October 2013

1. Executive Summary CAPSTONE Arresting the Military Suicide Epidemic through Intervention with Hyperbaric Oxygen Therapy (HBOT) The Center for Translational Medicine and International Hyperbaric Medical Foundation October 2013

2. The Bottom Line up Front We are taking action against the unprecedented suicide epidemic afflicting U. S. Veterans.There are 22 military suicides a day, over 8,000 a year. Another 45 military a day – more than 16,000 a year – attempt suicide and fail. Many suicides come from or are motivated by the hundreds of thousands of battlefield casualties who suffer from Traumatic Brain Injury (TBI, the signature injury of Afghan and Iraq wars) and Post Traumatic Stress Disorder (PTSD) and remain disabled and untreated. Despite $1.5+ billion and seven years, the Army has yet to design and develop, let alone discover and deploy, an effective treatment for the disabling symptoms and effects of TBI/PTSD brain injury. Our current success in the use of Hyperbaric Oxygen Therapy (HBOT) to treat and help heal over 125 wounded servicemen and women, and the worldwide science behind the use of HBOT for TBI/PTSD, argues for action to TREAT NOW. We need $2.5M to fund the CAPSTONE Project. CAPSTONE Arresting the Military Suicide Epidemic

3. Suicide Epidemic: The Problem Suicides among veterans are at 22+ per day; another 1,300+ attempt suicide every month. Nearly 40% of OIF/OEF veterans are diagnosed with a mental illness – and that’s just those who ask for help. One third receive minimal care; another third receive no care at all. Estimates are that over 600,000 veteran servicemen and women are injured and are denied effective treatment. Nearly 5 million people in the US are suffering with brain injury and psychological problems. That number grows by ~250,000 each year. The VA, DoD and medicine in general fail to adequately coordinate and integrate tracking, diagnosis, prescriptions, treatment, analysis and follow-on adjustments. The VA estimates its case backlog at ~800,000. CAPSTONE Arresting the Military Suicide Epidemic

4. The Center for Translational Medicine (CTM) and International Hyperbaric Medical Foundation (IHMF) CAPSTONE Mission. The CTM and IHMF are using HBOT, integrative medicine and adaptive clinical trials to treat brain-injured combat veterans and others to head off the suicide epidemic, improve quality of care, and conduct science to improve patient diagnoses, treatments, support and quality of life. Cardinal Rule in an Epidemic: Early Detection, Early Response CAPSTONE Arresting the Military Suicide Epidemic

5. The Concept: The Capstone Alliance is formed from qualifying HBOT-capable civilian clinics across the country. Your contribution will fund immediate treatment and analysis of data from TBI/PTSD casualties. It will also lay the groundwork for a definitive FDA Clinical Trial. From this project, military and Veteran communities, Congress, DOD, VA, and FDA – as well as citizens across the country – will be able to see and understand that the tragic and disgraceful U. S. military suicide epidemic can – and must – be quickly and cost-effectively reversed. Cost effective, immediate civilian treatment of TBI/PTSD casualties is available now. The FDA Clinical Trial can then produce the approval necessary to make HBOT treatment widely available under a new, approved indication. CAPSTONE Arresting the Military Suicide Epidemic

6. The Treatment: HBOT has been formally approved for 14 applications by the FDA. These applications provide dramatic healing action to a number of injuries, especially wound healing. Oxygen under pressure has been applied to Navy divers for the brain injury “decompression sickness” for over 60 years. At 1.5 atmospheres as used for TBI/PTSD, HBOT is accepted as safe; and 15 years of repeated success in treating brain injury off label and a wealth of documented data and science have established both its safety and efficacy. The Army and the VA deny this treatment to the wounded for political and economic reasons, despite overwhelming science and evidence. CAPSTONE Arresting the Military Suicide Epidemic

7. CAPSTONE: The Costs The cost of the Capstone effort and FDA trial startup totals $2,500,000. The HBOT 1.5 treatment (with robust data collection) for 60 subjects, based on 40 treatments each, totals $1,250,000. Administrative costs for the Capstone trial and startup costs for the clinical trial total $1,250,000. Negotiations with the FDA will determine the design and additional funding required for an acceptable, new application FDA-sanctioned trial. By way of contrast, the expected costs of sustaining an untreated TBI/PTSD patient for life are conservatively estimated at $30,000 per year over an estimated 50-year remaining life span, nearly $1.5M per patient. Thus, the cost to treat and heal TBI/PTSD wounded warriors with HBOT is less than 2% of the costs to leave them untreated. The costs to society in terms of suicide, homelessness, joblessness, injury to families, incarceration and social and medical services – to say nothing of the reduced quality of life for the wounded and their loved ones – are incalculable. CAPSTONE Arresting the Military Suicide Epidemic

8. The Resistance: The Army is the leader for the U. S. government effort to address the TBI/PTSD casualty and suicide epidemic. HBOT use has been stalled for years by a negative attitude toward HBOT and the Army’s traditional resistance to change. The Army has a deservedly negative reputation for failure to address major epidemics of wartime wounding: witness the 1970s Vietnam Agent Orange 22-year delay to recognize and treat the wounded, and the 1990s Gulf War Syndrome delay in treating that continues to this day. The Congress has been unwilling to date to take dispositive action on TBI/PTSD. The standard of care by the military in treating brain injury includes over 100 drugs. NONE of the drugs currently used and paid for by Tricare and the VA to treat our brain injured veterans are FDA-approved to treat TBI. All are being used "off-label." Nearly all of the anti-depressants carry FDA Black Box warnings urging caution in 17-24 year olds because of the increased risk of suicide. The costs run into the billions. CAPSTONE Arresting the Military Suicide Epidemic

9. The CAPSTONE Alliance Team: • The Honorable Martin R. Hoffman, Former Secretary of the Army • Robert Mozayeni, MD, Director, Translational Medicine Group • Stephen N. Xenakis, MD, Brigadier General USA (ret.), Founder CTM • The Honorable PattManey, BG, USAR (ret.), Judge in Okaloosa County, FL • Paul G. Harch, MD, Director, LSUHSC/Medical Center of Louisiana, New • Orleans Hyperbaric Medicine and Wound Care Department • Stephen D. Reimers, P.E., Secretary/Treasurer of IHMF and the sponsor of • NBIRR, the IHMF and owner of Reimers Systems • ADM Tim Fanning, Navy League • Robert L. Beckman, Ph.D., Chief Knowledge Officer, Center for Translational • Medicine CAPSTONE Arresting the Military Suicide Epidemic

10. Scientific and Evidence-Based Medicine underlying CAPSTONE [1] A Phase I Study of Low-Pressure Hyperbaric Oxygen Therapy for Blast-Induced Post-Concussion Syndrome and Post-Traumatic Stress Disorder. Paul G. Harch, et al. JOURNAL OF NEUROTRAUMA 29:168–185 ( January 1, 2012) [2] HYPERBARIC OXYGEN THERPAY FOR CHRONIC COGNITIVE IMPAIRMENTS DUE TO TRAUMATIC BRAIN INJURY- RANDOMIZED PROSPECTIVE TRIAL. Rahav Boussi-Gross1, Haim Golan3. Gregori Fishlev1, Yair Bechor1, Olga Volkov3, Jacob Bergan1, Mony Friedman1, Eshel Ben-Jacob2,4,5, ShaiEfrati 1,2, 1The Institute of Hyperbaric Medicine, 2Research and Development Unit and 3Nuclear Medicine institute, AssafHarofeh Medical Center, Zerifin 70300, Israel affiliated to Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel. 4School of Physics and Astronomy, 5The Raymond and Beverly Sackler Faculty of Exact Sciences, Tel-Aviv University,Tel-Aviv 69978, Israel. [3] Summary report from the International Hyperbaric Medical Foundation, “The National Brain Injury Rescue and Rehabilitation Trial – a multicenter study of hyperbaric oxygen for mild traumatic brain injury." January 2013. [4] Army Trials Report from UHMS Conference, June 2013. Press Release: " DoD announces results of first three DoD-Sponsored trials using hyperbaric oxygen for mild traumatic brain injury" [5] Dr. George Mychaskiw II, DO, FAAP, FACOP, Editor-in-Chief of the Journal of Hyperbaric Medicine, the most prestigious journal on Hyperbaric Medicine in the world. [6] Efrati S, Fishlev G, Bechor Y, et al. Hyperbaric oxygen induces late neuroplasticity in post stroke patients - randomized, prospective trial. PLoS One 2013;8:e53716. CAPSTONE Arresting the Military Suicide Epidemic

11. Summary & Call to Action CAPSTONE can help interrupt the soldier brain injury cycle of discharge, homelessness, joblessness, violence, incarceration and potential suicide With immediate funding, CAPSTONE can pioneer in partnerships in integrated, comprehensive treatment of TBI & PTSD A comprehensive medical record can be coordinated and integrated throughout diagnosis, prescriptions, treatment, analysis and follow-on adjustments with eventual cessation of over-drugging Multidimensional analysis of whole-person data across cohorts of patient types can yield individualized care pathways CAPSTONE will leverage new analytic techniques that will shorten the cycle of adoption of treatments that are safe and effective Through CAPSTONE, the civilian sector must intervene, treat and heal, and force the military, the Congress and the medical community to do the right thing: TREAT NOW CAPSTONE Arresting the Military Suicide Epidemic

12. Additional Explanations CAPSTONE Arresting the Military Suicide Epidemic

13. 100% oxygen under pressure 1.5 – 2/0 ATA for brain injury 40-80 1 hr treatments 1-2 HBOT per day Used for more than 100 years for brain injury [first use in US by Roebling while building the Brooklyn bridge, 1870s. Dates to 1600s.] Safe, effective and scientifically validated worldwide What is Hyperbaric Oxygen Therapy (HBOT)? CAPSTONE Arresting the Military Suicide Epidemic

14. Upregulates growth factors Reduces edema/swelling Promotes neural pathway growth Activates senescent neurons [“sleeping”, not dead] Increases neuronal energy [ATP] Downregulates inflammation Reduces reperfusion injury [not enough O2] How it works - 5,769+* ways(~# of cellular processes studied) *Rink C, Roy S, Khan M, Ananth P, Kuppusamy P, Sen CK, Khanna S. Oxygen-sensitive outcomes and gene expression in acute ischemic stroke. J Cereb Blood Flow Metab. 2010 Feb 10. CAPSTONE Arresting the Military Suicide Epidemic

15. Accepted HBOT Indications 1.     Air or Gas Embolism2.    Carbon Monoxide Poisoning       Carbon Monoxide Poisoning Complicated By Cyanide Poisoning3.    ClostridialMyositis and Myonecrosis (Gas Gangrene)4.    Crush Injury, Compartment Syndrome and Other Acute Traumatic Ischemias5.    Decompression Sickness6.    Arterial Insufficiencies:             Central Retinal Artery Occlusion            Enhancement of Healing In Selected Problem Wounds7.    Severe Anemia8.    Intracranial Abscess9.    Necrotizing Soft Tissue Infections10.  Osteomyelitis (Refractory)11.   Delayed Radiation Injury (Soft Tissue and Bony Necrosis)12.  Compromised Grafts and Flaps13.  Acute Thermal Burn Injury 14. Idiopathic Sudden Sensorineural Hearing Loss (New! approved on October 8, 2011 by the UHMS Board of Directors) CAPSTONE Arresting the Military Suicide Epidemic

16. CAPSTONE Underlying Technologies Core grounding in integrative medicine Workflows and Business Rules. Integrative and translational medicine require clarity about every aspect of patient care. The CareVector Platform (CVP™) Repository forms the basis for collecting and analyzing all knowledge across the CTM. The Collaboration Forum. The platform contains a "blog space" where participants in the practice -- or across all practices -- can post, confer, share and read based on communities of interest. Health Navigator. Up-to-the-minute status reports based on patient data input. The Analytic Engine and Reporting. Bayesian calculators and statistical packages. Home Stream (tm). Wireless connections to mobile devices to allow on-demand and rule-based communication and inquiries about patient health and actions. The Neuropsychiatric Conditions and Infectious Diseases Registries. More comprehensive collection and analysis of multidimensional data. CAPSTONE Arresting the Military Suicide Epidemic

17. Going Forward Accelerate Reg. approval of HBOT 1.5 through funded treatments and approach to FDA Accelerate USG initiation of widespread, funded treatment of battle casualties with HBOT Accelerate Insurance Industry coverage of TBI and PTSD symptoms and treatments with HBOT Accelerate efficacy of Integrated, translational medicine –based TBI and PTSD treatment with HBOT 1.5 as foundation Develop coordinated multi-vets organization, multi-media search for  wounded and illegally/improperly separated TBI/PTSD casualties Provide argument for forward-area treatment of wounded during current one-day post-blast stand down period CAPSTONE Arresting the Military Suicide Epidemic

18. Transforming Clinical Pathways Diagnostics Treatment Plan Collaboration Throughout: Doctor – Patient – Support Network Workflows and Processes Protocols • Indications: • Psychological/ • Neurocognitive • Metabolic & • Infection; Genetic • Environmental: • Toxins • EMF • Psychiatric: Include • Social • Family History: Fully-Informed Consent Therapies On- and Off-label 21st EMR CareVector Platform Statistics, Clusters Bayesian etc. Web-Enabled Analysis & Feedback Track & Monitor CAPSTONE Arresting the Military Suicide Epidemic c