourse analysis was performed with the PRECEDE model as an analysis framework. RESULTS: Several barriers to participation were identified, such as the aversion of the Roma population to talk about cancer, refusal to anticipate a diagnosis that can cause suffering to the person and their family, poor knowledge of the disease and the preventive programmes, refusal to collect and handle samples, fear and shame about the colonoscopy, acceptance of divine will, difficulties in understanding and reading, and the perception of being discriminated by their ethnicity in the health sector. However, predisposing factors to participate in the screening programme also were identified, for example willingness to receive relevant information through more appropriate pathways, as well as their confidence in professional counselling. CONCLUSION: A willingness to receive the recommendation to participate and understanding information from health professionals have been identified. This will enable us to envisage potential strategies for approaching this population group. This could contribute to improved participation of the Roma population in colorectal cancer screening programmes and to open up new ways to promote preventive behaviours.

Humanización de la Sanidad y Salud Laboral: Implicaciones, estado de la cuestión y propuesta del Proyecto HU-CI / Humanizing healthcare and occupational health: implications, state of issue and proposal from HU-CI project

La evolución científica y técnica de la atención sanitaria mantienen un desarrollo exponencial que permite cada vez una mejor asistencia a los pacientes, nuevas formas de tratamiento y crecientes índices de supervivencia. Sin embargo, estos importantes avances que enriquecen la atención a la salud, en muchas ocasiones, han ido invadiendo espacio al propio acto humano de la atención a la persona. Potenciar organizaciones más humanizadas implicará establecer acciones dirigidas al ambiente y lugar de trabajo, así como a todos los agentes implicados (pacientes, familiares y profesionales). Con dicha finalidad, las políticas de Humanización y su aplicación al contexto sanitario son una realidad en nuestros días y están concretándose en algunas propuestas específicas en determinadas organizaciones, con el apoyo de algunos organismos oficiales. En el presente trabajo, señalamos la interacción entre los objetivos de dichas políticas de humanización y las metas de la salud laboral en contextos asistenciales. Se exploran áreas comunes de trabajo dirigidas al bienestar del profesional sanitario, posibilidades de gestión integral de ambos conceptos, y se expone un ejemplo concreto como es el Proyecto de Humanización de las Unidades de Cuidados Intensivos (HU-CI) (AU)

The scientific and technical evolution of health care keeps growing exponentially, thus allowing a better patient care, new treatment forms and increasing survival rates. However, these important advances that improve health care have in many cases invaded the space that once belonged to the human act of caring. Promoting more humanized organizations will imply to establish actions directed to the environment and the workplace, as well as to all involved agents (patients, relatives and professionals). To that end, the humanization policies and their application to the health context are a reality in our days. These policies are being materialized in some specific proposals of certain organizations with the support of some official agencies. In this present work, we point out the interaction between the objectives of these humanization policies and the goals of occupational health in health care contexts. Common areas of work promoting the wellbeing for health professionals and the possibilities of integral management of both concepts are explored. Lastly, we provide a concrete example, like the Humanization Project of Intensive Care Units (HU-CI) (AU)

Phase 1/2 study of rilotumumab (AMG 102), a hepatocyte growth factor inhibitor, and erlotinib in patients with advanced non-small cell lung cancer.

BACKGROUND: Activation of the mesenchymal-epidermal transition factor (MET) tyrosine kinase and its ligand, hepatocyte growth factor (HGF), is implicated in resistance to epidermal growth factor receptor (EGFR) inhibitors. In this phase 1/2 trial, rilotumumab (an anti-HGF antibody) combined with erlotinib was evaluated in patients with metastatic, previously treated non-small cell lung cancer. METHODS: In phase 1, a dose de-escalation design was adopted with rilotumumab starting at 15 mg/kg intravenously every 3 weeks and oral erlotinib 150 mg daily. In phase 2, the disease control rate (DCR) (according to Response Evaluation Criteria in Solid Tumors) of the combination was evaluated using a Simon 2-stage design. The biomarkers examined included 10 plasma-circulating molecules associated with the EGFR and MET pathways. RESULTS: Without indications for de-escalation, the recommended phase 2 dose was dose level 0. Overall, 45 response-evaluable patients were enrolled (13 with squamous carcinoma, 32 with adenocarcinoma; 2 had confirmed EGFR mutations, 33 had confirmed wild-type [WT] EGFR, and 7 had KRAS mutations). The DCR for all patients was 60% (90% confidence interval [CI], 47.1%-71.3%). Median progression-free survival was 2.6 months (90% CI, 1.4-2.7 months), and median overall survival was 6.6 months (90% CI, 5.6-8.9 months). Among patients with WT EGFR, the DCR was 60.6% (90% CI, 46.3%-73.3%), median progression-free survival was 2.6 months (90% CI, 1.4-2.7 months), and median overall survival was 7.0 months (90% CI, 5.6-13.4 months). Elevated baseline levels of neuregulin 1 were associated with longer progression-free survival (hazard ratio, 0.41; 95% CI, 0.19-0.87), whereas elevated amphiregulin levels were associated with more rapid progression (hazard ratio, 2.14; 95% CI, 1.48-3.08). CONCLUSIONS: Combined rilotumumab and erlotinib had an acceptable safety profile, and the DCR met the prespecified criteria for success. In the EGFR WT group, the DCR exceeded published reports for erlotinib alone. High circulating levels of neuregulin 1 may indicate sensitivity to this combination. Cancer 2017;123:2936-44. © 2017 American Cancer Society.

eIF4E threshold levels differ in governing normal and neoplastic expansion of mammary stem and luminal progenitor cells.

Translation initiation factor eIF4E mediates normal cell proliferation, yet induces tumorigenesis when overexpressed. The mechanisms by which eIF4E directs such distinct biologic outputs remain unknown. We found that mouse mammary morphogenesis during pregnancy and lactation is accompanied by increased cap-binding capability of eIF4E and activation of the eIF4E-dependent translational apparatus, but only subtle oscillations in eIF4E abundance. Using a transgenic mouse model engineered so that lactogenic hormones stimulate a sustained increase in eIF4E abundance in stem/progenitor cells of lactogenic mammary epithelium during successive pregnancy/lactation cycles, eIF4E overexpression increased self-renewal, triggered DNA replication stress, and induced formation of premalignant and malignant lesions. Using complementary in vivo and ex vivo approaches, we found that increasing eIF4E levels rescued cells harboring oncogenic c-Myc or H-RasV12 from DNA replication stress and oncogene-induced replication catastrophe. Our findings indicate that distinct threshold levels of eIF4E govern its biologic output in lactating mammary glands and that eIF4E overexpression in the context of stem/progenitor cell population expansion can initiate malignant transformation by enabling cells to evade DNA damage checkpoints activated by oncogenic stimuli. Maintaining eIF4E levels below its proneoplastic threshold is an important anticancer defense in normal cells, with important implications for understanding pregnancy-associated breast cancer.