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Antimicrobial de-escalation refers to reducing the spectrum of antibiotics used in treating bacterial infections. This strategy is widely recommended in many antimicrobial stewardship programs and is believed to reduce patients’ exposure to broad-spectrum antibiotics and prevent resistance. However, the ecological benefits of de-escalation have not been universally observed in clinical studies. This paper conducts computer simulations to assess the ecological effects of de-escalation on the resistance prevalence ofPseudomonas aeruginosa—a frequent pathogen causing nosocomial infections. Synthetic data produced by the models are then used to estimate the sample size and study period needed to observe the predicted effects in clinical trials. Our results show that de-escalation can reduce colonization and infections caused by bacterial strains resistant to the empiric antibiotic, limit the use of broad-spectrum antibiotics, and avoid inappropriate empiric therapies. Further, we show that de-escalation could reduce the overall super-infection incidence, and this benefit becomes more evident under good compliance with hand hygiene protocols among health care workers. Finally, we find that any clinical study aiming to observe the essential effects of de-escalation should involve at least ten arms and last for four years—a size never attained in prior studies. This study explains the controversial findings of de-escalation in previous clinical studies and illustrates how mathematical models can inform outcome expectations and guide the design of clinical studies. 

In this work, we develop a new set of Bayesian models to perform registration of real-valued functions. A Gaussian process prior is assigned to the parameter space of time warping functions, and a Markov chain Monte Carlo (MCMC) algorithm is utilized to explore the posterior distribution. While the proposed model can be defined on the infinite-dimensional function space in theory, dimension reduction is needed in practice because one cannot store an infinite-dimensional function on the computer. Existing Bayesian models often rely on some pre-specified, fixed truncation rule to achieve dimension reduction, either by fixing the grid size or the number of basis functions used to represent a functional object. In comparison, the new models in this paper randomize the truncation rule. Benefits of the new models include the ability to make inference on the smoothness of the functional parameters, a data-informative feature of the truncation rule, and the flexibility to control the amount of shape-alteration in the registration process. For instance, using both simulated and real data, we show that when the observed functions exhibit more local features, the posterior distribution on the warping functions automatically concentrates on a larger number of basis functions. Supporting materials including code and data to perform registration and reproduce some of the results presented herein are available online. 

The ongoing COVID-19 pandemic has killed at least 1.1 million people in the United States and over 6.7 million globally. Accurately estimating the age-specific infection fatality rate (IFR) of SARS-CoV-2 for different populations is crucial for assessing and understanding the impact of COVID-19 and for appropriately allocating vaccines and treatments to at-risk groups. We estimated age-specific IFRs of wild-type SARS-CoV-2 using published seroprevalence, case, and death data from New York City (NYC) from March to May 2020, using a Bayesian framework that accounted for delays between key epidemiological events. IFRs increased 3-4-fold with every 20 years of age, from 0.06% in individuals between 18–45 years old to 4.7% in individuals over 75. We then compared IFRs in NYC to several city- and country-wide estimates including England, Switzerland (Geneva), Sweden (Stockholm), Belgium, Mexico, and Brazil, as well as a global estimate. IFRs in NYC were higher for individuals younger than 65 years old than most other populations, but similar for older individuals. IFRs for age groups less than 65 decreased with income and increased with income inequality measured using the Gini index. These results demonstrate that the age-specific fatality of COVID-19 differs among developed countries and raises questions about factors underlying these differences, including underlying health conditions and healthcare access.