Results of the First Clinical Study in Humans That Combines Hyperbaric Oxygen Pretreatment with Autologous Peripheral Blood Stem Cell Transplantation.

Patients undergoing high-dose chemotherapy and autologous hematopoietic cell transplantation (auto-HCT) are at risk for multiple morbidities, including mucosal inflammation and neutropenic fever, both related to neutropenia. Evidence from our preclinical work in an umbilical cord blood (UCB) transplantation murine model suggests that treatment with hyperbaric oxygen (HBO) before UCB infusion improves UCB CD34+ cell engraftment by reducing erythropoietin levels. A pilot clinical trial using HBO in patients undergoing UCB transplantation showed improvement in kinetics of blood count recovery. In this study, we evaluated HBO in combination with auto-HCT. Our primary aim was to determine the safety of HBO in this setting and secondarily to determine its efficacy in reducing time to neutrophil and platelet engraftment compared with matched historic controls. Patients with multiple myeloma, non-Hodgkin lymphoma, and Hodgkin disease eligible for auto-HCT were included. On day 0, patients received HBO treatment consisting of exposure to 2.5 atmosphere absolutes for a total of 90 minutes, in a monoplace hyperbaric chamber, breathing 100% oxygen. Six hours after the start of HBO, peripherally mobilized stem/progenitor cells were infused and patients were followed daily for toxicity and blood count recovery. All patients received daily granulocyte colony-stimulating factor starting on day +5 and until absolute neutrophil count (ANC) of ≥1500 or ANC of 500 for 3 consecutive days. A matched historic cohort of 225 patients who received auto-HCT between January 2008 and December 2012 was chosen for comparison and matched on sex, age, conditioning regimen, and disease type. We screened 26 patients for this study; 20 were treated and included in the primary analysis, and 19 completed the HBO therapy and were included in the secondary analysis. Although the median time to neutrophil count recovery was 11 days in both the HBO and control cohorts, the Kaplan-Meier estimates of the full distributions indicate that the time to neutrophil recovery was generally about 1 day sooner for HBO versus historical controls (log-rank P = .005; range, 9 to 13 for HBO patients and 7 to 18 for controls). The median time to platelet count recovery was 16 days (range, 14 to 21) for HBO versus 18 days (range, 11 to 86) for controls (log-rank P < .0001). In the secondary analysis comparing the HBO cohort who completed HBO therapy (n = 19) with our historical cohort, we evaluated neutropenic fever, growth factor use, mucositis, day +100 disease responses, and blood product use. HBO was associated with less growth factor use (median 6 days in HBO cohort versus median 8 days in controls, P < .0001). Packed RBC and platelet transfusion requirements were not statistically different between the 2 cohorts. Mucositis incidence was significantly lower in the HBO cohort (26.3% in HBO cohort versus 64.2% in controls, P = .002). HBO therapy appears to be well tolerated in the setting of high-dose therapy and auto-HCT. Prospective studies are needed to confirm potential benefits of HBO with respect to earlier blood count recovery, reduced mucositis, and growth factor use, and a cost-benefit analysis is warranted. © 2019 American Society for Blood and Marrow Transplantation.

Long-term results of a pilot study evaluating hyperbaric oxygen therapy to improve umbilical cord blood engraftment.

Umbilical cord blood (UCB) transplantation is a promising option for hematopoietic stem cell transplantation in patients with hematologic malignancies who lack an HLA-matched sibling or well-matched unrelated donor; however, it has a higher incidence of delayed or failed engraftment because cell doses are low and bone marrow homing is inefficient. We have demonstrated that pre-treating irradiated immune-deficient mice with hyperbaric oxygen (HBO) prior to UCB CD34+ cell transplantation lowered host systemic erythropoietin (EPO) and improved UCB CD34+ cell homing and engraftment. These findings suggested that EPO-EPO-R signaling plays a role in UCB CD34+ homing and engraftment. In a pilot clinical trial, we showed that recipients of HBO therapy prior to UCB cell infusion had reduced systemic EPO, which was associated with improved kinetics of blood count recovery. Although early clinical outcomes at day 100 were encouraging, with improved overall survival, the long-term effects of HBO therapy on UCB-transplanted patients were not evaluated. In this study, we examined the long-term outcome of patients in our pilot study, compared with a historic control group, and correlated their clinical outcomes to serum EPO response to HBO. While 50% of HBO-treated patients received single UCB units, ~ 90% of the control patients received double UCB units. Although HBO patients had much better rates of survival at 6 months, their 1-year survival did not significantly differ from the control group. HBO-treated patients had on average lower relapse and non-relapse mortality rates, and less chronic graft versus host disease (GVHD), but had increased acute GVHD. However, these differences were not statistically significant, probably because of the small sample size. In the HBO-treated cohort, immune reconstitution analysis showed significant improvement in early B cell recovery, with a trend toward improvement in early NK cell recovery. When we evaluated the ratio of 8 h to baseline EPO levels, we found a non-significant trend toward lower EPO values in those who neither relapsed nor died by 1 year, compared to those who died or relapsed. This result suggests that EPO response to HBO may be associated with better outcomes. Disease progression-free survival was also improved in those who had more than 80% reduction in EPO levels in response to HBO. Our study highlights the long-term safety of HBO therapy when used prior to UCB transplantation. Future UCB transplant patients who receive HBO should have their serum EPO response measured, as it may be a marker of relapse/mortality.

Erythropoietin modulation is associated with improved homing and engraftment after umbilical cord blood transplantation.

Umbilical cord blood (UCB) engraftment is in part limited by graft cell dose, generally one log less than that of bone marrow (BM)/peripheral blood (PB) cell grafts. Strategies toward increasing hematopoietic stem/progenitor cell (HSPC) homing to BM have been assessed to improve UCB engraftment. Despite recent progress, a complete understanding of how HSPC homing and engraftment are regulated is still elusive. We provide evidence that blocking erythropoietin (EPO)-EPO receptor (R) signaling promotes homing to BM and early engraftment of UCB CD34+ cells. A significant population of UCB CD34+ HSPC expresses cell surface EPOR. Exposure of UCB CD34+ HSPC to EPO inhibits their migration and enhances erythroid differentiation. This migratory inhibitory effect was reversed by depleting EPOR expression on HSPC. Moreover, systemic reduction in EPO levels by hyperbaric oxygen (HBO) used in a preclinical mouse model and in a pilot clinical trial promoted homing of transplanted UCB CD34+ HSPC to BM. Such a systemic reduction of EPO in the host enhanced myeloid differentiation and improved BM homing of UCB CD34+ cells, an effect that was overcome with exogenous EPO administration. Of clinical relevance, HBO therapy before human UCB transplantation was well-tolerated and resulted in transient reduction in EPO with encouraging engraftment rates and kinetics. Our studies indicate that systemic reduction of EPO levels in the host or blocking EPO-EPOR signaling may be an effective strategy to improve BM homing and engraftment after allogeneic UCB transplantation. This clinical trial was registered at www.ClinicalTrials.gov (#NCT02099266).

Improved Knowledge, Attitudes, and Behaviors After Implementation of TeamSTEPPS Training in an Academic Emergency Department: A Pilot Report.

TeamSTEPPS is a validated, formal patient safety curriculum created by the Agency for Healthcare Research and Quality (AHRQ) for the development of high-functioning multidisciplinary teams. TeamSTEPPS was implemented in an academic emergency department (ED), including all ED hospital staff as well as physicians and residents. It was hypothesized that extensive interprofessional education combined with implementation of specific tools would increase knowledge of TeamSTEPPS principles, attitudes, and behaviors. The TeamSTEPPS knowledge test and the AHRQ Hospital Survey attitude test were administered at 0, 45, and 90 days after training. Behaviors were evaluated using an observation tool that was developed to document huddle occurrence. Knowledge and attitudes significantly improved 45 days from baseline (P < .05) and were sustained by day 90. In this pilot study, the implementation of TeamSTEPPS training in a multidisciplinary team in an academic ED led to increased knowledge and improved communication attitudes. Adoption of a specific behavior, the huddle, also was observed.

Effect of weather on medical patient volume at Kansas Speedway mass gatherings.

INTRODUCTION: Provision for the safety and health care of persons attending mass-gathering events presents unique challenges to organizers. This study was designed to determine the factors that contribute to patients seeking medical care during these events. METHODS: We performed a retrospective review of patient care records for visits that occurred during race weekends at the Kansas Speedway from April 2007 to October 2010. Data were collected regarding the overall gathering size of each event to calculate the number of patient encounters per 10,000 attendees. Patients' final disposition was determined to calculate the transfer-to-hospital rate per 10,000 attendees. Weather data, including temperature, humidity, and precipitation, were documented for each event. Negative binomial regression was used to test the relationship between weather factors and the rate of patient encounters. RESULTS: Twenty-two event days over 6 race weekends were evaluated, with a total of 1305 patients (58% male; mean age: 37 years), a mean patient encounter rate of 13 per 10,000 attendees, and a mean transfer-to-hospital rate of 0.24 per 10,000 attendees. Our regression model demonstrated that each 0.55°C (1°F) increase in daily mean temperature was associated with a 4% increase in the rate of total complaints (P = .03) and a 6% increase in major trauma presentations (P = .019). Major trauma events were 2.4 times more frequent at ambient temperatures >17.2°C (63°F) (P = .03). Each inch of precipitation was associated with a 61% decrease in total patient volume (P = .05). CONCLUSION: Weather factors significantly and predictably affect the use of medical services at the Kansas Speedway. Such data regarding mass-gathering events can be used for resource planning.

Pharmacist-acquired medication histories in a university hospital emergency department.

PURPOSE: A study was conducted to identify discrepancies between medication histories taken by emergency department (ED) providers (physicians, nurses, and medical students) and medication histories taken by clinical pharmacists. METHODS: During a three-month period, a clinical pharmacist was assigned to the ED in a 475-bed, tertiary care teaching facility that serves as a level I trauma center. On the arrival of a patient, ED providers completed a standard assessment that included the patient's medication history. Patients to be admitted through the ED were interviewed by the clinical pharmacist. In addition to a medication history, the pharmacist collected the patient's height, weight, immunization history, and allergy information. The medication history obtained by the ED provider was compared with the history obtained by the clinical pharmacist, and discrepancies were documented. RESULTS: The clinical pharmacists in the ED performed 286 medication histories; 34 were excluded. The remaining 252 histories taken were used in the study. The pharmacists identified 1096 home medications versus 817 home medications documented by ED providers. Of the 817 home medications documented by the ED, the regimens of 637 (78%) were incomplete and were supplemented with dosing information by the pharmacists. Pharmacists reported 375 medication allergies versus 350 reported by ED providers. Immunization histories were obtained in 252 of the 252 (100%) pharmacist-acquired medication histories versus 45 of the 252 (18%) acquired by ED personnel. CONCLUSION: Pharmacist-acquired medication histories in the ED were more complete than those acquired by other health professionals.