scholarly journals Indirect Detection of Burkholderia pseudomallei Infection in a US Marine After Training in Australia

2020 ◽  
Vol 7 (5) ◽  
Author(s):  
Derek T Larson ◽  
Kevin L Schully ◽  
Ammarah Spall ◽  
James V Lawler ◽  
Ryan C Maves
Keyword(s):  
Burkholderia Pseudomallei ◽  
Capsular Polysaccharide ◽  
Community Hospital ◽  
Point Of Care ◽  
Cervical Lymphadenopathy ◽  
The United States ◽  
Indirect Detection ◽  
United States Marine Corps ◽  
Serious Infections ◽  
Appropriate Therapy

Abstract In 2012, the United States Marine Corps began annual deployments around Australia, including highly endemic areas for Burkholderia pseudomallei. B. pseudomallei infection, or melioidosis, is difficult to diagnose, and culture remains the gold standard. Accurate and timely diagnosis is essential, however, to ensuring appropriate therapy. Ten days after returning from Australia, a Marine presented to a community hospital with massive cervical lymphadenopathy, fever, and cough. Computed tomography demonstrated scattered pulmonary infiltrates with small cavitations; lymphadenopathy involving the cervical, supraclavicular, and mediastinal nodes; and splenomegaly. Sputum and blood cultures were negative. Empiric antimicrobial therapy with ceftazidime was initiated for suspected melioidosis. Retrospectively, a prototype iSTAT cartridge modified to detect B. pseudomallei capsular polysaccharide antigen was used to test a specimen of the patient’s blood and was determined to be positive. Over the course of therapy, B. pseudomallei capsular antigen levels in blood declined as the patient improved. The leveraging of an existing point-of-care (POC) analyzer to create a rapid diagnostic assay for melioidosis provides a template for rapid POC diagnostics that could significantly improve the ability of clinicians to deliver timely and appropriate therapy for serious infections.

scholarly journals Development of Rapid Enzyme-Linked Immunosorbent Assays for Detection of Antibodies to Burkholderia pseudomallei

2016 ◽  
Vol 54 (5) ◽  
pp. 1259-1268 ◽  
Author(s):  
Vichaya Suttisunhakul ◽  
Vanaporn Wuthiekanun ◽  
Paul J. Brett ◽  
Srisin Khusmith ◽  
Nicholas P. J. Day ◽  
...  
Keyword(s):  
Burkholderia Pseudomallei ◽  
Capsular Polysaccharide ◽  
The United States ◽  
Serum Samples ◽  
Hemagglutination Assay ◽  
Content Type ◽  
Healthy Donors ◽  
Indirect Hemagglutination ◽  
Polysaccharide Antigens ◽  
Immunosorbent Assays

Burkholderia pseudomallei, the causative agent of melioidosis, is an environmental bacillus found in northeast Thailand. The mortality rate of melioidosis is ∼40%. An indirect hemagglutination assay (IHA) is used as a reference serodiagnostic test; however, it has low specificity in areas where the background seropositivity of healthy people is high. To improve assay specificity and reduce the time for diagnosis, four rapid enzyme-linked immunosorbent assays (ELISAs) were developed using two purified polysaccharide antigens (O-polysaccharide [OPS] and 6-deoxyheptan capsular polysaccharide [CPS]) and two crude antigens (whole-cell [WC] antigen and culture filtrate [CF] antigen) ofB. pseudomallei. The ELISAs were evaluated using serum samples from 141 culture-confirmed melioidosis patients from Thailand along with 188 healthy donors from Thailand and 90 healthy donors from the United States as controls. The areas under receiver operator characteristic curves (AUROCC) using Thai controls were high for the OPS-ELISA (0.91), CF-ELISA (0.91), and WC-ELISA (0.90), while those of CPS-ELISA (0.84) and IHA (0.72) were lower. AUROCC values using U.S. controls were comparable to those of the Thai controls for all ELISAs except IHA (0.93). Using a cutoff optical density (OD) of 0.87, the OPS-ELISA had a sensitivity of 71.6% and a specificity of 95.7% for Thai controls; for U.S. controls, specificity was 96.7%. An additional 120 serum samples from tuberculosis, scrub typhus, or leptospirosis patients were evaluated in all ELISAs and resulted in comparable or higher specificities than using Thai healthy donors. Our findings suggest that antigen-specific ELISAs, particularly the OPS-ELISA, may be useful for serodiagnosis of melioidosis in areas where it is endemic and nonendemic.

scholarly journals Learning health systems in primary care: a systematic scoping review

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Danielle M. Nash ◽  
Zohra Bhimani ◽  
Jennifer Rayner ◽  
Merrick Zwarenstein
Keyword(s):  
Primary Care ◽  
Quality Improvement ◽  
Health Systems ◽  
Scoping Review ◽  
Early Stage ◽  
Point Of Care ◽  
The United States ◽  
Stage Of Development ◽  
Integrated Health ◽  
Google Search

Abstract Background Learning health systems have been gaining traction over the past decade. The purpose of this study was to understand the spread of learning health systems in primary care, including where they have been implemented, how they are operating, and potential challenges and solutions. Methods We completed a scoping review by systematically searching OVID Medline®, Embase®, IEEE Xplore®, and reviewing specific journals from 2007 to 2020. We also completed a Google search to identify gray literature. Results We reviewed 1924 articles through our database search and 51 articles from other sources, from which we identified 21 unique learning health systems based on 62 data sources. Only one of these learning health systems was implemented exclusively in a primary care setting, where all others were integrated health systems or networks that also included other care settings. Eighteen of the 21 were in the United States. Examples of how these learning health systems were being used included real-time clinical surveillance, quality improvement initiatives, pragmatic trials at the point of care, and decision support. Many challenges and potential solutions were identified regarding data, sustainability, promoting a learning culture, prioritization processes, involvement of community, and balancing quality improvement versus research. Conclusions We identified 21 learning health systems, which all appear at an early stage of development, and only one was primary care only. We summarized and provided examples of integrated health systems and data networks that can be considered early models in the growing global movement to advance learning health systems in primary care.

scholarly journals Neutrophil Extracellular Traps Exhibit Antibacterial Activity against Burkholderia pseudomallei and Are Influenced by Bacterial and Host Factors

2012 ◽  
Vol 80 (11) ◽  
pp. 3921-3929 ◽  
Author(s):  
Donporn Riyapa ◽  
Surachat Buddhisa ◽  
Sunee Korbsrisate ◽  
Jon Cuccui ◽  
Brendan W. Wren ◽  
...  
Keyword(s):  
Burkholderia Pseudomallei ◽  
Capsular Polysaccharide ◽  
Neutrophil Extracellular Traps ◽  
Polymorphonuclear Neutrophils ◽  
Dependent Manner ◽  
Predisposing Factor ◽  
Bacterial Killing ◽  
Content Type ◽  
Extracellular Traps ◽  
Type Iii Protein Secretion

ABSTRACTBurkholderia pseudomalleiis the causative pathogen of melioidosis, of which a major predisposing factor is diabetes mellitus. Polymorphonuclear neutrophils (PMNs) kill microbes extracellularly by the release of neutrophil extracellular traps (NETs). PMNs play a key role in the control of melioidosis, but the involvement of NETs in killing ofB. pseudomalleiremains obscure. Here, we showed that bactericidal NETs were released from human PMNs in response toB. pseudomalleiin a dose- and time-dependent manner.B. pseudomallei-induced NET formation required NADPH oxidase activation but not phosphatidylinositol-3 kinase, mitogen-activated protein kinases, or Src family kinase signaling pathways.B. pseudomalleimutants defective in the virulence-associated Bsa type III protein secretion system (T3SS) or capsular polysaccharide I (CPS-I) induced elevated levels of NETs. NET induction by such mutants was associated with increased bacterial killing, phagocytosis, and oxidative burst by PMNs. Taken together the data imply that T3SS and the capsule may play a role in evading the induction of NETs. Importantly, PMNs from diabetic subjects released NETs at a lower level than PMNs from healthy subjects. Modulation of NET formation may therefore be associated with the pathogenesis and control of melioidosis.

scholarly journals Real-world safety of palbociclib in breast cancer patients in the United States: a new user cohort study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Daniel C. Beachler ◽  
Cynthia de Luise ◽  
Aziza Jamal-Allial ◽  
Ruihua Yin ◽  
Devon H. Taylor ◽  
...  
Keyword(s):  
Breast Cancer ◽  
United States ◽  
Pulmonary Embolism ◽  
Cohort Study ◽  
Real World ◽  
The United States ◽  
Elevated Risk ◽  
Breast Cancer Patients ◽  
Increased Risk ◽  
Serious Infections

Abstract Background There is limited real-world safety information on palbociclib for treatment of advanced stage HR+/HER2- breast cancer. Methods We conducted a cohort study of breast cancer patients initiating palbociclib and fulvestrant from February 2015 to September 2017 using the HealthCore Integrated Research Database (HIRD), a longitudinal claims database of commercial health plan members in the United States. The historical comparator cohort comprised patients initiating fulvestrant monotherapy from January 2011 to January 2015. Propensity score matching and Cox regression were used to estimate hazard ratios for various safety events. For acute liver injury (ALI), additional analyses and medical record validation were conducted. Results There were 2445 patients who initiated palbociclib including 566 new users of palbociclib-fulvestrant, and 2316 historical new users of fulvestrant monotherapy. Compared to these historical new users of fulvestrant monotherapy, new users of palbociclib-fulvestrant had a greater than 2-fold elevated risk for neutropenia, leukopenia, thrombocytopenia, stomatitis and mucositis, and ALI. Incidence of anemia and QT prolongation were more weakly associated, and incidences of serious infections and pulmonary embolism were similar between groups after propensity score matching. After adjustment for additional ALI risk factors, the elevated risk of ALI in new users of palbociclib-fulvestrant persisted (e.g. primary ALI algorithm hazard ratio (HR) = 3.0, 95% confidence interval (CI) = 1.1–8.4). Conclusions This real-world study found increased risks of several adverse events identified in clinical trials, including neutropenia, leukopenia, and thrombocytopenia, but no increased risk of serious infections or pulmonary embolism when comparing new users of palbociclib-fulvestrant to fulvestrant monotherapy. We observed an increased risk of ALI, extending clinical trial findings of significant imbalances in grade 3/4 elevations of alanine aminotransferase (ALT).

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