Exome sequencing identifies breast cancer susceptibility genes and defines the contribution of coding variants to breast cancer risk.

Linkage and candidate gene studies have identified several breast cancer susceptibility genes, but the overall contribution of coding variation to breast cancer is unclear. To evaluate the role of rare coding variants more comprehensively, we performed a meta-analysis across three large whole-exome sequencing datasets, containing 26,368 female cases and 217,673 female controls. Burden tests were performed for protein-truncating and rare missense variants in 15,616 and 18,601 genes, respectively. Associations between protein-truncating variants and breast cancer were identified for the following six genes at exome-wide significance (P < 2.5 × 10-6): the five known susceptibility genes ATM, BRCA1, BRCA2, CHEK2 and PALB2, together with MAP3K1. Associations were also observed for LZTR1, ATR and BARD1 with P < 1 × 10-4. Associations between predicted deleterious rare missense or protein-truncating variants and breast cancer were additionally identified for CDKN2A at exome-wide significance. The overall contribution of coding variants in genes beyond the previously known genes is estimated to be small.

Ultrasound-Based Assessment of Preperitoneal Fat as a Surrogate Marker of Cardiovascular Risk: Comparative Study Between People Living with HIV and Controls.

Optimal management of cardiovascular disease should start with the identification of subjects at subclinical stages. However, available tools are not always accurate or affordable. We assess the usefulness of ultrasound-guided measurement of abdominal fat layers as a surrogate marker of cardiovascular risk. We performed a cross-sectional, case-control, exploratory, pilot study in 10 people living with HIV (PLWH) and 10 HIV-uninfected subjects (control group) matched for age, sex, and body mass index. All participants were men 45-60 years of age, with no active disease or previous abdominal surgery; the PLWH group had been virologically suppressed for ≥2 years under stable antiretroviral therapy. The thickness of abdominal superficial and deep subcutaneous fat, preperitoneal fat, omental (periaortic) fat, and retroperitoneal (perirenal) fat was compared between both groups. Correlations between fat layers and traditional markers of cardiovascular risk were assessed. The thickness of most layers was always higher among PLWH. The differences were statistically significant for the preperitoneal fat layer (p = .04). The presence of atherosclerotic plaque was correlated with the preperitoneal fat layer in the PLWH group (odds ratio = 1.49, p = .02), and metabolic syndrome was correlated with superficial subcutaneous fat, although this was low (odds ratio = 0.54, p = .02). In the control group, several associations were found between carotid intima media thickness and abdominal fat layers. All abdominal fat layers were thicker in the PLWH group, especially preperitoneal fat, and several associations were found between specific fat layers and traditional cardiovascular risk markers. Our results suggest that the thickness of abdominal fat layers, assessed by ultrasound, could be a marker of cardiovascular risk. However, further studies with larger populations are required to confirm these findings.

POLRMT as a Novel Susceptibility Gene for Cardiotoxicity in Epirubicin Treatment of Breast Cancer Patients.

Anthracyclines are among the most used chemotherapeutic agents in breast cancer (BC). However their use is hampered by anthracycline-induced cardiotoxicity (AIC). The currently known clinical and genetic risk factors do not fully explain the observed inter-individual variability and only have a limited ability to predict which patients are more likely to develop this severe toxicity. To identify novel predictive genes, we conducted a two-stage genome-wide association study in epirubicin-treated BC patients. In the discovery phase, we genotyped over 700,000 single nucleotide variants in a cohort of 227 patients. The most interesting finding was rs62134260, located 4kb upstream of POLRMT (OR = 5.76, P = 2.23 × 10-5). We replicated this association in a validation cohort of 123 patients (P = 0.021). This variant regulates the expression of POLRMT, a gene that encodes a mitochondrial DNA-directed RNA polymerase, responsible for mitochondrial gene expression. Individuals harbouring the risk allele had a decreased expression of POLRMT in heart tissue that may cause an impaired capacity to maintain a healthy mitochondrial population in cardiomyocytes under stressful conditions, as is treatment with epirubicin. This finding suggests a novel molecular mechanism involved in the development of AIC and may improve our ability to predict patients who are at risk.

Manejo de medidas de bioseguridad en el personal de enfermería que labora en el área de emergencia del hospital general norte de Guayaquil IESS los ceibos / Management of biosecurity measures for nursing personnel working in the emergency area of the Hospital General Norte de Guayaquil IESS Los Ceibos

Las medidas de Bioseguridad son un conjunto de normas preventivas que debe aplicar el personal de salud y de enfermería para evitar el contagio por la exposición de agentes infecciosos, sean físicos, químicos o biológicos. Objetivo: Determinar el manejo de las medidas de bioseguridad del personal de enfermería del servicio de emergencia del Hospital General Norte de Guayaquil IESS Los Ceibos. Fundamentándose en la gran problemática del manejo de los riesgos biológicos en el personal sanitario, que con frecuencia omite aplicar normas de seguridad, lo que aumenta el riesgo de contraer una enfermedad infectocontagiosa de tipo laboral. Materiales y métodos: La metodología empleada fue diseño descriptivo, con corte transversal, Cuali-cuantitativo. La recolección de datos se la realizó mediante la aplicación de cuestionarios pre estructurado, los cuales ayudaron a establecer el nivel de conocimientos y manejo de las medidas de bioseguridad por parte del personal. La muestra la conformaron 90 enfermeras y enfermeros que laboran en el área de emergencia. Resultados: Los resultados revelaron que el nivel de conocimiento del personal de enfermería es alto o adecuado con un porcentaje promedio de 77,67%, por ende, el 22,33% del personal desconoce estas medidas preventivas o tiene conocimiento deficiente. Con respecto a la aplicación de las medidas de bioseguridad se obtuvo un porcentaje general de 47%, es decir se considera la aplicación de estas normas por parte del personal deficiente e insuficiente. Conclusión: Se menciona que hay riesgos en el área de emergencia, prevaleciendo entre ellos el biológico de acuerdo a la opinión del personal encuestado, por otra parte, se determinó un conocimiento eficiente de las medidas de bioseguridad, pero su aplicación en relación al conocimiento es deficiente, situación que incrementa el riesgo laboral(AU)

Biosafety measures are a set of preventive rules to be applied by health and nursing personnel to avoid contagion by exposure to infectious agents, whether physical, chemical or biological. Objective: To determine the management biosecurity measures of the nursing staff of the emergency service of the Hospital General Norte de Guayaquil IESS Los Ceibos. Based on the great problem of the management of biological risks in health personnel, who often fail to apply safety standards, which increases the risk of contracting an occupational infectious-contagious disease. Materials and methods: The methodology used was a descriptive, cross-sectional, qualitative-quantitative design. Data collection was carried out through the application of pre-structured questionnaires, which helped to establish the level of knowledge and management biosafety measures by the personnel. The sample consisted of 90 nurses working in the emergency area. The results: The results revealed that the level of knowledge of the nursing personnel is high or adequate with an average percentage of 77.67%; therefore, 22.33% of the personnel are unaware of these preventive measures or have deficient knowledge. With respect to the application biosecurity measures, an overall percentage of 47% was obtained, i.e. the application of these norms by of personnel is considered deficient and insufficient. Conclusion: It is mentioned that there are risks in the emergency area, prevailing among them the biological risk, according to the opinion of the personnel surveyed. On the other hand, an efficient knowledge of the biosecurity measures was determined, but their application in relation to the knowledge is deficient, a situation that increases the occupational risk(AU)

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

BACKGROUND: Genetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking. METHODS: We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes. We evaluated missense-variant associations according to domain and classification of pathogenicity. RESULTS: Protein-truncating variants in 5 genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a risk of breast cancer overall with a P value of less than 0.0001. Protein-truncating variants in 4 other genes (BARD1, RAD51C, RAD51D, and TP53) were associated with a risk of breast cancer overall with a P value of less than 0.05 and a Bayesian false-discovery probability of less than 0.05. For protein-truncating variants in 19 of the remaining 25 genes, the upper limit of the 95% confidence interval of the odds ratio for breast cancer overall was less than 2.0. For protein-truncating variants in ATM and CHEK2, odds ratios were higher for estrogen receptor (ER)-positive disease than for ER-negative disease; for protein-truncating variants in BARD1, BRCA1, BRCA2, PALB2, RAD51C, and RAD51D, odds ratios were higher for ER-negative disease than for ER-positive disease. Rare missense variants (in aggregate) in ATM, CHEK2, and TP53 were associated with a risk of breast cancer overall with a P value of less than 0.001. For BRCA1, BRCA2, and TP53, missense variants (in aggregate) that would be classified as pathogenic according to standard criteria were associated with a risk of breast cancer overall, with the risk being similar to that of protein-truncating variants. CONCLUSIONS: The results of this study define the genes that are most clinically useful for inclusion on panels for the prediction of breast cancer risk, as well as provide estimates of the risks associated with protein-truncating variants, to guide genetic counseling. (Funded by European Union Horizon 2020 programs and others.).

Silicone microbubbles after anti-vascular endothelial growth factor injections in patients with wet age-related macular degeneration: incidence, quantification and secondary optical coherence tomography artfacts.

PURPOSE: To report the incidence and quantity of silicone oil microbubbles and the relationship with the number of intravitreal anti-vascular endothelial growth factor (VEGF) injections and evaluate if microbubbles induce artefacts on optical coherence tomography (OCT) images. METHODS: Observational, descriptive, cross-sectional study. Patients with wet age-related macular degeneration were included who had been treated for 1 year minimally with anti-VEGF injections repackaged in the hospital pharmacy. Detection and quantification of silicone microbubbles by mydriatic biomicroscopic examination were conducted 1 month after the last injection. The numbers of microbubbles were quantified on a scale of 0-3: 0, none; 1 scarce (1-10 microbubbles); 2 moderate (10-30); or 3 numerous (>30). Shadowing on OCT images was classified as 0-3: 0, none; 1 obscuring some retinal layers; 2 obscuring all retinal layers; or 3 obscuring the retinal thickness. RESULTS: The study included 142 eyes of 98 patients (mean age, 82.4 years + 7.3; range, 65-97) treated with 2377 injections. Microbubbles were detected in 127 (89.4%) eyes, 62 (43.6%) with numerous microbubbles and 36 (25.4%) and 29 (20.4%), respectively, with scarce and moderate numbers. A positive correlation was found between the numbers of injections and intravitreal silicone (rho, 0.7). Optical coherence tomography (OCT) artefacts were detected in 11 eyes; the artefacts obscured all retinal layers in three eyes. No significant relationship could be established between the appearance of floaters and the microbubbles. CONCLUSION: The presence and number of silicone microbubbles were correlated with the number of intravitreal injections. Microbubbles can produce OCT artefacts, which can hinder the treatment decision.

Potential prescribing issues among older HIV-infected subjects in a Mediterranean cohort: Does the current prevalence give cause for concern?

AIMS: To determine the prevalence of potential prescribing issues (PPI) in HIV-infected subjects aged ≥65 years according to the Beers and STOPP/START criteria and antiretroviral drug-drug interactions (Liverpool website). Secondary objectives were to assess the concordance between Beers and STOPP/START criteria in our population, and to identify the drugs most frequently involved in PPI. METHODS: Cross-sectional cohort study based on a systematic review of the electronic drug prescriptions confirmed by an interview of 91 HIV-infected patients aged ≥65 years. Discrepancies between prescription criteria were assessed using crosstabs and compared using the χ2 test or Fisher exact test. RESULTS: The mean age was 72.1 (5.6) years, 75.8% had ≥3 comorbidities and 59.3% polypharmacy. PPI were identified in 87.9%: 71.4% by STOPP/START and 45.1% by Beers. Comparing both criteria, 56.9% of PPI by STOPP/START were detected by Beers, while 92.5% of those detected by the Beers criteria were detected by STOPP/START (P < .001). Amber/red flag interactions between antiretrovirals and comedications were found in 45.1%: 3 severe (red) in 2 patients (2.2%). The most frequent drugs involved in PPI were benzodiazepines (>30%). Cobicistat was the drug most frequently involved in potential interactions (42.2%). CONCLUSION: The prevalence of PPI among older HIV-infected persons gives cause for concern, as it is almost 90%. Optimization strategies, including a critical review of the treatment plan, should be implemented in clinical routine by a multidisciplinary team, in particular in patients with multiple comorbidities and polypharmacy. The STOPP/START criteria seem to detect more PPI, mainly for European populations.

A phase III, randomized, double blinded trial of platinum based chemotherapy with or without atezolizumab followed by niraparib maintenance with or without atezolizumab in patients with recurrent ovarian, tubal, or peritoneal cancer and platinum treatment free interval of more than 6 months: ENGOT-Ov41/GEICO 69-O/ANITA Trial.

BACKGROUND: Platinum based chemotherapy is the treatment of choice for ovarian cancer patients with a platinum treatment free interval of >6 months. Niraparib is an oral poly (ADP-ribose) polymerase inhibitor approved as maintenance therapy after a response to platinum rechallenge, regardless of BRCA status. Atezolizumab is a humanized monoclonal antibody targeting programmed death-ligand 1 (PD-L1). A combination of poly (ADP-ribose) polymerase inhibitor and anti-PD-L1/programmed cell death protein 1 (PD-1) has shown synergy in preclinical models and promising clinical activity. PRIMARY OBJECTIVE: To determine whether the addition of atezolizumab to carboplatin based chemotherapy and to subsequent maintenance with niraparib improves progression free survival compared with placebo in patients with recurrent disease and a platinum treatment free interval of >6 months. TRIAL DESIGN: The Atezolizumab and NIraparib Treatment Association (ANITA) trial is a GEICO (Grupo Español de Investigación en Cáncer de Ovario) led phase III, randomized, double-blinded, multicenter European Network for Gynecological Oncological Trials (ENGOT) study. Patients will be randomized to arm A (control arm) consisting of platinum based chemotherapy (investigator's choice) plus a placebo of atezolizumab followed by maintenance niraparib plus a placebo of atezolizumab, or to arm B (experimental arm) consisting of platinum based chemotherapy (investigator's choice) plus atezolizumab followed by maintenance niraparib plus atezolizumab. MAJOR INCLUSION/EXCLUSION CRITERIA: Inclusion criteria are women aged over 18 years, diagnosed with relapsed high grade serous, endometrioid, or undifferentiated ovarian, fallopian tube, or primary peritoneal carcinoma. Patients are eligible if they received no more than two previous lines of chemotherapy, relapsed ≥6 months after the last platinum containing regimen, and have at least one measurable lesion according to the response evaluation criteria in solid tumors, version 1.1. PRIMARY ENDPOINT: The primary endpoint for this study is progression free survival. SAMPLE SIZE: Approximately 414 patients will be recruited and randomized in a 1:1 ratio, with the aim of demonstrating a benefit in progression free survival for the experimental arm with a hazard ratio of O.7, using a two sided alpha of 0.05 and a power of 80%. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The trial was launched in the fourth quarter of 2018 and is estimated to close in the second quarter of 2021. Mature results for progression free survival are expected to be presented by 2023. TRIAL REGISTRATION: Clinicaltrials.gov NCT03598270.

Therapeutic Vaccination Refocuses T-cell Responses Towards Conserved Regions of HIV-1 in Early Treated Individuals (BCN 01 study).

BACKGROUND: Strong and broad antiviral T-cell responses targeting vulnerable sites of HIV-1 will likely be a critical component for any effective cure strategy. METHODS: BCN01 trial was a phase I, open-label, non-randomized, multicenter study in HIV-1-positive individuals diagnosed and treated during early HIV-1 infection to evaluate two vaccination regimen arms, which differed in the time (8 versus 24 week) between the ChAdV63.HIVconsv prime and MVA.HIVconsv boost vaccinations. The primary outcome was safety. Secondary endpoints included frequencies of vaccine-induced IFN-γ+ CD8+ T cells, in vitro virus-inhibitory capacity, plasma HIV-1 RNA and total CD4+ T-cells associated HIV-1 DNA. (NCT01712425). FINDINGS: No differences in safety, peak magnitude or durability of vaccine-induced responses were observed between long and short interval vaccination arms. Grade 1/2 local and systemic post-vaccination events occurred in 22/24 individuals and resolved within 3 days. Weak responses to conserved HIV-1 regions were detected in 50% of the individuals before cART initiation, representing median of less than 10% of their total HIV-1-specific T cells. All participants significantly elevated these subdominant T-cell responses, which after MVA.HIVconsv peaked at median (range) of 938 (73-6,805) IFN-γ SFU/106 PBMC, representing on average 58% of their total anti-HIV-1 T cells. The decay in the size of the HIV-1 reservoir was consistent with the first year of early cART initiation in both arms. INTERPRETATION: Heterologous prime-boost vaccination with ChAdV63-MVA/HIVconsv was well-tolerated and refocused pre-cART T-cell responses towards more protective epitopes, in which immune escape is frequently associated with reduced HIV-1 replicative fitness and which are common to most global HIV-1 variants. FUNDING: HIVACAT Catalan research program for an HIV vaccine and Fundació Gloria Soler. Vaccine manufacture was jointly funded by the Medical Research Council (MRC) UK and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreements (G0701669. RESEARCH IN CONTEXT: Evidence Before this Study: T cells play an important role in the control of HIV infection and may be particularly useful for HIV-1 cure by killing cells with reactivated HIV-1. Evidence is emerging that not all T-cell responses are protective and mainly only those targeting conserved regions of HIV-1 proteins are effective, but typically immunologically subdominant, while those recognizing hypervariable, easy-to-escape immunodominant 'decoys' do not control viremia and do not protect from a loss of CD4 T cells. We pioneered a vaccine strategy focusing T-cell responses on the most conserved regions of the HIV-1 proteome using an immunogen designated HIVconsv. T cells elicited by the HIVconsv vaccines in HIV-uninfected UK and Kenyan adults inhibited in vitro replication of HIV-1 isolates from 4 major global clades A, B, C and D.Added Value of this Study: The present study demonstrated the concept that epitopes subdominant in natural infection, when taken out of the context of the whole HIV-1 proteome and presented to the immune system by a potent simian adenovirus prime-poxvirus MVA boost regimen, can induce strong responses in patients on antiretroviral treatment and efficiently refocus HIV-1-specific T-cells to the protective epitopes delivered by the vaccine.Implications of all the Available Evidence: Nearly all HIV-1 vaccine strategies currently emphasize induction of broadly neutralizing Abs. The HIVconsv vaccine is one of a very few approaches focussing exclusively on elicitation of T cells and, therefore, can complement antibody induction for better prevention and cure. Given the cross-clade reach on the HIVconsv immunogen design, if efficient, the HIVconsv vaccines could be deployed globally. Effective vaccines will likely be a necessary component in combination with other available preventive measures for halting the HIV-1/AIDS epidemic.

Determinantes de la innovación en empresas propiedad del Estado: evidencia para las empresas públicas de Ecuador / Determinantes da inovação nas empresas estatais: evidência para as empresas públicas no Equador / Drivers of innovation in state-owned enterprises: evidence to public enterprises from Ecuador

Resumen Los estudios de innovación en la actualidad no toman en cuenta o tienden a ignorar la innovación en las empresas públicas (EP) y sus efectos sobre otras organizaciones. Evidencia reciente muestra que las EP no son necesariamente inferiores a sus contrapartes privadas (Kowalski, Büge, Sztajerowska, & Egeland, 2013). Este trabajo investiga por primera vez mediante un estudio empírico los determinantes de la innovación en las EP de Ecuador. Identifica determinantes internos y externos de la innovación y su efecto en la probabilidad de innovación en EP. Además, se incluye la variable cuidado ambiental como determinante interno; esta variable no ha sido analizada en trabajos previos sobre innovación en EP. Los datos utilizados provienen de la encuesta de actividades de ciencia y tecnología e innovación de Ecuador (ACTI) publicada en el 2014. El modelo propuesto se estima mediante una regresión lineal de tipo logit. Los resultados muestran que existen determinantes que tienen efecto positivo sobre la probabilidad de innovación y que son de dos tipos: internos (trabajadores, capacitación, adquisición de tecnología y cuidado ambiental) y externos (gobierno, mediante el programa de apoyo a la gestión de calidad).

Resumo Os estudos de inovação atualmente não levam em conta e tendem a ignorar a inovação nas empresas públicas (EP) e seus efeitos sobre outras organizações. Evidências recentes mostram que as EP não são necessariamente inferiores às empresas privadas (Kowalski et al., 2013). Este artigo investiga pela primeira vez através de um estudo empírico os determinantes da inovação em EP no Equador. Identifica os determinantes internos e externos da inovação e seu efeito sobre a probabilidade de inovação no EP. Além disso, a variável cuidado ambiental é incluída como um determinante interno; esta variável não foi analisada em estudos anteriores sobre a inovação em EP. Os dados são da pesquisa de atividades de ciência, tecnologia e inovação do Equador (ACTI), publicado em 2014. O modelo proposto é avaliado por meio de uma regressão linear de tipo logit. Os resultados mostram que existem determinantes que têm efeito positivo sobre a probabilidade de inovação e são de dois tipos: internos (funcionários, treinamento, aquisição de tecnologia e cuidado ambiental) e externos (governo, mediante o apoio para gestão de qualidade).

Abstract The current studies on innovation do not consider or tend to ignore innovation in Public Enterprises (PE) and their effects on other organizations. Recent evidence shows that PE are not necessarily inferior to their private counterparts (Kowalski, Büge, Sztajerowska, & Egeland, 2013). This article investigates the determinants of innovation in PE of Ecuador, for the first time, through an empirical study. It identifies internal and external determinants of innovation and the effect on the probability of innovation in PE. In addition, the variable environmental care is included as an internal determinant; this variable has not been analyzed in previous work on innovation in PE. The data used come from the Survey of Activities of Science, Technology, and Innovation of Ecuador (ACTI) published in 2014. The proposed model is estimated by logit linear regression. The results show that there are determinants that have a positive effect on the probability of innovation and they are of two types: internal (workers training, technology acquisition and environmental care) and external (government, through the support program for quality management).

NEU Screen Shows High Accuracy in Detecting Cognitive Impairment in Older Persons Living With HIV.

The NEUrocognitive (NEU) Screen is a practical tool proposed to screen for HIV-associated cognitive impairment in the clinical setting. This is a pencil-and-paper method that can be applied rapidly (≤10 minutes for administration) and has no copyright limitations. In this study, we aimed at investigating its diagnostic accuracy in an older population of persons living with HIV (PLWH), with cutoffs set at 30, 40, 50, and 60 years. Data were collected from a sample of 368 PLWH who underwent a comprehensive neuropsychological tests battery (gold standard). Results of statistical tests showed that accuracy of the NEU Screen increased with age of the participants. The highest degree of precision, with a sensitivity of 91% and specificity of 92%, was obtained for people ages 60 years or older (correct classification: 91%). These optimal results point to the great potential of the NEU Screen as a tool for detecting cognitive disorders in older PLWH.

Cutaneous and Mucosal Manifestations Associated with Celiac Disease.

Celiac disease (CD) is an immune-mediated, gluten-induced enteropathy that affects predisposed individuals of all ages. Many patients with CD do not report gastrointestinal symptoms making it difficult to reach an early diagnosis. On the other hand, CD is related to a wide spectrum of extra-intestinal manifestations, with dermatitis herpetiformis (DH) being the best characterized. These associated conditions may be the clue to reaching the diagnosis of CD. Over the last few years, there have been multiple reports of the association between CD and several cutaneous manifestations that may improve with a gluten-free diet (GFD). The presence of some of these skin diseases, even in the absence of gastrointestinal symptoms, should give rise to an appropriate screening method for CD. The aim of this paper is to describe the different cutaneous manifestations that have been associated with CD and the possible mechanisms involved.

Genomic characterization of individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced lung cancer.

Single nucleotide polymorphisms (SNPs) may modulate individual susceptibility to carcinogens. We designed a genome-wide association study to characterize individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced non-small cell lung cancer (NSCLC), and we validated our results. We hypothesized that this strategy would enrich the frequencies of the alleles that contribute to the observed traits. We genotyped 2.37 million SNPs in 95 extreme phenotype individuals, that is: heavy smokers that either developed NSCLC at an early age (extreme cases); or did not present NSCLC at an advanced age (extreme controls), selected from a discovery set (n = 3631). We validated significant SNPs in 133 additional subjects with extreme phenotypes selected from databases including >39,000 individuals. Two SNPs were validated: rs12660420 (pcombined  = 5.66 × 10-5 ; ORcombined  = 2.80), mapping to a noncoding transcript exon of PDE10A; and rs6835978 (pcombined  = 1.02 × 10-4 ; ORcombined  = 2.57), an intronic variant in ATP10D. We assessed the relevance of both proteins in early-stage NSCLC. PDE10A and ATP10DmRNA expressions correlated with survival in 821 stage I-II NSCLC patients (p = 0.01 and p < 0.0001). PDE10A protein expression correlated with survival in 149 patients with stage I-II NSCLC (p = 0.002). In conclusion, we validated two variants associated with extreme phenotypes of high and low risk of developing tobacco-induced NSCLC. Our findings may allow to identify individuals presenting high and low risk to develop tobacco-induced NSCLC and to characterize molecular mechanisms of carcinogenesis and resistance to develop NSCLC.

Optimal Use of Transient Elastography and Acoustic Radiation Force Impulse to Stage Liver Fibrosis in HIV/HCV-Coinfected Patients in Clinical Practice.

OBJECTIVES: Liver fibrosis (LF) is crucial for the individualized management of patients with hepatitis C virus (HCV). We evaluated the concordance between two noninvasive methods for staging LF, transient elastography (TE) and acoustic radiation force impulse (ARFI), in patients coinfected with human immunodeficiency virus and HCV. We propose an algorithm for optimal use of both techniques in routine clinical practice. METHODS: A total of 89 human immunodeficiency virus/HCV-coinfected patients underwent TE and ARFI on the same day. The kappa index was used to assess concordance between the techniques. An algorithm combining ARFI and TE was proposed based on the independent factors associated with a kappa index greater than or equal to 0.70, obtained from a multiple regression analysis. We performed a cost-effectiveness analysis. The study was approved by our institutional review board and all patients signed the informed consent. RESULTS: Concordance between TE and ARFI for F2, F3, and F4 was 0.55, 0.59, and 0.69, respectively. Ultrasound normal spleen size (odds ratio [OR], 0.20; 95% confidence interval [CI], 0.05-0.91) and high viral load (OR, 0.36; 95% CI, 0.17-0.77) reduced the probability of agreement between TE and ARFI, whereas ultrasound normal left liver lobe size (OR, 3.32; 95% CI, 1.21-9.10) increased this probability. The algorithm revealed that LF was adequately assessed in 74.16%, with 25.84% of patients misclassified. The incremental cost-effectiveness ratio of TE compared with ARFI to increase concordance by 1% was €8.86. CONCLUSIONS: Concordance between TE and ARFI was moderate. In the algorithm we proposed, ARFI was cost-effective as a first technique for the staging of LF in the study population.

Estado de salud bucal en pobladores del municipio de Palma S / State of oral health in Palma Soriano citizens

Se realizó un estudio descriptivo y transversal de 150 habitantes del municipio de Palma Soriano en la provincia de Santiago de Cuba, durante el 2015, quienes pertenecían a 5 consultorios del médico de la familia y fueron seleccionados mediante un muestro estratificado en grupos etarios de interés, con vistas a determinar el estado de salud bucal en ellos, para lo cual se consideraron algunas variables del modelo de encuesta de salud bucodental de la Organización Mundial de la Salud, modificada en el 2003. Entre los resultados sobresalientes de la serie se obtuvo que predominara el sexo femenino, 92,8 % no presentaba alteraciones en la articulación temporomandibular, 75,3 % no padecía enfermedad periodontal alguna, la cual se observó mayormente en las edades de 35-44 años, y el tratamiento protésico parcial fuera el más empleado. Igualmente, el índice de dientes cariados, obturados y perdidos fue de 1,1 a los 12 años y reveló una mayor afectación en el grupo etario de 60-74 años por el componente dientes perdidos.

A descriptive and cross-sectional study of 150 inhabitants from Palma Soriano in Santiago de Cuba, was carried out during 2015 who belonged to 5 family doctor's offices and were selected by means of a stratified sampling in age groups of interest, aimed at determining the state of oral health in them, for which some variables of the dental oral health survey pattern of the World Health Organization were considered and modified in 2003. Among the outstanding results of the series it was obtained that the female sex prevailed, 92.8% didn't present disorders in the temporomandibular joint, 75.3% didn't suffer from any periodontal disease, which was mostly observed in persons aged 35 to 44, and the prosthetic partial treatment was the most used. In the same way, the decayed, filled and lost teeth index was 1.1 at 12 years and it revealed a higher damage in the 60-74 age group due to the lost teeth component.

Disability-adjusted-life-years losses in postmenopausal women with osteoporosis: a burden of illness study.

BACKGROUND: To estimate the disability-adjusted life years (DALY) in a nationwide representative sample of postmenopausal women with osteoporosis. The effects of drug-based therapy and risk factors for osteoporotic bone fractures on DALY losses were also explored. METHODS: DALY were estimated based on participant's clinical characteristics and Health-Related Quality-of-Life (HRQoL) data obtained from a cross-sectional, epidemiological one-visit study (the GINERISK study). The study enrolled postmenopausal women (at least 12-months after their last menstrual period) with osteoporosis, above 18-years old, who attended Spanish outpatient Gynaecology clinics. HRQoL was assessed using the generic SF-12v2 questionnaire, which was used to derive disutility values. Mortality rates were extracted from the Spanish national statistics database. Factors explored to be associated with DALY losses were examined using ANOVA, ANCOVA and MANCOVA models. RESULTS: DALY could be computed in 2,782 (67%) out of 4,157 postmenopausal women, with a mean (95% CI) age of 61.0 (60.7-61.2) years. Overall individual undiscounted DALY per woman were 6.1 (5.9-6.2), resulting to be significantly higher in women with severe osteoporosis with prior bone fracture; 7.8 (7.2-8.4) compared to osteoporotic women [5.8 (5.6-6.0)] or postmenopausal women with a BMD > -2.5 T-score that received a drug-based therapy [6.2 (5.8-6.5)]; F = 27.0 (P < 0.01). Models explaining the variation in the levels of health based on the use of a selective estrogen receptor modulator (SERM) or possession of risk factors for osteoporotic BF were found (P < 0.05). CONCLUSIONS: DALY losses were considerable amongst postmenopausal women with osteoporosis. Not having a prior bone fracture, being older, using a SERM and having less osteoporotic risk factors were all linked to less DALY losses.

Classification models for neurocognitive impairment in HIV infection based on demographic and clinical variables.

OBJECTIVE: We used demographic and clinical data to design practical classification models for prediction of neurocognitive impairment (NCI) in people with HIV infection. METHODS: The study population comprised 331 HIV-infected patients with available demographic, clinical, and neurocognitive data collected using a comprehensive battery of neuropsychological tests. Classification and regression trees (CART) were developed to obtain detailed and reliable models to predict NCI. Following a practical clinical approach, NCI was considered the main variable for study outcomes, and analyses were performed separately in treatment-naïve and treatment-experienced patients. RESULTS: The study sample comprised 52 treatment-naïve and 279 experienced patients. In the first group, the variables identified as better predictors of NCI were CD4 cell count and age (correct classification [CC]: 79.6%, 3 final nodes). In treatment-experienced patients, the variables most closely related to NCI were years of education, nadir CD4 cell count, central nervous system penetration-effectiveness score, age, employment status, and confounding comorbidities (CC: 82.1%, 7 final nodes). In patients with an undetectable viral load and no comorbidities, we obtained a fairly accurate model in which the main variables were nadir CD4 cell count, current CD4 cell count, time on current treatment, and past highest viral load (CC: 88%, 6 final nodes). CONCLUSION: Practical classification models to predict NCI in HIV infection can be obtained using demographic and clinical variables. An approach based on CART analyses may facilitate screening for HIV-associated neurocognitive disorders and complement clinical information about risk and protective factors for NCI in HIV-infected patients.

Prevalence of ischemic heart disease and management of coronary risk in daily clinical practice: results from a Mediterranean cohort of HIV-infected patients.

BACKGROUND: There are conflicting data on the prevalence of coronary events and the quality of the management of modifiable cardiovascular risk factors (CVRF) in HIV-infected patients. METHODS: We performed a retrospective descriptive study to determine the prevalence of coronary events and to evaluate the management of CVRF in a Mediterranean cohort of 3760 HIV-1-infected patients from April 1983 through June 2011. RESULTS: We identified 81 patients with a history of a coronary event (prevalence 2.15%); 83% of them suffered an acute myocardial infarction. At the time of the coronary event, CVRF were highly prevalent (60.5% hypertension, 48% dyslipidemia, and 16% diabetes mellitus). Other CVRF, such as smoking, hypertension, lack of exercise, and body mass index, were not routinely assessed. After the coronary event, a significant decrease in total cholesterol (P = 0.025) and LDL-cholesterol (P = 0.004) was observed. However, the percentage of patients who maintained LDL-cholesterol > 100 mg/dL remained stable (from 46% to 41%, P = 0.103). Patients using protease inhibitors associated with a favorable lipid profile increased over time (P = 0.028). CONCLUSIONS: The prevalence of coronary events in our cohort is low. CVRF prevalence is high and their management is far from optimal. More aggressive interventions should be implemented to diminish cardiovascular risk in HIV-infected patients.

Evaluación de la satisfacción en salud: un reto en la atención estomatológica / Evaluation of satisfaction in health: a challenge in the stomatological care

Se realizó un estudio descriptivo y transversal durante 2013 para evaluar el grado de satisfacción de 5 proveedores de salud bucal (2 especialistas en estomatología general integral y 3 licenciados en atención estomatológica) con la atención que brindan y de 195 usuarios (148 escolares y 47 preescolares) con el servicio recibido, pertenecientes al Policlínico Universitario "Josué País García" de Santiago de Cuba, mediante criterios, indicadores y estándares. En los primeros, solo uno de los 13 criterios resultó adecuado; en los segundos, el total de la muestra manifestó estar satisfecho con la atención recibida.

A descriptive and cross sectional study was carried out during 2013 to evaluate the satisfaction degree of 5 oral health suppliers (2 specialists in comprehensive general stomatology and 3 graduates in stomatological care) with the care they provide and from 195 users (148 scholars and 47 preschool) with the received service, belonging to "Josué País García" University Polyclinic in Santiago de Cuba, by means of criteria, indicators and standards. In the first ones, just one of the 13 criteria was appropriate; in the second ones, the total of the sample manifested to be satisfied with the received care.