Standardizing Care of Neuro-oncology Patients Using a Customized Electronic Medical Record Toolkit.

OBJECTIVE: To develop and implement a customized toolkit within the electronic medical record (EMR) to standardize care of patients with brain tumors. PATIENTS AND METHODS: We built a customized structured clinical documentation support toolkit to capture standardized data at office visits. We detail the process by which this toolkit was conceptualized and developed. Toolkit development was a physician-led process to determine a work flow and necessary elements to support best practices as defined by the neuro-oncology clinical team. RESULTS: We have developed in our EMR system a customized work flow for clinical encounters with neuro-oncology patients. In addition to providing a road map for clinical care by our neuro-oncology team, the toolkit is designed to maximize discrete data capture. Several hundred fields of discrete data are captured through the toolkit in the context of our routine office visits. We describe the characteristics of patients seen at our clinic, the adoption of the toolkit, current initiatives supported by the toolkit, and future applications. CONCLUSION: The EMR can be effectively structured to standardize office visits and improve discrete data capture. This toolkit can be leveraged to support quality improvement and practice-based research initiatives at the point of care in a neuro-oncology practice.

Neuroprotective Efficacy of a Sigma 2 Receptor/TMEM97 Modulator (DKR-1677) after Traumatic Brain Injury.

Compounds targeting the sigma 2 receptor, which we recently cloned and showed to be identical with transmembrane protein 97 (σ2R/TMEM97), are broadly applicable therapeutic agents currently in clinical trials for imaging in breast cancer and for treatment of Alzheimer's disease and schizophrenia. These promising applications coupled with our previous observation that the σ2R/TMEM97 modulator SAS-0132 has neuroprotective attributes and improves cognition in wild-type mice suggests that modulating σ2R/TMEM97 may also have therapeutic benefits in other neurodegenerative conditions such as traumatic brain injury (TBI). Herein, we report that DKR-1677, a novel derivative of SAS-0132 with increased affinity and selectivity for σ2R/Tmem97 ( Ki = 5.1 nM), is neuroprotective after blast-induced and controlled cortical impact (CCI) TBI in mice. Specifically, we discovered that treatment with DKR-1677 decreases axonal degeneration after blast-induced TBI and enhances survival of cortical neurons and oligodendrocytes after CCI injury. Furthermore, treatment with DKR-1677 preserves cognition in the Morris water maze after blast TBI. Our results support an increasingly broad role for σ2R/Tmem97 modulation in neuroprotection and suggest a new approach for treating patients suffering from TBI.

An Adult Zebrafish Model Reveals that Mucormycosis Induces Apoptosis of Infected Macrophages.

Mucormycosis is a life-threatening fungal infection caused by various ubiquitous filamentous fungi of the Mucorales order, although Rhizopus spp. and Mucor spp. are the most prevalent causal agents. The limited therapeutic options available together with a rapid progression of the infection and a difficult early diagnosis produce high mortality. Here, we developed an adult zebrafish model of Mucor circinelloides infection which allowed us to confirm the link between sporangiospore size and virulence. Transcriptomic studies revealed a local, strong inflammatory response of the host elicited after sporangiospore germination and mycelial tissue invasion, while avirulent and UV-killed sporangiospores failed to induce inflammation and were rapidly cleared. Of the 857 genes modulated by the infection, those encoding cytokines, complement factors, peptidoglycan recognition proteins, and iron acquisition are particularly interesting. Furthermore, neutrophils and macrophages were similarly recruited independently of sporangiospore virulence and viability, which results in a robust depletion of both cell types in the hematopoietic compartment. Strikingly, our model also reveals for the first time the ability of mucormycosis to induce the apoptosis of recruited macrophages but not neutrophils. The induction of macrophage apoptosis, therefore, might represent a key virulence mechanism of these fungal pathogens, providing novel targets for therapeutic intervention in this lethal infection.

Validity and reliability of the Neurobehavioral Evaluation of Infant Development (VANEDELA). Screening Instrument from one to 24 months in primary health care in Mexico / Validez y confiabilidad del instrumento de tamizaje Valoración Neuroconductual del Desarrollo del Lactante (VANEDELA) de uno a 24 meses en el primer nivel de atención en México

Abstract: Introduction: Early identification of developmental delays or disabilities in children is a challenge and a global concern. In Mexico, the prevalence of childhood disability is 6%, and it is estimated that 25% of the unattended delays will have consequences on their potential. VANEDELA is a rapid screening test to detect and prevent developmental disorders in primary health care. Objective: To determine the external validity and test-retest reliability of the behavioral (DB) and reflex (DR) developmental formats of the VANEDELA screening test, compared with the diagnostic test of Gesell's Developmental Schedule Test. Method: Descriptive, transversal, and prospective study in 379 infants aged one to 24 months attending the Neurodevelopment Monitoring Laboratory / INP and the ISSSTE Tlalpan Family Medicine Clinic from 2011 to 2014. Measurements: A set of four aspects was evaluated including validity by external criteria: sensitivity, specificity, positive-negative predictive criteria, and test-retest reliability. Results: In the DB format, we found a 79% - 89% sensitivity (S) and a 83% - 95% specificity (Sp). In the DR format, a 18% - 35% sensitivity and a 81% - 96% specificity were found. Using both DB-DR formats, we found a 82% - 89% sensitivity and 72% to 91% specificity, and a test-retest reliability .62-1. Discussion and conclusion: The VANEDELA increased its validity parameters with respect to the previous assessment with adequate stability. The DB formats and the DB-DR combination of VANEDELA have an adequate validity based on external criteria, making them suitable for use in primary health care.

Resumen: Introducción: La identificación temprana de retrasos o discapacidades del desarrollo en los niños es un reto y una preocupación mundial. En México, la prevalencia de discapacidad infantil es del 6% y se estima que un 25% de los retrasos no atendidos tendrán consecuencias en su potencial alcanzado. El VANEDELA es una prueba de tamizaje rápido para detectar y prevenir alteraciones del desarrollo en el primer nivel de atención. Objetivo: Determinar la validez (criterio externo) y confiabilidad (test-retest) de los formatos de conductas (CD) y reacciones del desarrollo (RD) de la prueba de tamizaje VANEDELA, contrastado con la Prueba Diagnóstica de Desarrollo de Gesell. Método: Estudio descriptivo, transversal y prospectivo en 379 lactantes de uno a 24 meses que asistieron al Laboratorio de Seguimiento del Neurodesarrollo del INP y la Clínica de Medicina Familiar Tlalpan del ISSSTE de 2011 a 2012. Mediciones: Validez por criterio externo, sensibilidad y especificidad, validez predictiva positiva y negativa; confiabilidad test-retest (intervalo de siete días). Resultados: En el formato CD, se encontró sensibilidad (S) de 79% a 89% y especificidad (E) de 83% a 95%. Utilizando ambos formatos CD-RD, se encontraron una sensibilidad de 82% a 89% y una especificidad de 72% a 91%. Test-retest .62-1. Discusión y conclusión: El VANEDELA aumentó sus parámetros de validez con respecto a la valoración anterior, estabilidad adecuada. Los formatos CD y la combinación CD-RD del VANEDELA poseen una adecuada validez por criterio externo y estabilidad test-retest, para ser utilizada en el primer nivel de atención.

Risk factors and outcomes of organ-space surgical site infections after elective colon and rectal surgery.

BACKGROUND: Organ-space surgical site infections (SSI) are the most serious and costly infections after colorectal surgery. Most previous studies of risk factors for SSI have analysed colon and rectal procedures together. The aim of the study was to determine whether colon and rectal procedures have different risk factors and outcomes for organ-space SSI. METHODS: A multicentre observational prospective cohort study of adults undergoing elective colon and rectal procedures at 10 Spanish hospitals from 2011 to 2014. Patients were followed up until 30 days post-surgery. Surgical site infection was defined according to the Centers for Disease Control and Prevention criteria. Oral antibiotic prophylaxis (OAP) was considered as the administration of oral antibiotics the day before surgery combined with systemic intravenous antibiotic prophylaxis. RESULTS: Of 3,701 patients, 2,518 (68%) underwent colon surgery and 1,183 (32%) rectal surgery. In colon surgery, the overall SSI rate was 16.4% and the organ-space SSI rate was 7.9%, while in rectal surgery the rates were 21.6% and 11.5% respectively (p < 0.001). Independent risk factors for organ-space SSI in colon surgery were male sex (Odds ratio -OR-: 1.57, 95% CI: 1.14-2.15) and ostomy creation (OR: 2.65, 95% CI: 1.8-3.92) while laparoscopy (OR: 0.5, 95% CI: 0.38-0.69) and OAP combined with intravenous antibiotic prophylaxis (OR: 0.7, 95% CI: 0.51-0.97) were protective factors. In rectal surgery, independent risk factors for organ-space SSI were male sex (OR: 2.11, 95% CI: 1.34-3.31) and longer surgery (OR: 1.49, 95% CI: 1.03-2.15), whereas OAP with intravenous antibiotic prophylaxis (OR: 0.49, 95% CI: 0.32-0.73) was a protective factor. Among patients with organ-space SSI, we found a significant difference in the overall 30-day mortality, being higher in colon surgery than in rectal surgery (11.5% vs 5.1%, p = 0.04). CONCLUSIONS: Organ-space SSI in colon and rectal surgery has some differences in terms of incidence, risk factors and outcomes. These differences could be considered for surveillance purposes and for the implementation of preventive strategies. Administration of OAP would be an important measure to reduce the OS-SSI rate in both colon and rectal surgeries.

RNAi-Based Functional Genomics Identifies New Virulence Determinants in Mucormycosis.

Mucorales are an emerging group of human pathogens that are responsible for the lethal disease mucormycosis. Unfortunately, functional studies on the genetic factors behind the virulence of these organisms are hampered by their limited genetic tractability, since they are reluctant to classical genetic tools like transposable elements or gene mapping. Here, we describe an RNAi-based functional genomic platform that allows the identification of new virulence factors through a forward genetic approach firstly described in Mucorales. This platform contains a whole-genome collection of Mucor circinelloides silenced transformants that presented a broad assortment of phenotypes related to the main physiological processes in fungi, including virulence, hyphae morphology, mycelial and yeast growth, carotenogenesis and asexual sporulation. Selection of transformants with reduced virulence allowed the identification of mcplD, which encodes a Phospholipase D, and mcmyo5, encoding a probably essential cargo transporter of the Myosin V family, as required for a fully virulent phenotype of M. circinelloides. Knock-out mutants for those genes showed reduced virulence in both Galleria mellonella and Mus musculus models, probably due to a delayed germination and polarized growth within macrophages. This study provides a robust approach to study virulence in Mucorales and as a proof of concept identified new virulence determinants in M. circinelloides that could represent promising targets for future antifungal therapies.

Hybrid treatment of penetrating aortic ulcer.

Penetrating atherosclerotic aortic ulcer is a rare entity with poor prognosis in the setting of acute aortic syndrome. In the literature, cases like the present one, located in the aortic arch, starting with chest pain and evolving with dysphonia, are even rarer. The present report emphasizes the role played by computed tomography in the diagnosis of penetrating atherosclerotic ulcer as well as in the differentiation of this condition from other acute aortic syndromes. Additionally, the authors describe a new therapeutic approach represented by a hybrid endovascular surgical procedure for treatment of the disease.

A úlcera aórtica penetrante é uma entidade rara e de prognóstico desfavorável dentro da síndrome aórtica aguda. Mais raros ainda, na literatura, são os casos como o aqui relatado, localizado no arco aórtico, que começa com dor torácica e evolui com disfonia. O presente caso enfatiza o papel da tomografia computadorizada no diagnóstico da úlcera aórtica penetrante e na sua diferenciação de outras entidades dentro da síndrome aórtica aguda. Apresenta também um avanço terapêutico nessa doença, constituído por tratamento híbrido endovascular e cirúrgico.

Hybrid treatment of penetrating aortic ulcer / Tratamento híbrido de úlcera aórtica penetrante

Abstract Penetrating atherosclerotic aortic ulcer is a rare entity with poor prognosis in the setting of acute aortic syndrome. In the literature, cases like the present one, located in the aortic arch, starting with chest pain and evolving with dysphonia, are even rarer. The present report emphasizes the role played by computed tomography in the diagnosis of penetrating atherosclerotic ulcer as well as in the differentiation of this condition from other acute aortic syndromes. Additionally, the authors describe a new therapeutic approach represented by a hybrid endovascular surgical procedure for treatment of the disease.

A úlcera aórtica penetrante é uma entidade rara e de prognóstico desfavorável dentro da síndrome aórtica aguda. Mais raros ainda, na literatura, são os casos como o aqui relatado, localizado no arco aórtico, que começa com dor torácica e evolui com disfonia. O presente caso enfatiza o papel da tomografia computadorizada no diagnóstico da úlcera aórtica penetrante e na sua diferenciação de outras entidades dentro da síndrome aórtica aguda. Apresenta também um avanço terapêutico nessa doença, constituído por tratamento híbrido endovascular e cirúrgico.

Multifrequency interrogation of nanostructured gas sensor arrays: a tool for analyzing response kinetics.

This paper presents a unique perspective on enhancing the physicochemical mechanisms of two distinct highly sensitive nanostructured metal oxide micro hot plate gas sensors by utilizing an innovative multifrequency interrogation method. The two types of sensors evaluated here employ an identical silicon transducer geometry but with a different morphological structure of the sensitive film. While the first sensing film consists of self-ordered tungsten oxide nanodots, limiting the response kinetics of the sensor-chemical species pair only to the reaction phenomena occurring at the sensitive film surface, the second modality is a three-dimensional array of tungsten oxide nanotubes, which in turn involves both the diffusion and adsorption of the gas during its reaction kinetics with the sensitive film itself. By utilizing the proposed multifrequency interrogation methodology, we demonstrate that the optimal temperature modulation frequencies employed for the nanotubes-based sensors to selectively detect hydrogen, carbon monoxide, ethanol, and dimethyl methyl phosphonate (DMMP) are significantly higher than those utilized for the nanodot-based sensors. This finding helps understand better the amelioration in selectivity that temperature modulation of metal oxides brings about, and, most importantly, it sets the grounds for the nanoengineering of gas-sensitive films to better exploit their practical usage.

Smoking risk factors and gender differences among Spanish high school students.

The objectives of the present study were to analyze the pattern of tobacco use among Spanish adolescents, as well as to determine gender differences in specific risk factors of cigarette use. The study sample was made up of 1,483 boys and 1,358 girls, aged 12-16 (M = 14). Participants were asked to answer an ad-hoc instrument to evaluate the pattern of use, perceived availability, risk of harm, family- and peer-use, engagement in leisure activities, drive for thinness, and self-esteem. Results showed no gender differences in the pattern of use. With regard to risk and protector factors, a predictive analysis showed that peer-related variables were the most determinant for tobacco use both for boys and girls. Some gender differences were also detected: Playing sports was protective for boys only, and listening to music for girls only. Drive for thinness and self-esteem were not related to tobacco use for either boys or girls. These findings help increase our understanding of smoking risk factors in adolescence and to pay special attention to the group of friends when planning prevention programs to reduce risk factors.

[Cost-effectiveness of a cervical cancer screening programme in the Algarve region, Portugal]. / Análisis coste-efectividad del programa de detección sistemática del cáncer cervical en la región del Algarve, Portugal.

BACKGROUND: Economic evaluation of health care is an instrument of support to decision-making in the allocation of resources between different options. The current study was conducted with a view to implement an organised mass-screening programme. The objective was to evaluate the cost-effectiveness of three options: two programmes to be implemented that are called "Pap screenings" and "Thin-prep screening", and the strategy currently in place called "Spontaneous screening". METHODS: The analysis was undertaken from the Health Care System perspective. The analytic horizon was 10 years. Direct medical costs were estimated and discounted at a rate of 5%. Effectiveness was estimated as number of preinvasive carcinomas detected and life years gained. The cost-effectiveness ratio was estimated for the three options and incremental cost-effectiveness was estimated by comparison of the options to be implemented with the current strategy. A sensitivity analysis was conducted on the key variables. RESULTS: The average cost per carcinoma detected was 1,199 euros with "Pap screening", 3,148 euros with "spontaneous screening" and 4,619 euros with "Thin-prep screening". The average cost per life year gained was 29 euros with "Pap screening", 77 euros with "Spontaneous screening" and 114 euros with "Thin-prep screening". "Pap screening" had an additional cost of 623 euros per additional carcinoma detected and 15 euros per additional life year gained. "Thin-prep screening" had an additional cost of 6,350 euros per additional carcinoma detected and 156 euros per additional life year gained. CONCLUSIONS: "Pap screening" had the best cost-effectiveness relation and the lowest additional cost-effectiveness.