Presentation to National Alliance for Radiation Readiness November 16, 2011 Large-Scale Testing for ARS after a Nuclear Detonation

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? THE CHALLENGE

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 TESTING ONE MILLION PEOPLE?

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. SHORT TIME FRAME FOR SCREENING

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. A POPULATION ON THE MOVE

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? THE THOUGHT EXPERIMENT

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 POSSIBLE METHODS

Chromosomal Dicentrics –Gold standard –Not performed in most laboratories –Specially trained personnel –Takes time for results –Current national capacity is tests week. May be able to increase to 1000 week in next few years. POSSIBLE METHODS FOR SCREENING

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 POSSIBLE METHODS

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 ABSOLUTE LYMPHOCYTE COUNT

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 ALC: CATEGORIES OF TRIAGE

Performed in all clinical laboratories as part of CBC/d Automation No special training of technicians ALC: ADVANTAGES

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 WHO WOULD PERFORM ALCS?

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 NATIONAL LABORATORY CHAINS

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…….? CHALLENGES