Association between Burn Location and Psychological Distress: A Burn Model System National Database Study.

Burn injuries often lead to psychological distress, from depression and anxiety to adjustment concerns and posttraumatic stress. There is some evidence that the anatomical location of burn injuries (e.g., head/neck, feet) has a specific negative impact on psychological functioning. The purpose of this study was to examine the associations between burn injury location and emotional distress. First, we administered self-report questionnaires to burn survivors with ≤ 5% TBSA at a single adult outpatient burn clinic. Second, we used a cross-sectional analysis of the Burn Model System National Database. The mean values of each measure of psychological distress (i.e., quality of life, self-esteem, depression, posttraumatic stress, anxiety, and, for contrast, posttraumatic growth) were examined for each anatomical location for those participants with a burn in those anatomical areas against those with burn in other areas, Using Kruskal-Wallis tests to compare psychological distress, we found no significant differences in outcome measures in either sample analyzed in our study. These findings contrast with prior literature indicating the negative psychological impact of burn injuries to certain locations in the body. Further research should explore whether larger burns (i.e., greater than 5% TBSA) affecting critical areas of the body may be associated with psychological distress.

Fluoride varnish applications provided in general dental practice for children of primary school age in three areas of the UK.

Introduction Dental guidelines recommend professional application of fluoride varnish (FV) at least twice a year for children from the age of three.Methods NHS dental claims data were reviewed for children born in 2009 for the five-year period 2015-2019 and who attended the dentist in one of three geographical areas, labelled as Bristol, Birmingham and Cardiff. Data for 14,566 children were included in the study.Results Only 3.5% of children had been provided with ten or more FV applications at the dentist in the five-year period. Children in the Cardiff region fared less well for fluoride applications than their Bristol and Birmingham counterparts, including children that were seemingly at high risk of caries for part of the time period reviewed. For all three regions, the mean number of FV applications increased with an increase in the number of fillings provided.Conclusion Awareness of the apparent lack of FV application in the dental surgery may provide an opportunity to improve child dental health.

Enhancing pain care with the American Pain Society Patient Outcome Questionnaire for use in the emergency department (APS-POQ-RED): validating a patient-reported outcome measure.

BACKGROUND: In general, the quality of pain care in emergency departments (ED) is poor, despite up to 80% of all ED patients presenting with pain. This may be due to the lack of well-validated patient-reported outcome measures (PROMs) of pain care in the ED setting. The American Pain Society-Patient Outcome Questionnaire-Revised Edition (APS-POQ-R), with slight modification for ED patients, is a potentially useful PROM for the adult ED, however it is yet to be completely validated. METHODS: Adult patients, who had presented with moderate to severe acute pain, were recruited at two large inner-city EDs in Australia. A modified version of the APS-POQ-R was administered at the completion of their ED care. Responses were randomly split into three groups and underwent multiple rounds of exploratory and confirmatory factor analysis with testing for construct, convergent, divergent validity and internal consistency. RESULTS: A total of 646 ED patients (55.6% female), with a median age of 48.3 years, and moderate to severe pain on arrival, completed the ED-modified APS-POQ-R. Psychometric evaluation resulted in a reduced nine-question tool, which measures three constructs (pain relief and satisfaction (α=0.891), affective distress (α=0.823) and pain interference (α=0.908)) and demonstrated construct, convergent, divergent validity, and internal consistency. CONCLUSIONS: This new tool, which we refer to as the American Pain Society-Patient Outcome Questionnaire-Revised for the ED (APS-POQ-RED), should form the basis for reporting patient-reported outcomes of ED pain care in future quality improvement and research.

Correlation of Fabrication Methods and Enhanced Wear Performance in Nanoporous Anodic Aluminum Oxide with Incorporated Molybdenum Disulfide (MoS2) Nanomaterials.

Wear performance is integral to component longevity, minimizing industrial waste and excess energy costs in a wide variety of applications. Anodized aluminum oxide (AAO) has many beneficial properties leading to its wide use across industries as a surface treatment for many aluminum components, but the wear properties of the coating could be improved significantly. Here, we used an electrochemical method to incorporate molybdenum disulfide (MoS2), a nanomaterial used as a dry lubricant, to modify alloys of aluminum during AAO preparation. Using Raman spectroscopy and tribological scratch measurements, we thoroughly characterized the structure and wear behavior of the films. The MoS2 deposition procedure was optimal on aluminum 5052 anodized in higher acid concentrations, with friction coefficients at around 0.05 (~10× better than unmodified AAO). Changing anodization conditions to produce harder films with smaller pores led to worsened wear properties, likely because of lower MoS2 content. Studying a commercial MoS2/AAO film of a different Al alloy (7075) showed that a heat treatment step intended to fully convert all deposited MoSx species to MoS2 can adversely affect wear in some alloys. While Al 6061 and 1100 produced films with worse wear performance compared to Al 5052 or 7075, our results show evidence that acid cleaning after initial anodization likely removes residual alloying elements, affecting MoS2 incorporation. This study demonstrates a nanomaterial modified AAO film with superior wear characteristics to unmodified AAO and relates fabrication procedure, film structure, and practical performance.

An anti-TNF-glucocorticoid receptor modulator antibody-drug conjugate is efficacious against immune-mediated inflammatory diseases.

Glucocorticoids (GCs) are efficacious drugs used for treating many inflammatory diseases, but the dose and duration of administration are limited because of severe side effects. We therefore sought to identify an approach to selectively target GCs to inflamed tissue. Previous work identified that anti-tumor necrosis factor (TNF) antibodies that bind to transmembrane TNF undergo internalization; therefore, an anti-TNF antibody-drug conjugate (ADC) would be mechanistically similar, where lysosomal catabolism could release a GC receptor modulator (GRM) payload to dampen immune cell activity. Consequently, we have generated an anti-TNF-GRM ADC with the aim of inhibiting pro-inflammatory cytokine production from stimulated human immune cells. In an acute mouse model of contact hypersensitivity, a murine surrogate anti-TNF-GRM ADC inhibited inflammatory responses with minimal effect on systemic GC biomarkers. In addition, in a mouse model of collagen-induced arthritis, single-dose administration of the ADC, delivered at disease onset, was able to completely inhibit arthritis for greater than 30 days, whereas an anti-TNF monoclonal antibody only partially inhibited disease. ADC treatment at the peak of disease was also able to attenuate the arthritic phenotype. Clinical data for a human anti-TNF-GRM ADC (ABBV-3373) from a single ascending dose phase 1 study in healthy volunteers demonstrated antibody-like pharmacokinetic profiles and a lack of impact on serum cortisol concentrations at predicted therapeutic doses. These data suggest that an anti-TNF-GRM ADC may provide improved efficacy beyond anti-TNF alone in immune mediated diseases while minimizing systemic side effects associated with standard GC treatment.

The long and short of it: benchmarking viromics using Illumina, Nanopore and PacBio sequencing technologies.

Viral metagenomics has fuelled a rapid change in our understanding of global viral diversity and ecology. Long-read sequencing and hybrid assembly approaches that combine long- and short-read technologies are now being widely implemented in bacterial genomics and metagenomics. However, the use of long-read sequencing to investigate viral communities is still in its infancy. While Nanopore and PacBio technologies have been applied to viral metagenomics, it is not known to what extent different technologies will impact the reconstruction of the viral community. Thus, we constructed a mock bacteriophage community of previously sequenced phage genomes and sequenced them using Illumina, Nanopore and PacBio sequencing technologies and tested a number of different assembly approaches. When using a single sequencing technology, Illumina assemblies were the best at recovering phage genomes. Nanopore- and PacBio-only assemblies performed poorly in comparison to Illumina in both genome recovery and error rates, which both varied with the assembler used. The best Nanopore assembly had errors that manifested as SNPs and INDELs at frequencies 41 and 157 % higher than found in Illumina only assemblies, respectively. While the best PacBio assemblies had SNPs at frequencies 12 and 78 % higher than found in Illumina-only assemblies, respectively. Despite high-read coverage, long-read-only assemblies recovered a maximum of one complete genome from any assembly, unless reads were down-sampled prior to assembly. Overall the best approach was assembly by a combination of Illumina and Nanopore reads, which reduced error rates to levels comparable with short-read-only assemblies. When using a single technology, Illumina only was the best approach. The differences in genome recovery and error rates between technology and assembler had downstream impacts on gene prediction, viral prediction, and subsequent estimates of diversity within a sample. These findings will provide a starting point for others in the choice of reads and assembly algorithms for the analysis of viromes.

Developing Robust Clinical Text Deep Learning Models - A "Painless" Approach.

The success of deep learning in natural language processing relies on ample labelled training data. However, models in the health domain often face data inadequacy due to the high cost and difficulty of acquiring training data. Developing such models thus requires robustness and performance on new data. A generalised incremental multiphase framework is proposed for developing robust and performant clinical text deep learning classifiers. It incorporates incremental multiphases for training data size assessments, cross-validation setup to avoid test data bias, and robustness testing through inter/intra-model significance analysis. The framework's effectiveness and generalisation were confirmed by the task of identifying patients presenting in 'pain' to the emergency department.

A compiled dataset of ready-mix concrete Environmental Product Declarations for life cycle assessment.

The carbon footprint of a concrete structure is directly affected by the selected concrete mixture proportions. To better understand the influence of different concrete mixtures, data was collected from Environmental Product Declarations (EPDs). Data from 39,213 U.S.A. ready-mix concrete EPDs was obtained from public repositories provided by the American Society for Testing and Materials and the National Ready Mixed Concrete Association. The EPDs in .pdf format were analyzed using a custom Python script to extract useful information for building designers, sustainability practitioners, and researchers including: life cycle assessment (LCA) midpoints (Global Warming Potential, Ozone Depletion Potential, Acidification Potential, Photochemical Ozone Creation Potential, Abiotic Depletion, Total Waste Disposed, and Consumption of Freshwater), concrete strength classes, declared unit, concrete curing time, production components, concrete manufacturers' company and plant locations, and additional LCA information. Both the dataset and an example of the Python script used to extract the information from the EPDs are provided. This dataset enables users to quickly assess the environmental impacts (including the Global Warming Potential) of different concrete mixtures without the need for extensive data collection and analysis. In summary, this dataset provides environmental information about concrete mixtures to aid civil engineering and architectural researchers, sustainability consultants, building engineering practitioners, and environmental policymakers to make sustainability-informed decisions when specifying concrete in the U.S.A.

Determinants of fatigue in emergency department clinicians who wear personal protective equipment.

OBJECTIVE: To determine the independent predictors for clinician fatigue and decline in cognitive function following a shift in the ED during early stages of the COVID-19 pandemic. METHODS: This was a prospective, quasi-experimental study conducted in a metropolitan adult tertiary-referral hospital ED over 20 weeks in 2021. The participants were ED doctors and nurses working clinical shifts in an ED isolation area or high-risk zone (HRZ) with stringent personal protective equipment (PPE). The participants' objective and subjective fatigue was measured by the Samn-Perelli fatigue score and a psychomotor vigilance 'smart game' score, respectively. Postural signs/symptoms and urine specific gravity (SG) were measured as markers of dehydration. RESULTS: Sixty-three participants provided data for 263 shifts. Median (interquartile range) age was 33 (28-38) years, 73% were female. Worsening fatigue score was associated with working afternoon shifts (afternoon vs day, adjusted odds ratio [aOR] 5.16 [95% confidence interval (CI) 1.32-20.02]) and in non-HRZ locations (HRZ vs non-HRZ, aOR 0.23 [95% CI 0.06-0.87]). Worsening cognitive function (game score) was associated with new onset postural symptoms (new vs no symptoms, aOR 4.14 [95% CI 1.34-12.51]) and afternoon shifts (afternoon vs day, aOR 3.13 [95% CI 1.16-8.44]). Working in the HRZ was not associated with declining cognitive function. Thirty-four (37%) of the 92 participants had an end of shift urine SG >1.030. CONCLUSION: Working afternoon shifts was associated with fatigue. There was no association between HRZ allocation and fatigue, but our study was limited by a low COVID workload and fluctuating PPE requirements in the non-HRZs. Workplace interventions that target the prevention of fatigue in ED clinicians working afternoon shifts should be prioritised.

The Importance of Research Experience With a Scoreless Step 1: A Student Survey at a Community-Based Medical School.

PURPOSE: As of January 26, 2022, the United States Medical Licensing Examination (USLME) step 1 exam went from a scored test to pass-fail step 1 (PFS1). The authors were interested in surveying medical students at a community-based medical school to observe their perceptions of the importance of student research given this recent change. METHOD: A Qualtrics survey was disseminated to medical students (years 1-4) via school emails. Data were analyzed using the Mann-Whitney test to assess Likert scale scores, and narrative comments were grouped as qualitative feedback. Survey dissemination and analysis of data were both conducted at a large community-based medical school. RESULTS: The survey sampled 104 students categorized into pre-clerkship (PC) and clerkship (CL) years, with a response rate of 33%. A contradiction was found, as indicated by the higher number (p = 0.047) of clerkship students interested in Primary Care/Family medicine residency compared to pre-clerkship students at 41% and 59%, respectively. Whereas participants who indicated they are interested in pursuing a competitive specialty for residency were 51% of pre-clerkship students over 41% of clerkship students (p = 0.047). Additionally, given the assessment change to pass/fail, students did in fact believe that residencies would now view research as a higher assessed component than before (79% pre-clerkship and 72% clerkship). However, a minority of students said that they increased their research efforts (41% and 47%). Most students supported the research opportunity improvements proposed in our survey. CONCLUSIONS: Efforts to make the step 1 exam pass/fail may have alleviated some stress related to performance but may have increased the perception of the importance of other components in a student's residency application. Our survey highlights how medical students at a community-based medical school perceive this change and how it has affected their research efforts.

Bioavailable Microbial Metabolites of Flavanols Demonstrate Highly Individualized Bioactivity on In Vitro ß-Cell Functions Critical for Metabolic Health.

Dietary flavanols are known for disease preventative properties but are often poorly absorbed. Gut microbiome flavanol metabolites are more bioavailable and may exert protective activities. Using metabolite mixtures extracted from the urine of rats supplemented with flavanols and treated with or without antibiotics, we investigated their effects on INS-1 832/13 ß-cell glucose stimulated insulin secretion (GSIS) capacity. We measured insulin secretion under non-stimulatory (low) and stimulatory (high) glucose levels, insulin secretion fold induction, and total insulin content. We conducted treatment-level comparisons, individual-level dose responses, and a responder vs. non-responder predictive analysis of metabolite composition. While the first two analyses did not elucidate treatment effects, metabolites from 9 of the 28 animals demonstrated significant dose responses, regardless of treatment. Differentiation of responders vs. non-responder revealed that levels of native flavanols and valerolactones approached significance for predicting enhanced GSIS, regardless of treatment. Although treatment-level patterns were not discernable, we conclude that the high inter-individual variability shows that metabolite bioactivity on GSIS capacity is less related to flavanol supplementation or antibiotic treatment and may be more associated with the unique microbiome or metabolome of each animal. These findings suggest flavanol metabolite activities are individualized and point to the need for personalized nutrition practices.

Computed tomography brain scan utilization in patients with headache presenting to emergency departments: a multinational study.

BACKGROUND AND IMPORTANCE: Recommended indications for emergency computed tomography (CT) brain scans are not only complex and evolving, but it is also unknown whether they are being followed in emergency departments (EDs). OBJECTIVE: To determine the CT utilization and diagnostic yield in the ED in patients with headaches across broad geographical regions. DESIGN: Secondary analysis of data from a multinational cross-sectional study of ED headache presentations over one month in 2019. SETTING AND PARTICIPANTS: Hospitals from 10 participating countries were divided into five geographical regions [Australia and New Zealand (ANZ); Colombia; Europe: Belgium, France, UK, and Romania; Hong Kong and Singapore (HKS); and Turkey). Adult patients with nontraumatic headache as the primary presenting complaint were included. Patients were identified from ED management systems. OUTCOME MEASURES AND ANALYSIS: The outcome measures were CT utilization and diagnostic yield. CT utilization was calculated using a multilevel binary logistic regression model to account for clustering of patients within hospitals and regions. Imaging data (CT requests and reports) were sourced from radiology management systems. MAIN RESULTS: The study included 5281 participants. Median (interquartile range) age was 40 (29-55) years, 66% were women. Overall mean CT utilization was 38.5% [95% confidence interval (CI), 30.4-47.4%]. Regional utilization was highest in Europe (46.0%) and lowest in Turkey (28.9%), with HKS (38.0%), ANZ (40.0%), and Colombia (40.8%) in between. Its distribution across hospitals was approximately symmetrical. There was greater variation in CT utilization between hospitals within a region than between regions (hospital variance 0.422, region variance 0.100). Overall mean CT diagnostic yield was 9.9% (95% CI, 8.7-11.3%). Its distribution across hospitals was positively skewed. Regional yield was lower in Europe (5.4%) than in other regions: Colombia (9.1%), HKS (9.7%), Turkey (10.6%), and ANZ (11.2%). There was a weak negative correlation between utilization and diagnostic yield ( r  = -0.248). CONCLUSION: In this international study, there was a high variation (28.9-46.6%) in CT utilization and diagnostic yield (5.4-11.2%) across broad geographic regions. Europe had the highest utilization and the lowest yield. The study findings provide a foundation to address variation in neuroimaging in ED headache presentations.

A Small Step Toward Generalizability: Training a Machine Learning Scoring Function for Structure-Based Virtual Screening.

Over the past few years, many machine learning-based scoring functions for predicting the binding of small molecules to proteins have been developed. Their objective is to approximate the distribution which takes two molecules as input and outputs the energy of their interaction. Only a scoring function that accounts for the interatomic interactions involved in binding can accurately predict binding affinity on unseen molecules. However, many scoring functions make predictions based on data set biases rather than an understanding of the physics of binding. These scoring functions perform well when tested on similar targets to those in the training set but fail to generalize to dissimilar targets. To test what a machine learning-based scoring function has learned, input attribution, a technique for learning which features are important to a model when making a prediction on a particular data point, can be applied. If a model successfully learns something beyond data set biases, attribution should give insight into the important binding interactions that are taking place. We built a machine learning-based scoring function that aimed to avoid the influence of bias via thorough train and test data set filtering and show that it achieves comparable performance on the Comparative Assessment of Scoring Functions, 2016 (CASF-2016) benchmark to other leading methods. We then use the CASF-2016 test set to perform attribution and find that the bonds identified as important by PointVS, unlike those extracted from other scoring functions, have a high correlation with those found by a distance-based interaction profiler. We then show that attribution can be used to extract important binding pharmacophores from a given protein target when supplied with a number of bound structures. We use this information to perform fragment elaboration and see improvements in docking scores compared to using structural information from a traditional, data-based approach. This not only provides definitive proof that the scoring function has learned to identify some important binding interactions but also constitutes the first deep learning-based method for extracting structural information from a target for molecule design.

Fishing for Trouble: A Novel Surgical Technique for Penetrating Fishhook Injuries of the Eyelid.

Fishhook injuries commonly occur and may present as ophthalmic surgical emergencies. Choosing the appropriate removal technique is critical and depends on the involved extra- and intra-ocular structures and hook characteristics. We describe the case of a challenging fishhook removal where a novel surgical technique was developed. An eight-year-old boy presented with a full-thickness fishhook injury to the eyelid. During removal surgery, the thickness and density of the fishhook prevented surgical tools from transecting the shank. A novel approach was deemed necessary for safe removal, termed the clamp and retract technique. To our knowledge, this is its first documented use in the literature.

PREdiction and Diagnosis using Imaging and Clinical biomarkers Trial in Traumatic Brain Injury (PREDICT-TBI) study protocol: an observational, prospective, multicentre cohort study for the prediction of outcome in moderate-to-severe TBI.

INTRODUCTION: Traumatic brain injury (TBI) is a heterogeneous condition with a broad spectrum of injury severity, pathophysiological processes and variable outcomes. For moderate-to-severe TBI survivors, recovery is often protracted and outcomes can range from total dependence to full recovery. Despite advances in medical treatment options, prognosis remains largely unchanged. The objective of this study is to develop a machine learning predictive model for neurological outcomes at 6 months in patients with a moderate-to-severe TBI, incorporating longitudinal clinical, multimodal neuroimaging and blood biomarker predictor variables. METHODS AND ANALYSIS: A prospective, observational, cohort study will enrol 300 patients with moderate-to-severe TBI from seven Australian hospitals over 3 years. Candidate predictors including demographic and general health variables, and longitudinal clinical, neuroimaging (CT and MRI), blood biomarker and patient-reported outcome measures will be collected at multiple time points within the acute phase of injury. The predictor variables will populate novel machine learning models to predict the Glasgow Outcome Scale Extended 6 months after injury. The study will also expand on current prognostic models by including novel blood biomarkers (circulating cell-free DNA), and the results of quantitative neuroimaging such as Quantitative Susceptibility Mapping and Dynamic Contrast Enhanced MRI as predictor variables. ETHICS AND DISSEMINATION: Ethical approval has been obtained by the Royal Brisbane and Women's Hospital Human Research Ethics Committee, Queensland. Participants or their substitute decision-maker/s will receive oral and written information about the study before providing written informed consent. Study findings will be disseminated by peer-review publications and presented at national and international conferences and clinical networks. TRIAL REGISTRATION NUMBER: ACTRN12620001360909.

Electrodeposition and analysis of thick bismuth films.

Due to its unique physical and chemical properties, bismuth is an attractive candidate for a wide range of applications such as battery anodes, radiation shielding, and semiconductors, to name a few. This work presents the electrodeposition of mechanically stable and homogenous bismuth films at micron-scale thicknesses. A simple one-step electrodeposition process using either a pulse/reverse or direct current source yielded thick, homogenous, and mechanically stable bismuth films. Morphology, electrochemical behavior, adhesion, and mechanical stability of bismuth coatings plated with varying parameters were characterized via optical profilometry, cyclic voltammetry, electron microscopy, and tribology. Scratch testing on thick electroplated coatings (> 100 µm) revealed similar wear resistance properties between the pulse/reverse plated and direct current electroplated films. This study presents a versatile bismuth electroplating process with the possibility to replace lead in radiation shields with an inexpensive, non-toxic metal, or to make industrially relevant electrocatalytic devices.

Clinical characteristics of Aboriginal and Torres Strait Islander emergency department patients with suspected acute coronary syndrome.

OBJECTIVES: To describe the demographics, presentation characteristics, clinical features and cardiac outcomes for Aboriginal and Torres Strait Islander patients who present to a regional cardiac referral centre ED with suspected acute coronary syndrome (ACS). METHODS: This was a single-centre observational study conducted at a regional referral hospital in Far North Queensland, Australia from November 2017 to September 2018 and January 2019 to December 2019. Study participants were 278 Aboriginal and Torres Strait Islander people presenting to an ED and investigated for suspected ACS. The main outcome measure was the proportion of patients with ACS at index presentation and differences in characteristics between those with and without ACS. RESULTS: ACS at presentation was diagnosed in 38.1% of patients (n = 106). The mean age of patients with ACS was 53.5 years (SD 9.5) compared with 48.7 years (SD 12.1) in those without ACS (P = 0.001). Patients with ACS were more likely to be male (63.2% vs 39.0%, P < 0.001), smokers (70.6% vs 52.3%, P = 0.002), have diabetes (56.6% vs 38.4%, P = 0.003) and have renal impairment (24.5% vs 10.5%, P = 0.002). CONCLUSIONS: Aboriginal and Torres Strait Islander patients with suspected ACS have a high burden of traditional cardiac risk factors, regardless of whether they are eventually diagnosed with ACS. These patients may benefit from assessment for coronary artery disease regardless of age at presentation.

Impact of COVID-19 pandemic on emergency department patient volume and flow: Two countries, two hospitals.

OBJECTIVES: COVID-19 greatly disrupted the provision of emergency care across the globe. ED service delivery was urgently redesigned as human and material resources were mobilised, and patients with respiratory symptoms were isolated. This study aimed to compare ED patient volume and flow metrics before and during the COVID-19 pandemic. METHODS: An observational study was conducted in two large urban EDs in Brisbane, Australia and Seoul, Republic of Korea. Patient volume and flow were quantified using ED presentation numbers and service times, respectively. Daily case numbers, waiting, treatment and admission delay times were compared between 2019 and 2020/2021 using time series plots. Outcomes were further classified by triage category and age group. Trends were examined alongside a timeline of health service and government policies. RESULTS: There were reductions in daily presentations for the least urgent triage categories during the early phase of the pandemic. The caseloads for the most urgent triage categories were unaffected. The trends were similar in both EDs. A reduction in waiting and admission delay times but not treatment times coincided with reduced presentations in Brisbane. This pattern gradually reversed as presentations returned to baseline. In Seoul, admission delay times returned to pre-pandemic levels despite a persistent reduction in presentation numbers. CONCLUSIONS: Total daily presentations varied considerably according to government mandated social restrictions and testing requirements in both EDs. The reductions in waiting and admission delay times corresponded with improvements in hospital capacity.

The Constitutionality of Medicare Drug-Price Negotiation under the Takings Clause.

In recent months, pharmaceutical manufacturers have brought legal challenges to a provision of the 2022 Inflation Reduction Act (IRA) empowering the federal government to negotiate the prices Medicare pays for certain prescription medications. One key argument made in these filings is that price negotiation is a "taking" of property and violates the Takings Clause of the US Constitution. Through original case law and health policy analysis, we show that government price negotiation and even price regulation of goods and services, including patented goods, are constitutional under the Takings Clause. Finding that the IRA violates the Takings Clause would radically upend settled constitutional law and jeopardize the US's most important state and federal health care programs.