The Landscape of NIAID-funded Observational COVID-19 Cohort Studies.

The spread of SARS-CoV-2 since late 2019 represented an unprecedented public health emergency, which included a need to fully understand COVID-19 disease across all ages and populations. In response, the US National Institute of Allergy and Infectious Diseases (NIAID) rapidly funded epidemiology studies that monitored COVID-19. However, the diversity and breadth of the populations studied in NIAID-funded COVID-19 observational cohorts were not easy to extrapolate because of siloed approaches to collect and report data within NIAID. Here, we describe the effort to develop a harmonized cohort study reporting tool that includes common epidemiological data elements as well as NIAID priorities. We report its implementation to analyze metadata from 58 COVID-19 cohort studies funded February 2020 to June 2021, visualize key metadata including geographic distribution, study duration, participant demographics, sample types collected, and scientific priorities addressed. A bibliographic analysis highlights the scientific publications and citations across these funded studies and demonstrates their enormous impact on the COVID-19 field. These analyses highlight how common data elements and reporting tools can assist funding agencies to capture the landscape and potential gaps during public health responses and how they can assist in decision making.

The C Protein Is Recruited to Measles Virus Ribonucleocapsids by the Phosphoprotein.

Measles virus (MeV), like all viruses of the order Mononegavirales, utilizes a complex consisting of genomic RNA, nucleoprotein, the RNA-dependent RNA polymerase, and a polymerase cofactor, the phosphoprotein (P), for transcription and replication. We previously showed that a recombinant MeV that does not express another viral protein, C, has severe transcription and replication deficiencies, including a steeper transcription gradient than the parental virus and generation of defective interfering RNA. This virus is attenuated in vitro and in vivo However, how the C protein operates and whether it is a component of the replication complex remained unclear. Here, we show that C associates with the ribonucleocapsid and forms a complex that can be purified by immunoprecipitation or ultracentrifugation. In the presence of detergent, the C protein is retained on purified ribonucleocapsids less efficiently than the P protein and the polymerase. The C protein is recruited to the ribonucleocapsid through its interaction with the P protein, as shown by immunofluorescence microscopy of cells expressing different combinations of viral proteins and by split luciferase complementation assays. Forty amino-terminal C protein residues are dispensable for the interaction with P, and the carboxyl-terminal half of P is sufficient for the interaction with C. Thus, the C protein, rather than being an "accessory" protein as qualified in textbooks so far, is a ribonucleocapsid-associated protein that interacts with P, thereby increasing replication accuracy and processivity of the polymerase complex.IMPORTANCE Replication of negative-strand RNA viruses relies on two components: a helical ribonucleocapsid and an RNA-dependent RNA polymerase composed of a catalytic subunit, the L protein, and a cofactor, the P protein. We show that the measles virus (MeV) C protein is an additional component of the replication complex. We provide evidence that the C protein is recruited to the ribonucleocapsid by the P protein and map the interacting segments of both C and P proteins. We conclude that the primary function of MeV C is to improve polymerase processivity and accuracy, rather than uniquely to antagonize the type I interferon response. Since most viruses of the Paramyxoviridae family express C proteins, their primary function may be conserved.

A 15-year review of characteristics and outcomes of patients leaving against medical advice.

PURPOSE: Discharging against medical advice can have significant, detrimental effects on burn patient outcomes as well as higher hospital readmission rates and healthcare expenditures. The goal of this study is to identify characteristics of patients who left against medical advice and suggest solutions to mitigate these factors. Data were collected at our American Burn Association verified Burn Unit over a 15-year period. RESULTS: Between 2007 and 2022, 37 patients were identified as having left against medical advice from the burn unit. The average patient age was 37 years old with 64.9% being male, and 70.2% were identified as having a substance abuse history. The majority (51.4%) had Medicaid or State health insurance, 29.7% had no insurance, and 18.9% had private insurance. The mechanism of injury was most commonly frostbite (43.2%). The majority sustained < 1% total body surface area injuries. Most (83.7%) had social work and/or case management involved during their admission, and all (100%) had their involvement if the length of admission was greater than one day. Over half (59.5%) returned to the ED within 2 weeks with complications. CONCLUSIONS: This study found that patients discharging against medical advice from the burn unit suffered from smaller injuries, often due to cold related injuries. These patients had comorbid substance abuse or psychiatric histories, and the majority had Medicaid or state health insurance. Recruiting interdisciplinary care members, including social work, psychiatry, and addiction medicine, early may help these patients by encouraging completion of their hospital care and setting up crucial follow-up care.

Palliative treatment for malignant gastrointestinal obstruction with peritoneal carcinomatosis: enteral stenting versus surgery.

Background and study aims Management of malignant gastrointestinal obstruction (MGIO) is more challenging in the presence of peritoneal carcinomatosis (PC). Outcomes data to guide the management of MGIO with PC are lacking. We aimed to compare the clinical outcomes and adverse events between endoscopic and surgical palliation and identify predictors of stent success in patients with MGIO with PC. Patients and methods Consecutive inpatients with MGIO with PC between 2000 and 2018 who underwent palliative surgery or enteral stenting were included. Clinical success was defined as relief of obstructive symptoms. Results Fifty-seven patients with enteral stenting and 40 with palliative surgery were compared. The two groups did not differ in rates of technical success, 30-day mortality, or recurrence. Clinical success from a single intervention (63.2 % versus 95 %), luminal patency duration (27 days vs. 145 days), and survival length (148 days vs. 336 days) favored palliative surgery (all P  < 0.05) but the patients in the surgery group had a trend toward better Eastern Cooperative Oncology Group (ECOG) status. The rate of adverse events (AEs) (10.5 % vs. 50 %), the severity of AEs, and length of hospital stay (4.5 days vs. 9 days) favored enteral stenting ( P  < 0.05). The need for more than one stent was associated with a higher likelihood of stent failure. Conclusions Our study suggests that enteral stenting is safer and associated with a shorter hospital stay than palliative surgery, although unlike other MGIOs, clinical success is lower in MGIO with PC. Identification of the right candidates and potential predictors of clinical success in ECOG-matched large-scale studies is needed to validate these results.