VA Radiation & Physical Exposure ServiceDepleted Uranium (DU) andToxic Embedded Fragments Melissa A. McDiarmid, MD, MPH Joanna Gaitens, PhD, MSN/MPH Katherine S. Squibb, PhD VA Maryland Health Care System University of Maryland Baltimore, USA
Disclaimer The views expressed in this presentation are those of the author and do not necessarily represent the position of the Department of Veterans Affairs or the United States Government I have no known conflicts of interest other than that I work for the Department of Veterans Affairs
Topics we will cover: Environmental exposures of concern to Veterans: Depleted Uranium (DU), Toxic Embedded Fragments The potential toxicity of DU and retained embedded fragments Programs available through the VA for Veterans with concerns about these exposures How Veterans enroll in these programs
What is Depleted Uranium? By-product of uranium enrichment process through which 235U is extracted from natural uranium for use as nuclear fuel Leftover is “depleted” with 235U/238U isotopic ratio = 0.245%
Isotopic Comparison of Natural and Depleted Uranium Natural Depleted Radioactivity Uranium Uranium Concentration Concentration Isotope Ci/g of isotopes of isotopes 234 U 6200.0 0.0058% 0.001% 235* U 2.2 0.72% 0.2% 238 U 0.33 99.28% 99.8% Relative Radioactivity 1 0.6
Chemical vs Radiological Toxicity Chemical toxicity U234 = U235 = U238 Radiological toxicity Specific activity: U234 >>> U235 > U238 so Natural U > DU Primary decay = alpha particles and gamma rays
Military Uses of DU Tank armor for increased resistance to enemy projectiles Munitions to increase penetrating power Used in battle for first time in 1991 Gulf War
Gulf War I and OEF/OIF Exposures to DU Friendly-fire incidents exposed US soldiers to: DU shrapnel Aerosolized DU oxides Inhalation, ingestion, wound contamination Burning of munitions storage facility Decontamination of military equipment
DU Embedded Fragment
Potential Toxicity of DU Systemic effects due to release of U ions to circulation and uptake by organs Specific target organs of U Kidney Bone Primarily chemical toxicity of U Local effects on tissue surrounding DU embedded fragments May be combination of chemical toxicity and radioactivity of U
Mission of the DU Follow-Up Program Since 1993: To provide clinical surveillance for the „friendly fire‟ DU-exposed GWI Veterans Since 1998: To provide biologic monitoring by mail for DU for all GWI and OIF Veterans
The next several slides will cover: Depleted Uranium Follow-Up Program Purpose Surveillance protocol Findings Depleted Uranium Mail-In Surveillance Program Purpose Findings
Purpose of DU Friendly Fire Victim Surveillance Determine health effects, if any, in DU exposed populations (GWI, OEF, OIF) Develop methods to measure DU exposure in this novel exposure mode (embedded fragments) Examine surgical and medical management of embedded fragments– still an issue!
Surveillance Protocol during Biennial Inpatient Evaluation Complete history (medical, social, family, reproductive, occupationa l exposure, partner) Extensive laboratory studies (hematology, serum chemistry, neuroendocrine, urinalysis, urine, sem en and blood uranium, renal markers, semen analysis) Chromosomal analysis (mutations, chromosomal aberrations) Neurocognitive testing Focus group/risk communication
Summary of Surveillance through 2009 Gulf War I OIF Year DU-exposed Non-exposed DU-exposed Total1993-4 33 33 1997 29 38 67 1999 21 + 29 new 50 2001 31 + 8 new 39 2003 32 32 2005 30 + 4 new 3 37 2007 32 + 3 new 2 (1 new) 37 2009 36 + 2 new 2 4079 unique cases have been evaluated from Gulf War I4 Unique cases have been evaluated from OIF
Mean Urine Uranium Levels through 2007 100 Thun 1975 = 65.1 µg/L for the 2009 Cohort 10Urine Uranium (μg U/g creatinine) 1 Occupational Decision Level = 0.8 µg/L Dietary Limit = 0.365 g/L DU Cut point = 0.1 µg/g creatinine 0.1 NHANES 95th% = 0.043 µg/g creatinine No shrapnel; No DU (n=19) 0.01 Shrapnel; No DU (n=2) No shrapnel; DU (n=2) Shrapnel; DU (n=13) 0.001 Samples Ranked from Low to High (n=36)
Clinical Findings No clinically significant differences detected between low and high uranium exposure groups Hematology Neuroendocrine Chemistries Neurocognitive
Second Activity of DU Program: To provide urine uraniumsurveillance by mail for any Veteran requesting testing
Purpose of the DU Urine Biomonitoring Program Determine urine uranium concentrations in Veterans from GWI and forward Passively survey for exposure scenarios linked to DU exposure other than friendly fire Provide assistance to Veterans‟ primary care providers in interpreting results and answering Veterans questions
Summary of Mail-in Activity through May 31, 2010 GWI TOTAL OIF Sampling kits 1682 requested > 2915 N > 4597 Total uranium only 476 Samples tested Total uranium as of 5/31/10 & DU 1847 Total uranium N = 3136 & DU 813 Positive for DU 3 1 N = 4**All friendly fire
Toxic Embedded FragmentSurveillance Center (TEFSC) and Registry
Background Traumatic injuries via contact with improvised explosive devices (IEDs) are a major concern in Iraq, and increasingly in Afghanistan More than 40,000 soldiers with traumatic injuries may have retained embedded fragments. IEDs are packed with heterogeneous material that may lead to local and systemic adverse health effects.
VHA directed to address the issue of embedded fragments Presidential Task Force Recommendation P-7 directed the VHA to establish a registry and medical surveillance program for Veterans with embedded fragments
Health concerns related to embedded fragments Local effects Risk of the development of tumors at the fragment sites Systemic effects Risk of target organ effects arising from chemicals released from fragments
Fate of DU Metal Fragments in Rat Muscle In SituCorrelation of radiographic appearance with histologic appearance. (A) Thickfibrotic capsule with shards of corroded DU in lumen; (B) thick cellular capsulelined by squamous metaplasia, particles, and shards of corroded DU in wall andlumen; (C) particles and shards of disintegrated DU fragment scatteredthroughout a soft tissue sarcoma (Hahn et al, 2002).
Embedded DU Fragment in 1991 Gulf War Veteran 1995 film 2001 filmChange in DU fragment appearance over time;suggests oxidation in situ and removal is warranted.
New Alloy Used in Munitions: W/Ni/Co Metastatic tumors caused by implanted tungsten alloy (W/Ni/Co) fragments in rats Rhabdomyosarcomas rapidly metastasize to lung Survival time is significantly reducedKalinich et al. Env. Hlth Perspec.113: 729-734, 2005
Evidence supports development of Toxic Embedded Fragment Surveillance Center (TEFSC) Local Effects Evidence from DU Program and medical device and fragment literature New studies of metal implanted animals with new tungsten alloy (W, Co, Ni) demonstrating rapid carcinogenesis Systemic Effects Known renal, reproductive and neurological effects of metals (e.g. Pb, Cd, Ni, Mn, Cu)
The next several slides will cover: Toxic Embedded Fragment Surveillance Center Mission Specific functions of TEFSC VA’s Embedded Fragment Registry Purpose of the registry Eligibility criteria Screening process for identifying eligible veterans Data captured in the registry
VA Toxic Embedded Fragment Surveillance Center Established at Baltimore VA Medical Center Mission: To provide care and active medical surveillance for Veterans with retained embedded fragments
Functions of TEFSC Fragment Characterization Biomonitoring & Medical Surveillance Registry Development Case Consultation
Analyzing fragment composition is an essential function of TEFSC Chemical analysis of removed fragments Surface chemistry Total fragment composition Analysis of tissue surrounding fragments Chemical analysis of tissue Characterization of tissue morphology Histology- proliferative cells, neoplastic cells
Summary of Composition of Fragments fromMilitary Personnel 2006-2008 (AFIP data)* 407 fragments analyzed 337 Metals 70 Non-Metals 44 Organic materials 336 non-radioactive 10 plastic & polymers 1 radioactive alloys (steel & brass) 1 fabric and 1 wood and non-alloyed metals 26 Stones Fe, Cu, Al, Ni, Pb, Zn with DU with traces of traces of other elements Al, Cr, Cu, Ti, Zn including Cr, Mn, Sn, Sb, Ti, W *Division of Biophysical Toxicology, Armed Forces Institute of Pathology Centeno JA, et al. (2009)
Fragment data informs biomonitoring and medical surveillance protocol Fragment composition data helps: Identify a list of toxicants to include in biomonitoring panels Identify outcomes of concern and means of surveillance Identify potential biomarkers of early effect
Fragment Analysis Process1. TEFSC sends fragment collection kit torequesting VA2. VA obtains fragment from Veteran andmails completed kit to TEFSC3. Fragment is analyzed4. TEFSC sends result letters toVeteran and VA Provider
Biological Specimens also provide insight into exposure Toxicants of interest Metals: Al, As, Cd, Cr, Co, Cu, Fe, Mn, Ni, Pb, U, W, Zn Plastics/polymer components: Isocyanate, Acrylics, Diethylhexylphthalates Others: Based on fragment analysis data Biological Specimens Urine, blood, other body fluids when indicated
Biological Monitoring Process 1. TEFSC sends kit is sent to requesting VA 2. Veteran provides 24-hour urine sample and completes questionnaire 3. VA mails completed kit to Baltimore VA 4. Specimen and questionnaire are analyzed 5. TEFSC sends result letters to Veteran and VA Provider
Surveillance protocol involves periodic follow-up to identify potential health outcomes Perform baseline urinalysis based on chemical composition of removed fragment(s) Perform periodic follow up urinalysis to identify specific biomarkers of exposure and effects based on baseline results Conduct periodic radiologic surveillance of embedded fragment location and shape Consider target organ surveillance for toxicants of concern
Purpose of the VA Embedded Fragment Registry To track, monitor and provide appropriate medical care and follow up for Veterans with embedded fragments resulting from injuries sustained during their tour of duty Identify Veterans who served in Iraq and Afghanistan and who have embedded fragments Identify health concerns associated with embedded fragments Develop medical and surgical management guidelines for Veterans with embedded fragments
Any Veteran who served in Operation Enduring Freedom or Operation Iraqi Freedomwho has or likely has a retained fragment as the result of an injury received while serving in the area of conflict are eligible for inclusion into the registry.
Individuals with embedded fragments are identified by both the VA and the DoD The VA has created a process to screen Veterans for embedded fragments at their local VA facility DoD is creating their own “Embedded Metal Fragment Registry” The DoD and VA are collaborating to ensure that all Veterans who have embedded fragments are identified and receive appropriate follow-up care.
The VA Screening process for Veterans with fragments uses the “Clinical Reminder” system
Screening Questions Do you have or suspect you have a retained fragment as the result of an injury received while serving in the area of conflict? - Were you injured by a bullet? - Were you injured as a result of a blast or explosion? - Were you in or on a vehicle at the time of the blast or explosion? - Was the blast or explosion caused by: IED, RPG, land mine, grenade, enemy fire, friendly fire, don‟t know, or other? - Did you have shrapnel, fragments or bullets removed during surgery? - If yes, were they sent to the lab for analysis? - Do you have retained shrapnel, fragments or bullets in your body? - If yes, have they been documented by radiograph?
Screening information isautomatically captured in the VA’s Embedded Fragment RegistryThe VA‟s registry will also identify if the individual is in DoD‟s registry AND if the individual had a fragment removed and analyzed by DoD. Then TEFSC determines if the following services are needed: Fragment analysis Biological monitoring Clinical Consultation
The Embedded Fragment Registry will capture “basic” data Screening Details Answers to screening question Local VA contact person Referral Status Demographic Information Healthcare Information Contact information for Primary Care Provider VA facility where Veteran receives care
…and Exposure/Health Details Injury and exposure information Developed standardized exposure questionnaire Biomonitoring data Tests ordered, analyses methods, results, interpretation of results, tracking information Fragment analysis data Analyses methods, results, interpretation of results, tracking information Health outcomes Results of specific clinical tests ICD-9 codes
Much of the registry data will come from existing data sourcesData Registry SourcesScreening dataDemographic information Patient‟s electronic medical recordHealthcare informationHealth outcome dataBiomonitoring Data Baltimore VA Lab systemFragment Data DoD electronic files
Conclusion The registry will help the VA and the DoD refine how cases are identified andprovide appropriate medical care forindividuals with embedded fragments.
Toxic Embedded Fragment Surveillance Center andDepleted Uranium Program 1-800-815-7533