scholarly journals 742. Evaluation of Chagas Disease Diagnostic Testing Practices in Four Hospital Systems in California and Texas

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S469-S469
Author(s):  
Emily A Kelly ◽  
Jose I Echeverri Alegre ◽  
Katherine Promer ◽  
Jesica Hayon ◽  
Roumen Iordanov ◽  
...  
Keyword(s):  
San Francisco ◽  
Chagas Disease ◽  
Diagnostic Testing ◽  
The United States ◽  
Institutional Review Boards ◽  
Medical Provider ◽  
Confirmatory Testing ◽  
Diagnostic Practices ◽  
Early Results ◽  
Hospital Systems

Abstract Background Chagas disease (CD) is a neglected parasitic disease that affects >6 million people in the Americas, including >200,000 people in the United States (US). Medical provider knowledge of CD is key to decreasing morbidity and transmission; however, few studies have assessed diagnostic practices in US health systems serving at-risk patients. Our study aimed to describe existing provider approaches to diagnosing CD in California and Texas. Methods Site-based research teams at four hospital systems (the University of California [UC] San Francisco [UCSF], San Diego [UCSD], Irvine [UCI], and the Harris Health System [HHS] in Houston, TX) retrospectively identified patients ≥18 years old tested for CD between 2016-2019 and systematically extracted electronic medical record data using complementary electronic data entry forms. Specifically, eligible patients were identified using laboratory orders at UCSF and UCI, while the remaining sites employed SlicerDicer (Epic Systems). This study was approved by institutional review boards at each site. Results We identified 333 patients tested for CD, including 109 from UCSF, 88 from UCSD, 25 from UCI, and 111 from HHS. These patients had 125, 99, 31, and 181 tests sent to commercial laboratories, respectively. Test reactivity varied by system with the greatest percent reactivity among tests ordered at UCI (23%) followed by UCSD (16%), HHS (15%), and UCSF (10%). Among patients who screened positive for CD by commercial assays, confirmatory testing through the Centers for Disease Control and Prevention was sought for 100% at UCI; 59% at HHS, 55% at UCSF, and 40% at UCSD. The medical specialty that most often ordered CD testing was Cardiology at all UC sites (UCSF, 50%; UCSF, 55%; UCI, 35%) and Internal Medicine at HHS (46%; Cardiology ordered 13%). Only one recorded CD test was ordered by an Obstetrics/Gynecology service at any site. Conclusion These early results report positivity rates between our healthcare systems and demonstrate inconsistency in attaining recommended confirmatory testing, as well as a paucity of CD testing ordered through Obstetrics/Gynecology despite risk of congenital transmission. These findings suggest areas of opportunity to improve provider awareness and lay a foundation for standardizing CD diagnostic practices in the US. Disclosures Caryn Bern, MD, MPH, UpToDate (Wolters Kluwer) (Other Financial or Material Support, Author Royalties)

scholarly journals Lead Identification to Clinical Candidate Selection

2014 ◽  
Vol 20 (1) ◽  
pp. 101-111 ◽  
Author(s):  
R. Jeffrey Neitz ◽  
Steven Chen ◽  
Frantisek Supek ◽  
Vince Yeh ◽  
Danielle Kellar ◽  
...  
Keyword(s):  
San Francisco ◽  
Chagas Disease ◽  
Colorimetric Assay ◽  
The United States ◽  
Ergosterol Biosynthesis ◽  
Screening Methods ◽  
Ergosterol Biosynthesis Inhibitors ◽  
Approved Drugs ◽  
The University ◽  
Fda Approved Drugs

Chagas disease affects 8 million people worldwide and remains a main cause of death due to heart failure in Latin America. The number of cases in the United States is now estimated to be 300,000, but there are currently no Food and Drug Administration (FDA)–approved drugs available for patients with Chagas disease. To fill this gap, we have established a public-private partnership between the University of California, San Francisco and the Genomics Institute of the Novartis Research Foundation (GNF) with the goal of delivering clinical candidates to treat Chagas disease. The discovery phase, based on the screening of more than 160,000 compounds from the GNF Academic Collaboration Library, led to the identification of new anti-Chagas scaffolds. Part of the screening campaign used and compared two screening methods, including a colorimetric-based assay using Trypanosoma cruzi expressing β-galactosidase and an image-based, high-content screening (HCS) assay using the CA-I/72 strain of T. cruzi. Comparing molecules tested in both assays, we found that ergosterol biosynthesis inhibitors had greater potency in the colorimetric assay than in the HCS assay. Both assays were used to inform structure-activity relationships for antiparasitic efficacy and pharmacokinetics. A new anti– T. cruzi scaffold derived from xanthine was identified, and we describe its development as lead series.

scholarly journals Geospatial Spread of Antimicrobial Resistance, Bacterial and Fungal Threats to COVID-19 Survival, and Point-of-Care Solutions

2020 ◽  
Author(s):  
Gerald J. Kost
Keyword(s):  
Antimicrobial Resistance ◽  
San Francisco ◽  
Point Of Care ◽  
Diagnostic Testing ◽  
The United States ◽  
Pathogen Resistance ◽  
Standards Of Care ◽  
Healthcare Personnel ◽  
Diagnostic Challenge ◽  
Antimicrobial Drugs

ABSTRACT Context. Point-of-care testing (POCT) is inherently spatial, that is, performed where needed, and intrinsically temporal, because it accelerates decision making. POCT efficiency and effectiveness have the potential to facilitate antimicrobial resistance (AMR) detection, decrease risks of co-infections for critically ill COVID-19 patients, and improve the cost-effectiveness of healthcare. Objectives. To assess AMR identification using POCT, describe the United States AMR Diagnostic Challenge, and improve global standards of care for infectious diseases. Data Sources PubMed, WWW, and other sources were searched for papers focusing on AMR and POCT. EndNote X9.1 (Clarivate Analytics) consolidated abstracts, URLs, and PDFs representing ~500 articles assessed for relevance. Panelist insights at Tri•Con 2020 in San Francisco and finalist POC technologies competing for a US $20,000,000 AMR prize are summarized. Conclusions. Co-infections represent high risks for COVID-19 patients. POCT potentially will help target specific pathogens, refine choices for antimicrobial drugs, and prevent excess morbidity and mortality. POC assays that identify patterns of pathogen resistance can help tell us how infected individuals spread AMR, where geospatial hotspots are located, when delays cause death, and how to deploy preventative resources. Shared AMR data “clouds” could help reduce critical care burden during pandemics and optimize therapeutic options, similar to use of antibiograms in individual hospitals. Multidisciplinary healthcare personnel should learn the principles and practice of POCT, so they can meet needs with rapid diagnostic testing. The stakes are high. AMR is projected to cause millions of deaths annually and cumulative financial loses in the trillions by 2050.

scholarly journals Malaria Diagnostic Practices in U.S. Laboratories in 2017

2018 ◽  
Vol 56 (8) ◽  
Author(s):  
Christopher Prestel ◽  
Kathrine R. Tan ◽  
Francisca Abanyie ◽  
Robert Jerris ◽  
Julie R. Gutman
Keyword(s):  
United States ◽  
Blood Smear ◽  
Diagnostic Testing ◽  
Malaria Diagnosis ◽  
The United States ◽  
Diagnostic Practices ◽  
Similar Survey ◽  
American Society ◽  
Delays In Diagnosis ◽  
Diagnostic Capabilities

ABSTRACT In the United States, the gold standard for malaria diagnosis is microscopic blood smear examination. Because malaria is not endemic in the United States, diagnostic capabilities may be limited, causing delays in diagnosis and increased morbidity and mortality. A survey of the malaria diagnostic practices of U.S. laboratories was conducted from June to July 2017; members of the American Society for Microbiology's listserv received a questionnaire inquiring about malaria diagnostic test availability, techniques, and reporting. Results were assessed using the Clinical and Laboratory Standards Institute (CLSI) guidelines for malaria diagnostics. After excluding incomplete and duplicate responses, responses representing 175 laboratories were included. Most labs (99%) received at least one specimen annually for malaria diagnosis, and 31% reported receiving only 1 to 10 specimens. The majority (74%) diagnosed five or fewer cases of malaria per year. Most (90%) performed blood smears on-site. Two-thirds (70%) provided initial blood smear results within 4 h. Although diagnostic testing for malaria was available 24/7 at 74% (141) of responding laboratories, only 12% (17) met criteria for analysis and reporting of malaria testing, significantly more than reported in a similar survey in 2010 (3%; P < 0.05). The majority of laboratories surveyed had the capability for timely diagnosis of malaria; few comply with CLSI guidelines. Inexperience may factor into this noncompliance; many laboratories see few to no cases of malaria per year. Although reported adherence to CLSI guidelines was higher than in 2010, there is a need to further improve laboratory compliance with recommendations.

scholarly journals Anaphylactic Reactions Due to Triatoma protracta (Hemiptera, Reduviidae, Triatominae) and Invasion into a Home in Northern California, USA

Insects ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 1018
Author(s):  
Norman L. Beatty ◽  
Zoe S. White ◽  
Chanakya R. Bhosale ◽  
Kristen Wilson ◽  
Anthony P. Cannella ◽  
...  
Keyword(s):  
United States ◽  
Chagas Disease ◽  
Diagnostic Testing ◽  
The United States ◽  
Allergic Reactions ◽  
Serological Testing ◽  
Clinical Investigations ◽  
Mendocino County ◽  
Chronic Chagas Disease ◽  
Discrete Typing Unit

Background: Triatoma protracta is a triatomine found naturally throughout many regions of California and has been shown to invade human dwellings and bite residents. A man living in Mendocino County, California, reported developing anaphylactic reactions due to the bite of an “unusual bug”, which he had found in his home for several years. Methods: We conducted environmental, entomological, and clinical investigations to examine the risk for kissing bug invasion, presence of Trypanosoma cruzi, and concerns for Chagas disease at this human dwelling with triatomine invasion. Results: Home assessment revealed several risk factors for triatomine invasion, which includes pack rat infestation, above-ground wooden plank floor without a concrete foundation, canine living in the home, and lack of residual insecticide use. Triatomines were all identified as Triatoma protracta. Midgut molecular analysis of the collected triatomines revealed the detection of T. cruzi discrete typing unit I among one of the kissing bugs. Blood meal PCR-based analysis showed these triatomines had bitten humans, canine and unidentified snake species. The patient was tested for chronic Chagas disease utilizing rapid diagnostic testing and laboratory serological testing, and all were negative. Conclusions: Triatoma protracta is known to invade human dwellings in the western portions of the United States. This is the first report of T. cruzi-infected triatomines invading homes in Mendocino County, California. Triatoma protracta is a known vector responsible for autochthonous Chagas disease within the United States, and their bites can also trigger serious systemic allergic reactions, such as anaphylaxis.

scholarly journals Chagas Disease in the United States: A Perspective on Diagnostic Testing Limitations and Next Steps

2021 ◽  
Author(s):  
Natasha S. Hochberg ◽  
Alyse Wheelock ◽  
Davidson H. Hamer ◽  
Rachel Marcus ◽  
Melissa S. Nolan ◽  
...  
Keyword(s):  
United States ◽  
Chagas Disease ◽  
Diagnostic Testing ◽  
The United States ◽  
Tropical Disease ◽  
Neglected Tropical Disease

Chagas disease is a neglected tropical disease that affects an estimated 300,000 people in the United States. This perspective piece reviews diagnostic challenges and proposes next steps to address these shortfalls.

Craft Beer's Unlikely Alchemist

2019 ◽  
Vol 19 (4) ◽  
pp. 78-90
Author(s):  
Theresa McCulla
Keyword(s):  
San Francisco ◽  
Assembly Line ◽  
The United States ◽  
Risk Tolerance ◽  
Small Scale ◽  
Intellectual Curiosity ◽  
Brewing Industry ◽  
Washing Machine ◽  
Craft Beer ◽  
History Of

In 1965, Frederick (Fritz) Maytag III began a decades-long revitalization of Anchor Brewing Company in San Francisco, California. This was an unexpected venture from an unlikely brewer; for generations, Maytag's family had run the Maytag Washing Machine Company in Iowa and he had no training in brewing. Yet Maytag's career at Anchor initiated a phenomenal wave of growth in the American brewing industry that came to be known as the microbrewing—now “craft beer”—revolution. To understand Maytag's path, this article draws on original oral histories and artifacts that Maytag donated to the Smithsonian Institution's National Museum of American History via the American Brewing History Initiative, a project to document the history of brewing in the United States. The objects and reflections that Maytag shared with the museum revealed a surprising link between the birth of microbrewing and the strategies and culture of mass manufacturing. Even if the hallmarks of microbrewing—a small-scale, artisan approach to making beer—began as a backlash against the mass-produced system of large breweries, they relied on Maytag's early, intimate connections to the assembly-line world of the Maytag Company and the alchemy of intellectual curiosity, socioeconomic privilege, and risk tolerance with which his history equipped him.

The “Japanese Turn” in Fine Dining in the United States, 1980–2020

2020 ◽  
Vol 20 (2) ◽  
pp. 45-54
Author(s):  
Samuel H. Yamashita
Keyword(s):  
United States ◽  
New York ◽  
Los Angeles ◽  
San Francisco ◽  
San Francisco Bay Area ◽  
The United States ◽  
First Century ◽  
Further Training ◽  
Bay Area ◽  
Wide Acceptance

In the 1970s, Japanese cooks began to appear in the kitchens of nouvelle cuisine chefs in France for further training, with scores more arriving in the next decades. Paul Bocuse, Alain Chapel, Joël Robuchon, and other leading French chefs started visiting Japan to teach, cook, and sample Japanese cuisine, and ten of them eventually opened restaurants there. In the 1980s and 1990s, these chefs' frequent visits to Japan and the steady flow of Japanese stagiaires to French restaurants in Europe and the United States encouraged a series of changes that I am calling the “Japanese turn,” which found chefs at fine-dining establishments in Los Angeles, New York City, and later the San Francisco Bay Area using an ever-widening array of Japanese ingredients, employing Japanese culinary techniques, and adding Japanese dishes to their menus. By the second decade of the twenty-first century, the wide acceptance of not only Japanese ingredients and techniques but also concepts like umami (savory tastiness) and shun (seasonality) suggest that Japanese cuisine is now well known to many American chefs.

423 Safety and preliminary efficacy of intratumoral cavrotolimod (AST-008), a spherical nucleic acid TLR9 agonist, in combination with pembrolizumab in patients with advanced solid tumors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A449-A449
Author(s):  
Steven O’Day ◽  
Cesar Perez ◽  
Trisha Wise-Draper ◽  
Glenn Hanna ◽  
Shailender Bhatia ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Solid Tumors ◽  
San Francisco ◽  
Institutional Review Boards ◽  
Advanced Solid Tumors ◽  
Phase 2 ◽  
Serious Adverse Events ◽  
Tlr9 Agonist ◽  
Phase 1B ◽  
Spherical Nucleic Acids

BackgroundSpherical nucleic acids (SNAs) are nanostructures consisting of radially oriented, densely packed oligonucleotides arranged in a spherical 3D architecture. SNAs have different properties than linear oligonucleotides, including increased cellular uptake, which may enhance efficacy. Cavrotolimod (AST-008) is an SNA toll-like receptor 9 (TLR9) agonist designed to robustly activate innate and adaptive immune responses. Cavrotolimod is in development for the treatment of advanced solid tumors in combination with PD-1 blockade. Prior studies demonstrated that cavrotolimod, alone and in combination with PD-1 blockade, increased circulating levels of Th1-type cytokines and activated peripheral T cells and NK cells.MethodsAST-008-102 is an ongoing Phase 1b/2 study (NCT03684785). The Phase 1b dose escalation stage examined intratumoral (IT) cavrotolimod at doses of 2, 4, 8, 16, and 32 mg in combination with pembrolizumab in patients with advanced solid tumors. Cavrotolimod was dosed once weekly for 8 weeks and once every 3 weeks thereafter. The Phase 2 dose expansion stage is examining cavrotolimod 32 mg IT in combination with IV pembrolizumab for the treatment of advanced Merkel cell carcinoma (MCC) and in combination with IV cemiplimab for the treatment of advanced cutaneous squamous cell carcinoma (CSCC). Both cohorts are enrolling patients with documented progression of disease on PD-(L)1 blockade. This analysis provides interim results of the Phase 1b stage.ResultsIn the Phase 1b stage, 20 patients were enrolled across all planned dose levels. No dose-limiting toxicities, grade (G)4 toxicities, or treatment-related serious adverse events (AEs) were observed. The most common AEs were injection site reactions (ISRs) and flu-like symptoms. All treatment-related AEs were < G3 except agitation and ISR (1 each). At data cutoff, ORR is 21% (4 of 19 evaluable patients) in a heterogeneous population with solid tumors. All 4 responders (2 melanoma and 2 MCC patients) have ongoing responses, with duration of response exceeding 52 weeks in 2 patients. Three of 4 responders had disease progression on PD-1 blockade at the time of enrollment, and one patient had a prior response to PD-1 blockade, but subsequently relapsed off therapy. Regression of both injected and noninjected lesions was observed. Gene expression analyses demonstrated increased IT infiltration by cytotoxic immune cells in both injected and noninjected tumors. The highest dose (32 mg) was selected for the Phase 2 stage.ConclusionsIT administration of cavrotolimod appears to be safe and well tolerated in combination with pembrolizumab. Durable responses have occurred in patients previously experiencing progressive disease on PD-1 blockade.Trial RegistrationNCT03684785Ethics ApprovalThe study was approved by Institutional Review Boards of Dana-Farber Cancer Institute (IRB #18-584), John Wayne Cancer Institute (WIRB #20183064), University of Miami (IRB #20180957), University of Iowa (IRB #201810763), University of Cincinnati (WIRB #20183064), University of Washington (WIRB #20183064), MSKCC (IRB #20-174), UC San Francisco (WIRB #20183064), U Colorado (WIRB #20183064), Northwestern (IRB #STU00211083), U Arizona (WIRB #20183064), UC Irvine (WIRB #20183064), U Pitt (WIRB #20183064), and Washington University (WIRB #20183064).

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