Background: The COVID-19 pandemic has presented unique challenges for rapidly designing, initiating, and delivering therapeutic clinical trials. PRINCIPLE (Platform Randomised Trial of Treatments in the Community for Epidemic and Pandemic Illnesses) is the UK national platform investigating repurposed therapies for COVID-19 treatment of older people in the community at high risk of complications. Standard methods of patient recruitment were failing to meet the required pace and scale of enrolment. This paper describes the development and appraisal of a near real-time, data-driven, ethical approach for enhancing recruitment in community care by contacting people with a recent COVID-19 positive test result from the central NHS Test and Trace service within approximately 24\u201348 h of their test result. Methods: A multi-disciplinary team was formed to solve the technical, ethical, public perception, logistical and information governance issues required to provide a near-real time (approximately within 24\u201348 h of receiving a positive test) feed of potential trial participants from test result data to the research team. PRINCIPLE was also given unique access to the Summary Care Record (SCR) to ensure safe prescribing, and to enable the trial team to quickly and safely bring consented patients into the trial. A survey of the public was used to understand public perceptions of the use of test data for this proposed methodology. Results: Prior to establishing the data service, PRINCIPLE registered on average 87 participants per week. This increased by up to 87 additional people registered per week from the test data, contributing to an increase from 1013 recruits to PRINCIPLE at the start of October 2020 to 2802 recruits by 20 December 2020. Whilst procedural caveats were identified by the public consultation, out of 2639 people contacted by PRINCIPLE following a positive test result, no one raised a concern about being approached. Conclusions: This paper describes a novel approach to using near-real time NHS operational data to recruit community-based patients within a few days of presentation with acute illness. This approach increased recruitment and reduced time between positive test and randomisation, allowing more rapid evaluation of treatments and increased safety for participants. End-to-end public and patient involvement in the design of the approach provided evidence to inform information governance decisions. Trial registration: PRINCIPLE is funded by UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research. EudraCT number: 2020-001209-22. 26/03/2020 ISRCTN registry: ISRCTN86534580. 20/03/2020 REC number: 20/SC/058 IRAS number: 281958
\n \n\n \n \nINTRODUCTION: Opioid prescribing trends have been investigated in many countries. However, the patterns of over-the-counter purchases of opioids without a prescription, such as codeine combinations, are mostly unknown. OBJECTIVE: We aimed to assess national sales and expenditure trends of over-the-counter codeine-containing products purchased in countries with available data over 6 years. METHODS: We conducted a retrospective observational study using electronic point-of-sale data from the human data science company, IQVIA, for countries that had such data, including Argentina, Belgium, Brazil, Bulgaria, Canada, Croatia, Estonia, Finland, France, Germany, Greece, Ireland, Italy, Japan, Latvia, Lithuania, Mexico, the Netherlands, Poland, Portugal, Romania, Russia, Serbia, Slovakia, Slovenia, South Africa, Spain, Switzerland, Thailand, the UK, and the USA. We calculated annual mean sales (dosage units/1000 population) and public expenditure (\u00a3/1000 population) for each country between April 2013 and March 2019 and adjusted for data coverage reported by IQVIA. We quantified changes over time and the types of products sold. RESULTS: In total, 31.5 billion dosage units (adjusted: 42.8 billion dosage units) of codeine, costing \u00a32.55 billion (adjusted: \u00a33.68 billion), were sold over the counter in 31 countries between April 2013 and March 2019. Total adjusted sales increased by 11% (from 3911 dosage units/1000 population in 2013 to 4358 in 2019) and adjusted public expenditure increased by 72% (from \u00a3263/1000 in 2013 to \u00a3451/1000 in 2019). Sales were not equally distributed; South Africa sold the most (36 mean dosage units/person), followed by Ireland (30 mean dosage units/person), France (20 mean dosage units/person), the UK (17.2 mean dosage units/person), and Latvia (16.8 mean dosage units/person). Types of products (n\u2009=\u2009569) and formulations (n\u2009=\u200912) sold varied. CONCLUSION: In many parts of the world, substantial numbers of people may be purchasing and consuming codeine in over-the-counter products. Clinicians should ask patients about their use of over-the-counter products, and public health measures are required to improve the collection of sales data and the safety of such products. STUDY PROTOCOL PRE-REGISTRATION: https://osf.io/ay4mc . The pre-print version of this work is available on medRxiv: https://doi.org/10.1101/2021.04.21.21255888 .
\n \n\n \n \nBACKGROUND: There is concern about medium to long-term adverse outcomes following acute Coronavirus Disease 2019 (COVID-19), but little relevant evidence exists. We aimed to investigate whether risks of hospital admission and death, overall and by specific cause, are raised following discharge from a COVID-19 hospitalisation. METHODS AND FINDINGS: With the approval of NHS-England, we conducted a cohort study, using linked primary care and hospital data in OpenSAFELY to compare risks of hospital admission and death, overall and by specific cause, between people discharged from COVID-19 hospitalisation (February to December 2020) and surviving at least 1 week, and (i) demographically matched controls from the 2019 general population; and (ii) people discharged from influenza hospitalisation in 2017 to 2019. We used Cox regression adjusted for age, sex, ethnicity, obesity, smoking status, deprivation, and comorbidities considered potential risk factors for severe COVID-19 outcomes. We included 24,673 postdischarge COVID-19 patients, 123,362 general population controls, and 16,058 influenza controls, followed for \u2264315 days. COVID-19 patients had median age of 66 years, 13,733 (56%) were male, and 19,061 (77%) were of white ethnicity. Overall risk of hospitalisation or death (30,968 events) was higher in the COVID-19 group than general population controls (fully adjusted hazard ratio [aHR] 2.22, 2.14 to 2.30, p < 0.001) but slightly lower than the influenza group (aHR 0.95, 0.91 to 0.98, p = 0.004). All-cause mortality (7,439 events) was highest in the COVID-19 group (aHR 4.82, 4.48 to 5.19 versus general population controls [p < 0.001] and 1.74, 1.61 to 1.88 versus influenza controls [p < 0.001]). Risks for cause-specific outcomes were higher in COVID-19 survivors than in general population controls and largely similar or lower in COVID-19 compared with influenza patients. However, COVID-19 patients were more likely than influenza patients to be readmitted or die due to their initial infection or other lower respiratory tract infection (aHR 1.37, 1.22 to 1.54, p < 0.001) and to experience mental health or cognitive-related admission or death (aHR 1.37, 1.02 to 1.84, p = 0.039); in particular, COVID-19 survivors with preexisting dementia had higher risk of dementia hospitalisation or death (age- and sex-adjusted HR 2.47, 1.37 to 4.44, p = 0.002). Limitations of our study were that reasons for hospitalisation or death may have been misclassified in some cases due to inconsistent use of codes, and we did not have data to distinguish COVID-19 variants. CONCLUSIONS: In this study, we observed that people discharged from a COVID-19 hospital admission had markedly higher risks for rehospitalisation and death than the general population, suggesting a substantial extra burden on healthcare. Most risks were similar to those observed after influenza hospitalisations, but COVID-19 patients had higher risks of all-cause mortality, readmission or death due to the initial infection, and dementia death, highlighting the importance of postdischarge monitoring.
\n \n\n \n \nIntroductionSevere mental illness (SMI) is associated with significant morbidity and mortality. People living with SMI often receive complex medication regimens. Optimising these regimens can be challenging. Non-adherence is common and addressing it requires a collaborative approach to decision making. MEDIATE uses a realist approach with extensive engagement with experts-by-experience to make sense of the complexities and identify potential solutions.Realist research is used to unpack and explain complexity using programme theory/theories that contain causal explanations of outcomes, expressed as context\u2013mechanism\u2013outcome\u2013configurations. The programme theory/theories will enable MEDIATE to address its aim of understanding what works, for whom, in what circumstances, to optimise medication use with people living with SMI.Method and analysisMEDIATE will be conducted over six stages. In stage 1, we will collaborate with our service user/family carer lived experience group (LEG) and practitioner stakeholder group (SG), to determine the focus. In stage 2, we will develop initial programme theories for what needs to be done, by whom, how and why, and in what contexts to optimise medication use. In stage 3, we will develop and run searches to identify secondary data to refine our initial programme theories.Stage 4 involves selection and appraisal: documents will be screened by title, abstract/keywords and full text against inclusion and exclusion criteria. In stage 5, relevant data will extracted, recorded and coded. Data will be analysed using a realist logic with input from the LEG and SG. Finally, in stage 6, refined programme theories will be developed, identifying causal explanations for key outcomes and the strategies required to change contexts to trigger the key mechanisms that produce these outcomes.Ethics and disseminationPrimary data will not be collected, and therefore, ethical approval is not required. MEDIATE will be disseminated via publications, conferences and form the basis for future grant applications.PROSPERO registration numberCRD42021280980.
\n \n\n \n \nIntroductionMusic and dance are increasingly used as adjunctive arts-in-health interventions in high-income settings, with a growing body of research suggesting biopsychosocial benefits. Such low-cost, low-resource interventions may have application in low-resource settings such as Uganda. However, research on perceptions of patients and healthcare professionals regarding such approaches is lacking.MethodsWe delivered sample sessions of music and dance for chronic respiratory disease (CRD) to patients and healthcare professionals. Seven participants took part in one singing and dance sample session. One patient completed only the dance session. We then conducted an exploratory qualitative study using thematic analysis of semistructured interviews with healthcare professionals and patients regarding (1) the role of music and dance in Ugandan life and (2) the perceived acceptability and feasibility of using music and dance in CRD management in Uganda.ResultsWe interviewed 19 participants, made up of 11 patients with long-term respiratory conditions and 8 healthcare professionals, who were selected by purposeful convenience sampling. Four key themes were identified from interview analysis: music and dance (1) were central components of daily life; (2) had an established role supporting health and well-being; and (3) had strong therapeutic potential in respiratory disease management. The fourth theme was (4) the importance of modulating demographic considerations of culture, religion and age.ConclusionMusic and dance are central to life in Uganda, with established roles supporting health and well-being. These roles could be built on in the development of music and dance interventions as adjuncts to established components of CRD disease management like pulmonary rehabilitation. Through consideration of key contextual factors and codevelopment and adaptation of interventions, such approaches are likely to be well received.
\n \n\n \n \nIn resource-stretched emergency departments, people accompanying patients play key roles in patients\u2019 care. This article presents analysis of the ways health professionals and accompanying persons talked about admission decisions and caring roles. The authors used an ethnographic case study design involving participant observation and semi-structured interviews with 13 patients, 17 accompanying persons and 26 health care professionals in four National Health Service hospitals in south-west England. Focused analysis of interactional data revealed that professionals\u2019 standardization of the patient\u2013carer relationship contrasted with accompanying persons\u2019 varied connections with patients. Accompanying persons could directly or obliquely express willingness, ambivalence and resistance to supporting patients\u2019 care. The drive to avoid admissions can lead health professionals to deploy conversational skills to enlist accompanying persons for discharge care without exploring the meanings of their particular relationship with the patients. Taking a relationship-centered approach could improve the attention to accompanying persons as co-producers of health care and participants in decision-making.
\n \n\n \n \nBackgroundHospital emergency admissions have risen annually, exacerbating pressures on emergency departments (EDs) and acute medical units. These pressures have an adverse impact on patient experience and potentially lead to suboptimal clinical decision-making. In response, a variety of innovations have been developed, but whether or not these reduce inappropriate admissions or improve patient and clinician experience is largely unknown.AimsTo investigate the interplay of service factors influencing decision-making about emergency admissions, and to understand how the medical assessment process is experienced by patients, carers and practitioners.MethodsThe project used a multiple case study design for a mixed-methods analysis of decision-making about admissions in four acute hospitals. The primary research comprised two parts: value stream mapping to measure time spent by practitioners on key activities in 108 patient pathways, including an embedded study of cost; and an ethnographic study incorporating data from 65 patients, 30 carers and 282 practitioners of different specialties and levels. Additional data were collected through a clinical panel, learning sets, stakeholder workshops, reading groups and review of site data and documentation. We used a realist synthesis approach to integrate findings from all sources.FindingsPatients\u2019 experiences of emergency care were positive and they often did not raise concerns, whereas carers were more vocal. Staff\u2019s focus on patient flow sometimes limited time for basic care, optimal communication and shared decision-making. Practitioners admitted or discharged few patients during the first hour, but decision-making increased rapidly towards the 4-hour target. Overall, patients\u2019 journey times were similar, although waiting before being seen, for tests or after admission decisions, varied considerably. The meaning of what constituted an \u2018admission\u2019 varied across sites and sometimes within a site. Medical and social complexity, targets and \u2018bed pressure\u2019, patient safety and risk, each influenced admission/discharge decision-making. Each site responded to these pressures with different initiatives designed to expedite appropriate decision-making. New ways of using hospital \u2018space\u2019 were identified. Clinical decision units and observation wards allow potentially dischargeable patients with medical and/or social complexity to be \u2018off the clock\u2019, allowing time for tests, observation or safe discharge. New teams supported admission avoidance: an acute general practitioner service filtered patients prior to arrival; discharge teams linked with community services; specialist teams for the elderly facilitated outpatient treatment. Senior doctors had a range of roles: evaluating complex patients, advising and training juniors, and overseeing ED activity.ConclusionsThis research shows how hospitals under pressure manage complexity, safety and risk in emergency care by developing \u2018ground-up\u2019 initiatives that facilitate timely, appropriate and safe decision-making, and alternative care pathways for lower-risk, ambulatory patients. New teams and \u2018off the clock\u2019 spaces contribute to safely reducing avoidable admissions; frontline expertise brings value not only by placing senior experienced practitioners at the front door of EDs, but also by using seniors in advisory roles. Although the principal limitation of this research is its observational design, so that causation cannot be inferred, its strength is hypothesis generation. Further research should test whether or not the service and care innovations identified here can improve patient experience of acute care and safely reduce avoidable admissions.FundingThe National Institute for Health Research (NIHR) Health Services and Delivery Research programme (project number 10/1010/06). This research was supported by the NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula.
\n \n\n \n \n\u00a9 2017 The Author(s). Background: Fragmented care results in poor outcomes for individuals with complexity of need. Person-centred coordinated care (P3C) is perceived to be a potential solution, but an absence of accessible evidence and the lack of a scalable 'blue print' mean that services are 'experimenting' with new models of care with little guidance and support. This paper presents an approach to the implementation of P3C using collaborative action, providing examples of early developments across this programme of work, the core aim of which is to accelerate the spread and adoption of P3C in United Kingdom primary care settings. Methods: Two centrally funded United Kingdom organisations (South West Collaboration for Leadership in Applied Health Research and Care and South West Academic Health Science Network) are leading this initiative to narrow the gap between research and practice in this urgent area of improvement through a programme of service change, evaluation and research. Multi-stakeholder engagement and co-design are core to the approach. A whole system measurement framework combines outcomes of importance to patients, practitioners and health organisations. Iterative and multi-level feedback helps to shape service change while collecting practice-based data to generate implementation knowledge for the delivery of P3C. The role of the research team is proving vital to support informed change and challenge organisational practice. The bidirectional flow of knowledge and evidence relies on the transitional positioning of researchers and research organisations. Results: Extensive engagement and embedded researchers have led to strong collaborations across the region. Practice is beginning to show signs of change and data flow and exchange is taking place. However, working in this way is not without its challenges; progress has been slow in the development of a linked data set to allow us to assess impact innovations from a cost perspective. Trust is vital, takes time to establish and is dependent on the exchange of services and interactions. If collaborative action can foster P3C it will require sustained commitment from both research and practice. This approach is a radical departure from how policy, research and practice traditionally work, but one that we argue is now necessary to deal with the most complex health and social problems.
\n \n\n \n \nBackground: Community engagement (CE) is increasingly accepted as a critical aspect of health research, because of its potential to make research more ethical, relevant and well implemented. While CE activities linked to health research have proliferated in Low and Middle Income Countries (LMICs), and are increasingly described in published literature, there is a lack of conceptual clarity around how engagement is understood to \u2018work\u2019, and the aims and purposes of engagement are varied and often not made explicit. Ultimately, the evidence base for engagement remains underdeveloped. Methods: To develop explanations for how and why CE with health research contributes to the pattern of outcomes observed in published literature, we conducted a realist review of CE with malaria research \u2013 a theory driven approach to evidence synthesis. Results: We found that community engagement relies on the development of provisional \u2018working relationships\u2019 across differences, primarily of wealth, power and culture. These relationships are rooted in interactions that are experienced as relatively responsive and respectful, and that bring tangible research related benefits. Contextual factors affecting development of working relationships include the facilitating influence of research organisation commitment to and resources for engagement, and constraining factors linked to the prevailing \u2018dominant health research paradigm context\u2019, such as: differences of wealth and power between research centres and local populations and health systems; histories of colonialism and vertical health interventions; and external funding and control of health research. Conclusions: The development of working relationships contributes to greater acceptance and participation in research by local stakeholders, who are particularly interested in research related access to health care and other benefits. At the same time, such relationships may involve an accommodation of some ethically problematic characteristics of the dominant health research paradigm, and thereby reproduce this paradigm rather than challenge it with a different logic of collaborative partnership.
\n \n\n \n \nObjectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To investigate differences in the effectiveness of individual-level smoking cessation interventions by socioeconomic indicators, to estimate the potential that an intervention might increase or decrease health inequalities due to tobacco use.
\n \n\n \n \nObjectives Colchicine has been proposed as a COVID-19 treatment, but its effect on time to recovery is unknown. We aimed to determine whether colchicine is effective at reducing time to recovery and COVID-19 related hospitalisations/deaths among people in the community. Design Prospective, multicentre, open-label, multi-arm, adaptive Platform Randomised Trial of Treatments in the Community for Epidemic and Pandemic Illnesses (PRINCIPLE). Setting National trial run remotely from a central trial site and at multiple primary care centres across the United Kingdom. Participants Adults aged \u226565, or \u226518 years with comorbidities or shortness of breath, and unwell \u226414 days with suspected COVID-19 in the community. Interventions Participants were randomised to usual care, usual care plus colchicine (500\u00b5g daily for 14 days), or usual care plus other interventions. Main outcome measures The co-primary endpoints were time to first self-reported recovery, and hospitalisation/death related to COVID-19, within 28 days, analysed using Bayesian models. The hypothesis for the time to recovery endpoint is evaluated first, and if superiority is declared on time to recovery, the hypothesis for the second co-primary endpoint of hospitalisation/death is then evaluated. To determine futility, we pre-specified a clinically meaningful benefit in time to first reported recovery as a hazard ratio of 1.2 or larger (equating to approximately 1.5 days benefit in the colchicine arm, assuming 9 days recovery in the usual care arm). Results The trial opened on April 2, 2020, with randomisation to colchicine starting on March 04, 2021 and stopping on May 26, 2021, because the pre-specified time to recovery futility criterion was met. The primary analysis model included 2755 SARS-CoV-2 positive participants, randomised to colchicine (n=156), usual care (n=1145), and other treatments (n=1454). Time to first self-reported recovery was similar in the colchicine group compared with usual care with an estimated hazard ratio of 0.919 [95% credible interval 0.72 to 1.16] and an estimated increase of 1.14 days [\u22121.86 to 5.21] in median time to self-reported recovery for colchicine versus usual care. The probability of meaningful benefit in time to recovery was very low at 1.8%. Results were similar in comparisons with concurrent controls. COVID-19 related hospitalisations/deaths were similar in the colchicine group versus usual care, with an estimated odds ratio of 0.76 [0.28 to 1.89] and an estimated difference of \u22120.4% [\u22122.7% to 2.4]. One serious adverse event occurred in the colchicine group and one in usual care. Conclusions Colchicine did not improve time to recovery in people at higher risk of complications with COVID-19 in the community. Trial registration ISRCTN86534580.
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