Background Genuine uncertainty on superiority of one intervention over the other is called equipoise. Physician-investigators in randomized controlled trials need equipoise at least in studies with more than minimal risks. Ideally, this equipoise is also present in patient-participants. In pediatrics, data on equipoise are lacking. We hypothesize that 1) lack of equipoise at enrolment among parents may reduce recruitment; 2) lack of equipoise during participation may reduce retention in patients assigned to a less favoured treatment-strategy. Methods We compared preferences of (...) parents/patients at enrolment, documented by a questionnaire, with preferences developed during follow-up by an interview-study to investigate equipoise of child-participants and parents in the BeSt-for-Kids-study. This trial in new-onset Juvenile Idiopathic Arthritis-patients consists of three strategies. One strategy comprises initial treatment with a biological disease-modifying-antirheumatic-drug, currently not standard-of-care. Semi-structured interviews were conducted with 23 parents and 7 patients, median 11 months after enrolment. Results Initially most parents and children were not in equipoise. Parents/patients who refused participation, regularly declined due to specific preferences. Many participating families preferred the biological-first-strategy. They participated to have a chance for this initial treatment, and would even consider stopping trial-participation when not randomized for it. Their conviction of superiority of the biological-first strategy was based on knowledge from internet and close relations. According to four parents, the physician-investigator preferred the biological-first-strategy, but the majority stated that she had no preferred strategy. In phase 2, preferences tended to change to the treatment actually received. Conclusions Lack of equipoise during enrolment did not reduce study recruitment, mainly due to the fact that preferred treatment was only available within the study. Still, when developing a trial it is important to evaluate whether the physicians’ research question is in line with preferences of the patient-group. By exploring so-called ‘informed patient-group’-equipoise, successful recruitment may be enhanced and bias avoided. In our study, lack of equipoise during trial-participation did not reduce retention in those assigned to a less favoured option. We observed a change for preference towards treatment actually received, possibly explained by comparable outcomes in all three arms. (shrink)

We examined if cancer patients' health-related quality of life (HRQoL) scores on the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 are affected by the specific time point, before or during treatment, at which the questionnaire is completed, and whether this could bias the overall treatment comparison analyses. A 'completion-time window' variable was created on three closed EORTC randomised control trials in lung (non-small cell lung cancer, NSCLC) and colorectal cancer (CRC) to indicate when the QLQ-30 was completed (...) relative to chemotherapy cycle dates, defined as 'before', 'on' and 'after'. HRQoL mean scores were calculated using a linear mixed model. Statistically significant differences (P < 0.05) were observed on 6 and 5 scales for 'on' and 'after' comparisons in the NSCLC and two-group CRC trial, respectively. As for the three-group CRC trial, several statistical differences were observed in the 'before' to 'on' and the 'on' to 'after' comparisons. For all three trials, including the 'completion-time window' variable in the model resulted in a better fit, but no substantial changes in the treatment effects were noted. We showed that considering the exact timing of completion within specified windows resulted in statistical and potentially clinically significant differences, but it did not alter the conclusions of treatment comparison in these studies. (shrink)

The encounter between Socrates and Thrasymachus in Republic I is notoriously baffling. Most of what is said seems straightforward, and the issues at stake are ones of common concern, but the argument remains elusive. The purpose of this paper is to investigate the nature and grounds of this elusiveness, and to show that some of it can be dispelled by a sufficiently free-ranging exegesis that bears in mind the general character of Plato’s writing.

We show how a simple nonlinear dynamical system (the discrete quadratic iteration on the unit segment) can be the basis for modelling the embryogenesis process. Such an approach, even though being crude, can nevertheless prove to be useful when looking with the two main involved processes:i) on one hand the cell proliferation under successive divisions ii) on the other hand, the differentiation between cell lineages. We illustrate this new approach in the case of Caenorhabditis elegans by looking at the early (...) stages of embryogenesis, up to several hundreds of cells (lima bean larval stage). We show how the many results that have been obtained by several groups can be interpreted in terms of values for the parameters controlling the dynamical system. Furthermore, we can extend the model to the cases of genetic mutations. More precisely the teratogenetic and lethal effects are associated with abnormal variation of the control parameters with time. (shrink)

First published in 1945. In this work the author seeks to correct the misinterpretation and incorrect labelling of Shelley's thought. While not neglecting Shelley as a poet, this book focuses on his contributions made to the general movement of political and philosophical thought of his era and by so doing his relevance to contemporary issues. This title will be of interest to students of literature.