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National Alliance for Radiation Readiness November 16, 2011

Large-Scale Testing for ARS after a Nuclear Detonation . National Alliance for Radiation Readiness November 16, 2011. The Challenge. As a result of a ground burst 10kt nuclear detonation in a major city:

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National Alliance for Radiation Readiness November 16, 2011

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  1. Large-Scale Testing for ARS after a Nuclear Detonation National Alliance for Radiation ReadinessNovember 16, 2011

  2. The Challenge • As a result of a ground burst 10kt nuclear detonation in a major city: • Many thousands of people would be exposed to life-threatening doses of radiation from fallout • Medical interventions could save many of these people • Resources (medicines, hospital beds, transportation) would be limited and therefore victims must be triaged • How can the patients most likely to benefit from medical intervention be rapidly and accurately identified?

  3. Testing One Million People? • Modeling estimates ~100,000 people may develop ARS from fallout • It may not be obvious early on who these people are • early symptoms are non-specific and unreliable • Many other concurrent reasons for symptoms • “Worried well”, stress reaction, normal illnesses, head injuries, ear drum rupture, etc • Geographic information may not be sufficient • Testing many times the 100,000 may be needed to identify all those with impending ARS. • Reasonable to estimate that in a metro area of 3 million, 1 million people may need to be screened

  4. Short Time Frame for screening • Countermeasures (bone marrow stimulators) are most effective if given early—within 1-2 days. • Getting patients to care (RITN or other) may take days. • Many patients with ARS will have a latent period of several days before the onset of severe illness.

  5. A Population On The Move • Many of the people in the area of the detonation will evacuate (informed or not) and they may be on the move for days given transportation and lodging challenges. • They may first present for screening in other cities or towns. • They may not be in the same place if they need follow-up testing. • They may not be in the same place when they become seriously ill.

  6. The Thought Experiment • Can 1 million people be screened for ARS over a 24 hour period (starting within 1-2 days of a nuclear detonation) regardless of where they are and have their results be immediately available to any clinician anywhere in the country using only existing technology and systems?

  7. Possible Methods • Time to vomiting • Most people exposed to >2 Sv will vomit within 4 hours • However, vomiting is non-specific and unreliable (many false positives and false negatives) • Severe, repetitive vomiting may be more reliable • Absence of any nausea or vomiting indicates less risk of significant exposure

  8. Possible Methods for screening • Chromosomal Dicentrics • Gold standard • Not performed in most laboratories • Specially trained personnel • Takes time for results • Current national capacity is 50-100 tests week. May be able to increase to 1000 week in next few years.

  9. Possible Methods • Investigational: • Electroparamagentic spin resonance (EPS) of dental enamel-Ideally performed on extracted teeth but can be done one nails and teeth in head • Stress gene and protein signature • Metabolomics (urine) • Ocular albumin • others • All early stage R&D

  10. Absolute Lymphocyte Count • Predictable time-dependent decrease in ALC after radiation exposure • If time of exposure known, approximate whole body dose can be estimated • For single test, measurement at 48 hour is most useful • Serial testing adds value • Comparison to neutrophil count adds value

  11. ALC: Categories of Triage • ALC enables prioritizing patients most like to benefit from treatment (hospitalization, G-CSF, blood products, antibiotics): • Too low to benefit from treatment (will die even with treatment) • Too high to need treatment (will recover without treatment) • Treatment can make the difference between life and death

  12. ALC: Advantages • Performed in all clinical laboratories as part of CBC/d • Automation • No special training of technicians

  13. Who would perform ALCs? • After a nuclear detonation some local hospital labs may be destroyed • Other hospitals’ labs may be overwhelmed with medical surge (trauma, prompt radiation, evacuated patients, etc) • Deployable labs have limited capacity— • With people on the move, where to deploy to? • Physician office and clinic labs: low volume and slow • Need for ability to track/match results with patients as they move

  14. National Laboratory Chains • 2 major national laboratory chains serve the US • LabCorp (1700 patient care sites, 51 major laboratories) • Quest Diagnostics (2000 patient care sites, 37 major laboratories) • Both possess transportation fleets including fixed-wing aircraft Together they believe that they possess have the capacity to do 1 million ALCs in a 24 hour period Both have extensive internet portals that allow patient tracking of results; most physicians and most Americans already are registered with one or both

  15. Challenges • Many challenges to implementation • Reagent Supply Chain-JIT inventory principles • Interoperability between IT systems • Need to integrate smaller labs • Logistics of phlebotomy • Phlebotomy supplies • Physician order rules • Some states require Rx for labwork • None seem insurmountable • Next steps…….?

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