Pre-COVID-19 pandemic health-related behaviours in children (2018-2020) and association with being tested for SARS-CoV-2 and testing positive for SARS-CoV-2 (2020-2021): a retrospective cohort study using survey data linked with routine health data in Wales, UK

Objectives
Examine if pre-COVID-19 pandemic (prior March 2020) health-related behaviours during primary school are associated with (1) being tested for SARS-CoV-2 and (2) testing positive between 1 March 2020 and 31 August 2021.

Design
Retrospective cohort study using an online cohort survey (January 2018 to February 2020) linked with routine PCR SARS-CoV-2 test results.

Setting
Children attending primary schools in Wales (2018–2020), UK, who were part of the Health and Attainment of Pupils in a Primary Education Network (HAPPEN)_school network.

Participants
Complete linked records of eligible participants were obtained for n=7062 individuals. 39.1% (n=2764) were tested (age 10.6±0.9; 48.9% girls) and 8.1% (n=569) tested positive for SARS-CoV-2 (age 10.6±1.0; 54.5% girls).

Main outcome measures
Logistic regression of health-related behaviours and demographics were used to determine the ORs of factors associated with (1) being tested for SARS-CoV-2 and (2) testing positive for SARS-CoV-2.

Results
Consuming sugary snacks (1–2 days/week OR=1.24, 95% CI 1.04 to 1.49; 5–6 days/week OR=1.31, 95% CI 1.07 to 1.61; reference 0 days), can swim 25 m (OR=1.21, 95% CI 1.06 to 1.39) and age (OR=1.25, 95% CI 1.16 to 1.35) were associated with an increased likelihood of being tested for SARS-CoV-2. Eating breakfast (OR=1.52, 95% CI 1.01 to 2.27), weekly physical activity ≥60 min (1–2 days OR=1.69, 95% CI 1.04 to 2.74; 3–4 days OR=1.76, 95% CI 1.10 to 2.82; reference 0 days), out-of-school club participation (OR=1.06, 95% CI 1.02 to 1.10), can ride a bike (OR=1.39, 95% CI 1.00 to 1.93), age (OR=1.16, 95% CI 1.05 to 1.28) and girls (OR=1.21, 95% CI 1.00 to 1.46) were associated with an increased likelihood of testing positive for SARS-CoV-2. Living in least deprived areas (quintile 4 OR=0.64, 95% CI 0.46 to 0.90; quintile 5 OR=0.64, 95% CI 0.46 to 0.89) compared with the most deprived (quintile 1) was associated with a decreased likelihood.

Conclusions
Associations may be related to parental health literacy and monitoring behaviours. Physically active behaviours may include coparticipation with others and exposure to SARS-CoV-2. A risk-versus-benefit approach must be considered in relation to promoting these health behaviours, given the importance of health-related behaviours such as childhood physical activity for development.

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Settembre 2022

Negative consequences of failing to communicate uncertainties during a pandemic: an online randomised controlled trial on COVID-19 vaccines

Objective
To examine the impact of the government communicating uncertainties relating to COVID-19 vaccine effectiveness on vaccination intention and trust after people are exposed to conflicting information.

Design
Experimental design where participants were randomly allocated to one of two groups.

Setting
Online.

Participants
328 adults from a UK research panel.

Intervention
Participants received either certain or uncertain communications from a government representative about COVID-19 vaccine effectiveness, before receiving conflicting information about effectiveness.

Main outcome measures
Vaccination intention and trust in government.

Results
Compared with those who received the uncertain announcement from the government, participants who received the certain announcement reported a greater loss of vaccination intention (d=0.34, 95% CI (0.12 to 0.56), p=0.002) and trust (d=0.34, 95% CI (0.12 to 0.56), p=0.002) after receiving conflicting information.

Conclusions
Communicating with certainty about COVID-19 vaccines reduces vaccination intention and trust if conflicting information arises, whereas communicating uncertainties can protect people from the negative impact of exposure to conflicting information. There are likely to be other factors affecting vaccine intentions, which we do not account for in this study.

Trial registration number
Open Science Framework: https://osf.io/c73px/.

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Settembre 2022

Severe COVID-19 anxiety among adults in the UK: protocol for a cohort study and nested feasibility trial of modified cognitive-behavioural therapy for health anxiety

Introduction
Some people are so anxious about COVID-19 that it impairs their functioning. However, little is known about the course of severe COVID-19 anxiety or what can be done to help people who experience it.

Methods and analysis
Cohort study with a nested feasibility trial with follow-up at 3 and 6 months. We recruited 306 people who were aged 18 and over, lived in the UK and had severe COVID-19 anxiety (indicated by a score of 9 or more on the Coronavirus Anxiety Scale (CAS)). To take part in the nested feasibility trial, participants also had to have a score of 20 or more on the Short Health Anxiety Inventory. We excluded people from the trial if they had had COVID-19 within the previous 4 weeks, if they were currently self-isolating or if they were already receiving psychological treatment.
We publicised the study nationally through adverts, social media and posts on message boards. We also recruited participants via clinicians working in primary and secondary care NHS services in London. All those in the active arm will be offered 5–10 sessions of remotely delivered modified cognitive–behavioural therapy for health anxiety (CBT-HA). We will examine the proportion of participants who remain above threshold on the CAS at 3 and 6 months and factors that influence levels of COVID-19 anxiety over 6 months using mixed effects logistic regression. The key feasibility metrics for the nested trial are the level of uptake of CBT-HA and the rate of follow-up.

Ethics and dissemination
Approved by Leicester Central Research Ethics Committee (reference: 20/EM/0238). The results of the study will be published in peer-reviewed scientific journals.

Trial registration number
ISRCTN14973494.

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Settembre 2022

Lactobacillus gallinarum modulates the gut microbiota and produces anti-cancer metabolites to protect against colorectal tumourigenesis

Objective
Using faecal shotgun metagenomic sequencing, we identified the depletion of Lactobacillus gallinarum in patients with colorectal cancer (CRC). We aimed to determine the potential antitumourigenic role of L. gallinarum in colorectal tumourigenesis.

Design
The tumor-suppressive effect of L. gallinarum was assessed in murine models of CRC. CRC cell lines and organoids derived from patients with CRC were cultured with L. gallinarum or Escherichia coli MG1655 culture-supernatant to evaluate cell proliferation, apoptosis and cell cycle distribution. Gut microbiota was assessed by 16S ribosomal DNA sequencing. Antitumour molecule produced from L. gallinarum was identified by liquid chromatography mass spectrometry (LC-MS/MS) and targeted mass spectrometry.

Results
L. gallinarum significantly reduced intestinal tumour number and size compared with E. coli MG1655 and phosphate-buffered saline in both male and female murine intestinal tumourigenesis models. Faecal microbial profiling revealed enrichment of probiotics and depletion of pathogenic bacteria in L. gallinarum-treated mice. Culturing CRC cells with L. gallinarum culture-supernatant (5%, 10% and 20%) concentration-dependently suppressed cell proliferation and colony formation. L. gallinarum culture-supernatant significantly promoted apoptosis in CRC cells and patient-derived CRC organoids, but not in normal colon epithelial cells. Only L. gallinarum culture-supernatant with fraction size

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Settembre 2022

Immature neutrophils bring anti-PD-1 therapy in NASH-HCC to maturity

Liver cancer remains a global health burden, and hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancer cases. HCC can have viral causes, for example, chronic hepatitis B virus or hepatitis C virus infections, and non-viral causes such as non-alcoholic steatohepatitis (NASH) or alcohol-related liver cirrhosis. Particularly HCC related to NASH increased tremendously over the past decade and is expected to rise further. NASH, the advanced form of non-alcoholic fatty liver diseases (NAFLD), is characterised by chronic liver inflammation as a consequence of lipid accumulation and metabolic injury in the liver. This inflammatory hepatic environment in NASH is critical for driving HCC, so that HCC can even develop in non-cirrhotic NASH livers.1 The introduction of immune checkpoint inhibition (ICI) as the new first-line systemic therapy for HCC has raised substantial concerns whether ‘T-cell activation’ with ICI as part of the tumour defence would be similarly…

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Settembre 2022

Multicountry study protocol of COCOON: COntinuing Care in COVID-19 Outbreak global survey of New, expectant, and bereaved parent experiences

Introduction
Globally, the COVID-19 pandemic has significantly disrupted the provision of healthcare and efficiency of healthcare systems and is likely to have profound implications for pregnant and postpartum women and their families including those who experience the tragedy of stillbirth or neonatal death. This study aims to understand the psychosocial impact of COVID-19 and the experiences of parents who have accessed maternity, neonatal and bereavement care services during this time.

Methods and analysis
An international, cross-sectional, online and/or telephone-based/face-to-face survey is being administered across 15 countries and available in 11 languages. New, expectant and bereaved parents during the COVID-19 pandemic will be recruited. Validated psychometric scales will be used to measure psychosocial well-being. Data will be analysed descriptively and by assessing multivariable associations of the outcomes with explanatory factors. In seven of these countries, bereaved parents will be recruited to a nested, qualitative interview study. The data will be analysed using a grounded theory analysis (for each country) and thematic framework analysis (for intercountry comparison) to gain further insights into their experiences.

Ethics and dissemination
Ethics approval for the multicountry online survey, COCOON, has been granted by the Mater Misericordiae Human Research Ethics Committee in Australia (reference number: AM/MML/63526). Ethics approval for the nested qualitative interview study, PUDDLES, has been granted by the King’s College London Biomedical & Health Sciences, Dentistry, Medicine and Natural & Mathematical Sciences Research Ethics Subcommittee (reference number: HR-19/20-19455) in the UK. Local ethics committee approvals were granted in participating countries where required. Results of the study will be published in international peer-reviewed journals and through parent support organisations. Findings will contribute to our understanding of delivering maternity care services, particularly bereavement care, in high-income, lower middle-income and low-income countries during this or future health crises.

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Settembre 2022

Development and validation of a dynamic 48-hour in-hospital mortality risk stratification for COVID-19 in a UK teaching hospital: a retrospective cohort study

Objectives
To develop a disease stratification model for COVID-19 that updates according to changes in a patient’s condition while in hospital to facilitate patient management and resource allocation.

Design
In this retrospective cohort study, we adopted a landmarking approach to dynamic prediction of all-cause in-hospital mortality over the next 48 hours. We accounted for informative predictor missingness and selected predictors using penalised regression.

Setting
All data used in this study were obtained from a single UK teaching hospital.

Participants
We developed the model using 473 consecutive patients with COVID-19 presenting to a UK hospital between 1 March 2020 and 12 September 2020; and temporally validated using data on 1119 patients presenting between 13 September 2020 and 17 March 2021.

Primary and secondary outcome measures
The primary outcome is all-cause in-hospital mortality within 48 hours of the prediction time. We accounted for the competing risks of discharge from hospital alive and transfer to a tertiary intensive care unit for extracorporeal membrane oxygenation.

Results
Our final model includes age, Clinical Frailty Scale score, heart rate, respiratory rate, oxygen saturation/fractional inspired oxygen ratio, white cell count, presence of acidosis (pH

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Settembre 2022

Impact of COVID-19 on college students at one of the most diverse campuses in the USA: a factor analysis of survey data

Objective
This survey study is designed to understand the impact of the COVID-19 pandemic on stress among specific subpopulations of college students.

Design, settings and participants
An online questionnaire was sent to the students from University of Nevada, Las Vegas, between October 2020 and December to assess the psychological impact of COVID-19. A total of 2091 respondents signed the consent form online and their responses were collected.

Main outcome measures
Measures of psychological stress, as prescribed by the Perceived Stress Scale (PSS-10). An explanatory factor analysis was carried out on the PSS-10 results. We subsequently analysed each factor using stepwise linear regression that focused on various sociodemographic groups.

Results
A two-factor model was obtained using the explanatory factor analysis. After comparing with the past studies that investigated the factor structure of the PSS-10 scale, we identified these two factors as ‘anxiety’ and ‘irritability’. The subsequent stepwise linear regression analysis suggested that gender and age (p

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Settembre 2022

Developing digital contact tracing tailored to haulage in East Africa to support COVID-19 surveillance: a protocol

Introduction
At the peak of Uganda’s first wave of SARS-CoV-2 in May 2020, one in three COVID-19 cases was linked to the haulage sector. This triggered a mandatory requirement for a negative PCR test result at all ports of entry and exit, resulting in significant delays as haulage drivers had to wait for 24–48 hours for results, which severely crippled the regional supply chain.
To support public health and economic recovery, we aim to develop and test a mobile phone-based digital contact tracing (DCT) tool that both augments conventional contact tracing and also increases its speed and efficiency.

Methods and analysis
To test the DCT tool, we will use a stratified sample of haulage driver journeys, stratified by route type (regional and local journeys).
We will include at least 65% of the haulage driver journeys ~83 200 on the network through Uganda. This allows us to capture variations in user demographics and socioeconomic characteristics that could influence the use and adoption of the DCT tool. The developed DCT tool will include a mobile application and web interface to collate and intelligently process data, whose output will support decision-making, resource allocation and feed mathematical models that predict epidemic waves.
The main expected result will be an open source-tested DCT tool tailored to haulage use in developing countries.
This study will inform the safe deployment of DCT technologies needed for combatting pandemics in low-income countries.

Ethics and dissemination
This work has received ethics approval from the School of Public Health Higher Degrees, Research and Ethics Committee at Makerere University and The Uganda National Council for Science and Technology. This work will be disseminated through peer-reviewed publications, our websites https://project-thea.org/ and Github for the open source code https://github.com/project-thea/.

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Settembre 2022

Running on empty: a longitudinal global study of psychological well-being among runners during the COVID-19 pandemic

Objectives
There are indications that the COVID-19 pandemic has had a profound negative effect on psychological well-being. Here, we investigated this hypothesis using longitudinal data from a large global cohort of runners, providing unprecedented leverage for understanding how the temporal development in the pandemic pressure relates to well-being across countries.

Design
Prospective cohort study.

Setting
Global.

Participants
We used data from the worldwide Garmin-RUNSAFE cohort that recruited runners with a Garmin Connect account, which is used for storing running activities tracked by a Garmin device. A total of 7808 Garmin Connect users from 86 countries participated.

Primary and secondary outcome measures
From 1 August 2019 (prepandemic) to 31 December 2020, participants completed surveys every second week that included the five-item WHO Well-Being Index (WHO-5). Pandemic pressure was proxied by the number of COVID-19-related deaths per country, retrieved from the Coronavirus Resource Centre at Johns Hopkins University. Panel data regression including individual- and time-fixed effects was used to study the association between country-level COVID-19-related deaths over the past 14 days and individual-level self-reported well-being over the past 14 days.

Results
The 7808 participants completed a total of 125 409 WHO-5 records over the study period. We found a statistically significant inverse relationship between the number of COVID-19-related deaths and the level of psychological well-being—independent of running activity and running injuries (a reduction of 1.42 WHO-5 points per COVID-19-related death per 10 000 individuals, p

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Settembre 2022

Correction: Citation impact and social media visibility of Great Barrington and John Snow signatories for COVID-19 strategy

Ioannidis JP. Citation impact and social media visibility of Great Barrington and John Snow signatories for COVID-19 strategy. BMJ Open 2022;12:e052891. doi: 10.1136/bmjopen-2021-052891. The methods section does not indicate the statistical tests being used. The statistical tests are: (i) the Fisher’s exact test for 2×2 tables (ii) the Mann-Whitney U test for two groups. The Kardashian K-index was originally presented in satirical tone in an article,1 but has been used in numerous studies as a measure of an author’s scholarly output compared to their social media presence. The competing interests declaration of the author has been disputed, particularly the author’s relationships to researchers closely linked to the Great Barrington Declaration, most notably Jay Bhattacharya and Scott Atlas. Please see the rapid responses to the article for the criticisms and the author’s response. The author has now provided a more detailed statement relating to his…

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Settembre 2022