Assessment of immunological anti-platelet factor 4 antibodies for vaccine-induced thrombotic thrombocytopenia (VITT) in a large Australian cohort: A multicenter study comprising 1284 patients.

BACKGROUND: Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare complication of adenovirus-based vaccines aimed to prevent and minimize COVID-19 and related pathophysiology. OBJECTIVES: To describe patterns of testing for anti-platelet factor 4 (PF4) antibodies using various ELISA assays in a large Australian cohort and comparative functional platelet activation assays in a subset. PATIENTS/METHODS: Asserachrom HPIA IgG ELISA was performed in 1284 patients over a period of 12 months, supplemented in select cohorts by comparative ELISA using three other methods (n = 78-179), three different functional assays (flow cytometry, serotonin release assay, and/or Multiplate; n = 476), and rapid immunological chemiluminescence anti-PF4 assay (n = 460), in a multicenter study. RESULTS: For first episode presentations, 190/1284 (14.8%) ELISA tests were positive. Conversely, most (445/460; 96.7%) chemiluminescence anti-PF4 test results were negative. All functional assays showed associations of higher median ELISA optical density with functional positivity and with high rates of ELISA positivity (64.0% to 85.2%). Data also identified functional positivity in 14.8%-36.0% of ELISA negative samples, suggesting false negative VITT by HPIA IgG ELISA in upward of one third of assessable cases. CONCLUSION: To our knowledge, this is the largest multicenter evaluation of anti-PF4 testing for investigation of VITT. Discrepancies in test results (ELISA vs. ELISA or ELISA vs. functional assay) in some patients highlighted limitations in relying on single methods (ELISA and functional) for PF4 antibody detection in VITT, and also highlights the variability in phenotypic test presentation and pathomechanism of VITT.

Developing a Survey Tool to Assess Implementation of Evidence-Based Chronic Disease Prevention in Public Health Settings Across Four Countries.

Background: Understanding the contextual factors that influence the dissemination and implementation of evidence-based chronic disease prevention (EBCDP) interventions in public health settings across countries could inform strategies to support the dissemination and implementation of EBCDP interventions globally and more effectively prevent chronic diseases. A survey tool to use across diverse countries is lacking. This study describes the development and reliability testing of a survey tool to assess the stage of dissemination, multi-level contextual factors, and individual and agency characteristics that influence the dissemination and implementation of EBCDP interventions in Australia, Brazil, China, and the United States. Methods: Development of the 26-question survey included, a narrative literature review of extant measures in EBCDP; qualitative interviews with 50 chronic disease prevention practitioners in Australia, Brazil, China, and the United States; review by an expert panel of researchers in EBCDP; and test-retest reliability assessment. Results: A convenience sample of practitioners working in chronic disease prevention in each country completed the survey twice (N = 165). Overall, this tool produced good to moderately reliable responses. Generally, reliability of responses was higher among practitioners from Australia and the United States than China and Brazil. Conclusions: Reliability findings inform the adaptation and further development of this tool. Revisions to four questions are recommended before use in China and revisions to two questions before use in Brazil. This survey tool can contribute toward an improved understanding of the contextual factors that public health practitioners in Australia, Brazil, China, and the United States face in their daily chronic disease prevention work related to the dissemination and implementation of EBCDP interventions. This understanding is necessary for the creation of multi-level strategies and policies that promote evidence-based decision-making and effective prevention of chronic diseases on a more global scale.