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BACKGROUND: Predicting hospital length of stay (LoS) for patients with COVID-19 infection is essential to ensure that adequate bed capacity can be provided without unnecessarily restricting care for patients with other conditions. Here, we demonstrate the utility of three complementary methods for predicting LoS using UK national- and hospital-level data. METHOD: On a national scale, relevant patients were identified from the COVID-19 Hospitalisation in England Surveillance System (CHESS) reports. An Accelerated Failure Time (AFT) survival model and a truncation corrected method (TC), both with underlying Weibull distributions, were fitted to the data to estimate LoS from hospital admission date to an outcome (death or discharge) and from hospital admission date to Intensive Care Unit (ICU) admission date. In a second approach we fit a multi-state (MS) survival model to data directly from the Manchester University NHS Foundation Trust (MFT). We develop a planning tool that uses LoS estimates from these models to predict bed occupancy. RESULTS: All methods produced similar overall estimates of LoS for overall hospital stay, given a patient is not admitted to ICU (8.4, 9.1 and 8.0 days for AFT, TC and MS, respectively). Estimates differ more significantly between the local and national level when considering ICU. National estimates for ICU LoS from AFT and TC were 12.4 and 13.4 days, whereas in local data the MS method produced estimates of 18.9 days. CONCLUSIONS: Given the complexity and partiality of different data sources and the rapidly evolving nature of the COVID-19 pandemic, it is most appropriate to use multiple analysis methods on multiple datasets. The AFT method accounts for censored cases, but does not allow for simultaneous consideration of different outcomes. The TC method does not include censored cases, instead correcting for truncation in the data, but does consider these different outcomes. The MS method can model complex pathways to different outcomes whilst accounting for censoring, but cannot handle non-random case missingness. Overall, we conclude that data-driven modelling approaches of LoS using these methods is useful in epidemic planning and management, and should be considered for widespread adoption throughout healthcare systems internationally where similar data resources exist.
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COVID-19/terapia , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Idoso , COVID-19/epidemiologia , Análise de Dados , Inglaterra/epidemiologia , Feminino , Número de Leitos em Hospital , Planejamento Hospitalar/métodos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The implementation of new antimicrobial resistance stewardship programs is crucial in optimizing antibiotic use. However, prescription choices can be difficult during empiric therapy; clinicians must balance the survival benefits of broader spectrum antibiotics with associated increases in resistance. The aim of this study was to evaluate the overall feasibility of switching to narrow spectrum antibiotics during the empiric treatment of E. coli bacteraemia by quantifying changes in resistance rates, antibiotic usage, and mortality using a deterministic state-transition model. Three unique model scenarios (A, B, and C), each representing a progressively broader spectrum empiric treatment regimen, were used to compare outcomes at 5 years. We show that the empiric use of the narrowest spectrum (first-line) antibiotics can lead to reductions in resistance to second-line antibiotics and the use of third-line antibiotics, but they also lead to increases in resistance to first-line therapy and higher mortality. Crucially, we find that shortening the duration of empiric and overall treatment, as well as reducing the baseline mortality rate, are important for increasing the feasibility of switching to narrow spectrum antibiotics in the empiric treatment of E. coli bacteraemia. We provide a flexible model design to investigate optimal treatment approaches for other bacterial infections.
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Antibacterianos , Bacteriemia , Infecções por Escherichia coli , Escherichia coli , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Humanos , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Escherichia coli/efeitos dos fármacos , Gestão de Antimicrobianos/métodos , Farmacorresistência Bacteriana/efeitos dos fármacos , Modelos TeóricosRESUMO
Vast amounts of pathogen genomic, demographic and spatial data are transforming our understanding of SARS-CoV-2 emergence and spread. We examined the drivers of molecular evolution and spread of 291,791 SARS-CoV-2 genomes from Denmark in 2021. With a sequencing rate consistently exceeding 60%, and up to 80% of PCR-positive samples between March and November, the viral genome set is broadly whole-epidemic representative. We identify a consistent rise in viral diversity over time, with notable spikes upon the importation of novel variants (e.g., Delta and Omicron). By linking genomic data with rich individual-level demographic data from national registers, we find that individuals aged < 15 and > 75 years had a lower contribution to molecular change (i.e., branch lengths) compared to other age groups, but similar molecular evolutionary rates, suggesting a lower likelihood of introducing novel variants. Similarly, we find greater molecular change among vaccinated individuals, suggestive of immune evasion. We also observe evidence of transmission in rural areas to follow predictable diffusion processes. Conversely, urban areas are expectedly more complex due to their high mobility, emphasising the role of population structure in driving virus spread. Our analyses highlight the added value of integrating genomic data with detailed demographic and spatial information, particularly in the absence of structured infection surveys.
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COVID-19 , Genoma Viral , SARS-CoV-2 , Humanos , Dinamarca/epidemiologia , COVID-19/epidemiologia , COVID-19/virologia , COVID-19/transmissão , SARS-CoV-2/genética , SARS-CoV-2/classificação , Genoma Viral/genética , Adulto , Pessoa de Meia-Idade , Idoso , Adolescente , Adulto Jovem , Evolução Molecular , Masculino , Feminino , Pré-Escolar , Criança , Filogenia , LactenteRESUMO
PURPOSE: In this work, the authors present some of the key results found during early efforts to model the COVID-19 outbreak inside a UK prison. In particular, this study describes outputs from an idealised disease model that simulates the dynamics of a COVID-19 outbreak in a prison setting when varying levels of social interventions are in place, and a Monte Carlo-based model that assesses the reduction in risk of case importation, resulting from a process that requires incoming prisoners to undergo a period of self-isolation prior to admission into the general prison population. DESIGN/METHODOLOGY/APPROACH: Prisons, typically containing large populations confined in a small space with high degrees of mixing, have long been known to be especially susceptible to disease outbreaks. In an attempt to meet rising pressures from the emerging COVID-19 situation in early 2020, modellers for Public Health England's Joint Modelling Cell were asked to produce some rapid response work that sought to inform the approaches that Her Majesty's Prison and Probation Service (HMPPS) might take to reduce the risk of case importation and sustained transmission in prison environments. FINDINGS: Key results show that deploying social interventions has the potential to considerably reduce the total number of infections, while such actions could also reduce the probability that an initial infection will propagate into a prison-wide outbreak. For example, modelling showed that a 50% reduction in the risk of transmission (compared to an unmitigated outbreak) could deliver a 98% decrease in total number of cases, while this reduction could also result in 86.8% of outbreaks subsiding before more than five persons have become infected. Furthermore, this study also found that requiring new arrivals to self-isolate for 10 and 14 days prior to admission could detect up to 98% and 99% of incoming infections, respectively. RESEARCH LIMITATIONS/IMPLICATIONS: In this paper we have presented models which allow for the studying of COVID-19 in a prison scenario, while also allowing for the assessment of proposed social interventions. By publishing these works, the authors hope these methods might aid in the management of prisoners across additional scenarios and even during subsequent disease outbreaks. Such methods as described may also be readily applied use in other closed community settings. ORIGINALITY/VALUE: These works went towards informing HMPPS on the impacts that the described strategies might have during COVID-19 outbreaks inside UK prisons. The works described herein are readily amendable to the study of a range of addition outbreak scenarios. There is also room for these methods to be further developed and built upon which the timeliness of the original project did not permit.
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Viral reproduction of SARS-CoV-2 provides opportunities for the acquisition of advantageous mutations, altering viral transmissibility, disease severity, and/or allowing escape from natural or vaccine-derived immunity. We use three mathematical models: a parsimonious deterministic model with homogeneous mixing; an age-structured model; and a stochastic importation model to investigate the effect of potential variants of concern (VOCs). Calibrating to the situation in England in May 2021, we find epidemiological trajectories for putative VOCs are wide-ranging and dependent on their transmissibility, immune escape capability, and the introduction timing of a postulated VOC-targeted vaccine. We demonstrate that a VOC with a substantial transmission advantage over resident variants, or with immune escape properties, can generate a wave of infections and hospitalisations comparable to the winter 2020-2021 wave. Moreover, a variant that is less transmissible, but shows partial immune-escape could provoke a wave of infection that would not be revealed until control measures are further relaxed.
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COVID-19/transmissão , Evasão da Resposta Imune/genética , Modelos Biológicos , Pandemias/estatística & dados numéricos , SARS-CoV-2/patogenicidade , Adolescente , Adulto , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Simulação por Computador , Previsões/métodos , Humanos , Pessoa de Meia-Idade , Mutação , Pandemias/prevenção & controle , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Processos Estocásticos , Reino Unido/epidemiologia , Vacinação/estatística & dados numéricos , Adulto JovemRESUMO
During an infectious disease outbreak, biases in the data and complexities of the underlying dynamics pose significant challenges in mathematically modelling the outbreak and designing policy. Motivated by the ongoing response to COVID-19, we provide a toolkit of statistical and mathematical models beyond the simple SIR-type differential equation models for analysing the early stages of an outbreak and assessing interventions. In particular, we focus on parameter estimation in the presence of known biases in the data, and the effect of non-pharmaceutical interventions in enclosed subpopulations, such as households and care homes. We illustrate these methods by applying them to the COVID-19 pandemic.