Methods and processes for development of a CONSORT extension for reporting pilot randomized controlled trials.

BACKGROUND: Feasibility and pilot studies are essential components of planning or preparing for a larger randomized controlled trial (RCT). They are intended to provide useful information about the feasibility of the main RCT-with the goal of reducing uncertainty and thereby increasing the chance of successfully conducting the main RCT. However, research has shown that there are serious inadequacies in the reporting of pilot and feasibility studies. Reasons for this include a lack of explicit publication policies for pilot and feasibility studies in many journals, unclear definitions of what constitutes a pilot or feasibility RCT/study, and a lack of clarity in the objectives and methodological focus. All these suggest that there is an urgent need for new guidelines for reporting pilot and feasibility studies. OBJECTIVES: The aim of this paper is to describe the methods and processes in our development of an extension to the Consolidated Standards of Reporting Trials (CONSORT) Statement for reporting pilot and feasibility RCTs, that are executed in preparation for a future, more definitive RCT. METHODS/DESIGN: There were five overlapping parts to the project: (i) the project launch-which involved establishing a working group and conducting a review of the literature; (ii) stakeholder engagement-which entailed consultation with the CONSORT group, journal editors and publishers, the clinical trials community, and funders; (iii) a Delphi process-used to assess the agreement of experts on initial definitions and to generate a reporting checklist for pilot RCTs, based on the 2010 CONSORT statement extension applicable to reporting pilot studies; (iv) a consensus meeting-to discuss, add, remove, or modify checklist items, with input from experts in the field; and (v) write-up and implementation-which included a guideline document which gives an explanation and elaboration (E&E) and which will provide advice for each item, together with examples of good reporting practice. This final part also included a plan for dissemination and publication of the guideline. CONCLUSIONS: We anticipate that implementation of our guideline will improve the reporting completeness, transparency, and quality of pilot RCTs, and hence benefit several constituencies, including authors of journal manuscripts, funding agencies, educators, researchers, and end-users

Confirmed SARS-CoV-2 infection in Scottish neonates 2020-2022: a national, population-based cohort study

Objectives: To examine neonates in Scotland aged 0–27 days with SARS-CoV-2 infection confirmed by viral testing; the risk of confirmed neonatal infection by maternal and infant characteristics; and hospital admissions associated with confirmed neonatal infections. Design: Population-based cohort study. Setting and population: All live births in Scotland, 1 March 2020–31 January 2022. Results: There were 141 neonates with confirmed SARS-CoV-2 infection over the study period, giving an overall infection rate of 153 per 100 000 live births (141/92 009, 0.15%). Among infants born to women with confirmed infection around the time of birth, the confirmed neonatal infection rate was 1812 per 100 000 live births (15/828, 1.8%). Two-thirds (92/141, 65.2%) of neonates with confirmed infection had an associated admission to neonatal or (more commonly) paediatric care. Six of these babies (6/92, 6.5%) were admitted to neonatal and/or paediatric intensive care; however, none of these six had COVID-19 recorded as their main diagnosis. There were no neonatal deaths among babies with confirmed infection. Implications and relevance: Confirmed neonatal SARS-CoV-2 infection was uncommon over the first 23 months of the pandemic in Scotland. Secular trends in the neonatal confirmed infection rate broadly followed those seen in the general population, although at a lower level. Maternal confirmed infection at birth was associated with an increased risk of neonatal confirmed infection. Two-thirds of neonates with confirmed infection had an associated admission to hospital, with resulting implications for the baby, family and services, although their outcomes were generally good. Ascertainment of confirmed infection depends on the extent of testing, and this is likely to have varied over time and between groups: the extent of unconfirmed infection is inevitably unknown

Benefits of Stimulus Congruency for Multisensory Facilitation of Visual Learning

Background. Studies of perceptual learning have largely focused on unisensory stimuli. However, multisensory interactions are ubiquitous in perception, even at early processing stages, and thus can potentially play a role in learning. Here, we examine the effect of auditory-visual congruency on visual learning. Methodology/Principle Findings. Subjects were trained over five days on a visual motion coherence detection task with either congruent audiovisual, or incongruent audiovisual stimuli. Comparing performance on visual-only trials, we find that training with congruent audiovisual stimuli produces significantly better learning than training with incongruent audiovisual stimuli or with only visual stimuli. Conclusions/ Significance. This advantage from stimulus congruency during training suggests that the benefits of multisensory training may result from audiovisual interactions at a perceptual rather than cognitive level

Feasibility and acceptance of electronic quality of life assessment in general practice: an implementation study

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Cross-Modal Prediction in Speech Perception

Speech perception often benefits from vision of the speaker's lip movements when they are available. One potential mechanism underlying this reported gain in perception arising from audio-visual integration is on-line prediction. In this study we address whether the preceding speech context in a single modality can improve audiovisual processing and whether this improvement is based on on-line information-transfer across sensory modalities. In the experiments presented here, during each trial, a speech fragment (context) presented in a single sensory modality (voice or lips) was immediately continued by an audiovisual target fragment. Participants made speeded judgments about whether voice and lips were in agreement in the target fragment. The leading single sensory context and the subsequent audiovisual target fragment could be continuous in either one modality only, both (context in one modality continues into both modalities in the target fragment) or neither modalities (i.e., discontinuous). The results showed quicker audiovisual matching responses when context was continuous with the target within either the visual or auditory channel (Experiment 1). Critically, prior visual context also provided an advantage when it was cross-modally continuous (with the auditory channel in the target), but auditory to visual cross-modal continuity resulted in no advantage (Experiment 2). This suggests that visual speech information can provide an on-line benefit for processing the upcoming auditory input through the use of predictive mechanisms. We hypothesize that this benefit is expressed at an early level of speech analysis

Cost-minimization analysis in a blind randomized trial on small-incision versus laparoscopic cholecystectomy from a societal perspective: sick leave outweighs efforts in hospital savings

Background: After its introduction, laparoscopic cholecystectomy rapidly expanded around the world and was accepted the procedure of choice by consensus. However, analysis of evidence shows no difference regarding primary outcome measures between laparoscopic and small-incision cholecystectomy. In absence of clear clinical benefit it may be interesting to focus on the resource use associated with the available techniques, a secondary outcome measure. This study focuses on a difference in costs between laparoscopic and small-incision cholecystectomy from a societal perspective with emphasis on internal validity and generalisability Methods: A blinded randomized single-centre trial was conducted in a general teaching hospital in The Netherlands. Patients with reasonable to good health diagnosed with symptomatic cholecystolithiasis scheduled for cholecystectomy were included. Patients were randomized between laparoscopic and small-incision cholecystectomy. Total costs were analyzed from a societal perspective. Results: Operative costs were higher in the laparoscopic group using reusable laparoscopic instruments (difference 203 euro; 95% confidence interval 147 to 259 euro). There were no significant differences in the other direct cost categories (outpatient clinic and admittance related costs), indirect costs, and total costs. More than 60% of costs in employed patients were caused by sick leave. Conclusion: Based on differences in costs, small-incision cholecystectomy seems to be the preferred operative technique over the laparoscopic technique both from a hospital and societal cost perspective. Sick leave associated with convalescence after cholecystectomy in employed patients results in considerable costs to society

Top-down and bottom-up modulation in processing bimodal face/voice stimuli

<p>Abstract</p> <p>Background</p> <p>Processing of multimodal information is a critical capacity of the human brain, with classic studies showing bimodal stimulation either facilitating or interfering in perceptual processing. Comparing activity to congruent and incongruent bimodal stimuli can reveal sensory dominance in particular cognitive tasks.</p> <p>Results</p> <p>We investigated audiovisual interactions driven by stimulus properties (bottom-up influences) or by task (top-down influences) on congruent and incongruent simultaneously presented faces and voices while ERPs were recorded. Subjects performed gender categorisation, directing attention either to faces or to voices and also judged whether the face/voice stimuli were congruent in terms of gender. Behaviourally, the unattended modality affected processing in the attended modality: the disruption was greater for attended voices. ERPs revealed top-down modulations of early brain processing (30-100 ms) over unisensory cortices. No effects were found on N170 or VPP, but from 180-230 ms larger right frontal activity was seen for incongruent than congruent stimuli.</p> <p>Conclusions</p> <p>Our data demonstrates that in a gender categorisation task the processing of faces dominate over the processing of voices. Brain activity showed different modulation by top-down and bottom-up information. Top-down influences modulated early brain activity whereas bottom-up interactions occurred relatively late.</p

The Impact of Spatial Incongruence on an Auditory-Visual Illusion

The sound-induced flash illusion is an auditory-visual illusion--when a single flash is presented along with two or more beeps, observers report seeing two or more flashes. Previous research has shown that the illusion gradually disappears as the temporal delay between auditory and visual stimuli increases, suggesting that the illusion is consistent with existing temporal rules of neural activation in the superior colliculus to multisensory stimuli. However little is known about the effect of spatial incongruence, and whether the illusion follows the corresponding spatial rule. If the illusion occurs less strongly when auditory and visual stimuli are separated, then integrative processes supporting the illusion must be strongly dependant on spatial congruence. In this case, the illusion would be consistent with both the spatial and temporal rules describing response properties of multisensory neurons in the superior colliculus.status: publishe

The M/GP5 Glycoprotein Complex of Porcine Reproductive and Respiratory Syndrome Virus Binds the Sialoadhesin Receptor in a Sialic Acid-Dependent Manner

The porcine reproductive and respiratory syndrome virus (PRRSV) is a major threat to swine health worldwide and is considered the most significant viral disease in the swine industry today. In past years, studies on the entry of the virus into its host cell have led to the identification of a number of essential virus receptors and entry mediators. However, viral counterparts for these molecules have remained elusive and this has made rational development of new generation vaccines impossible. The main objective of this study was to identify the viral counterparts for sialoadhesin, a crucial PRRSV receptor on macrophages. For this purpose, a soluble form of sialoadhesin was constructed and validated. The soluble sialoadhesin could bind PRRSV in a sialic acid-dependent manner and could neutralize PRRSV infection of macrophages, thereby confirming the role of sialoadhesin as an essential PRRSV receptor on macrophages. Although sialic acids are present on the GP3, GP4 and GP5 envelope glycoproteins, only the M/GP5 glycoprotein complex of PRRSV was identified as a ligand for sialoadhesin. The interaction was found to be dependent on the sialic acid binding capacity of sialoadhesin and on the presence of sialic acids on GP5. These findings not only contribute to a better understanding of PRRSV biology, but the knowledge and tools generated in this study also hold the key to the development of a new generation of PRRSV vaccines

Application of prolonged microdialysis sampling in carboplatin-treated cancer patients

Purpose: To better understand the mechanisms underlying (in)sensitivity of tumors to anticancer drugs, assessing intra-tumor drug pharmacokinetics (PKs) could be important. We explored the feasibility of microdialysis in tumor tissue for multiple days in a clinical setting, using carboplatin as model drug. Methods: Plasma and microdialysate samples from tumor and adipose normal tissues were collected up to 47 h after dosing in eight carboplatin-treated patients with an accessible (sub)cutaneous tumor. Results: Pharmacokinetics were evaluable in tumor tissue in 6/8 patients and in adipose normal tissue in 3/8 patients. Concentration-time curves of unbound platinum in both the tissues followed the pattern of the curves in plasma, with exposure ratios of tissue versus plasma ranging from 0.64 to 1.46. Conclusions: Microdialysis can be successfully employed in ambulant patients for multiple days, which enables one to study tissue PK of anticancer drugs in normal and malignant tissues in more detail