Multi-ancestry Genome-Wide Association Study of Early Childhood Caries.

Early childhood caries (ECC) is the most common non-communicable childhood disease. It is an important health problem with known environmental and social/behavioral influences that lacks evidence for specific associated genetic risk loci. To address this knowledge gap, we conducted a genome-wide association study of ECC in a multi-ancestry population of U.S. preschool-age children (n=6,103) participating in a community-based epidemiologic study of early childhood oral health. Calibrated examiners used ICDAS criteria to measure ECC with the primary trait using the dmfs index with decay classified as macroscopic enamel loss (ICDAS ≥3). We estimated heritability, concordance rates, and conducted genome-wide association analyses to estimate overall genetic effects; the effects stratified by sex, household water fluoride, and dietary sugar; and leveraged the combined gene/gene-environment effects using the 2-degree-of-freedom (2df) joint test. The common genetic variants explained 24% of the phenotypic variance (heritability) of the primary ECC trait and the concordance rate was higher with a higher degree of relatedness. We identified 21 novel non-overlapping genome-wide significant loci for ECC. Two loci, namely RP11-856F16 . 2 (rs74606067) and SLC41A3 (rs71327750) showed evidence of association with dental caries in external cohorts, namely the GLIDE consortium adult cohort (n=∼487,000) and the GLIDE pediatric cohort (n=19,000), respectively. The gene-based tests identified TAAR6 as a genome-wide significant gene. Implicated genes have relevant biological functions including roles in tooth development and taste. These novel associations expand the genomics knowledge base for this common childhood disease and underscore the importance of accounting for sex and pertinent environmental exposures in genetic investigations of oral health.

Adaptación transcultural y validez de un pictograma para evaluar necesidades de comunicación en adultos con vía aérea artificial en cuidados intensivos / Transcultural adaptation and validity of a pictogram to assess communication needs in adults with artificial airway in intensive care

Objetivo Realizar la adaptación transcultural y validez de un pictograma para evaluar necesidades de comunicación en adultos con vía aérea artificial en UCI en Cartagena, Colombia. Método Estudio de validación de escalas, población constituida por todos los pacientes que estuvieron hospitalizados en seis UCI de Cartagena, Colombia. La muestra fue conformada por 181 pacientes adultos con vía aérea artificial, y se determinó la adaptación al español (traducción, retro-traducción, revisión por expertos, versión pre-final, prueba piloto, versión final), la validez facial por acuerdo de expertos, la validez de contenido con el índice de Lawshe modificado por Tristán (punto de corte 0,58), el análisis de factor exploratorio (AFE) con la prueba de esfericidad de Barlett y gráfico de Catell, y la consistencia interna medida a través del estadístico alfa Cronbach. Resultados Participaron pacientes con edades entre 19 y 88años (media, 54±17); el 91,71% expresaron necesidades frecuentes de acompañamiento, conocer fecha y hora; el 61% de los expertos estuvieron de acuerdo con los ítems adaptados transculturalmente. El índice de validez de contenido (IVC) general fue de 0,86, con acuerdo en comprensión de once ítems. El AFE sugirió retener 13 reactivos y 3 factores (percepción/cognición, eliminación e intercambio, confort), que explican el constructo. La consistencia interna alfa de Cronbach fue de 0,64. Conclusiones El material pictográfico versión español mostró ser un instrumento multidimensional compuesto por 18 ítems agrupados en 3 factores, por lo que se recomienda aplicarlo al paciente con vía aérea artificial y establecer una comunicación como punto preliminar de los cuidados enfermeros. (AU)

Objective To perform the cross-cultural adaptation and validity of a pictogram to assess communication needs in adults with artificial airway in ICU in Cartagena, Colombia. Method Scale validation study, population comprising all the patients who were hospitalized in six ICU of Cartagena-Colombia. The sample was made up of 181 adult patients with artificial airway, the adaptation to Spanish was determined (translation, backtranslation, expert review, pre-final version, pilot test, final version), facial validity by expert agreement, content validity with the Lawshe index modified by Tristan (cut-off point 0.58), exploratory factor analysis (AFE) with the Bartlett's test of sphericity and Cattell's graph; internal consistency measured through the Cronbach alpha statistic. Results Patients between the ages of 19 and 88years participated (mean: 54±17); 91.71% expressed frequent needs for accompaniment, knowing date and time; 61% of the experts agreed with the cross-culturally adapted items, the overall Content Validity Index (CVI) was 0.86 with agreement in understanding eleven items. The AFE suggested retaining 13 items and 3 factors (perception/cognition, elimination and exchange, comfort), which explain the construct. The internal alpha Cronbach consistency was 0.64. Conclusions The pictographic material, Spanish version, was shown to be a multidimensional instrument composed of 18 items grouped in 3 factors. Therefore, it is recommended it be applied to the patient with artificial airway and to establish communication as a preliminary point of care in nursing. (AU)

Transcultural adaptation and validity of a pictogram to assess communication needs in adults with artificial airway in intensive care.

OBJECTIVE: To perform the cross-cultural adaptation and validity of a pictogram to assess communication needs in adults with artificial airway in ICU in Cartagena, Colombia. METHOD: Scale validation study, population comprising all the patients who were hospitalized in six ICU of Cartagena-Colombia. The sample was made up of 181 adult patients with artificial airway, the adaptation to Spanish was determined (translation, backtranslation, expert review, pre-final version, pilot test, final version), facial validity by expert agreement, content validity with the Lawshe index modified by Tristan (cut-off point 0.58), exploratory factor analysis (AFE) with the Bartlett's test of sphericity and Cattell's graph; internal consistency measured through the Cronbach alpha statistic. RESULTS: Patients between the ages of 19 and 88 years participated (mean = 54 ±â€¯17), 91.71% expressed frequent needs for accompaniment, knowing date and time; 61% of the experts agreed with the cross-culturally adapted items, the overall Content Validity Index (CVI) was 0.86 with agreement in understanding eleven items. The AFE suggested retaining 13 items and 3 factors (perception/cognition, elimination and exchange, comfort), which explain the construct. The internal alpha Cronbach consistency was 0.64. CONCLUSIONS: The pictographic material, Spanish version, was shown to be a multidimensional instrument composed of 18 items grouped in 3 factors. Therefore, it is recommended it be applied to the patient with artificial airway and to establish communication as a preliminary point of care in nursing.

Effects of hospital pharmacist interventions on health outcomes in older polymedicated inpatients: a scoping review.

PURPOSE: To identify the evidence that supports the effect of interventions made by hospital pharmacists, individually or in collaboration with a multidisciplinary team, in terms of healthcare outcomes, a more effective utilization of resources and lower costs in older polymedicated inpatients. METHODS: We searched the following databases: MEDLINE, EMBASE and the Cochrane Library. We also conducted a hand search by checking the references cited in the primary studies and studies included in reviews identified during the process of research. Four review authors working by pairs searched for studies, extracted data, and drew up the results tables. RESULTS: Twenty-six studies were included in the review. In 13 of them pharmacists carried out their intervention exclusively while the patients were in hospital, whereas in 13 interventions were delivered during admission and after hospital discharge. Outcomes identified were mortality, length of stay, visits to the emergency department, readmissions and reported quality of life, among others. Pharmacist interventions were found to be beneficial in fifteen studies, specifically on hospital readmissions, visits to the emergency department and healthcare costs. CONCLUSION: There is no hard evidence demonstrating the effectiveness of hospital pharmacist interventions in older polymedicated patients. Mortality does not show as a relevant outcome. Other health care outcomes, such as hospital readmissions, visits to the emergency department and healthcare costs, seem to be more relevant and amenable to change. Interventions that include pharmacists in multidisciplinary geriatric teams seem to be more promising that isolated pharmacist interventions. Interventions prolonged after hospital discharge seem to be more appropriate that interventions delivered only during hospital admission. Better-designed studies should be conducted in the future to provide further insight into the effect of hospital pharmacist interventions.

Transcultural adaptation and validity of a pictogram to assess communication needs in adults with artificial airway in intensive care. / Adaptación transcultural y validez de un pictograma para evaluar necesidades de comunicación en adultos con vía aérea artificial en cuidados intensivos.

OBJECTIVE: To perform the cross-cultural adaptation and validity of a pictogram to assess communication needs in adults with artificial airway in ICU in Cartagena, Colombia. METHOD: Scale validation study, population comprising all the patients who were hospitalized in six ICU of Cartagena-Colombia. The sample was made up of 181 adult patients with artificial airway, the adaptation to Spanish was determined (translation, backtranslation, expert review, pre-final version, pilot test, final version), facial validity by expert agreement, content validity with the Lawshe index modified by Tristan (cut-off point 0.58), exploratory factor analysis (AFE) with the Bartlett's test of sphericity and Cattell's graph; internal consistency measured through the Cronbach alpha statistic. RESULTS: Patients between the ages of 19 and 88years participated (mean: 54±17); 91.71% expressed frequent needs for accompaniment, knowing date and time; 61% of the experts agreed with the cross-culturally adapted items, the overall Content Validity Index (CVI) was 0.86 with agreement in understanding eleven items. The AFE suggested retaining 13 items and 3 factors (perception/cognition, elimination and exchange, comfort), which explain the construct. The internal alpha Cronbach consistency was 0.64. CONCLUSIONS: The pictographic material, Spanish version, was shown to be a multidimensional instrument composed of 18 items grouped in 3 factors. Therefore, it is recommended it be applied to the patient with artificial airway and to establish communication as a preliminary point of care in nursing.

Metabolomics Insights in Early Childhood Caries.

Dental caries is characterized by a dysbiotic shift at the biofilm-tooth surface interface, yet comprehensive biochemical characterizations of the biofilm are scant. We used metabolomics to identify biochemical features of the supragingival biofilm associated with early childhood caries (ECC) prevalence and severity. The study's analytical sample comprised 289 children ages 3 to 5 (51% with ECC) who attended public preschools in North Carolina and were enrolled in a community-based cross-sectional study of early childhood oral health. Clinical examinations were conducted by calibrated examiners in community locations using International Caries Detection and Classification System (ICDAS) criteria. Supragingival plaque collected from the facial/buccal surfaces of all primary teeth in the upper-left quadrant was analyzed using ultra-performance liquid chromatography-tandem mass spectrometry. Associations between individual metabolites and 18 clinical traits (based on different ECC definitions and sets of tooth surfaces) were quantified using Brownian distance correlations (dCor) and linear regression modeling of log2-transformed values, applying a false discovery rate multiple testing correction. A tree-based pipeline optimization tool (TPOT)-machine learning process was used to identify the best-fitting ECC classification metabolite model. There were 503 named metabolites identified, including microbial, host, and exogenous biochemicals. Most significant ECC-metabolite associations were positive (i.e., upregulations/enrichments). The localized ECC case definition (ICDAS ≥1 caries experience within the surfaces from which plaque was collected) had the strongest correlation with the metabolome (dCor P = 8 × 10-3). Sixteen metabolites were significantly associated with ECC after multiple testing correction, including fucose (P = 3.0 × 10-6) and N-acetylneuraminate (p = 6.8 × 10-6) with higher ECC prevalence, as well as catechin (P = 4.7 × 10-6) and epicatechin (P = 2.9 × 10-6) with lower. Catechin, epicatechin, imidazole propionate, fucose, 9,10-DiHOME, and N-acetylneuraminate were among the top 15 metabolites in terms of ECC classification importance in the automated TPOT model. These supragingival biofilm metabolite findings provide novel insights in ECC biology and can serve as the basis for the development of measures of disease activity or risk assessment.

Alteración cardíaca en profesional sanitario con SARS-Cov2 tratado con hidroxicloroquina / Heart disorders in the context of hydroxychloroquine treatment for SARS-Cov2: a case report

Presentamos el caso clínico de una profesional sanitaria que ha sufrido una probable reacción adversa por hidroxicloroquina en el tratamiento dirigido para el SARS-Cov2. La paciente estuvo en tratamiento con hidroxicloroquina, azitromicina y cefditoreno y tras finalizar el tratamiento presentó alteraciones cardiovasculares tales como insuficiencia cardíaca y taquicardias. En el momento actual parece que el balance beneficio-riesgo es desfavorable al uso de la hidroxicloroquina en el tratamiento de la enfermedad por SARS-Cov2

We present the clinical case of a healthcare professional who has suffered a probable adverse reaction by hydroxychloroquine in the targeted treatment for SARS-Cov2. The patient was treated with hydroxychloroquine, azithromycin, and cefditoren, and after completing the treatment, she had cardiovascular disorders such as heart failure and tachycardia. At present, the benefit-risk balance appears to be unfavorable to the use of hydroxychloroquine in the treatment of SARS-Cov2 disease

On the origin of the highest ozone episodes in Spain.

The 2000-2015 occurrences of the highest ozone (O3) pollution episodes in Spain were evaluated to investigate their origin. To this end, data series available for urban and regional background (UB and RB), traffic (TR) and industrial (IN) sites were analysed separately and intercompared. Results evidenced that during these 16years mean O3 levels in the RB sites did not change significantly, and remained constantly high. However, there is a clear increase at the TR and UB sites. Although sensitivity analysis is needed to interpret the cause of this increasing trend, this might be caused probably by the lower O3 titration intensity due to the preferential abatement of NO vs NO2, as supported from the neutral trend of OX (NO2+O3) at these sites. We found that the exceedances of the hourly information threshold for O3 (>180µg/m3) are recorded mostly at UB and IN sites located in seven areas of Spain (specific hotspots or at the tail end of large urban plumes), and that these increased during summer heatwaves (i.e. 2003 and 2015). Although the external contribution of regional-to-subcontinental transported O3 might be relevant during the highest O3 episodes in the Western Mediterranean, our results evidenced that in the above specific areas, regional-local O3 production decisively contributes to the exceedances of the information threshold. Also that the human protection threshold and the AOT40 are more frequently exceeded in the Central, Southern and Mediterranean sides of the Iberian Peninsula. The design of effective episode abatement measures is quite complex in those conditions, due to both the nonlinearity of the chemical processes of O3 formation and destruction, and to the interplay with the complex meteorological setting, causing frequent recirculation and in situ aging of air masses. However, the combination of meteorological forecasting of the main recirculation processes and sensitivity analysis of NOX/VOC emission abatement measures might be powerful tools to evaluate the effectiveness of potential O3 mitigation strategies. Finally we would like to highlight that the current UB, RB, IN and TR classification (somewhat subjective) is not adequate to interpret the origin of O3 exceedances in complex areas of Southern Europe. Thus, a UB station recording exceedances, and located in a small city in the tail end of an urban plume of a large city, receives not only the contribution from its own UB, but mainly from the specific high O3 RB caused by the urban plume transport.

CTX-M-15-H30Rx-ST131 subclone is one of the main causes of healthcare-associated ESBL-producing Escherichia coli bacteraemia of urinary origin in Spain.

OBJECTIVES: The objective of this study was to assess the prevalence and molecular epidemiology of ESBL-producing Escherichia coli causing healthcare-associated (HCA) and community-associated (CA) bacteraemia of urinary origin (BUO) in Spain. METHODS: An observational cohort study was conducted at eight hospitals from different Spanish geographical areas (2010-11). BUO episodes (n = 425) were classified as HCA (n = 215) and CA (n = 210), and one blood isolate per episode was collected. Susceptibility testing was performed, ESBLs were screened by double-disc diffusion test and ESBL and OXA-1 genes were characterized (PCR and sequencing). Population structure (phylogenetic groups, XbaI-PFGE and MLST) and ST131 subtyping (PCR) were determined. Virulence genes were detected by PCR and virulence score, profiles and extraintestinal pathogenic E. coli (ExPEC) status calculated. RESULTS: ESBL-producing E. coli prevalence was 9.2% (39/425). ESBL-producing E. coli episodes were significantly associated with HCA-BUO episodes [14% (30/215) versus 4.3% (9/210); P = 0.001]. The highest non-susceptibility proportions corresponded to ciprofloxacin (97.4%), amoxicillin/clavulanate (74.4%), co-trimoxazole (69.2%) and tobramycin (61.5%). Of the 39 ESBL-producing E. coli isolates, 34 produced CTX-M enzymes (21 CTX-M-15, 11 CTX-M-14 and 2 CTX-M-1). Fifteen STs were identified, the B2-ST131 clone being the most prevalent (54%; 21/39). All ST131 isolates were ExPEC and had the highest virulence scores, but they showed less diversity in virulence profiles than other STs. The H30Rx subclone accounted for most ST131 isolates (20/21), co-produced CTX-M-15 (20/20) and OXA-1 (19/20) enzymes and was associated with HCA episodes (16/20). CONCLUSIONS: The CTX-M-15-ST131-H30Rx subclone is a relevant MDR pathogen causing BUO, mainly HCA episodes. The dominance of this subclone with comparatively less diversity of virulence profiles reflects the spread of a successful and MDR ESBL ST131 lineage in Spain.

Expresión del gen esp (enterococcus surface protein) de enterococcus faecalis en un modelo in vitro de dientes extraídos / Gene expression esp (enterococcus surface protein) of enterococcus faecalis in an in vitro model of extracted teeth

Objetivo: Determinar la presencia y expresión del gen esp en cepas clínicas de Enterococcus faecalis a partir de un modelo in vitro de dientes extraídos. Métodos: Se diseñó un sistema in vitro para evaluar la formación del biofilm mediante microscopía de fluorescencia y la expresión del gen esp. El sistema estuvo constituido por un diente humano previamente extraído, cortado y preparado que proporcionó, mediante su conducto radicular, una superficie adecuada para la formación del biofilm por parte de E. faecalis. El sistema dispuso de una cámara anaerobia que permitió el crecimiento de la bacteria en el caldo de cultivo y evitó su contaminación con otros microorganismos. Esta cámara estuvo constituida por un tubo de micro centrifuga estéril, cortado y unido por el extremo inferior al extremo apical del diente seccionado. Resultados: Los resultados que se obtuvieron tanto por microscopia de fluorescencia como por RT-PCR permitieron cuantificar el nivel de expresión del gen esp en las bacterias durante su crecimiento y formando el biofilm en la superficie de los conductos radiculares. Todas las cepas evaluadas presentan el gen esp. Sin embargo, el biofilm de la cepa CC02 expresó el gen esp cuatro veces más en comparación al gen esp de la cepa de referencia. Conclusión: La expresión del gen esp podría estar asociada con la formación de biofilm en E. faecalis y la adherencia a superficies abióticas. Podría convertirse en una diana terapéutica prometedora en los programas de control de infecciones persistentes por Enterococcus spp. asociados a la presencia de biofilm (AU)

Objective: To determine the presence and expression of Enterococcus faecalis Esp gene in several strains from an in vitro model on extracted teeth. Methods: An in vitro system was designed to evaluate the biofilm formation through fluorescence microscopy and gene expression that could be associated to biofilm formation. The system consisted of a previously extracted human tooth that was cut and prepared to provide by means of its root canal, an adequate surface for biofilm formation on behalf of Enterococcus faecalis. The system disposed an anaerobe chamber that allowed the growth of bacteria in broth culture and avoided contamination with other microorganisms. This chamber consisted of a sterile micro centrifuge tube, which was cut and united by its inferior end to the apical end of the sectioned tooth. Results: The results obtained with fluorescence microscopy and RT-PCR allowed the quantification of the Esp gene levels of expression in bacteria growing and forming biofilm in root canal surfaces. Conclusion: The expression of Esp gene is associated with biofilm formation in E. faecalis and in the adherence to abiotic surfaces. It could be a promising therapeutic target in control programs for the eradication of persistent infections associated with the presence of E faecalis in biofilm (AU)

MIRAgel: the immunohistochemical expression of CD3, CD34, and CD68 in the surrounding capsule.

PurposeTo study the immunohistochemical features of the capsule tissue surrounding MIRAgel episcleral buckles.Patients and methodsThis Institutional interventional clinical cohort study examined a consecutive series of 21 referred patients who required MIRAgel removal from July 2009 to July 2013. All patients with hydrated and fragmented MIRAgel episcleral buckles were included in this study. Capsule biopsies from MIRAgel episcleral buckles were obtained from all patients. Capsule specimens of seven patients with extruded silicone bands were processed as controls. Paraffin-embedded specimens were examined using light microscopy and immunohistochemistry (via the PAP horseradish peroxidase technique) to detect the expression of CD3, CD20, CD34 and CD68, and S-100 protein.ResultsInflammation with granuloma, which was primarily related to sutures, was found in all (n=36) of the MIRAgel specimens and foreign body granulomas with multinucleated giant cells, histiocytes, and macrophages (CD68+ cells) surrounded the MIRAgel fragments. Average number of CD68+ cells was higher (P<0.001) for MIRAgel than for silicone rubber. The lymphocytic inflammatory infiltrate related to the MIRAgel fragments was CD3+ and CD20- (delayed T cell-mediated immune response). Moderate neoangiogenesis was indicated by the presence of CD34+ cells.ConclusionsThe immunohistochemical analysis revealed that the immune system is able to identify the fragments of MIRAgel (after its hydrolytic degradation) as a foreign body during a delayed T cell-mediated immune response. The phagocytosis by macrophages likely triggers and perpetuates local disease. Removal of MIRAgel explants before hydrolysis should be considered.

Cesación tabáquica en fumador con EPOC grave: el ingreso es una oportunidad que debemos aprovechar / Smoking cessation in severe COPD smokers: admission is an opportunity we should take advantage of

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Finasteride administration potentiates the disruption of prepulse inhibition induced by forced swim stress.

Acute stress has been demonstrated to alter sensory gating processes, measured by the prepulse inhibition of the startle response (PPI). It is well known that brain and plasma levels of the neurosteroid allopregnanolone (ALLO) increase after acute environmental stress, fact that has been considered a homeostatic mechanism in restoring normal function following stress. Thus, it is of great interest to study the contribution of stress-altered plasma ALLO levels on PPI function. For this purpose, animals were injected with finasteride, an ALLO synthesis inhibitor, and submitted to swim stress before PPI testing. In order to obtain ALLO plasma levels, a separate set of animals that followed the same experimental procedure was used. We hypothesize that the blockade of ALLO production in response to stress can increase the stress-induced PPI disruption. In accordance with other authors, our results indicate that acute swim stress disrupted the normal PPI evolution (increase) related to the increase in prepulse intensities, and also decreased PPI at the highest prepulse intensity level (15 db above background). Finasteride potentiated the PPI decrease induced by swim stress in the intermediate prepulse intensity (10 db above background). As expected, plasma ALLO levels were increased in stressed animals and this increase was neutralized by prior finasteride administration. These results indicate that the neutralization of the physiological plasma ALLO levels increase after acute stress potentiates stress-induced PPI disruption. This data suggests that alterations in homeostatic ALLO synthesis mechanism may be linked to some neuropsychiatric disorders related to stress, such as anxiety/depression disorders.

Mejorando la prescripción de medicamentos en las personas mayores: una nueva edición de los criterios STOPP-START / Improving drug prescribing in the elderly: A new edition of STOPP/START criteria

La utilización inapropiada de los medicamentos en los pacientes mayores tiene graves consecuencias en su salud —aumento del riesgo de sufrir reacciones adversas o síndromes geriátricos, mayor morbimortalidad— y en el sistema sanitario —aumento de costes, estancias hospitalarias excesivas. Para detectar y prevenir la utilización inadecuada de fármacos se está imponiendo progresivamente el uso de criterios explícitos, que pueden usarse dentro de la evaluación geriátrica exhaustiva o como parte de la actuación de diversos equipos multidisciplinares geriátricos. Los criterios STOPP-START, publicados por vez primera en 2008 (y en español en 2009), se están imponiendo como criterios de referencia en el ámbito europeo. Se presenta aquí la versión en español de la nueva edición (2014) de estos criterios, recientemente publicados en inglés. Además, se revisan en este artículo las publicaciones que han usado la versión inicial de los criterios STOPP-START en España desde su aparición, con la intención de fomentar su utilización e investigación en los distintos niveles asistenciales (AU)

Inappropriate use of drugs in older patients may have an adverse impact on several individual health outcomes, such as increasing the prevalence of adverse drug reactions, morbidity and mortality, and geriatric syndromes, as well as on health care systems, such as increased costs and longer hospital stays. Explicit criteria of drug appropriateness are increasingly used to detect and prevent inappropriate use of drugs, either within a comprehensive geriatric assessment or as tool used by different multidisciplinary geriatric teams. STOPP-START criteria, first published in 2008 (in Spanish in 2009), are being adopted as reference criteria throughout Europe. The Spanish version of the new 2014 edition (recently published in English) of the STOPP-START criteria is presented here. A review of all the papers published in Spain using the former version of these criteria is also presented, with the intention of promoting their use and for research in different health care levels (AU)

Risk factors for severe sepsis in community-onset bacteraemic urinary tract infection: impact of antimicrobial resistance in a large hospitalised cohort.

OBJECTIVE: To determine risks factors associated with severe sepsis or septic shock (SS) at admission in patients with community-onset bacteraemic urinary tract infection (CO-BUTI) including the impact of multidrug-resistant (MDR) bacteria. METHODS: We analysed a prospective cohort of all consecutive episodes of CO-BUTI requiring hospitalisation in 8 tertiary hospitals of Spain between October 2010 and June 2011. RESULTS: Of an overall of 525 CO-BUTI episodes, 175 (33%) presented with SS at admission. MDR bacteria were isolated in 29% (51/175) of episodes with SS and in 33% (117/350) of those without SS (p = 0.32). The main MDR microorganism was Escherichia coli in both groups (25% and 28% respectively). Independent risk factors associated with SS at admission were: having fatal underlying conditions, McCabe score II/III (OR 1.90; 95%CI 1.23-2.92; p = 0.004), presence of an indwelling urethral catheter (OR 3.01; 95%CI 1.50-6.03; p = 0.002) and a history of urinary tract obstruction (OR 1.56; 95%CI 1.03-2.34; p = 0.03). After considering interactions, indwelling urethral catheters were a risk factor only for patients without fatal underlying conditions. CONCLUSIONS: SS at hospital admission occurred in a third of CO-BUTI. Mainly host factors, and not the causative microorganisms or antimicrobial resistance patterns had an impact on the presence of SS.

[Improving drug prescribing in the elderly: a new edition of STOPP/START criteria]. / Mejorando la prescripción de medicamentos en las personas mayores: una nueva edición de los criterios STOPP-START.

Inappropriate use of drugs in older patients may have an adverse impact on several individual health outcomes, such as increasing the prevalence of adverse drug reactions, morbidity and mortality, and geriatric syndromes, as well as on health care systems, such as increased costs and longer hospital stays. Explicit criteria of drug appropriateness are increasingly used to detect and prevent inappropriate use of drugs, either within a comprehensive geriatric assessment or as tool used by different multidisciplinary geriatric teams. STOPP-START criteria, first published in 2008 (in Spanish in 2009), are being adopted as reference criteria throughout Europe. The Spanish version of the new 2014 edition (recently published in English) of the STOPP-START criteria is presented here. A review of all the papers published in Spain using the former version of these criteria is also presented, with the intention of promoting their use and for research in different health care levels.

Maternal administration of flutamide during late gestation affects the brain and reproductive organs development in the rat male offspring.

We have previously demonstrated that male rats exposed to stress during the last week of gestation present age-specific impairments of brain development. Since the organization of the fetal developing brain is subject to androgen exposure and prenatal stress was reported to disrupt perinatal testosterone surges, the aim of this research was to explore whether abnormal androgen concentrations during late gestation affects the morphology of the prefrontal cortex (PFC), hippocampus (HPC) and ventral tegmental area (VTA), three major areas that were shown to be affected by prenatal stress in our previous studies. We administered 10-mg/kg/day of the androgen receptor antagonist flutamide (4'nitro-3'-trifluoromethylsobutyranilide) or vehicle injections to pregnant rats from days 15-21 of gestation. The antiandrogenic effects of flutamide were confirmed by the analysis of androgen-dependent developmental markers: flutamide-exposed rats showed reduced anogenital distance, delay in the completion of testis descent, hypospadias, cryptorchidism and atrophied seminal vesicles. Brain morphological studies revealed that prenatal flutamide decreased the number of MAP2 (a microtubule-associated protein type 2, present almost exclusively in dendrites) immunoreactive neuronal processes in all evaluated brain areas, both in prepubertal and adult offspring, suggesting that prenatal androgen disruption induces long-term reductions of the dendritic arborization of several brain structures, affecting the normal connectivity between areas. Moreover, the number of tyrosine hydroxylase (TH)-immunopositive neurons in the VTA of prepubertal offspring was reduced in flutamide rats but reach normal values at adulthood. Our results demonstrate that the effects of prenatal flutamide on the offspring brain morphology resemble several prenatal stress effects suggesting that the mechanism of action of prenatal stress might be related to the impairment of the organizational role of androgens on brain development.

2001-2012 trends on air quality in Spain.

This study aims at interpreting the 2001-2012 trends of major air pollutants in Spain, with a major focus on evaluating their relationship with those of the national emission inventories (NEI) and policy actions. Marked downward concentration trends were evidenced for PM10, PM2.5 and CO. Concentrations of NO2 and NOx also declined but in a lesser proportion at rural and traffic sites. At rural sites O3 has been kept constant, whereas it clearly increased at urban and industrial sites. Comparison of the air quality trends and major inflection points with those from NEIs, the National Energy Consumption and the calendar of the implementation of major policy actions allowed us to clearly identify major benefits of European directives on power generation and industrial sources (such as the Large Combustion Plants and the Integrated Pollution Prevention and Control Directives). This, together with a sharp 2007-2008 decrease of coal consumption has probably caused the marked parallel decline of SO2, NOx and for PM2.5 concentrations. Also the effect of the EURO 4 and 5 vehicle emission standards on decreasing emissions of PM and CO from vehicles is noticeable. The smooth decline in NO2-NOx levels is mostly attributed to the low efficiency of EURO 4 and 5 standards in reducing real life urban driving NO2 emissions. The low NOx decrease together with the complexity of the reactions of O3 formation is responsible for the constant O3 concentrations, or even the urban increase. The financial crisis has also contributed to the decrease of the ambient concentration of pollutants; however this caused a major reduction of the primary energy consumption from 2008 to 2009, and not from 2007 to 2008 when ambient air PM and SO2 sharply decreased. The meteorological influence was characterized by a 2008-2012 period favorable to the dispersion of pollutants when compared to the 2001-2007.

Phase I/II trial of vorinostat (SAHA) and erlotinib for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations after erlotinib progression.

OBJECTIVES: Vorinostat or suberoylanilide hydroxamic acid (SAHA) is a novel histone deacetylase inhibitor with demonstrated antiproliferative effects due to drug-induced accumulation of acetylated proteins, including the heat shock protein 90. We prospectively studied the activity of vorinostat plus erlotinib in EGFR-mutated NSCLC patients with progression to tyrosine kinase inhibitors. PATIENTS AND METHODS: We conducted this prospective, non-randomized, multicenter, phase I/II trial to evaluate the maximum tolerated dose, toxicity profile and efficacy of erlotinib and vorinostat. Patients with advanced NSCLC harboring EGFR mutations and progressive disease after a minimum of 12 weeks on erlotinib were included. The maximum tolerated dose of vorinostat plus erlotinib was used as recommended dose for the phase II (RDP2) to assess the efficacy of the combination. The primary end point was progression-free-survival rate at 12 weeks (PFSR12w). Pre-treatment plasma samples were required to assess T790M resistant mutation. RESULTS: A total of 33 patients were enrolled in the phase I-II trial. The maximum tolerated dose was erlotinib 150 mg p.o., QD, and 400mg p.o., QD, on days 1-7 and 15-21 in a 28-day cycle. Among the 25 patients treated at the RDP2, the most common toxicities included anemia, fatigue and diarrhea. No responses were observed. PFSR12w was 28% (IC 95%: 18.0-37.2); median progression-free survival (PFS) was 8 weeks (IC 95%: 7.43-8.45) and overall survival (OS) 10.3 months (95% CI: 2.4-18.1). CONCLUSION: Full dose of continuous erlotinib with vorinostat 400mg p.o., QD on alternative weeks can be safely administered. Still, the combination has no meaningful activity in EGFR-mutated NSCLC patients after TKI progression.