The Treatment In Morning versus Evening (TIME) study:Analysis of recruitment, follow-up and retention rates post-recruitment

Abstract Background The use of information technology (IT) is now the preferred method of capturing and storing clinical research data. The Treatment In Morning versus Evening (TIME) study predominantly uses electronic data capture and IT to compare morning dosing of hypertensive medication against evening dosing. Registration, consent, participant demographics and follow-up data are all captured via the study website. The aim of this article is to assess the success of the TIME methodology compared with similar studies. Methods To assess the TIME study, published literature on similar clinical trials was reviewed and compared against TIME recruitment, follow-up and email interaction data. Results The TIME website registered 31,695 individuals, 21,116 of whom were randomised. Recruitment cost per randomised participant varied by strategy: £17.40 by GP practice, £3.08 by UK Biobank and £58.82 for GoShare. Twelve-month follow-up retention rates were 96%. A total of 1089 participants have withdrawn from their assigned time of dosing, 2% of whom have declined follow-up by record linkage or further contact. When the TIME data are compared with similar study data, study recruitment is very successful. However, TIME suffers difficulties with participant follow-up and withdrawal rates similar to those of conventional studies. Conclusions The TIME study has been successful in recruitment. Follow-up, retention rates and withdrawal rates are all acceptable, but ongoing work is required to ensure participants remain engaged with the study. Various recruitment strategies are necessary, and all viable options should be encouraged to maintain participant engagement throughout the life of studies using IT

Methionine Sulfoxide Reductase A (MsrA) Deficient Mycoplasma genitalium Shows Decreased Interactions with Host Cells

Mycoplasma genitalium is an important sexually transmitted pathogen that affects both men and women. In genital-mucosal tissues, it initiates colonization of epithelial cells by attaching itself to host cells via several identified bacterial ligands and host cell surface receptors. We have previously shown that a mutant form of M. genitalium lacking methionine sulfoxide reductase A (MsrA), an antioxidant enzyme which converts oxidized methionine (Met(O)) into methionine (Met), shows decreased viability in infected animals. To gain more insights into the mechanisms by which MsrA controls M. genitalium virulence, we compared the wild-type M. genitalium strain (G37) with an msrA mutant (MS5) strain for their ability to interact with target cervical epithelial cell lines (HeLa and C33A) and THP-1 monocytic cells. Infection of epithelial cell lines with both strains revealed that MS5 was less cytotoxic to HeLa and C33A cell lines than the G37 strain. Also, the MS5 strain was more susceptible to phagocytosis by THP-1 cells than wild type strain (G37). Further, MS5 was less able to induce aggregation and differentiation in THP-1 cells than the wild type strain, as determined by carboxyfluorescein diacetate succinimidyl ester (CFSE) labeling of the cells, followed by counting of cells attached to the culture dish using image analysis. Finally, MS5 was observed to induce less proinflammatory cytokine TNF-α by THP-1 cells than wild type G37 strain. These results indicate that MsrA affects the virulence properties of M. genitalium by modulating its interaction with host cells

Using video-reflexive ethnography and simulation-based education to explore patient management and error recognition by pre-registration physiotherapists

Background: Upon graduation, physiotherapists are required to manage clinical caseloads involving deteriorating patients with complex conditions. In particular, emergency on-call physiotherapists are required to provide respiratory/ cardio-respiratory/cardiothoracic physiotherapy, out of normal working hours, without senior physiotherapist support. To optimise patient safety, physiotherapists are required to function within complex clinical environments, drawing on their knowledge and skills (technical and non-technical), maintaining situational awareness and filtering unwanted stimuli from the environment. Prior to this study, the extent to which final-year physiotherapy students were able to manage an acutely deteriorating patient in a simulation context and recognise errors in their own practice was unknown. Methods: A focused video-reflexive ethnography study was undertaken to explore behaviours, error recognition abilities and personal experiences of 21 final-year (pre-registration) physiotherapy students from one higher education institution. Social constructivism and complexity theoretical perspectives informed the methodological design of the study. Video and thematic analysis of 12 simulation scenarios and video-reflexive interviews were undertaken. Results: Participants worked within the professional standards of physiotherapy practice expected of entry-level physiotherapists. Students reflected appropriate responses to their own and others’ actions in the midst of uncertainty of the situation and physiological disturbances that unfolded during the scenario. However, they demonstrated a limited independent ability to recognise errors. Latent errors, active failures, error-producing factors and a series of effective defences to mitigate errors were identified through video analysis. Perceived influential factors affecting student performance within the scenario were attributed to aspects of academic and placement learning and the completion of a voluntary acute illness management course. The perceived value of the simulation scenario was enhanced by the opportunity to review their own simulation video with realism afforded by the scenario design. Conclusions: This study presents a unique insight into the experiences, skills, attitudes, behaviours and error recognition abilities of pre-registration physiotherapy students managing an acutely deteriorating patient in a simulation context. Findings of this research provide valuable insights to inform future research regarding physiotherapy practice, integration of educational methods to augment patient safety awareness and participant-led innovations in safe healthcare practice. Keywords: Error recognition, Deterioration, Physiotherapy, Simulation-based education, Video-reflexive ethnograph

3D ultrasound biomicroscopy for assessment of cartilage repair tissue: volumetric characterisation and correlation to established classification systems

Objective and sensitive assessment of cartilage repair outcomes lacks suitable methods. This study investigated the feasibility of 3D ultrasound biomicroscopy (UBM) to quantify cartilage repair outcomes volumetrically and their correlation with established classification systems. 32 sheep underwent bilateral treatment of a focal cartilage defect. One or two years post-operatively the repair outcomes were assessed and scored macroscopically (Outerbridge, ICRS-CRA), by magnetic resonance imaging (MRI, MOCART), and histopathology (O'Driscoll, ICRS-I and ICRS-II). The UBM data were acquired after MRI and used to reconstruct the shape of the initial cartilage layer, enabling the estimation of the initial cartilage thickness and defect volume as well as volumetric parameters for defect filling, repair tissue, bone loss and bone overgrowth. The quantification of the repair outcomes revealed high variations in the initial thickness of the cartilage layer, indicating the need for cartilage thickness estimation before creating a defect. Furthermore, highly significant correlations were found for the defect filling estimated from UBM to the established classification systems. 3D visualisation of the repair regions showed highly variable morphology within single samples. This raises the question as to whether macroscopic, MRI and histopathological scoring provide sufficient reliability. The biases of the individual methods will be discussed within this context. UBM was shown to be a feasible tool to evaluate cartilage repair outcomes, whereby the most important objective parameter is the defect filling. Translation of UBM into arthroscopic or transcutaneous ultrasound examinations would allow non-destructive and objective follow-up of individual patients and better comparison between the results of clinical trials