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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. Conclusions: 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.

Background Audiology clinics have many tools available to evaluate auditory and vestibular complaints. However, many tools lack established normative ranges across the life span. We conducted this study to establish reference ranges across the life span for audiology/vestibular measures commonly used to evaluate patients with traumatic brain injury. Materials and Methods In this repeated measures study, 75 adults, ages 18-65 years, without a history of traumatic brain injury, underwent robust auditory/vestibular evaluations three times over six months, including rotational chair, videonystagmography, computerized dynamic posturography, vestibular evoked myogenic potentials, and retinal fundoscopy. Results Age effect was notable for transient evoked otoacoustic emissions, pure-tone audiometry, auditory brainstem response, auditory middle latency response, and auditory-steady state response at 4000 hertz (Hz). Older participants (50-65 years) were more likely to have delayed latency horizontal saccades, positional nystagmus, slowed lower-extremity motor control responses, and delayed latency ocular vestibular evoked myogenic potentials. Low to mid-frequency horizontal (0.003-4 Hz) and mid-frequency vertical (1-3 Hz) vestibulo-ocular reflex, otolith-mediated reflexes, dynamic visual acuity and balance measures were generally not influenced by age. Females had larger static subjective visual testing offset angles, longer cervical vestibular evoked myogenic potential P1 latency, faster velocity horizontal saccades, and quicker motor control latency for large backward translations than age-matched males. Conclusion These reference ranges can be used to discern impairment within the auditory and vestibular pathway following traumatic brain injury in young to middle-aged adults. ID TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01925963.

Introduction Global outcomes can strengthen inferences from clinical trials. We evaluate global outcomes for persistent post-concussive symptoms (PCS) after mild traumatic brain injury (mTBI) in two clinical trials of hyperbaric oxygen (HBO2) in United States service members. Methods During study design, outcomes of symptom, cognitive, and functional impairments planned for a trial of HBO2 for PCS (HOPPS) were weighted and grouped into different domains to formulate the composite outcome total score. The composite outcome was compared between the intervention groups in HOPPS and those in a subsequent HBO2 trial (BIMA) for validation. Additionally, two post hoc global outcome measures were explored, including one composed of components that demonstrated favorable characteristics in both studies and another via components used in another TBI randomized trial (COBRIT). Results In total, 143 active-duty or veteran military personnel were randomized across the two studies. Composite total scores improved from baseline for HBO2 (mean ± SD -2.9±9.0) and sham (-2.9±6.6) groups in HOPPS but did not differ significantly between groups (p=0.33). In BIMA, 13-week changes from baseline favored the HBO2 group (-3.6±6.4) versus sham (-0.3±5.2; p=0.02). No between-group differences were found when COBRIT composite scoring was applied to BIMA. Overall, HBO2 effects were maximized when the post hoc global measure derived from both studies was applied to the data. Conclusions Composite total scores in HOPPS and BIMA were consistent with primary study results. The global measures considered may offer utility as endpoints to achieve maximal HBO2 effect in future trials of the mTBI population. Ids clinicaltrials.gov Identifiers NCT01611194 (BIMA) and NCT01306968 (HOPPS).

Introduction: Individuals with persistent symptoms after mild traumatic brain injury (mTBI) often have auditory complaints. In this study, we used the auditory brainstem response (ABR) to determine whether cochlear synaptopathy could explain auditory symptoms. Methods: 69 adult military service members with mTBI and 25 adults without brain injury (NCT01611194 and NCT01925963) completed pure-tone audiometry, ABR, and central auditory processing tests. All participants were male, ages 21-50. Results: 37/69 mTBI participants had measurable hearing loss, while another 20-30% had hearing complaints or tinnitus. While mTBI participants with measurable hearing loss had reduced wave I and III amplitude and decreased III-V interpeak latency, those with no measurable hearing loss did not significantly differ from controls on any ABR parameter. Those with measurable hearing loss were also more likely to have abnormal central auditory processing. mTBI participants with no measurable hearing loss but who reported hearing concerns had some ABR findings (III-V interpeak latency, I and V amplitudes, V/I amplitude ratio) more like the measurable hearing loss mTBI group than normative controls. Conclusion: Cochlear synaptopathy may have contributed to some of the auditory impairment in service members with mTBI with measurable hearing loss. However, these results are likely confounded by cochlear hair cell damage.

Study objective In this exploratory, double-blind, longitudinal sham-controlled trial of hyperbaric oxygen (HBO2) for military personnel with post concussive mild traumatic brain injury (mTBI), self-reports and objective measures of sleep-wake disturbances were assessed and compared to normals. Methods Self-reports consisting of Pittsburg Sleep Quality Index (PSQI), sleep diary, screening for obstructive sleep apnea (OSA) risk, restless legs syndrome (RLS), cataplexy, and objective actigraphic measures of sleep-wake were obtained on 71 military personnel with mTBI [baseline, 13 weeks and six months post-randomization (post-intervention)], of which 35 met post-traumatic stress disorder (PTSD) criteria, and 75 healthy volunteers (baseline). Baseline between-group and follow-up changes from baseline overall and within subgroups were evaluated. Mild TBI was defined as consisting of head injury associated loss of consciousness ( Results Sleep quality by self-reports was markedly degraded in the mTBI group at baseline compared to a normative cohort; insomnia 87.3 versus 2.8%, OSA risk 70% versus 1.3%, RLS 32.4% versus and 2.7%. (all p-values Conclusions Perceived sleep quality was markedly disrupted in mTBI military personnel and sleep-wake disturbances were prevalent compared to a normative cohort. HBO2 relative to sham improved some measures of sleep quality on the PSQI, but other measures of sleep were not significantly different.

Safety monitoring and successful blinding are important features of randomized, blinded clinical trials. We report chamber- and protocol-related adverse events (AEs) for participants enrolled in two randomized, double-blind clinical trials of hyperbaric oxygen (HBO2) for persistent post-concussive symptoms clinicaltrials.gov identifiers NCT01306968, HOPPS, and NCT01611194, BIMA), as well as the success of maintaining the blind with a low-pressure sham control arm. In both studies, participants were randomized to receive HBO2 (1.5 atmospheres absolute,99% oxygen) or sham chamber sessions (1.2 atmospheres absolute, room air). In 143 participants undergoing 4,245 chamber sessions, chamber-related adverse events were rare (1.1% in the HOPPS study, 2.2% in the BIMA study). Minor, non-limiting barotrauma was the most frequently reported. Rarely, some participants experienced headache with chamber sessions. No serious adverse events were associated with chamber sessions. An allocation questionnaire completed after intervention revealed that the sham control arm adequately protected the blind in both trials. Participants based allocation assumptions on symptom improvement or lack of symptom improvement and could not discern intervention arm by pressure, smell, taste, or gas flow.

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.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..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.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.

Individuals with persistent symptoms after mild traumatic brain injury (mTBI) often have auditory complaints. In this study, we used the auditory brainstem response (ABR) to determine whether cochlear synaptopathy could explain auditory symptoms.69 adult military service members with mTBI and 25 adults without brain injury (NCT01611194 and NCT01925963) completed pure-tone audiometry, ABR, and central auditory processing tests. All participants were male, ages 21-50.37/69 mTBI participants had measurable hearing loss, while another 20%-30% had hearing complaints or tinnitus. While mTBI participants with measurable hearing loss had reduced wave I and III amplitude and decreased III-V interpeak latency, those with no measurable hearing loss did not significantly differ from controls on any ABR parameter. Those with measurable hearing loss were also more likely to have abnormal central auditory processing. mTBI participants with no measurable hearing loss but who reported hearing concerns had some ABR findings (III-V interpeak latency, I and V amplitudes, V/I amplitude ratio) more like the measurable hearing loss mTBI group than normative controls.Cochlear synaptopathy may have contributed to some of the auditory impairment in service members with mTBI with measurable hearing loss. However, these results are likely confounded by cochlear hair cell damage.

Purpose: Military service members often report both affective and vestibular complaints after mild traumatic brain injury (mTBI), but associations between symptoms and vestibular deficits can be subtle and inconsistent. Methods: From two complementary studies, one of military service members with persistent post-concussive symptoms after mTBI (NCT01611194) and the other of adult volunteers with no history of brain injury (NCT01925963), affective symptoms were compared to postural control, gait, otolith and visuospatial function. Results: The studies enrolled 71 participants with mTBI and 75 normative controls. Participants with mTBI had significantly reduced postural equilibrium on the sensory organization test (SOT), and more so in those with high anxiety or post-traumatic stress. Cervical and ocular vestibular evoked myogenic potentials (cVEMP; oVEMP) showed prolonged latencies in mTBI participants compared to controls; oVEMPs were significantly delayed in mTBI participants with high anxiety, post-traumatic stress or depression. A subset of the mTBI group had abnormal tandem gait and high anxiety. Anxiety, posttraumatic stress, and depression did not correlate with performance on the 6-Minute Walk Test, visuospatial neuropsychological measures, and the Satisfaction with Life Scale in the mTBI group. Conclusions: In this study military service members with mTBI reported affective symptoms, concurrently with vestibular-balance concerns. Worse scores on affective measures were associated with abnormal findings on measures of postural control, gait and otolith function.

Background Dizziness and imbalance are common after mild traumatic brain injury (mTBI). Hyperbaric oxygen (HBO2) has been proposed for persistent post-concussive symptoms after mTBI, but its effect on vestibular function is unknown. Objective To describe balance function in military service-members before and after intervention, and to explore the influence of post-traumatic stress disorder (PTSD), anxiety, and depression on vestibular outcomes. Methods Seventy-one participants with mTBI and seventy-five healthy adults without brain injury were enrolled (NCT01611194 and NCT01925963). mTBI participants were randomized to 40 HBO2 sessions or 40 sham chamber sessions over 12 weeks. Normative controls received no intervention. Balance and neuropsychological function were measured at baseline, 13 weeks, and 6 months. Results The mTBI cohort performed worse than healthy controls on balance and gait measures and reported more affective symptoms. Some within-group improvements were noted at 13 weeks and 6 months. Significant between-intervention differences on balance measures were minimal but effects on postural control generally favored HBO2. Those with affective symptoms, particularly PTSD, had the most improvement in postural control and otolith function following 13 weeks of HBO2. Conclusion HBO2 may influence balance function after mTBI, particularly in those with affective symptoms.

Dermatomyositis is a life-altering inflammatory disorder of skin and muscle. Details regarding the natural course of this disorder, the effects of specific therapies on its progression, and the optimal therapeutic dosage and duration of prednisone are limited. We performed a retrospective medical record review of dermatomyositis patients at four medical centers. All patients were over the age of 21 and had a clinical diagnosis of dermatomyositis with pathological confirmation. We reviewed average muscle strength, corticosteroid use, creatine kinase levels, and supplemental immunosuppressant use during the 36-month period following each patient's initial assessment. One hundred patients participated with an average age of 50.1 years. Average muscle strength improved and prednisone requirements lessened six months after initial assessment. There was no difference in the mean change in muscle strength or cumulative corticosteroid use over 36 months among those initially treated with methotrexate, mycophenolate mofetil, pulse IVIG, or azathioprine. There was a 5% mortality rate in dermatomyositis patients due to infections. Treated dermatomyositis patients demonstrate the most significant improvement in strength during the first six-to-twelve months following their initial clinical assessment. Additional prospective studies are needed to determine the relative benefit of select immunosuppressant agents in preserving strength and reducing corticosteroid use in dermatomyositis.