Emerging Indications for Hyperbaric Oxygen Treatment: A Registry Cohort Study.

BACKGROUND: Hyperbaric oxygen (HBO2) treatment is used across a range of medical specialties for a variety of applications, particularly where hypoxia and inflammation are important contributors. HBO2 may be useful for new indications not currently approved by the Undersea and Hyperbaric Medical Society (UHMS) because of its hypoxia-relieving and anti-inflammatory effects. Identifying these new applications for HBO2 is difficult because individual centers may only treat a few cases and not track outcomes consistently. The web-based International Multicenter Registry for Hyperbaric Oxygen Therapy captures prospective outcomes data for patients treated with hyperbaric oxygen (HBO2) therapy. These data can then be used to identify new potential applications for HBO2, which has relevance for a range of medical specialties. OBJECTIVE: Although hyperbaric medicine has established indications, new ones continue to emerge. One objective of this registry study is to identify cases where HBO2 has been used for conditions falling outside of current UHMS-approved indications and present outcomes data for them. METHODS: This is a descriptive study based on a web-based, multi-center, international, registry of patients treated with HBO2. Centers agree to collect data on all patients treated using standard outcome measures and send deidentified data from individual centers to the central registry. HBO2 treatment programs in the United States, United Kingdom, and Australia participate. Demographic, outcome, complication, and treatment data, including pre- and post-treatment quality of life questionnaires (EQ-5D-5L) are collected on individuals referred for HBO2 treatment. RESULTS: Out of 9726 patient entries, 378 individuals were treated for 45 emerging indications. Post-acute sequelae of COVID (PASC) (149/378 40%), ulcerative colitis (47/378 12.4%), and Crohn's disease (40/378 11%), accounted for 62% of total cases. Calciphylaxis (20/378 5.3%), frostbite (18/378 4.8%), and peripheral-vascular-disease related wounds (12/378 3.2%) accounted for a further 13.2%. PASC patients reported significant improvement on the Neurobehavioral Symptom Inventory (NSI pre 30.6, NSI post 14.4, p<0.001). Crohn's disease patients reported significantly improved quality of life (EQ-5D pre 53.8, post 68.8) and 5 reported closing a fistula. Ulcerative colitis patients showed strong trends toward improved quality of life and lower reported lower scores on a bowel questionnaire examining frequency, blood, pain, and urgency. A subset of calciphylaxis and arterial ulcer patients also reported improvement. CONCLUSIONS: HBO2 is being used for a wide range of possible applications across various medical specialties for its hypoxia-relieving and anti-inflammatory effects. Results show statistically significant improvements in patient-reported outcomes for inflammatory bowel disease and PASC. HBO2 is also being used for frostbite, pyoderma gangrenosum, pterygium, hypospadias repair, and facial filler procedures. Other indications show evidence for improvement and the case series for all indications is growing in the registry. CLINICALTRIAL: Derr1-10.2196/18857. INTERNATIONAL REGISTERED REPORT: RR2-10.2196/18857.

International Multicenter Registry for Hyperbaric Oxygen Therapy: Results through June 2021.

Introduction: The International Multicenter Registry for Hyperbaric Oxygen Therapy (International Report Registered Identifier DERR1-10.2196/18857) was established in 2011 to capture outcomes and complications data for both Undersea and Hyperbaric Medical Society (UHMS) approved and selected unapproved hyperbaric oxygen (HBO2) therapy indications. Methods: A Research Electronic Data Capture (REDCap) template was designed and distributed to all participating centers for prospective data collection. Centers contributed de-identified demographic, treatment, complications, and outcome data. This report provides summary data on sites and enrollment, as well as pre- and post-treatment data on quality of life (EQ-5D-5L questionnaire), head and neck radiationoutcomes, non-healing wounds (Strauss score), and idiopathic sudden sensorineural hearing loss. Data were analyzed mainly using the Wilcoxon signed-rank test. Results: Twenty-two centers contributed data for 2,880 patients. The most common UHMS-approved indication was delayed radiation injury, followed by enhancement of wound healing, and carbon monoxide poisoning. One hundred and twenty-five patients were treated for non-UHMS approved indications. Quality of life, head and neck radiation symptoms, Strauss wound scores, and hearing were significantly improved after HBO2. Complication rates were low and comparable to previous reports. The registry also offered the ability to analyze factors that affect outcomes, such as smoking and severity of hearing loss. Discussion: The registry accrues prospective data on defined outcomes from multiple centers and allows for analysis of factors affecting outcomes. This registry does not have a control group, which is a limitation. Nevertheless, the registry provides a unique, comprehensive dataset on HBO2 outcomes from multiple centers internationally.

Development of an International, Multicenter, Hyperbaric Oxygen Treatment Registry and Research Consortium: Protocol for Outcome Data Collection and Analysis.

BACKGROUND: Hyperbaric oxygen (HBO2)-oxygen at pressures higher than atmospheric-is approved for 14 indications by the Undersea and Hyperbaric Medical Society. HBO2's main effect is to increase oxygen content in plasma and body tissues, which can counteract hypoxia or ischemia. Laboratory studies show that HBO2 has effects beyond relieving hypoxia (eg, promoting angiogenesis in irradiated tissue, anti-inflammatory effects, radiosensitization of tumors, hypoxia preconditioning, and fungal growth inhibition) and has potential to treat conditions such as inflammatory bowel disease and pyoderma gangrenosum. Lack of consistently collected outcome data on a large cohort of individuals receiving HBO2 therapy limits its use for both established and new indications. A course of therapy often involves 30-40 visits to a hyperbaric chamber, so the number of patients seen at any given center is constrained by chamber capacity. As a result, published HBO2 outcome data tend to be from small case series because few patients with a particular condition are treated at a given center. To solve this problem, a registry that collects and pools data systematically from multiple institutions has been established. OBJECTIVE: The aim of this study is to collect consistent outcome data across multiple hyperbaric centers to assess treatment effectiveness and establish a research consortium. METHODS: A consortium of hyperbaric centers who have agreed to collect consistent outcome data on all patients seen has been assembled. Data are collected at each participating center using Research Electronic Data Capture (REDCap), a web-based, data collection system used frequently for research. Standard outcome measures have been defined for each condition, which are programmed into the REDCap data collection templates. Governance is through a consortium agreement that defines data security, data sharing, publications, liability, and other issues. Centers obtain Institutional Review Board (IRB) and ethics approval to participate, either from their own institutions or by relying on the IRB at the coordinating center at Dartmouth College. Dissemination will occur through a yearly report and by publications based on the data in the registry. RESULTS: Early results from some common indications show significant pretreatment to posttreatment changes. Additional indications and outcome measures are being added using the procedures outlined in the consortium agreement. CONCLUSIONS: The registry collects consistent outcome information for a therapy that needs further study and a stronger evidence base. It also overcomes the challenge of collecting data from an adequate number of patients for both established and emerging indications by combining data collection from multiple centers. The data entry requirements should be within the capabilities of existing staff at any given hyperbaric center. By using REDCap, the registry can be expanded to include detailed information on particular indications and long-term follow-up on selected patients without significantly increasing the basic data entry requirements. Through the registry, a network of enrolled hyperbaric centers has been established that provides the basis for a clinical trial network. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18857.

Hyperbaric oxygen therapy is well tolerated and effective for ulcerative colitis patients hospitalized for moderate-severe flares: a phase 2A pilot multi-center, randomized, double-blind, sham-controlled trial.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) markedly increases tissue oxygen delivery. Case series suggest it may have a potential therapeutic benefit in ulcerative colitis (UC). We investigated the therapeutic potential of HBOT as an adjunct to steroids for UC flares requiring hospitalization. METHODS: The study was terminated early due to poor recruitment with 18 of the planned 70 patients enrolled. UC patients hospitalized for moderate-severe flares (Mayo score ≥6, endoscopic sub-score ≥2) were block randomized to steroids + daily HBOT (n = 10) or steroids + daily sham hyperbaric air (n = 8). Patients were blinded to study assignment, and assessments were performed by a blinded gastroenterologist. Primary outcome was the clinical remission rate at study day 5 (partial Mayo score ≤2 with no sub-score >1). Key secondary outcomes were: clinical response (reduction in partial Mayo score ≥2, rectal bleeding sub-score of 0-1) and progression to second-line therapy (colectomy or biologic therapy) during the hospitalization. RESULTS: A significantly higher proportion of HBOT-treated patients achieved clinical remission at study day 5 and 10 (50 vs. 0%, p = 0.04). HBOT-treated patients less often required progression to second-line therapy during the hospitalization (10 vs. 63%, p = 0.04). The proportion requiring in-hospital colectomy specifically as second-line therapy for medically refractory UC was lower in the HBOT group compared to sham (0 vs. 38%, p = 0.07). There were no serious adverse events. CONCLUSION: In this small, proof-of-concept, phase 2A trial, the use of HBOT as an adjunctive therapy to steroids for UC patients hospitalized for moderate-severe flares resulted in higher rates of clinical remission, and a reduction in rates of progression to second-line therapy during the hospitalization. Larger well-powered trials are needed, however, to provided definitive evidence of therapeutic benefit.

Hyperbaric oxygen for patients with above-knee amputations, persistent ischemia, and nonreconstructable vascular disease.

We describe four patients with above-knee amputations whose stump wounds failed to heal. After numerous revascularization attempts, these patients were diagnosed with nonreconstructable pelvic and groin vascular disease and were facing hip disarticulation. With the addition of hyperbaric oxygen treatment to vigilant wound care and negative pressure therapy, these patients healed their amputation stumps and were fit with prostheses. At their most recent follow-up, all patients were ambulating and using their prostheses.

Unusual neurological syndrome induced by atmospheric pressure change.

BACKGROUND: We describe a case of a 46-yr-old female who developed hypertension, tachycardia, dysarthria, and leg weakness provoked by pressure changes associated with flying. Typically during the landing phase of flight, she would feel dizzy and note that she had difficulty with speech and leg weakness. After the flight the leg weakness persisted for several days. The symptoms were mitigated when she took a combined alpha-beta blocker (labetalol) prior to the flight. CASE STUDY: To determine if these symptoms were related to atmospheric pressure change, she was referred for testing in a hyperbaric chamber. She was exposed to elevated atmospheric pressure (maximum 1.2 ATA) while her heart rate and blood pressure were monitored. Within 1 min she developed tachycardia and hypertension. She also quickly developed slurred speech, left arm and leg weakness, and sensory changes in her left leg. She was returned to sea level pressure and her symptoms gradually improved. A full neurological workup has revealed no explanation for these findings. She has no air collections, cysts, or other anatomic findings that could be sensitive to atmospheric pressure change. DISCUSSION: The pattern is most consistent with a vascular event stimulated by altitude exposure. This case suggests that atmospheric pressure change can produce neurological symptoms, although the mechanism is unknown.

Impact of a hospital-wide hand hygiene initiative on healthcare-associated infections: results of an interrupted time series.

BACKGROUND: Evidence that hand hygiene (HH) reduces healthcare-associated infections has been available for almost two centuries. Yet HH compliance among healthcare professionals continues to be low, and most efforts to improve it have failed. OBJECTIVE: To improve healthcare workers' HH, and reduce healthcare-associated infections. DESIGN: 3-year interrupted time series with multiple sequential interventions and 1-year post-intervention follow-up. SETTING: Teaching hospital in rural New Hampshire. INTERVENTIONS: In five categories: (1) leadership/accountability; (2) measurement/feedback; (3) hand sanitiser availability; (4) education/training; and (5) marketing/communication. MEASUREMENT: Monthly changes in observed HH compliance (%) and rates of healthcare-associated infection (including Staphylococcus aureus infections, Clostridium difficile infections and bloodstream infections) per 1000 inpatient days. The subset of S aureus infections attributable to the operating room served as a tracer condition. We used statistical process control charts to identify significant changes. RESULTS: HH compliance increased significantly from 41% to 87% (p<0.01) during the initiative, and improved further to 91% (p<0.01) the following year. Nurses achieved higher HH compliance (93%) than physicians (78%). There was a significant, sustained decline in the healthcare-associated infection rate from 4.8 to 3.3 (p<0.01) per 1000 inpatient days. The rate of S aureus infections attributable to the operating room rose, while the rate of other S aureus infections fell. CONCLUSIONS: Our initiative was associated with a large and significant hospital-wide improvement in HH which was sustained through the following year and a significant, sustained reduction in the incidence of healthcare-associated infection. The observed increased incidence of the tracer condition supports the assertion that HH improvement contributed to infection reduction. Persistent variation in HH performance among different groups requires further study.