Preparedness for a 'no-notice' mass-casualty incident: a nuclear detonation scenario.

PURPOSE: An effective response for a mass-casualty incident requires understanding the relevant basic science and physical impact; detailed preparedness among jurisdictions; and clear, sequential response planning, including formal operational exercises, logistics, interagency, and public-private coordination, rapid activation of resilience, and continual improvement from lessons learned and new knowledge. This ConRad 2021 meeting report describes steps for civilian medical and public health response planning for a nuclear detonation; the utility of this type of planning for broader application; and extension of this planning to the international community. CONCLUSION: A nuclear detonation requires a response within minutes to what will be a large-scale disaster complicated by radiation, including some elements that are similar to a broad range of incidents. The response could be further complicated if multiple incidents occur simultaneously. Required are detailed planning, preparedness and scripting for an immediate operational response, addressing clinical manifestations of evolving radiation illness, and flexibility to adapt to a rapidly changing situation. This need translates into the use of just-in-time information; effective, credible communication; situational awareness on a global scale; and a template upon which to apply capabilities in a multi-sector response. This effort is greatly facilitated using a 'playbook' approach, the basics of which are presented.

Mitigating the risk of radiation-induced cancers: limitations and paradigms in drug development.

The United States radiation medical countermeasures (MCM) programme for radiological and nuclear incidents has been focusing on developing mitigators for the acute radiation syndrome (ARS) and delayed effects of acute radiation exposure (DEARE), and biodosimetry technologies to provide radiation dose assessments for guiding treatment. Because a nuclear accident or terrorist incident could potentially expose a large number of people to low to moderate doses of ionising radiation, and thus increase their excess lifetime cancer risk, there is an interest in developing mitigators for this purpose. This article discusses the current status, issues, and challenges regarding development of mitigators against radiation-induced cancers. The challenges of developing mitigators for ARS include: the long latency between exposure and cancer manifestation, limitations of animal models, potential side effects of the mitigator itself, potential need for long-term use, the complexity of human trials to demonstrate effectiveness, and statistical power constraints for measuring health risks (and reduction of health risks after mitigation) following relatively low radiation doses (<0.75 Gy). Nevertheless, progress in the understanding of the molecular mechanisms resulting in radiation injury, along with parallel progress in dose assessment technologies, make this an opportune, if not critical, time to invest in research strategies that result in the development of agents to lower the risk of radiation-induced cancers for populations that survive a significant radiation exposure incident.

The U.S. government's medical countermeasure portfolio management for nuclear and radiological emergencies: synergy from interagency cooperation.

Following the attacks of 11 September 2001, emergency preparedness within the U.S. Department of Health and Human Services, as well as at the Department of Defense and other federal agencies, received higher visibility, new mandates and increased funding. Emergency deployment teams increased the frequency of drills to enable better response to the health consequences of mass-casualty incidents. Interagency coordination has also continued to increase to more efficiently and effectively leverage federal resources toward emergency medical preparedness for both civilian and military populations.

Rapid radiation dose assessment for radiological public health emergencies: roles of NIAID and BARDA.

A large-scale radiological incident would result in an immediate critical need to assess the radiation doses received by thousands of individuals to allow for prompt triage and appropriate medical treatment. Measuring absorbed doses of ionizing radiation will require a system architecture or a system of platforms that contains diverse, integrated diagnostic and dosimetric tools that are accurate and precise. For large-scale incidents, rapidity and ease of screening are essential. The National Institute of Allergy and Infectious Diseases of the National Institutes of Health is the focal point within the Department of Health and Human Services (HHS) for basic research and development of medical countermeasures for radiation injuries. The Biomedical Advanced Research and Development Authority within the HHS Office of the Assistant Secretary for Preparedness and Response coordinates and administers programs for the advanced development and acquisition of emergency medical countermeasures for the Strategic National Stockpile. Using a combination of funding mechanisms, including funds authorized by the Project BioShield Act of 2004 and those authorized by the Pandemic and All-Hazards Preparedness Act of 2006, HHS is enhancing the nation's preparedness by supporting the radiation dose assessment capabilities that will ensure effective and appropriate use of medical countermeasures in the aftermath of a radiological or nuclear incident.

Biomarkers and imaging: physics and chemistry for noninvasive analyses.

The era of 'modern medicine' has changed its name to 'molecular medicine', and reflects a new age based on personalized medicine utilizing molecular biomarkers in the diagnosis, staging and monitoring of therapy. Alzheimer's disease has a classical biomarker determined at autopsy with the histologic staining of amyloid accumulation in the brain. Today we can diagnose Alzheimer's disease using the same classical pathologic biomarker, but now using a noninvasive imaging probe to image the amyloid deposition in a patient and potentially provide treatment strategies and measure their effectiveness. Molecular medicine is the exploitation of biomarkers to detect disease before overt expression of pathology. Physicians can now find, fight and follow disease using imaging, and the need for other disease biomarkers is in high demand. This review will discuss the innovative physical and molecular biomarker probes now being developed for imaging systems and we will introduce the concepts needed for validation and regulatory acceptance of surrogate biomarkers in the detection and treatment of disease.

Imaging characteristics of a novel technetium Tc 99m-labeled platelet glycoprotein IIb/IIIa receptor antagonist in patients With acute deep vein thrombosis or a history of deep vein thrombosis.

BACKGROUND: The diagnosis of recurrent deep vein thrombosis (DVT) is challenging. Imaging with radiolabeled peptides offers a new approach for detecting acute DVT. Technetium Tc 99m ((99m)Tc)-apcitide binds with high affinity and specificity to the glycoprotein IIb/IIIa receptors expressed on activated platelets and, therefore, (99m)Tc-apcitide scintigraphy should be negative with residual abnormalities caused by old, inactive thrombi and positive with new, active thrombi. METHODS: In a prospective multicenter study, (99m)Tc-apcitide imaging was performed on 38 patients with a newly diagnosed first DVT (group 1) and 40 patients with previous DVT, symptoms of postthrombotic syndrome, and chronic intraluminal abnormalities on ultrasonography (group 2). Images were interpreted in a blinded fashion by 2 experts and by newly trained nuclear medicine physicians. The sensitivity and specificity of (99m)Tc-apcitide were determined by calculating the proportion of scans in group 1 patients that were read as "positive for acute DVT" and the proportion of scans in group 2 patients that were read as "negative for acute DVT," respectively. RESULTS: When read by 2 experts, ( 99m)Tc-apcitide had a sensitivity of 92% for both readers and specificities of 82% and 90%. Agreement between the experts was excellent. However, the accuracy and interreader agreement for newly trained nuclear medicine physicians were lower. CONCLUSIONS: Technetium Tc 99m-apcitide scintigraphy has potential utility in suspected recurrent DVT because it detects most acute thrombi and has few false-positive results in patients with previous DVT. However, the accuracy appears to depend on the training and experience of the interpreters.