Is the impact of hospital performance data greater in patients who have compared hospitals?

<p>Abstract</p> <p>Background</p> <p>Public information on average has limited impact on patients' hospital choice. However, the impact may be greater in consumers who have compared hospitals prior to their hospital choice. We therefore assessed whether patients who have compared hospitals based their hospital choice mainly on public information, rather than e.g. advice of their general practitioner and consider other information important than patients who have not compared hospitals.</p> <p>Methods</p> <p>337 new surgical patients completed an internet-based questionnaire. They were asked whether they had compared hospitals prior to their hospital choice and which factors influenced their choice. They were also asked to select between four and ten items of hospital information (total: 41 items) relevant for their future hospital choice. These were subsequently used in a hospital choice experiment in which participants were asked to compare hospitals in an Adaptive Choice-Based Conjoint analysis to estimate which of the hospital characteristics had the highest Relative Importance (RI).</p> <p>Results</p> <p>Patients who have compared hospitals more often used public information for their hospital choice than patients who have not compared hospitals (12.7% vs. 1.5%, p < 0.001). However, they still mostly relied on their own (47.9%) and other people's experiences (31%) rather than to base their decision on public information. Both groups valued physician's expertise (RI 20.2 [16.6-24.8] in patients comparing hospitals vs. 16.5 [14.2-18.8] in patients not comparing hospitals) and waiting time (RI 15.1 [10.7-19.6] vs. 15.6 [13.2-17.9] respectively) as most important public information. Patients who have compared hospitals assigned greater importance to information on wound infections (p = 0.010) and respect for patients (p = 0.022), but lower importance to hospital distance (p = 0.041).</p> <p>Conclusion</p> <p>Public information has limited impact on patient's hospital choice, even in patients who have actually compared hospitals prior to hospital choice.</p

An Event-Related fMRI Study of Phonological Verbal Working Memory in Schizophrenia

Background: While much is known about the role of prefrontal cortex (PFC) in working memory (WM) deficits of schizophrenia, the nature of the relationship between cognitive components of WM and brain activation patterns remains unclear. We aimed to elucidate the neural correlates of the maintenance component of verbal WM by examining correct and error trials with event-related fMRI. Methodology/Findings: Twelve schizophrenia patients (SZ) and thirteen healthy control participants (CO) performed a phonological delayed-matching-to-sample-task in which a memory set of three nonsense words was presented, followed by a 6-seconds delay after which a probe nonsense word appeared. Participants decided whether the probe matched one of the targets, and rated the confidence of their decision. Blood-oxygen-level-dependent (BOLD) activity during WM maintenance was analyzed in relation to performance (correct/error) and confidence ratings. Frontal and parietal regions exhibited increased activation on correct trials for both groups. Correct and error trials were further segregated into true memory, false memory, guess, and true error trials. True memory trials were associated with increased bilateral activation of frontal and parietal regions in both groups but only CO showed deactivation in PFC. There was very little maintenancerelated cortical activity during guess trials. False memory was associated with increased left frontal and parietal activation in both groups. Conclusion: These findings suggest that a wider network of frontal and parietal regions support WM maintenance in correct trials compared with error trials in both groups. Furthermore, a more extensive and dynamic pattern of recruitment of the frontal and parietal networks for true memory was observed in healthy controls compared with schizophrenia patients. These results underscore the value of parsing the sources of memory errors in fMRI studies because of the non-linear nature of the brain-behavior relationship, and suggest that group comparisons need to be interpreted in more specific behavioral contexts

Functional Analysis of the Cytoskeleton Protein MreB from Chlamydophila pneumoniae

In rod-shaped bacteria, the bacterial actin ortholog MreB is considered to organize the incorporation of cell wall precursors into the side-wall, whereas the tubulin homologue FtsZ is known to tether incorporation of cell wall building blocks at the developing septum. For intracellular bacteria, there is no need to compensate osmotic pressure by means of a cell wall, and peptidoglycan has not been reliably detected in Chlamydiaceae. Surprisingly, a nearly complete pathway for the biosynthesis of the cell wall building block lipid II has been found in the genomes of Chlamydiaceae. In a previous study, we discussed the hypothesis that conservation of lipid II biosynthesis in cell wall-lacking bacteria may reflect the intimate molecular linkage of cell wall biosynthesis and cell division and thus an essential role of the precursor in cell division. Here, we investigate why spherical-shaped chlamydiae harbor MreB which is almost exclusively found in elongated bacteria (i.e. rods, vibrios, spirilla) whereas they lack the otherwise essential division protein FtsZ. We demonstrate that chlamydial MreB polymerizes in vitro and that polymerization is not inhibited by the blocking agent A22. As observed for MreB from Bacillus subtilis, chlamydial MreB does not require ATP for polymerization but is capable of ATP hydrolysis in phosphate release assays. Co-pelleting and bacterial two-hybrid experiments indicate that MreB from Chlamydophila (Chlamydia) pneumoniae interacts with MurF, MraY and MurG, three key components in lipid II biosynthesis. In addition, MreB polymerization is improved in the presence of MurF. Our findings suggest that MreB is involved in tethering biosynthesis of lipid II and as such may be necessary for maintaining a functional divisome machinery in Chlamydiaceae

A Study of T Cell Tolerance to the Tumor-Associated Antigen MDM2: Cytokines Can Restore Antigen Responsiveness, but Not High Avidity T Cell Function

BACKGROUND: Most tumor-associated antigens (TAA) currently used for immunotherapy of cancer are also expressed in normal tissues, which may induce tolerance and impair T cell-mediated immunity. However, there is limited information about how physiological expression in normal tissues alters the function of TAA-specific T cells. METHODOLOGY/PRINCIPAL FINDINGS: We used a T cell receptor transgenic model to study how MDM2 expression in normal tissues affects the function of T cells specific for this TAA that is found at high levels in many different types of tumors. We found that some MDM2-specific T cells escaped thymic deletion and persisted in the peripheral T cell pool. When stimulated with antigen, these T cells readily initiated cell division but failed to proliferate and expand, which was associated with a high rate of apoptosis. Both IL-2 and IL-15 efficiently rescued T cell survival and antigen-specific T cell proliferation, while IL-7 and IL-21 were ineffective. Antigen-stimulated T cells showed impaired expression of the effector molecules CD43, granzyme-B and IFN-γ, a defect that was completely restored when T cells were stimulated in the presence of IL-2. In contrast, IL-15 and IL-21 only restored the expression of CD43 and granzyme-B, but not IFN-γ production. Finally, peptide titration experiments with IL-2 rescued T cells indicated that they were of lower avidity than non-tolerant control T cells expressing the same TCR. CONCLUSIONS/SIGNIFICANCE: These data indicate that cytokines can rescue the antigen-specific proliferation and effector function of MDM2-specific T cells, although this does not lead to the recovery of high avidity T cell function. This study sheds light on possible limitations of immunotherapy approaches that target widely expressed TAA, such as MDM2

Substance use risk profiles and associations with early substance use in adolescence

We examined whether anxiety sensitivity, hopelessness, sensation seeking, and impulsivity (i.e., revised version of the Substance Use Risk Profile Scale) would be related to the lifetime prevalence and age of onset of alcohol, tobacco, and cannabis use, and to polydrug use in early adolescence. Baseline data of a broader effectiveness study were used from 3,783 early adolescents aged 11–15 years. Structural equation models showed that hopelessness and sensation seeking were indicative of ever-used alcohol, tobacco or cannabis and for the use of more than one substance. Furthermore, individuals with higher levels of hopelessness had a higher chance of starting to use alcohol or cannabis at an earlier age, but highly anxiety sensitive individuals were less likely to start using alcohol use at a younger age. Conclusively, early adolescents who report higher levels of hopelessness and sensation seeking seem to be at higher risk for an early onset of substance use and poly substance use

A Single-Blind randomized controlled trial to evaluate the effect of extended counseling on uptake of pre-antiretroviral care in eastern uganda

<p>Abstract</p> <p>Background</p> <p>Many newly screened people living with HIV (PLHIV) in Sub-Saharan Africa do not understand the importance of regular pre-antiretroviral (ARV) care because most of them have been counseled by staff who lack basic counseling skills. This results in low uptake of pre-ARV care and late treatment initiation in resource-poor settings. The effect of providing post-test counseling by staff equipped with basic counseling skills, combined with home visits by community support agents on uptake of pre-ARV care for newly diagnosed PLHIV was evaluated through a randomized intervention trial in Uganda.</p> <p>Methods</p> <p>An intervention trial was performed consisting of post-test counseling by trained counselors, combined with monthly home visits by community support agents for continued counseling to newly screened PLHIV in Iganga district, Uganda between July 2009 and June 2010, Participants (N = 400) from three public recruitment centres were randomized to receive either the intervention, or the standard care (the existing post-test counseling by ARV clinic staff who lack basic training in counseling skills), the control arm. The outcome measure was the proportion of newly screened and counseled PLHIV in either arm who had been to their nearest health center for clinical check-up in the subsequent three months +2 months. Treatment was randomly assigned using computer-generated random numbers. The statistical significance of differences between the two study arms was assessed using chi-square and t-tests for categorical and quantitative data respectively. Risk ratios and 95% confidence intervals were used to assess the effect of the intervention.</p> <p>Results</p> <p>Participants in the intervention arm were 80% more likely to accept (take up) pre-ARV care compared to those in the control arm (RR 1.8, 95% CI 1.4-2.1). No adverse events were reported.</p> <p>Conclusions</p> <p>Provision of post-test counseling by staff trained in basic counseling skills, combined with home visits by community support agents had a significant effect on uptake of pre-ARV care and appears to be a cost-effective way to increase the prerequisites for timely ARV initiation.</p> <p>Trial registration</p> <p>The trial was registered by Current Controlled Trials Ltd C/OBioMed Central Ltd as <a href="http://www.controlled-trials.com/ISRCTN94133652">ISRCTN94133652</a> and received financial support from Sida and logistical support from the European Commission.</p

Multicentre RCT and economic evaluation of a psychological intervention together with a leaflet to reduce risk behaviour amongst men who have sex with men (MSM) prescribed post-exposure prophylaxis for HIV following sexual exposure (PEPSE): A protocol

Background: Post-exposure prophylaxis (PEP) following sexual exposure to HIV has been recommended as a method of preventing HIV infection in the UK. Men who have sex with men (MSM) are the group most affected by HIV in the UK and their sexual risk taking behaviour is reported to be increasing. One-to-one behavioural interventions, such as motivational interviewing (MI) have been recommended to reduce HIV in high risk groups. The Information, Motivation and Behavioral skills (IMB) model has been shown to provide a good basis for understanding and predicting HIV-relevant health behaviour and health behaviour change, however the IMB has yet to be applied to PEP after risky sexual exposure. The primary aim of this trial is to examine the impact of MI augmented with information provision and behavioural skills building (informed by the IMB Model), over and above usual care, on risky sexual behaviour in MSM prescribed PEP after potential sexual exposure. A secondary aim of this research is to examine the impact of the intervention on adherence to PEP. This study will also provide estimates of the cost-effectiveness of the intervention. Methods: A manualised parallel group randomised controlled trial with economic evaluation will be conducted. The primary outcome is the proportion of risky sexual practices. Secondary outcomes include: i) Levels of adherence to PEP treatment; ii) Number of subsequent courses of PEP; iii) Levels of motivation to avoid risky sexual behaviours; iv) Levels of HIV risk-reduction information/knowledge; v) Levels of risk reduction behavioural skills; vi) Diagnosis of anal gonorrhoea, Chlamydia and/or HIV. 250 participants will be asked to self-complete a questionnaire at four time points during the study (at 0,3,6,12 months). The intervention will consist of a two-session, fixed duration, telephone administered augmented MI intervention based on the IMB model. A newly developed treatment manual will guide the selection of persuasive communication strategies as appropriate for each participant and will be based on underlying change mechanisms specified by the IMB theoretical framework. Information provision and skills building will also be included in the intervention package through the use of information leaflets and tailored action plans. Fidelity of intervention delivery will be assessed. Discussion: The results from this NIHR funded study will identify whether it is appropriate and cost-effective to intervene using one-to-one telephone calls with MSM seeking PEP. If the intervention is effective, further work will be needed on training staff to deliver the intervention competently

Lung cancer risk among German male uranium miners: a cohort study, 1946–1998

From 1946 to 1990 extensive uranium mining was conducted in the southern parts of the former German Democratic Republic. The overall workforce included several 100 000 individuals. A cohort of 59 001 former male employees of the Wismut Company was established, forming a large retrospective uranium miners' cohort for the time period 1946–1998. Mean duration of follow-up was 30.5 years with a total of 1 801 630 person-years. Loss to follow-up was low at 5.3%. Of the workers, 16 598 (28.1%) died during the study period. Based on 2388 lung cancer deaths, the radon-related lung cancer risk is evaluated. The excess relative risk (ERR) per working level month (WLM) was estimated as 0.21% (95% CI: 0.18–0.24). It was dependent on time since exposure and on attained age. The highest ERR/WLM was observed 15–24 years after exposure and in the youngest age group (<55 years of age). While a strong inverse exposure-rate effect was detected for high exposures, no significant association was detected at exposures below 100 WLM. Excess relative risk /WLM was not modified by duration of exposure. The results would indicate the need to re-estimate the effects of risk modifying factors in current risk models as duration of exposure did not modify the ERR/WLM and there was only a modest decline of ERR/WLM with increasing time since exposure

The Impact of Local Genome Sequence on Defining Heterochromatin Domains

Characterizing how genomic sequence interacts with trans-acting regulatory factors to implement a program of gene expression in eukaryotic organisms is critical to understanding genome function. One means by which patterns of gene expression are achieved is through the differential packaging of DNA into distinct types of chromatin. While chromatin state exerts a major influence on gene expression, the extent to which cis-acting DNA sequences contribute to the specification of chromatin state remains incompletely understood. To address this, we have used a fission yeast sequence element (L5), known to be sufficient to nucleate heterochromatin, to establish de novo heterochromatin domains in the Schizosaccharomyces pombe genome. The resulting heterochromatin domains were queried for the presence of H3K9 di-methylation and Swi6p, both hallmarks of heterochromatin, and for levels of gene expression. We describe a major effect of genomic sequences in determining the size and extent of such de novo heterochromatin domains. Heterochromatin spreading is antagonized by the presence of genes, in a manner that can occur independent of strength of transcription. Increasing the dosage of Swi6p results in increased heterochromatin proximal to the L5 element, but does not result in an expansion of the heterochromatin domain, suggesting that in this context genomic effects are dominant over trans effects. Finally, we show that the ratio of Swi6p to H3K9 di-methylation is sequence-dependent and correlates with the extent of gene repression. Taken together, these data demonstrate that the sequence content of a genomic region plays a significant role in shaping its response to encroaching heterochromatin and suggest a role of DNA sequence in specifying chromatin state