Duty, desire or indifference? A qualitative study of patient decisions about recruitment to an epilepsy treatment trial

BACKGROUND: Epilepsy is a common neurological condition, in which drugs are the mainstay of treatment and drugs trials are commonplace. Understanding why patients might or might not opt to participate in epilepsy drug trials is therefore of some importance, particularly at a time of rapid drug development and testing; and the findings may also have wider applicability. This study examined the role of patient perceptions in the decision-making process about recruitment to an RCT (the SANAD Trial) that compared different antiepileptic drug treatments for the management of new-onset seizures and epilepsy. METHODS: In-depth interviews with 23 patients recruited from four study centres. All interviews were tape-recorded and transcribed; the transcripts were analysed thematically using a qualitative data analysis package. RESULTS: Of the nineteen informants who agreed to participate in SANAD, none agreed for purely altruistic reasons. The four informants who declined all did so for very specific reasons of self-interest. Informants' perceptions of the nature of the trial, of the drugs subject to trial, and of their own involvement were all highly influential in their decision-making. Informants either perceived the trial as potentially beneficial or unlikely to be harmful, and so agreed to participate; or as potentially harmful or unlikely to be beneficial and so declined to participate. CONCLUSION: Most patients applied 'weak altruism', while maintaining self-interest. An emphasis on the safety and equivalence of treatments allowed some patients to be indifferent to the question of involvement. There was evidence that some participants were subject to 'therapeutic misconceptions'. The findings highlight the individual nature of trials but nonetheless raise some generic issues in relation to their design and conduct

A high resolution search for the tensor glueball candidate [xi] (2230) Crystal Barrel Collaboration

We report results of a high resolution search for the tensor glueball candidate ξ(2230) in a p̄p formation experiment. π0π0 and ηη decay channels were measured in a scan of the mass region 2220 MeV to 2240 MeV. No evidence for the existence of ξ(2230) was found. 95% confidence upper limits for the possible existence of ξ are presented

A thematic analysis of factors influencing recruitment to maternal and perinatal trials

Background: Recruitment of eligible participants remains one of the biggest challenges to successful completion of randomised controlled trials (RCTs). Only one third of trials recruit on time, often requiring a lengthy extension to the recruitment period. We identified factors influencing recruitment success and potentially effective recruitment strategies. Methods: We searched MEDLINE and EMBASE from 1966 to December Week 2, 2006, the Cochrane Library Methodology Register in December 2006, and hand searched reference lists for studies of any design which focused on recruitment to maternal/perinatal trials, or if no studies of maternal or perinatal research could be identified, other areas of healthcare. Studies of nurses' and midwives' attitudes to research were included as none specifically about trials were located. We synthesised the data narratively, using a basic thematic analysis, with themes derived from the literature and after discussion between the authors. Results: Around half of the included papers (29/53) were specific to maternal and perinatal healthcare. Only one study was identified which focused on factors for maternal and perinatal clinicians and only seven studies considered recruitment strategies specific to perinatal research. Themes included: participant assessment of risk; recruitment process; participant understanding of research; patient characteristics; clinician attitudes to research and trials; protocol issues; and institutional or organisational issues. While no reliable evidence base for strategies to enhance recruitment was identified in any of the review studies, four maternal/perinatal primary studies suggest that specialised recruitment staff, mass mailings, physician referrals and strategies targeting minority women may increase recruitment. However these findings may only be applicable to the particular trials and settings studied. Conclusion: Although factors reported by both participants and clinicians which influence recruitment were quite consistent across the included studies, studies comparing different recruitment strategies were largely missing. Trials of different recruitment strategies could be embedded in large multicentre RCTs, with strategies tailored to the factors specific to the trial and institution.Rebecca L Tooher, Philippa F Middleton and Caroline A Crowthe

Reasons for facebook usage: data from 46 countries

info:eu-repo/semantics/publishedVersio

Generational distribution of a Candida glabrata population: Resilient old cells prevail, while younger cells dominate in the vulnerable host.

Similar to other yeasts, the human pathogen Candida glabrata ages when it undergoes asymmetric, finite cell divisions, which determines its replicative lifespan. We sought to investigate if and how aging changes resilience of C. glabrata populations in the host environment. Our data demonstrate that old C. glabrata are more resistant to hydrogen peroxide and neutrophil killing, whereas young cells adhere better to epithelial cell layers. Consequently, virulence of old compared to younger C. glabrata cells is enhanced in the Galleria mellonella infection model. Electron microscopy images of old C. glabrata cells indicate a marked increase in cell wall thickness. Comparison of transcriptomes of old and young C. glabrata cells reveals differential regulation of ergosterol and Hog pathway associated genes as well as adhesion proteins, and suggests that aging is accompanied by remodeling of the fungal cell wall. Biochemical analysis supports this conclusion as older cells exhibit a qualitatively different lipid composition, leading to the observed increased emergence of fluconazole resistance when grown in the presence of fluconazole selection pressure. Older C. glabrata cells accumulate during murine and human infection, which is statistically unlikely without very strong selection. Therefore, we tested the hypothesis that neutrophils constitute the predominant selection pressure in vivo. When we altered experimentally the selection pressure by antibody-mediated removal of neutrophils, we observed a significantly younger pathogen population in mice. Mathematical modeling confirmed that differential selection of older cells is sufficient to cause the observed demographic shift in the fungal population. Hence our data support the concept that pathogenesis is affected by the generational age distribution of the infecting C. glabrata population in a host. We conclude that replicative aging constitutes an emerging trait, which is selected by the host and may even play an unanticipated role in the transition from a commensal to a pathogen state.post-print10768 K

Clinical and Economic Evaluation of a Proteomic Biomarker Preterm Birth Risk Predictor: Cost-Effectiveness Modeling of Prenatal Interventions Applied to Predicted Higher-Risk Pregnancies Within a Large and Diverse Cohort

Objectives: Preterm birth occurs in more than 10% of U.S. births and is the leading cause of U.S. neonatal deaths, with estimated annual costs exceeding $25 billion USD. Using real-world data, we modeled the potential clinical and economic utility of a prematurity-reduction program comprising screening in a racially and ethnically diverse population with a validated proteomic biomarker risk predictor, followed by case management with or without pharmacological treatment. Methods: The ACCORDANT microsimulation model used individual patient data from a prespecified, randomly selected sub-cohort (N = 847) of a multicenter, observational study of U.S. subjects receiving standard obstetric care with masked risk predictor assessment (TREETOP; NCT02787213). All subjects were included in three arms across 500 simulated trials: standard of care (SoC, control); risk predictor/case management comprising increased outreach, education and specialist care (RP-CM, active); and multimodal management (risk predictor/case management with pharmacological treatment) (RP-MM, active). In the active arms, only subjects stratified as higher risk by the predictor were modeled as receiving the intervention, whereas lower-risk subjects received standard care. Higher-risk subjects\u27 gestational ages at birth were shifted based on published efficacies, and dependent outcomes, calibrated using national datasets, were changed accordingly. Subjects otherwise retained their original TREETOP outcomes. Arms were compared using survival analysis for neonatal and maternal hospital length of stay, bootstrap intervals for neonatal cost, and Fisher\u27s exact test for neonatal morbidity/mortality (significance, p \u3c .05). Results: The model predicted improvements for all outcomes. RP-CM decreased neonatal and maternal hospital stay by 19% (p = .029) and 8.5% (p = .001), respectively; neonatal costs\u27 point estimate by 16% (p = .098); and moderate-to-severe neonatal morbidity/mortality by 29% (p = .025). RP-MM strengthened observed reductions and significance. Point estimates of benefit did not differ by race/ethnicity. Conclusions: Modeled evaluation of a biomarker-based test-and-treat strategy in a diverse population predicts clinically and economically meaningful improvements in neonatal and maternal outcomes

The gut microbiota of Colombians differs from that of Americans, Europeans and Asians

ABSTRACT: The composition of the gut microbiota has recently been associated with health and disease, particularly with obesity. Some studies suggested a higher proportion of Firmicutes and a lower proportion of Bacteroidetes in obese compared to lean people; others found discordant patterns. Most studies, however, focused on Americans or Europeans, giving a limited picture of the gut microbiome. To determine the generality of previous observations and expand our knowledge of the human gut microbiota, it is important to replicate studies in overlooked populations. Thus, we describe here, for the first time, the gut microbiota of Colombian adults via the pyrosequencing of the 16S ribosomal DNA (rDNA), comparing it with results obtained in Americans, Europeans, Japanese and South Koreans, and testing the generality of previous observations concerning changes in Firmicutes and Bacteroidetes with increasing body mass index (BMI). Results: We found that the composition of the gut microbiota of Colombians was significantly different from that of Americans, Europeans and Asians. The geographic origin of the population explained more variance in the composition of this bacterial community than BMI or gender. Concerning changes in Firmicutes and Bacteroidetes with obesity, in Colombians we found a tendency in Firmicutes to diminish with increasing BMI, whereas no change was observed in Bacteroidetes. A similar result was found in Americans. A more detailed inspection of the Colombian dataset revealed that five fiber-degrading bacteria, including Akkermansia, Dialister, Oscillospira, Ruminococcaceae and Clostridiales, became less abundant in obese subjects. Conclusion: We contributed data from unstudied Colombians that showed that the geographic origin of the studied population had a greater impact on the composition of the gut microbiota than BMI or gender. Any strategy aiming to modulate or control obesity via manipulation of this bacterial community should consider this effect

Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants

Background: Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may reduce the risk of cognitive delay among extremely-low-birth-weight infants with anemia. Methods: We performed an open, multicenter trial in which infants with a birth weight of 1000 g or less and a gestational age between 22 weeks 0 days and 28 weeks 6 days were randomly assigned within 48 hours after delivery to receive red-cell transfusions at higher or lower hemoglobin thresholds until 36 weeks of postmenstrual age or discharge, whichever occurred first. The primary outcome was a composite of death or neurodevelopmental impairment (cognitive delay, cerebral palsy, or hearing or vision loss) at 22 to 26 months of age, corrected for prematurity. Results: A total of 1824 infants (mean birth weight, 756 g; mean gestational age, 25.9 weeks) underwent randomization. There was a between-group difference of 1.9 g per deciliter (19 g per liter) in the pretransfusion mean hemoglobin levels throughout the treatment period. Primary outcome data were available for 1692 infants (92.8%). Of 845 infants in the higher-threshold group, 423 (50.1%) died or survived with neurodevelopmental impairment, as compared with 422 of 847 infants (49.8%) in the lower-threshold group (relative risk adjusted for birth-weight stratum and center, 1.00; 95% confidence interval [CI], 0.92 to 1.10; P = 0.93). At 2 years, the higher- and lower-threshold groups had similar incidences of death (16.2% and 15.0%, respectively) and neurodevelopmental impairment (39.6% and 40.3%, respectively). At discharge from the hospital, the incidences of survival without severe complications were 28.5% and 30.9%, respectively. Serious adverse events occurred in 22.7% and 21.7%, respectively. Conclusions: In extremely-low-birth-weight infants, a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity