Targeting ESR1 mutation-induced transcriptional addiction in breast cancer with BET inhibition.

Acquired mutations in the ligand-binding domain (LBD) of the gene encoding estrogen receptor α (ESR1) are common mechanisms of endocrine therapy resistance in patients with metastatic ER+ breast cancer. The ESR1 Y537S mutation, in particular, is associated with development of resistance to most endocrine therapies used to treat breast cancer. Employing a high-throughput screen of nearly 1,200 Federal Drug Administration-approved (FDA-approved) drugs, we show that OTX015, a bromodomain and extraterminal domain (BET) inhibitor, is one of the top suppressors of ESR1 mutant cell growth. OTX015 was more efficacious than fulvestrant, a selective ER degrader, in inhibiting ESR1 mutant xenograft growth. When combined with abemaciclib, a CDK4/6 inhibitor, OTX015 induced more potent tumor regression than current standard-of-care treatment of abemaciclib + fulvestrant. OTX015 has preferential activity against Y537S mutant breast cancer cells and blocks their clonal selection in competition studies with WT cells. Thus, BET inhibition has the potential to both prevent and overcome ESR1 mutant-induced endocrine therapy resistance in breast cancer.

Selective Adsorption of Aqueous Diclofenac Sodium, Naproxen Sodium, and Ibuprofen Using a Stable Fe3O4-FeBTC Metal-Organic Frameworka.

The FeBTC metal-organic framework (MOF) incorporated with magnetite is proposed as a novel material to solve water contamination with last generation pollutants. The material was synthesized by in situ solvothermal methods, and Fe3O4 nanoparticles were added during FeBTC MOF synthesis and used in drug adsorption. X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and Raman spectroscopy characterized the materials, with N2-physisorption at 77 K. Pseudo-second-order kinetic and Freundlich models were used to describe the adsorption process. The thermodynamic study revealed that the adsorption of three drugs was a feasible, spontaneous exothermic process. The incorporation of magnetite nanoparticles in the FeBTC increased the adsorption capacity of pristine FeBTC. The Fe3O4-FeBTC material showed a maximum adsorption capacity for diclofenac sodium (DCF), then by ibuprofen (IB), and to a lesser extent by naproxen sodium (NS). Additionally, hybridization of the FeBTC with magnetite nanoparticles reinforced the most vulnerable part of the MOF, increasing the stability of its thermal and aqueous media. The electrostatic interaction, H-bonding, and interactions in the open-metal sites played vital roles in the drug adsorption. The sites' competition in the multicomponent mixture's adsorption showed selective adsorption (DCF) and (NS). This work shows how superficial modification with a low-surface-area MOF can achieve significant adsorption results in water pollutants.

Successful treatment of dermato-neuro syndrome with plasmapheresis.

Altered mental status can have many causes ranging from emergent intracranial pathologies to more insidious, systemic toxic aetiologies. We report a rare case of dermato-neuro syndrome in a 71-year-old man with a known history of scleromyxoedema. The patient initially presented with encephalopathy which quickly progressed to generalised tonic-clonic seizures and coma. While his presentation fits with other, although rare, cases of dermato-neuro syndrome, it is imperative to rule out lethal, more common causes of altered mentation. Due to the rarity and difficulty in diagnosis of dermato-neuro syndrome, there is a significant debate regarding the optimal management as there are no standardised treatment protocols. In our case, the patient was successfully treated with plasmapheresis resulting in improved neurologic function.

Short-term CDK4/6 Inhibition Radiosensitizes Estrogen Receptor-Positive Breast Cancers.

PURPOSE: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have improved progression-free survival for metastatic, estrogen receptor-positive (ER+) breast cancers, but their role in the nonmetastatic setting remains unclear. We sought to understand the effects of CDK4/6 inhibition (CDK4/6i) and radiotherapy in multiple preclinical breast cancer models. EXPERIMENTAL DESIGN: Transcriptomic and proteomic analyses were used to identify significantly altered pathways after CDK4/6i. Clonogenic assays were used to quantify the radiotherapy enhancement ratio (rER). DNA damage was quantified using γH2AX staining and the neutral comet assay. DNA repair was assessed using RAD51 foci formation and nonhomologous end joining (NHEJ) reporter assays. Orthotopic xenografts were used to assess the efficacy of combination therapy. RESULTS: Palbociclib significantly radiosensitized multiple ER+ cell lines at low nanomolar, sub IC50 concentrations (rER: 1.21-1.52) and led to a decrease in the surviving fraction of cells at 2 Gy (P < 0.001). Similar results were observed in ribociclib-treated (rER: 1.08-1.68) and abemaciclib-treated (rER: 1.19-2.05) cells. Combination treatment decreased RAD51 foci formation (P < 0.001), leading to a suppression of homologous recombination activity, but did not affect NHEJ efficiency (P > 0.05). Immortalized breast epithelial cells and cells with acquired resistance to CDK4/6i did not demonstrate radiosensitization (rER: 0.94-1.11) or changes in RAD51 foci. In xenograft models, concurrent palbociclib and radiotherapy led to a significant decrease in tumor growth. CONCLUSIONS: These studies provide preclinical rationale to test CDK4/6i and radiotherapy in women with locally advanced ER+ breast cancer at high risk for locoregional recurrence.

Algorithm to filter the noise in the spectral intensity of ultrashort laser pulses.

We have developed an algorithm to filter the noise in the spectral intensity of ultrashort laser pulses. The filtering procedure consists of smoothing the noise by using the Savitzky-Golay filter, removing the offset, and using a super-Gaussian window to truncate the frequencies of the spectrum. We have modeled bandwidth-limited ultrashort pulses with Gaussian modulated frequencies to show the estimation of the carrier wavelength, reconstruction of the intensity pulse profile, and pulse duration after applying the algorithm. Theoretical results are presented for pulse durations between 5 fs and 100 fs with a carrier wavelength of 825 nm and three different amounts of signal-to-noise ratio (SNR): 30 dB, 20 dB, and 15 dB, normally found in experiments. The algorithm is also applied to an experimental spectral intensity from a homemade Ti:sapphire laser that produces pulses of about 20 fs at 825 nm at 100 MHz. We will show that using only a low-pass Fourier filter and removing offset is not enough to recover the spectral intensity when a large SNR is present, which may be the case when the ultrashort laser beam has been manipulated to compensate for the group velocity dispersion of an external optical system. In cases like this, the use of the Savitzky-Golay filter prior to the super-Gaussian filter improves the recovery of the carrier wavelength and the spectral intensity. We will also show that the algorithm presented in this paper is suitable for experimental analysis and requires limited user intervention.

Impact of frequency-dependent spherical aberration in the focusing of ultrashort pulses.

In this paper, the temporal and spatial intensity pulse distributions are calculated around the focal region of an optical system using a combination of ray tracing and a wave propagation method. We analyze how to measure the width of the intensity pulse distributions to estimate pulse duration and spot size in order to study the impact of the variation of spherical aberration with frequency in a pulse on the intensity distributions. Two experimental techniques used in the laboratory are also modeled: the knife-edge test to measure spatial distribution and the intensity autocorrelation technique to measure the temporal distribution. We use two measuring criteria, the full-width half-maximum (FWHM) and standard deviation (σ), to compare the spatial and temporal intensity distributions of the calculated diffraction patterns and those obtained from the simulated experimental techniques. We show that the FWHM is not a good criterion, since it gives different results in the measured intensity distributions in time and space when they are measured directly from the theoretical modeling and when they are measured from the modeled experimental techniques used in the laboratory. The standard deviation, however, is a consistent criterion, giving the same results for the calculated intensity distributions and the modeled experiments.

Correction to: Targeted degradation of activating estrogen receptor α ligand-binding domain mutations in human breast cancer.

In the original publication of the article, the spelling of the sixth author's given name was incorrect. The corrected author name should read as "Wadie David". The original article has been corrected.

Targeted degradation of activating estrogen receptor α ligand-binding domain mutations in human breast cancer.

PURPOSE: Studies have identified several estrogen receptor α (ERα) ligand-binding domain (LBD) somatic mutations in endocrine therapy resistant, metastatic ER-positive breast cancers. The most common mutations, Tyr537Ser (Y537S) and Asp538Gly (D538G), are detected in ~ 30% of endocrine resistant metastatic breast cancer patients. These ESR1 mutations induce the agonist conformation of ERα, confer an estrogen-independent phenotype, and promote drug resistance to antiestrogens. METHODS: ER-positive, estrogen-dependent MCF-7 cells were engineered to express either the Y537S or D538G mutants using CRISPR knock-in (cY537S and cD538G). These cells were used to screen several estrogen receptor degrader (ERD) compounds synthesized using the Proteolysis Targeting Chimeras (PROTAC) method to induce degradation of ERα via the ubiquitin-proteasome pathway. RESULTS: Wild-type MCF-7 and ERα LBD mutant cells were treated with ERD-148 (10 pM-1 µM) and assayed for cellular proliferation using the PrestoBlue cell viability assay. ERD-148 attenuated ER-dependent growth with IC50 values of 0.8, 10.5, and 6.1 nM in MCF-7, cY537S, and cD538G cells, respectively. Western blot analysis showed that MCF-7 cells treated with 1 nM ERD-148 for 24 h exhibited reduced ERα protein expression as compared to the mutants. The ER-regulated gene, GREB1, demonstrated significant downregulation in parental and mutant cells after 24 h of ERD-148 treatment at 10 nM. Growth of the ER-negative, estrogen-independent MDA-MB-231 breast cancer cells was not inhibited by ERD-148 at the ~ IC90 observed in the ER-positive cells. CONCLUSION: ERD-148 inhibits the growth of ER-positive breast cancer cells via downregulating ERα with comparable potency to Fulvestrant with marginal non-specific toxicity.

Hydrochlorothizide-induced acute generalised exanthematous pustulosis presenting with bilateral periorbital impetigo.

Acute generalised exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction characterised by the appearance of erythematous plaques and papules with overlying non-follicular pinpoint pustules. Drugs are the cause of AGEP in approximately 90% of cases. The most common causes include anti-infective agents (aminopenicillins, quinolones, antibacterial sulfonamides and terbinafine), antimalarials and diltiazem. To the best of our knowledge, to date there has only been one report of hydrochlorothiazide-induced AGEP. There has never been a case report of losartan-induced AGEP. Here, we present a case of AGEP that is the second case purportedly caused by hydrochlorothiazide.

Ecological significance of dorsal polymorphism in a Batesian mimic snake.

Batesian mimicry is the process in which harmless species adopt the appearance of a dangerous, aposematic species. In some prey species, both Batesian mimetic and non-Batesian morphs coexist, presupposing that both morphs have to be evolutionarily advantageous. The viperine snake, Natrix maura, exhibits a zigzag dorsal pattern and antipredatory behavior that mimics European vipers. This snake also has a striped dorsal pattern that coexists with the zigzag pattern. We have examined whether individuals belonging to different geographically structured clades were more likely to exhibit a certain dorsal pattern, and whether the zigzag pattern has a protective function by exposing artificial snakes to predation in natural environments, in addition to comparing antipredatory behavior between zigzag and striped snakes also in natural environments. Our results indicate that the striped pattern was not geographically structured, but habitat-dependent. Aerial predators less frequently attacked zigzag plasticine models than striped or unpatterned models. We detected a shift in antipredator behavior between the 2 morphs, as Batesian mimicking N. maura responded to an approaching potential predator by remaining immobile or fleeing at shorter distances than did striped ones. We conclude that Batesian mimics maintain the cryptic and aposematic value by resembling vipers, whereas in open habitats the non-Batesian mimic has altered its antipredator behavior to maintain its fitness.

Comprehensive Mutation and Copy Number Profiling in Archived Circulating Breast Cancer Tumor Cells Documents Heterogeneous Resistance Mechanisms.

Addressing drug resistance is a core challenge in cancer research, but the degree of heterogeneity in resistance mechanisms in cancer is unclear. In this study, we conducted next-generation sequencing (NGS) of circulating tumor cells (CTC) from patients with advanced cancer to assess mechanisms of resistance to targeted therapy and reveal opportunities for precision medicine. Comparison of the genomic landscapes of CTCs and tissue metastases is complicated by challenges in comprehensive CTC genomic profiling and paired tissue acquisition, particularly in patients who progress after targeted therapy. Thus, we assessed by NGS somatic mutations and copy number alterations (CNA) in archived CTCs isolated from patients with metastatic breast cancer who were enrolled in concurrent clinical trials that collected and analyzed CTCs and metastatic tissues. In 76 individual and pooled informative CTCs from 12 patients, we observed 85% concordance in at least one or more prioritized somatic mutations and CNA between paired CTCs and tissue metastases. Potentially actionable genomic alterations were identified in tissue but not CTCs, and vice versa. CTC profiling identified diverse intra- and interpatient molecular mechanisms of endocrine therapy resistance, including loss of heterozygosity in individual CTCs. For example, in one patient, we observed CTCs that were either wild type for ESR1 (n = 5/32), harbored the known activating ESR1 p.Y537S mutation (n = 26/32), or harbored a novel ESR1 p.A569S (n = 1/32). ESR1 p.A569S was modestly activating in vitro, consistent with its presence as a minority circulating subclone. Our results demonstrate the feasibility and potential clinical utility of comprehensive profiling of archived fixed CTCs. Tissue and CTC genomic assessment are complementary, and precise combination therapies will likely be required for effective targeting in advanced breast cancer patients.Significance: These findings demonstrate the complementary nature of genomic profiling from paired tissue metastasis and circulating tumor cells from patients with metastatic breast cancer. Cancer Res; 78(4); 1110-22. ©2017 AACR.

Feasibility of a multifaceted educational strategy for strengthening rural primary health care.

OBJECTIVE:: To evaluate the feasibility and acceptability of a comprehensive educational strategy designed to improve care quality in rural areas of Mexico. MATERIALS AND METHODS:: A demonstration study was performed in 18 public rural health centers in Mexico, including an educational intervention that consists of the following steps: Development of the strategy; Selection and training of instructors (specialist physicians from the referral hospital and multidisciplinary field teams); Implementation of the strategy among health care teams for six priority causes of visit, through workshops, individual tutorials, and round-table case-review sessions. Feasibility and acceptability were evaluated using checklists, direct observation, questionnaires and in-depth interviews with key players. RESULTS:: Despite some organizational barriers, the strategy was perceived as worthy by the participants because of the personalized tutorials and the improved integration of health teams within their usual professional practice. CONCLUSION:: The educational strategy proved to be acceptable; its feasibility for usual care conditions will depend on the improvement of organizational processes at rural facilities.

Feasibility of a multifaceted educational strategy for strengthening rural primary health care / Factibilidad de una estrategia educativa multifacética para fortalecer la atención primaria rural

Abstract: Objective: To evaluate the feasibility and acceptability of a comprehensive educational strategy designed to improve care quality in rural areas of Mexico. Materials and methods: A demonstration study was performed in 18 public rural health centers in Mexico, including an educational intervention that consists of the following steps: Development of the strategy; Selection and training of instructors (specialist physicians from the referral hospital and multidisciplinary field teams); Implementation of the strategy among health care teams for six priority causes of visit, through workshops, individual tutorials, and round-table case-review sessions. Feasibility and acceptability were evaluated using checklists, direct observation, questionnaires and in-depth interviews with key players. Results: Despite some organizational barriers, the strategy was perceived as worthy by the participants because of the personalized tutorials and the improved integration of health teams within their usual professional practice. Conclusion: The educational strategy proved to be acceptable; its feasibility for usual care conditions will depend on the improvement of organizational processes at rural facilities.

Resumen: Objetivo: Evaluar la factibilidad y aceptabilidad de una estrategia educativa multifacética de mejora de calidad de atención en áreas rurales de México. Material y métodos: Se realizó un estudio de demostración con una intervención educativa a equipos de salud en 18 centros de salud rurales en México, que incluyó desarrollo de la estrategia; selección y capacitación de instructores (especialistas del hospital de referencia y equipos asesores multidisciplinarios); implementación de la estrategia educativa para seis motivos prioritarios de atención, mediante talleres, asesorías individualizadas y sesiones de revisión de casos. Se evaluaron factibilidad y aceptabilidad mediante listas de cotejo, observación directa, cuestionarios y entrevistas a profundidad con actores clave. Resultados: A pesar de algunas barreras organizacionales, la estrategia fue percibida como valiosa por los participantes, por la asesoría personalizada y la integración de los equipos de salud en su práctica profesional. Conclusión: La estrategia educativa es aceptable para áreas rurales; su factibilidad en la operación usual dependerá de mejoras organizacionales de los servicios.

Mode-coupling enhancement by pump astigmatism correction in a Ti:Sapphire femtosecond laser.

To pump a solid-state femtosecond laser cavity, a beam from a CW laser is focused by a single lens into the laser crystal. To increase the output power of the laser, the overlap of the laser mode with the pump mode should be maximized. This is particularly important in the so-called mode coupling and the Kerr-lens mode locking (KLM) operation, where the change in beam waist at the position of the gain medium is exploited to enhance the mode overlap with the pump laser in the crystal. In this paper, the astigmatism in the pump beam is reduced by tilting the pump lens. A Gaussian beam is propagated through the complete focusing system-pump lens, tilted spherical mirror, and crystal cut at Brewster's angle-to show the astigmatism inside the crystal as a function of the tilt of the pump lens. A genetic algorithm is presented to optimize the mode coupling between the pump and laser beam inside the crystal by tilting the pump lens. Experimental results are presented to verify the design, showing an increase in the output power of the laser cavity of about 20%.

Heterogeneous estrogen receptor expression in circulating tumor cells suggests diverse mechanisms of fulvestrant resistance.

Fulvestrant is a dose dependent selective estrogen receptor (ER) down-regulator (SERD) used in ER-positive metastatic breast cancer (MBC). Nearly all patients develop resistance. We performed molecular analysis of circulating tumor cells (CTC) to gain insight into fulvestrant resistance. Preclinical studies were performed with cultured breast cancer cells spiked into human blood and analyzed on the CellSearch(®) system. Clinical data are limited to a subset of patients with ER-positive MBC from a previously reported pilot trial whose disease was progressing on fulvestrant (N = 7) or aromatase inhibitors (AIs) (N = 10). CTCs were enumerated and phenotyped for ER and B-cell lymphoma (BCL2) using the CellSearch(®) CXC kit. In preclinical modeling, tamoxifen and AIs resulted in stabilized ER expression, whereas fulvestrant eliminated it. Five of seven patients progressing on fulvestrant had ≥5CTC/7.5 ml WB. Two of these five, treated with 500 mg/month fulvestrant, had no detectable CTC-expression of ER and BCL2 (an ER regulated gene). Three patients had heterogeneous CTC-ER and BCL2 expression indicating incomplete degradation of the ER target by fulvestrant. Two of these patients received 250 mg/month whereas the third patient received 500 mg/month fulvestrant. Her cancer harbored a mutation (Y537S) in the estrogen receptor alpha gene (ESR1). All seven ER positive patients progressing on AIs had heterogeneous CTC-ER expression. These results suggest heterogeneous mechanisms of resistance to fulvestrant, including insufficient dosage, ESR1 mutation, or conversion to dependence on non-ER pathways. CTC enumeration, phenotyping, and genotyping might identify patients who would benefit from fulvestrant dose escalation versus switching to alternative therapies.

The CYP17A1 inhibitor abiraterone exhibits estrogen receptor agonist activity in breast cancer.

Cytochrome P450 17A1 (CYP17A1) is the requisite enzyme for synthesis of sex steroids, including estrogens and androgens. As such, inhibition of CYP17A1 is a target for inhibiting the growth of hormone-dependent cancers including prostate and breast cancer. Abiraterone, is a first in class potent and selective CYP17A1 inhibitor that has been approved for the treatment of castration-resistant prostate cancer. Given that, androgens are the precursors for estrogen production, it has been proposed that abiraterone could be an effective form of treatment for estrogen receptor (ER)-positive breast cancer, though its utility in this context has yet to be established. Abiraterone has a core steroid-like chemical structure, and so we hypothesized that it may bind to nuclear steroid receptors including ER and have estrogenic activity. We tested this hypothesis by investigating abiraterone's ability to directly modulate ER signaling in breast cancer cell line models. We show that abiraterone directly activates ER, induces ER-target gene expression, and elicits estrogen-response-element reporter activity in the ER-positive cell lines MCF-7 and T47D. Abiraterone also induced cell proliferation by ~2.5-fold over vehicle in both MCF-7 and T47D cells. Importantly, abiraterone-induced cell proliferation and ER-activity was blocked by the selective estrogen receptor downregulator (SERD) fulvestrant, confirming that abiraterone directly acts at the ER. These data suggest that abiraterone should be combined with other ER antagonists when used for the clinical management of ER-positive breast cancer.

[Discrimination and homophobia associated to the human immunodeficiency virus epidemic]. / Mapeo político de la discriminación y homofobia asociadas con la epidemia de VIH en México.

OBJECTIVE: To describe a political mapping on discrimination and homophobia associated to human immunodeficiency virus (HIV) in the context of public institutions in Mexico. MATERIALS AND METHODS: The political mapping was conducted in six Mexican states. Stakeholders who were involved in HIV actions from public and private sectors were included. Semistructured interviews were applied to explore homophobia and discrimination associated with HIV. Information was systematized using the Policy Maker software, which is a good support for analyzing health policies. RESULTS: Discriminatory and homophobic practices in the public domain occurred, damaging people´s integrity via insults, derision and hate crimes. Most stakeholders expressed a supportive position to prevent discrimination and homophobia and some of them had great influence on policy-making decisions. It was found that state policy frameworks are less specific in addressing these issues. CONCLUSIONS: Homophobia and discrimination associated to HIV are still considered problematic in Mexico. Homophobia is a very sensitive issue that requires further attention. Also, an actual execution of governmental authority requires greater enforcement of laws against discrimination and homophobia.

[VALIDATION OF A COMPUTER PROGRAM FOR DETECTION OF MALNUTRITION HOSPITAL AND ANALYSIS OF HOSPITAL COSTS]. / VALIDACIÓN DE UN PROGRAMA INFORMÁTICO PARA DETECCIÓN DE LA DESNUTRICIÓN HOSPITALARIA Y ANÁLISIS DEL COSTE HOSPITALARIO.

BACKGROUND: one of the methods of diagnosis of malnutrition is serum albumin, for the simplicity of its determination and low cost. OBJECTIVES: the main objective is to validate and implement a computer program based on the determination of serum albumin, allowing early detection and treatment to malnourished or at risk of malnutrition patients, still another objective evaluation of costs by diagnosis-related groups. METHODS: the study design is cohort, dynamic and prospective, which are included hospital discharge from november 2012 until march 2014, being the study population of patients over age 14 who enter the various services of a Medical Surgical Hospital of the Granada's Hospital Complex Univesity, whose numbers are lower serum albumin 3.5 g/dL, for a total of 307 patients. RESULTS: of the 307 patients, 141 are malnourished (program sensitivity: 45.9%). 54.7% of patients were male and 45.3% female. The mean age of 65.68 years. The median length of stay is 16 days. 13.4% of patients have died. The average cost of GRD is € 5 958.30 and said average cost after detecting malnutrition is € 11 376.48. CONCLUSIONS: the algorithm that implements the software identifies nearly half of patients hospitalized malnourished. It is essential to record the diagnosis of malnutrition.

Introducción: uno de los métodos de diagnóstico de la desnutrición es la albúmina sérica, por la sencillez de su determinación y bajo coste. Objetivos: el objetivo principal es validar e implementar un programa informático, basado en la determinación de albúmina sérica, que permita detectar y tratar precozmente a los pacientes desnutridos o en riesgo de desnutrición, siendo otro objetivo la evaluación de costes por grupos relacionados por el diagnóstico. Métodos: el diseño del estudio es de tipo cohorte, dinámico y prospectivo, en el que se han incluido las altas hospitalarias desde noviembre del año 2012 hasta marzo del año 2014, siendo la población de estudio los pacientes mayores de 14 años que ingresen en los diversos servicios de un Hospital Médico Quirúrgico del Complejo Hospitalario Universitario de Granada, cuyas cifras de albúmina sérica sean menores de 3,5 g/dL, siendo el total de 307 pacientes. Resultados: de los 307 pacientes, 141 presentan desnutrición (sensibilidad del programa: 45,9%). El 54,7% de los pacientes son hombres y el 45,3% mujeres. La edad media es de 65,68 años. La mediana de la estancia es de 16 días. El 13,4% de los pacientes han fallecido. El coste medio de los GRD es de 5.958,30 € y dicho coste medio después de detectar la desnutrición es de 11.376,48 €. Conclusiones: el algoritmo que implementa el programa informático identifica a casi la mitad de los pacientes hospitalizados desnutridos. Es fundamental registrar el diagnóstico de desnutrición.

Validación de un programa informático para detección de la desnutrición hospitalaria y análisis del coste hospitalario / Validation of a computer program for detection of malnutrition hospital and analysis of hospital costs

Introducción: uno de los métodos de diagnóstico de la desnutrición es la albúmina sérica, por la sencillez de su determinación y bajo coste. Objetivos: el objetivo principal es validar e implementar un programa informático, basado en la determinación de albúmina sérica, que permita detectar y tratar precozmente a los pacientes desnutridos o en riesgo de desnutrición, siendo otro objetivo la evaluación de costes por grupos relacionados por el diagnóstico. Métodos: el diseño del estudio es de tipo cohorte, dinámico y prospectivo, en el que se han incluido las altas hospitalarias desde noviembre del año 2012 hasta marzo del año 2014, siendo la población de estudio los pacientes mayores de 14 años que ingresen en los diversos servicios de un Hospital Médico Quirúrgico del Complejo Hospitalario Universitario de Granada, cuyas cifras de albú- mina sérica sean menores de 3,5 g/dL, siendo el total de 307 pacientes. Resultados: de los 307 pacientes, 141 presentan desnutrición (sensibilidad del programa: 45,9%). El 54,7% de los pacientes son hombres y el 45,3% mujeres. La edad media es de 65,68 años. La mediana de la estancia es de 16 días. El 13,4% de los pacientes han fallecido. El coste medio de los GRD es de 5.958,30€ y dicho coste medio después de detectar la desnutrición es de 11.376,48€. Conclusiones: el algoritmo que implementa el programa informático identifica a casi la mitad de los pacientes hospitalizados desnutridos. Es fundamental registrar el diagnóstico de desnutrición (AU)

Background: one of the methods of diagnosis of malnutrition is serum albumin, for the simplicity of its determination and low cost. Objectives: the main objective is to validate and implement a computer program based on the determination of serum albumin, allowing early detection and treatment to malnourished or at risk of malnutrition patients, still another objective evaluation of costs by diagnosis-related groups. Methods: the study design is cohort, dynamic and prospective, which are included hospital discharge from november 2012 until march 2014, being the study population of patients over age 14 who enter the various services of a Medical Surgical Hospital of the Granada´s Hospital Complex Univesity, whose numbers are lower serum albumin 3.5 g/dL, for a total of 307 patients. Results: of the 307 patients, 141 are malnourished (program sensitivity: 45.9%). 54.7% of patients were male and 45.3% female. The mean age of 65.68 years. The median length of stay is 16 days. 13.4% of patients have died. The average cost of GRD is €5 958.30 and said average cost after detecting malnutrition is €11376.48. Conclusions: the algorithm that implements the software identifies nearly half of patients hospitalized malnourished. It is essential to record the diagnosis of malnutrition (AU)

Mapeo político de la discriminación y homofobia asociadas con la epidemia de VIH en México / Discrimination and homophobia associated to the human immunodeficiency virus epidemic

Objetivo. Presentar un mapeo político sobre discriminación y homofobia asociadas con la epidemia del virus de la inmunodeficiencia humana (VIH) en entornos institucionales públicos. Material y métodos. Se realizó un mapeo político con actores clave en seis estados de México, a quienes se les aplicó una entrevista semiestructurada para explorar la discriminación y homofobia asociadas con el VIH. La información se sistematizó mediante matrices de contenido por categorías y el software PolicyMaker. Resultados. Se documentaron prácticas discriminatorias y homofóbicas lesivas a la integridad como la denostación, la burla y los crímenes de odio. La mayoría de actores se manifestaron en contra de la discriminación y la homofobia; algunos de ellos influyeron de manera importante en la formulación de políticas para prevenir la discriminación y la homofobia. Sin embargo, los marcos normativos estatales fueron poco específicos. Conclusiones. Son persistentes las prácticas discriminatorias y la homofobia asociadas con el VIH, por lo cual se requiere mayor atención en los estados y es necesario impulsar políticas para prevenirlas, así como la observancia del cumplimiento de las leyes estatales.

Objective. To describe a political mapping on discrimination and homophobia associated to human immunodeficiency virus (HIV) in the context of public institutions in Mexico. Materials and methods. The political mapping was conducted in six Mexican states. Stakeholders who were involved in HIV actions from public and private sectors were included. Semistructured interviews were applied to explore homophobia and discrimination associated with HIV. Information was systematized using the Policy Maker software, which is a good support for analyzing health policies. Results. Discriminatory and homophobic practices in the public domain occurred, damaging people´s integrity via insults, derision and hate crimes. Most stakeholders expressed a supportive position to prevent discrimination and homophobia and some of them had great influence on policy-making decisions. It was found that state policy frameworks are less specific in addressing these issues. Conclusions. Homophobia and discrimination associated to HIV are still considered problematic in Mexico. Homophobia is a very sensitive issue that requires further attention. Also, an actual execution of governmental authority requires greater enforcement of laws against discrimination and homophobia.