The effective reproduction number, Rt, is a key time-varying prognostic for the growth rate of any infectious disease epidemic. Significant changes in Rt can forewarn about new transmissions within a ...population or predict the efficacy of interventions. Inferring Rt reliably and in real-time from observed time-series of infected (demographic) data is an important problem in population dynamics. The renewal or branching process model is a popular solution that has been applied to Ebola and Zika virus disease outbreaks, among others, and is currently being used to investigate the ongoing COVID-19 pandemic. This model estimates Rt using a heuristically chosen piecewise function. While this facilitates real-time detection of statistically significant Rt changes, inference is highly sensitive to the function choice. Improperly chosen piecewise models might ignore meaningful changes or over-interpret noise-induced ones, yet produce visually reasonable estimates. No principled piecewise selection scheme exists. We develop a practical yet rigorous scheme using the accumulated prediction error (APE) metric from information theory, which deems the model capable of describing the observed data using the fewest bits as most justified. We derive exact posterior prediction distributions for infected population size and integrate these within an APE framework to obtain an exact and reliable method for identifying the piecewise function best supported by available epidemic data. We find that this choice optimises short-term prediction accuracy and can rapidly detect salient fluctuations in Rt, and hence the infected population growth rate, in real-time over the course of an unfolding epidemic. Moreover, we emphasise the need for formal selection by exposing how common heuristic choices, which seem sensible, can be misleading. Our APE-based method is easily computed and broadly applicable to statistically similar models found in phylogenetics and macroevolution, for example. Our results explore the relationships among estimate precision, forecast reliability and model complexity.
Nosocomial spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been widely reported, but the transmission pathways among patients and healthcare workers (HCWs) are unclear. ...Identifying the risk factors and drivers for these nosocomial transmissions is critical for infection prevention and control interventions. The main aim of our study was to quantify the relative importance of different transmission pathways of SARS-CoV-2 in the hospital setting.
This is an observational cohort study using data from 4 teaching hospitals in Oxfordshire, United Kingdom, from January to October 2020. Associations between infectious SARS-CoV-2 individuals and infection risk were quantified using logistic, generalised additive and linear mixed models. Cases were classified as community- or hospital-acquired using likely incubation periods of 3 to 7 days. Of 66,184 patients who were hospitalised during the study period, 920 had a positive SARS-CoV-2 PCR test within the same period (1.4%). The mean age was 67.9 (±20.7) years, 49.2% were females, and 68.5% were from the white ethnic group. Out of these, 571 patients had their first positive PCR tests while hospitalised (62.1%), and 97 of these occurred at least 7 days after admission (10.5%). Among the 5,596 HCWs, 615 (11.0%) tested positive during the study period using PCR or serological tests. The mean age was 39.5 (±11.1) years, 78.9% were females, and 49.8% were nurses. For susceptible patients, 1 day in the same ward with another patient with hospital-acquired SARS-CoV-2 was associated with an additional 7.5 infections per 1,000 susceptible patients (95% credible interval (CrI) 5.5 to 9.5/1,000 susceptible patients/day) per day. Exposure to an infectious patient with community-acquired Coronavirus Disease 2019 (COVID-19) or to an infectious HCW was associated with substantially lower infection risks (2.0/1,000 susceptible patients/day, 95% CrI 1.6 to 2.2). As for HCW infections, exposure to an infectious patient with hospital-acquired SARS-CoV-2 or to an infectious HCW were both associated with an additional 0.8 infection per 1,000 susceptible HCWs per day (95% CrI 0.3 to 1.6 and 0.6 to 1.0, respectively). Exposure to an infectious patient with community-acquired SARS-CoV-2 was associated with less than half this risk (0.2/1,000 susceptible HCWs/day, 95% CrI 0.2 to 0.2). These assumptions were tested in sensitivity analysis, which showed broadly similar results. The main limitations were that the symptom onset dates and HCW absence days were not available.
In this study, we observed that exposure to patients with hospital-acquired SARS-CoV-2 is associated with a substantial infection risk to both HCWs and other hospitalised patients. Infection control measures to limit nosocomial transmission must be optimised to protect both staff and patients from SARS-CoV-2 infection.
Infection with SARS-CoV-2 virus is associated with a wide range of symptoms. The REal-time Assessment of Community Transmission -1 (REACT-1) study monitored the spread and clinical manifestation of ...SARS-CoV-2 among random samples of the population in England from 1 May 2020 to 31 March 2022. We show changing symptom profiles associated with the different variants over that period, with lower reporting of loss of sense of smell or taste for Omicron compared to previous variants, and higher reporting of cold-like and influenza-like symptoms, controlling for vaccination status. Contrary to the perception that recent variants have become successively milder, Omicron BA.2 was associated with reporting more symptoms, with greater disruption to daily activities, than BA.1. With restrictions lifted and routine testing limited in many countries, monitoring the changing symptom profiles associated with SARS-CoV-2 infection and effects on daily activities will become increasingly important.
Aim
To assess the content and completeness of Youtube™ as an information source for patients undergoing root canal treatment procedures.
Methodology
YouTube™ (https://www.youtube.com/) was searched ...for information using three relevant treatment search terms (‘endodontics’, ‘root canal’ and ‘root canal treatment’). After exclusions (language, no audio, >15 min, duplicates), 20 videos per search term were selected. General video assessment included duration, ownership, views, age, likes/dislikes, target audience and video/audio quality, whilst content was analysed under six categories (‘aetiology’, ‘anatomy’, ‘symptoms’, ‘procedure’, ‘postoperative course’ and ‘prognosis’). Content was scored for completeness level and statistically analysed using anova and post hoc Tukey's test (P < 0.05).
Results
To obtain 60 acceptable videos, 124 were assessed. Depending on the search term employed, the video content and ownership differed markedly. There was wide variation in both the number of video views and ‘likes/dislikes’. The average video age was 788 days. In total, 46% of videos were ‘posted’ by a dentist/specialist source; however, this was search term specific rising to 70% of uploads for the search ‘endodontic’, whilst laypersons contributed 18% of uploads for the search ‘root canal treatment’. Every video lacked content in the designated six categories, although ‘procedure’ details were covered more frequently and in better detail than other categories. Videos posted by dental professional (P = 0.046) and commercial sources (P = 0.009) were significantly more complete than videos posted by laypeople.
Conclusions
YouTube™ videos for endodontic search terms varied significantly by source and content and were generally incomplete. The danger of patient reliance on YouTube™ is highlighted, as is the need for endodontic professionals to play an active role in directing patients towards alternative high‐quality information sources.
Regular rapid testing can provide twofold benefilts: identifying infectious individuals and providing positive tests sufficiently early during infection that treatment with antivirals can effectively ...inhibit development of severe disease. Here, we provide a quantitative illustration of the extent of nirmatrelvir-associated treatment benefits that are accrued among high-risk populations when rapid tests are administered at various intervals. Strategies for which tests are administered more frequently are associated with greater reductions in the risk of hospitalization, with weighted risk ratios for testing every other day to once every 2 weeks ranging from 0.17 (95% CI: 0.11-0.28) to 0.77 (95% CI: 0.69-0.83) and correspondingly, higher proportions of the infected population benefiting from treatment, ranging from 0.26 (95% CI: 0.18-0.34) to 0.92 (95% CI: 0.80-0.98), respectively. Importantly, reduced treatment delays, coupled with increased test and treatment coverage, have a critical influence on average treatment benefits, confirming the significance of access.
Estimating the case-fatality risk (CFR)-the probability that a person dies from an infection given that they are a case-is a high priority in epidemiologic investigation of newly emerging infectious ...diseases and sometimes in new outbreaks of known infectious diseases. The data available to estimate the overall CFR are often gathered for other purposes (e.g., surveillance) in challenging circumstances. We describe two forms of bias that may affect the estimation of the overall CFR-preferential ascertainment of severe cases and bias from reporting delays-and review solutions that have been proposed and implemented in past epidemics. Also of interest is the estimation of the causal impact of specific interventions (e.g., hospitalization, or hospitalization at a particular hospital) on survival, which can be estimated as a relative CFR for two or more groups. When observational data are used for this purpose, three more sources of bias may arise: confounding, survivorship bias, and selection due to preferential inclusion in surveillance datasets of those who are hospitalized and/or die. We illustrate these biases and caution against causal interpretation of differential CFR among those receiving different interventions in observational datasets. Again, we discuss ways to reduce these biases, particularly by estimating outcomes in smaller but more systematically defined cohorts ascertained before the onset of symptoms, such as those identified by forward contact tracing. Finally, we discuss the circumstances in which these biases may affect non-causal interpretation of risk factors for death among cases.
Rabies has been a widely feared disease for thousands of years, with records of rabid dogs as early as ancient Egyptian and Mesopotamian texts. The reputation of rabies as being inevitably fatal, ...together with its ability to affect all mammalian species, contributes to the fear surrounding this disease. However, the widely held view that exposure to the rabies virus is always fatal has been repeatedly challenged. Although survival following clinical infection in humans has only been recorded on a handful of occasions, a number of studies have reported detection of rabies-specific antibodies in the sera of humans, domestic animals, and wildlife that are apparently healthy and unvaccinated. These 'seropositive' individuals provide possible evidence of exposure to the rabies virus that has not led to fatal disease. However, the variability in methods of detecting these antibodies and the difficulties of interpreting serology tests have contributed to an unclear picture of their importance. In this review, we consider the evidence for rabies-specific antibodies in healthy, unvaccinated individuals as indicators of nonlethal rabies exposure and the potential implications of this for rabies epidemiology. Our findings indicate that whilst there is substantial evidence that nonlethal rabies exposure does occur, serology studies that do not use appropriate controls and cutoffs are unlikely to provide an accurate estimate of the true prevalence of nonlethal rabies exposure.
During the COVID-19 pandemic, national testing programmes were conducted worldwide on unprecedented scales. While testing behaviour is generally recognised as dynamic and complex, current literature ...demonstrating and quantifying such relationships is scarce, despite its importance for infectious disease surveillance and control. Here, we characterise the impacts of SARS-CoV-2 transmission, disease susceptibility/severity, risk perception, and public health measures on SARS-CoV-2 PCR testing behaviour in England over 20 months of the pandemic, by linking testing trends to underlying epidemic trends and contextual meta-data within a systematic conceptual framework. The best-fitting model describing SARS-CoV-2 PCR testing behaviour explained close to 80% of the total deviance in NHS test data. Testing behaviour showed complex associations with factors reflecting transmission level, disease susceptibility/severity (e.g. age, dominant variant, and vaccination), public health measures (e.g. testing strategies and lockdown), and associated changes in risk perception, varying throughout the pandemic and differing between infected and non-infected people.
Flooding due to extreme weather threatens crops and ecosystems. To understand variation in gene regulatory networks activated by submergence, we conducted a high-resolution analysis of chromatin ...accessibility and gene expression at three scales of transcript control in four angiosperms, ranging from a dryland-adapted wild species to a wetland crop. The data define a cohort of conserved submergence-activated genes with signatures of overlapping cis regulation by four transcription factor families. Syntenic genes are more highly expressed than nonsyntenic genes, yet both can have the cis motifs and chromatin accessibility associated with submergence up-regulation. Whereas the flexible circuitry spans the eudicot-monocot divide, the frequency of specific cis motifs, extent of chromatin accessibility, and degree of submergence activation are more prevalent in the wetland crop and may have adaptive importance.
We derive and validate a novel and analytic method for estimating the probability that an epidemic has been eliminated (i.e. that no future local cases will emerge) in real time. When this ...probability crosses 0.95 an outbreak can be declared over with 95% confidence. Our method is easy to compute, only requires knowledge of the incidence curve and the serial interval distribution, and evaluates the statistical lifetime of the outbreak of interest. Using this approach, we show how the time-varying under-reporting of infected cases will artificially inflate the inferred probability of elimination, leading to premature (false-positive) end-of-epidemic declarations. Contrastingly, we prove that incorrectly identifying imported cases as local will deceptively decrease this probability, resulting in delayed (false-negative) declarations. Failing to sustain intensive surveillance during the later phases of an epidemic can therefore substantially mislead policymakers on when it is safe to remove travel bans or relax quarantine and social distancing advisories. World Health Organisation guidelines recommend fixed (though disease-specific) waiting times for end-of-epidemic declarations that cannot accommodate these variations. Consequently, there is an unequivocal need for more active and specialised metrics for reliably identifying the conclusion of an epidemic.
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