A proof-of-concept trial of HELIOX with different fractions of helium in a human study modeling upper airway obstruction.

BACKGROUND: Helium in oxygen (HELIOX) can relieve airway obstruction and lower the work of breathing because it increases the threshold at which turbulent gas flow is induced. Less turbulent and more laminar flow lowers the work of breathing. According to guidelines, the fraction of Helium in HELIOX should be maximized (e.g. to 79%). Here, we investigate whether HELIOX with less than 60% of Helium is able to relieve the sensation of dyspnea in healthy volunteers. METHODS: 44 volunteers underwent resistive loading breathing different gases (medical air and HELIOX with a fraction of 25%, 50% or 75% helium in oxygen) in a double-blinded crossover design. Subjects rated their degree of dyspnea (primary outcome parameter) and the variability of noninvasively measured systolic blood pressure was assessed. RESULTS: Dyspnea was significantly reduced by HELIOX-containing mixtures with a fraction of helium of 25% or more. Similarly, blood pressure variability was reduced significantly even with helium 25% during respiratory loading with the higher load, whereas with the smaller load an effect could only be obtained with the highest helium fraction of 75%. CONCLUSION: In this clinical trial, HELIOX with less than 60% of helium in oxygen decreased the sensation of dyspnea and blood pressure variability, a surrogate parameter for airway obstruction. Therefore, higher oxygen fractions might be applied without losing the helium-related benefits for the treatment of upper airway obstruction. TRIAL REGISTRATION: Registration with clinical trials (NCT00788788) and EMA (EudraCT number: 2006-005289-37).

Pharyngeal selective brain cooling is associated with reduced CNS cortical lesion after experimental traumatic brain injury in rats.

Therapeutic hypothermia (TH) is still being explored as a therapeutic option after traumatic brain injury (TBI) but clinical data has not supported its efficacy. Experimental approaches were promising, but clinical data did not support its efficacy in the treatment of TBI. A novel approach of pharyngeal selective brain cooling (pSBC), recently introduced by our group, has been accompanied by superior neurofunctional, sensorimotor, and cognitive outcomes. This work is now extended by data on histomorphological and physical outcomes after pSBC in a model of experimental TBI. Male Sprague-Dawley rats were subjected to lateral fluid-percussion (LFP) brain injury, and randomized to the following experimental groups: (1) TBI with pSBC, (2) TBI without pSBC, and (3) sham animals. On day post-injury (DPI) 14, the animals were sacrificed and their brains were harvested for immunohistochemistry using the following antibodies: (1) glial fibrillary acidic protein (GFAP), (2) neurofilament (NF), and (3) synaptophysin (SY). In pSBC animals brain temperature was selectively lowered to 33 ± 0.5°C within 15 min post-injury, and maintained for 180 min after induction, while keeping rectal temperatures at physiological levels. Animals that had undergone pSBC showed a significantly faster recovery of body weight starting on DPI 3, and had gained substantially more weight than TBI-only animals on DPI 14 (p < 0.001), indicating superior physical recovery. Areas of cortical damage were significantly smaller in pSBC animals compared to TBI-only animals (p < 0.01). pSBC was associated with preservation of cortical tissue ipsilateral to the lesion, and superior physical recovery after experimental TBI. These results complement earlier reports in which pSBC was associated with superior neurofunctional and cognitive outcomes using the same experimental model.

Job requirements compared to medical school education: differences between graduates from problem-based learning and conventional curricula.

BACKGROUND: Problem-based Learning (PBL) has been suggested as a key educational method of knowledge acquisition to improve medical education. We sought to evaluate the differences in medical school education between graduates from PBL-based and conventional curricula and to what extent these curricula fit job requirements. METHODS: Graduates from all German medical schools who graduated between 1996 and 2002 were eligible for this study. Graduates self-assessed nine competencies as required at their day-to-day work and as taught in medical school on a 6-point Likert scale. Results were compared between graduates from a PBL-based curriculum (University Witten/Herdecke) and conventional curricula. RESULTS: Three schools were excluded because of low response rates. Baseline demographics between graduates of the PBL-based curriculum (n = 101, 49% female) and the conventional curricula (n = 4720, 49% female) were similar. No major differences were observed regarding job requirements with priorities for "Independent learning/working" and "Practical medical skills". All competencies were rated to be better taught in PBL-based curriculum compared to the conventional curricula (all p < 0.001), except for "Medical knowledge" and "Research competence". Comparing competencies required at work and taught in medical school, PBL was associated with benefits in "Interdisciplinary thinking" (Delta + 0.88), "Independent learning/working" (Delta + 0.57), "Psycho-social competence" (Delta + 0.56), "Teamwork" (Delta + 0.39) and "Problem-solving skills" (Delta + 0.36), whereas "Research competence" (Delta--1.23) and "Business competence" (Delta--1.44) in the PBL-based curriculum needed improvement. CONCLUSION: Among medical graduates in Germany, PBL demonstrated benefits with regard to competencies which were highly required in the job of physicians. Research and business competence deserve closer attention in future curricular development.

Pharyngeal selective brain cooling improves neurofunctional and neurocognitive outcome after fluid percussion brain injury in rats.

Therapeutic hypothermia (TH) after cardiac arrest reduces mortality and improves neurological outcome. Experimental TH after traumatic brain injury (TBI) indicated similar effects, but benefits were not reproducible in large clinical trials. Therefore, a novel approach of pharyngeal selective brain cooling (pSBC) was tested in respect to neurological outcome in a model of experimental TBI. Male Sprague-Dawley rats were subjected to lateral fluid percussion (LFP) brain injury and received pSBC for 3h post-injury. All animals were examined for neuromotor and sensorimotor dysfunction and coordination: before and after injury, and during recovery on day post-injury (DPI) 7 and 14 using (i) the standardized Composite Neuroscore (NS) test and (ii) the Rotarod test. Recovery of cognitive function was assessed on days 10-14 using (iii) the Barnes Circular Maze (BCM). In pSBC-animals, brain temperature was selectively lowered to 33 +/- 0.5 degrees C at 15 min post-injury, keeping rectal temperature at a physiologic level. All animals subjected to TBI via LFP showed an identical pattern of severe neurofunctional impairment at 24 h after injury. In the time course of the experiment, pSBC-animals showed superior neurofunctional recovery on DPI 7 (p = 0.03) and 14 (p = 0.002). Similarly, distance, time, and maximum speed on the Rota-Rod were significantly increased in pSBC-animals on DPI 7 (p < 0.01) and 14 (p < 0.01), as well as latency, distance, and mean number of errors in the BCM on DPI 14 (p < 0.01). The novel approach of pSBC was associated with improved neuromotor, sensormotor, and neurocognitive outcome after experimental TBI.