Design and implementation of a digital site-less clinical study of serial rapid antigen testing to identify asymptomatic SARS-CoV-2 infection.

Background: Rapid antigen detection tests (Ag-RDT) for SARS-CoV-2 with emergency use authorization generally include a condition of authorization to evaluate the test's performance in asymptomatic individuals when used serially. We aim to describe a novel study design that was used to generate regulatory-quality data to evaluate the serial use of Ag-RDT in detecting SARS-CoV-2 virus among asymptomatic individuals. Methods: This prospective cohort study used a siteless, digital approach to assess longitudinal performance of Ag-RDT. Individuals over 2 years old from across the USA with no reported COVID-19 symptoms in the 14 days prior to study enrollment were eligible to enroll in this study. Participants throughout the mainland USA were enrolled through a digital platform between October 18, 2021 and February 15, 2022. Participants were asked to test using Ag-RDT and molecular comparators every 48 hours for 15 days. Enrollment demographics, geographic distribution, and SARS-CoV-2 infection rates are reported. Key Results: A total of 7361 participants enrolled in the study, and 492 participants tested positive for SARS-CoV-2, including 154 who were asymptomatic and tested negative to start the study. This exceeded the initial enrollment goals of 60 positive participants. We enrolled participants from 44 US states, and geographic distribution of participants shifted in accordance with the changing COVID-19 prevalence nationwide. Conclusions: The digital site-less approach employed in the "Test Us At Home" study enabled rapid, efficient, and rigorous evaluation of rapid diagnostics for COVID-19 and can be adapted across research disciplines to optimize study enrollment and accessibility.

Finding a Needle in a Haystack: Design and Implementation of a Digital Site-less Clinical Study of Serial Rapid Antigen Testing to Identify Asymptomatic SARS-CoV-2 Infection.

Background: Rapid antigen tests (Ag-RDT) for SARS-CoV-2 with Emergency Use Authorization generally include a condition of authorization to evaluate the test's performance in asymptomatic individuals when used serially. Objective: To describe a novel study design to generate regulatory-quality data to evaluate serial use of Ag-RDT in detecting SARS-CoV-2 virus among asymptomatic individuals. Design: Prospective cohort study using a decentralized approach. Participants were asked to test using Ag-RDT and molecular comparators every 48 hours for 15 days. Setting: Participants throughout the mainland United States were enrolled through a digital platform between October 18, 2021 and February 15, 2022. Ag-RDTs were completed at home, and molecular comparators were shipped to a central laboratory. Participants: Individuals over 2 years old from across the U.S. with no reported COVID-19 symptoms in the 14 days prior to study enrollment were eligible to enroll in this study. Measurements: Enrollment demographics, geographic distribution, and SARS-CoV-2 infection rates are reported. Key Results: A total of 7,361 participants enrolled in the study, and 492 participants tested positive for SARS-CoV-2, including 154 who were asymptomatic and tested negative to start the study. This exceeded the initial enrollment goals of 60 positive participants. We enrolled participants from 44 U.S. states, and geographic distribution of participants shifted in accordance with the changing COVID-19 prevalence nationwide. Limitations: New, complex workflows required significant operational and data team support. Conclusions: The digital site-less approach employed in the 'Test Us At Home' study enabled rapid, efficient, and rigorous evaluation of rapid diagnostics for COVID-19, and can be adapted across research disciplines to optimize study enrollment and accessibility.

Making the Leap from Research Laboratory to Clinic: Challenges and Opportunities for Next-Generation Sequencing in Infectious Disease Diagnostics.

Next-generation DNA sequencing (NGS) has progressed enormously over the past decade, transforming genomic analysis and opening up many new opportunities for applications in clinical microbiology laboratories. The impact of NGS on microbiology has been revolutionary, with new microbial genomic sequences being generated daily, leading to the development of large databases of genomes and gene sequences. The ability to analyze microbial communities without culturing organisms has created the ever-growing field of metagenomics and microbiome analysis and has generated significant new insights into the relation between host and microbe. The medical literature contains many examples of how this new technology can be used for infectious disease diagnostics and pathogen analysis. The implementation of NGS in medical practice has been a slow process due to various challenges such as clinical trials, lack of applicable regulatory guidelines, and the adaptation of the technology to the clinical environment. In April 2015, the American Academy of Microbiology (AAM) convened a colloquium to begin to define these issues, and in this document, we present some of the concepts that were generated from these discussions.

The Oral Bacterial Communities of Children with Well-Controlled HIV Infection and without HIV Infection.

The oral microbial community (microbiota) plays a critical role in human health and disease. Alterations in the oral microbiota may be associated with disorders such as gingivitis, periodontitis, childhood caries, alveolar osteitis, oral candidiasis and endodontic infections. In the immunosuppressed population, the spectrum of potential oral disease is even broader, encompassing candidiasis, necrotizing gingivitis, parotid gland enlargement, Kaposi's sarcoma, oral warts and other diseases. Here, we used 454 pyrosequencing of bacterial 16S rRNA genes to examine the oral microbiome of saliva, mucosal and tooth samples from HIV-positive and negative children. Patient demographics and clinical characteristics were collected from a cross-section of patients undergoing routine dental care. Multiple specimens from different sampling sites in the mouth were collected for each patient. The goal of the study was to observe the potential diversity of the oral microbiota among individual patients, sample locations, HIV status and various dental characteristics. We found that there were significant differences in the microbiome among the enrolled patients, and between sampling locations. The analysis was complicated by uneven enrollment in the patient cohorts, with only five HIV-negative patients enrolled in the study and by the rapid improvement in the health of HIV-infected children between the time the study was conceived and completed. The generally good oral health of the HIV-negative patients limited the number of dental plaque samples that could be collected. We did not identify significant differences between well-controlled HIV-positive patients and HIV-negative controls, suggesting that well-controlled HIV-positive patients essentially harbor similar oral flora compared to patients without HIV. Nor were significant differences in the oral microbiota identified between different teeth or with different dental characteristics. Additional studies are needed to better characterize the oral microbiome in children and those with poorly-controlled HIV infections.

Group A beta streptococcal infections in children after oral or dental trauma: a case series of 5 patients.

Group A streptococcus (GAS) produces a variety of disease processes in children. Severe invasive diseases such as necrotizing fasciitis can result. Traumatic dental injuries are common in the pediatric population, although the role of dental injuries in invasive GAS disease is not well characterized. In this article, we describe our retrospective series of 5 cases of GAS infection following oral or dental trauma in children.

A meta-analysis of the placebo rates of remission and response in clinical trials of active ulcerative colitis.

BACKGROUND & AIMS: Knowledge of the placebo outcomes and understanding specific study features that influence these outcomes is important for designing future clinical trials evaluating therapy of ulcerative colitis (UC). The aims of this study were to estimate the placebo rates of remission and response in placebo-controlled, randomized clinical trials for active UC and to identify factors influencing these rates. METHODS: We performed a systematic review and meta-analysis of placebo-controlled, randomized clinical trials evaluating therapies for active UC identified from MEDLINE from 1966 through 2005. RESULTS: Forty studies met the inclusion criteria. The pooled estimates of the placebo rates of remission and response were 13% (95% confidence interval, 9%-18%; range, 0%-40%; median, 12%) and 28% (95% confidence interval, 23%-33%; range, 0%-67%; median, 30%), respectively, both with significant heterogeneity. Studies that used more stringent definitions of outcomes had lower placebo rates of remission and response. Study duration, number of study visits, disease duration, baseline composite and rectal bleeding scores of the disease activity index, and inclusion of endoscopic mucosal healing as the remission definition all were associated with the placebo remission rate. CONCLUSIONS: Rates of remission in the placebo arm of UC clinical trials ranges from 0% to 40%. The placebo remission rates are influenced by the trial length, number of study visits, use of stricter remission definitions, and design features that enroll patients with more active disease. These factors should be considered when designing future placebo-controlled clinical trials in patients with active UC.