A Framework for Comparative Evaluation of Dosimetric Methods to Triage a Large Population Following a Radiological Event.

BACKGROUND: To prepare for a possible major radiation disaster involving large numbers of potentially exposed people, it is important to be able to rapidly and accurately triage people for treatment or not, factoring in the likely conditions and available resources. To date, planners have had to create guidelines for triage based on methods for estimating dose that are clinically available and which use evidence extrapolated from unrelated conditions. Current guidelines consequently focus on measuring clinical symptoms (e.g., time-to-vomiting), which may not be subject to the same verification of standard methods and validation processes required for governmental approval processes of new and modified procedures. Biodosimeters under development have not yet been formally approved for this use. Neither set of methods has been tested in settings involving large-scale populations at risk for exposure. OBJECTIVE: To propose a framework for comparative evaluation of methods for such triage and to evaluate biodosimetric methods that are currently recommended and new methods as they are developed. METHODS: We adapt the NIH model of scientific evaluations and sciences needed for effective translational research to apply to biodosimetry for triaging very large populations following a radiation event. We detail criteria for translating basic science about dosimetry into effective multi-stage triage of large populations and illustrate it by analyzing 3 current guidelines and 3 advanced methods for biodosimetry. CONCLUSIONS: This framework for evaluating dosimetry in large populations is a useful technique to compare the strengths and weaknesses of different dosimetry methods. It can help policy-makers and planners not only to compare the methods' strengths and weaknesses for their intended use but also to develop an integrated approach to maximize their effectiveness. It also reveals weaknesses in methods that would benefit from further research and evaluation.

Medical response to a major radiologic emergency: a primer for medical and public health practitioners.

UNLABELLED: There are several types of serious nuclear or radiologic emergencies that would require a specialized medical response. Four scenarios of great public health, economic, and psychologic impact are the detonation of a nuclear weapon, the meltdown of a nuclear reactor, the explosion of a large radiologic dispersal device ("dirty bomb"), or the surreptitious placement of a radiation exposure device in a public area of high population density. With any of these, medical facilities that remain functional may have to deal with large numbers of ill, wounded, and probably contaminated people. Special care and/or handling will be needed for those with trauma, blast injuries, or thermal burns as well as significant radiation exposures or contamination. In addition, radiologists, nuclear medicine specialists, and radiation oncologists will be called on to perform a number of diverse and critically important tasks, including advising political and public health leaders, interfacing with the media, managing essential resources, and, of course, providing medical care. This article describes the medical responses needed following a radiologic or nuclear incident, including the symptoms of and specific treatments for acute radiation syndrome and other early health effects. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09090330/-/DC1.

Use of Clinical Decision Guidance as a New Public Health Tool for the Medical Management of Internal Contamination in Radiological Mass Casualty Scenarios.

This review is a discussion of special issues associated with the medical and public health management of persons at risk of internal contamination from radionuclides, following various radiological mass-casualty scenarios, as well as definition, discussion and use of the Clinical Decision Guidance (CDG) in such scenarios. Specific medical countermeasures are available for reducing the internal radiation dose and the subsequent stochastic and deterministic risks to persons internally contaminated with radionuclides from nuclear power plant, fuel processing and nuclear weapon accidents/incidents. There is a public health need for rapidly identifying and quantifying the 'source term' of such radiation exposures and assessment of the associated committed doses, so that appropriate medical countermeasure(s) can be given as soon as possible. The CDG, which was initially defined in NCRP-161, was specifically developed to be a new public health tool for facilitating the integration of local community healthcare professionals into the general medical, mass casualty, triage and treatment response of internally contaminated populations.

Medical management of the acute radiation syndrome: recommendations of the Strategic National Stockpile Radiation Working Group.

Physicians, hospitals, and other health care facilities will assume the responsibility for aiding individuals injured by a terrorist act involving radioactive material. Scenarios have been developed for such acts that include a range of exposures resulting in few to many casualties. This consensus document was developed by the Strategic National Stockpile Radiation Working Group to provide a framework for physicians in internal medicine and the medical subspecialties to evaluate and manage large-scale radiation injuries. Individual radiation dose is assessed by determining the time to onset and severity of nausea and vomiting, decline in absolute lymphocyte count over several hours or days after exposure, and appearance of chromosome aberrations (including dicentrics and ring forms) in peripheral blood lymphocytes. Documentation of clinical signs and symptoms (affecting the hematopoietic, gastrointestinal, cerebrovascular, and cutaneous systems) over time is essential for triage of victims, selection of therapy, and assignment of prognosis. Recommendations based on radiation dose and physiologic response are made for treatment of the hematopoietic syndrome. Therapy includes treatment with hematopoietic cytokines; blood transfusion; and, in selected cases, stem-cell transplantation. Additional medical management based on the evolution of clinical signs and symptoms includes the use of antimicrobial agents (quinolones, antiviral therapy, and antifungal agents), antiemetic agents, and analgesic agents. Because of the strong psychological impact of a possible radiation exposure, psychosocial support will be required for those exposed, regardless of the dose, as well as for family and friends. Treatment of pregnant women must account for risk to the fetus. For terrorist or accidental events involving exposure to radioiodines, prophylaxis against malignant disease of the thyroid is also recommended, particularly for children and adolescents.

Persistence of micronuclei in lymphocytes of cancer patients after radiotherapy.

To verify the applicability of the micronucleus (MN) yield in peripheral blood lymphocytes (PBLs) as a quantitative biodosimeter for monitoring in vivo ionizing radiation damage, we applied the cytokinesis-blocked micronucleus assay in PBLs of cancer patients treated with partial-body radiotherapy. Dosimetric information on these 13 patients represented a wide range in the number of fractions, cumulative tumor dose, total integral dose, and equivalent total-body absorbed dose. We found in PBLs of these patients that (1) the MN yield increased linearly with the equivalent total-body absorbed dose (r = 0.8, P = 0.002), (2) the distributions of the MN yields deviated significantly from Poisson, and (3) there was a general decline in MN yields with increasing length of follow-up, but with considerable variation between individuals. The average rate of decline was found to be linear and was correlated with the equivalent total-body absorbed dose (r = 0.7, P = 0.007). Further, at 19-75 months of follow-up time, seven patients showed higher MN yields than their respective levels before radiotherapy, indicating the persistence of radiation-induced residual cytogenetic damage. Our findings suggest that the MN yield in human PBLs offers a reliable acute and perhaps chronic biodosimeter for in vivo radiation dose estimation. After the completion of radiotherapy, the persistence of elevated MN yield in PBLs is a reflection of the surviving population of radiation-induced genetically aberrant cells.

Role of dicentric analysis in an overarching biodosimetry strategy for use following a nuclear detonation in an urban environment.

In the moments immediately following a nuclear detonation, casualties with a variety of injuries including trauma, burns, radiation exposure, and combined injuries would require immediate assistance. Accurate and timely radiation dose assessments, based on patient history and laboratory testing, are absolutely critical to support adequately the triage and treatment of those affected. This capability is also essential for ensuring the proper allocation of scarce resources and will support longitudinal evaluation of radiation-exposed individuals and populations. To maximize saving lives, casualties must be systematically triaged to determine what medical interventions are needed, the nature of those interventions, and who requires intervention immediately. In the National Strategy for Improving the Response and Recovery for an Improvised Nuclear Device (IND) Attack, the U.S. Department of Homeland Security recognized laboratory capacity for radiation biodosimetry as having a significant gap for performing mass radiation dose assessment. The anticipated demand for radiation biodosimetry exceeds its supply, and this gap is partly linked to the limited number and analytical complexity of laboratory methods for determining radiation doses within patients. The dicentric assay is a key component of a cytogenetic biodosimetry response asset, as it has the necessary sensitivity and specificity for assessing medically significant radiation doses. To address these shortfalls, the authors have developed a multimodal strategy to expand dicentric assay capacity. This strategy includes the development of an internet-based cytogenetics network that would address immediately the labor intensive burden of the dicentric chromosome assay by increasing the number of skilled personnel to conduct the analysis. An additional option that will require more time includes improving surge capabilities by combining resources available within the country's 150 clinical cytogenetics laboratories. Key to this intermediate term effort is the fact that geneticists and technicians may be experts in matters related to identifying chromosomal abnormalities related to genetic disorders, but they are not familiar with dosimetry for which training and retraining will be required. Finally, long-term options are presented to improve capacity focus on ways to automate parts of the dicentric chromosome assay method.

Dose-dependent analysis of acute medical effects of mixed neutron-gamma radiation from selected severe 235U or 239Pu criticality accidents in USSR, United States, and Argentina.

Eight of the most severe cases of acute radiation disease (ARS) known to have occurred in humans (as the result of criticality accidents) had survival times less than 120 h (herein defined as "early death"). These accidents were analyzed and are discussed with respect to the specific accident scenarios and the resulting accident-specific, mixed neutron-gamma radiation clinical dose distributions. This analysis concludes that the cardiovascular system appears to be the most critical organ system failure for causing "early death" following approximate total body, mixed gamma-neutron radiation doses greater than 40-50 Gy. The clinical data also suggest that there was definite chest dose dependence in the resulting survival times for these eight workers, who unfortunately suffered profound radiation injury and unusual clinical effects from such high dose radiation exposures. In addition, "toxemic syndrome" is correlated with the irradiation of large volumes of soft tissues. Doses to the hands or legs greater than 80-100 Gy or radiation lung injury also play significant but secondary roles in causing "early death" in accidents delivering chest doses greater than 50 Gy.