Adam Webber

Dalhousie University, Halifax, Nova Scotia, Canada

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Publications (6)18.37 Total impact

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    ABSTRACT: In animals, central nervous system inflammation increases drug accumulation in the brain partly due to a loss of central nervous system drug efflux transporter function at the blood-brain barrier. To determine whether a similar loss of active drug efflux occurs in humans after acute inflammatory brain injury. Observational human pharmacokinetic study. Medical-surgical-neurosurgical intensive care unit at a university-affiliated, Canadian tertiary care center. Patients with acute inflammatory brain injury, including subarachnoid hemorrhage (n = 10), intracerebral and/or intraventricular hemorrhage (n = 4), or closed head trauma (n = 2) who received morphine intravenously after being fitted with cerebrospinal fluid ventriculostomy and peripheral arterial catheters. We correlated the cerebrospinal fluid distribution of morphine, morphine-3-glucuronide, and morphine-6-glucuronide with the cerebrospinal fluid and plasma concentration of the proinflammatory cytokine interleukin-6 and the passive marker of blood-brain barrier permeability, albumin. Acute brain injury produced a robust inflammatory response in the central nervous system as reflected by the elevated concentration of interleukin-6 in cerebrospinal fluid. Penetration of morphine metabolites into the central nervous system increased in proportion to the neuroinflammatory response as demonstrated by the positive correlation between cerebrospinal fluid interleukin-6 exposure and the area under the curve cerebrospinal fluid/plasma ratio for morphine-3-glucuronide (r = .49, p < .001) and morphine-6-glucuronide (r = .51, p < .001). In contrast, distribution of morphine into the brain was not linked with cerebrospinal fluid interleukin-6 exposure (r = .073, p = .54). Albumin concentrations in plasma and cerebrospinal fluid were consistently in the normal range, indicating that the physical integrity of the blood-brain barrier was likely undisturbed. Our results suggest that central nervous system inflammation following acute brain injury may selectively inhibit the activity of specific drug efflux transporters within the blood-brain barrier. This finding may have significant implications for patients with neuroinflammatory conditions when administered centrally acting drugs normally excluded from the brain by such transporters.
    No preview · Article · Oct 2009 · Critical care medicine
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    ABSTRACT: To test the hypothesis that, in comparison with a heavier, larger and more expensive manual tilt-in-space wheelchair, a lightweight manual wheelchair equipped with new rear antitip devices provides comparable mean sitting pressures in the tilted position, each of eight able-bodied participants sat for 8 mins in each wheelchair, upright, and tilted back (38-39 degrees). The mean (+/-SD) sitting pressures (of all active sensors in a force-sensing array) at the eighth minute in the upright and tilted positions with the new rear antitip device wheelchair were 58.6 (+/-14.0) and 45.8 (+/-9.3) mm Hg (a 20.7% reduction) (P = 0.005). For the tilt-in-space wheelchair, the mean values were 55.7 (+/-13.9) and 47.2 (+/-10.8) mm Hg (a 26.3% reduction) (P = 0.008). There were no significant differences between the wheelchairs in the upright (P = 0.843) or tilted (P = 0.624) positions. A lightweight manual wheelchair equipped with a new rear antitip device provides equivalent reductions of sitting pressures in the tilted position to a comparably tilted tilt-in-space wheelchair.
    No preview · Article · Nov 2008 · American journal of physical medicine & rehabilitation / Association of Academic Physiatrists
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    ABSTRACT: To test the hypothesis that, in comparison with a commercially available tilt-in-space wheelchair, a lightweight manual wheelchair equipped with a new, rear anti-tip device (Arc-RAD) provides caregivers with improved wheelchair-handling performance, less exertion, and greater satisfaction. Within-participant comparisons. Rehabilitation center. Able-bodied participants (n=19) simulating caregivers and simulating wheelchair users (n=7). Caregiver participants were trained (50-75 min) in wheelchair-handling skills. Each participant was tested in both wheelchairs, in random order. To evaluate wheelchair-handling skills, we used the total percentage score on the Wheelchair Skills Test (WST), version 3.2. For exertion, we used a visual analog scale (in percent). For satisfaction, we used the Quebec Users' Evaluation of Satisfaction with assistive Technology (QUEST; range of values, 8-40), version 2. Mean percentage WST scores +/- SD for the Arc-RAD and tilt-in-space wheelchairs were 95.9%+/-4.2%, and 91.9%+/-4.8%, respectively (P=.008). The mean perceived exertions during Arc-RAD and tilt-in-space wheelchair use were 26.1%+/-20.4% and 46.6%+/-23.2% (P=.003). The mean total QUEST satisfaction scores for the Arc-RAD and tilt-in-space wheelchairs were 35.1+/-3.8 and 28.4+/-4.7 (P=.002). In comparison with the larger and heavier tilt-in-space wheelchair, a lightweight manual wheelchair equipped with a new rear anti-tip design allows 4.4% better wheelchair-handling performance, 44% less exertion, and 23.6% greater wheelchair satisfaction.
    No preview · Article · Oct 2008 · Archives of physical medicine and rehabilitation
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    ABSTRACT: The primary objective of this study was to test the hypotheses that a wheelie training method that begins in a high-rolling-resistance (RR) setting (1) improves the success rate and (2) reduces the training time. Our secondary objectives were to assess the effects of other factors (e.g., age, gender) on training time and to acquire data on the perceptions of the participants that would assist us in refining our training methods. Randomized controlled study including 48 able-bodied participants with no significant wheelchair experience. Each participant was taught the wheelie skill, using up to five training sessions. Participants in the conventional group did all of their training on a smooth, level, tile surface. The RR group began training in a high-RR setting (rear wheels initially prevented from moving at all, progressing to being on 12-cm-thick foam that permitted some movement) before moving to the tile surface. Outcome measures were success rate (%), training time (mins) to achieve wheelie competence (defined as the ability to perform two consecutive 30-sec wheelies within a 1.5-m-diameter circle, assessed at least 2 days after training), and a questionnaire. The success rates for those in the conventional and RR groups were 96% and 100%, respectively (P = 1.000). The mean (+/-SD) training times for the conventional and RR groups were 55.9 mins (+/-27.1) and 51.8 mins (+/-18.7) (P = 0.549). Training time was not significantly affected by trainer or age, but it was affected by sex, with women requiring an average of 21.4 mins more than men (P = 0.002). Perceptions of participants in both groups about the training were positive. Of the participants in the RR group, 14 (74%) perceived the RR technique as "very effective," and five (26%) perceived it as "moderately effective." Neither success rate nor training time for wheelie skill acquisition by able-bodied learners are improved by a training method using high RR. Women require more time to learn than men. Learners using the RR technique perceive it to be effective. These results have implications for training practices.
    Full-text · Article · Apr 2008 · American Journal of Physical Medicine & Rehabilitation
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    ABSTRACT: To test the hypotheses that, compared with participants using manual wheelchairs equipped with conventional rear anti-tip devices (C-RADs), those using a new RAD design that deploys through an arc (Arc-RAD) perform RAD-relevant wheelchair skills better and as safely. A randomized controlled study. A rehabilitation center. Participants (N=30) including 16 able-bodied and 14 wheelchair users. Participants were provided with wheelchair skills training (up to 2.4h). Total percentage score on a set of 23 RAD-relevant skills of the Wheelchair Skills Test (WST, version 3.2) administered a minimum of 3 days after training. For the C-RAD and Arc-RAD groups, the mean +/- standard deviation RAD-relevant WST scores were 32.3%+/-8.5% and 85.1%+/-18.9% (Kruskal-Wallis, P<.001). Of the 23 RAD-relevant individual skills, the success rates for the Arc-RAD group were at least 20% higher (the criterion we set for clinical significance) in 17 (74%). For the C-RAD group, the success rate was 0% for the 12 wheelie-dependent skills, the 13-cm-high obstacle, and the 15-cm level change ascent. There were no serious adverse effects in either group. The new RAD design allows much better performance on relevant wheelchair skills than the conventional design without compromising safety.
    Full-text · Article · Mar 2008 · Archives of physical medicine and rehabilitation
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    Richard Hall · Cecilia de Antueno · Adam Webber
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    ABSTRACT: We reviewed the publication record of all protocols submitted to the Capital District Health Authority Research Ethics Board (REB) in Halifax, Nova Scotia, for the period 1995-1996. Because of a heightened awareness of the issue, we hypothesized that there would be less publication bias (a failure to report negative results) and a higher publication rate from completed studies, than previously reported. Closed studies were identified from the REB database. Publications were identified by the investigators, requests from sponsors, and a literature review. For each publication, we identified authors, title, journal, number of subjects enrolled, and whether or not the publication was a report of a randomized clinical trial. Comparisons were done using a Student's t test, the Chi-square statistic, or Fisher's exact test as appropriate. From the database of closed studies, 106 remained unpublished, while completed investigations resulted in 84 publications (44% publication rate). The median time to publication was 32.5 months. Publication of statistically significant results occurred in 71/84 trials. Publication of protocols submitted by departments ranged from 91% (anesthesia; 10/11) to 25% [nursing; 2/8 (P<0.05)]. Trials investigating new drugs in Phase 3 or 4 studies were more likely to be published than trials investigating agents in Phase 1 or 2 (P<0.05), and were less likely to be published if sponsored by a pharmaceutical company (P<0.05). Publication bias continues to be a problem, particularly for early phase investigative studies. Our results suggest that a different approach is required to reduce publication bias. The role that REBs and peer-reviewed journals might play requires further exploration.
    Full-text · Article · Jun 2007 · Canadian Journal of Anaesthesia