Relevant gender differences in epidemiological profile, exposure to first antiretroviral regimen and survival in the Spanish AIDS Research Network Cohort.

BACKGROUND The possible differences in the disease spectrum and prognosis of HIV infection in women and men is a major point of concern. Women are under-represented in randomized clinical trials and in some cohorts. Discordant results have often been obtained depending on the setting. METHODS We assessed gender differences in clinical and epidemiological features, antiretroviral treatment (ART) exposure and survival in two multicentre cohorts of HIV-positive subjects in Spain: CoRIS-MD and CoRIS. Competing risk regression models were used to assess gender effect on time to start ART and time to first ART change, and a Cox regression model to estimate gender effect on time to death. RESULTS Between January 1996 and December 2008, 1,953 women and 6,072 men naive to ART at study entry were included. The trend analysis over time showed the percentage of women in the younger (<20 years) and older (>50 years) strata increased significantly (P<0.001) from 0.5% and 1.8% in 1996 to 4.9% and 4.2% in 2008, respectively. By competing risk analysis women started ART earlier than men (adjusted subhazard ratio [ASHR] 1.21, 95% CI 1.11, 1.31) in CoRIS cohort, while in CoRIS-MD none of these differences were observed. In both cohorts women showed a shorter time to the first ART change (ASHR 1.10, 95% CI 1.01, 1.19). Pregnancy and patient's/physician's decisions as reasons for changing were more frequent in women than in men in CoRIS. In the Cox regression model, gender was not associated with differences in survival. CONCLUSIONS In two large cohorts in Spain, we observed relevant gender differences in epidemiological characteristics and antiretroviral exposure outcomes, while survival differences were not attributable to gender.

Preinfarction angina prior to first myocardial infarction does not influence long-term prognosis: a retrospective study with subgroup analysis in elderly and diabetic patients.

BACKGROUND AND HYPOTHESIS Although prodromal angina occurring shortly before an acute myocardial infarction (MI) has protective effects against in-hospital complications, this effect has not been well documented after initial hospitalization, especially in older or diabetic patients. We examined whether angina 1 week before a first MI provides protection in these patients. METHODS A total of 290 consecutive patients, 143 elderly (>64 years of age) and 147 adults (<65 years of age), 68 of whom were diabetic (23.4%) and 222 nondiabetic (76.6%), were examined to assess the effect of preceding angina on long-term prognosis (56 months) after initial hospitalization for a first MI. RESULTS No significant differences were found in long-term complications after initial hospitalization in these adult and elderly patients according to whether or not they had prodromal angina (44.4% with angina vs 45.4% without in adults; 45.5% vs 58% in elderly, P < 0.2). Nor were differences found according to their diabetic status (61.5% with angina vs 72.7% without in diabetics; 37.3% vs 38.3% in nondiabetics; P = 0.4). CONCLUSION The occurrence of angina 1 week before a first MI does not confer long-term protection against cardiovascular complications after initial hospitalization in adult or elderly patients, whether or not they have diabetes.

Nutrient patterns and their food sources in an International Study Setting: report from the EPIC study.

BACKGROUND Compared to food patterns, nutrient patterns have been rarely used particularly at international level. We studied, in the context of a multi-center study with heterogeneous data, the methodological challenges regarding pattern analyses. METHODOLOGY/PRINCIPAL FINDINGS We identified nutrient patterns from food frequency questionnaires (FFQ) in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study and used 24-hour dietary recall (24-HDR) data to validate and describe the nutrient patterns and their related food sources. Associations between lifestyle factors and the nutrient patterns were also examined. Principal component analysis (PCA) was applied on 23 nutrients derived from country-specific FFQ combining data from all EPIC centers (N = 477,312). Harmonized 24-HDRs available for a representative sample of the EPIC populations (N = 34,436) provided accurate mean group estimates of nutrients and foods by quintiles of pattern scores, presented graphically. An overall PCA combining all data captured a good proportion of the variance explained in each EPIC center. Four nutrient patterns were identified explaining 67% of the total variance: Principle component (PC) 1 was characterized by a high contribution of nutrients from plant food sources and a low contribution of nutrients from animal food sources; PC2 by a high contribution of micro-nutrients and proteins; PC3 was characterized by polyunsaturated fatty acids and vitamin D; PC4 was characterized by calcium, proteins, riboflavin, and phosphorus. The nutrients with high loadings on a particular pattern as derived from country-specific FFQ also showed high deviations in their mean EPIC intakes by quintiles of pattern scores when estimated from 24-HDR. Center and energy intake explained most of the variability in pattern scores. CONCLUSION/SIGNIFICANCE The use of 24-HDR enabled internal validation and facilitated the interpretation of the nutrient patterns derived from FFQs in term of food sources. These outcomes open research opportunities and perspectives of using nutrient patterns in future studies particularly at international level.

Progression rate of self-propelled feeding tubes in critically ill patients.

OBJECTIVE: Gaining postpyloric access in ventilated, sedated ICU patients usually requires time-consuming procedures such as endoscopy. Recently, a feeding tube has been introduced that migrates spontaneously into the jejunum in surgical patients. The study aimed at assessing the rate of migration of this tube in critically ill patients. DESIGN: Prospective descriptive trial. SETTING: Surgical ICU in a tertiary University Hospital. PATIENTS: One hundred and five consecutive surgical ICU patients requiring enteral feeding were enrolled, resulting in 128 feeding-tube placement attempts. METHODS: A self-propelled tube was used and followed up for 3 days: progression was assessed by daily contrast-injected X-ray. Severity of illness was assessed with SAPS II and organ failure assessed with SOFA score. RESULTS: The patients were aged 55+/-19 years (mean+/-SD) with SAPS II score of 45+/-18. Of the 128 tube placement attempts, 12 could not be placed in the stomach; eight were accidentally pulled out while in gastric position due to the necessity to avoid fixation during the progression phase. Among organ failures, respiratory failure predominated, followed by cardiovascular. By day 3, the postpyloric progression rate was 63/128 tubes (49%). There was no association between migration and age, or SAPS II score, but the progression rate was significantly poorer in patients with hemodynamic failure. Use of norepinephrine and morphine were negatively associated with tube progression (P<0.001), while abdominal surgery was not. In ten patients, jejunal tubes were placed by endoscopy. CONCLUSION: Self-propelled feeding tubes progressed from the stomach to the postpyloric position in 49% of patients, reducing the number of endoscopic placements: these tubes may facilitate enteral nutrient delivery in the ICU.

Use of Two-Part Regression Calibration Model to Correct for Measurement Error in Episodically Consumed Foods in a Single-Replicate Study Design: EPIC Case Study.

In epidemiologic studies, measurement error in dietary variables often attenuates association between dietary intake and disease occurrence. To adjust for the attenuation caused by error in dietary intake, regression calibration is commonly used. To apply regression calibration, unbiased reference measurements are required. Short-term reference measurements for foods that are not consumed daily contain excess zeroes that pose challenges in the calibration model. We adapted two-part regression calibration model, initially developed for multiple replicates of reference measurements per individual to a single-replicate setting. We showed how to handle excess zero reference measurements by two-step modeling approach, how to explore heteroscedasticity in the consumed amount with variance-mean graph, how to explore nonlinearity with the generalized additive modeling (GAM) and the empirical logit approaches, and how to select covariates in the calibration model. The performance of two-part calibration model was compared with the one-part counterpart. We used vegetable intake and mortality data from European Prospective Investigation on Cancer and Nutrition (EPIC) study. In the EPIC, reference measurements were taken with 24-hour recalls. For each of the three vegetable subgroups assessed separately, correcting for error with an appropriately specified two-part calibration model resulted in about three fold increase in the strength of association with all-cause mortality, as measured by the log hazard ratio. Further found is that the standard way of including covariates in the calibration model can lead to over fitting the two-part calibration model. Moreover, the extent of adjusting for error is influenced by the number and forms of covariates in the calibration model. For episodically consumed foods, we advise researchers to pay special attention to response distribution, nonlinearity, and covariate inclusion in specifying the calibration model.

Liver safety assessment: required data elements and best practices for data collection and standardization in clinical trials.

A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials. In a breakout session, workshop attendees discussed necessary data elements and standards for the accurate measurement of DILI risk associated with new therapeutic agents in clinical trials. There was agreement that in order to achieve this goal the systematic acquisition of protocol-specified clinical measures and lab specimens from all study subjects is crucial. In addition, standard DILI terms that address the diverse clinical and pathologic signatures of DILI were considered essential. There was a strong consensus that clinical and lab analyses necessary for the evaluation of cases of acute liver injury should be consistent with the US Food and Drug Administration (FDA) guidance on pre-marketing risk assessment of DILI in clinical trials issued in 2009. A recommendation that liver injury case review and management be guided by clinicians with hepatologic expertise was made. Of note, there was agreement that emerging DILI signals should prompt the systematic collection of candidate pharmacogenomic, proteomic and/or metabonomic biomarkers from all study subjects. The use of emerging standardized clinical terminology, CRFs and graphic tools for data review to enable harmonization across clinical trials was strongly encouraged. Many of the recommendations made in the breakout session are in alignment with those made in the other parallel sessions on methodology to assess clinical liver safety data, causality assessment for suspected DILI, and liver safety assessment in special populations (hepatitis B, C, and oncology trials). Nonetheless, a few outstanding issues remain for future consideration.

The administration of atomoxetine during alcohol deprivation induces a time-limited increase in alcohol consumption after relapse.

The administration of selective serotonin reuptake inhibitors (SSRIs) typically used as antidepressants increases alcohol consumption after an alcohol deprivation period in rats. However, the appearance of this effect after the treatment with selective noradrenaline reuptake inhibitors (SNRIs) has not been studied. In the present work we examined the effects of a 15-d treatment with the SNRI atomoxetine (1, 3 and 10 mg/kg, i.p.) in male rats trained to drink alcohol solutions in a 4-bottle choice test. The treatment with atomoxetine (10 mg/kg, i.p.) during an alcohol deprivation period increased alcohol consumption after relapse. This effect only lasted one week, disappearing thereafter. Treatment with atomoxetine did not cause a behavioral sensitized response to a challenge dose of amphetamine (1.5 mg/kg, i.p.), indicating the absence of a supersensitive dopaminergic transmission. This effect is markedly different from that of SSRI antidepressants that produced both long-lasting increases in alcohol consumption and behavioral sensitization. Clinical implications are discussed.

Spatial and temporal country-wide survey of temephos resistance in Brazilian populations of Aedes aegypti

The organophosphate temephos has been the main insecticide used against larvae of the dengue and yellow fever mosquito (Aedes aegypti) in Brazil since the mid-1980s. Reports of resistance date back to 1995; however, no systematic reports of widespread temephos resistance have occurred to date. As resistance investigation is paramount for strategic decision-making by health officials, our objective here was to investigate the spatial and temporal spread of temephos resistance in Ae. aegypti in Brazil for the last 12 years using discriminating temephos concentrations and the bioassay protocols of the World Health Organization. The mortality results obtained were subjected to spatial analysis for distance interpolation using semi-variance models to generate maps that depict the spread of temephos resistance in Brazil since 1999. The problem has been expanding. Since 2002-2003, approximately half the country has exhibited mosquito populations resistant to temephos. The frequency of temephos resistance and, likely, control failures, which start when the insecticide mortality level drops below 80%, has increased even further since 2004. Few parts of Brazil are able to achieve the target 80% efficacy threshold by 2010/2011, resulting in a significant risk of control failure by temephos in most of the country. The widespread resistance to temephos in Brazilian Ae. aegypti populations greatly compromise effective mosquito control efforts using this insecticide and indicates the urgent need to identify alternative insecticides aided by the preventive elimination of potential mosquito breeding sites.

Frequency and characteristics of familial melanoma in Spain: the FAM-GEM-1 Study.

INTRODUCTION Familial history of melanoma is a well-known risk factor for the disease, and 7% melanoma patients were reported to have a family history of melanoma. Data relating to the frequency and clinical and pathological characteristics of both familial and non-familial melanoma in Spain have been published, but these only include patients from specific areas of Spain and do not represent the data for the whole of Spain. PATIENTS AND METHODS An observational study conducted by the Spanish Group of Melanoma (GEM) analyzed the family history of patients diagnosed with melanoma between 2011 and 2013 in the dermatology and oncology departments. RESULTS In all, 1047 patients were analyzed, and 69 (6.6%) fulfilled criteria for classical familial melanoma (two or more first-degree relatives diagnosed with melanoma). Taking into account other risk factors for familial melanoma, such as multiple melanoma, pancreatic cancer in the family or second-degree relatives with melanoma, the number of patients fulfilling the criteria increased to 165 (15.8%). Using a univariate analysis, we determined that a Breslow index of less than 1 mm, negative mitosis, multiple melanoma, and a history of sunburns in childhood were more frequent in familial melanoma patients, but a multivariate analysis revealed no differences in any pathological or clinical factor between the two groups. CONCLUSIONS Similar to that observed in other countries, familial melanoma accounts for 6.6% of melanoma diagnoses in Spain. Although no differences in the multivariate analysis were found, some better prognosis factors, such as Breslow index, seem more frequent in familial melanoma, which reflect a better early detection marker and/or a different biological behavior.

Immediate Effects of Neurodynamic Sliding versus Muscle Stretching on Hamstring Flexibility in Subjects with Short Hamstring Syndrome.

Background. Hamstring injuries continue to affect active individuals and although inadequate muscle extensibility remains a commonly accepted factor, little is known about the most effective method to improve flexibility. Purpose. To determine if an isolated neurodynamic sciatic sliding technique would improve hamstring flexibility to a greater degree than stretching or a placebo intervention in asymptomatic subjects with short hamstring syndrome (SHS). Study Design. Randomized double-blinded controlled trial. Methods. One hundred and twenty subjects with SHS were randomized to 1 of 3 groups: neurodynamic sliding, hamstring stretching, and placebo control. Each subject's dominant leg was measured for straight leg raise (SLR) range of motion (ROM) before and after interventions. Data were analyzed with a 3 × 2 mixed model ANOVA followed by simple main effects analyses. Results. At the end of the study, more ROM was observed in the Neurodynamic and Stretching groups compared to the Control group and more ROM in the Neurodynamic group compared to Stretching group. Conclusion. Findings suggest that a neurodynamic sliding technique will increase hamstring flexibility to a greater degree than static hamstring stretching in healthy subjects with SHS. Clinical Relevance. The use of neurodynamic sliding techniques to improve hamstring flexibility in sports may lead to a decreased incidence in injuries; however, this needs to be formally tested.

The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML.

Role of Age and Sex in the Diagnosis of Early-stage Malignant Melanoma: A Cross-Sectional study.

Age and sex have been identified as predictors of outcome in malignant melanoma (MM). This aim of this multicentre, cross-sectional study was to analyse the role of age and sex as explanatory variables for the diagnosis of thin MM. A total of 2430 patients with MM were recruited. Cases of in situ-T1 MM were more frequent than T2-T4 MM (56.26% vs. 43.74%). Breslow thickness increased throughout decades of life (analysis of variance (ANOVA) p < 0.001), with a weak correlation between Breslow thickness and patient's age (r   = 0.202, p < 0.001). Breslow thickness was significantly less in women (1.79 vs. 2.38 mm, p = 0.0001). Binary logistic regression showed a significant (p < 0.001) odds ratio for age 0-29 years (1.18), and 30-59 years (1.16), and for women (1.09). Age and sex explained 3.64% of the variation observed in Tis-T1 frequency (R2 = 0.0364). Age and sex appear to explain a low percentage of the variation in the early detection of MM.

Disentangling reasons for low Y chromosome variation in the greater white-toothed shrew (Crocidura russula).

Y chromosome variation is determined by several confounding factors including mutation rate, effective population size, demography, and selection. Disentangling these factors is essential to better understand the evolutionary properties of the Y chromosome. We analyzed genetic variation on the Y chromosome, X chromosome, and mtDNA of the greater white-toothed shrew, a species with low variance in male reproductive success and limited sex-biased dispersal, which enables us to control to some extent for life-history effects. We also compared ancestral (Moroccan) to derived (European) populations to investigate the role of demographic history in determining Y variation. Recent colonization of Europe by a small number of founders (combined with low mutation rates) is largely responsible for low diversity observed on the European Y and X chromosomes compared to mtDNA. After accounting for mutation rate, copy number, and demography, the Y chromosome still displays a deficit in variation relative to the X in both populations. This is possibly influenced by directional selection, but the slightly higher variance in male reproductive success is also likely to play a role, even though the difference is small compared to that in highly polygynous species. This study illustrates that demography and life-history effects should be scrutinized before inferring strong selective pressure as a reason for low diversity on the Y chromosome.

Contextual effects on subjective national identity and nationalist vote in Catalonia

The important inflow of foreign population to western countries has boosted the study of acculturation processes among scholars in the last decades. By using the case of Catalonia, a receiver region of international and national migration since the fifties, this paper seeks to intersect a classic acculturation model and a newly reemerging literature in political science on contextual determinants on individual behavior. Does the context matters for understanding individual’s subjective national identity and, therefore, its voting behavior? Multilevel models show that environment matters. Percentage of Spain-born population in the town is statistically significant to account for variance in the subjective national identity and nationalist vote, even after controlling for age, sex, origin, language and left – right orientation and other contextual factors. This conclusion invites researchers not to underestimate the direct effect of the environment on individual outcomes such as feelings of belonging and vote orientation in contexts of rival identities.

X-chromosome SNP analyses in 11 human Mediterranean populations show a high overall genetic homogeneity except in North-west Africans (Moroccans).

BACKGROUND: Due to its history, with a high number of migration events, the Mediterranean basin represents a challenging area for population genetic studies. A large number of genetic studies have been carried out in the Mediterranean area using different markers but no consensus has been reached on the genetic landscape of the Mediterranean populations. In order to further investigate the genetics of the human Mediterranean populations, we typed 894 individuals from 11 Mediterranean populations with 25 single-nucleotide polymorphisms (SNPs) located on the X-chromosome. RESULTS: A high overall homogeneity was found among the Mediterranean populations except for the population from Morocco, which seemed to differ genetically from the rest of the populations in the Mediterranean area. A very low genetic distance was found between populations in the Middle East and most of the western part of the Mediterranean Sea.A higher migration rate in females versus males was observed by comparing data from X-chromosome, mt-DNA and Y-chromosome SNPs both in the Mediterranean and a wider geographic area.Multilocus association was observed among the 25 SNPs on the X-chromosome in the populations from Ibiza and Cosenza. CONCLUSION: Our results support both the hypothesis of (1) a reduced impact of the Neolithic Wave and more recent migration movements in NW-Africa, and (2) the importance of the Strait of Gibraltar as a geographic barrier. In contrast, the high genetic homogeneity observed in the Mediterranean area could be interpreted as the result of the Neolithic wave caused by a large demic diffusion and/or more recent migration events. A differentiated contribution of males and females to the genetic landscape of the Mediterranean area was observed with a higher migration rate in females than in males. A certain level of background linkage disequilibrium in populations in Ibiza and Cosenza could be attributed to their demographic background.