Optimised patient information materials and recruitment to a study of behavioural activation in older adults : an embedded study within a trial [version 1; peer review: awaiting peer review]

YesPrinted participant information about randomised controlled trials is often long, technical and difficult to navigate. Improving information materials is possible through optimisation and user-testing, and may impact on participant understanding and rates of recruitment. Methods: A study within a trial (SWAT) was undertaken within the CASPER trial. Potential CASPER participants were randomised to receive either the standard trial information or revised information that had been optimised through information design and user testing. Results: A total of 11,531 patients were randomised in the SWAT. Rates of recruitment to the CASPER trial were 2.0% in the optimised information group and 1.9% in the standard information group (odds ratio 1.027; 95% CI 0.79 to 1.33; p=0.202). Conclusions: Participant information that had been optimised through information design and user testing did not result in any change to rate of recruitment to the host trial. Registration: ISRCTN ID ISRCTN02202951; registered on 3 June 2009.UK National Institute of Health Research Health Technology Assessment Programme (project number 08/19/04)This article is included in the Studies Within A Trial (SWAT) collection (https://f1000research.com/collections/swat

Factors associated with the development of septic shock in patients with candidemia: A post hoc analysis from two prospective cohorts

Background: Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was to identify variables associated with septic shock development in a large population of patients with candidemia. Methods: A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes occurring from September 2016 to February 2018 were analyzed to assess variables associated with septic shock development defined according to The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3). Results: Of 317 candidemic patients, 99 (31.2%) presented septic shock attributable to candidemia. Multivariate logistic regression analysis identifies the following factors associated with septic shock development: age > 50 years (OR 2.57, 95% CI 1.03-6.41, p = 0.04), abdominal source of the infection (OR 2.18, 95% CI 1.04-4.55, p = 0.04), and admission to a general ward at the time of candidemia onset (OR 0.21, 95% CI, 0.12-0.44, p = 0.001). Septic shock development was independently associated with a greater risk of 30-day mortality (OR 2.14, 95% CI 1.08-4.24, p = 0.02). Conclusions: Age and abdominal source of the infection are the most important factors significantly associated with the development of septic shock in patients with candidemia. Our findings suggest that host factors and source of the infection may be more important for development of septic shock than intrinsic virulence factors of organisms

Can user testing of a clinical trial patient information sheet make it fit-for-purpose? - a randomized controlled trial

Background: The participant information sheet (PIS) provided to potential trial participants is a critical part of the process of valid consent. However, there is long-standing concern that these lengthy and complex documents are not fit-for-purpose. This has been supported recently through the application of a performance-based approach to testing and improving readability called user testing. This method is now widely used to improve patient medicine leaflets - determining whether people can find and understand key facts. This study applied for the first time a controlled design to determine whether a PIS developed through user testing had improved readability over the original, using a sheet from a UK trial in acute myeloid leukemia (AML16). Methods: In the first phase the performance of the original PIS was tested on people in the target group for the trial. There were three rounds of testing including 50 people in total - with the information revised according to its performance after each of the first 2 rounds. In the second phase, the revised PIS was compared with the original in a parallel groups randomised controlled trial (RCT) A total of 123 participants were recruited and randomly allocated to read one version of the PIS to find and show understanding of 21 key facts. Results: The first, developmental phase produced a revised PIS significantly altered in its wording and layout. In the second, trial phase 66% of participants who read the revised PIS were able to show understanding of all aspects of the trial, compared with 15% of those reading the original version (Odds Ratio 11.2; Chi-square = 31.5 p < .001). When asked to state a preference, 87.1% participants chose the revised PIS (Sign test p < .001). Conclusions: The original PIS for the AML16 trial may not have enabled valid consent. Combining performance-based user testing with expertise in writing for patients and information design led to a significantly improved and preferred information sheet. User testing is an efficient method for indicating strengths and weaknesses in trial information, and Research Ethics Committees and Institutional Review Boards should consider requesting such testing, to ensure that PIS are fit-for-purpose

Genomic research, publics and experts in Latin America: Nation, race and body

The articles in this issue highlight contributions that studies of Latin America can make to wider debates about the effects of genomic science on public ideas about race and nation. We argue that current ideas about the power of genomics to transfigure and transform existing ways of thinking about human diversity are often overstated. If a range of social contexts are examined, the effects are uneven. Our data show that genomic knowledge can unsettle and reinforce ideas of nation and race; it can be both banal and highly politicized. In this introduction, we outline concepts of genetic knowledge in society; theories of genetics, nation and race; approaches to public understandings of science; and the Latin American contexts of transnational ideas of nation and race

Have we seen the geneticisation of society? Expectations and evidence

Abby Lippman’s geneticization thesis, of the early 1990s, argued and anticipated that with the rise of genetics, increasing areas of social and health related activities would come to be understood and defined in genetic terms leading to major changes in society, medicine and health care. We review the considerable literature on geneticization and consider how the concept stands both theoretically and empirically across scientific, clinical, popular and lay discourse and practice. Social science scholarship indicates that relatively little of the original claim of the geneticization thesis has been realised, highlighting the development of more complex and dynamic accounts of disease in scientific discourse and the complexity of relationships between bioscientific, clinical and lay understandings. This scholarship represents a shift in social science understandings of the processes of sociotechnical change, which have moved from rather simplistic linear models to an appreciation of disease categories as multiply understood. Despite these shifts, we argue that a genetic imaginary persists, which plays a performative role in driving investments in new gene-based developments. Understanding the enduring power of this genetic imaginary and its consequences remains a key task for the social sciences, one which treats ongoing genetic expectations and predictions in a sceptical yet open way

Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19

Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log10 at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19