The dark side of coproduction: do the costs outweigh the benefits for health research?

BACKGROUND: Coproduction, a collaborative model of research that includes stakeholders in the research process, has been widely advocated as a means of facilitating research use and impact. We summarise the arguments in favour of coproduction, the different approaches to establishing coproductive work and their costs, and offer some advice as to when and how to consider coproduction. DEBATE: Despite the multiplicity of reasons and incentives to coproduce, there is little consensus about what coproduction is, why we do it, what effects we are trying to achieve, or the best coproduction techniques to achieve policy, practice or population health change. Furthermore, coproduction is not free risk or cost. Tensions can arise throughout coproduced research processes between the different interests involved. We identify five types of costs associated with coproduced research affecting the research itself, the research process, professional risks for researchers and stakeholders, personal risks for researchers and stakeholders, and risks to the wider cause of scholarship. Yet, these costs are rarely referred to in the literature, which generally calls for greater inclusion of stakeholders in research processes, focusing exclusively on potential positives. There are few tools to help researchers avoid or alleviate risks to themselves and their stakeholders. CONCLUSIONS: First, we recommend identifying specific motivations for coproduction and clarifying exactly which outcomes are required for whom for any particular piece of research. Second, we suggest selecting strategies specifically designed to enable these outcomes to be achieved, and properly evaluated. Finally, in the absence of strong evidence about the impact and process of coproduction, we advise a cautious approach to coproduction. This would involve conscious and reflective research practice, evaluation of how coproduced research practices change outcomes, and exploration of the costs and benefits of coproduction. We propose some preliminary advice to help decide when coproduction is likely to be more or less useful

New roles for the major human 3'-5' exonuclease TREX1 in human disease

Aicardi-Goutières syndrome (AGS), Systemic Lupus Erythematosus (SLE), Familial Chilblain Lupus (FCL) and Retinal Vasculopathy and Cerebral Leukodystrophy (RVCL) {a new term encompassing three independently described conditions with a common etiology—Cerebroretinal Vasculopathy (CRV), Hereditary Vascular Retinopathy (HVR) and Hereditary Endotheliopathy, Retinopathy and Nephropathy (HERNS)}—have previously been regarded as distinct entities. However, recent genetic analysis has demonstrated that each of these diseases maps to chromosome 3p21 and can be caused by mutations in TREX1, the major human 3'–5' exonuclease. In this review, we discuss the putative functions of TREX1 in relationship to the clinical, genetic and functional characteristics of each of these conditions

Prehospital Management of Pediatric Behavioral Health Emergencies: A Scoping Review

Pediatric behavioral health emergencies (BHE) are increasing in prevalence, yet there are no evidence-based guidelines or protocols for prehospital management. The primary objective of this scoping review is to identify prehospital-specific pediatric BHE research and publicly available emergency medical services (EMS) protocols for pediatric BHE. Secondary objectives include identifying the next priorities for research and EMS protocol considerations for children with neurodevelopmental conditions. This is a scoping review comprised of a research literature search for publications from 2012-2022 and an internet search for publicly available EMS protocols from the United States. Included publications contain data on the epidemiology of pediatric BHE or describe prehospital management of pediatric BHE. EMS protocols were included if they had advisements specific to pediatric BHE. A total of 50 research publications and EMS protocols from 43 states were screened. Seven publications and four protocols were included in this study. Research studies indicated an increase in pediatric BHE over the last decade, but few papers discuss current prehospital management (n=4). Two EMS protocols were specific to pediatric BHE or pediatric agitation, and the other two EMS protocols focused on adult populations with integrated pediatric recommendations. All four EMS protocols encouraged nonpharmaceutical interventions prior to the use of pharmacologic restraints. Although there is a substantial rise in pediatric BHE, there is sparse research data and clinical EMS protocols to support best practices for prehospital pediatric BHE management. This scoping review identifies important future research aims to inform best practices for the prehospital management of pediatric BHE

Examination of Disparities in Prehospital Encounters for Pediatric Asthma Exacerbations

INTRODUCTION: There are disparities in multiple aspects of pediatric asthma care; however, prehospital care disparities are largely undescribed. This study\u27s objective was to examine racial and geographic disparities in emergency medical services (EMS) medication administration to pediatric patients with asthma. METHODS: This is a substudy of the Early Administration of Steroids in the Ambulance Setting: An Observational Design Trial, which includes data from pediatric asthma patients ages 2-18 years. We examined rates of EMS administration of systemic corticosteroids and inhaled bronchodilators by patient race. We geocoded EMS scene addresses, characterized the locations\u27 neighborhood-based conditions and resources relevant to children using the Child Opportunity Index (COI) 2.0, and analyzed associations between EMS scene address COI with medications administered by EMS. RESULTS: A total of 765 patients had available racial data and 825 had scene addresses that were geocoded to a COI. EMS administered at least 1 bronchodilator to 84.7% ( CONCLUSIONS: There were no racial differences in EMS administration of medications to pediatric asthma patients. However, there were significantly higher rates of EMS bronchodilator administration for encounters in low/very low COIs. That latter finding may reflect inequities in asthma exacerbation severity for patients living in disadvantaged areas

Cerenkov Luminescence Imaging and Flexible Autoradiography for specimen margin assessment during breast-conserving cancer surgery

Background Among women with breast cancer who undergo breast-conserving surgery (BCS), 20-25% require further surgery due to close or involved margins. Improved techniques are needed to assess resection margins.PurposeThe study aims were to assess the feasibility of the combined techniques of Cerenkov Luminescence Imaging - Flexible AutoRadiography (CLI-FAR) to assess excision specimen margins in women undergoing BCS and to determine the diagnostic performance of intraoperative CLI-FAR imaging with postoperative histopathology as the reference standard..Materials and Methods Women undergoing BCS were recruited prospectively at a single centre over thirteen months. Patients were injected with 250MBq +/- 10MBq of 18F-fluorodeoxyglucose (18F-FDG), 145 minutes before surgery and the excised specimens were imaged intraoperatively. The surgically excised tumour was initially imaged using conventional x-ray, and margins suspected to be involved by tumor were then imaged using CLI-FAR. CLI-FAR imaging was performed using the LightPath system® (Lightpoint®), an in vitro diagnostic device designed to identify and locate positron-emitting radionuclides. Any suspicious margin underwent an immediate re-excision in the form of cavity shavings. Sensitivity, specificity, positive and negative predictive value whilst considering histopathological assessment as the golden standard were used to assess the performance of CLI-FAR.ResultsIn all, 54 specimens were imaged in 52 patients with a total of 104 margins reviewed using CLI-FAR. The results showed a specificity of 97.8% (89/91, 95% CI: 95.0%, 100.6%), sensitivity of 76.9% (10/13, 95% CI: 68.3%, 85.0%), PPV of 83.3% (10/12, 95% CI: 76.2%, 90.5%) and NPV of 96.7% (89/92, 95% CI: 93.3%, 100.2%). In all, 8 patients had 10 positive margins on CLI-FAR imaging and were treated accordingly. CLI-FAR imaging reduced the re-excision rate by (17.3/25) 69%. ConclusionCLI-FAR imaging is a promising technique for intraoperative margin assessment in women undergoing BCS for invasive breast cancer. <br/

High-Resolution Genotyping of the Endemic Salmonella Typhi Population during a Vi (Typhoid) Vaccination Trial in Kolkata

Typhoid fever is caused by the bacterium Salmonella enterica serovar Typhi (S. Typhi) and is a major health problem especially in developing countries. Vaccines against typhoid are commonly used by travelers but less so by residents of endemic areas. We used single nucleotide polymorphism (SNP) typing to investigate the population structure of 372 S. Typhi bacteria isolated from typhoid patients during a typhoid disease burden study and Vi anti-typhoid vaccine trial in Kolkata, India. Approximately sixty thousand people were enrolled for fever surveillance for 19 months prior to, and 24 months following, vaccination of one third of the study population against typhoid (May 2003–December 2006, vaccinations given December 2004). We detected a diverse population of S. Typhi, including 21 different genetic forms (haplotypes) of the bacteria. The most common (69%) were of a haplogroup known as H58, which included all multidrug resistant isolates (bacteria resistant to the antibiotics chloramphenicol, ampicillin and co-trimoxazole). Resistance to quinolones, a class of antibiotics commonly used to treat typhoid fever, was particularly high among a subgroup of H58 (H58-G). Vi vaccination did not obviously impact on the haplotype distribution of the S. Typhi circulating during the study period

A study protocol for applying the co-creating knowledge translation framework to a population health study

BACKGROUND: Population health research can generate significant outcomes for communities, while Knowledge Translation (KT) aims to expressly maximize the outcomes of knowledge producing activity. Yet the two approaches are seldom explicitly combined as part of the research process. A population health study in Port Lincoln, South Australia offered the opportunity to develop and apply the co-KT Framework to the entire research process. This is a new framework to facilitate knowledge formation collaboratively between researchers and communities throughout a research to intervention implementation process. DESIGN: This study employs a five step framework (the co-KT Framework) that is formulated from engaged scholarship and action research principles. By following the steps a knowledge base will be cumulatively co-created with the study population that is useful to the research aims. Step 1 is the initiating of contact between the researcher and the study contexts, and the framing of the research issue, achieved through a systematic data collection tool. Step 2 refines the research issue and the knowledge base by building into it context specific details and conducting knowledge exchange events. Step 3 involves interpreting and analysing the knowledge base, and integrating evidence to inform intervention development. In Step 4 the intervention will be piloted and evaluated. Step 5 is the completion of the research process where outcomes for improvement will be instituted as regular practice with the facilitation of the community. In summary, the model uses an iterative knowledge construction mechanism that is complemented by external evidence to design interventions to address health priorities within the community. DISCUSSION: This is a systematic approach that operationalises the translational cycle using a framework for KT practice. It begins with the local context as its foundation for knowledge creation and ends with the development of contextually applicable interventions. It will be of interest to those involved in KT research, participatory action research, population health research and health care systems studies. The co-KT Framework is a method for embedding the principles of KT into all stages of a community-based research process, in which research questions are framed by emergent data from each previous stage.Kathryn Powell, Alison Kitson, Elizabeth Hoon, Jonathan Newbury, Anne Wilson and Justin Beilb

The structure of the tetrasialoganglioside from human brain

Autosomal dominant retinal vasculopathy with cerebral leukodystrophy is a microvascular endotheliopathy with middle- age onset. In nine families, we identified heterozygous C- terminal frameshift mutations in TREX1, which encodes a 3'-5' exonuclease. These truncated proteins retain exonuclease activity but lose normal perinuclear localization. These data have implications for the maintenance of vascular integrity in the degenerative cerebral microangiopathies leading to stroke and dementias