Patient-Reported Outcome Measures Following Hyperbaric Oxygen Therapy for Radiation Cystitis: Early Results From the Multicenter Registry for Hyperbaric Oxygen Therapy.

PURPOSE: Our purpose was to determine changes in patient-reported hematuria and urinary symptoms after hyperbaric oxygen (HBO2) treatment for radiation cystitis (RC). MATERIALS AND METHODS: We analyzed prospectively collected data from the Multicenter Registry for Hyperbaric Oxygen Therapy Consortium accumulated within a week of beginning and ending HBO2. Measures included the modified Radiation Therapy Oncology Group (RTOG) Hematuria Scale, Urinary Distress Inventory Short Form, and EuroQol Five Dimension Five Level instrument. RTOG hematuria and Urinary Distress Inventory Short Form scores were compared using the sign test. Logistic regression was used to evaluate characteristics associated with hematuria improvement. RESULTS: A total of 470 registry patients had RC. The median age, number of HBO2 sessions, and years after radiation were 73 (IQR 12) years, 39 (IQR 10) sessions, and 5 (IQR 8) years, respectively. Eighty-four percent of patients (393/470) had prostate cancer‒related radiation. EuroQol Five Dimension Five Level scores improved from 0.83 (IQR 0.14) to 0.85 (IQR 0.22; P < .001. Three hundred seventy patients had complete RTOG hematuria scores that improved from 2 (IQR 2) to 0 (IQR 2; P < .001. Two hundred forty-six patients had complete Urinary Distress Inventory Short Form ratings that decreased from 33.3 (IQR 44) to 22.2 (IQR 33; P < .001). Regression analysis of those with visible hematuria before HBO2 showed lower improvement odds associated with higher HBO2 hematuria scores (odds ratio [OR] 0.44, 95% CI 0.26-0.73; P < .01), a smoking history (OR 0.44, 95% CI 0.21-0.92; P = .03), or a nonprostate cancer history (OR 0.32, 95% CI 0.10-0.99; P = .05). CONCLUSIONS: HBO2 for RC improved reported hematuria, urinary function, and quality of life. Higher baseline hematuria scores, smoking, and nonprostate cancer history were associated with lower odds of hematuria improvement.

A randomized trial of one versus three hyperbaric oxygen sessions for acute carbon monoxide poisoning.

Introduction: Hyperbaric oxygen (HBO2) improves outcome in patients with acute carbon monoxide (CO) poisoning, but optimal dose/timing are unknown. In this double-blind, sham-controlled randomized trial, we compared neuropsychological sequelae at six weeks and six months in patients receiving three HBO2 sessions or one HBO2 session and two sham chamber sessions after acute CO poisoning. Methods: After completing one HBO2 session (3.0 ATA, 60 minutes, 2.0 ATA, 65 minutes), CO-poisoned patients were randomized (1:1): two sham chamber sessions (1 ATA air, 120 minutes) or two additional HBO2sessions (2.0 ATA, 90 minutes at pressure, 120 minutes in chamber) completed within 24 hours. Eligible patients were >24 hours from accidental poisoning, English-speaking, and not intubated. We planned 150 participants. Results: The study was stopped early for enrollment futility. From 2006 to 2016, we screened 395 patients: 136 were deemed eligible to participate, and 75 signed informed consent. Two were later withdrawn for past brain injury/PTSD (one sham, one HBO2), and one for performance validity (sham). Of the 72 analyzed, mean age was 42 ± 15 years, 40 (56%) were male, 20 (28%) had loss of consciousness, and mean initial carboxyhemoglobin was 22 ± 9%. The rate of six-week neuropsychological sequelae was 50% in the one-HBO2 session group and 55% in the three-HBO2 sessions group (p = 0.80), and at six months was 42% versus 46%, respectively (p = 0.76). Conclusions: There was no difference in the rate of neuropsychological sequelae in those who received three HBO2 sessions and those who received one HBO2 sessions and two sham sessions. The higher rate of neuropsychological sequelae compared to an earlier study may be due to neuropsychological test-retest effects or previously identified risk factors for cognitive sequelae (age, duration of poisoning, cerebellar dysfunction). This study's rates of cognitive difficulties, affective complaints, and other symptoms suggest brain injury after CO poisoning is common.

Effect of barometric pressure on single-breath carbon monoxide diffusing capacity.

BACKGROUND: Single-breath diffusing capacity for carbon monoxide (DLCO) quantifies gas transfer in the lungs. DLCO measurement is affected by barometric pressure (Pb) and alveolar partial pressure of oxygen (PAO2). The current equations for adjusting DLCO for Pb and PAO2 may not be accurate given advances in test performance and technology. We quantify changes in DLCO with alterations in Pb in normal and COPD subjects, determine the accuracy of the current Pb and PAO2 adjustment equations and develop updated adjustment equations. METHODS: We measured DLCO in 13 normal and 10 COPD subjects at 1330 m altitude and in a hypobaric/hyperbaric chamber at altitudes of sea-level and 2500 m; six normal subjects were tested at 3600 m. We determined if there were significant differences in DLCO between altitudes. We developed an equation for adjusting DLCO for changes in Pb from sea-level. We compared this equation with the existing Pb adjustment equation in normal and COPD subjects. We determined the accuracy of the current PAO2 adjustment equation and developed a new PAO2 adjustment equation. RESULTS: DLCO significantly increased with decreasing Pb. We developed a Pb adjustment equation that adjusts DLCO measured at altitudes between 1330 m and 3600 m to sea-level values. This Pb adjustment equation yields DLCO results that are not significantly different than the currently recommended equation. We developed a more accurate PAO2 adjustment equation. CONCLUSION: DLCO measurement is significantly affected by altitude. We developed equations that accurately adjust DLCO for changes in Pb and PAO2 in normal and COPD subjects.

Computer clinical decision support that automates personalized clinical care: a challenging but needed healthcare delivery strategy.

How to deliver best care in various clinical settings remains a vexing problem. All pertinent healthcare-related questions have not, cannot, and will not be addressable with costly time- and resource-consuming controlled clinical trials. At present, evidence-based guidelines can address only a small fraction of the types of care that clinicians deliver. Furthermore, underserved areas rarely can access state-of-the-art evidence-based guidelines in real-time, and often lack the wherewithal to implement advanced guidelines. Care providers in such settings frequently do not have sufficient training to undertake advanced guideline implementation. Nevertheless, in advanced modern healthcare delivery environments, use of eActions (validated clinical decision support systems) could help overcome the cognitive limitations of overburdened clinicians. Widespread use of eActions will require surmounting current healthcare technical and cultural barriers and installing clinical evidence/data curation systems. The authors expect that increased numbers of evidence-based guidelines will result from future comparative effectiveness clinical research carried out during routine healthcare delivery within learning healthcare systems.

Decompression sickness with incidental pulmonary cyst.

Decompression sickness (DCS) is a known complication of scuba diving. DCS occurs when bubbles are formed as pressure is reduced during and after ascent from a dive, following inert gas uptake during the dive. The bubbles cause inflammation and hypoxia. The definitive treatment for decompression sickness is hyperbaric oxygen therapy. We present a case of a healthy 16-year-old male who presented with decompression sickness and an incidental pulmonary cyst discovered by chest CT, likely congenital. The patient was successfully treated with U.S. Navy Treatment Table 6 (TT6) for his decompression sickness, but he continued to have chest pain, requiring hospitalization and consultation with pediatric pulmonology and cardiothoracic surgery from the cyst. Three years later he complained of chest pain with changes in altitude. Chest CT showed persistence of this cyst, and additional cysts. Case conference with pulmonologists and chest radiologist could not offer a definite etiology without lung biopsy, felt to not be indicated. We believe that the changes in pressure/volumes during the dives and TT6 exacerbated his pulmonary cyst.

Three cases of clinically significant inaccurate carboxyhemoglobin measurement.

Background: Clinicians often rely on measurement of carboxyhemoglobin (COHb) to confirm or rule out a diagnosis of carbon monoxide (CO) poisoning. Methods: We report two cases of false negative COHb in patients with CO poisoning and one case of false positive COHb in a patient without CO poisoning. Results: In the first case, a 20-year-old male developed headache, confusion, and near-syncope while operating a gasoline-powered pressure washer in an enclosed space. In the emergency department (ED), his COHb was 1.8%, but this level was disregarded, and he was referred for hyperbaric oxygen. His COHb just before hyperbaric oxygen was 4.1%, and later analysis of his blood collected at ED arrival revealed a COHb of 20.1%. The referral ED blood gas machine calibration and controls were within specification. In the second case, a 45-year-old male presented with several others to the ED with symptoms of CO poisoning after exposure at a conference. All others had elevated COHb levels, but his COHb was 2%. He was discharged but returned shortly with continued symptoms and requested his COHb be repeated. The repeat COHb was 17% (84 minutes after the first). After three hours of oxygen, his COHb was 7%. In the final case, an 83-year-old non-smoking male presented to an ED with breathlessness and tachypnea and was diagnosed with COVID-19 pneumonia. His COHb was 7.1%, but he reported living in an all-electric home. Another adult who lived with him and rode with him to the ED was asymptomatic and had a COHb of 3%. Later, COHb of 1.9% was measured from blood collected at ED arrival, and gas chromatography/mass spectrometry confirmed this result (2%). Conclusions: COHb levels are not always accurate. Clinicians should use clinical judgment to manage their patients, including rejecting laboratory values that do not fit the clinical situation.

High oxygen concentrations inhibit Acanthamoeba spp.

Efficacious treatments against Acanthamoeba Keratitis (AK) is challenging, often ineffective and linked to the intragenotype variation in the drug efficacy. Increased oxygen can facilitate host response and can inhibit some organisms. Herein, we report the effect of increased oxygen concentrations on Acanthamoeba spp. growth and its effect on ROS (reactive oxygen species) production. The exposition to pure oxygen could reduce cell growth by at least 60% for Acanthamoeba castellanii Neff, Acanthamoeba polyphaga, and Acanthamoeba griffini. The increase in ROS production confirming that oxygen cell's growth inhibition was due to oxidative stress. Further studies are needed to determine oxygen saturation level, time of oxygen exposition, and number of sessions needed to eliminate the parasite.

Physiologic and biochemical rationale for treating COVID-19 patients with hyperbaric oxygen.

The SARS-Cov-2 (COVID-19) pandemic remains a major worldwide public health issue. Initially, improved supportive and anti-inflammatory intervention, often employing known drugs or technologies, provided measurable improvement in management. We have recently seen advances in specific therapeutic interventions and in vaccines. Nevertheless, it will be months before most of the world's population can be vaccinated to achieve herd immunity. In the interim, hyperbaric oxygen (HBO2) treatment offers several potentially beneficial therapeutic effects. Three small published series, one with a propensity-score-matched control group, have demonstrated safety and initial efficacy. Additional anecdotal reports are consistent with these publications. HBO2 delivers oxygen in extreme conditions of hypoxemia and tissue hypoxia, even in the presence of lung pathology. It provides anti-inflammatory and anti-proinflammatory effects likely to ameliorate the overexuberant immune response common to COVID-19. Unlike steroids, it exerts these effects without immune suppression. One study suggests HBO2 may reduce the hypercoagulability seen in COVID patients. Also, hyperbaric oxygen offers a likely successful intervention to address the oxygen debt expected to arise from a prolonged period of hypoxemia and tissue hypoxia. To date, 11 studies designed to investigate the impact of HBO2 on patients infected with SARS-Cov-2 have been posted on clinicaltrials.gov. This paper describes the promising physiologic and biochemical effects of hyperbaric oxygen in COVID-19 and potentially in other disorders with similar pathologic mechanisms.

Enabling a learning healthcare system with automated computer protocols that produce replicable and personalized clinician actions.

Clinical decision-making is based on knowledge, expertise, and authority, with clinicians approving almost every intervention-the starting point for delivery of "All the right care, but only the right care," an unachieved healthcare quality improvement goal. Unaided clinicians suffer from human cognitive limitations and biases when decisions are based only on their training, expertise, and experience. Electronic health records (EHRs) could improve healthcare with robust decision-support tools that reduce unwarranted variation of clinician decisions and actions. Current EHRs, focused on results review, documentation, and accounting, are awkward, time-consuming, and contribute to clinician stress and burnout. Decision-support tools could reduce clinician burden and enable replicable clinician decisions and actions that personalize patient care. Most current clinical decision-support tools or aids lack detail and neither reduce burden nor enable replicable actions. Clinicians must provide subjective interpretation and missing logic, thus introducing personal biases and mindless, unwarranted, variation from evidence-based practice. Replicability occurs when different clinicians, with the same patient information and context, come to the same decision and action. We propose a feasible subset of therapeutic decision-support tools based on credible clinical outcome evidence: computer protocols leading to replicable clinician actions (eActions). eActions enable different clinicians to make consistent decisions and actions when faced with the same patient input data. eActions embrace good everyday decision-making informed by evidence, experience, EHR data, and individual patient status. eActions can reduce unwarranted variation, increase quality of clinical care and research, reduce EHR noise, and could enable a learning healthcare system.

Patterns of cardiac dysfunction after carbon monoxide poisoning.

Objective: To describe the structural sequelae of carbon monoxide (CO) poisoning on the heart assessed using stress cardiac MRI (CMR). CO poisoning is common. While acute cardiac injury is frequent among survivors, the mid- and long-term effects of CO on the myocardium are unclear. Methods: CMR studies performed between the years 2005 and 2014 for a primary diagnosis of CO poisoning at a tertiary care center were reviewed by an experienced cardiologist. Variables of interest were compared between patients with normal and abnormal studies to identify factors associated with cardiac dysfunction. Results: Eighty-eight patients underwent stress CMR, age 34 years (range 11-70); 49% were male, 74 had acute poisoning and 14 had chronic poisoning (CO exposure for longer than 24 hours). Time from CO poisoning to imaging was 24 months (1 day-120 months). Patients were stratified into four categories, which included those with acute poisoning imaged: ≤12 months; 12-60 months; >60 months from the event; and those with chronic poisoning. Overall, 26 studies (30%) were abnormal. The most common findings were: left ventricular systolic dysfunction in 14 patients, right ventricular systolic dysfunction in nine, and LV dilatation in six. Abnormalities were mild in most cases and were equally prevalent in all four patient categories. Dyspnea at the time of follow-up was more frequent among those with abnormal studies. Conclusion: Mild alterations in ventricular structure and function are frequent in survivors of CO poisoning. Myocardial scarring is rare, suggesting that acute hypoxic injury may not fully explain these abnormalities.

Hyperbaric oxygen as a treatment for COVID-19 infection?

Recently the internet has been abuzz with new ideas to treat COVID-19, including hyperbaric oxygen (HBO2) therapy, undoubtedly driven by the fact that until recently there have been few therapeutic options for this highly contagious and often lethal infection. . . . Refractory hypoxemia is certainly treatable with hyperbaric oxygen due to the obvious effect of increasing inspired oxygen partial pressure (PO2), the major reason for using HBO2 for its established indications. However, the length of time during which patients can safely be administered HBO2 inside a chamber is limited, due to practical issues of confinement and isolation from other necessary medical interventions, but also because of oxygen toxicity.

Gunshot damage to monoplace hyperbaric chamber acrylic.

Introduction: Health care workers are vulnerable to workplace violence, including active shooter incidents. Little is known about how firearms could damage monoplace chamber acrylic and whether a breached pressurized chamber presents additional threat to the patient or bystanders. Methods: In a remote area where firearm discharge is permitted, we tested the durability of sections of monoplace hyperbaric chamber acrylic under various firearm discharges. Firearms were discharged at acrylic sections from a distance of 17 feet at 45 degrees and 10 degrees from perpendicular while wearing protective gear. Firearm calibers ranged from .22 caliber handgun to 5.56 mm AR-15 rifle. We also conducted similar testing on a monoplace hyperbaric chamber pressurized with >99% oxygen to a differential pressure of 14.7 psig (2.0 atmospheres absolute at sea level). Handguns were remotely fired at a distance of 12 feet from the chamber (30 degrees from perpendicular), while the rifles were fired at a distance of 60 feet from the chamber. Result: Higher-caliber handguns penetrated or fractured the acrylic sections only after multiple shots. The tested rifles caused full-thickness penetration and fracture with a single shot. However, the pressurized monoplace hyperbaric chamber required two shots from the AR-15 rifle, separated by approximately 60 mm, to penetrate the acrylic, resulting in rapid depressurization. The chamber otherwise remained intact, with no explosion or conflagration observed. Conclusion: An intact or pressurized chamber performs differently than stand-alone acrylic sections under firearms testing. In a worst-case active shooter scenario, the pressurized monoplace chamber tested posed no additional threat to bystanders beyond the significant risk of ricochet.

Carbon monoxide poisoning.

Despite established exposure limits and safety standards as well as the availability of carbon monoxide (CO) alarms, each year 50,000 people in the United States visit emergency departments for CO poisoning. Carbon monoxide poisoning can occur from brief exposures to high levels of CO or from longer exposures to lower levels. Common symptoms can include headaches, nausea and vomiting, dizziness, general malaise, and altered mental status. Some patients may have chest pain, shortness of breath, and myocardial ischemia, and may require mechanical ventilation and treatment of shock. Individuals poisoned by CO often develop brain injury manifested by neurological problems, including cognitive sequelae, anxiety and depression, persistent headaches, dizziness, sleep problems, motor weakness, vestibular and balance problems, gaze abnormalities, peripheral neuropathies, hearing loss, tinnitus, Parkinsonian-like syndrome, and other problems. In addition, some will have cardiac issues or other ailments. While breathing oxygen hastens the removal of carboxyhemoglobin (COHb), hyperbaric oxygen (HBO2) hastens COHb elimination and favorably modulates inflammatory processes instigated by CO poisoning, an effect not observed with breathing normobaric oxygen. Hyperbaric oxygen improves mitochondrial function, inhibits lipid peroxidation transiently, impairs leukocyte adhesion to injured microvasculature, and reduces brain inflammation caused by the CO-induced adduct formation of myelin basic protein. Based upon three supportive randomized clinical trials in humans and considerable evidence from animal studies, HBO2 should be considered for all cases of acute symptomatic CO poisoning. Hyperbaric oxygen is indicated for CO poisoning complicated by cyanide poisoning, often concomitantly with smoke inhalation.

Carbon monoxide poisonings in hotels and motels: The problem silently continues.

Carbon monoxide poisoning remains common in the United States. One component of effective prevention involves identification of scenarios in which poisoning occurs to guide development of appropriate interventions. This study was conducted to determine the significance of the problem of carbon monoxide poisoning occurring in US hotels, motels and resorts. This is a population-based case series of guests staying at US hotels, motels, and resorts from 2005 to 2018. Details of incidents and individuals poisoned with carbon monoxide were collected from online searches and professional experience of the authors. Data extracted included number of incidents and individuals poisoned, age of those poisoned, outcomes, source of carbon monoxide, and lodging type. From January 1, 2005 to December 31, 2018, 905 guests were poisoned in 115 identified incidents, including 22 fatalities. Children represented 16% of those poisoned and 27% of fatalities. Type of lodgings were hotels, motels, and resorts of all classes and located in a majority of states. Most poisonings were caused by natural gas fueled appliances and could likely have been prevented by an in-room carbon monoxide alarm. To reduce morbidity and mortality from unintentional CO poisoning in lodging facilities, government should mandate installation of in-room CO alarms, similar to the current requirement for smoke alarms.

Central auditory processing disorders after mild traumatic brain injury.

Auditory processing disorders are common following mild traumatic brain injury (mTBI), but the neurocircuitry involved is not well understood. The present study used functional MRI to examine auditory cortex activation patterns during a passive listening task in a normative population and mTBI patients with and without clinical central auditory processing deficits (APD) as defined by the SCAN-3:A clinical battery. Patients with mTBI had overall patterns of lower auditory cortex activation during the listening tasks as compared to normative controls. A significant lateralization pattern (pairwise t-test; p⟨0.05) was observed in normative controls and in those with mTBI and APD during single-side stimulation. Additionally, baseline connectivity between left and right auditory cortices was lower in mTBI patients than in controls (p=0.01) and significantly reduced in the mTBI with APD group (p=0.008). Correlation was also observed between bilateral task-related activation and competing words subscore of the SCAN-3:A. These findings suggest the passive listening task is well suited to probe auditory function in military personnel with an mTBI diagnosis. Further, the study supports the use of multiple approaches for detecting and assessing central auditory deficits to improve monitoring of short- and long-term outcomes.

Quantitative analysis tool for clinical functional MRI in mild traumatic brain injury.

Functional magnetic resonance imaging (fMRI) has been available commercially for clinical diagnostic use for many years. However, both clinical interpretation of fMRI by a neuroradiologist and quantitative analysis of fMRI data can require significant personnel resources that exceed reimbursement. In this report, a fully automated computer-based quantification methodology (Enumerated Auditory Response, EAR) has been developed to provide an auditory fMRI assessment of patients who have suffered a mild traumatic brain injury. Fifty-five study participants with interpretable auditory fMRI sequence data were assessed by EAR analysis, as well as both clinical radiologist fMRI interpretation and voxelwise general linear model (GLM) analysis. Comparison between the clinical interpretation and the two computer analysis methods resulted in 67% concordance (identical), 32% nearconcordance (one level difference), and 1% discordant. Comparison between the clinical computer-based quantification (EAR) and GLM analysis yielded significant correlations in right and left ear responses (p⟨0.05) for the full subject group. Automated fMRI quantification analysis equivalent to EAR might be appropriate for both future research projects with constrained resources, as well as possible routine clinical use.

Reference ranges and stability of auditory and vestibular measures in a comprehensive assessment battery for traumatic brain injury.

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.

Hidden hearing deficits in military service members with persistent post concussive symptoms.

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.