A survey of knowledge, perceptions and use of core outcome sets among clinical trialists.

BACKGROUND: Core outcome sets (COS) are standardised sets of outcomes, which represent the minimum outcomes that should be measured and reported in clinical trials. COS can enhance comparability across health trials by reducing heterogeneity of outcome measurement and reporting and potentially minimising selective outcome reporting. Examining what researchers involved in trials know and think about COS is essential to increase awareness and promote COS uptake. The aim of this study is therefore to examine clinical trialists' knowledge, perceptions and experiences of COS. METHODS: An online survey design was used. Participants were clinical trialists, operationalised for the current study as researchers named as the contact person on a trial registered on the International Standard Randomised Controlled Trial Number (ISRCTN) Trial repository between 1 January 2019 and 21 July 2020. Survey items assessed clinical trialists' familiarity with and understanding of COS, along with experiences of COS use and development. RESULTS: Of 1913 clinical trialists contacted to participate, 62 (3%) completed the survey. Forty (65%) participants were familiar with COS and, of those familiar with COS, 21 (55%) had been involved in a trial that used a COS. Of clinical trialists who used COS in a trial(s), less than half (n = 9, 41%) reported that all COS outcomes were used. The main barriers to using COS are poor knowledge about COS (n = 43, 69%) and difficulties identifying relevant COS (n = 42, 68%). Clinical trialists also reported perceptions of COS as restrictive and often containing too many outcomes. The main enablers to using COS are clear understanding (n = 51, 82%) and perceived importance of COS (n = 44, 71%). CONCLUSIONS: Enhancing clinical trialists' use of all COS outcomes is needed to reduce outcome heterogeneity and enhance comparability across trial findings. Enhancing awareness of COS importance among researchers and funders is needed to ensure that COS are developed and used by clinical trialists. Education and training may further promote awareness and understanding of COS.

The impact of behavioural risk factors on communicable diseases: a systematic review of reviews.

BACKGROUND: The coronavirus (COVID-19) pandemic has highlighted that individuals with behavioural risk factors commonly associated with non-communicable diseases (NCDs), such as smoking, harmful alcohol use, obesity, and physical inactivity, are more likely to experience severe symptoms from COVID-19. These risk factors have been shown to increase the risk of NCDs, but less is known about their broader influence on communicable diseases. Taking a wide focus on a range of common communicable diseases, this review aimed to synthesise research examining the impact of behavioural risk factors commonly associated with NCDs on risks of contracting, or having more severe outcomes from, communicable diseases. METHODS: Literature searches identified systematic reviews and meta-analyses that examined the association between behavioural risk factors (alcohol, smoking, illicit drug use, physical inactivity, obesity and poor diet) and the contraction/severity of common communicable diseases, including infection or associated pathogens. An a priori, prospectively registered protocol was followed (PROSPERO; registration number CRD42020223890). RESULTS: Fifty-three systematic reviews were included, of which 36 were also meta-analyses. Reviews focused on: tuberculosis, human immunodeficiency virus, hepatitis C virus, hepatitis B virus, invasive bacterial diseases, pneumonia, influenza, and COVID-19. Twenty-one reviews examined the association between behavioural risk factors and communicable disease contraction and 35 examined their association with communicable disease outcomes (three examined their association with both contraction and outcomes). Fifty out of 53 reviews (94%) concluded that at least one of the behavioural risk factors studied increased the risk of contracting or experiencing worse health outcomes from a communicable disease. Across all reviews, effect sizes, where calculated, ranged from 0.83 to 8.22. CONCLUSIONS: Behavioural risk factors play a significant role in the risk of contracting and experiencing more severe outcomes from communicable diseases. Prevention of communicable diseases is likely to be most successful if it involves the prevention of behavioural risk factors commonly associated with NCDs. These findings are important for understanding risks associated with communicable disease, and timely, given the COVID-19 pandemic and the need for improvements in future pandemic preparedness. Addressing behavioural risk factors should be an important part of work to build resilience against any emerging and future epidemics and pandemics.

Decision support-tools for early detection of infection in older people (aged> 65 years): a scoping review.

BACKGROUND: Infection is more frequent, and serious in people aged > 65 as they experience non-specific signs and symptoms delaying diagnosis and prompt treatment. Monitoring signs and symptoms using decision support tools (DST) is one approach that could help improve early detection ensuring timely treatment and effective care. OBJECTIVE: To identify and analyse decision support tools available to support detection of infection in older people (> 65 years). METHODS: A scoping review of the literature 2010-2021 following Arksey and O'Malley (2005) framework and PRISMA-ScR guidelines. A search of MEDLINE, Cochrane, EMBASE, PubMed, CINAHL, Scopus and PsycINFO using terms to identify decision support tools for detection of infection in people > 65 years was conducted, supplemented with manual searches. RESULTS: Seventeen papers, reporting varying stages of development of different DSTs were analysed. DSTs largely focussed on specific types of infection i.e. urine, respiratory, sepsis and were frequently hospital based (n = 9) for use by physicians. Four DSTs had been developed in nursing homes and one a care home, two of which explored detection of non- specific infection. CONCLUSIONS: DSTs provide an opportunity to ensure a consistent approach to early detection of infection supporting prompt action and treatment, thus avoiding emergency hospital admissions. A lack of consideration regarding their implementation in practice means that any attempt to create an optimal validated and tested DST for infection detection will be impeded. This absence may ultimately affect the ability of the workforce to provide more effective and timely care, particularly during the current covid-19 pandemic.

The public health impact of loneliness during the COVID-19 pandemic.

BACKGROUND: Social distancing measures have been effective in mitigating the spread of COVID-19; however, they have imposed a significant burden on population mental health and well-being. This study aimed to identify factors associated with loneliness during the COVID-19 pandemic, and to describe the relationship between loneliness and the risk of worsening health outcomes and behaviours. METHODS: Data for 8,960 adults were drawn from a national cross-sectional survey undertaken in Wales between January and June 2021. Participants self-reported changes to health and behaviour since the start of the pandemic. Logistic regression was used to identify factors associated with loneliness, and the impact of loneliness on self-reported changes in physical health, physical fitness, mental health, weight, alcohol consumption and social relations in comparison with pre-pandemic experiences. RESULTS: Groups most at risk of loneliness were those aged < 35 years, women (odds ratio [95% confidence interval]: 1.86 [1.70-2.05]), those with chronic health conditions (1.43 [1.29-1.58]) and the unemployed (2.18 [1.76-2.70]). Loneliness was a strong predictor of worsening health outcomes and behaviours, with those reporting often feeling lonely being at increased odds of worsening physical health (3.29 [2.80-3.86]), physical fitness (2.22 [1.90-2.60]), mental health (8.33 [6.95-9.99]), weight (1.39 [1.19-1.62]), alcohol consumption (1.37 [1.12,-1.66]) and social relations (2.45 [2.07-2.89]) during the pandemic. CONCLUSION: This study established an association between loneliness and self-reported worsening health during the pandemic, and identified factors increasing the risk of loneliness. The effect that social control measures have on loneliness should influence the design of future public health policy.

An evaluation of the Time to Move workplace physical activity intervention

Background Workplace physical activity interventions have shown positive outcomes for employee health, productivity and absenteeism (1,2). However, the majority prescribe the duration and/or type of activity to be undertaken. In response to strong public opinion that employers should do more to improve the health of their workforce, Public Health Wales, the public health agency for Wales, developed a 12-month pilot physical activity initiative - Time to Move (TTM). TTM allowed participants to use one hour/week (pro rata) of paid work time for any physical activity. We evaluated TTM to understand its impact and identify learning. Methods Using pre-experimental time series design, data were collected from participating employees: baseline (June-August 2018), mid-initiative (December 2018) and at 12-months (June-August 2019). Using validated scales where possible, questionnaires recorded: physical activity (MET-minutes/week), general health (0, poor-100, good), mental well-being (SWEMWBS), job satisfaction (1, very dissatisfied-5, very satisfied) and demographics. Biometric measures (baseline, 12-months) included Body Mass Index (BMI) and blood pressure. Analyses used descriptive statistics, bivariate analysis and generalized linear modelling. Focus groups explored participants' perceptions of TTM, analysed thematically. Results 542 participants completed all measures (63.1% of baseline). Compared to baseline, at 12-months 57.7% reported increased physical activity (30.6% decreased;11.6% no change) with 75.3% meeting UK activity guidelines (58.8% baseline). Those with the lowest levels of physical activity at baseline (n = 223) increased their weekly moderate activity by > 2.5 hours, whilst those with moderate activity (n = 269) increased by 58 minutes/week. A small improvement was reported in mental well-being (mean scores;22.4 baseline, 23.2 12-months), with participants with low mental well-being at baseline improving the most. Self-reported health and job satisfaction also improved. However, BMI and blood pressure changes were non-meaningful. Employee attitudes to TTM were positive. Organisational support was a motivating factor for participation, with competing demands a barrier. Conclusions The provision of paid time to engage in physical activity can improve employee health and well-being. TTM provides an example of how organisations can promote physical activity and change workplace culture. However, further research should explore the long-term impact of the intervention, including the potential impact of COVID-19-related restrictions.

Associations between adverse childhood experiences, attitudes towards COVID-19 restrictions and vaccine hesitancy: a cross-sectional study

ObjectivesAdverse childhood experiences (ACEs) can affect life-course health and well-being, including risk-taking behaviour and trust. This study explored associations between ACEs and trust in health information on COVID-19, attitudes towards and compliance with COVID-19 restrictions and vaccine hesitancy.DesignNational cross-sectional telephone survey using a sample of landline and mobile numbers stratified by Health Board, deprivation quintile and age group.SettingHouseholds in Wales during national COVID-19 restrictions (December 2020 to March 2021).Participants2285 Welsh residents aged ≥18 years.MeasuresNine ACEs;low trust in National Health Service (NHS) COVID-19 information;supporting removal of social distancing and mandatory face coverings;breaking COVID-19 restrictions;and vaccine hesitancy (rejection or uncertainty of vaccination).ResultsIncreasing ACE counts were independently related to low trust in NHS COVID-19 information, feeling unfairly restricted by government and ending mandatory face coverings. High ACE counts (4+ vs 0 ACEs) were also associated with supporting removal of social distancing. Breaking COVID-19 restrictions increased with ACE count with likelihood doubling from no ACEs to 4+ ACEs. Vaccine hesitancy was threefold higher with 4+ ACEs (vs 0 ACEs) and higher in younger age groups. Thus, modelled estimates of vaccine hesitancy ranged from 3.42% with no ACEs, aged ≥70 years, to 38.06% with 4+ ACEs, aged 18–29 years.ConclusionsACEs are common across populations of many countries. Understanding how they impact trust in health advice and uptake of medical interventions could play a critical role in the continuing response to COVID-19 and controlling future pandemics. Individuals with ACEs suffer greater health risks throughout life and may also be excluded from interventions that reduce infection risks. While pandemic responses should consider how best to reach those suffering from ACEs, longer term, better compliance with public health advice is another reason to invest in safe and secure childhoods for all children.

An evaluation of a short film promoting kindness in Wales during COVID-19 restrictions #TimeToBeKind.

BACKGROUND: In response to successive COVID-19 restrictions in Wales, the Welsh ACE Support Hub launched the #TimeToBeKind campaign in March 2021. The campaign used a short film broadcast on national television and promoted on social media to encourage behaviour change for kindness. We evaluated the #TimeToBeKind campaign film to identify whether watching the film would result in increased intention to act in ways that promote kindness to others and if intentions were associated with being emotionally affected by the film. METHODS: A mixed methods evaluation was employed, using a short online survey and interaction with the film on the Twitter social media platform. The online survey measured public (n = 390) attitudes towards the film including feelings invoked, and behavioural intentions for acts of kindness as a result of viewing the film. Tweets which interacted with the film (n = 59; likes, re-tweets or comments), and tweet sentiment (positive, negative, or neutral) towards the film were also explored. RESULTS: The majority of participants reported positive attitudes to the film and agreed that they understood the campaign message (91.8%). 67.9% reported that the film made them feel upset or sad and for 22.6% the film resonated with their lockdown experience. As a result of seeing the film, 63.6% reported intentions to be kinder to others, 65.6% intended to try and help other members of their community, and 70.5% were more likely to check in on friends, family and neighbours. A higher proportion of individuals who were emotionally affected by the film (e.g. upset or sad, hopeful or encouraged, gained something positive) and those for whom the film resonated with their lockdown experience reported increased kindness behavioural intentions as a result of seeing the film. CONCLUSIONS: Film can be an effective tool to promote behaviour change for kindness. Films that provoke strong emotional reactions can still be perceived positively and lead to behaviour change. With the COVID-19 pandemic accelerating a move online for many, the findings of the present evaluation are relevant to how public health messaging can adapt and utilise this space to target individuals and promote behaviour change.

Factors influencing wellbeing in young people during COVID-19: A survey with 6291 young people in Wales.

COVID-19 infection and the resultant restrictions has impacted all aspects of life across the world. This study explores factors that promote or support wellbeing for young people during the pandemic, how they differ by age, using a self-reported online survey with those aged 8-25 in Wales between September 2020 and February 2021. Open-ended responses were analysed via thematic analysis to provide further context. A total of 6,291 responses were obtained from 81 education settings across Wales (including primary and secondary schools as well as sixth form, colleges and universities). Wellbeing was highest in primary school children and boys and lowest in those who were at secondary school children, who were girls and, those who preferred not to give a gender. Among primary school children, higher wellbeing was seen for those who played with lots of others (rather than alone), were of Asian ethnicity (OR 2.17, 95% CI: 1.26 to 4.3), had a safe play area (OR: 2.4, 95% CI: 1.67 to 2.56) and had more sleep. To support their wellbeing young people reported they would like to be able to play with their friends more. Among secondary school children those who were of mixed ethnicity reported lower wellbeing (OR: 5.14, 95% CI: 1.68 to 15.79). To support their wellbeing they reported they would like more support with mental health (due to anxiety and pressure to achieve when learning online). This study found self-reported wellbeing differed by gender, ethnicity and deprivation and found younger children report the need for play and to see friends to support wellbeing but older children/young people wanted more support with anxiety and educational pressures.

Placing health equity at the heart of the COVID-19 recovery: data analysis from the first Welsh Health Equity Status Report initiative

Background The Welsh Health Equity Status Report initiative (WHESRi) applies an innovative WHO framework to map the wider impacts of COVID-19 on health equity. The framework is a mechanism to promote policy action and commitment for health equity and identifies five essential conditions needed to live a healthy life;namely, health services, income security, living conditions, social and human capital, and working conditions. We used the framework to assess the immediate health equity impacts of COVID-19 in Wales. Methods Ten relevant variables from Public Health Wales' public engagement survey on health and wellbeing during COVID-19 (captured April 3–July 25, 2020) were mapped to each of the five essential conditions, as defined by the European Health Equity Status Report initiative. Variables were chosen based on alignment to the essential conditions, research objectives and data quality. Estimated marginal means were disaggregated by sociodemographic factors on a nationally representative study sample ranging from 862 to 4747 participants (dependent on duration for which question was asked). Ethical approval was not required as per guidance from the National Health Service Health Research Association ethics decision tool. Findings The WHESRi framework allowed the assessment and quantification of the immediate impacts of COVID-19 on the wider determinants of health through the lens of the five essential conditions. For example, in relation to income security, a significantly higher proportion (181 [50·6%] of 358;p<0·05) of survey respondents aged 18–24 years reported being worried about losing their job, or not being able to find one, than any other age group. Of those respondents aged 18–24 years, 54·4% (p<0·05) of men (equivalent to 78 000) reported being worried, compared with 44·3% (p<0·05) of women (equivalent to 72 000), a difference of 10·1%. Interpretation Application of the WHESRi framework allowed us to draw a holistic picture of health and its determinants at the population level. This application has highlighted quantifiable differences in impacts between population groups, and encouraged the dialogue around policy action. A priority moving forward is to apply the framework to vulnerable population groups and population health priorities to assess the health equity impacts according to factors such as rurality, disability, and ethnicity. Our findings resulting from the application of this WHO framework can be used to enable an equitable and sustainable recovery from the pandemic;they form part of a European initiative for health equity and provide learning to other countries from Wales' role as an innovation site. Funding None.

Health and financial costs of adverse childhood experiences in 28 European countries: a systematic review and meta-analysis.

BACKGROUND: Adverse childhood experiences (ACEs) are associated with increased health risks across the life course. We aimed to estimate the annual health and financial burden of ACEs for 28 European countries. METHODS: In this systematic review and meta-analysis, we searched MEDLINE, CINAHL, PsycINFO, Applied Social Sciences Index and Abstracts, Criminal Justice Databases, and Education Resources Information Center for quantitative studies (published Jan 1, 1990, to Sept 8, 2020) that reported prevalence of ACEs and risks of health outcomes associated with ACEs. Pooled relative risks were calculated for associations between ACEs and harmful alcohol use, smoking, illicit drug use, high body-mass index, depression, anxiety, interpersonal violence, cancer, type 2 diabetes, cardiovascular disease, stroke, and respiratory disease. Country-level ACE prevalence was calculated using available data. Country-level population attributable fractions (PAFs) due to ACEs were generated and applied to 2019 estimates of disability-adjusted life-years. Financial costs (US$ in 2019) were estimated using an adapted human capital approach. FINDINGS: In most countries, interpersonal violence had the largest PAFs due to ACEs (range 14·7-53·5%), followed by harmful alcohol use (15·7-45·0%), illicit drug use (15·2-44·9%), and anxiety (13·9%-44·8%). Harmful alcohol use, smoking, and cancer had the highest ACE-attributable costs in many countries. Total ACE-attributable costs ranged from $0·1 billion (Montenegro) to $129·4 billion (Germany) and were equivalent to between 1·1% (Sweden and Turkey) and 6·0% (Ukraine) of nations' gross domestic products. INTERPRETATION: Availability of ACE data varies widely between countries and country-level estimates cannot be directly compared. However, findings suggest ACEs are associated with major health and financial costs across European countries. The cost of not investing to prevent ACEs must be recognised, particularly as countries look to recover from the COVID-19 pandemic, which interrupted services and education, and potentially increased risk factors for ACEs. FUNDING: WHO Regional Office for Europe.

Preclinical development of a molecular clamp-stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2.

OBJECTIVES: Efforts to develop and deploy effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue at pace. Here, we describe rational antigen design through to manufacturability and vaccine efficacy of a prefusion-stabilised spike (S) protein, Sclamp, in combination with the licensed adjuvant MF59 'MF59C.1' (Seqirus, Parkville, Australia). METHODS: A panel recombinant Sclamp proteins were produced in Chinese hamster ovary and screened in vitro to select a lead vaccine candidate. The structure of this antigen was determined by cryo-electron microscopy and assessed in mouse immunogenicity studies, hamster challenge studies and safety and toxicology studies in rat. RESULTS: In mice, the Sclamp vaccine elicits high levels of neutralising antibodies, as well as broadly reactive and polyfunctional S-specific CD4+ and cytotoxic CD8+ T cells in vivo. In the Syrian hamster challenge model (n = 70), vaccination results in reduced viral load within the lung, protection from pulmonary disease and decreased viral shedding in daily throat swabs which correlated strongly with the neutralising antibody level. CONCLUSION: The SARS-CoV-2 Sclamp vaccine candidate is compatible with large-scale commercial manufacture, stable at 2-8°C. When formulated with MF59 adjuvant, it elicits neutralising antibodies and T-cell responses and provides protection in animal challenge models.