Control of hyperglycaemia in paediatric intensive care (CHiP): study protocol.

BACKGROUND: There is increasing evidence that tight blood glucose (BG) control improves outcomes in critically ill adults. Children show similar hyperglycaemic responses to surgery or critical illness. However it is not known whether tight control will benefit children given maturational differences and different disease spectrum. METHODS/DESIGN: The study is an randomised open trial with two parallel groups to assess whether, for children undergoing intensive care in the UK aged <or= 16 years who are ventilated, have an arterial line in-situ and are receiving vasoactive support following injury, major surgery or in association with critical illness in whom it is anticipated such treatment will be required to continue for at least 12 hours, tight control will increase the numbers of days alive and free of mechanical ventilation at 30 days, and lead to improvement in a range of complications associated with intensive care treatment and be cost effective. Children in the tight control group will receive insulin by intravenous infusion titrated to maintain BG between 4 and 7.0 mmol/l. Children in the control group will be treated according to a standard current approach to BG management. Children will be followed up to determine vital status and healthcare resources usage between discharge and 12 months post-randomisation. Information regarding overall health status, global neurological outcome, attention and behavioural status will be sought from a subgroup with traumatic brain injury (TBI). A difference of 2 days in the number of ventilator-free days within the first 30 days post-randomisation is considered clinically important. Conservatively assuming a standard deviation of a week across both trial arms, a type I error of 1% (2-sided test), and allowing for non-compliance, a total sample size of 1000 patients would have 90% power to detect this difference. To detect effect differences between cardiac and non-cardiac patients, a target sample size of 1500 is required. An economic evaluation will assess whether the costs of achieving tight BG control are justified by subsequent reductions in hospitalisation costs. DISCUSSION: The relevance of tight glycaemic control in this population needs to be assessed formally before being accepted into standard practice

Molecular basis of structure and function of the microvillus membrane of intestinal epithelial cells

Correlation of molecular structure with biochemical functions of the plasma membrane of the microvilli of intestinal epithelial cells has been investigated by biochemical and electron microscopic procedures. Repeating particles, measuring approximately 60 &#197;in diameter, were found on the surface of the microvilli membrane which had been isolated or purified from rabbit intestinal epithelial cells and negatively stained with phosphotungstic acid. These particles were proved to be inherent components of the microvillus membrane, attached to the outer surface of its trilaminar structure, and were designated as the elementary particles of the microvilli of intestinal epithelial cells. Biochemical and electron microscopic identification of these elementary particles has been carried out by isolation of the elementary particles with papain from the isolated microvillus membrane, followed by purification of the particles by chromatographies on DEAE-cellulose and Sephadex columns. The partially purified particles containing invertase and leucine aminopeptidase are similar in size and structure to those of the elementary particles in the microvillus membrane. Evidence indicates that each of the elementary particles coincide with or include an enzyme molecule such as disaccharidase or peptidase, which carry out the terminal hydrolytic digestion of carbohydrates and proteins, respectively, on the surface of the microvillus membrane. Magnesium ionactivated adenosine triphosphatase and alkaline phosphatase cannot be solubilized with papain but remains in the smooth-surface membrane after the elementary particles have been removed. Cytochemical electron microscopic observation revealed that the active site of magnesium ion-activated adenosine triphosphatase is localized predominantly in the inner surface of the trilaminar structure of the microvillus membrane.</p

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

National Coordinating Centre for Research Methodology; Medical Research Council, UK Department of Health; Chief Scientist OfficeNot peer reviewedPublisher PD

COVID-19 restrictions increased perceptions of social isolation for older people discharged home after rehabilitation: A mixed-methods study

ObjectiveTo explore older persons perceptions of the impact of COVID-19 restrictions on participating in community activities after discharge from inpatient rehabilitation. MethodsMixed-methods study design. Participants were older adults who were discharged home following inpatient rehabilitation. Interviews were conducted with 70 participants, with a variety of diagnoses, 8 weeks after discharge from inpatient rehabilitation. Frequency of participation in domestic, leisure/work and outdoor activities was measured using the Frenchay Activities Index (FAI). Qualitative analysis was completed using qualitative content analysis and triangulated with FAI scores. ResultsIn all, 70 older adults (mean age: 73.0 years, SD: 9.9; 59% female) participated in the study. The overarching theme was that participants felt socially isolated following discharge from rehabilitation, with COVID-19 restrictions increasing perceptions of social isolation and complicating their return to participating in community activities. The four categories informing the overarching theme were as follows: physical health was the primary limitation to participation in community activities; COVID-19 restrictions limited participation in social activities and centre-based physical rehabilitation; low uptake of videoconferencing to facilitate socialisation and rehabilitation; and reduced incidental physical activity. Mean FAI score was 21.2 (SD 7.8), indicating that participants were moderately active. Participants most commonly performed domestic activities (mean: 10.0, SD: 4.1), followed by outdoor activities (mean: 6.6, SD: 3.5) and leisure/work activities (mean: 4.5, SD: 2.5). ConclusionsCOVID-19 restrictions exacerbated perceptions of social isolation and the limitations already imposed by poor physical health after discharge from rehabilitation. The findings highlight the need for rehabilitation that addresses the psychological and social dimensions of community reintegration

Loud calls in male crested macaques, Macaca nigra: a signal of dominance in a tolerant species

Compared to other mammals, sexual signals occur particularly often within the primate order. Nevertheless, little is known so far about the pressures under which these signals evolved. We studied loud calls in wild crested macaques to examine whether these are used as a sexual signal, particularly as a signal of dominance, in this species. Since the structure of loud calls may be influenced by the context in which they are uttered, we tested for contextual differences in call structure. Only males uttered loud calls and analysis of 194 loud calls given by 15 males showed that call structure encoded the caller's identity as well as his social status. Dominance rank was also reflected in the frequency with which males called with alpha males calling most often. The structure of loud calls, however, was not influenced by context. Our findings consolidate the assumption that, in crested macaques, loud calls serve as a signal of dominance, most probably used to prevent contests between males for mates. We herewith provide the first direct evidence for a signal of dominance in a tolerant primate species and discuss why this signal occurs in only one sex

A Multi-Faceted Strategy for Evidence Translation Reduces Healthcare Waiting Time: A Mixed Methods Study Using the RE-AIM Framework

Background: Waiting lists are often thought to be inevitable in healthcare, but strategies that address patient flow by reducing complexity, combining triage with initial management, and/or actively managing the relationship between supply and demand can work. One such model, Specific Timely Appointments for Triage (STAT), brings these elements together and has been found in multiple trials to reduce waiting times by 30–40%. The next challenge is to translate this knowledge into practice.Method: A multi-faceted knowledge translation strategy, including workshops, resources, dissemination of research findings and a community of practice (CoP) was implemented. A mixed methods evaluation of the strategy was conducted based on the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework, drawing on an internal database and a survey of workshop and CoP participants.Results: Demonstrating reach, at July 2020 an internal database held details of 342 clinicians and managers from 64 health services who had participated in the workshop program (n = 308) and/or elected to join an online CoP (n = 227). 40 of 69 (58%) respondents to a survey of this population reported they had adopted the model, with some providing data demonstrating that the STAT model had been efficacious in reducing waiting time. Perceived barriers to implementation included an overwhelming existing waiting list, an imbalance between supply and demand and lack of resources.Conclusion: There is high quality evidence from trials that STAT reduces waiting time. Using the RE-AIM framework, this evaluation of a translation strategy demonstrates uptake of evidence to reduce waiting time in health services.</jats:p

Volunteer Bias in Recruitment, Retention, and Blood Sample Donation in a Randomised Controlled Trial Involving Mothers and Their Children at Six Months and Two Years: A Longitudinal Analysis

BACKGROUND: The vulnerability of clinical trials to volunteer bias is under-reported. Volunteer bias is systematic error due to differences between those who choose to participate in studies and those who do not. METHODS AND RESULTS: This paper extends the applications of the concept of volunteer bias by using data from a trial of probiotic supplementation for childhood atopy in healthy dyads to explore 1) differences between a) trial participants and aggregated data from publicly available databases b) participants and non-participants as the trial progressed 2) impact on trial findings of weighting data according to deprivation (Townsend) fifths in the sample and target populations. 1) a) Recruits (n = 454) were less deprived than the target population, matched for area of residence and delivery dates (n = 6,893) (mean [SD] deprivation scores 0.09[4.21] and 0.79[4.08], t = 3.44, df = 511, p<0.001). b) i) As the trial progressed, representation of the most deprived decreased. These participants and smokers were less likely to be retained at 6 months (n = 430[95%]) (OR 0.29,0.13-0.67 and 0.20,0.09-0.46), and 2 years (n = 380[84%]) (aOR 0.68,0.50-0.93 and 0.55,0.28-1.09), and consent to infant blood sample donation (n = 220[48%]) (aOR 0.72,0.57-0.92 and 0.43,0.22-0.83). ii) Mothers interested in probiotics or research or reporting infants' adverse events or rashes were more likely to attend research clinics and consent to skin-prick testing. Mothers participating to help children were more likely to consent to infant blood sample donation. 2) In one trial outcome, atopic eczema, the intervention had a positive effect only in the over-represented, least deprived group. Here, data weighting attenuated risk reduction from 6.9%(0.9-13.1%) to 4.6%(-1.4-+10.5%), and OR from 0.40(0.18-0.91) to 0.56(0.26-1.21). Other findings were unchanged. CONCLUSIONS: Potential for volunteer bias intensified during the trial, due to non-participation of the most deprived and smokers. However, these were not the only predictors of non-participation. Data weighting quantified volunteer bias and modified one important trial outcome. TRIAL REGISTRATION: This randomised, double blind, parallel group, placebo controlled trial is registered with the International Standard Randomised Controlled Trials Register, Number (ISRCTN) 26287422. Registered title: Probiotics in the prevention of atopy in infants and children

Post-mortem assessment in vascular dementia: advances and aspirations.

BACKGROUND: Cerebrovascular lesions are a frequent finding in the elderly population. However, the impact of these lesions on cognitive performance, the prevalence of vascular dementia, and the pathophysiology behind characteristic in vivo imaging findings are subject to controversy. Moreover, there are no standardised criteria for the neuropathological assessment of cerebrovascular disease or its related lesions in human post-mortem brains, and conventional histological techniques may indeed be insufficient to fully reflect the consequences of cerebrovascular disease. DISCUSSION: Here, we review and discuss both the neuropathological and in vivo imaging characteristics of cerebrovascular disease, prevalence rates of vascular dementia, and clinico-pathological correlations. We also discuss the frequent comorbidity of cerebrovascular pathology and Alzheimer's disease pathology, as well as the difficult and controversial issue of clinically differentiating between Alzheimer's disease, vascular dementia and mixed Alzheimer's disease/vascular dementia. Finally, we consider additional novel approaches to complement and enhance current post-mortem assessment of cerebral human tissue. CONCLUSION: Elucidation of the pathophysiology of cerebrovascular disease, clarification of characteristic findings of in vivo imaging and knowledge about the impact of combined pathologies are needed to improve the diagnostic accuracy of clinical diagnoses

Vocal Learning and Auditory-Vocal Feedback

Vocal learning is usually studied in songbirds and humans, species that can form auditory templates by listening to acoustic models and then learn to vocalize to match the template. Most other species are thought to develop vocalizations without auditory feedback. However, auditory input influences the acoustic structure of vocalizations in a broad distribution of birds and mammals. Vocalizations are dened here as sounds generated by forcing air past vibrating membranes. A vocal motor program may generate vocalizations such as crying or laughter, but auditory feedback may be required for matching precise acoustic features of vocalizations. This chapter discriminates limited vocal learning, which uses auditory input to fine-tune acoustic features of an inherited auditory template, from complex vocal learning, in which novel sounds are learned by matching a learned auditory template. Two or three songbird taxa and four or ve mammalian taxa are known for complex vocal learning. A broader range of mammals converge in the acoustic structure of vocalizations when in socially interacting groups, which qualifies as limited vocal learning. All birds and mammals tested use auditory-vocal feedback to adjust their vocalizations to compensate for the effects of noise, and many species modulate their signals as the costs and benefits of communicating vary. This chapter asks whether some auditory-vocal feedback may have provided neural substrates for the evolution of vocal learning. Progress will require more precise definitions of different forms of vocal learning, broad comparative review of their presence and absence, and behavioral and neurobiological investigations into the mechanisms underlying the skills.PostprintPeer reviewe