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Single-agent anti-PD1 checkpoint inhibitors convey outstanding clinical benefits in a small fraction (∼20%) of patients with advanced hepatocellular carcinoma (aHCC) but the molecular mechanisms determining response are unknown. To fill this gap, we herein analyze the molecular and immune traits of aHCC in patients treated with anti-PD1.
Their in vitro performance is excellent; their real-world efficacy awaits more data.
Annals of Internal Medicine, Volume 175, Issue 10, Page 1475, October 2022.
A large observational Dutch study suggests post–COVID-19 conditions occur in 1 of 8 people.
Introduction
Since 2020, the world has been going through a viral pandemic with a high morbidity and mortality rate along with the potential to evolve from an acute infection to post-acute and long-COVID, which is still in the process of elucidation. Diagnostic and prognostic research is essential to understand the complexity of factors and contexts involving the illness’s process. This protocol introduces a study strategy to analyse predictors, sequelae, and repercussions of COVID-19 in adults and older adults with different disease severities in the State of Paraná, Brazil.
Methods and analysis
A mixed-methods sequential explanatory design. The quantitative data will be conducted by an ambispective cohort study, which will explore the manifestations of COVID-19 for 18 months, with nearly 3000 participants with confirmed diagnoses of COVID-19 (reverse transcription-PCR test) between March and December of 2020, retrieved from national disease reporting databases, over 18 years old, living in a Brazilian State (Paraná) and who survived the viral infection after being discharged from a health service. Data collection will be conducted through telephone interviews, at two different occasions: the first will be a recall 12 months after the acute phase as a retrospective follow-up, and the second will be another prospective interview, with data of the following 6 months. For the qualitative step, Grounded Theory will be used; participants will be selected from the cohort population. The first sample group will be composed of people who were discharged from the intensive care unit, and other sample groups will be composed according to theoretical saturation. The qualitative data will follow the temporal design and classification of the disease provided for in the cohort.
Ethics and dissemination
Ethics approval was granted by the State University of Maringá, under opinion number: 4 165 272 and CAAE: 34787020.0.0000.0104 on 21 July 2020, and Hospital do Trabalhador (Worker’s Hospital), which is accountable for the Health Department of the State of Paraná, under opinion number: 4 214 589 and CAAE: 34787020.0.3001.5225 on 15 August 2020. The participants will verbally consent to the research, their consent will be recorded, and the informed consent form will be sent by mail or email. Outcomes will be widely disseminated through peer-reviewed manuscripts, conference presentations, media and reports to related authorities.
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/.
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.
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.
Paul Burton (Moderna). «I dati preclinici di una piattaforma utilizzata per oltre 750 milioni di persone in tutto il mondo permetteranno di stare al passo con l’evoluzione di questo virus»
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…
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
Al via le somministrazioni del vaccino bivalente su Omicron 1. Ma a fine mese potrebbe arrivare quello aggiornato sulla sottovariante Omicron 5
Circulation, Volume 146, Issue 10, Page 802-804, September 6, 2022.
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
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.
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
