Hospital length of stay for COVID-19 patients: Data-driven methods for forward planning.

From Europe PMC via Jisc Publications RouterHistory: ppub 2021-07-01, epub 2021-07-22Publication status: PublishedFunder: Medical Research Council; Grant(s): MR/R502236/1Funder: Royal Society; Grant(s): 202562/Z/16/Z, INF/R2/180067BackgroundPredicting 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.MethodOn 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.ResultsAll 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.ConclusionsGiven 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

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Insights gained from early modelling of COVID-19 to inform the management of outbreaks in UK prisons

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

Possible future waves of SARS-CoV-2 infection generated by variants of concern with a range of characteristics

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 vaccinederived 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 e ect of potential variants of concern (VOCs). Calibrating to the situation in England in May 2021, we nd 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

Hospital Length of Stay For COVID-19 Patients: Data-Driven Methods for Forward Planning

Abstract 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

Using statistics and mathematical modelling to understand infectious disease outbreaks: COVID-19 as an example

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

Challenges in control of COVID-19: Short doubling times and long delay to effect of interventions

The unconstrained growth rate of COVID-19 is crucial for measuring the impact of interventions, assessing worst-case scenarios, and calibrating mathematical models for policy planning. However, robust estimates are limited, with scientific focus on the time-insensitive basic reproduction number R0. Using multiple countries, data streams and methods, we consistently estimate that European COVID-19 cases doubled every three days when unconstrained, with the impact of physical distancing interventions typically seen about nine days after implementation, during which time cases grew eight-fold. The combination of fast growth and long detection delays explains the struggle in countries' response better than large values of R0 alone, and warns against relaxing physical distancing measures too quickly. Testing and tracing are fundamental in shortening such delays, thus preventing cases from escalating unnoticed