Search

Background: Few randomized trials of public health and social measures were carried out during the COVID-19 pandemic. We report on the major barriers we faced when we tried to run such trials. Methods: We reviewed all randomized trials proposed and initiated by the Centre for Epidemic Interventions Research in Norway during the COVID-19 pandemic. Results: Of the 18 proposed trials, 11 trials were not implemented. One of the key legal and ethical barriers to conducting the trials was the Norwegian Health Research Act, which demands informed consent from all participants who are exposed to an intervention. A lack of sufficient political support was also a challenge, as was unpredictability, due to shifting disease incidence and changing recommendations from the authorities. Conclusion: Strengthening the evidence base for public health and social measures in pandemics will require political and public understanding and support and a legal framework that allows for the conduct of such trials. [ABSTRACT FROM AUTHOR]

Importance: Understanding the susceptibility and infectiousness of children and adolescents in comparison to adults is important to appreciate their role in the COVID-19 pandemic. Objective: To determine SARS-CoV-2 susceptibility and infectiousness of children and adolescents with adults as comparator for three variants (wild-type, alpha, delta) in the household setting. We aimed to identify the effects independent of vaccination or prior infection. Data sources: We searched EMBASE, PubMed and medRxiv up to January 2022. Study selection: Two reviewers independently identified studies providing secondary household attack rates (SAR) for SARS-CoV-2 infection in children (0–9 years), adolescents (10–19 years) or both compared with adults (20 years and older). Data extraction and synthesis: Two reviewers independently extracted data, assessed risk of bias and performed a random-effects meta-analysis model. Main outcomes and measures: Odds ratio (OR) for SARS-CoV-2 infection comparing children and adolescents with adults stratified by wild-type (ancestral type), alpha, and delta variant, respectively. Susceptibility was defined as the secondary attack rate (SAR) among susceptible household contacts irrespective of the age of the index case. Infectiousness was defined as the SAR irrespective of the age of household contacts when children/adolescents/adults were the index case. Results: Susceptibility analysis: We included 27 studies (308,681 contacts), for delta only one (large) study was available. Compared to adults, children and adolescents were less susceptible to the wild-type and delta, but equally susceptible to alpha. Infectiousness analysis: We included 21 studies (201,199 index cases). Compared to adults, children and adolescents were less infectious when infected with the wild-type and delta. Alpha -related infectiousness remained unclear, 0–9 year old children were at least as infectious as adults. Overall SAR among household contacts varied between the variants. Conclusions and relevance: When considering the potential role of children and adolescents, variant-specific susceptibility, infectiousness, age group and overall transmissibility need to be assessed. [ABSTRACT FROM AUTHOR]

HEV is the most common cause of acute hepatitis globally. This review summarizes the latest knowledge on the epidemiology, clinical characteristics, testing, and treatment of HEV infection. We also focused on Bangladesh to highlight the distinct challenges and the possible remedies. In low-income settings, the virus is mainly transmitted between people by fecal contamination of drinking water causing large outbreaks, and sporadic cases. The disease is usually mild and self-limiting acute hepatitis. Still, pregnant women and their offspring in low-income countries are at particular risk for severe disease, with up to 20% maternal mortality. Despite the high burden of the disease, HEV remains a relatively neglected virus, with detection hampered by costly tests and a lack of suitable treatments. Molecular PCR diagnostics, together with ELISA antibody tests, remain the preferred methods for diagnosis of HEV; however, rapid bedside diagnostics are available and could offer a practical alternative, especially in low-income countries. One vaccine (HEV 239) is only available in China and Pakistan, as efficacy against the other genotypes remains uncertain. The effectiveness trial conducted in Bangladesh might lead the way in gathering more efficacy data and could, together with improved surveillance and raised awareness, dramatically reduce the global burden of HEV. [ABSTRACT FROM AUTHOR]

Background: Histone deacetylase inhibitors (HDACis) like vorinostat are promising radiosensitisers in prostate cancer, but their effect under hypoxia is not known. We investigated gene expression associated with radiosensitisation of normoxic and hypoxic prostate cancer cells by vorinostat.Methods: Cells were exposed to vorinostat under normoxia or hypoxia and subjected to gene expression profiling before irradiation and clonogenic survival analysis.Results: Pretreatment with vorinostat led to radiosensitisation of the intrinsically radioresistant DU 145 cells, but not the radiosensitive PC-3 and 22Rv1 cells, and was independent of hypoxia status. Knockdown experiments showed that the sensitisation was not caused by repression of hypoxia-inducible factor HIF1 or tumour protein TP53. Global deregulation of DNA repair and chromatin organisation genes was associated with radiosensitisation under both normoxia and hypoxia. A radiosensitisation signature with expression changes of 56 genes was generated and valid for both conditions. For eight signature genes, baseline expression also correlated with sensitisation, showing potential as pretreatment biomarker. The hypoxia independence of the signature was confirmed in a clinical data set.Conclusions: Pretreatment with HDACi may overcome radioresistance of hypoxic prostate tumours by similar mechanisms as under normoxia. We propose a gene signature to predict radiosensitising effects independent of hypoxia status. [ABSTRACT FROM AUTHOR]