Stepped wedge cluster randomised trials: a review of the statistical methodology used and available

Background: Previous reviews have focussed on the rationale for employing the stepped wedge design (SWD), the areas of research to which the design has been applied and the general characteristics of the design. However these did not focus on the statistical methods nor addressed the appropriateness of sample size methods used.This was a review of the literature of the statistical methodology used in stepped wedge cluster randomised trials. Methods: Literature Review. The Medline, Embase, PsycINFO, CINAHL and Cochrane databases were searched for methodological guides and RCTs which employed the stepped wedge design. Results: This review identified 102 trials which employed the stepped wedge design compared to 37 from the most recent review by Beard et al. 2015. Forty six trials were cohort designs and 45 % (n = 46) had fewer than 10 clusters. Of the 42 articles discussing the design methodology 10 covered analysis and seven covered sample size. For cohort stepped wedge designs there was only one paper considering analysis and one considering sample size methods. Most trials employed either a GEE or mixed model approach to analysis (n = 77) but only 22 trials (22 %) estimated sample size in a way which accounted for the stepped wedge design that was subsequently used. Conclusions: Many studies which employ the stepped wedge design have few clusters but use methods of analysis which may require more clusters for unbiased and efficient intervention effect estimates. There is the need for research on the minimum number of clusters required for both types of stepped wedge design. Researchers should distinguish in the sample size calculation between cohort and cross sectional stepped wedge desi

Neuropsychological changes in isolated REM sleep behavior disorder: A systematic review and meta-analysis of cross-sectional and longitudinal studies

The aim of this meta-analysis is twofold: (a) to assess cognitive impairments in isolated rapid eye movement (REM) sleep behavior disorder (iRBD) patients compared to healthy controls (HC); (b) to quantitatively estimate the risk of developing a neurodegenerative disease in iRBD patients according to baseline cognitive assessment. To address the first aim, cross-sectional studies including polysomnography-confirmed iRBD patients, HC, and reporting neuropsychological testing were included. To address the second aim, longitudinal studies including polysomnography-confirmed iRBD patients, reporting baseline neuropsychological testing for converted and still isolated patients separately were included. The literature search was conducted based on PRISMA guidelines and the protocol was registered at PROSPERO (CRD42021253427). Cross-sectional and longitudinal studies were searched from PubMed, Web of Science, Scopus, and Embase databases. Publication bias and statistical heterogeneity were assessed respectively by funnel plot asymmetry and using I2. Finally, a random-effect model was performed to pool the included studies. 75 cross-sectional (2,398 HC and 2,460 iRBD patients) and 11 longitudinal (495 iRBD patients) studies were selected. Cross-sectional studies showed that iRBD patients performed significantly worse in cognitive screening scores (random-effects (RE) model = –0.69), memory (RE model = –0.64), and executive function (RE model = –0.50) domains compared to HC. The survival analyses conducted for longitudinal studies revealed that lower executive function and language performance, as well as the presence of mild cognitive impairment (MCI), at baseline were associated with an increased risk of conversion at follow-up. Our study underlines the importance of a comprehensive neuropsychological assessment in the context of iRBD

Combining modifiable risk factors and risk of dementia: a systematic review and meta-analysis

Objective: To systematically review the literature relating to the impact of multiple co-occurring modifiable risk factors for cognitive decline and dementia. Design A systematic review and meta-analysis of the literature relating to the impact of co-occurring key risk factors for incident cognitive decline and dementia. All abstracts and full text were screened independently by two reviewers and each article assessed for bias using a standard checklist. A fixed effects meta-analysis was undertaken. Data sources: Databases Medline, Embase and PsycINFO were searched from 1999 to 2017. Eligibility criteria: For inclusion articles were required to report longitudinal data from participants free of cognitive decline at baseline, with formal assessment of cognitive function or dementia during follow-up, and an aim to examine the impact of additive or clustered comorbid risk factor burden in with two or more core modifiable risk factors. Results: Seventy-nine full-text articles were examined. Twenty-two articles (18 studies) were included reporting data on >40 000 participants. Included studies consistently reported an increased risk associated with greater numbers of intraindividual risk factors or unhealthy behaviours and the opposite for healthy or protective behaviours. A meta-analysis of studies with dementia outcomes resulted in a pooled relative risk for dementia of 1.20 (95% CI 1.04 to 1.39) for one risk factor, 1.65 (95% CI 1.40 to 1.94) for two and 2.21 (95% CI 1.78 to 2.73) for three or more, relative to no risk factors. Limitations include dependence on published results and variations in study outcome, cognitive assessment, length of follow-up and definition of risk factor exposure. Conclusions: The strength of the reported associations, the consistency across studies and the suggestion of a dose response supports a need to keep modifiable risk factor exposure to a minimum and to avoid exposure to additional modifiable risks. Further research is needed to establish whether particular combinations of risk factors confer greater risk than others

Mental healthcare pathways for urban Aboriginal children

Social and emotional wellbeing problems are the chief health issue experienced by young Australians. The small amount of information available suggests that Aboriginal young people experience even higher levels of mental health related harm. Little is known about the pathways that Aboriginal children and adolescents with mental health concerns take when accessing specialized care and to what extent services are available, accessible and culturally appropriate. Further, although GPs are generally considered the gatekeepers to accessing specialist mental health services it is unclear the extent to which they feel confident and equipped to detect, assess and refer children for suspected mental health concerns, particularly in Aboriginal children. This compilation of work sought to understand whether current guidelines and treatment pathways meet the needs of Aboriginal young people presenting with SEWB-related concerns and the extent to which GPs, nurses and Aboriginal Health Workers feel confident and equipped to deal with the mental health concerns they see in the children they deal with in their work at the Aboriginal Community Controlled Health Services (ACCHSs). To gain this understanding two systematic reviews and a qualitative study were conducted.The research reported in this paper is a project of the Australian Primary Health Care Research Institute which is supported by a grant from the Australian Government Department of Health and Ageing under the Primary Health Care Research Evaluation and Development Strategy.This work was supported through grants to SEARCH from the Australian Primary Care Research Institute, the National Health and Medical Research Council of Australia (grant numbers 358457, 512685, 1023998 and 1035378), the NSW Ministry of Health, beyondblue and the Rio Tinto Aboriginal Fund. The CRE and SEARCH are conducted in partnership with the AH&MRC and four Aboriginal medical services across NSW: Awabakal Limited, Riverina Medical and Dental Aboriginal Corporation, Sydney West Aboriginal Health Service, and Tharawal Aboriginal Corporation

Pain shared, pain halved? Cooperation as a coping strategy for innovation barriers

The paper analyses the relationship between the perception of barriers to innovation and the firm’s propensity to cooperate to mitigate their effect. First, we look at whether cooperation with research organizations or private firms is associated with experiencing different types of barriers, for example, financial constraints, lack of human capital or uncertain market demand. Second, we test whether experiencing several types of barriers simultaneously has a super-modular effect on the propensity to cooperate tout court, and the choice of cooperation partner. We find that having to face a single, specific constraint leads to firms ‘sharing the pain’ with cooperation partners—both research organization and other firms. However, the results of a super-modularity test show that having to cope with different barriers is a deterrent to establishing cooperation agreements, especially when firms lack finance, adequate skills and information on technology or markets. The paper adds to the innovation literature by identifying the factors associated with firms’ coping with different barriers by applying a selective cooperation strategy

University–industry linkages and academic engagements: individual behaviours and firms’ barriers. Introduction to the special section

The article introduces the special section on “University–industry linkages and academic engagements: Individual behaviours and firms’ barriers”. We first revisit the latest developments of the literature and policy interest on university–industry research. We then build upon the extant literature and unpack the concept of academic engagement by further exploring the heterogeneity of UI linkages along a set of dimensions and actors involved. These are: (1) Incentives and behaviours of individual academic entrepreneurs; (2) Firms’ barriers to cooperation with public research institutions; (3) Individual behaviours, incentives and organizational bottlenecks in late developing countries. We summarize the individual contributions along these dimensions. There are overlooked individual characteristics that affect the degree of engagement of academics and scholars in cooperating with other organizations, of which gender and the non-academic background of individuals are most crucial. The notion of academic engagement should be enlarged to aspects that go beyond the commercialization or patenting of innovation, but embrace social and economic impact more at large. From the perspective of the firm, barriers to innovation might exert an effect on the likelihood to cooperate with universities and public research institutes, most especially to cope with lack of finance or access to frontier knowledge. We finally propose a research agenda that addresses the challenges ahead

White Paper 4: Challenges In Biomedicine & Health

Publicado en Madrid, 231 p. ; 17 cm.A lesson that we have learned from the pandemia caused by coronavirus is that solutions in health require coordinated actions. Beside this and other emerging and re-emerging infectious diseases, millions of Europeans are suffering a plethora of disorders that are currently acquiring epidemic dimensions, including cancer, rare diseases, pain and food allergies, among others. New tools for prevention, diagnosis and treatment need to be urgently designed and implemented using new holistic and multidisciplinary approaches at three different levels (basic research, translational/clinical and public/social levels) and involving researchers, clinicians, industry and all stakeholders in the health system. The CSIC is excellently positioned to lead and coordinate these challenges in Biomedicine and Health.Peer reviewe

Cycle-finite module categories

We describe the structure of module categories of finite dimensional algebras over an algebraically closed field for which the cycles of nonzero nonisomorphisms between indecomposable finite dimensional modules are finite (do not belong to the infinite Jacobson radical of the module category). Moreover, geometric and homological properties of these module categories are exhibited

Transferring research from a university to the United Kingdom National Health Service : The implications for impact

This is an Open Access article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.The aim of this article is to inform readers of the author's reflections on the experience of transferring universitybased research into the commercial sector, and of the processes and strategies employed when preparing for impact in so doing. Concepts for the transfer are illustrated by the author's reflection on aspects that arose during the birthing and subsequent start-up of a university spin-off, Pathways2Wellbeing, a form of reflection-on-action. This is the vehicle for the adaption required to transfer research into the delivery of a specialised clinic in the United Kingdom National Health Service for people with medically unexplained, persistent, bodily symptoms such as fibromyalgia, chronic fatigue and chronic pain. It is hoped that the article will provide readers with an insight into how knowledge transfer can take place through engagement with stakeholders to create an exchange of knowledges to result in impact on health service policy for service users, despite the challenges, and the enablers that facilitated this process. The reflections on the process of knowledge transfer and the implications for impact are underpinned by relevant theory.Peer reviewedFinal Published versio

Growth‐Factor Free Multicomponent Nanocomposite Hydrogels That Stimulate Bone Formation

Synthetic osteo‐promoting materials that are able to stimulate and accelerate bone formation without the addition of exogenous cells or growth factors represent a major opportunity for an aging world population. A co‐assembling system that integrates hyaluronic acid tyramine (HA‐Tyr), bioactive peptide amphiphiles (GHK‐Cu2+), and Laponite (Lap) to engineer hydrogels with physical, mechanical, and biomolecular signals that can be tuned to enhance bone regeneration is reported. The central design element of the multicomponent hydrogels is the integration of self‐assembly and enzyme‐mediated oxidative coupling to optimize structure and mechanical properties in combination with the incorporation of an osteo‐ and angio‐promoting segments to facilitate signaling. Spectroscopic techniques are used to confirm the interplay of orthogonal covalent and supramolecular interactions in multicomponent hydrogel formation. Furthermore, physico‐mechanical characterizations reveal that the multicomponent hydrogels exhibit improved compressive strength, stress relaxation profile, low swelling ratio, and retarded enzymatic degradation compared to the single component hydrogels. Applicability is validated in vitro using human mesenchymal stem cells and human umbilical vein endothelial cells, and in vivo using a rabbit maxillary sinus floor reconstruction model. Animals treated with the HA‐Tyr‐HA‐Tyr‐GHK‐Cu2+ hydrogels exhibit significantly enhanced bone formation relative to controls including the commercially available Bio‐Oss