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Purpose The Outcome Monitoring After Cardiac Surgery (OMACS) cohort study was set-up with the aim of establishing a rich source of biological samples and health status data from patients who undergo cardiac surgery. The objectives were to use these data to inform the design of new clinical studies and to provide samples and data to answer research questions.Participants Recruitment began on 23 May 2016 and ended 31 May 2022. Adult patients undergoing cardiac surgery at University Hospitals Bristol and Weston NHS Foundation Trust were screened and approached for consent. Participants could optionally consent to provide biological samples (urine, blood and waste tissue) in addition to data. A total of 4068 patients consented to participate in the study with 2027 consenting to donate samples. Participants were sent quality-of-life follow-up questionnaires at 3 and 12 months after surgery. The clinical data were collected from hospital records/databases.Findings to date The OMACS population appears to be representative of the wider cardiac surgery population with similar preoperative demography to those reported on the UK surgery population. To date, eight studies have been carried out by research teams using data from a total of 1165 OMACS participants. Two Studies Within A Trial have been performed by the OMACS study team. The format of the study patient information leaflet was not significantly associated with an increased recruitment rate, and an alternative theory-informed cover letter included with the 12-month follow-up questionnaires was not associated with an increase in questionnaire completion. Additional exploratory research carried out within the OMACS study has been presented at international conferences.Future plans The OMACS study is now closed. The cohort’s data and samples will be available to share with researchers, providing an opportunity to answer a variety of research questions (eg, evaluating predictors of adverse outcomes after cardiac surgery such as biomarkers, surgical methods and pre-existing conditions). The data and samples will be available for sharing in a linked anonymised format.Trial registration number ISRCTN90204321 (date assigned: 21 January 2015).

Opsoclonus-myoclonus syndrome is a rare neurological condition characterized by opsoclonus, myoclonus, ataxia, irritability, and sleep disturbances. In pediatric patients, symptoms usually start between 16 and 18 months of age; opsoclonus-myoclonus syndrome presentation in children under 6 months is rare. Approximately 50% of cases are associated with neuroblastoma. We report an early onset presentation of opsoclonus-myoclonus syndrome in a previously healthy, 3-month-old female infant. The diagnostic workup revealed no abnormalities. The patient underwent monthly cycles of dexamethasone pulses and intravenous immunoglobulin with a favorable response. After a few months, the patient presented intermittent opsoclonus before the next scheduled pulse so from the 9th cycle onwards, the intravenous immunoglobulin dose was increased to 2 g/kg. After 9 months of treatment, she was diagnosed with a latent Mycobacterium tuberculosis infection. Due to this infection, dexamethasone pulses were discontinued, and intravenous immunoglobulin treatment was maintained with clinical improvement The patient received 18 intravenous immunoglobulin cycles, leaving her with a score of one on the Mitchell-Pike scale. Developmental milestones have been attained according to age. Despite the range of therapeutic options for managing opsoclonus-myoclonus syndrome described in the literature, the efficacy of these available therapies needs to be better established. A modified upfront approach with dexamethasone and intravenous immunoglobulin could be an option in settings where rituximab is unavailable.

Abstract Background In February 2021, the UK Department of Health and Social Care sought evidence on the safety and immunogenicity of COVID-19 and influenza vaccine co-administration to inform the 2021/2022 influenza vaccine policy. Co-administration could support vaccine uptake and reduce healthcare appointments. ComFluCOV was a randomised controlled trial designed to provide this evidence. This report outlines the methods used to deliver the trial in 6 months to answer an urgent public health question as part of the COVID-19 pandemic response. Methods ComFluCOV was commissioned by the Department of Health and Social Care and was managed by the Bristol Trials Centre, a UK-registered clinical trials unit. It was classed as an Urgent Public Health trial which facilitated fast-track regulatory approvals. Trial materials and databases were developed using in-house templates and those used in other COVID-19 vaccine trials. Participants were recruited by advertising, and via a trial website. Electronic trial systems enabled daily review of participant data. Weekly virtual meetings were held with stakeholders and trial sites. Results ComFluCOV was delivered within 6 months from inception to reporting, and trial milestones to inform the Department of Health and Social Care policy were met. Set-up was achieved within 1 month. Regulators provided expedited reviews, with feedback ahead of submission. Recruitment took place at 12 sites. Over 380 site staff were trained. Overall, 679 participants were recruited in two months. The final report to the Department of Health and Social Care was submitted in September 2021, following a preliminary safety report in May 2021. Trial results have been published. Conclusion The rapid delivery of ComFluCOV was resource intensive. It was made possible in part due to a unique set of circumstances created by the pandemic situation including measures put in place to support urgent public health research and public support for COVID-19 vaccine research. Elements of the trial could be adopted to increase efficiency in ‘non-pandemic’ situations including working with a clinical trials unit to enable immediate mobilisation of a team of experienced researchers, greater sharing of resources between clinical trials units, use of electronic trial systems and virtual meetings. Trial registration ISRCTN14391248, submitted on 17/03/2021. Registered on 30/03/2021.

Abstract Background For the potential benefits of trials to reach all that they should, trials must be designed to ensure that those taking part reflect the population who will receive the intervention. However, adults with impaired capacity to consent are frequently excluded from trials — partly because researchers are unfamiliar with the legal and ethical frameworks and lack the necessary methodological expertise. Researchers identified a need for guidance on designing more inclusive trials. Building on the NIHR INCLUDE initiative, we developed the INCLUDE Impaired Capacity to Consent Framework to help researchers design inclusive trials. Methods The framework was developed over five phases: (1) establishing the scope and content of the framework and adapting the INCLUDE Ethnicity Framework for this population; (2) scoping the relevance of the framework to different populations and piloting in a range of trials; (3) consulting people living with impairing conditions and carers to explore their views about the framework and identify missing content areas; (4) refining the framework; and (5) the development of an implementation toolkit of resources to support researchers using the framework. Results The framework has two parts: a set of four key questions to help researchers identify who should be included in their trial, and a series of worksheets covering intervention design, recruitment and consent processes, data collection and analysis, and public involvement and dissemination. It is supported by a summary of the ethical and legal frameworks and a website of resources on capacity and consent. Implementation resources include infographics and animations, a library of completed frameworks, and facilitated workshops for researchers. The framework and toolkit were launched at a webinar (November 2022), with polling demonstrating an increase in attendees’ awareness about research involving adults lacking capacity. A post-webinar survey found that stakeholders viewed the framework and toolkit as valuable tools to facilitate greater inclusion of this under-served population in trials. The framework is available online: https://www.capacityconsentresearch.com/include-impaired-capacity-to-consent-framework.html . Conclusions The INCLUDE Impaired Capacity to Consent Framework and implementation toolkit can support researchers to design more inclusive trials and other types of research studies. Further engagement, including with funders who are key to ensuring uptake, and evaluation is needed.

Abstract Background In early 2021, the Department of Health and Social Care in the UK called for research on the safety and immunogenicity of concomitant administration of COVID-19 and influenza vaccines. Co-administration of these vaccines would facilitate uptake and reduce the number of healthcare visits required. The ComFluCOV trial was designed to deliver the necessary evidence in time to inform the autumn (September–November) 2021 vaccination policy. This paper presents the statistical methodology applied to help successfully deliver the trial results in 6 months. Methods ComFluCOV was a parallel-group multicentre randomised controlled trial managed by the Bristol Trials Centre. Two study statisticians, supported by a senior statistician, worked together on all statistical tasks. Tools were developed to aid the pre-screening process. Automated data monitoring reports of clinic data and electronic diaries were produced daily and reviewed by the trial team and feedback provided to sites. Analyses were performed independently in parallel, and derivations and results of all outcomes were compared. Results Set-up was achieved in less than a month, and 679 participants were recruited over 8 weeks. A total of 537 [at least] daily reports outlining recruitment, protocol adherence, and data quality, and 695 daily reports of participant electronic diaries identifying any missed diary entries and adverse events were produced over a period of 16 weeks. A preliminary primary outcome analysis of validated data was reported to the Department of Health and Social Care in May 2021. The database was locked 6 weeks after the final participant follow-up and final analyses completed 3 weeks later. A pre-print publication was submitted within 14 days of the results being made available. The results were reported 6 months after first discussions about the trial. Conclusion The statistical methodologies implemented in ComFluCOV helped to deliver the study in the timescale set. Working in a new clinical area to tight timescales was challenging. Having two statisticians working together on the study provided a quality assurance process that enabled analyses to be completed efficiently and ensured data were interpreted correctly. Processes developed could be applied to other studies to maximise quality, reduce the risk of errors, and overall provide enhanced validation methods. Trial registration ISRCTN14391248, registered on 30 March 2021

Introduction More than 30 000 cardiac surgery procedures are performed in the UK each year, however, postoperative complications and long-term failure of interventions are common, leading to repeated surgeries. This represents a significant burden on the patient and health service.Routinely, patients are discharged to their general practitioner 6 weeks postoperatively and research studies typically only report short-term outcomes up to 1 year after surgery, together this makes long-term outcomes of cardiac surgery difficult to monitor. Further, traditional research methods have yet to advance understanding of what causes early complications and why surgical interventions fail.Methods and analysis This prospective cohort study will characterise participants undergoing cardiac surgery at baseline, describe short-term, medium-term and long-term health outcomes postoperatively and collect tissue samples.All eligible adult patients undergoing cardiac surgery at the Bristol Heart Institute, UK will be approached for consent. Recruitment is expected to continue for up to 10 years resulting in the largest cohort of cardiac patients reported to date. Blood, urine and waste tissue samples will be collected during admission. Samples, along with anonymised data, will be used to investigate outcomes and inform predictive models of complications associated with cardiac surgery.Data about the surgical admission will be obtained from hospital databases and medical notes. Participants may be monitored up to 5 years postoperatively using data obtained from NHS digital. Participants will complete health questionnaires 3 months and 12 months postoperatively.The analysis of data and tissue samples to address specific research questions will require separate research protocols and ethical approval.Ethics and dissemination This study was approved by the East Midlands Nottingham 2 Research Ethics Committee.Findings will be disseminated through peer-reviewed publications and presentation at national and international meetings. Participants will be informed of results in annual newsletters.Trial registration number ISRCTN90204321.

Objectives:. To investigate the differences in clinical course, ventilator mechanics, and outcomes of patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection compared with a historical cohort of acute respiratory distress syndrome. Design:. Comparative case-control study. Setting:. Multicenter, comprehensive tertiary healthcare facility in Detroit, MI. Patients/Subjects:. Adult patients hospitalized with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection were compared with patients hospitalized with acute respiratory distress syndrome prior to the coronavirus disease 2019 pandemic (control). Interventions:. None. MEASUREMENTS AND Main Results:. We included 384 patients in the analysis. Inpatient mortality was significantly higher in patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection compared with controls (64% vs 49%; p = 0.007). Despite both groups demonstrating similar ventilatory function and Sequential Organ Failure Assessment score on day 1 of intubation, with similar lung compliance throughout the study period, patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection demonstrated progressive hypoxia compared with controls across the study period. Similarly, higher positive end-expiratory pressure levels and increased use of paralytics were observed in the patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection group. On univariate analysis of the entire cohort, significant risk factors for inpatient mortality included coronavirus disease 2019 infection (p = 0.007), older age (p < 0.001), high Sequential Organ Failure Assessment score (p = 0.003), vasopressor use (p = 0.039), paralytic use (p < 0.001), higher positive end-expiratory pressure levels on day 3 (p = 0.027) and day 7 (p < 0.001), in addition to acute respiratory distress syndrome severity on both days 3 (p = 0.008) and 7 (p < 0.001). Multivariate analysis identified coronavirus disease 2019 infection (odds ratio, 1.939; p = 0.021), older age (odds ratio, 1.042; p < 0.001), paralytic use (odds ratio, 3.366; p < 0.001), and higher Sequential Organ Failure Assessment score (odds ratio, 1.152; p = 0.027) as significant predictors of mortality across the entire cohort. Conclusions:. Patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection demonstrated higher mortality compared with control patients hospitalized with acute respiratory distress syndrome prior to the pandemic, with progressive hypoxia throughout the study period, despite similar lung mechanics and initial Sequential Organ Failure Assessment score. Coronavirus disease 2019 infection, older age, paralytic use, and higher Sequential Organ Failure Assessment scores were independent risk factors for 28-day mortality across the entire cohort.

Introduction Mesothelioma remains a lethal cancer. To date, systemic therapy with pemetrexed and a platinum drug remains the only licensed standard of care. As the median survival for patients with mesothelioma is 12.1 months, surgery is an important consideration to improve survival and/or quality of life. Currently, only two surgical trials have been performed which found that neither extensive (extra-pleural pneumonectomy) or limited (partial pleurectomy) surgery improved survival (although there was some evidence of improved quality of life). Therefore, clinicians are now looking to evaluate pleurectomy decortication, the only radical treatment option left.Methods and analysis The MARS 2 study is a UK multicentre open parallel group randomised controlled trial comparing the effectiveness and cost-effectiveness of surgery—(extended) pleurectomy decortication—versus no surgery for the treatment of pleural mesothelioma. The study will test the hypothesis that surgery and chemotherapy is superior to chemotherapy alone with respect to overall survival. Secondary outcomes include health-related quality of life, progression-free survival, measures of safety (adverse events) and resource use to 2 years. The QuinteT Recruitment Intervention is integrated into the trial to optimise recruitment.Ethics and dissemination Research ethics approval was granted by London – Camberwell St. Giles Research Ethics Committee (reference 13/LO/1481) on 7 November 2013. We will submit the results for publication in a peer-reviewed journal.Trial registration numbers ISRCTN—ISRCTN44351742 and ClinicalTrials.gov—NCT02040272.

TThis paper builds upon a foundational paper (under review) which explores the rudiments of the quantum perspective of learning. The quantum perspective of learning uses the principles of exchange theory or borrowed theory from the field of quantum holism pioneered by quantum physicist David Bohm (1971, 1973) to understand learning in a new way. Bohm proposes that everything exists as wholes, rather than as parts, and that everything is connected. Similarly, the quantum perspective of learning proposes that individuals learn in holistic ways as they interact with temporal and in infinitely extending virtual worlds. Further, according to the quantum perspective of learning, learners have infinite potential. In this paper, the quantum perspective of learning is examined utilizing a combination of Schunk’s (1991) and Ertmer and Newby’s (1993) definitive questions for aligning learning theory with instructional design. These seven definitive questions focus on how learning happens, influential factors in learning, the role of memory, transfer of knowledge, modalities of learning that can best explain the quantum perspective of learning, applicable assumptions, and a discussion of how instruction can be organized to optimize learning. Examples of strategies that facilitate the quantum perspective of learning are provided.