Hyperbaric oxygen for refractory osteomyelitis.

Refractory osteomyelitis is defined as a chronic osteomyelitis that persists or recurs after appropriate interventions have been performed or where acute osteomyelitis has not responded to accepted management techniques [1]. To date, no randomized clinical trials examining the effects of hyperbaric oxygen (HBO2) therapy on refractory osteomyelitis exist, and the number of new osteomyelitis clinical trials conducted over the past decade has been limited. However, based on a comprehensive review of the scientific literature, the addition of HBO2 therapy to routine surgical and antibiotic treatment of previously refractory osteomyelitis appears to be both safe and ultimately improves infection resolution rates. In most cases, the best clinical results are obtained when HBO2 treatment is administered in conjunction with culture-directed antibiotics and initiated soon after clinically indicated surgical debridement. Where extensive surgical debridement or removal of fixation hardware is relatively contraindicated (e.g., cranial, spinal, sternal, or pediatric osteomyelitis), a trial of culture-directed antibiotics and HBO2 therapy prior to undertaking more than limited surgical interventions provides a reasonable prospect for osteomyelitis cure. HBO2 therapy is ordinarily delivered on a once daily basis, five-seven days per week, for 90-120 minutes using 2.0-3.0 atmospheres absolute (ATA) pressure. Where prompt clinical improvement is seen, the existing regimen of antibiotics and HBO2 therapy should be continued for approximately four to six weeks. Typically, 20-40 HBO2 sessions are required to achieve sustained therapeutic benefit. In contrast, if prompt clinical response is not noted or osteomyelitis recurs after this initial treatment period, then continuation of the current antibiotic and HBO2 treatment regimen is unlikely to be effective. Instead, clinical management strategies should be reassessed and additional surgical debridement and/or modification of antibiotic therapy considered. Subsequent reinstitution of HBO2 therapy will again help maximize the overall chances for treatment success in these persistently refractory patients.

Extended follow-up in a randomized trial of hyperbaric oxygen for persistent post-concussive symptoms.

To date, several Department of Defense (DoD) and civilian studies have evaluated hyperbaric oxygen for mild forms of traumatic brain injury. Prior to the DoD-sponsored "Brain Injury and Mechanisms of Action of Hyperbaric Oxygen for Persistent Post-Concussive Symptoms after Mild Traumatic Brain Injury (mTBI) (BIMA)" trial, none included post-intervention follow-up beyond three to six months. Post-hoc attempts at long-term follow-up were complicated by low participation and potential self-selection bias. BIMA planned for follow-up through 12 months but was amended to add post-concussive and post-traumatic stress disorder, quality of life, pain, depression, anxiety, and alcohol use assessments at 24 and 36 months. A total of 42 of 71 BIMA participants consented to extendedfollow-up, and 40 and 14 completed a 24- or 36-month visit, respectively, representing an overall response rate of 59% and 20%. Participants who completed extended follow-up were similar to the study group that did not in terms of demographics, perceived intervention allocation, and initial response to intervention. There were no significant differences at 24 or 36 months between intervention groups, and group mean scores were near pre-intervention values. This return to baseline could be due to waning treatment effect, selection bias, or participant or perception effects. Though BIMA implemented several participant retention strategies, more frequent participant contact and increased compensation might improve long-term retention in future studies. clinicaltrials.gov Identifier NCT01611194.

Hyperbaric oxygen for mTBI-associated PCS and PTSD: Pooled analysis of results from Department of Defense and other published studies.

BACKGROUND: Some clinical trials report improvement in persistent post-concussive symptoms (PCS) with hyperbaric oxygen (HBO2) following mild traumatic brain injury (mTBI), but questions remain regarding the utility of HBO2 for PCS, the effects of HBO2 on post-traumatic stress disorder (PTSD), and the influences of sham control exposures. METHODS: A systematic review and pooled analysis was conducted to summarize available evidence for HBO2 in mTBI-associated PCS ± PTSD. Data aggregated from four Department of Defense (DoD) studies with participant-level data (n=254) were grouped into pooled HBO2 and sham intervention groups. Changes from baseline to post-intervention on PCS, PTSD, and neuropsychological measures were assessed using linear mixed models to evaluate main intervention and intervention-by-baseline PTSD effects. Potential dose-response relationships to oxygen partial pressures were investigated. Intervention effects from three other published studies with summary-level participant data (n=135) were also summarized.. RESULTS: Pooled DoD data analyses indicated trends toward improvement favoring HBO2 for PCS (Rivermead Total Score: -2.3, 95% CI [-5.6, 1.0], p=0.18); PTSD (PTSD Checklist Total Score: -2.7, 95% CI [-5.8, 0.4], p=0.09); and significant improvement in verbal memory (CVLT-II Trial 1-5 Free Recall: 3.8; 95% CI [1.0, 6.7], p=0.01). A dose-response trend to increasing oxygen partial pressure was also found, with a greater HBO2 effect in mTBI-associated PTSD suggested. The direction of results was consistent with other published studies. CONCLUSION: A definitive clinical trial, with an appropriate control group, should be considered to identify the optimal HBO2 dosing regimen for individuals with mTBI-associated PTSD ± PCS.

Hyperbaric oxygen for persistent post-concussive symptoms: long-term follow-up.

We report results of an observational cohort study investigating long-term follow-up in participants from two completed United States military trials of hyperbaric oxygen (HBO2) for persistent post-concussive symptoms (PCS), as well as challenges in recruitment and retention in active-duty military personnel. After informed consent, participants completed an electronic survey assessing PCS, post-traumatic stress disorder (PTSD), anxiety, depression and quality of life. Of 132 HBO2 study participants, 40 (30%) completed the survey (42 could not be contacted; 50 were lost to follow-up or declined). All were male, age 28.1 ±6.6 years (mean ±1SD). Time to follow-up was 39.2 ±6.1 months. At follow-up, participants reported continued symptoms of PTSD, depression, anxiety and reduced quality of life. Among DARPA/VCU study participants, total PCS scores worsened in the 1.5 atmospheres absolute (ATA) equivalent HBO2 group (mean change 7.4 ±15.8) and improved in the sham (-8.0 ±7.7) and 2.0 atmospheres absolute equivalent HBO2 groups (-3.3 ±7.4). Individual changes varied widely, range -23 to +28 points. In participants from the HOPPS study, total PCS scores worsened in all groups: local care (10.5 ±8.7), sham (7.9 ±11.9) and 1.5 ATA HBO2 (1.0 ±19.4). In this limited, cross-sectional sample, PCS and PTSD symptoms did not appear to improve over time by descriptive analyses. Low participation rates and potential response bias limit our ability to perform statistical hypothesis testing and to draw conclusions from these data. Future studies should prospectively plan longitudinal follow-up and regular engagement with participants to minimize attrition.

Hyperbaric oxygen for blast-related postconcussion syndrome: three-month outcomes.

OBJECTIVE: Mild traumatic brain injury (mTBI) and postconcussion syndrome (PCS) are common among military combatants. Hyperbaric oxygen (HBO2 ) is a proposed treatment for these conditions, but it has not been rigorously studied. The objective of this study was to determine the effects of HBO2 by 3 months post compression at 2 commonly employed dosing levels to treat PCS; whether specific subgroups may have benefited; and if no overall effect was found, whether benefit is masked by other conditions. METHODS: This randomized, double-blind, sham-controlled study was conducted at the Naval Air Station in Pensacola, Florida on 61 male Marines with a history of mTBI and PCS. Intervention consisted of 40 once daily 60-minute hyperbaric chamber compressions at 2.0 atmospheres absolute (ATA) at 1 of 3 randomly preassigned oxygen fractions, resulting in respective blinded groups with an oxygen-breathing exposure equivalent to (1) surface air (sham), (2) 100% oxygen at 1.5ATA, or (3) 100% oxygen at 2.0ATA. The main outcome measure was the Rivermead Post-Concussion Questionnaire-16 (RPQ-16) collected before compressions and at 2 later points. RESULTS: The interaction of time by intervention group was not significant for improvement on the RPQ-16. Nor was there evidence of efficacy on the RPQ-16 for any subgroup. No significant time by intervention interaction was found for any functional, cognitive, or psychomotor secondary outcome measure at an unadjusted 0.05 significance level. INTERPRETATION: Using a randomized control trial design and analysis including a sham, results showed no evidence of efficacy by 3 months post-compression to treat the symptomatic, cognitive, or behavioral sequelae of PCS after combat-related mTBI.

The effect of hyperbaric oxygen on persistent postconcussion symptoms.

BACKGROUND: The high incidence of persistent postconcussion symptoms in service members with combat-related mild traumatic brain injury has prompted research in the use of hyperbaric oxygen (HBO2) for management. OBJECTIVE: The effects of HBO2 on persistent postconcussion symptoms in 60 military service members with at least 1 combat-related mild traumatic brain injury were examined in a single-center, double-blind, randomized, sham-controlled, prospective trial at the Naval Medicine Operational Training Center at Naval Air Station Pensacola. METHODS: Over a 10-week period, subjects received a series of 40, once-daily, hyperbaric chamber compressions at 2.0 atmospheres absolute (ATA). During each session, subjects breathed 1 of 3 preassigned oxygen fractions (10.5%, 75%, or 100%) for 60 minutes, resulting in an oxygen exposure equivalent to breathing surface air, 100% oxygen at 1.5 ATA, or 100% oxygen at 2.0 ATA, respectively. Individual, subscale and total item responses on the Rivermead Postconcussion Symptom Questionnaire and individual and total Posttraumatic Disorder Checklist-Military Version were measured just prior to intervention and immediately postintervention. RESULTS: Between-group testing of pre- and postintervention means revealed no significant differences on individual or total scores on the Posttraumatic Disorder Checklist-Military Version or Rivermead Postconcussion Symptom Questionnaire, demonstrating a successful randomization and no significant main effect for HBO2 at 1.5 or 2.0 ATA equivalent compared with the sham compression. Within-group testing of pre- and postintervention means revealed significant differences on several individual items for each group and difference in the Posttraumatic Disorder Checklist-Military Version total score for the 2.0 ATA HBO2 group. DISCUSSION: The primary analyses of between group differences found no evidence of efficacy for HBO2. The scattered within group differences are threatened by Type 2 errors and could be explained by nonspecific effects. CONCLUSION: This study demonstrated that HBO2 at either 1.5 or 2.0 ATA equivalent had no effect on postconcussion symptoms after mild traumatic brain injury when compared with sham compression.

Hyperbaric oxygen for post-concussion syndrome: design of Department of Defense clinical trials.

The current wars in the Middle East have resulted in between 10-20% of U.S. service members with mild traumatic brain injury (mTBI). While anecdotal reports have associated hyperbaric oxygen (HBO2) with improved outcomes after mTBI, controlled research is lacking. The Department of Defense (DoD), in collaboration with the Department of Veterans Affairs (DVA), has a comprehensive program examining this issue. The DoD's four randomized controlled trials will enroll a total of 242 service members with post-concussion syndrome and expose them to a range of control, sham and HBO2 conditions for 40 sessions over a period of eight to 11 weeks. Compression pressures will range from 1.2 atm abs (sham) to 2.4 atm abs, and oxygen concentration will range from room air (sham and control) to 100%. Outcomes measures include both subjective and objective measures performed at baseline, at exposure completion, and at three to 12 months' follow-up. This integrated program of clinical trials investigating the efficacy of HBO2 in service members with persistent symptoms following mTBI exposure will be important to define practice guidelines and, if needed, for the development of definitive clinical trials in this population.

Comparison of treatment recompression tables for neurologic decompression illness in swine model.

BACKGROUND: Significant reductions in ambient pressure subject an individual to risk of decompression illness (DCI); with incidence up to 35 per 10,000 dives. In severe cases, the central nervous system is often compromised (>80%), making DCI among the most morbid of diving related injuries. While hyperbaric specialists suggest initiating recompression therapy with either a Treatment Table 6 (TT6) or 6A (TT6A), the optimal initial recompression treatment for severe DCI is unknown. METHODS: Swine were exposed to an insult dive breathing air at 7.06 ATA (715.35 kPa) for 24 min followed by rapid decompression at a rate of 1.82 ATA/min (184.41 kPa/min). Swine that developed neurologic DCI within 1 hour of surfacing were block randomized to one of four United States Navy Treatment Tables (USN TT): TT6, TT6A-air (21% oxygen, 79% nitrogen), TT6A-nitrox (50% oxygen, 50% nitrogen), and TT6A-heliox (50% oxygen, 50% helium). The primary outcome was the mean number of spinal cord lesions, which was analyzed following cord harvest 24 hours after successful recompression treatment. Secondary outcomes included spinal cord lesion incidence and gross neurologic outcomes based on a pre- and post- modified Tarlov assessment. We compared outcomes among these four groups and between the two treatment profiles (i.e. TT6 and TT6A). RESULTS: One-hundred and forty-one swine underwent the insult dive, with 61 swine meeting inclusion criteria (43%). We found no differences in baseline characteristics among the groups. We found no significant differences in functional neurologic outcomes (p = 0.77 and 0.33), spinal cord lesion incidence (p = 0.09 and 0.07), or spinal cord lesion area (p = 0.51 and 0.17) among the four treatment groups or between the two treatment profiles, respectively. While the trends were not statistically significant, animals treated with TT6 had the lowest rates of functional deficits and the fewest spinal cord lesions. Moreover, across all animals, functional neurologic deficit had strong correlation with lesion area pathology (Logistic Regression, p < 0.01, Somers' D = 0.74). CONCLUSIONS: TT6 performed as well as the other treatment tables and is the least resource intensive. TT6 is the most appropriate initial treatment for neurologic DCI in swine, among the tables that we compared.

Buprenorphine physician-pharmacist collaboration in the management of patients with opioid use disorder: results from a multisite study of the National Drug Abuse Treatment Clinical Trials Network.

BACKGROUND AND AIMS: Physician and pharmacist collaboration may help address the shortage of buprenorphine-waivered physicians and improve care for patients with opioid use disorder (OUD). This study investigated the feasibility and acceptability of a new collaborative care model involving buprenorphine-waivered physicians and community pharmacists. DESIGN: Nonrandomized, single-arm, open-label feasibility trial. SETTING: Three office-based buprenorphine treatment (OBBT) clinics and three community pharmacies in the United States. PARTICIPANTS: Six physicians, six pharmacists, and 71 patients aged ≥18 years with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) OUD on buprenorphine maintenance. INTERVENTION: After screening, eligible patients' buprenorphine care was transferred from their OBBT physician to a community pharmacist for 6 months. MEASUREMENTS: Primary outcomes included recruitment, treatment retention and adherence, and opioid use. Secondary outcomes were intervention fidelity, pharmacists' use of prescription drug monitoring program (PDMP), participant safety, and satisfaction with treatment delivery. FINDINGS: A high proportion (93.4%, 71/76) of eligible participants enrolled into the study. There were high rates of treatment retention (88.7%) and adherence (95.3%) at the end of the study. The proportion of opioid-positive urine drug screens (UDSs) among complete cases (i.e. those with all six UDSs collected during 6 months) at month 6 was (4.9%, 3/61). Intervention fidelity was excellent. Pharmacists used PDMP at 96.8% of visits. There were no opioid-related safety events. Over 90% of patients endorsed that they were "very satisfied with their experience and the quality of treatment offered," that "treatment transfer from physician's office to the pharmacy was not difficult at all," and that "holding buprenorphine visits at the same place the medication is dispensed was very or extremely useful/convenient." Similarly, positive ratings of satisfaction were found among physicians/pharmacists. CONCLUSIONS: A collaborative care model for people with opioid use disorder that involves buprenorphine-waivered physicians and community pharmacists appears to be feasible to operate in the United States and have high acceptability to patients.

Randomized, Sham-Controlled, Feasibility Trial of Hyperbaric Oxygen for Service Members With Postconcussion Syndrome: Cognitive and Psychomotor Outcomes 1 Week Postintervention.

Background Mild traumatic brain injury (mTBI) and residual postconcussion syndrome (PCS) are common among combatants of the recent military conflicts in Iraq and Afghanistan. Hyperbaric oxygen (HBO2) is a proposed treatment but has not been rigorously studied for this condition. Objectives In a secondary analysis, examine for possible effects on psychomotor (balance and fine motor) and cognitive performance 1 week after an HBO2 intervention in service members with PCS after mTBI. Methods A randomized, double-blind, sham control, feasibility trial comparing pretreatment and posttreatment was conducted in 60 male active-duty marines with combat-related mTBI and PCS persisting for 3 to 36 months. Participants were randomized to 1 of 3 preassigned oxygen fractions (10.5%, 75%, or 100%) at 2.0 atmospheres absolute (ATA), resulting in respective groups with an oxygen exposure equivalent to (1) breathing surface air (Sham Air), (2) 100% oxygen at 1.5 ATA (1.5 ATAO2), and (3) 100% oxygen at 2.0 ATA (2.0 ATAO2). Over a 10-week period, participants received 40 hyperbaric chamber sessions of 60 minutes each. Outcome measures, including computerized posturography (balance), grooved pegboard (fine motor speed/dexterity), and multiple neuropsychological tests of cognitive performance, were collected preintervention and 1-week postintervention. Results Despite the multiple sensitive cognitive and psychomotor measures analyzed at an unadjusted 5% significance level, this study demonstrated no immediate postintervention beneficial effect of exposure to either 1.5 ATAO2 or 2.0 ATAO2 compared with the Sham Air intervention. Conclusions These results do not support the use of HBO2 to treat cognitive, balance, or fine motor deficits associated with mTBI and PCS.