**6. Implications of the science**

For over four years, clinical and "evidence-based" medicine continue to show that HBOT is safe and effective in treating brain injuries. Objective analysis of the data from all the pivotal RCTs and crossover studies show in over 700 patients that positive improvements result from HBOT treatment protocols. And objective analyses of the studies and data reinforce the findings and the clinical evidence [52].

Dr. Wolf is a principle co-author of the first Army study. This recent USAF paper reanalyzing the data in the cornerstone DOD/VA/Army study concludes: "This pilot study demonstrated no obvious harm [and] both groups showed improvement in scores and thus a benefit. Subgroup analysis of cognitive changes and PCL-M results regarding PTSD demonstrated a relative risk of improvement.... There is a potential gain and no potential loss. The VA/Clinical Practice Guidelines define a "B evidence rating" as "a recommendation that clinicians provide (the service) to eligible patients. At least fair evidence was found that the intervention improves health outcomes and concludes that benefits outweigh harm .... Hyperbaric oxygen therapy for mild traumatic brain injury and PTSD should be considered a legitimate adjunct therapy if future studies demonstrate similar findings or show comparable improvement to standard-of-care or research-related treatment modalities." [53] Subsequent studies meet those criteria.

The Journal of Hyperbaric Medicine is the most prestigious journal on Hyperbaric Medicine in the world. In 2012 its editor wrote: " While we applaud good science, there comes a point.. .. of stagnation as the standard of evidence required for the blessing of organized medicine exceeds reality (where most of us live.… I feel, as do many of my colleagues, that there is sufficient clinical and research evidence to justify the use of [HBOT] as a standard-of-care treatment for [TBI] that should be reimbursed by CMS and Tricare…. I have no doubt that, over the next several years, [HBOT] will be proven beyond a reasonable doubt to be one of the most effective treatments for [TBI]…. There is a preponderance of evidence now to justify the use and funding for the treatment…." [54] Wang et al. concur: "Compelling evidence suggests the advantage of hyperbaric oxygen therapy (HBOT) in traumatic brain injury. ...Patients undergoing hyperbaric therapy achieved significant improvement. ... with a lower overall mortality, suggesting its utility as a standard intensive care regimen in traumatic brain injury." [55].

The Samueli Institute wrote of DoD studies: "Results showed that both the HBO and sham procedures were associated with significant improvements in post-concussion symptoms and secondary outcomes, including PTSD (which most participants had), depression, sleep quality, satisfaction with life, and physical, cognitive, and mental health functioning.. .. these results are consistent with 2 other sham-controlled clinical trials among service members and veterans involving a range of HBOT doses. ... The most remarkable lesson of this study was the difference in clinical outcomes between the 2 chamber procedures (HBO 1.5 ATA and 'sham' air 1.3 ATA) and routine post-concussion care. ... These findings reinforce the argument that effective interventions [i.e., the current standard of care practiced by military medicine] do not yet exist within the present structure of care or that routine post-concussion interventions within the [DOD or VHA] may even have iatrogenic effects that contribute to symptom persistence, the equivalent of a negative placebo (nocebo) effect." [56].

While this research has been going on, the VA has been quietly conducting a controlled "demonstration project" to monitor the effects of HBOT for "PTSDonly" veterans. For nearly three years, first two and now five sites around the US are using HBOT to treat PTSD and TBI patients: Tulsa OK, Travis AFB, Joint Base Sam Houston, Tampa, and Fargo ND. While the numbers are small, the results are

**129**

*Hyperbaric Oxygenation in the Treatment of Traumatic Brain Injury*

service members or veterans and in improving their lives." [58].

**7. NOTE BENE: the sham and placebo controversies in HBOT**

Expert commentary on the issues surrounding the HBOT "sham" revealed the fundamental flaws in the DoD/VA/Army research [60]. In a sham treatment, the researcher goes through the motions without actually performing the treatment. The intent is to have an inert or medically inactive procedure or substance used to compare results with active substances. A placebo is often used with half the people in a drug trial to help show whether the drug being studied is more effective than an inactive "sugar pill." The results of each group are compared. [NOTE: Debate continues on whether it is possible, under the circumstances of HBOT treatment, to

The placebo effect is very difficult, if not impossible, to prove in HBOT studies on patients suffering from PPCS that accompanies TBI. Further studies cannot ignore a placebo, but the overwhelmingly positive effects in so many, and so widely different studies, make the likelihood of a placebo unusual. [NOTE: when physiologic changes, such as both structural and functional increases in brain mass and activity are noted – as they were not in DoD/VA/Army studies, since they refuse to perform such objective science – it is impossible to ascribe the changes to the placebo effect. In numerous of the non-government published peer-reviewed studies on the use of HBOT for TBI, however, such positive transformations have been noted in the treated patients. Objective evidence of changes are shown in peerreviewed research using such methods as SPECT scans, RightEye, qEEG, etc. Those

A worldwide surge of challenges arose when the DoD/Army/VA studies purported to use a sham in their studies and reported that HBOT "does not work." [62] International researchers and authorities could read that both the data and the discussion in all the purported randomized controlled studies said virtually the same thing: "Both intervention groups [sham and treated] demonstrated improved outcomes compared with PCS care alone" [63] Dr. Pierre Marois spoke for many: "By definition "sham" is "something false or empty". Hyperbaric treatments at 1.2 ATA substantially increase the amount of dissolved oxygen in the blood and simultaneously induce cascades of metabolic changes and genes activation. Therefore, the supposedly sham treatment of Miller's study is not close to being a placebo." [64].

extremely positive. 30 out of 30 patients have all shown positive medical improvement [57]. Significantly, numerous of the participants are diagnosed with TBI by the VA or have been found to have undiagnosed TBI. Either way, the overwhelming number of patients have improved significantly. These results are significant for reasons related to previous attempts to treat PTSD. The National Academies, writing in 2014 stated: "DoD and VA are spending substantial time, money, and effort on the management of PTSD in service members and veterans [\$9.3Billion+ through 2014] [yet] neither department knows with certainty whether those many programs and services are actually successful in reducing the prevalence of PTSD in

A Summary of the positive findings in the studies sponsored by DoD/VA/ Army is instructive. They find that HBOT "offered statistical and in some measures clinically significant improvement over local routine TBI care." They even note the improvements in all groups when measured against the no-treatment group. Even their "expert" consultants wrote that HBOT heals brain injuries. The Army's premier researcher, Dr. Scott Miller, despite seeming to be looking for "the final nail in the coffin" of HBOT, says on the Veterans Affairs web site: "People did get better

*DOI: http://dx.doi.org/10.5772/intechopen.94401*

and we can't ignore those results." [59].

construct a true sham-controlled study.]

changes can only be the effect of exposure to HBOT [61].]

#### *Hyperbaric Oxygenation in the Treatment of Traumatic Brain Injury DOI: http://dx.doi.org/10.5772/intechopen.94401*

*Advancement and New Understanding in Brain Injury*

For over four years, clinical and "evidence-based" medicine continue to show that HBOT is safe and effective in treating brain injuries. Objective analysis of the data from all the pivotal RCTs and crossover studies show in over 700 patients that positive improvements result from HBOT treatment protocols. And objective analyses of the studies and data reinforce the findings and the clinical evidence [52]. Dr. Wolf is a principle co-author of the first Army study. This recent USAF paper

reanalyzing the data in the cornerstone DOD/VA/Army study concludes: "This pilot study demonstrated no obvious harm [and] both groups showed improvement in scores and thus a benefit. Subgroup analysis of cognitive changes and PCL-M results regarding PTSD demonstrated a relative risk of improvement.... There is a potential gain and no potential loss. The VA/Clinical Practice Guidelines define a "B evidence rating" as "a recommendation that clinicians provide (the service) to eligible patients. At least fair evidence was found that the intervention improves health outcomes and concludes that benefits outweigh harm .... Hyperbaric oxygen therapy for mild traumatic brain injury and PTSD should be considered a legitimate adjunct therapy if future studies demonstrate similar findings or show comparable improvement to standard-of-care or research-related treatment modalities." [53]

The Journal of Hyperbaric Medicine is the most prestigious journal on Hyperbaric Medicine in the world. In 2012 its editor wrote: " While we applaud good science, there comes a point.. .. of stagnation as the standard of evidence required for the blessing of organized medicine exceeds reality (where most of us live.… I feel, as do many of my colleagues, that there is sufficient clinical and research evidence to justify the use of [HBOT] as a standard-of-care treatment for [TBI] that should be reimbursed by CMS and Tricare…. I have no doubt that, over the next several years, [HBOT] will be proven beyond a reasonable doubt to be one of the most effective treatments for [TBI]…. There is a preponderance of evidence now to justify the use and funding for the treatment…." [54] Wang et al. concur: "Compelling evidence suggests the advantage of hyperbaric oxygen therapy (HBOT) in traumatic brain injury. ...Patients undergoing hyperbaric therapy achieved significant improvement. ... with a lower overall mortality, suggesting its

utility as a standard intensive care regimen in traumatic brain injury." [55]. The Samueli Institute wrote of DoD studies: "Results showed that both the HBO and sham procedures were associated with significant improvements in post-concussion symptoms and secondary outcomes, including PTSD (which most participants had), depression, sleep quality, satisfaction with life, and physical, cognitive, and mental health functioning.. .. these results are consistent with 2 other sham-controlled clinical trials among service members and veterans involving a range of HBOT doses. ... The most remarkable lesson of this study was the difference in clinical outcomes between the 2 chamber procedures (HBO 1.5 ATA and 'sham' air 1.3 ATA) and routine post-concussion care. ... These findings reinforce the argument that effective interventions [i.e., the current standard of care practiced by military medicine] do not yet exist within the present structure of care or that routine post-concussion interventions within the [DOD or VHA] may even have iatrogenic effects that contribute to symptom persistence, the equivalent of a

While this research has been going on, the VA has been quietly conducting a controlled "demonstration project" to monitor the effects of HBOT for "PTSDonly" veterans. For nearly three years, first two and now five sites around the US are using HBOT to treat PTSD and TBI patients: Tulsa OK, Travis AFB, Joint Base Sam Houston, Tampa, and Fargo ND. While the numbers are small, the results are

**6. Implications of the science**

Subsequent studies meet those criteria.

negative placebo (nocebo) effect." [56].

**128**

extremely positive. 30 out of 30 patients have all shown positive medical improvement [57]. Significantly, numerous of the participants are diagnosed with TBI by the VA or have been found to have undiagnosed TBI. Either way, the overwhelming number of patients have improved significantly. These results are significant for reasons related to previous attempts to treat PTSD. The National Academies, writing in 2014 stated: "DoD and VA are spending substantial time, money, and effort on the management of PTSD in service members and veterans [\$9.3Billion+ through 2014] [yet] neither department knows with certainty whether those many programs and services are actually successful in reducing the prevalence of PTSD in service members or veterans and in improving their lives." [58].

A Summary of the positive findings in the studies sponsored by DoD/VA/ Army is instructive. They find that HBOT "offered statistical and in some measures clinically significant improvement over local routine TBI care." They even note the improvements in all groups when measured against the no-treatment group. Even their "expert" consultants wrote that HBOT heals brain injuries. The Army's premier researcher, Dr. Scott Miller, despite seeming to be looking for "the final nail in the coffin" of HBOT, says on the Veterans Affairs web site: "People did get better and we can't ignore those results." [59].
