Androgen deficiency is associated with a better prognosis in glioblastoma.

BACKGROUND: The androgen receptor (AR) has been demonstrated to play a role in the pathogenesis of glioblastoma; however, the implications of circulating testosterone levels in the biology of glioblastoma remain unknown. AIM: This study aimed to analyze the association between circulating testosterone levels and the prognosis of patients with glioblastoma. METHODS: Forty patients with primary glioblastoma were included in the study. The main prognostic endpoint was progression-free survival (PFS). Circulating testosterone levels were used to determine the state of androgen deficiency (AD). AR expression was analyzed by reverse-transcriptase polymerase chain reaction, Western blot, and immunofluorescence. Survival analysis was performed using the log-rank test and univariate and multivariate Cox regression analysis. RESULTS: Most of the patients showed AR expression, and it was mainly located in the cytoplasm, as well as in the nucleus of tumor cells. Patients with AD presented a better PFS than those patients with normal levels (252.0 vs. 135.0 days; p = 0.041). Furthermore, normal androgenic status was an independent risk factor for progression in a multivariate regression model (hazard ratio = 6.346; p = 0.004). CONCLUSION: Circulating testosterone levels are associated with the prognosis of glioblastoma because patients with AD show a better prognosis than those with normal androgenic status.

Hepatitis C virus infection screening reduces mortality and is cost-effective independently of the intervention test

Introduction: chronic infection due to hepatitis C virus (HCV)is frequently asymptomatic even in advanced stages of liverdisease. Implementation of a screening program based ondifferent HCV tests may enable an earlier diagnosis of HCVliver disease and subsequent application of highly effectivetreatment.Patients and methods: a Markov model which comparesthree different screening strategies for hepatitis C versus noscreening in low-risk prevalence (general population) andhigh-risk prevalence population (people who inject drugs orprison population) was designed, taking into account age atthe start of screening and participation. The three strategieswere: a) serological detection of antibodies against the HCV;b) dried blood spot test (DBS) to detect antibodies againstHCV; and c) detection of ribonucleic acid (RNA) from HCV.Quality-adjusted life-years (QALY) were taken as a measurement of effectiveness. The incremental cost-effectivenessratio (ICER) was calculated and a deterministic and probabilistic sensitivity analysis was performed.Results: all three screening strategies were found to becost-effective, with an ICER of €13,633, €12,015 and €12,328/QALY for antiHCV, DBS-antiHCV and DBS-RNA HCV, respectively. There was a decrease in mortality due to liver disease in comparison to no screening for antiHCV (40.7 % and52 %), DBS-antiHCV (45 % and 80 %) and DBS-RNA HCV (45.2 % and 80 %) for low-prevalence and high-prevalencepopulations, respectively.Conclusion: all test interventions for HCV screening arecost-effective for the early detection of HCV infection, alsoachieving a reduction in mortality. Thus, implementationof screening programs for HCV should not be halted by decisions on monetary policy. (AU)

Androgen Receptor Activity Is Associated with Worse Survival in Glioblastoma.

BACKGROUND: Some evidence about the role of the androgen receptor (AR) in pathogenesis of glioblastoma have been reported, but no study has focused on measuring the activity of the AR in GB. Therefore, the aim of this work is to study the role of AR and its activity as prognostic biomarkers in glioblastoma (GB). METHODS: Molecular and clinical data from The Cancer Genome Atlas database were used. The AR-expression at protein-level was obtained from reversed phase protein array (RPPA) assays. The AR-activity was determined by calculating the AR-score, an index calculated by using the expression (at RNA-level) of 13 androgen-responsive-genes. Univariate and multivariate Cox-regression analyses were performed. Finally, a correlation analysis was conducted between protein expression data and the AR-score. RESULTS: Two-hundred and thirty-three patients were included. RPPA data showed a mean AR abundance of 0.027(Statistical Deviation = 0.38) in GB. The univariate Cox-regression analysis showed that the AR-Score was associated with a worse prognosis (Hazard Ratio (HR) = 1.070) while the AR-expression did not show any relationship with survival (HR = 0.869). The association of the AR-score with worse overall survival (OS) was still significant in the multivariate analysis (HR = 1.054). The highest correlation coefficients between the AR-score and RPPA were identified in a group of proteins involved in apoptotic process regulation. CONCLUSIONS: GB patients with a high AR-activity present a worse prognosis in terms of OS. Thus, the activity of the AR may have a pathogenic role in GB. In this regard, the activation of the AR in GB may be associated with a dysregulation of apoptosis.

Sexual behaviour and poor hygiene are related to recent hepatitis a virus community outbreaks

OBJECTIVES: there has been a global increase in the incidence of hepatitis A infection. The aim of this study was to examine the characteristics of the increase in our region and the degree of adherence to the recommended hygienic measures after discharge from hospital. METHODS: demographic, clinical and biochemical variables were collected from patients with acute hepatitis A in our health area. The patients were grouped as follows: January 2010 to December 2016 (historical cohort) and January 2017 to October 2017 (recent cohort). A phylogenetic analysis was also performed in the recent cohort. One month after discharge, bacterial growth was evaluated by a culture of the dominant hand imprint and were compared with a control group. RESULTS: a total of 110 cases were registered with a median age of 36.3 years (range 3-89) and 77.3 % were male. The incidence was 0.82/100,000 inhabitants/year and 22.75/100,000 inhabitants/year in the historical and recent cohorts, respectively. Patients in the recent cohort were more frequently male (52.6 % vs. 82.4 %, p = 0.008) and younger (51.7 [3-89] vs. 33.4 [4-74] years, p < 0.001). In addition, 63.8 % of the recent cohort were men who had sex with other men and had unsafe sexual practices (37.5 %). Phylogenetic analysis showed a predominance of genotype A and a high frequency of the VRD 521-2016 sequence. A higher growth of enterobacteria was observed in patients with hepatitis A compared to the control group (7.3 % vs. 1.2 %, p = 0.005), despite specific hygienic measures given at discharge. CONCLUSIONS: a recent outbreak of hepatitis A in our area was related with gender, younger age and sexual practices. Hepatitis A infected subjects showed a poor adherence to hygienic measures. Our data suggests the need for policies that encourage preventive actions, particularly vaccination in this high-risk group

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Sexual behaviour and poor hygiene are related to recent hepatitis a virus community outbreaks.

OBJECTIVES: there has been a global increase in the incidence of hepatitis A infection. The aim of this study was to examine the characteristics of the increase in our region and the degree of adherence to the recommended hygienic measures after discharge from hospital. METHODS: demographic, clinical and biochemical variables were collected from patients with acute hepatitis A in our health area. The patients were grouped as follows: January 2010 to December 2016 (historical cohort) and January 2017 to October 2017 (recent cohort). A phylogenetic analysis was also performed in the recent cohort. One month after discharge, bacterial growth was evaluated by a culture of the dominant hand imprint and were compared with a control group. RESULTS: a total of 110 cases were registered with a median age of 36.3 years (range 3-89) and 77.3 % were male. The incidence was 0.82/100,000 inhabitants/year and 22.75/100,000 inhabitants/year in the historical and recent cohorts, respectively. Patients in the recent cohort were more frequently male (52.6 % vs. 82.4 %, p = 0.008) and younger (51.7 [3-89] vs. 33.4 [4-74] years, p < 0.001). In addition, 63.8 % of the recent cohort were men who had sex with other men and had unsafe sexual practices (37.5 %). Phylogenetic analysis showed a predominance of genotype A and a high frequency of the VRD 521-2016 sequence. A higher growth of enterobacteria was observed in patients with hepatitis A compared to the control group (7.3 % vs. 1.2 %, p = 0.005), despite specific hygienic measures given at discharge. CONCLUSIONS: a recent outbreak of hepatitis A in our area was related with gender, younger age and sexual practices. Hepatitis A infected subjects showed a poor adherence to hygienic measures. Our data suggests the need for policies that encourage preventive actions, particularly vaccination in this high-risk group.

Effect of high-intensity ultrasound treatment in combination with transglutaminase and nanoparticles on structural, mechanical, and physicochemical properties of quinoa proteins/chitosan edible films.

The effect of high-intensity ultrasound (US) combined with transglutaminase treatment (TG) and the inclusion of nanoparticles (Np) on the structural, mechanical, barrier, and physicochemical properties of quinoa protein/chitosan composite edible films were evaluated. Structurally it was observed that the maximum temperatures of the thermal degradation increased with the use of combined US and TG treatment, generating films with superior thermal stability. FTIR results showed that in the amide zone I oscillations of the polypeptide structure were related to the stretching vibrations of CO in the US/TG-Np edible film. Which has generally been associated with changes in the structure and formation of covalent bonds by the action of TG. The US improved mechanical properties by increasing the tensile strength (with or without the application of TG). While combining US-TG produced a significant increase in thickness, decrease in elongation percentage, and increase in tensile strength. Which can be attributed to cross-linking produced by TG. Water vapour permeability increased in all cases. In general, the combination of US-TG treatments showed a more pronounced effect on the structure and mechanical properties.

Patients with suboptimal hepatitis B virus diagnostic characterization are at risk of liver fibrosis progression.

BACKGROUND: Many patients with chronic hepatitis B virus infection remain infradiagnosed and untreated. In a national health system with unrestricted access to treatment, our aims were to assess the level of compliance with clinical guidelines and the characteristics and risk of fibrosis progression in patients with suboptimal diagnosis. METHODS: In a cohort of patients with positive hepatitis B surface antigen from January 2011 to December 2013, data were registered to assess characteristics and compliance with guidelines. For assessing the risk of liver fibrosis, positive hepatitis B surface antigen patients from January 2008 to December 2013 were grouped depending on DNA request. Liver fibrosis was estimated by serological scores. RESULTS: Of 41 158 subjects with hepatitis B surface antigen request, 351 (0.9%) tested positive, and DNA was not available from 110 patients (66.4% male, mean 42.4 ± 14.5 years) after a median of 25.6 months (range 12.0-43.5). Most of these patients (76%) were assessed by primary care. Half of the patients (47.2%) showed hypertransaminasemia, at least significant fibrosis, or both conditions. After long follow-up (mean 90.1 ± 45.2 months), these patients had a higher risk of achieving at least significant fibrosis during follow-up (log-rank 8.73; P = 0.003). CONCLUSION: In more than one-third of patients with positive hepatitis B surface antigen, DNA was not requested despite showing hypertransaminasemia and significant fibrosis. Patients without DNA request are at high risk of liver fibrosis progression. Thus, educational measures and other strategies are necessary, especially targeting primary care, to improve access to treatment.

Risk of liver fibrosis progression in patients with suboptimal diagnosis of hepatitis C virus infection.

OBJECTIVE: Many hepatitis C virus (HCV)-infected patients have a suboptimal diagnosis. Particularly, the characteristics and risk of fibrosis progression of HCV antibody-positive patients without RNA testing are unknown. METHODS: Patients with a positive HCV antibody performed during 2005-2007 were classified based on RNA request and result until January 2017. Fibrosis was estimated with serologic scores. RESULTS: Of the 38 246 HCV tests performed, 791 (2.01%) patients tested positive. At the end of the follow-up (median 128.6 months, range 109.8-145.9), 49.43% (n = 391) of the subjects did not have RNA testing, 13.02% (n = 103) had undetectable RNA, and 37.55% (n = 297) had detectable RNA. After excluding patients without data for AST to platelet ratio index calculation (n = 334), patients without RNA testing (n = 122) compared with RNA undetectable (n = 92) were more frequently men (68.9 versus 46.7%), alcohol (52.6 versus 38.2%) and drug (53.0 versus 39.1%) users, lacking social support (50.4 versus 29.3%), and showed higher basal fibrosis. Patients without RNA testing had a significantly higher increase in the percentage of patients with ≥F2 (P = 0.035) and cirrhosis (P = 0.022). The relative risk for ≥F2 and cirrhosis in patients without RNA testing was 3.03 [95% confidence interval (CI): 1.54-5.98] and 4.31 (95% CI: 1.42-13.10), respectively. Non-RNA request was an independent predictor factor for progression to cirrhosis. CONCLUSION: In our cohort, patients with positive HCV antibody without RNA testing were more likely to be people at risk of social exclusion with an increased risk of fibrosis progression, because non-RNA request was a predictor for cirrhosis. Therefore, we urge support measures and strategies to link to care these difficult-to-treat populations.

Predictive factors for not undergoing RNA testing in patients found to have hepatitis C serology and impact of an automatic alert.

The process of diagnosis and linkage to care in cases of hepatitis C virus (HCV) infection remains an obstacle to disease control. The aims of this study were to evaluate predictive factors for not undergoing RNA testing among patients with positive HCV serology and impact of incorporating an automated electronic alert with recommendations in clinical practice. We collected HCV antibody tests requested from October 2011 to September 2014 to evaluate the rate of RNA testing and predictive factors for not undergoing RNA testing. Since October 2014, an automated alert notification has been implemented to remind physicians for testing RNA after a positive HCV test and referral to specialist care. 41 403 HCV antibody tests were requested from 34 073 patients. 870 (2.55%) patients tested positive. After a median of follow-up of 57.0 months (range 45.6-82.1), 37.6% did not have RNA testing. The independent predictors for not undergoing RNA testing were primary care serology requests (P < 0.001), no history of drug use (P = 0.005) and a lack of social support (P = 0.015). The intervention impact was evaluated in a pre-alert cohort (October 2011-September 2014) and a post-alert cohort (October 2014-September 2015). After the incorporation of the alert, the rate of RNA testing increased from 62.4% to 77.7% (P < 0.001). Incomplete assessment of HCV infection is a challenge in primary care. The implementation of an automated alert for recommending RNA testing after a positive HCV antibody test is feasible in clinical practice and increases the rate of patients with RNA testing.

Board characteristics, governance objectives, and hospital performance: An empirical analysis of German hospitals.

BACKGROUND: There is a growing need for hospital supervisory boards to support hospital management in different areas, including (financial) monitoring, resource provision, stakeholder relationships, and strategic decision-making. Little is currently known about how boards' emphases on these various governance objectives contribute to performance. PURPOSE: Using a dominant logics perspective, this article aims to detect the governance logics that hospital boards emphasize, to determine whether there are distinct clusters of hospitals with the same sets of emphases, and to show how cluster membership relates to board characteristics and financial performance. METHODOLOGY: Using factor analysis, we identify latent classes of governance objectives and use hierarchical cluster analysis to detect distinct clusters with varying emphasis on the classes. We then use multinomial regression to explore the associations between cluster membership and board characteristics (size, gender diversity, and occupational diversity) and examine the associations between clusters and financial performance using OLS regression. RESULTS: Classes of objectives reflecting three governance theories-agency theory, stewardship theory, and stakeholder theory-can be distinguished, and hospitals can be divided into four clusters based on their board's relative emphasis on the classes. Cluster membership is significantly associated with board characteristics. There is also a significant association between cluster membership and hospital financial performance, with two of three groups performing significantly better than the reference group. CONCLUSION: High performance in hospitals can be the result of governance logics, which, compared to simple board characteristics, are associated with better financial outcomes. PRACTICE IMPLICATIONS: Hospitals can influence the emphasis placed on different governance objectives and enhance organizational success by creating boards that are small enough to be effective yet diverse enough to profit from a wide variety of expertise and experience.

Health systems: changes in hospital efficiency and profitability.

This study investigates potential changes in hospital performance after health system entry, while differentiating between hospital technical and cost efficiency and hospital profitability. In the first stage we obtained (bootstrapped) data envelopment analysis (DEA) efficiency scores. Then, genetic matching is used as a novel matching procedure in this context along with a difference-in-difference approach within a panel regression framework. With the genetic matching procedure, independent and health system hospitals are matched along a number of environmental and organizational characteristics. The results show that health system entry increases hospital technical and cost efficiency by between 0.6 and 3.4 % in four alternative post-entry periods, indicating that health system entry has not a transitory but rather a permanent effect on hospital efficiency. Regarding hospital profitability, the results reveal an increase in hospital profitability only 1 year after health system entry, and the estimations suggest that this effect is a transitional phenomenon. Overall, health system entry may serve as an appropriate management instrument for decision makers to increase hospital performance.

Cooperation for a competitive position: The impact of hospital cooperation behavior on organizational performance.

BACKGROUND: Several public policy initiatives, particularly those involving managed care, aim to enhance cooperation between partners in the health care sector because it is expected that such cooperation will reduce costs and generate additional revenue. However, empirical evidence regarding the effects of cooperation on hospital performance is scarce, particularly with respect to creating a comprehensive measure of cooperation behavior. PURPOSE: The aim of this study is to investigate the impact of hospital cooperation behavior on organizational performance. We differentiate between horizontal and vertical cooperation using two alternative measures-cooperation depth and cooperation breadth-and include the interaction effects between both cooperation directions. METHODOLOGY: Data are derived from a survey of German hospitals and combined with objective performance information from annual financial statements. Generalized linear regression models are used. FINDINGS: The study findings provide insight into the nature of hospitals' cooperation behavior. In particular, we show that there are negative synergies between horizontal administrative cooperation behavior and vertical cooperation behavior. Whereas the depth and breadth of horizontal administrative cooperation positively affect financial performance (when there is no vertical cooperation), vertical cooperation positively affects financial performance (when there is no horizontal administrative cooperation) only when cooperation is broad (rather than deep). PRACTICAL IMPLICATIONS: Horizontal cooperation is generally more effective than vertical cooperation at improving financial performance. Hospital managers should consider the negative interaction effect when making decisions about whether to recommend a cooperative relationship in a horizontal or vertical direction. In addition, managers should be aware of the limited financial benefit of cooperation behavior.

The impact of the board's strategy-setting role on board-management relations and hospital performance.

BACKGROUND: The appropriate governance of hospitals largely depends on effective cooperation between governing boards and hospital management. Governing boards play an important role in strategy-setting as part of their support for hospital management. However, in certain situations, this active strategic role may also generate discord within this relationship. PURPOSE: The objective of this study is to investigate the impact of the roles, attributes, and processes of governing boards on hospital performance. We examine the impact of the governing board's strategy-setting role on board-management collaboration quality and on financial performance while also analyzing the interaction effects of board diversity and board activity level. METHODOLOGY: The data are derived from a survey that was sent simultaneously to German hospitals and their associated governing board, combined with objective performance information from annual financial statements and quality reports. We use a structural equation modeling approach to test the model. FINDINGS: The results indicate that different board characteristics have a significant impact on hospital performance (R = .37). The strategy-setting role and board-management collaboration quality have a positive effect on hospital performance, whereas the impact of strategy-setting on collaboration quality is negative. We find that the positive effect of strategy-setting on performance increases with decreasing board diversity. When board members have more homogeneous backgrounds and exhibit higher board activity levels, the negative effect of the strategy-setting on collaboration quality also increases. PRACTICE IMPLICATIONS: Active strategy-setting by a governing board may generally improve hospital performance. Diverse members of governing boards should be involved in strategy-setting for hospitals. However, high board-management collaboration quality may be compromised if managerial autonomy is too highly restricted. Consequently, hospitals should support board-management collaboration about empowered contrasting board roles.

ACE gene polymorphism and erythropoietin in endurance athletes at moderate altitude.

PURPOSE: To determine the role of the ACE (I/D) gene polymorphism on erythropoietic response in endurance athletes after natural exposure to moderate altitude. METHODS: Erythropoietic activity was measured in 63 male endurance athletes following natural exposure to moderate altitude (2200 m) during 48 h. Erythropoietin (EPO) levels and hemoglobin (Hb) concentrations were measured at baseline and 12, 24, and 48 h after reaching the set altitude. Reticulocyte counts were determined at baseline and 48 h thereafter. Subjects were grouped into two groups (responders and nonresponders) based on significant increase in EPO levels (median: > 16.5 ng x m(-1)) after 24 h at altitude. ACE gene polymorphism was ascertained by polymerase chain reaction (DD, 31 (49%); ID, 24 (38%); II, 8 (13%)). RESULTS: Overall, EPO levels significantly increased at 12 (70%; P = 0.0001) and 24 h (72%; P = 0.0001) above baseline concentration following exposure to 2200 m. Thereafter, EPO concentration decreased at 48 h, but a significant increase in Hb levels (4.6 +/- 4%; P = 0.0001) and reticulocyte count (50.5 +/- 79%; P = 0.0001) was observed at the end of the experiment, suggesting negative feedback. There were no significant differences in EPO and Hb concentration profiles between subjects with DD genotype and those with other genotypes (ID/II). Moreover, responders (N = 42; DD, 50%; ID/II, 50%) and nonresponders (N = 21; DD, 48%; ID/II, 52%) showed a similar erythropoietic profile during the experiment and the ACE gene polymorphism did not influence the time course of the erythropoietic response. CONCLUSIONS: The ACE gene polymorphism does not influence erythropoietic activity in endurance athletes after short-term exposure to moderate altitude.

The ACE/DD genotype is associated with the extent of exercise-induced left ventricular growth in endurance athletes.

OBJECTIVES: We studied the impact of the angiotensin-converting enzyme (ACE)/DD genotype on morphologic and functional cardiac changes in adult endurance athletes. BACKGROUND: Trained athletes usually develop adaptive left ventricular hypertrophy (LVH), and ACE gene polymorphisms may regulate myocardial growth. However, little is known about the impact of the ACE/DD genotype and D allele dose on the cardiac changes in adult endurance athletes. METHODS; Echocardiographic studies (including tissue Doppler) were performed in 61 male endurance athletes ranging in age from 25 to 40 years, with a similar period of training (15.6 +/- 4 h/week for 12.6 +/- 5.7 years). The ACE genotype (insertion [I] or deletion [D] alleles) was ascertained by polymerase chain reaction (DD = 27, ID = 31, and II = 3). Athletes with the DD genotype were compared with their ID counterparts. RESULTS: The DD genotype was associated with a higher left ventricular mass index (LVMI) than the ID genotype (162.6 +/- 36.5 g/m(2) vs. 141.6 +/- 34 g/m(2), p = 0.031), regardless of other confounder variables. As a result, 70.4% of DD athletes and only 42% of ID athletes met the criteria for LVH (p = 0.037). Although systolic and early diastolic myocardial velocities were similar in DD and ID subjects, a more prolonged E-wave deceleration time (DT) was observed in DD as compared with ID athletes, after adjusting for other biologic variables (210 +/- 48 ms vs. 174 +/- 36 ms, respectively; p = 0.008). Finally, a positive association between DT and myocardial systolic peak velocity (medial and lateral peak S(m)) was only observed in DD athletes (p = 0.013, r = 0.481). CONCLUSIONS: The ACE/DD genotype is associated with the extent of exercise-induced LVH in endurance athletes, regardless of other known biologic factors.