The primary practice of healthcare artificial intelligence (AI) starts with model development, often using state-of-the-art AI, retrospectively evaluated using metrics lifted from the AI literature like AUROC and DICE score. However, good performance on these metrics may not translate to improved clinical outcomes. Instead, we argue for a better development pipeline constructed by working backward from the end goal of positively impacting clinically relevant outcomes using AI, leading to considerations of causality in model development and validation, and subsequently a better development pipeline.
View Article and Find Full Text PDFPhage therapy is a promising antibacterial strategy, especially given that drug-resistant bacterial infections are escalating worldwide. Because phages are not active against all strains of a given species, phages being considered for therapeutic use would ideally be tested against bacterial isolates from individual patients prior to administration. Standardized, clinically validated phage susceptibility testing (PST) methods are needed for assessing phage activity.
View Article and Find Full Text PDFIntroduction: Illness severity scoring tools, such as PRISM III/IV, PIM-3, and PELOD-2, are widely used in pediatric critical care research. However, their application is hindered by complex calculation processes, privacy concerns with third-party online calculators, and challenges in accurate implementation within statistical packages.
Methods: We have developed a comprehensive, open-source toolkit for implementing the PIM-3, Simplified PIM-3, and PELOD-2 scores.
Proteomics is making important contributions to drug discovery, from target deconvolution to mechanism of action (MoA) elucidation and the identification of biomarkers of drug response. Here we introduce decryptE, a proteome-wide approach that measures the full dose-response characteristics of drug-induced protein expression changes that informs cellular drug MoA. Assaying 144 clinical drugs and research compounds against 8,000 proteins resulted in more than 1 million dose-response curves that can be interactively explored online in ProteomicsDB and a custom-built Shiny App.
View Article and Find Full Text PDFObjective: Staphylococcus aureus fracture-related infections (FRIs) are associated with significant morbidity in part because conventional antibiotic therapies have limited ability to eradicate S. aureus in sessile states. Therefore, the objective of this study was to assess the feasibility of using Staphylococcal bacteriophages for FRI by testing the activity of a library of Staphylococcal bacteriophage therapeutics against historically preserved S.
View Article and Find Full Text PDFStandardized approaches to phage susceptibility testing (PST) are essential to inform selection of phages for study in patients with bacterial infections. There is no reference standard for assessing bacterial susceptibility to phage. We compared agreement between PST performed at three centers: two centers using a liquid assay standardized between the sites with the third, a plaque assay.
View Article and Find Full Text PDFBackground: Blood cultures are overused in pediatric ICUs (PICUs), which may lead to unnecessary antibiotic use and antibiotic resistance. Using a participatory ergonomics (PE) approach, the authors disseminated a quality improvement (QI) program for optimizing blood culture use in PICUs to a national 14-hospital collaborative. The objective of this study was to evaluate the dissemination process and its impact on blood culture reduction.
View Article and Find Full Text PDFBackground: Pediatric anesthesia has evolved to a high level of patient safety, yet a small chance remains for serious perioperative complications, even in those traditionally considered at low risk. In practice, prediction of at-risk patients currently relies on the American Society of Anesthesiologists Physical Status (ASA-PS) score, despite reported inconsistencies with this method.
Aims: The goal of this study was to develop predictive models that can classify children as low risk for anesthesia at the time of surgical booking and after anesthetic assessment on the procedure day.
Mechanical ventilation is a life-saving treatment in the Intensive Care Unit (ICU), but often causes patients to be at risk of further respiratory complication. We created a statistical model utilizing electronic health record and physiologic vitals data to predict the Center for Disease Control and Prevention (CDC) defined Ventilator Associated Complications (VACs). Further, we evaluated the effect of data temporal resolution and feature generation method choice on the accuracy of such a constructed model.
View Article and Find Full Text PDFBackground: Cardiac arrest is a leading cause of mortality prior to discharge for children admitted to the pediatric intensive care unit. To address this problem, we used machine learning to predict cardiac arrest up to three hours in advance.
Methods: Our data consists of 240 Hz ECG waveform data, 0.
Introduction: Treating recurrent multidrug resistant (MDR) urosepsis in pediatric transplant recipients can be challenging. Particularly when antibiotics fail to prevent future occurrence and the nidus is seemingly undiscoverable. While there is an increasing amount of data on phage therapy, to our knowledge, there are no published cases involving pediatric renal transplant recipients.
View Article and Find Full Text PDFA small subset of acidic hot springs sampled in Yellowstone National Park yielded rod-shaped viruses which lysed liquid host cultures and formed clear plaques on lawns of host cells. Three isolates chosen for detailed analysis were found to be genetically related to previously described isolates of the Sulfolobus islandicus rod-shaped virus (SIRV), but distinct from them and from each other. Functional stability of the new isolates was assessed in a series of inactivation experiments.
View Article and Find Full Text PDFBackground: has the ability to exhibit resistance to a broad range of antibiotics, highlighting the importance of identifying alternative or adjunctive treatment options, such as phages.
Patients And Methods: We report the case of a 25-year-old male who experienced an accidental electrocution resulting in exposed calvarium in the left parieto-temporal region, complicated by a difficult-to-treat (DTR-) infection. Cefiderocol was the sole antibiotic with consistent activity against six bacterial isolates obtained from the infected region over a 38 day period.
We present a case of refractory methicillin-resistant Staphylococcus aureus that was successfully treated with a combination of antibiotics, systemic phage and intranasal phage therapy.
View Article and Find Full Text PDFSelective androgen receptor modulators (SARMs) have been developed as an alternate to traditional anabolic steroids due to their favorable effects on the bones and muscles without androgenic side effects. They are very popular among athletes and bodybuilders and are available online or over the counter. The FDA has warned of their side effects including liver injury.
View Article and Find Full Text PDFBackground: Given the specificity of bacteriophage attachment receptors, a single bacterial isolate is currently utilized to match to a bacteriophage therapeutic, thereby extrapolating activity to all bacteria in vivo. Consistently, the main bacteriophage attachment receptor for Staphylococcus aureus is teichoic acid, and it is known that this receptor has phenotypic variations in different in vivo environments. Consequently, the aim of this study was to determine whether bacteriophage activity is similar across all in vivo prosthetic joint infection environments.
View Article and Find Full Text PDFBackground: The care of pediatric trauma patients is delivered by multidisciplinary care teams with high fluidity that may vary in composition and organization depending on the time of day.
Objective: This study aims to identify and describe diurnal variations in multidisciplinary care teams taking care of pediatric trauma patients using social network analysis on electronic health record (EHR) data.
Methods: Metadata of clinical activities were extracted from the EHR and processed into an event log, which was divided into 6 different event logs based on shift (day or night) and location (emergency department, pediatric intensive care unit, and floor).