Search

Background: People with intellectual disabilities are at much higher risk of preventable deaths compared to the general community. However, studies identifying the cause of death in people with intellectual disability are generally based on one primary cause which is frequently attributed to the person's disability. Therefore, the aim of this study was to identify the most common associated causes that may have contributed to the deaths of Australians with intellectual or learning disabilities, particularly those that may be avoidable. Methods: Linked data that had previously been used to identify underlying causes of deaths were re-analysed to determine other contributing causes of death in Australians with intellectual disabilities aged under 65 years who accessed disability services between July 2013 and June 2018. Findings: Two thousand three hundred and thirty-three deaths occurred among 180,790 people with intellectual disability. Contributing causes of death with the greatest disparities compared to the general community were lung diseases due to external agents (adjusted rate ratio (RR) 70.6 (95% confidence interval [95% CI] 63.7-78.2), influenza and pneumonia (RR 18.3; 95% CI 16.4-20.4), and coronary heart disease (RR 3.3; 95% CI 2.8--3.8). Conclusions: Analysing all contributing causes of death in people with intellectual disabilities can ensure that the higher rates of preventable deaths in people with intellectual disability are identified and addressed earlier in the disability and health sectors.

Recent studies elaborating on the L2 learning experience component of the L2 Motivational Self System (Dörnyei, 2005, 2009), especially through a narrative identity perspective, mark a new direction in L2 motivation research. This paper extends this work by exploring the connection between the L2 learning experience and ideal L2 self components. Emerging from different theoretical origins, these components have proved difficult to reconcile. Especially in an EFL environment such as Japan, where learners may lack well-defined goals for their English learning beyond university entrance, investigations into the role of L2 learning experience in developing ideal L2 selves can offer practical value to both learners and teachers alike. Adopting an L2 narrative identity perspective (Dörnyei & Ryan, 2015), this study portrays the case of a Japanese pre-service elementary school teacher. Qualitative data was collected from her participation in an undergraduate English-through-drama course. Dramaturgical coding analysis revealed two interconnected L2 narrative dynamics related to her overarching ideal L2 self: one professional and one personal. Evidence is discussed for the tracing of these ideal L2 self-conceptualizations back to key episodes in her L2 learning experience. An important functional interrelation is suggested between L2 learning experience and the development of ideal L2 self-guides.

Storylines of Family Medicine is a 12-part series of thematically linked essays with accompanying illustrations that explore the many dimensions of family medicine, as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world. In 'V: ways of thinking-honing the therapeutic self', authors present the following sections: 'Reflective practice in action', 'The doctor as drug-Balint groups', 'Cultivating compassion', 'Towards a humanistic approach to doctoring', 'Intimacy in family medicine', 'The many faces of suffering', 'Transcending suffering' and 'The power of listening to stories.' May readers feel a deeper sense of their own therapeutic agency by reflecting on these essays.

The goal of this project was to determine whether various measures of mammary development differed between gilts and multiparous sows at the end of gestation. During gestation, Yorkshire × Landrace gilts (n = 19) and sows (second and third gestations, n = 17) were fed one daily meal of a conventional corn-based diet, where the amount fed was based on body weight (BW) and backfat thickness (BF) at mating. On day 110 ± 1 of gestation, a jugular blood sample was obtained from all gilts and sows to measure insulin-like growth factor-1 (IGF-1), glucose, free fatty acids, and urea. On that same day, BW and BF were measured and animals were euthanized. Mammary glands from one side of the udder were dissected for compositional analyses. The fifth gland of the contralateral row of mammary glands was sampled for histology and immunohistochemical localization of Ki67. There was less total parenchyma (1,437.4 vs. 2,004.7 ± 127.1 g; P  0.10), while extraparenchymal tissue weight tended to be less in gilts than sows (P = 0.07). All components within the parenchyma differed by parity (P

Abstract Background Australia hosts over 680,000 international students, contributing $47.8 billion to the Australian economy in 2023, and Chinese students rank first among all nationalities. However, despite their considerable numbers, research focusing on their access to healthcare services is scant. This study aimed to explore barriers and supports regarding the utilisation of healthcare services among Chinese international students studying in Australia. Methods Semi-structured interviews were conducted in Chinese between October and December 2023 with 25 Chinese international students (age range, 19–30; female/male, n = 18/7; undergraduate/postgraduate/doctoral, n = 1/18/6) enrolled in three Australian universities to understand the healthcare challenges they encountered and the coping strategies they recommended. These interviews were recorded, and thematic analysis was applied to the interview data. An adapted social-ecological model was used to identify barriers and pragmatic strategies to deal with the challenges at different levels. Results Chinese international students in Australia faced healthcare barriers at different levels. Individual barriers included language and cultural disparities, lack of knowledge about the healthcare system, and reluctance to seek help. Institutional barriers involved high costs, difficulties regarding appointments, and procedures related to the referral system. Policy barriers included insurance coverage and reimbursement issues. The students interviewed for this study proposed individual-level strategies, such as trying various methods to reduce language barriers, seeking information online, and using online resources and consultations. A central appointment platform and multilingual medical service were recommended from students to medical institutions, while medical service guidance and psychological support were suggested to education institutions. Higher-level strategies were also reported, which were mainly pertaining to insurance terms and coverage for overseas students and improving the accessibility of medical information. Conclusions Our study identifies barriers to healthcare access for Chinese international students in Australia, including culture-specific challenges. To mitigate these issues, we recommend self-directed health promotion, targeted support by education institutions, enhanced cross-cultural communication and expanded telemedicine by hospitals, and attention to insurance coverage. Future research should explore optimising these approaches to improve support systems and policy frameworks.

Abstract Background Achondroplasia and mandibulofacial dysostosis with microcephaly (MFDM) are rare monogenic, dominant disorders, caused by gain-of-function fibroblast growth factor receptor 3 (FGFR3) gene variants and loss-of-function elongation factor Tu GTP binding domain-containing 2 (EFTUD2) gene variants, respectively. The coexistence of two distinct Mendelian disorders in a single individual is uncommon and challenges the traditional paradigm of a single genetic disorder explaining a patient’s symptoms, opening new avenues for diagnosis and management. Case Presentation We present a case of a female patient initially diagnosed with achondroplasia due to a maternally inherited pathogenic FGFR3 variant. She was referred to our genetic department due to her unusually small head circumference and short stature, which were both significantly below the expected range for achondroplasia. Additional features included distinctive facial characteristics, significant speech delay, conductive hearing loss, and epilepsy. Given the complexity of her phenotype, she was recruited to the DDD (Deciphering Developmental Disorders) study and the 100,000 Genomes project for further investigation. Subsequent identification of a complex EFTUD2 intragenic rearrangement confirmed an additional diagnosis of mandibulofacial dysostosis with microcephaly (MFDM). Conclusion This report presents the first case of a dual molecular diagnosis of achondroplasia and mandibulofacial dysostosis with microcephaly in the same patient. This case underscores the complexity of genetic diagnoses and the potential for coexistence of multiple genetic syndromes in a single patient. This case expands our understanding of the molecular basis of dual Mendelian disorders and highlights the importance of considering the possibility of dual molecular diagnoses in patients with phenotypic features that are not fully accounted for by their primary diagnosis.

This paper examines the teacher's role in developing students' self-regulated learning (SRL) by examining the beliefs and practices of one primary school teacher. The paper then describes how the teacher applied these in her classroom and how students benefitted. Data were collected via interviews, classroom observations, and informal conversations. Findings suggest that although the teacher held positive beliefs that emphasise behavioural, cognitive, and motivated components of SRL, there was less focus on meta-cognition and strategic actions. Nonetheless, classroom observation data revealed that the teacher actively engaged students in meta-cognition and strategic actions. This implies that the teacher had an implicit understanding of her emphasis on these important components of SRL. It also shows that the teacher's SRL-supportive beliefs and practices were not well-aligned. We believe that a more candid cognisance of meta-cognition and strategic actions may help teachers to directly promote SRL. The study has implications for teacher education and professional development programmes.

The purpose of this study was to examine the effects of cooperative learning (CL) on the academic achievement of student teachers. A mixed-methods sequential explanatory design was implemented in which quantitative data were collected first, followed by qualitative data to clarify the results of the experimental study. Achievement test, interviews, and classroom observations were used for data collection. The results showed that there was a significant difference between the achievement of students in the experimental and control groups in favour of students in the experimental group (p < 0.01). Follow-up interviews and classroom observations indicated that CL creates a suitable learning environment for students, and it strengthens their life skills. Implementing CL in a university classroom provided opportunities for student teachers to learn how to apply CL in their school classrooms. This study was used to firstly, provide insights into student teachers' perceptions of their CL experiences and secondly, to help explain these experiences in more depth.

Abstract Subretinal fibrosis is a major untreatable cause of poor outcomes in neovascular age-related macular degeneration. Mouse models of subretinal fibrosis all possess a degree of invasiveness and tissue damage not typical of fibrosis progression. This project characterises JR5558 mice as a model to study subretinal fibrosis. Fundus and optical coherence tomography (OCT) imaging was used to non-invasively track lesions. Lesion number and area were quantified with ImageJ. Retinal sections, wholemounts and Western blots were used to characterise alterations. Subretinal lesions expand between 4 and 8 weeks and become established in size and location around 12 weeks. Subretinal lesions were confirmed to be fibrotic, including various cell populations involved in fibrosis development. Müller cell processes extended from superficial retina into subretinal lesions at 8 weeks. Western blotting revealed increases in fibronectin (4 wk and 8 wk, p

Abstract Introduction Anti-vascular endothelial growth factor (VEGF) is generally given using pro re nata or “treat-and-extend” (T&E) regimens for neovascular age-related macular degeneration (nAMD). Randomized clinical trials have reported that T&E is superior to Pro re nata (PRN), but results from clinical trials may not always be replicated in clinical practice. Real-world data comparing T&E and PRN regimens for nAMD are limited. The objective of this work was to report 24-month outcomes of PRN versus T&E regimens for ranibizumab and aflibercept to treat nAMD in routine clinical practice. Methods We conducted a retrospective analysis of data from a prospectively designed observational outcomes registry, the Fight Retinal Blindness! Project (FRB). Treatment-naïve eyes starting nAMD treatment with at least three injections using a T&E or PRN regimen were tracked by using the FRB. The primary outcome was the mean change in visual acuity (VA) measured by the number of letters read on a logarithm of the minimum angle of resolution chart at 2 years versus baseline. The secondary outcome was the number of injections at 2 years. Results From January 1, 2015 to January 31, 2019, 3313 eyes from 2948 patients with nAMD were included: 1243 eyes from 1065 patients were classified as PRN and 2070 eyes from 1935 patients started a T&E regimen. At 24 months, patients on the T&E regimen experienced significantly greater mean (95% confidence interval) improvement in VA than those on PRN (+ 4.2 [3.1, 5.2] vs. + 1.3 [0.1, 2.6] letters; p

Abstract Background Health system fragmentation directly contributes to poor health and social outcomes for older adults with multiple chronic conditions and their care partners. Older adults often require support from primary care, multiple specialists, home care, community support services, and other health-care sectors and communication between these providers is unstructured and not standardized. Integrated and interprofessional team-based models of care are a recommended strategy to improve health service delivery to older adults with complex needs. Standardized assessment instruments deployed on digital platforms are considered a necessary component of integrated care. The aim of this study was to develop strategies to leverage an electronic wellness instrument, interRAI Check Up Self Report, to support integrated health and social care for older adults and their care partners in a community in Southern Ontario, Canada. Methods Group concept mapping, a participatory mixed-methods approach, was conducted. Participants included older adults, care partners, and representatives from: home care, community support services, specialized geriatric services, primary care, and health informatics. In a series of virtual meetings, participants generated ideas to implement the interRAI Check Up and rated the relative importance of these ideas. Hierarchical cluster analysis was used to map the ideas into clusters of similar statements. Participants reviewed the map to co-create an action plan. Results Forty-one participants contributed to a cluster map of ten action areas (e.g., engagement of older adults and care partners, instrument’s ease of use, accessibility of the assessment process, person-centred process, training and education for providers, provider coordination, health information integration, health system decision support and quality improvement, and privacy and confidentiality). The health system decision support cluster was rated as the lowest relative importance and the health information integration was cluster rated as the highest relative importance. Conclusions Many person-, provider-, and system-level factors need to be considered when implementing and using an electronic wellness instrument across health- and social-care providers. These factors are highly relevant to the integration of other standardized instruments into interprofessional team care to ensure a compassionate care approach as technology is introduced.

Abstract Background Sharing trial results with participants is a moral imperative, but too often does not happen in appropriate ways. Methods We carried out semi-structured interviews with patients (n = 13) and site staff (n = 11), and surveyed 180 patients and 68 site staff who were part of the Show RESPECT study, which tested approaches to sharing results with participants in the context of the ICON8 ovarian cancer trial (ISRCTN10356387). Qualitative and free-text data were analysed thematically, and findings used to develop the SHOW RESPECT adaptable framework of considerations for planning how to share trial results with participants. This paper presents the framework, with illustrations drawn from the Show RESPECT study. Results Our adaptable ‘SHOW RESPECT’ framework covers (1) Supporting and preparing trial participants to receive results, (2) HOw will the results reach participants?, (3) Who are the trial participants?, (4) REsults—what do they show?, (5) Special considerations, (6) Provider—who will share results with participants?, (7) Expertise and resources, (8) Communication tools and (9) Timing of sharing results. While the data upon which the framework is based come from a single trial, many of our findings are corroborated by findings from other studies in this area, supporting the transferability of our framework to trials beyond the UK ovarian cancer setting in which our work took place. Conclusions This adaptable ‘SHOW RESPECT’ framework can guide researchers as they plan how to share aggregate trial results with participants. While our data are drawn from a single trial context, the findings from Show RESPECT illustrate how approaches to communication in a specific trial can influence patient and staff experiences of feedback of trial results. The framework generated from these findings can be adapted to fit different trial contexts and used by other researchers to plan the sharing of results with their own participants. Trial registration ISRCTN96189403. Registered on February 26, 2019. Show RESPECT was supported by the Medical Research Council (MC_UU_12023/24 and MC_UU_00004/08) and the NIHR CRN.

Abstract Background Retaining participants in randomised controlled trials (RCTs) is challenging and trial teams are often required to use strategies to ensure retention or improve it. Other than monetary incentives, there is no requirement to disclose the use of retention strategies to the participant. Additionally, not all retention strategies are developed at the planning stage, i.e. post-funding during protocol development, but some protocols include strategies for participant retention as retention is considered and planned for early in the trial planning stage. It is yet unknown if these plans are communicated in the corresponding participant information leaflets (PILs). The purpose of our study was to determine if PILs communicate plans to promote participant retention and, if so, are these outlined in the corresponding trial protocol. Methods Ninety-two adult PILs and their 90 corresponding protocols from Clinical Trial Units (CTUs) in the UK were analysed. Directed (deductive) content analysis was used to analyse the participant retention text from the PILs. Data were presented using a narrative summary and frequencies where appropriate. Results Plans to promote participant retention were communicated in 81.5% (n = 75/92) of PILs. Fifty-seven percent (n = 43/75) of PILs communicated plans to use “combined strategies” to promote participant retention. The most common individual retention strategy was telling the participants that data collection for the trial would be scheduled during routine care visits (16%; n = 12/75 PILs). The importance of retention and the impact that missing or deleted data (deleting data collected prior to withdrawal) has on the ability to answer the research question were explained in 6.5% (n = 6/92) and 5.4% (n = 5/92) of PILs respectively. Out of the 59 PILs and 58 matching protocols that both communicated plans to use strategies to promote participant retention, 18.6% (n = 11/59) communicated the same information, the remaining 81.4% (n = 48/59) of PILs either only partially communicated (45.8%; n = 27/59) the same information or did not communicate the same information (35.6%; n = 21/59) as the protocol with regard to the retention strategy(ies). Conclusion Retention strategies are frequently communicated to potential trial participants in PILs; however, the information provided often differs from the content in the corresponding protocol. Participant retention considerations are best done at the planning stage of the trial and we encourage trial teams to be consistent in the communication of these strategies in both the protocol and PIL.

Māori, as substantial stakeholders in the fishery sector, must play a major role in any imagined or proposed transition to a blue economy. This paper provides the results from a project examining how to indigenise the blue economy in Aotearoa New Zealand, outlining the underlying theory and providing results from five case studies. The paper explores three key thematic constraints identified in consultation with the Māori fishing sector, namely: centralisation of power; quota fragmentation; and product commodification. It concludes that there is a need to focus on: redressing the imbalance between iwi and hapū by providing quota for hapū while providing wrap around financial and capacity support, incorporating local experts in decision making, and creating community clusters; overcoming fragmentation through joint ventures and hybrid governance structures and a focus on quota optimisation; and increasing market differentiation through research, innovation, and branding and marketing initiatives.

Cooperative learning (CL) is a teaching and learning pedagogy that has been used widely in school but there is limited information on instructors' perceptions of CL nor observations of how CL is implemented in higher education settings. In this study, we used an interpretative-qualitative approach to investigate the advantages and challenges of embedding CL in instructors' teaching in Iran and Australia. Data were collected through interviews and observations and thematic analysis method was used to analyse the data. Results showed that despite challenges such as the lack of familiarity with CL and how it can be implemented in university curricula, issues associated with assessment, and time constraints, CL created an interactive, pleasant, and safe environment for deep learning in both countries. The findings showed that there were challenges in Iran such as a tendency to use traditional approaches to teaching, insufficient understanding of how to establish teamwork, and a lack of up-to-date teaching resources. In Australia, changing courses, working with external students, catering for individual differences, and building positive relationships were some of the challenges of implementing CL. We believe that these challenges can be overcome if university instructors are prepared to address them.

Background Clinical trials are fundamental to healthcare, however, they also contribute to anthropogenic climate change. Following previous work to develop and test a method and guidance to calculate the carbon footprint of clinical trials, we have now applied the guidance to 10 further UK and international, academically sponsored clinical trials to continue the identification of hotspots and opportunities for lower carbon trial design.Methods 10 collaborating clinical trial units (CTUs) self-identified and a trial was selected from their portfolio to represent a variety of designs, health areas and interventions. Trial activity data was collated by trial teams across 10 modules spanning trial setup through to closure, then multiplied by emission factors provided in the guidance to calculate the carbon footprint. Feedback was collected from trial teams on the process, experience and ease of use of the guidance.Results We footprinted 10 trials: 6 investigational medicinal product trials, 1 nutritional, 1 surgical, 1 health surveillance and one complex intervention trial. Six of these were completed and four ongoing (two in follow-up and two recruiting). The carbon footprint of the 10 trials ranged from 16 to 765 tonnes CO2e. Common hotspots were identified as CTU emissions, trial-specific patient assessments and trial team meetings and travel. Hotspots for specific trial designs were also identified. The time taken to collate activity data and complete carbon calculations ranged from 5 to 60 hours. The draft guidance was updated to include new activities identified from the 10 trials and in response to user feedback.Discussion There are opportunities to reduce the impact of trials across all modules, particularly trial-specific meetings and travel, patient assessments and laboratory practice. A trial’s carbon footprint should be considered at the design stage, but work is required to make this common place.

Abstract Strong Thermal Emission Velocity Enhancement (STEVE), is a captivating optical phenomenon typically observed in the mid‐latitude ionosphere. This paper presents an intriguing observation of a STEVE event at high‐latitudes, approximately 10 degrees poleward of previously documented observations. This event was recorded in Yellowknife, Canada, by a TREx RGB imager and a citizen scientist. Swarm satellites traversed the latitude of the observation, measuring extreme westwards ion drift velocities exceeding 4 km/s. Such velocities are more typically associated with the subauroral region located at mid‐latitudes, rather than at the high‐latitudes reported here. Significantly, this event occurred without a substorm, which differs from previous STEVE observations. While high‐latitude radars detected fast ionospheric equatorward flows, GOES satellite did not record any injections. These observations suggest that the inner magnetosphere is highly inflated. This unique case study raises new questions surrounding subauroral dynamics and the influence of magnetospheric configurations on ionospheric responses.

Background The most common cause of preventable death after injury is haemorrhage. Resuscitative endovascular balloon occlusion of the aorta is intended to provide earlier, temporary haemorrhage control, to facilitate transfer to an operating theatre or interventional radiology suite for definitive haemostasis. Objective To compare standard care plus resuscitative endovascular balloon occlusion of the aorta versus standard care in patients with exsanguinating haemorrhage in the emergency department. Design Pragmatic, multicentre, Bayesian, group-sequential, registry-enabled, open-label, parallel-group randomised controlled trial to determine the clinical and cost-effectiveness of standard care plus resuscitative endovascular balloon occlusion of the aorta, compared to standard care alone. Setting United Kingdom Major Trauma Centres. Participants Trauma patients aged 16 years or older with confirmed or suspected life-threatening torso haemorrhage deemed amenable to adjunctive treatment with resuscitative endovascular balloon occlusion of the aorta. Interventions Participants were randomly assigned 1 : 1 to: standard care, as expected in a major trauma centre standard care plus resuscitative endovascular balloon occlusion of the aorta. Main outcome measures Primary: Mortality at 90 days. Secondary: Mortality at 6 months, while in hospital, and within 24, 6 and 3 hours; need for haemorrhage control procedures, time to commencement of haemorrhage procedure, complications, length of stay (hospital and intensive care unit-free days), blood product use. Health economic: Expected United Kingdom National Health Service perspective costs, life-years and quality-adjusted life-years, modelled over a lifetime horizon. Data sources Case report forms, Trauma Audit and Research Network registry, NHS Digital (Hospital Episode Statistics and Office of National Statistics data). Results Ninety patients were enrolled: 46 were randomised to standard care plus resuscitative endovascular balloon occlusion of the aorta and 44 to standard care. Mortality at 90 days was higher in the standard care plus resuscitative endovascular balloon occlusion of the aorta group (54%) compared to the standard care group (42%). The odds ratio was 1.58 (95% credible interval 0.72 to 3.52). The posterior probability of an odds ratio > 1 (indicating increased odds of death with resuscitative endovascular balloon occlusion of the aorta) was 86.9%. The overall effect did not change when an enthusiastic prior was used or when the estimate was adjusted for baseline characteristics. For the secondary outcomes (3, 6 and 24 hours mortality), the posterior probability that standard care plus resuscitative endovascular balloon occlusion of the aorta was harmful was higher than for the primary outcome. Additional analyses to account for intercurrent events did not change the direction of the estimate for mortality at any time point. Death due to haemorrhage was more common in the standard care plus resuscitative endovascular balloon occlusion of the aorta group than in the standard care group. There were no serious adverse device effects. Resuscitative endovascular balloon occlusion of the aorta is less costly (probability 99%), due to the competing mortality risk but also substantially less effective in terms of lifetime quality-adjusted life-years (probability 91%). Limitations The size of the study reflects the relative infrequency of exsanguinating traumatic haemorrhage in the United Kingdom. There were some baseline imbalances between groups, but adjusted analyses had little effect on the estimates. Conclusions This is the first randomised trial of the addition of resuscitative endovascular balloon occlusion of the aorta to standard care in the management of exsanguinating haemorrhage. All the analyses suggest that a strategy of standard care plus resuscitative endovascular balloon occlusion of the aorta is potentially harmful. Future work The role (if any) of resuscitative endovascular balloon occlusion of the aorta in the pre-hospital setting remains unclear. Further research to clarify its potential (or not) may be required. Trial registration This trial is registered as ISRCTN16184981. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/199/09) and is published in full in Health Technology Assessment; Vol. 28, No. 54. See the NIHR Funding and Awards website for further award information. Plain language summary Trauma (physical injury) is a major cause of death and disability. The most common cause of preventable death after injury is uncontrolled bleeding. Resuscitative endovascular balloon occlusion of the aorta is a technique whereby a small balloon is inflated in the aorta (main blood vessel) which aims to limit blood loss until an operation can be done to stop the bleeding. In this study, which is the first randomised trial in the world of this technique, we investigated whether adding resuscitative endovascular balloon occlusion of the aorta to the standard care received in a major trauma centre reduced the risk of death in trauma patients who had life-threatening uncontrolled bleeding. The study took place in 16 major trauma centres in the United Kingdom. Ninety adult trauma patients with confirmed or suspected uncontrolled bleeding took part and were randomly divided into two groups: (1) those who received standard care and (2) those who received standard care plus resuscitative endovascular balloon occlusion of the aorta. We followed participants for 6 months using routinely collected data from the National Health Service and from the Trauma Audit Research Network registry. We also contacted surviving patients at 6 months to ask about their quality of life. In the standard care group, 42% of participants died within 90 days of their injury compared to 54% of participants in the standard care plus resuscitative endovascular balloon occlusion of the aorta group. Risk of death was also higher in the standard care plus resuscitative endovascular balloon occlusion of the aorta group at all other time points (3, 6 and 24 hours, in hospital and at 6 months). Overall, the study showed that the use of resuscitative endovascular balloon occlusion of the aorta in hospital increased the risk of death. Scientific summary Background Trauma is a major cause of death and disability. Trauma (physical injury) disproportionately affects the young, killing those who might otherwise have lived long and productive lives. The most common cause of preventable death after injury is haemorrhage. The addition of resuscitative endovascular balloon occlusion of the aorta (REBOA) to current standard care is intended to provide earlier, temporary haemorrhage control, to facilitate transfer to an operating theatre or interventional radiology suite, for definitive haemostasis. Objectives The UK-REBOA trial was a pragmatic, multicentre, Bayesian, open-label, group-sequential, parallel-group randomised controlled trial comparing standard care plus REBOA versus standard care in patients with exsanguinating haemorrhage in the emergency room. The study included an elicitation exercise, an embedded mixed-methods process evaluation and a health economic evaluation. The primary clinical outcome was 90-day mortality (defined as death within 90 days of injury, before or after discharge from hospital). Secondary clinical outcomes included 3-, 6- and 24-hour mortality, in-hospital mortality, 6-month mortality, length of stay (in hospital and intensive care unit), 24-hour blood product use, need for haemorrhage control procedures (operation or angioembolisation), time to commencement of haemorrhage control procedure, complications/safety data and functional outcome [measured using the extended Glasgow Outcome Scale (GOS-E)] at discharge. Economic outcomes were 6-month (within trial) and lifetime (modelled) UK NHS perspective costs, life-years and quality-adjusted life-years (QALYs) [calculated using EuroQol Group’s 5-dimension health status 5-level questionnaire (EQ-5D-5L)], 6-month quality of life (measured using EQ-5D-5L). Methods Trauma patients were recruited in 16 UK major trauma centres. Trauma patients aged (or believed to be aged) 16 years or older, with confirmed or suspected life-threatening torso haemorrhage thought to be amenable to adjunctive treatment with REBOA were eligible. Women known (or thought to be) pregnant and those with injuries deemed unsurvivable were excluded. The trauma team leader assessed the patients for eligibility. Patients who were eligible for inclusion in the trial were incapacitated and unable to give consent at the time of eligibility assessment and randomisation. There was also not sufficient time to consult a surrogate decision-maker, or even an independent medical practitioner, for advice about including the patient. Enrolment therefore took place without prior consent following Research Ethics Committee approval for this approach. Consent for continuing participation (i.e. data collection) was sought by a member of the UK-REBOA trial team once patients were no longer in a critical condition (defined as being cared for in a ward area rather than an intensive care unit or high-dependency unit) or from a personal (or nominated professional) consultee. The trauma team leader enrolled the participant using a dedicated, secure website, available on a handheld device (smartphone, tablet) or desktop computer which is linked directly to the 24-hour randomisation system at the Centre for Healthcare Randomised Trials, based in the Health Services Research Unit, University of Aberdeen. Patients were randomised into one of the two intervention arms, in a 1 : 1 allocation ratio, in randomly generated blocks of two or four. Standard care: Patients allocated to the control group received ‘standard care’, as expected in a specialist major trauma centre. Such treatment typically included intubation, blood transfusion including blood products in a 1 : 1 : 1 ratio, interventions such as tourniquet application, and early operative or endovascular haemorrhage control. Treatment could also have included open aortic occlusion of the thoracic or abdominal aorta. Standard care plus REBOA: Patients allocated to this arm of the trial additionally received the technique of endovascular aortic occlusion, for the purpose of resuscitation, as part of an overall treatment strategy. The addition of REBOA to current standard care was intended to provide earlier, temporary haemorrhage control, to facilitate transfer to an operating theatre or interventional radiology suite for definitive haemostasis. The trial sought to evaluate the technique of REBOA rather than a specific brand of device, and therefore permitted the use of any licensed occlusion balloon, and did not prescribe or mandate a particular product. The trial had an integrated training programme to ensure familiarity with the REBOA procedure. In patients who had been randomised to the standard care plus REBOA arm of the trial, clinicians could decide not to insert the balloon occlusion device if: the patient’s haemodynamic status improved (as a result of other resuscitative measures), if they were deemed to no longer have life-threatening torso haemorrhage requiring adjunctive treatment with REBOA; they deteriorated (to the point of imminent death); or there was technical difficulty in obtaining arterial access, and it was felt that operative control of haemorrhage could be obtained more quickly. The data collection strategy for the UK-REBOA trial was designed to minimise the burden on participants and clinicians, and for the avoidance of duplication. The randomisation system collected balloon inflation/deflation times. The trial drew on routinely collected data, primarily from the Trauma Audit and Research Network (TARN) registry which includes demographic, injury, treatment and outcome data (including the GOS-E and EQ-5D-5L). Mortality and hospital resource use data were also sought from NHS Digital. The main analysis was based on the intention-to-treat principle. There were two planned interim analyses of survival and a final analysis of all outcomes after follow-up was complete. Baseline and follow-up data were summarised using descriptive statistics and graphical summaries. Treatment effects are presented with 95% credible intervals for the primary and secondary outcomes. Elicitation exercise An elicitation exercise involving 20 subject matter experts (12 emergency medicine physicians, 3 pre-hospital care doctors, 4 surgeons and 1 intensivist) was undertaken to derive prior probability distributions to help contextualise the interpretation for the primary and secondary outcomes of the trial. Subject matter experts, on average, estimated in-hospital and 90-day mortality in this patient group, without the use of REBOA, to be in excess of 50%. Mortality at earlier time points (6 and 24 hours) was estimated to be closer to 25%. The elicited data, and the resulting prior probability distributions, indicate that the experts, on average, had a favourable opinion of REBOA, that is they expect the addition of REBOA to standard care to improve mortality at all time points. Clinical results Sixteen recruitment sites were opened in a staggered manner. Recruitment commenced in October 2017, was halted in March 2020 due to COVID-19, and restarted in July 2020. The second interim analysis (including 80 participants) triggered one of the pre-specified stopping rules, and recruitment closed in March 2022, by which time 90 participants had been recruited. Forty-four participants were randomised to standard care (2 of whom did receive REBOA) and 46 were randomised to standard care plus REBOA (19 of whom had the catheter inserted and balloon inserted and the remaining 27 progressed to different time points along this pathway). The groups were well-matched in terms of age, gender, comorbidities, mechanism of injury and injury severity. In the standard care arm, the median age was 39 years (interquartile range 30–56 years) and 77% were male. In the standard care plus REBOA arm, the median age was 46 years (interquartile range 33–62) and 61% were male. The median Injury Severity Score in both arms was 41 (interquartile range 29–50), with the majority classed as having very severe injury. Of the 46 patients allocated to standard care plus REBOA treatment, 25 (54%) died within 90 days. Of the 43 standard care patients for whom primary outcome data are available, 18 (42%) died within 90 days. Using the minimally informative prior, the odds of 90-day mortality were 1.58 for patients allocated to the standard care plus REBOA arm (95% credible interval 0.72 to 3.52). The posterior probability of an odds ratio > 1 (i.e. that REBOA was harmful) was 86.9%. The direction of the estimate did not change when an enthusiastic (the elicited) prior was used or when the estimate was adjusted for baseline characteristics. For the secondary outcomes (3-, 6- and 24-hour mortality), the posterior probability that REBOA was harmful was higher than for the primary outcome. Additional analyses to account for intercurrent events did not change the direction of the estimate for mortality at 3, 6 and 24 hours, at 90 days or 6 months, or in-hospital mortality. Death due to haemorrhage was more common in the standard care plus REBOA group than in the standard care group. The mean number of days spent in intensive care and in hospital were lower in the standard care plus REBOA group compared to the standard care group, partly because of the higher number of earlier deaths in the standard care plus REBOA arm. There were no serious adverse device effects. Health economics We costed individual components of resources and summed these to generate a total cost for the whole initial hospitalisation admission period. Total NHS resource use for the index hospitalisation was obtained from patient-level data in TARN and the key resource use variables for costing included time of arrival, time of emergency department departure, time of first operation, time of death/discharge, number and type of operative procedures and volume of blood transfusions that were required. Secondary care contacts and episodes of care that were commenced between the date of discharge from the index hospitalisation through 6 months post randomisation were sourced, where available, through linkage of patient records to the Hospital Episode Statistics database. All costs are reported from a UK NHS perspective in Great British pounds (GBP) (year 2020-1). Quality of life was measured using the EQ-5D-5L prior to patient’s discharge from their index hospitalisation and at 6 months post admission. EQ-5D-5L asks respondents to report any problems on a given day across five dimensions of mobility, self-care, usual activities, anxiety/depression and pain. The data were available from TARN and supplemented with data collected by the local trial teams. EQ-5D-5L data were cross-walked to the 3L version and valued using UK general population preference tariffs. Baseline utility was set equal to the unconscious state (−0.402) and utility following death was set to 0. QALYs were calculated using an area under the curve approach assuming linear extrapolation between time points. From the within-trial health economic analysis, participants in the standard care plus REBOA arm of the study incurred lower costs {index hospital admission: mean cost £57,384 [standard deviation (SD) £62,863]} compared to those in standard care [mean cost £116,064 (SD £128,957)]. Lower costs in the standard care plus REBOA arm of the study were mainly due to lower use of hospital resources (length of stay, etc.) due to the competing risk of death (i.e. a higher number of deaths in the REBOA plus standard care group). Similarly, life-years accrued and QALYs over 6 months post randomisation were also lower in standard care plus REBOA compared to standard care due to a greater proportion of trial participants dying, with mortality also occurring earlier in the follow-up period for the REBOA arm. The mean life-years gained in the standard care plus REBOA arm was 0.232 (SD 0.247) compared to 0.305 (SD 0.236) in the standard care arm. When modelled over a full lifetime horizon, standard care plus REBOA is less costly (probability 99%), due to the competing risk of mortality but is also substantially less effective in terms of QALYs accrued over a lifetime horizon (probability 91%). The findings are robust to a range of scenario analyses undertaken, with the probability of standard care being the optimal treatment strategy ranging from 66% to 81% at a threshold value of a QALY = £50,000. Process evaluation The process evaluation was conducted in two phases; both phases involved interviews with clinical and research staff based at recruitment sites. Phase 1 was designed to identify barriers during trial initial and set-up; Phase 2 focused on exploring barriers and facilitators of recruitment into the trial and intervention delivery. A behavioural framework was used in Phase 2 to direct analysis and generate solutions designed to enhance trial practices, which included regular online meetings between the principal investigators from each site, updates to training materials and delivery, and e-mail/Twitter feedback on recruitment activity. Conclusions This is the first randomised trial ever to be conducted examining the potential clinical effectiveness of REBOA for the management of exsanguinating haemorrhage. All the analyses conducted suggest with high probability that a strategy of standard care plus REBOA is harmful. Implications for health care: The continuing use of REBOA, at least in the UK in-hospital setting, should be re-evaluated. Implications for research: The role (if any) of REBOA in the pre-hospital setting remains unclear. Further research to clarify its potential (or not) may be required. Trial registration This trial is registered as ISRCTN16184981. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/199/09) and will be published in full in Health Technology Assessment; Vol. 28, No. 54. See the NIHR Funding and Awards website for further award information.

This paper reports on the relationship between language teacher practices and their collaborations with other teachers through professional development. The paper argues that there is a link between the disposition to use evidence-based practices in language teaching, and ongoing reinforcement of such practices through dialogic exchange in professional practice sessions. Furthermore, the paper understands the learning and development of such disposition as a career-long endeavour, first encountered in quality teacher education programs and then continued by committing to ongoing professional development. Survey data were collected from a group of language teachers from various second languages in primary and secondary schools in [state removed], Australia after they had participated in a workshop on language teaching methodology. The teachers reported extensive use of evidence-based language learning strategies in their classrooms. The paper argues that this disposition is grounded in the ongoing commitment of these teachers to stay in dialogic exchange with colleagues during professional development.

Abstract Introduction Informed consent for participation in an RCT is an important ethical and legal requirement. In placebo surgical trials, further issues are raised, and to date, this has not been explored. Patient information leaflets (PILs) are a core component of the informed consent process. This study aimed to investigate the key content of PILs for recently completed placebo-controlled trials of invasive procedures, including surgery, to highlight areas of good practice, identify gaps in information provision for trials of this type and provide recommendations for practice. Methods PILs were sought from trials included in a recent systematic review of placebo-controlled trials of invasive procedures, including surgery. Trial characteristics and data on surgical and placebo interventions under evaluation were extracted. Directed content analysis was applied, informed by published regulatory and good practice guidance on PIL content and existing research on placebo-controlled surgical trials. Results were analysed using descriptive statistics and presented as a narrative summary. Results Of the 62 eligible RCTs, authors of 59 trials were contactable and 14 PILs were received for analysis. At least 50% of all PILs included content on general trial design. Explanations of how the placebo differs or is similar to the surgical intervention (i.e. fidelity) were reported in 6 (43%) of the included PILs. Over half (57%) of the PILs included information on the potential therapeutic benefits of the surgical intervention. One (7%) included information on potential indirect therapeutic benefits from invasive components of the placebo. Five (36%) presented the known risks of the placebo intervention, whilst 8 (57%) presented information on the known risks of the surgical intervention. A range of terms was used across the PILs to describe the placebo component, including ‘control’, ‘mock’ and ‘sham’. Conclusion Developers of PILs for placebo-controlled surgical trials should carefully consider the use of language (e.g. sham, mock), be explicit about how the placebo differs (or is similar) to the surgical intervention and provide balanced presentations of potential benefits and risks of the surgical intervention separately from the placebo. Further research is required to determine optimal approaches to design and deliver this information for these trials.

Abstract Background Recruiting participants to clinical trials is an ongoing challenge, and relatively little is known about what recruitment strategies lead to better recruitment. Recruitment interventions can be considered complex interventions, often involving multiple components, targeting a variety of groups, and tailoring to different groups. We used the Template for Intervention Description and Replication (TIDieR) reporting checklist (which comprises 12 items recommended for reporting complex interventions) to guide the assessment of how recruitment interventions are described. We aimed to (1) examine to what extent we could identify information about each TIDieR item within recruitment intervention studies, and (2) observe additional detail for each item to describe useful variation among these studies. Methods We identified randomized, nested recruitment intervention studies providing recruitment or willingness to participate rates from two sources: a Cochrane review of trials evaluating strategies to improve recruitment to randomized trials, and the Online Resource for Research in Clinical triAls database. First, we assessed to what extent authors reported information about each TIDieR item. Second, we developed descriptive categorical variables for 7 TIDieR items and extracting relevant quotes for the other 5 items. Results We assessed 122 recruitment intervention studies. We were able to extract information relevant to most TIDieR items (e.g., brief rationale, materials, procedure) with the exception of a few items that were only rarely reported (e.g., tailoring, modifications, planned/actual fidelity). The descriptive variables provided a useful overview of study characteristics, with most studies using various forms of informational interventions (55%) delivered at a single time point (90%), often by a member of the research team (59%) in a clinical care setting (41%). Conclusions Our TIDieR-based variables provide a useful description of the core elements of complex trial recruitment interventions. Recruitment intervention studies report core elements of complex interventions variably; some process elements (e.g., mode of delivery, location) are almost always described, while others (e.g., duration, fidelity) are reported infrequently, with little indication of a reason for their absence. Future research should explore whether these TIDieR-based variables can form the basis of an approach to better reporting of elements of successful recruitment interventions.

Abstract Background Pain from osteoarthritis (OA) is one of the top causes of disability worldwide, but effective treatment is lacking. Nociceptive factors are released by activated synovial macrophages in OA, but depletion of synovial macrophages paradoxically worsens inflammation and tissue damage in previous studies. Rather than depleting macrophages, we hypothesized that inhibiting macrophage activation may improve pain without increasing tissue damage. We aimed to identify key mechanisms mediating synovial macrophage activation and test the role of STAT signaling in macrophages on pain outcomes in experimental knee OA. Methods We induced experimental knee OA in rats via knee destabilization surgery, and performed RNA sequencing analysis on sorted synovial tissue macrophages to identify macrophage activation mechanisms. Liposomes laden with STAT1 or STAT6 inhibitors, vehicle (control), or clodronate (depletion control) were delivered selectively to synovial macrophages via serial intra-articular injections up to 12 weeks after OA induction. Treatment effects on knee and hindpaw mechanical pain sensitivity were measured during OA development, along with synovitis, cartilage damage, and synovial macrophage infiltration using histopathology and immunofluorescence. Lastly, crosstalk between drug-treated synovial tissue and articular chondrocytes was assessed in co-culture. Results The majority of pathways identified by transcriptomic analyses in OA synovial macrophages involve STAT signaling. As expected, macrophage depletion reduced pain, but increased synovial tissue fibrosis and vascularization. In contrast, STAT6 inhibition in macrophages led to marked, sustained improvements in mechanical pain sensitivity and synovial inflammation without worsening synovial or cartilage pathology. During co-culture, STAT6 inhibitor-treated synovial tissue had minimal effects on healthy chondrocyte gene expression, whereas STAT1 inhibitor-treated synovium induced changes in numerous cartilage turnover-related genes. Conclusion These results suggest that STAT signaling is a major mediator of synovial macrophage activation in experimental knee OA. STAT6 may be a key mechanism mediating the release of nociceptive factors from macrophages and the development of mechanical pain sensitivity. Whereas therapeutic depletion of macrophages paradoxically increases inflammation and fibrosis, blocking STAT6-mediated synovial macrophage activation may be a novel strategy for OA-pain management without accelerating tissue damage.