Test In Healthy Volunteers Research Articles

Evaluation of Different Near-Infrared Spectroscopy Devices for Assessing Tissue Oxygenation with a Vascular Occlusion Test in Healthy Volunteers

Near-infrared spectroscopy devices can measure peripheral tissue oxygen saturation (StO₂). This study aims to compare StO₂ using INVOS® and different O3™ settings (O3^25:75 and O3^30:70). Twenty adults were recruited. INVOS® and O3™ probes were placed simultaneously on 1 side of forearm. After baseline measurement, the vascular occlusion test was initiated. The baseline value, rate of deoxygenation and reoxygenation, minimum and peak StO₂, and time from cuff release to peak value were measured. The parameters were compared using ANOVA and Kruskal-Wallis tests. Bonferroni’s correction and Mann-Whitney pairwise comparison were used for post hoc analysis. The agreement between StO₂ of devices was evaluated using Bland-Altman plots. INVOS® baseline value was higher (79.7 ± 6.4%) than that of O3^25:75 and O3^30:70 (62.4 ± 6.0% and 63.7 ± 5.5%, respectively, p < 0.001). The deoxygenation rate was higher with INVOS® (10.6 ± 2.1%/min) than with O3^25:75 and O3^30:70 (8.4 ± 2.2%/min, p = 0.006 and 7.5 ± 2.1%/min, p < 0.001). The minimum and peak StO₂ were higher with INVOS®. No significant difference in the reoxygenation rate was found between the devices and settings. The time to reach peak after cuff deflation was faster with INVOS® (both p < 0.001). Other parameters were similar. There were no differences between the different O3™ settings. There were differences in StO₂ measurements between the devices, and these devices should not be interchanged. Differences were not observed between O3™ device settings.

Brain functional connectivity during storage based on resting state functional magnetic resonance imaging with synchronous urodynamic testing in healthy volunteers.

The aim of the study was to elucidate the correlation between spatially distinct brain areas with a full bladder from the perspective of functional connectivity using resting-state functional magnetic resonance imaging (rs-fMRI) with simultaneous urodynamic testing in healthy volunteers. The brain regions with full and empty bladders were reported via rs-fMRI using a 3T magnetic resonance system. Then, we identified brain regions that are activated during bladder filling by calculating the amplitude of low-frequency fluctuation (ALFF) values using brain imaging software (DPABI and SPM8) and empirically derived six regions of interest (ROI) from analysis of activation were used as seeds for resting-state functional connectivity (rs-FC) analysis with the rest of the brain to examine differences in the two conditions. Statistical analysis was performed with a paired t-test and statistical significance was defined as a P < 0.01. Twenty-two healthy volunteers (11 men and 11 women) 35-64years of age were enrolled. The rs-fMRI scans of 22 healthy volunteers were analyzed. After motion correction, two subjects were excluded. Meaningful data were obtained on 20 of these subjects. Compared with an empty bladder, functional connection enhancement was noted mainly in the right inferior orbitofrontal cortex and bilateral calcarine gyrus, the left lingual gyrus, left fusiform gyrus, left superior occipital gyrus, right insula, right inferior temporal gyrus, superior parietal lobe, left insula, right lingual gyrus, right fusiform gyrus, left parahippocampal gyrus, right inferior temporal gyrus, superior parietal lobe, left calcarine gyrus, bilateral lingual gyrus, prefrontal cortex, including the middle frontal gyrus and superior frontal gyrus, the right middle temporal gyrus, bilateral posterior cingulate cortex, and right precuneus. The decrease in functional connection was mainly located in the right inferior orbitofrontal cortex, prefrontal cortex, including the superior frontal gyrus, orbitofrontal cortex, and anterior cingulate cortex, the left inferior orbitofrontal cortex, right insula, middle occipital gyrus, angular gyrus, inferior frontal gyrus, right insula, middle temporal gyrus, inferior parietal lobe, middle occipital gyrus, supplementary motor area, superior frontal gyrus, left insula, bilateral posterior cingulate cortex, bilateral precuneus, middle occipital gyrus, and right middle temporal lobe. There were significant changes in the functional connectivity of the brain between full and empty bladders in healthy volunteers, which suggests that the central neural processes involved in storage needs brain areas with integrated control. These findings are strong evidence for physicians to consider brain responses in urine storage and offer the provision of some normative data.

The reliability of inspiratory resistive load magnitude and detection testing

ObjectivesTo assess the test-retest reliability of inspiratory load detection and load magnitude perception tests in healthy volunteers. DesignCohort of convenience. SettingRespiratory physiology laboratory. ParticipantsTwenty healthy adults. InterventionsOn two separate occasions participants performed tests of inspiratory loading. Participants breathed through custom made resistive tubing and were asked to indicate when they detected a different resistance during inspiration. In a second test participants rated the magnitude of presented inspiratory loads using the modified Borg score. Main Outcome MeasuresIntra-class Correlation Coefficient (ICC2,1) values for repeated tests of inspiratory load detection threshold and load magnitude rating. ResultsICC2,1 values ranged from 0.657–0.786 for load detection testing and 0.739 to 0.969 for rating of load magnitude. ConclusionsThe tests are simple and reliable measures of inspiratory load detection and magnitude rating. They can be used in future research to determine the effectiveness of interventions to reduce the effort of breathing in health and disease.

Hypothalamic-Pituitary-Adrenal Axis Recovery Following the 1-mg Overnight Dexamethasone Suppression Test in Healthy Volunteers.

BackgroundThe recovery of hypothalamic-pituitary-adrenal (HPA) axis suppression following pharmacological doses of various steroids has been studied previously. However, no study has been conducted using the more commonly used 1-mg dexamethasone in the overnight dexamethasone suppression test (ODST). Hence, we aimed at evaluating HPA axis recovery after the 1-mg ODST.ObjectivesThis study aimed at investigating the pattern and time of recovery of the HPA axis following the 1-mg ODST in healthy subjects.MethodsTen healthy volunteers aged 18 - 40 years, BMI < 30 kg/m2, with neither exposure to steroids nor interfering drugs were included. The 1-mg ODST was performed, and the adrenocorticotropic hormone (ACTH) and cortisol samples were withdrawn at regular intervals. The serum cortisol of < 1.8 µg/dL was considered as HPA axis suppression, whereas the cortisol value equal to or more than baseline was deemed as recovery.ResultsCortisol and ACTH levels were suppressed in all subjects 9 hours following the 1-mg ODST. Although ACTH showed an early increase after 8 hours, the upsurge was noticed following 24 hours (mean ± SD, 34.42 ± 18 pg/mL). Later, cortisol accompanied ACTH, and both reached their baseline after 72 hours (mean ± SD, ACTH, 37.48 ± 12.44 pg/mL; cortisol, 8.45 ± 3.32 μg/dL). A small dip in ACTH and cortisol (mean ACTH, 23.84 pg/mL; mean cortisol, 2.3 μg/dL) was observed after 24 - 36 hours indicating the return of the diurnal rhythm before complete recovery.ConclusionsThe complete recovery of the HPA axis occurs only 72 hours following the 1-mg ODST. ACTH begins to recover as early as 8 hours after the maximal suppression and diurnal rhythm of ACTH and cortisol resume 24 to 36 hours later.

FUNCTIONAL ACTIVITY OF THE MUSCARINIC POSITIVE ALLOSTERIC MODULATOR VU319 DURING A PHASE 1 SINGLE ASCENDING DOSE STUDY

Introduction The development of neurotransmitter based cognitive enhancers for Alzheimer's disease have focused recently on allosteric modulation, as a way of reducing potential drug-limiting toxicities that have been the hallmark of earlier orthosteric compounds. VU319 is an investigational positive allosteric modulator of the M1 muscarinic acetylcholine receptor that has recently finished initial testing in healthy volunteers. Cognitive tasks and event-related potentials (ERPs) have been used during the randomized, double-blind, placebo controlled Single Ascending Dose (SAD) study of VU319. This presentation includes both data from the initial SAD study, and the Food Effect substudy. The main pharmacodynamic objectives of the SAD were to identify early markers of functional engagement. Following the ascending dose cohorts, a Food Effect substudy was conducted to assess whether there was any change in the cognitive performance if VU319 was dosed with food compared to in a fasted state. Methods VU319 was given orally to 52 healthy volunteers aged 18-55?years. The SAD study tested 40 participants in five dose escalating cohorts of eight participants, in which six received VU319 and two received placebo. The Food Effect substudy consisted of 12 participants, in which ten received oral VU319 and two received placebo. The five doses for the SAD study were 60, 120, 240, 400 and 600mg. Participants in the Food Effect substudy received VU319 at a single dose of 120mg. For the 5 cohorts of the SAD study, all participants were dosed in a fasted stated. In contrast, all 12 participants in the Food Effect substudy completed were dosed twice; once fasted, and once following breakfast. Cognitive and electrophysiological tasks were examined pre-dosing and at 5?hours post-dose. The tasks were selected for their sensitivity to cholinergic tone. Cognitive tasks tested spatial and sustained attention, episodic and working memory, perceptual vigilance and psychomotor speed. Recorded ERP examined auditory and visual discrimination using oddball tasks, and an incidental memory task in which participants passively observed novel and repeated complex images. Results The analysis showed a trend for improvements in cognitive and ERP performance on the higher doses of VU319 compared to placebo. Participants on the highest dose of VU319 responded significantly faster to targets on the continuous performance test compared to participants on placebo (p = 0.03, effect size d = 1.2). Additionally, on the incidental memory task, participants who received the higher two doses of VU319 exhibited larger P300 amplitudes compared to placebo, when present with repeated compared to novel images (d > 0.8). Examination of the relationship between plasma levels of VU319 and cognitive performance showed that the response time on the continuous performance task decreased in relation to increasing concentration of VU319 in the bloodstream. Conclusions We conclude that these results demonstrate potential enhancement of the cholinergic system functioning in healthy adults following a single dose of VU319. These results provide an indication of the potential measures that are sensitive to cognitive activity by VU319 and therefore provide a potential framework to examine the cognitive impact of multiple doses of VU319 in AD patients. This research was funded by: This work was supported by the following grants: VKC Hobbs Discovery Grant 4-04-218-9745, Alzheimer's Association PCTR-16-383171; NICHD U54 HD083211, NCATS UL1 TR000445, 2RO1MH082867, R01MH073676, R01MH86601, MH087965, MH093366.

Age-related cardiovascular response to tilt test in healthy volunteers of both sexes

This study aimed to assess the age-related changes in the cardiovascular response to tilt test in 90 healthy individuals of both sexes (age range: 18-60 years). Tilting was done at 600 for 10 min using a motorized tilt table. The blood pressure was recorded by a sphygmomanometer. The heart rate and peripheral capillary oxygen saturation were measured by a pulse oximeter. In males, significantly lesser changes in the systolic, diastolic and mean arterial pressure were observed in the old age (47-60 years) than the young (18-32 years) and middle age (33-46 years) groups. Significantly lesser responses in the heart rate and systolic blood pressure change were observed in the old age females compared to young age after tilting. The rise of diastolic blood pressure after tilting was lesser in the old age female compared to both young and middle-age females. In conclusion, the aging process is associated with attenuated cardiovascular response to tilt test in both males and females.

The vascular occlusion test using multispectral imaging: a validation study

Multispectral imaging (MSI) is a new, non-invasive method to continuously measure oxygenation and microcirculatory perfusion, but has limitedly been validated in healthy volunteers. The present study aimed to validate the potential of multispectral imaging in the detection of microcirculatory perfusion disturbances during a vascular occlusion test (VOT). Two consecutive VOT's were performed on healthy volunteers and tissue oxygenation was measured with MSI and near-infrared spectroscopy (NIRS). Correlations between the rate of desaturation, recovery and the hyperemic area under the curve (AUC) measured by MSI and NIRS were calculated. Fifty-eight volunteers were included. The MSI oxygenation curves showed identifiable components of the VOT, including a desaturation and recovery slope and hyperemic area under the curve, similar to those measured with NIRS. The correlation between the rate of desaturation measured by MSI and NIRS was moderate: r = 0.42 (p = 0.001) for the first and r = 0.41 (p = 0.002) for the second test. Our results suggest that non-contact multispectral imaging is able to measure changes in regional oxygenation and deoxygenation during a vascular occlusion test in healthy volunteers. When compared to measurements with NIRS, correlation of results was moderate to weak, most likely reflecting differences in physiology of the regions of interest and measurement technique.

Effects of omega-3 on thyroid function tests in healthy volunteers

Supplements play a pivotal role in medicine especially fish consumption or supplementation with omega 3. Omega-3 and thyroid hormones are important in keeping some essential body functions working normally and alterations of thyroid hormones levels can result in many pathological states. Our study aimed to investigate whether omega-3 supplementation (1000 mg/day for 2 months given orally) would affect thyroid hormones and thyroid-stimulating hormone in healthy volunteers with normal thyroid status. Normal thyroid status of the experimental group was well defined by serum levels of triiodothyronine (T3), thyroxine (T4), and by thyroid-stimulating hormone. Thyroid hormones (T3 and T4) levels were increased insignificantly in treated volunteers compared to the same volunteers before consumption of omega-3 (2.20 ± 0.37 to 2.23 ± 0.39 and 89.87 ± 9.93 to 90.98 ± 11.85 nmol/L, respectively). On the other hand, thyroid-stimulating hormone significantly increased after 2 months of omega-3 consumption (1.46 ± 0.47 to 1.68 ± 0.39 μIu/L). In conclusion, supplementation of omega-3 in the present study did not significantly modify either T3 or T4 and bodyweight in healthy volunteers. These data reinforce recommendations that indicate consumption of omega-3 is considered safe as far as thyroid function is concerned in healthy human volunteers. These findings advocate continued investigation of omega-3 for more than 2 months and higher dose to confirm its safety.

Effects of Intravenous GSK3858279 on a Battery of Evoked Pain Tests in Healthy Volunteers

Effects of Intravenous GSK3858279 on a Battery of Evoked Pain Tests in Healthy Volunteers

Cerebral blood flow changes during tilt table testing in healthy volunteers, as assessed by Doppler imaging of the carotid and vertebral arteries

ObjectivesUsing different techniques, reduction of cerebral blood flow (CBF) during orthostatic stress were demonstrated. One study reported flow reduction of the right internal carotid (ICA) and vertebral (VA) artery during orthostatic stress by Doppler imaging, with different effects on the 2 vessels. Global CBF changes, using this technique, have not been reported. Therefore, flow of the ICA, VA and global CBF were measured during head-up tilt testing. Methods33 healthy volunteers underwent tilt testing. At three time points (supine, half way and at the end of the test) Doppler imaging of the ICA and VA was performed, as well as PetCO2 measurements. ResultsGlobal CBF was significantly reduced by 4.5 ± 2.8% halfway the test and by 6.0 ± 3.4% at the end. All 4 artery flows were significantly reduced during the tilt, without differences between them. Despite small changes in PetCO2 there was a significant relation between de CBF decrease and PetCO2 decrease (p < 0.05). ConclusionsOrthostatic stress in HV results in a small but significant reduction of CBF by a homogenous reduction in the four cerebral vessels and is modulated by PetCO2 changes. SignificanceCBF changes can be measured during tilt testing using Doppler VA and ICA imaging.

EEG indices correlate with sustained attention performance in patients affected by diffuse axonal injury.

The aim of this study is to assess the ability of EEG-based indices in providing relevant information about cognitive engagement level during the execution of a clinical sustained attention (SA) test in healthy volunteers and DAI (diffused axonal injury)-affected patients. We computed three continuous power-based engagement indices (P β /P α , 1/P α , and P β / (P α + P θ )) from EEG recordings in a control group (n=7) and seven DAI-affected patients executing a 10-min Conners' "not-X" continuous performance test (CPT). A correlation analysis was performed in order to investigate the existence of relations between the EEG metrics and behavioral parameters in both the populations. P β /P α and 1/P α indices were found to be correlated with reaction times in both groups while P β / (P α + P θ ) and P β /P α also correlated with the errors rate for DAI patients. In line with previous studies, time course fluctuations revealed a first strong decrease of attention after 2min from the beginning of the test and a final fading at the end. Our results provide evidence that EEG-derived indices extraction and evaluation during SA tasks are helpful in the assessment of attention level in healthy subjects and DAI patients, offering motivations for including EEG monitoring in cognitive rehabilitation practice. Graphical abstract Three EEG-derived indices were computed from four electrodes montages in a population of seven healthy volunteers and a group of seven DAI-affected patients. Results show a significant correlation between the time course of the indices and behavioral parameters, thus demonstrating their usefulness in monitoring mental engagement level during a sustained attention task.

Comparison of functional ramp walk test and 6-min walk test in healthy volunteers: A new approach in functional capacity evaluation

Objective: Inclined surfaces or ramps are the common obstacles faced by elderly and cardiopulmonary disabled in accessing public amenities. Ramp walking is one of the most common functional demands to be met by a common man in the industrialized world. To assess the functional (uphill walking) capacity, we need a different functional stress test over the routinely used 6-min walk test (6MWT). Hence, a new 3-min steep ramp walk test (3MRWT) was constructed to meet the demands similar to an uphill walk and to provide more functional stress than routinely used 6MWT. Methodology: The observational, crossover study design was adopted for this study. Fifteen healthy participants (8 males, 7 females) performed both tests in a randomized order with a washout time of 6 h in between the tests. Walking distance to both ramp and ground, heart rate, blood pressure, saturation (SpO2), dyspnea, and fatigue with Borg exertion scale were compared prior and after the two walk tests. Results: The average distances covered in 6MWT were 510.5 ± 55.06 and 440.65 ± 25.08 meters and in 3MRWT were 270.18 ± 30.8, 230.05 ± 15.06 meters for male and female respectively. The difference between 3MRWT and 6MWT distances covered by the participants was statistically significant (t = 0.893). The mean difference between the heart rate, saturation and perceptions were highly significant (P < 0.001). Conclusion: The study results show that 3MRWT is valid over routinely administered 6MWT and may provide greater functional stress (uphill or ramp walk capacity) in a shorter duration in healthy individuals in assessing the maximal functional capacity in a ramp or uphill walking.

Consideration on the Accuracy of Watch for Physical Activity Tracker

Background: Obesity is one of the biggest drivers of preventable chronic diseases and healthcare costs in Worldwide. The most difficult aspect to take under consideration on the developing algorithms able to value the single session of kcal consumption in a single session of training are the hormonal factors. Objective: In this study we done a preliminary study on the comparison of two different watch (that provide an estimate of kilocalories consumed with and without heart rate monitor) with an indirect calorimetry device. The aim of this study was to understand if the watch could be considered for health use and the variable that can influence the valuation accuracy of the kcal consumption during a training session on gym. Methods: In this preliminary study we analyzed the indicators that influence the daily energy expenditure and possible device able to track it, considering possible limits of application. Therefore, we analyzed the critical issue emerged to track each indicator. Results: From this preliminary study was possible to show that the accuracy of the device could have important difference case by case. More information have to be done to the customer to understand the accuracy of the different device able to detect the kcal consumption because it can modify the diet of not professional people. We had problem with the synchronization of health rate monitor and the watch with Bluetooth mode in room with computer or a lot of IT equipment. Discussion: This preliminary study showed that could be more vital signals to take under consideration developing algorithm for the daily kcal consumption. More study are need to understand way we have a difference of accuracy during a reliable test in healthy volunteers. Metabolism aspect could be taken under consideration starting from consideration related on weight and high of subject. Conclusion: The conclusion was not permitted to have the algorithm used to detect the kcal consumption so we did some preliminary test. From as analysis we show a not constant accuracy for the watch 1 and watch 2 vs. the indirect calorimetry. This suggest that some more variable have to be taken under consideration in developing of device, as suggested from the literature.

Short-term effect of dark chocolate consumption on routine haemostasis testing

This experimental study was designed to investigate the sort-term impact of dark chocolate ingestion on routine haemostasis tests in healthy volunteers. The study population consisted in 15 healthy male volunteers who ingested 50 g of 90% cocoa chocolate within 3–5 min. Blood was drawn early in the morning, immediately before chocolate ingestion and 4 h afterwards, for assessment of activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrinogen. A significant increase of triglycerides (1.4 ± 0.6 versus 1.0 ± 0.5 mmol/L; p < .001), APTT (32.1 ± 2.2 versus 31.1 ± 2.0 s; p < .001) and PT (9.8 ± 0.5 versus 9.7 ± 0.4 s; p = .008) was observed 4 h after ingestion of dark chocolate, whereas fibrinogen values remained unchanged (2.6 ± 0.5 versus 2.5 ± 0.5 g/L; p = .063). Overall, we observed a mean percentage increase of 3.1% for APTT and 1.2% for PT. These results suggest that dark chocolate intake may have an impact on secondary haemostasis.

Paracetamol sharpens reflection and spatial memory: a double-blind randomized controlled study in healthy volunteers.

BackgroundAcetaminophen (APAP, paracetamol) mechanism for analgesic and antipyretic outcomes has been largely addressed, but APAP action on cognitive function has not been studied in humans. Animal studies have suggested an improved cognitive performance but the link with analgesic and antipyretic modes of action is incomplete. This study aims at exploring cognitive tests in healthy volunteers in the context of antinociception and temperature regulation. A double-blind randomized controlled study (NCT01390467) was carried out from May 30, 2011 to July 12, 2011.MethodsForty healthy volunteers were included and analyzed. Nociceptive thresholds, core temperature (body temperature), and a battery of cognitive tests were recorded before and after oral APAP (2 g) or placebo: Information sampling task for predecisional processing, Stockings of Cambridge for spatial memory, reaction time, delayed matching of sample, and pattern recognition memory tests. Analysis of variance for repeated measures adapted to crossover design was performed and a two-tailed type I error was fixed at 5%.ResultsAPAP improved information sampling task (diminution of the number of errors, latency to open boxes, and increased number of opened boxes; all P<0.05). Spatial planning and working memory initial thinking time were decreased (P=0.04). All other tests were not modified by APAP. APAP had an antinociceptive effect (P<0.01) and body temperature did not change.ConclusionThis study shows for the first time that APAP sharpens decision making and planning strategy in healthy volunteers and that cognitive performance and antinociception are independent of APAP effect on thermogenesis. We suggest that cognitive performance mirrors the analgesic rather than thermic cascade of events, with possibly a central role for serotonergic and cannabinoid systems that need to be explored further in the context of pain and cognition.

PRM4 - A Review Evaluating the Validity of Motion-Based Gaming Platforms to Measure Clinical Outcomes in Clinical Research

OBJECTIVES: Motion-based video game platforms provide the capability to track 3D body movements and may offer a versatile, easy to use and low-cost approach to measuring objective clinical outcomes. We reviewed published validation studies comparing clinical outcomes derived from video game platforms to gold-standard approaches. METHODS: We categorized studies in our review into three areas of application and summarized validation findings. We confined our review to studies using the Microsoft Kinect platform due to the volume of work in this area. RESULTS: Gait and balance: Five validation studies reported varied findings. One study in MS reported good correlation of most parameters with ClinROs; and a second study reported good validation of walk test parameters in Stroke patients. A treadmill test in healthy volunteers found Kinect underestimated joint flexion and over-estimated extension; and a further study was able to detect gait disturbances in MS during a speed-walking test compared to healthy volunteers although correlation to clinician assessment was modest (r=0.447). Kinect use during a battery of balance and dexterity tests in PD accurately measured the timing (ICCs: 0.940- 0.999) and gross spatial characteristics of clinically relevant movements, but spatial accuracy for smaller movements, such as toe tapping (ICC = 0.038), was poor. Upper extremity movement: Eight studies reported good validity in measurement of shoulder range of motion (r’s > 0.8, ICCs > 0.864). Spirometry: One study reported strong correlation of spirometry parameters (r>0.866) estimated using multiple sensors to generate a 3D image of the chest. CONCLUSIONS: Motion-based video gaming platforms offer potential for low-cost assessment of movement and mobility in large-scale clinical trials without reliance on specialist centers. Studies report good validity in some application areas. The ability to provide the level of accuracy needed in more rapid and finer movements requires more validation work.

1.12 - The Effects of SENS-111, A New H4R Antagonist, On Vertigo Induced by Caloric Test in Healthy Volunteers (HV) is Related to Plasma Concentrations

1.12 - The Effects of SENS-111, A New H4R Antagonist, On Vertigo Induced by Caloric Test in Healthy Volunteers (HV) is Related to Plasma Concentrations

Drug development in IBD: from novel target identification to early clinical trials

The two major forms of IBD, Crohn's disease (CD) and UC, are chronic inflammatory disorders, the pathogenesis of which involves a complex interplay of multiple factors.1 ,2 The introduction of...

Learning Curves Observed in Establishing Targeted Rate of Force Application in Pressure Pain Algometry.

Purpose: To determine whether learning curves can be observed with deliberate practice when the goal is to apply a consistent rate of force at 5 N/second during pressure pain threshold (PPT) testing in healthy volunteers. Methods: In this prospective study, 17 clinician participants completed PPT targeted rate-of-application testing with healthy volunteers using three different feedback paradigms. The resultant performances of ramp rate during 36 trials were plotted on a graph and examined to determine whether learning curves were observed. Results: Clinicians were not consistent in the rate of force applied. None demonstrated a learning curve over the course of 36 trials and three testing paradigms. Conclusion: The results of this study indicate that applying a consistent 5 N/second of force is difficult for practising clinicians. The lack of learning curves observed suggests that educational strategies for clinicians using PPT may need to change.

Hyperoxia Improves Hemodynamic Status During Head-up Tilt Testing in Healthy Volunteers: A Randomized Study.

Head-up tilt test is useful for exploring neurally mediated syncope. Adenosine is an ATP derivative implicated in cardiovascular disturbances that occur during head-up tilt test. The aim of the present study was to investigate the impact of hyperoxia on adenosine plasma level and on hemodynamic changes induced by head-up tilt testing.Seventeen healthy male volunteers (mean age 35 ± 11 years) were included in the study. The experiment consisted of 2 head-up tilt tests, 1 session with subjects breathing, through a mask, medical air (FiO2 = 21%) and 1 session with administration of pure oxygen (FiO2 = 100%) in double-blind manner. Investigations included continuous monitoring of hemodynamic data and measurement of plasma adenosine levels.No presyncope or syncope was found in 15 of the 17 volunteers. In these subjects, a slight decrease in systolic blood pressure was recorded during orthostatic stress performed under medical air exposure. In contrast, hyperoxia led to increased systolic blood pressure during orthostatic stress when compared with medical air. Furthermore, mean adenosine plasma levels decreased during hyperoxic exposure before (0.31 ± 0.08 μM) and during head-up tilt test (0.33 ± 0.09 μM) when compared with baseline (0.6 ± 0.1 μM). Adenosine plasma level was unchanged during medical air exposure at rest (0.6 ± 0.1 μM), and slightly decreased during orthostatic stress. In 2 volunteers, the head-up tilt test induced a loss of consciousness when breathing air. In these subjects, adenosine plasma level increased during orthostatic stress. In contrast, during hyperoxic exposure, the head-up tilt test did not induce presyncope or syncope. In these 2 volunteers, biological study demonstrated a decrease in adenosine plasma level at both baseline and during orthostatic stress for hyperoxic exposure compared with medical air.These results suggest that hyperoxia was able to increase blood pressure during head-up tilt test via a decrease in plasma adenosine concentration. Our results also suggest that adenosine receptor antagonists are worth trying in neurocardiogenic syncope.