The Clinical Course of a Severe Case of Malignant Catatonia.

Catatonia is a psychomotor syndrome predominantly associated with mental illness disorders, most commonly bipolar disorder and schizophrenia. Catatonia is classified as malignant when, in addition to catatonic symptoms, dysautonomia is present. Autonomic abnormalities can include changes in temperature, labile blood pressure, and changes in heart and respiratory rates. Because malignant catatonia is life-threatening, prompt recognition and management are essential to prevent mortality. We present a severe case of catatonia with malignant features that highlight the importance of early diagnosis and treatment.

Cardiovascular Dynamics in HIV: The Influence of Adrenal Function and Nutritional Status.

This interdisciplinary review explores the intricate nexus between HIV infection, nutrition, adrenal gland function, and cardiovascular health, highlighting a critical aspect of HIV management often overlooked in current literature. With the advent of antiretroviral therapy, the life expectancy of people living with HIV has dramatically improved, transforming HIV into a manageable chronic condition. However, this success brings forth new challenges, notably an increased risk of cardiovascular diseases among people living with HIV. We examine the normal physiology of the adrenal gland, including its role in mineral metabolism, a crucial facet of nutrition. We discuss the evolution of knowledge tying adrenal pathology to cardiovascular disease. We explore the impact of HIV on adrenal gland findings from a gross pathology perspective, as well as the clinical impact of adrenal insufficiency in HIV. The review further elucidates the role of nutrition in this context, considering the double burden of undernutrition and obesity prevalent in regions heavily affected by HIV. By aggregating findings from longitudinal studies and recent clinical trials, the review presents compelling evidence of increased cardiovascular disease among people living with HIV compared with people without HIV. It highlights the critical role of the adrenal glands in regulating nutrient metabolism and its implications for cardiovascular health, drawing attention to the potential for dietary interventions and targeted therapies to mitigate these risks. This review urges a paradigm shift in the management of HIV, advocating for a holistic approach that incorporates nutritional assessment and interventions into routine HIV care to address the complex interplay between HIV, adrenal function, and cardiovascular health. Through this lens, we offer insights into novel therapeutic strategies aimed at reducing cardiovascular risk in people living with HIV, contributing to the ongoing efforts to enhance the quality of life and longevity in this population.

Commercial vaccine provides cross-protection by reducing colonization of Salmonella enterica serovars Infantis and Hadar in turkeys.

Human foodborne outbreaks with antibiotic-resistant Salmonella enterica associated with contaminated poultry products have recently involved serogroup C serovars Infantis and Hadar. The current study evaluated a commercially available Salmonella vaccine for cross-protection against Infantis and Hadar serovars in turkeys. The live, attenuated S. Typhimurium (serogroup B) vaccine significantly reduced colonization of intestinal tissues (cecum, cecal tonsils, and cloaca) by serovars Infantis (C1) and Hadar (C2) and significantly limited systemic dissemination to the spleen. S. Infantis, but not S. Hadar, disseminated to bone marrow in non-vaccinated turkeys, but vaccination prevented S. Infantis dissemination to the bone marrow. The S. Infantis challenge strain contained the pESI megaplasmid, and virulence mechanism(s) residing on this plasmid may support dissemination and/or colonization of systemic niches such as myeloid tissue. Collectively, the data indicate that vaccinating turkeys with the serogroup B S. Typhimurium vaccine limited intestinal colonization and systemic dissemination by serogroup C serovars Infantis and Hadar.

Adult Ossabaw Pigs Prefer Fermented Sorghum Tea over Isocaloric Sweetened Water.

Ossabaw pigs (n = 11; 5-gilts, 6-barrows; age 15.6 ± 0.62 SD months) were exposed to a three-choice preference maze to evaluate preference for fermented sorghum teas (FSTs). After conditioning, pigs were exposed, in four sessions, to choices of white FST, sumac FST, and roasted sumac-FST. Then, pigs were exposed, in three sessions, to choices of deionized H2O (-control; avoidance), isocaloric control (+control; deionized H2O and sucrose), and blended FST (3Tea) (equal portions: white, sumac, and roasted sumac). When tea type was evaluated, no clear preference behaviors for tea type were observed (p > 0.10). When the 3Tea and controls were evaluated, pigs consumed minimal control (p < 0.01;18.0 ± 2.21% SEM), and they consumed great but similar volumes of +control and 3Tea (96.6 and 99.0 ± 2.21% SEM, respectively). Likewise, head-in-bowl duration was the least for -control, but 3Tea was the greatest (p < 0.01; 5.6 and 31.9 ± 1.87% SEM, respectively). Head-in-bowl duration for +control was less than 3Tea (p < 0.01; 27.6 vs. 31.9 ± 1.87% SEM). Exploration duration was the greatest in the area with the -control (p < 0.01; 7.1 ± 1.45% SEM), but 3Tea and +control exploration were not different from each other (1.4 and 3.0 ± 1.45% SEM, respectively). Regardless of tea type, adult pigs show preference for FST, even over +control. Adult pigs likely prefer the complexity of flavors, rather than the sweetness alone.

Geographic and Temporal Trends in COVID-Associated Acute Kidney Injury in the National COVID Cohort Collaborative.

BACKGROUND: AKI is associated with mortality in patients hospitalized with coronavirus disease 2019 (COVID-19); however, its incidence, geographic distribution, and temporal trends since the start of the pandemic are understudied. METHODS: Electronic health record data were obtained from 53 health systems in the United States in the National COVID Cohort Collaborative. We selected hospitalized adults diagnosed with COVID-19 between March 6, 2020, and January 6, 2022. AKI was determined with serum creatinine and diagnosis codes. Time was divided into 16-week periods (P1-6) and geographical regions into Northeast, Midwest, South, and West. Multivariable models were used to analyze the risk factors for AKI or mortality. RESULTS: Of a total cohort of 336,473, 129,176 (38%) patients had AKI. Fifty-six thousand three hundred and twenty-two (17%) lacked a diagnosis code but had AKI based on the change in serum creatinine. Similar to patients coded for AKI, these patients had higher mortality compared with those without AKI. The incidence of AKI was highest in P1 (47%; 23,097/48,947), lower in P2 (37%; 12,102/32,513), and relatively stable thereafter. Compared with the Midwest, the Northeast, South, and West had higher adjusted odds of AKI in P1. Subsequently, the South and West regions continued to have the highest relative AKI odds. In multivariable models, AKI defined by either serum creatinine or diagnostic code and the severity of AKI was associated with mortality. CONCLUSIONS: The incidence and distribution of COVID-19-associated AKI changed since the first wave of the pandemic in the United States. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_08_08_CJN0000000000000192.mp3.

Impact of a Blend of Microencapsulated Organic Acids and Botanicals on the Microbiome of Commercial Broiler Breeders under Clinical Necrotic Enteritis.

Previously, the supplementation of a microencapsulated blend of organic acids and botanicals improved the health and performance of broiler breeders under non-challenged conditions. This study aimed to determine if the microencapsulated blend impacted dysbiosis and necrotic enteritis (NE) in broiler breeders. Day-of-hatch chicks were assigned to non-challenge and challenge groups, provided a basal diet supplemented with 0 or 500 g/MT of the blend, and subjected to a laboratory model for NE. On d 20-21, jejunum/ileum content were collected for microbiome sequencing (n = 10; V4 region of 16S rRNA gene). The experiment was repeated (n = 3), and data were analyzed in QIIME2 and R. Alpha and beta diversity, core microbiome, and compositional differences were determined (significance at p ≤ 0.05; Q ≤ 0.05). There was no difference between richness and evenness of those fed diets containing 0 and 500 g/MT microencapsulated blend, but differences were seen between the non-challenged and challenged groups. Beta diversity of the 0 and 500 g/MT non-challenged groups differed, but no differences existed between the NE-challenged groups. The core microbiome of those fed 500 g/MT similarly consisted of Lactobacillus and Clostridiaceae. Furthermore, challenged birds fed diets containing 500 g/MT had a higher abundance of significantly different phyla, namely, Actinobacteriota, Bacteroidota, and Verrucomicrobiota, than the 0 g/MT challenged group. Dietary supplementation of a microencapsulated blend shifted the microbiome by supporting beneficial and core taxa.

Effects of Hops Treatment on Nitrogen Retention, Volatile Fatty Acid Accumulations, and Select Microbial Populations of Composting Poultry Litter Intended for Use as a Ruminant Feedstuff.

Poultry litter is a valuable crude protein feedstuff for ruminants, but it must be treated to kill pathogens before feeding. Composting effectively kills pathogens, but it risks losing ammonia to volatilization or leaching during degradation of uric acid and urea. Hops bitter acids also exert antimicrobial activity against certain pathogenic and nitrogen-degrading microbes. Consequently, the present studies were conducted to test if adding bitter acid-rich hop preparations to simulated poultry litter composts may improve nitrogen retention while simultaneously improving pathogen killing. Results from an initial study, testing doses of Chinook or Galena hops preparations designed to each deliver 79 ppm hops ß-acid, revealed that, after nine days simulated composting of wood chip litter, ammonia concentrations were 14% lower (p < 0.05) in Chinook-treated composts than untreated composts (13.4 ± 1.06 µmol/g). Conversely, urea concentrations were 55% lower (p < 0.05) in Galena-treated than untreated composts (6.2 ± 1.72 µmol/g). Uric acid accumulations were unaffected by hops treatments in this study but were higher (p < 0.05) after three days than after zero, six, or nine days of composting. In follow-up studies, Chinook or Galena hops treatments (delivering 2042 or 6126 ppm of ß-acid, respectively) for simulated composts (14 days) of wood chip litter alone or mixed 3:1 with ground Bluestem hay (Andropogon gerardii) revealed that these higher dosages had little effect on ammonia, urea, or uric acid accumulations when compared to untreated composts. Volatile fatty acid accumulations measured in these later studies were affected by the hops treatments, with butyrate accumulations being lower after 14 days in hops-treated composts than in untreated compost. In all studies, beneficial effects of Galena or Chinook hops treatments were not observed on the antimicrobial activity of the simulated composts, with composting by itself decreasing (p < 0.05) counts of select microbial populations by more than 2.5 log10 colony forming units/g compost dry matter. Thus, while hops treatments had little effect on pathogen control or nitrogen retention within the composted litter, they did lessen accumulations of butyrate, which may prevent adverse effects of this fatty acid on palatability of litter fed to ruminants.

Mesenteric fat cryolipolysis attenuates insulin resistance in the Ossabaw swine model of the metabolic syndrome.

BACKGROUND: The rising prevalence of insulin resistance (IR), metabolic syndrome, and type 2 diabetes are associated with increases in abdominal mesenteric fat. Adipocytes are sensitive to low temperatures, making cryolipolysis of mesenteric fat an attractive treatment modality to potentially reduce IR. OBJECTIVES: We aimed to determine whether (1) cryolipolysis is safe in reducing the volume of the mesenteric fat and (2) reduction in mesenteric fat volume reduces indices of IR and glycemic dysfunction. SETTING: Indiana University School of Medicine. METHODS: A novel cooling device and method delivered cryolipolysis in a controlled manner to avoid tissue ablative temperatures. Ossabaw pigs (n = 8) were fed a high-fat diet for 9 months to develop visceral obesity, IR, and metabolic syndrome. Following laparotomy, mesenteric fat cryolipolysis (MFC) was performed in 5 pigs, while 3 served as sham surgery controls. The volume of the mesenteric fat was measured by computed tomography and compared with indices of glucose intolerance before and at 3 and 6 months postprocedure. RESULTS: MFC safely reduced mesenteric fat volume by ∼30% at 3 months, which was maintained at 6 months. Body weight did not change in either the MFC or sham surgery control groups. Measure of glycemic control, insulin sensitivity, and blood pressure significantly improved after MFC compared with sham controls. CONCLUSION: MFC reduces the volume of mesenteric fat and improves glycemic control in obese, IR Ossabaw pigs, without adverse effects.

COVID-19-associated AKI in hospitalized US patients: incidence, temporal trends, geographical distribution, risk factors and mortality.

Background: Acute kidney injury (AKI) is associated with mortality in patients hospitalized with COVID-19, however, its incidence, geographic distribution, and temporal trends since the start of the pandemic are understudied. Methods: Electronic health record data were obtained from 53 health systems in the United States (US) in the National COVID Cohort Collaborative (N3C). We selected hospitalized adults diagnosed with COVID-19 between March 6th, 2020, and January 6th, 2022. AKI was determined with serum creatinine (SCr) and diagnosis codes. Time were divided into 16-weeks (P1-6) periods and geographical regions into Northeast, Midwest, South, and West. Multivariable models were used to analyze the risk factors for AKI or mortality. Results: Out of a total cohort of 306,061, 126,478 (41.0 %) patients had AKI. Among these, 17.9% lacked a diagnosis code but had AKI based on the change in SCr. Similar to patients coded for AKI, these patients had higher mortality compared to those without AKI. The incidence of AKI was highest in P1 (49.3%), reduced in P2 (40.6%), and relatively stable thereafter. Compared to the Midwest, the Northeast, South, and West had higher adjusted AKI incidence in P1, subsequently, the South and West regions continued to have the highest relative incidence. In multivariable models, AKI defined by either SCr or diagnostic code, and the severity of AKI was associated with mortality. Conclusions: Uncoded cases of COVID-19-associated AKI are common and associated with mortality. The incidence and distribution of COVID-19-associated AKI have changed since the first wave of the pandemic in the US.

Ontology-Based Classification and Analysis of Adverse Events Associated With the Usage of Chloroquine and Hydroxychloroquine.

Multiple methodologies have been developed to identify and predict adverse events (AEs); however, many of these methods do not consider how patient population characteristics, such as diseases, age, and gender, affect AEs seen. In this study, we evaluated the utility of collecting and analyzing AE data related to hydroxychloroquine (HCQ) and chloroquine (CQ) from US Prescribing Information (USPIs, also called drug product labels or package inserts), the FDA Adverse Event Reporting System (FAERS), and peer-reviewed literature from PubMed/EMBASE, followed by AE classification and modeling using the Ontology of Adverse Events (OAE). Our USPI analysis showed that CQ and HCQ AE profiles were similar, although HCQ was reported to be associated with fewer types of cardiovascular, nervous system, and musculoskeletal AEs. According to EMBASE literature mining, CQ and HCQ were associated with QT prolongation (primarily when treating COVID-19), heart arrhythmias, development of Torsade des Pointes, and retinopathy (primarily when treating lupus). The FAERS data was analyzed by proportional ratio reporting, Chi-square test, and minimal case number filtering, followed by OAE classification. HCQ was associated with 63 significant AEs (including 21 cardiovascular AEs) for COVID-19 patients and 120 significant AEs (including 12 cardiovascular AEs) for lupus patients, supporting the hypothesis that the disease being treated affects the type and number of certain CQ/HCQ AEs that are manifested. Using an HCQ AE patient example reported in the literature, we also ontologically modeled how an AE occurs and what factors (e.g., age, biological sex, and medical history) are involved in the AE formation. The methodology developed in this study can be used for other drugs and indications to better identify patient populations that are particularly vulnerable to AEs.

24-Hour Profiles of 11-Oxygenated C19 Steroids and Δ5-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency.

Background: Optimal management of androgen excess in 21-hydroxylase deficiency (21OHD) remains challenging. 11-oxygenated-C19 steroids (11-oxyandrogens) have emerged as promising biomarkers of disease control, but data regarding their response to treatment are lacking. Objective: To compare the dynamic response of a broad set of steroids to both conventional oral glucocorticoids (OG) and circadian cortisol replacement via continuous subcutaneous hydrocortisone infusion (CSHI) in patients with 21OHD based on 24-hour serial sampling. Participants and Methods: We studied 8 adults (5 women), ages 19-43 years, with poorly controlled classic 21OHD who participated in a single-center open-label phase I-II study comparing OG with CSHI. We used mass spectrometry to measure 15 steroids (including 11-oxyandrogens and Δ5 steroid sulfates) in serum samples obtained every 2 h for 24 h after 3 months of stable OG, and 6 months into ongoing CSHI. Results: In response to OG therapy, androstenedione, testosterone (T), and their four 11-oxyandrogen metabolites:11ß-hydroxyandrostenedione, 11-ketoandrostenedione, 11ß-hydroxytestosterone and 11-ketotestosterone (11KT) demonstrated a delayed decline in serum concentrations, and they achieved a nadir between 0100-0300. Unlike DHEAS, which had little diurnal variation, pregnenolone sulfate (PregS) and 17-hydoxypregnenolone sulfate peaked in early morning and declined progressively throughout the day. CSHI dampened the early ACTH and androgen rise, allowing the ACTH-driven adrenal steroids to return closer to baseline before mid-day. 11KT concentrations displayed the most consistent difference between OG and CSHI across all time segments. While T was lowered by CSHI as compared with OG in women, T increased in men, suggesting an improvement of the testicular function in parallel with 21OHD control in men. Conclusion: 11-oxyandrogens and PregS could serve as biomarkers of disease control in 21OHD. The development of normative data for these promising novel biomarkers must consider their diurnal variability.

Identification and Development of Therapeutics for COVID-19.

After emerging in China in late 2019, the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread worldwide, and as of mid-2021, it remains a significant threat globally. Only a few coronaviruses are known to infect humans, and only two cause infections similar in severity to SARS-CoV-2: Severe acute respiratory syndrome-related coronavirus, a species closely related to SARS-CoV-2 that emerged in 2002, and Middle East respiratory syndrome-related coronavirus, which emerged in 2012. Unlike the current pandemic, previous epidemics were controlled rapidly through public health measures, but the body of research investigating severe acute respiratory syndrome and Middle East respiratory syndrome has proven valuable for identifying approaches to treating and preventing novel coronavirus disease 2019 (COVID-19). Building on this research, the medical and scientific communities have responded rapidly to the COVID-19 crisis and identified many candidate therapeutics. The approaches used to identify candidates fall into four main categories: adaptation of clinical approaches to diseases with related pathologies, adaptation based on virological properties, adaptation based on host response, and data-driven identification (ID) of candidates based on physical properties or on pharmacological compendia. To date, a small number of therapeutics have already been authorized by regulatory agencies such as the Food and Drug Administration (FDA), while most remain under investigation. The scale of the COVID-19 crisis offers a rare opportunity to collect data on the effects of candidate therapeutics. This information provides insight not only into the management of coronavirus diseases but also into the relative success of different approaches to identifying candidate therapeutics against an emerging disease. IMPORTANCE The COVID-19 pandemic is a rapidly evolving crisis. With the worldwide scientific community shifting focus onto the SARS-CoV-2 virus and COVID-19, a large number of possible pharmaceutical approaches for treatment and prevention have been proposed. What was known about each of these potential interventions evolved rapidly throughout 2020 and 2021. This fast-paced area of research provides important insight into how the ongoing pandemic can be managed and also demonstrates the power of interdisciplinary collaboration to rapidly understand a virus and match its characteristics with existing or novel pharmaceuticals. As illustrated by the continued threat of viral epidemics during the current millennium, a rapid and strategic response to emerging viral threats can save lives. In this review, we explore how different modes of identifying candidate therapeutics have borne out during COVID-19.

Characterizing Long COVID: Deep Phenotype of a Complex Condition.

BACKGROUND: Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or "long COVID"), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies. METHODS: The Human Phenotype Ontology (HPO) is a widely used standard for exchange and analysis of phenotypic abnormalities in human disease but has not yet been applied to the analysis of COVID-19. FUNDING: We identified 303 articles published before April 29, 2021, curated 59 relevant manuscripts that described clinical manifestations in 81 cohorts three weeks or more following acute COVID-19, and mapped 287 unique clinical findings to HPO terms. We present layperson synonyms and definitions that can be used to link patient self-report questionnaires to standard medical terminology. Long COVID clinical manifestations are not assessed consistently across studies, and most manifestations have been reported with a wide range of synonyms by different authors. Across at least 10 cohorts, authors reported 31 unique clinical features corresponding to HPO terms; the most commonly reported feature was Fatigue (median 45.1%) and the least commonly reported was Nausea (median 3.9%), but the reported percentages varied widely between studies. INTERPRETATION: Translating long COVID manifestations into computable HPO terms will improve analysis, data capture, and classification of long COVID patients. If researchers, clinicians, and patients share a common language, then studies can be compared/pooled more effectively. Furthermore, mapping lay terminology to HPO will help patients assist clinicians and researchers in creating phenotypic characterizations that are computationally accessible, thereby improving the stratification, diagnosis, and treatment of long COVID. FUNDING: U24TR002306; UL1TR001439; P30AG024832; GBMF4552; R01HG010067; UL1TR002535; K23HL128909; UL1TR002389; K99GM145411.

Evaluation of Sodium Bisulfate on Reducing Salmonella Heidelberg Biofilm and Colonization in Broiler Crops and Ceca.

Salmonella Heidelberg (SH) on contaminated poultry causes economic and health risks to producers and consumers. We hypothesized that sodium bisulfate (SBS) would decrease SH biofilm on polyvinyl chloride (PVC) coupons and decrease the horizontal transfer of SH in broilers. Experiment 1: Salmonella Heidelberg biofilm was cultured with PVC coupons, which were treated with SBS at a pH of 3.5 for 10 min, 8 h, and 24 h. Experiment 2: Nine replicate pens per treatment were divided between two rooms. A seeder contact model was used to mimic a natural infection environment. Treatments consisted of tap water or sodium bisulfate in water at a pH of 3.5. Salmonella Heidelberg incidence and enumeration were measured in crops and ceca. Sodium bisulfate significantly reduced biofilm by 2.16 and 1.04 logs when treated for 8 and 24 h, respectively. Crop colonization was significantly decreased in trials 1 and 2 by 0.29 and 0.23 logs, respectively. Crop pH was significantly decreased in trial 2. Ceca colonization was significantly decreased in trial 1 by 0.39 logs. The results from the present study suggest that SBS may be administered to drinking water to decrease SH gut colonization and to reduce biofilm.

Pathogenesis, Symptomatology, and Transmission of SARS-CoV-2 through Analysis of Viral Genomics and Structure.

The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world and infected hundreds of millions of people with coronavirus disease 2019 (COVID-19). While this viral species was unknown prior to January 2020, its similarity to other coronaviruses that infect humans has allowed for rapid insight into the mechanisms that it uses to infect human hosts, as well as the ways in which the human immune system can respond. Here, we contextualize SARS-CoV-2 among other coronaviruses and identify what is known and what can be inferred about its behavior once inside a human host. Because the genomic content of coronaviruses, which specifies the virus's structure, is highly conserved, early genomic analysis provided a significant head start in predicting viral pathogenesis and in understanding potential differences among variants. The pathogenesis of the virus offers insights into symptomatology, transmission, and individual susceptibility. Additionally, prior research into interactions between the human immune system and coronaviruses has identified how these viruses can evade the immune system's protective mechanisms. We also explore systems-level research into the regulatory and proteomic effects of SARS-CoV-2 infection and the immune response. Understanding the structure and behavior of the virus serves to contextualize the many facets of the COVID-19 pandemic and can influence efforts to control the virus and treat the disease. IMPORTANCE COVID-19 involves a number of organ systems and can present with a wide range of symptoms. From how the virus infects cells to how it spreads between people, the available research suggests that these patterns are very similar to those seen in the closely related viruses SARS-CoV-1 and possibly Middle East respiratory syndrome-related CoV (MERS-CoV). Understanding the pathogenesis of the SARS-CoV-2 virus also contextualizes how the different biological systems affected by COVID-19 connect. Exploring the structure, phylogeny, and pathogenesis of the virus therefore helps to guide interpretation of the broader impacts of the virus on the human body and on human populations. For this reason, an in-depth exploration of viral mechanisms is critical to a robust understanding of SARS-CoV-2 and, potentially, future emergent human CoVs (HCoVs).

Treatment trends for advanced oropharyngeal squamous cell carcinoma in the era of human papillomavirus.

BACKGROUND: Given recent increase in prevalence of oropharyngeal squamous cell carcinoma (OPSCC) and advances in surgical capabilities, we sought to determine whether a change in frequency of surgery-based treatment for locally advanced OPSCC has occurred. METHODS: Patients with T3-T4b OPSCC in the National Cancer Database diagnosed from 2010 to 2016 were categorized as receiving primary surgery or radiation-based therapy and stratified by human papillomavirus (HPV) status. Trends in treatment selection and factors associated with treatment type were examined. RESULTS: 6566 patients with HPV-positive were included, of whom 489 (7.45%) received surgery and 4698 patients with HPV-negative, of whom 362 (7.71%) received surgery. The percentage of patients treated with surgery decreased from 11.8% to 5.9% for HPV-positive disease and from 9.8% to 6.3% for HPV-negative disease. Factors associated with surgery included younger age, health insurance, and treatment at academic centers. CONCLUSIONS: In HPV-positive and HPV-negative disease, the percentage of locally advanced OPSCC undergoing surgery-based therapy has decreased.

Ten Rules for Conducting Retrospective Pharmacoepidemiological Analyses: Example COVID-19 Study.

Since the beginning of the COVID-19 pandemic, pharmaceutical treatment hypotheses have abounded, each requiring careful evaluation. A randomized controlled trial generally provides the most credible evaluation of a treatment, but the efficiency and effectiveness of the trial depend on the existing evidence supporting the treatment. The researcher must therefore compile a body of evidence justifying the use of time and resources to further investigate a treatment hypothesis in a trial. An observational study can provide this evidence, but the lack of randomized exposure and the researcher's inability to control treatment administration and data collection introduce significant challenges. A proper analysis of observational health care data thus requires contributions from experts in a diverse set of topics ranging from epidemiology and causal analysis to relevant medical specialties and data sources. Here we summarize these contributions as 10 rules that serve as an end-to-end introduction to retrospective pharmacoepidemiological analyses of observational health care data using a running example of a hypothetical COVID-19 study. A detailed supplement presents a practical how-to guide for following each rule. When carefully designed and properly executed, a retrospective pharmacoepidemiological analysis framed around these rules will inform the decisions of whether and how to investigate a treatment hypothesis in a randomized controlled trial. This work has important implications for any future pandemic by prescribing what we can and should do while the world waits for global vaccine distribution.