Apixaban following discharge in hospitalised adults with COVID-19: Preliminary results from a multicentre, open-label, randomised controlled platform clinical trial.

BackgroundThe role of thromboprophylaxis in the post-acute phase of COVID-19 is uncertain due to conflicting results from randomised controlled trials and observational studies. We aimed to determine the effectiveness of post-hospital apixaban in reducing the rate of death and hospital readmission of hospitalised adults with COVID-19. MethodsHEAL COVID is an adaptive randomised open label multicentre platform trial recruiting participants from National Health Service Hospitals in the United Kingdom. Here we report the preliminary results of apixaban comparison of HEAL-COVID. Participants with a hospital admission related to confirmed COVID-19 and an expected date of discharge in the subsequent five days were randomised to either apixaban 2.5 mg twice daily or standard care (no anticoagulation) for 14 days. The primary outcome was hospital free survival at 12 months obtained through routine data sources. The trial was prospectively registered with ISRCTN (15851697) and Clincialtrials.gov (NCT04801940). FindingsBetween 19 May 2021 and 21 November 2022, 402 participants from 109 sites were randomised to apixaban and 399 to standard care. Seven participants withdrew from the apixaban group and one from the standard care group. Analysis was undertaken on an intention-to-treat basis. The apixaban arm was stopped on the recommendation of the oversight committees following an interim analysis due to no indication of benefit. Of the 402 participants randomised to apixaban, 117 experienced death or rehospitalisation during a median follow-up of 344{middle dot}5 days (IQR 125 to 365), and 123 participants receiving standard care experienced death or rehospitalisation during a median follow-up of 349 days (IQR 124 to 365). There was no statistical difference in the rate of death and rehospitalisation (HR: 0{middle dot}96 99%CI 0{middle dot}69-1{middle dot}34; p=0{middle dot}75). Three participants in the apixaban arm experienced clinically significant bleeding during treatment. InterpretationFourteen days of post-hospital anticoagulation with the direct oral anticoagulant apixaban did not reduce the rate of death or rehospitalisation of adults hospitalised with COVID-19. These data do not support the use of prophylactic post-hospital anticoagulation in adults with COVID-19. FundingHEAL-COVID is funded by the National Institute for Health and Care Research [NIHR133788] and the NIHR Cambridge Biomedical Research Centre [BRC-1215-20014*].

What is the long-term impact of COVID-19 on the Health-Related Quality of Life of individuals with mild symptoms (or non-hospitalised): A rapid review

The COVID-19 morbidities model has been widely used since 2020 to support Test and Trace and assess the cost-effectiveness of the COVID-19 vaccination programme. The current iteration of the Long COVID model covers several morbidities associated with COVID-19, which are essential to plan for elective care in the future and identify which services to prioritise. However, there are uncertainties in the model around the long-term health-related quality of life (HRQoL) impact of COVID-19, which is primarily based on data for severe COVID disease or hospitalised patients at present. The COVID-19 morbidities model requires updating to address gaps and reflect the latest HRQoL evidence. The aim of this rapid review was to provide updated HRQoL evidence for the COVID-19 morbidities model to better support decision-making in relation to COVID-19 policy. Thirteen primary studies were identified. People who had an initial mild COVID-19 illness or were not treated in hospital can have a decreased HRQoL post-COVID. However, the extent, severity, and duration of this is not consistent. The evidence on the long-term impact of a mild COVID-19 infection on HRQoL is uncertain. Implications for policy and practice include: O_LIAn initial mild COVID-19 illness can lead to a reduction in HRQoL and impaired mental health, but there is evidence indicating that patients can show significant recovery up to normal levels after one year. C_LIO_LIEmployers should be aware that employees may have prolonged experiences of impaired mental health, including anxiety, depression, and fatigue, following COVID-19 disease, even if their initial disease was mild (not hospitalised). C_LIO_LIPublic health agencies should make patients with mild COVID-19 disease aware of the potential for ongoing symptoms and ways to mitigate and manage them through raised awareness and education. C_LIO_LIHealth Boards should review their provision of long-COVID services in relation to the extent of impacts identified. C_LIO_LIBetter quality studies that report longitudinal follow-up data on HRQoL for a representative cohort of patients who have had mild COVID-19 are required. C_LI Funding statementThe Bangor Institute for Health and Medical Research, Bangor University was funded for this work by the Wales Covid-19 Evidence Centre, itself funded by Health & Care Research Wales on behalf of Welsh Government. Rapid Review DetailsO_ST_ABSReview conducted byC_ST_ABSBangor Institute for Health and Medical Research Rapid Review Team Review TeamO_LIDr Llinos Haf Spencer, l.spencer@bangor.ac.uk C_LIO_LIDr Annie Hendry, a.hendry@bangor.ac.uk C_LIO_LIMr Abraham Makanjuola, a.makanjuola@bangor.ac.uk C_LIO_LIMr Jacob Davies, j.davies@bangor.ac.uk C_LIO_LIMiss Kalpa Pisavadia, kalpa.pisavadia@bangor.ac.uk C_LIO_LIProfessor Dyfrig Hughes, d.a.hughes@bangor.ac.uk C_LIO_LIProfessor Deb Fitzsimmons, d.fitzsimmons@swansea.ac.uk C_LIO_LIProfessor Clare Wilkinson, c.wilkinson@bangor.ac.uk C_LIO_LIProfessor Rhiannon Tudor Edwards, r.t.edwards@bangor.ac.uk C_LI Review submitted to the WCEC inJuly 2022 Rapid Review report issued by the WCEC inAugust 2022 WCEC TeamAdrian Edwards, Ruth Lewis, Alison Cooper and Micaela Gal involved in drafting, Topline Summary, editing etc. This review should be cited asRR00040. Wales COVID-19 Evidence Centre. What is the long-term impact of COVID-19 on the Health-Related Quality of Life of individuals with mild symptoms (or non-hospitalised): A rapid review. July 2022. This report can be downloaded herehttps://healthandcareresearchwales.org/wales-covid-19-evidence-centre-report-library DisclaimerThe views expressed in this publication are those of the authors, not necessarily Health and Care Research Wales. The WCEC and authors of this work declare that they have no conflict of interest. TOPLINE SUMMARYO_ST_ABSWhat is a Rapid Review?C_ST_ABSOur rapid reviews use a variation of the systematic review approach, abbreviating or omitting some components to generate the evidence to inform stakeholders promptly whilst maintaining attention to bias. They follow the methodological recommendations and minimum standards for conducting and reporting rapid reviews, including a structured protocol, systematic search, screening, data extraction, critical appraisal, and evidence synthesis to answer a specific question and identify key research gaps. They take 1-2 months, depending on the breadth and complexity of the research topic/ question(s), extent of the evidence base, and type of analysis required for synthesis. Who is this summary for?The Department of Health and Social Care (DHSC), who have previously created a COVID-19 morbidities model to support the COVID-19 pandemic response. It will also inform Welsh Government policy through work conducted by the Technical Advisory Cell. Background / Aim of Rapid ReviewThe COVID-19 morbidities model has been widely used since 2020 to support Test and Trace and assess the cost-effectiveness of the COVID-19 vaccination programme. The current iteration of the Long COVID model covers several morbidities associated with COVID-19, which are essential to plan for elective care in the future and identify which services to prioritise. However, there are uncertainties in the model around the long-term health-related quality of life (HRQoL) impact of COVID-19, which is primarily based on data for severe COVID disease or hospitalised patients at present. The COVID-19 morbidities model requires updating to address gaps and reflect the latest HRQoL evidence. The aim of this Rapid Review was to provide updated HRQoL evidence for the COVID-19 morbidities model to better support decision-making in relation to COVID-19 policy. The latest edition of the model was published by the DHSC team in December 2020. The review focused on studies reporting on the long-term impact on HRQoL of patients who had experienced mild symptoms or were not treated in hospital. Inclusion was limited to studies that used validated HRQoL measures, which can be mapped onto EuroQol Quality of Life Measure - 5 dimensions (EQ-5D) and conducted in OECD countries. Two existing systematic reviews were used to identify relevant primary studies published before January 2021, with new searches focusing on the period between January 2021 to June 2022. Key FindingsThirteen primary studies were identified. Extent of the evidence baseO_LIMost studies (n=8) were cross-sectional surveys or reported on HRQoL outcomes at a single time point post-COVID (n=2). Only three studies (one of which was a case report) provided longitudinal follow-up data, which included changes from baseline or reported data at multiple time points. C_LIO_LIOnly two studies reported on HRQoL beyond six months follow-up: One study reported data at three months, six months, and twelve months follow-up and one study measured outcomes at six to eleven months. Five studies measured HRQoL at three months post COVID-19, one at four months, and one at five months. Three studies reported data at two months or less post COVID-19. C_LIO_LITwo studies (one was a case report) focused solely on patients with mild infection, whilst the remaining eleven studies also included patients with moderate or severe/critical COVID-19 illness. Three studies included participants categorised as non-hospitalised or hospitalised patients. twelve studies recruited patients attending outpatients or health care settings; one study recruited a general Swedish population who had a previous COVID-19 infection. C_LIO_LIThe studies were conducted in Turkey (n=2), Denmark (n=1), Sweden (n=1), USA (n=2), Chile (n=1), Ukraine (n=1), Mexico (n=1), Austria (n=2), and The Netherlands (n=2). No UK-based studies were identified. C_LI Recency of the evidence baseO_LIThree studies published in 2022 were conducted in 2021 (Akova & Gedikli, 2022; Bileviciute-Ljungar et al., 2022; Tanriverdi et al., 2022). C_LI Summary of resultsO_LIPeople who had an initial mild COVID-19 illness or were not treated in hospital can have a decreased HRQoL post-COVID. However, the extent, severity, and duration of this is not consistent. C_LI Best evidence availableO_LIHan et al., (2022) recruited outpatients who had mild initial COVID-19 disease and measured HRQoL at six to eleven months follow-up; 436/2092 (21%) outpatients responded to the survey. The findings indicated that the burden of persistent symptoms was significantly associated with poorer long-term health status, poorer quality of life, and psychological distress. C_LIO_LISiegerink et al., (2021) measured HRQoL at three months, six months, and twelve months follow-up, and recruited patients presenting at hospital with COVID-19, a proportion of whom were not hospitalised. At three months follow-up, 22% (n=9) of the non-hospitalised group reported abnormal Hospital Anxiety and Depression Scale (HADS) scores (cut-off at 16). After six months, this decreased to 16% (for n=4), and 14.8% at twelve months (n=4). C_LIO_LILabarca et al., (2021) reported a change from baseline in percentage satisfaction with HRQoL. They found 50% of the (n=18) mild (non-hospitalised) COVID-19 patients reported an individual change in HRQoL, categorised as a change of [≥] 10% on a Visual Analogue Scale (VAS) at four months follow-up. C_LI Policy ImplicationsO_LIAn initial mild COVID-19 illness can lead to a reduction in HRQoL and impaired mental health, but there is evidence indicating that patients can show significant recovery up to normal levels after one year. C_LIO_LIEmployers should be aware that employees may have prolonged experiences of impaired mental health, including anxiety, depression, and fatigue, following COVID-19 disease, even if their initial disease was mild (not hospitalised). C_LIO_LIPublic health agencies should make patients with mild COVID-19 disease aware of the potential for ongoing symptoms and ways to mitigate and manage them through raised awareness and education. C_LIO_LIHealth Boards should review their provision of long-COVID services in relation to the extent of impacts identified. C_LIO_LIBetter quality studies that report longitudinal follow-up data on HRQoL for a representative cohort of patients who have had mild COVID-19 are required. C_LI Strength of EvidenceO_LIThe evidence on the long-term impact of a mild COVID-19 infection on HRQoL is uncertain. C_LI

What innovations can address inequalities experienced by women and girls due to the COVID-19 pandemic across the different areas of life/domains: work, health, living standards, personal security, participation and education? Rapid Review

TOPLINE SUMMARYO_ST_ABSWhat is a Rapid Review?C_ST_ABSOur rapid reviews use a variation of the systematic review approach, abbreviating or omitting some components to generate the evidence to inform stakeholders promptly whilst maintaining attention to bias. They follow the methodological recommendations and minimum standards for conducting and reporting rapid reviews, including a structured protocol, systematic search, screening, data extraction, critical appraisal and evidence synthesis to answer a specific question and identify key research gaps. They take one to two months, depending on the breadth and complexity of the research topic/question(s), the extent of the evidence base and type of analysis required for synthesis. Background / Aim of Rapid ReviewThe COVID-19 pandemic has led to differential economic, health and social impacts illuminating prevailing gender inequalities (WEN Wales, 2020). This rapid review investigated evidence for effectiveness of interventions to address gender inequalities across the domains of work, health, living standards, personal security, participation, and education. Key FindingsO_ST_ABSExtent of the evidence baseC_ST_ABSO_LI21 studies were identified: 7 reviews, 6 commentaries and 8 primary studies C_LIO_LILimited evidence for the effectiveness of identified innovations in minority groups C_LIO_LIA lack of evaluation data for educational interventions C_LIO_LIA lack of evidence for cost-effectiveness of the identified interventions C_LIO_LI14 additional articles were identified in the grey literature but not used to inform findings (apart from the Education domain, where there was a lack of peer-reviewed evidence). C_LI Recency of the evidence baseO_LIAll studies were published in 2020-2021 C_LI Summary of findingsSome evidence supported interventions/innovations related to work: O_LIPermanent contracts, full-time hours, and national childcare programmes to increase income for women and thereby decrease the existing gender wage gap. C_LIO_LIMore frequent use of online platforms in the presentation of professional work can reduce gender disparities due to time saved in travel away from home. C_LI Some evidence supported interventions/innovations related to health: O_LILeadership in digital health companies could benefit from women developing gender-friendly technology that meets the health needs of women. C_LIO_LICreate authentic partnerships with black women and female-led organisations to reduce maternal morbidity and mortality (Bray & McLemore, 2021). C_LI Some evidence supported interventions/innovations related to living standards including: O_LIMulti-dimensional care provided to women and their children experiencing homelessness. C_LI Limited evidence supported interventions/innovations related to personal security including: O_LISpecific training of social workers, psychologists and therapists to empower women to use coping strategies and utilise services to gain protection from abusive partners. C_LIO_LIHelplines, virtual safe spaces smart phone applications and online counselling to address issues of violence and abuse for women and girls. C_LI Very limited evidence supported interventions/innovations related to participation including: O_LIUse of online platforms to reduce gender disparities in the presentation of academic/professional work. C_LIO_LIEnsuring equal representation, including women and marginalised persons, in pandemic response and recovery planning and decision-making. C_LI Limited evidence from the grey literature described interventions/innovations related to education including: O_LITeacher training curricula development to empower teachers to understand and challenge gender stereotypes in learning environments. C_LIO_LIEducation for girls to enable participation in STEM. C_LI Policy ImplicationsThis evidence can be used to map against existing policies to identify which are supported by the evidence, which are not in current policy and could be implemented and where further research/evaluation is needed. Further research is needed to evaluate the effectiveness of educational innovations, the effectiveness of the innovations in minority groups and the social value gained from interventions to address gender inequalities. Strength of EvidenceOne systematic review on mobile interventions targeting common mental disorders among pregnant and postpartum women was rated as high quality (Saad et al., 2021). The overall confidence in the strength of evidence was rated as low due to study designs. Searches did not include COVID specific resources or pre-prints. There may be additional interventions/innovations that have been implemented to reduce inequalities experienced by women and girls due to the COVID-19 pandemic but have not been evaluated or published in the literature and are therefore not included here.

Have infection control and prevention measures resulted in any adverse outcomes for care home and domiciliary care residents and staff?

TOPLINE SUMMARYO_ST_ABSWhat is a Rapid Review?C_ST_ABSOur rapid reviews use a variation of the systematic review approach, abbreviating or omitting some components to generate the evidence to inform stakeholders promptly whilst maintaining attention to bias. They follow the methodological recommendations and minimum standards for conducting and reporting rapid reviews, including a structured protocol, systematic search, screening, data extraction, critical appraisal and evidence synthesis to answer a specific question and identify key research gaps. They take 1-2 months, depending on the breadth and complexity of the research topic/question(s), the extent of the evidence base and type of analysis required for synthesis. Background / Aim of Rapid ReviewCare for older and vulnerable people must sustain core infection prevention and control (IPC) practices and remain vigilant for COVID-19 transmission to prevent virus spread and protect residents and healthcare professionals from severe infections, hospitalisations and death. However, these measures could potentially lead to adverse outcomes such as decreased mental wellbeing in patients and staff. A recent publication by Public Health England examines the effectiveness of IPC practices for reducing COVID-19 transmission in care homes (Duval et al., 2021). We explore evidence relating to adverse outcomes from IPC practices to help inform policy recommendations and identify gaps within the literature where further research can be prioritised. Key FindingsO_ST_ABSExtent of the evidence baseC_ST_ABSO_LI15 studies were identified: 14 primary studies and one rapid review C_LI Recency of the evidence baseO_LIOf the primary studies, six were published in 2020 and eight were published in 2021 C_LIO_LIThe rapid review was published in 2021. C_LI Summary of findingsThis rapid review focuses on adverse outcomes resulting from increased IPC measures put in place during the COVID-19 pandemic. Whilst there is some evidence to show that there may be a link between IPC measures and adverse outcomes, causation cannot be assumed. O_LIDuring the COVID-19 restrictions, the cognition, mental wellbeing and behaviour of residents in care homes were negatively affected C_LIO_LIIncreased IPC procedures during the COVID-19 pandemic increased stress and burden among care staff because of increased workload and dilemmas between adhering well to IPC procedures and providing the best care for the care recipients C_LIO_LICOVID-19 IPC procedures were not well developed at the beginning of the COVID-19 pandemic, but evidence from 2021 suggests that good adherence to IPC measures can enable visitations by family members and medical professionals into care homes C_LIO_LIOnly one study investigating domiciliary care was found. Therefore, it is difficult to make conclusions related specifically to this care setting C_LIO_LINo published studies have reported on the costs or cost-effectiveness of IPC measures or have explored the cost implications of adverse outcomes associated with IPC measures C_LI Best quality evidenceOnly one study was deemed as high quality based on the quality appraisal checklist ranking. This was a mixed methods study design (Tulloch et al., 2021). Policy ImplicationsSince March 2020, there have been many changes to government guidelines relating to procedures to keep the population safe from COVID-19 harm. Policies vary according to country, even within the UK. Important issues such as care home visitation policies have changed in such a way that care home staff have felt it difficult to keep up with the changes, which in itself increased the burden on those staff. The following implications were identified from this work: O_LIIPC policies should be clear, concise and tailored to care homes and domiciliary care settings C_LIO_LIIncreased attention to workforce planning is needed to ensure adequate staffing and to reduce individual burden C_LIO_LIRestrictions (e.g. visitation) for care home residents needs to be balanced by additional psychological support C_LIO_LIFurther research with robust methods in this area is urgently needed especially in the domiciliary care setting C_LI Strength of EvidenceOne limitation is the lack of high-quality evidence from the included studies. Confidence in the strength of evidence about adverse outcomes of COVID-19 IPC procedures was rated as low overall. Whilst the majority of studies achieved a moderate score based on the quality appraisal tools used, due to the nature of the methods used, the overall quality of evidence is low.

Impact of relaxing Covid-19 social distancing measures on rural North Wales: a simulation analysis

BackgroundSocial distancing policies aimed to limit Covid-19 are gradually being relaxed as nationally reported peaks in incident cases are passed. Population density is an important driver of national incidence rates; however peak incidences in rural regions may lag national figures by several weeks. We aimed to forecast the impact of relaxed social distancing rules on rural North Wales. MethodsDaily data on the deaths of people with a positive test for Covid-19 were obtained from Public Health Wales and the UK Government. Sigmoidal growth functions were fitted by non-linear least squares and model averaging used to extrapolate mortality over time. The dates of peak mortality incidences for North Wales, Wales and the UK; and the percentage predicted maximum mortality (as of 7th May 2020) were estimated. ResultsThe peak daily death rates in Wales and the UK were estimated to have occurred on the 14/04/2020 and 15/04/2020, respectively. For North Wales, this occurred on the 07/05/2020, corresponding to the date of analysis. The number of deaths reported in North Wales represents 31% of the predicted total cumulative number, compared with 71% and 60% for Wales and the UK, respectively. ConclusionPolicies governing the movement of people in the gradual release from lockdown are likely to impact significantly on areas -principally rural in nature- where cases of Covid-19, deaths and immunity are likely to be much lower than in populated areas. This is particularly difficult to manage across jurisdictions, such as between England and Wales, and in popular holiday destinations.