Karen Ethans

Efficacy of Botulinum Toxin A Injection for Neurogenic Detrusor Overactivity and Urinary Incontinence: A Randomized, Double-Blind Trial

PURPOSE We determined the efficacy of onabotulinumtoxinA for neurogenic detrusor overactivity secondary to spinal cord injury or multiple sclerosis. MATERIALS AND METHODS In a prospective, double-blind, multicenter study 57 patients 18 to 75 years old with neurogenic detrusor overactivity secondary to spinal cord injury or multiple sclerosis and urinary incontinence (defined as 1 or more occurrences daily) despite current antimuscarinic treatment were randomized to onabotulinumtoxinA 300 U (28) or placebo (29) via cystoscopic injection at 30 intradetrusor sites, sparing the trigone. Patients were offered open label onabotulinumtoxinA 300 U at week 36 and followed a further 6 months while 24 each in the treatment and placebo groups received open label therapy. The primary efficacy parameter was daily urinary incontinence frequency on 3-day voiding diary at week 6. Secondary parameters were changes in the International Consultation on Incontinence Questionnaire and the urinary incontinence quality of life scale at week 6. Diary and quality of life evaluations were also done after open label treatment. RESULTS The mean daily frequency of urinary incontinence episodes was significantly lower for onabotulinumtoxinA than for placebo at week 6 (1.31 vs 4.76, p <0.0001), and for weeks 24 and 36. Improved urodynamic and quality of life parameters for treatment vs placebo were evident at week 6 and persisted to weeks 24 to 36. The most common adverse event in each group was urinary tract infection. CONCLUSIONS In adults with antimuscarinic refractory neurogenic detrusor overactivity and multiple sclerosis onabotulinumtoxinA is well tolerated and provides clinically beneficial improvement for up to 9 months.

Efficacy and Safety of Tol Terodine in People With Neurogenic Detrusor Overactivity

Abstract Objective: To compare tolterodine with oxybutynin and placebo in people with neuragenie detrusor overactivity. Design: Prospective, randomized, double-blind, crossover trial plus open-label comparative stage. Participants: Ten participants with neuragenie detrusor overactivity due to spinal cord injury or multiple sclerosis who usedintermittent catheterization. Methods: Bladder capacity on cystometrogram, a 10-day record of catheterization volumes, number of incontinent episodes perday, and perceived dry mouth using a visual analog scale (VAS) were measured for the following: (a) a blinded comparison:tolterodine, 2 mg twice daily, vs placebo, twice daily; and (b) an unblinded comparison: oxybutynin vs tolterodine, each atself-selected doses (SSDs). Results: Tolterodine, 2 mg twice daily, was superior to placebo in enhancing catheterization volumes (P<0.0005) and reducingincontinence (P<0.001 ), but was comparable with placebo in cystometric bladder capacity. Efficacy of tolterodine SSD wascomparable with oxybutynin SSD with regard to catheterization volumes, degree of incontinence, and cystometric bladder capacity.The side effect profile (dry mouth) was comparable between tolterodine, 2 mg twice daily, and placebo, but differed significantlywhen comparing tolterodine SSD with oxybutynin SSD (P<0.05). Conclusion: T olterodine, when used at SSDs, is comparable with oxybutynin at SSDs in enhancing bladder volume and improvingcontinence, but with less dry mouth. T olterodine at the recommended dosage of 2 mg twice daily improves incontinence and bladdervolumes compared with placebo, and without significant dry mouth. Larger doses of tolterodine may be needed to achieve best effectin this population, but further studies are required.

Nabilone as an Adjunctive to Gabapentin for Multiple Sclerosis‐Induced Neuropathic Pain: A Randomized Controlled Trial

BACKGROUND Neuropathic pain (NPP) is a chronic syndrome suffered by patients with multiple sclerosis (MS), for which there is no cure. Underlying cellular mechanisms involved in its pathogenesis are multifaceted, presenting significant challenges in its management. METHODS A randomized, double-blind, placebo-controlled study involving 15 relapsing-remitting MS patients with MS-induced NPP was conducted to evaluate nabilone combined with gabapentin (GBP). Eligible patients stabilized on GBP (≥1,800 mg/day) with inadequate pain relief were recruited. Nabilone or placebo was titrated over 4 weeks (0.5 mg/week increase) followed by 5-week maintenance of 1 mg oral nabilone (placebo) twice daily. Primary outcomes included two daily patient-reported measures using a 100-mm visual analog scale (VAS), pain intensity (VASpain), and impact of pain on daily activities (VASimpact). Hierarchical regression modeling was conducted on each outcome to determine if within-person pain trajectory differed across study groups, during 63-day follow-up. RESULTS After adjustment for key patient-level covariates (e.g., age, sex, Expanded Disability Status Scale, duration of MS, baseline pain), a significant group × time(2) interaction term was reported for both the VASpain (P < 0.01) and VASimpact score (P < 0.01), demonstrating the adjusted rate of decrease for both outcomes was statistically greater in nabilone vs placebo study group. No significant difference in attrition rates was noted between treatments. Nabilone was well tolerated, with dizziness/drowsiness most frequently reported. CONCLUSION Nabilone as an adjunctive to GBP is an effective, well-tolerated combination for MS-induced NPP. The results of this study identify a novel therapeutic combination for use in this population of patients predisposed to tolerability issues that may otherwise prevent effective pain management.

A Randomized, Double-Blinded, Crossover Pilot Study Assessing the Effect of Nabilone on Spasticity in Persons With Spinal Cord Injury

OBJECTIVES To determine whether nabilone, a synthetic cannabinoid, alleviates spasticity in people with spinal cord injury (SCI). DESIGN A double-blind, placebo-controlled crossover study. SETTING Outpatient rehabilitation clinics. PARTICIPANTS We recruited volunteers (N=12) with SCI and spasticity. One subject, a paraplegic man, dropped out of the study because of an unrelated cause. Eleven subjects completed the study; all subjects were men with an average age of 42.36 years; 6 of them were persons with tetraplegia, and 5 were persons with paraplegia. INTERVENTIONS The subjects received either nabilone or placebo during the first 4-week period (0.5mg once a day with option to increase to 0.5mg twice a day), and then outcome measures were assessed. After a 2-week washout, subjects were crossed over to the opposite arm. MAIN OUTCOME MEASURES The primary outcome was the Ashworth Scale for spasticity in the most involved muscle group, in either the upper or lower extremities, chosen by the subject and clinician. The secondary outcomes included the sum of the Ashworth Scale in 8 muscle groups of each side of the body measured by the clinician; Spasm Frequency Scale and visual analog scale, reported by the subject; Wartenberg Pendulum Test, in order to quantify severity of spasticity; and the Clinicians and Subjects Global Impression of Change. RESULTS One subject dropped out during the placebo arm because of an unrelated urinary stricture, and 11 subjects completed the study. There was a significant decrease on active treatment for the Ashworth in the most involved muscle (mean difference +/- SD, .909+/-.85; P=.003), as well as the total Ashworth score (P=.001). There was no significant difference in other measures. Side effects were mild and tolerable. CONCLUSIONS Nabilone may be beneficial to reduce spasticity in people with SCI. We recommend a larger trial with a more prolonged treatment period and an option to slowly increase the dosage further.

A Meta-Analysis of Botulinum Toxin Sphincteric Injections in the Treatment of Incomplete Voiding After Spinal Cord Injury

OBJECTIVE To conduct a systematic review and meta-analysis to examine the effect of injecting botulinum toxin A (BTX-A) into the detrusor sphincter on improving bladder emptying in individuals with spinal cord injury (SCI). DATA SOURCES MEDLINE, CINAHL, EMBASE, and PsycINFO databases were searched for all relevant articles published from 1980 to September 2011. DATA SELECTION All trials examining the use of BTX-A injections into the detrusor sphincter for the treatment for incomplete bladder emptying after SCI were included if at least 50% of the study sample comprised subjects with SCI, and if the SCI sample size was 3 or greater. DATA EXTRACTION A standardized mean difference (SMD) ± SE and 95% confidence interval (CI) were calculated for each outcome of interest, and the results were pooled using a fixed or random effects model, as appropriate. Outcomes assessed included postvoid residual urine volume (PRV), detrusor pressure (PDet), and urethral pressure (UP). Effect sizes were interpreted as small, 0.2; moderate, 0.5; and large, 0.8. DATA SYNTHESIS A relatively limited number of studies (2 randomized controlled trials, 6 uncontrolled trials) were identified. The 8 studies included results from 129 subjects. There was a statistically significant decrease in PRV at 1 month (SMD=1.119±.140; 95% CI, .844-1.394; P<.001), with a pooled mean PRV decrease from 251.8 to 153.0 mL. There was a moderate statistical effect on PDet (SMD=.570±.217; 95% CI, .145-.995; P=.009); pooled PDet decreased from 88.7 to 20.5 cmH(2)O. A large statistical effect size on UP (SMD=.896±.291; 95% CI, .327-1.466; P=.002) and an improvement from 119.7 to 102.3 cmH(2)O were seen. The systematic review also indicated a 50% reduction in urinary tract infections based on 3 studies. Discontinuation or reduction in catheter usage was reported in 4 studies after BTX-A. CONCLUSIONS Results of the meta-analysis indicate that BTX-A is effective in reducing PRV and demonstrating a statistically significant reduction in PDet and UP 1 month postinjection. However, the clinical utility of BTX-A is yet to be determined.

Efficacy and safety of onabotulinumtoxinA therapy are sustained over 4 years of treatment in patients with neurogenic detrusor overactivity: Final results of a long‐term extension study

To present final efficacy/safety results from a prospective, long‐term extension trial of onabotulinumtoxinA for urinary incontinence (UI) due to neurogenic detrusor overactivity (NDO); patients received treatment for up to 4 years.

Spinal cord injury in Manitoba: a provincial epidemiological study

Abstract Objective: To define the epidemiological trends and identify populations at risk of traumatic and non-traumatic spinal cord injury (NTSCI) for the province of Manitoba, Canada. Methods: We reviewed records retrospectively for subjects in three cohorts (1981–1985, 1998–2002, and 2003–2007). A total of 553 individuals with spinal cord injury (SCI) were studied for variables such as age, level of injury, severity of injury, First Nations (FN) status, and etiology of injury. Results: Incidence of overall SCI has increased from 22.0 to 46.5 per million (P < 0.001). Incidence of NTSCI increased from 3.12 per million to 16.7 per million (P < 0.001). Incidence of traumatic spinal cord injury (TSCI) has increased from the 17.1 per million to 25.6 per million (P < 0.001). There was a significant increase in the mean age at injury from 30.23 to 45.768 years of age (P < 0.0001). Female and NTSCI have a higher mean and median age at injury. There was a significant (P = 0.0008) increase in the proportion of females with a most recent male/female ratio of 3.4:1. A temporal increase in incomplete injuries was observed (P < 0.0001). Incomplete and thoracic level injuries are more common with NTSCI. Conclusion: The results demonstrate that there are significant differences between NTSCI and TSCI in Manitoba, and that Manitoba trends in SCI are in keeping with those seen on a national and an international level. There is a high risk of SCI in Manitoba FN, for which preventive strategies need to be put in place, and higher resource structure geared towards. Additionally, the trend of older age at injury has significant implications for structuring acute care and rehabilitation programs for these individuals, enhancing the need for treating older and more medically complicated individuals with SCI.

Meta-Analysis of Botulinum Toxin A Detrusor Injections in the Treatment of Neurogenic Detrusor Overactivity After Spinal Cord Injury

OBJECTIVE To examine the effectiveness of botulinum toxin type A (BTX-A) on neurogenic detrusor overactivity (NDO) in individuals with spinal cord injury (SCI). DATA SOURCES MEDLINE, CINAHL, EMBASE, and PsycINFO databases were searched for all relevant articles published from 1980 to June 2012. STUDY SELECTION Trials examining the use of BTX-A injections into the detrusor wall in the treatment of NDO after SCI were included if (1) ≥ 50% of study sample comprised subjects post-SCI; (2) outcomes of interest were assessed before and after treatment with a single injection of BTX-A; and (3) the sample size was ≥ 3. DATA EXTRACTION A standardized mean difference ± SE (95% confidence interval) was calculated for at least 1 of the following outcomes in every study: postvoid residual urine volume, reflex detrusor volume, bladder capacity, bladder compliance, catheterization frequency, and maximum flow rate. Results from all studies were then pooled using a random-effects model. Treatment effect sizes were interpreted as small, >0.2; moderate, >0.5; or large, >0.8. DATA SYNTHESIS Fourteen studies representing data from 734 subjects were included. After BTX-A injection, large treatment effects were observed in postvoid residual urine volume, reflex detrusor volume, bladder capacity, bladder compliance, and catheterization frequency (P<.01). Rate of incontinence episodes was reduced from 23% to 1.31% after BTX-A treatment. No significant decrease in max flow rate was observed (P=.403). CONCLUSIONS Results of the meta-analysis indicate BTX-A is effective in treating NDO after SCI. The use of BTX-A was associated with a decrease in incontinence episodes, catheter use, and bladder pressures.

Barriers to Wheelchair Use in the Winter

OBJECTIVES To test the hypothesis that challenges to community participation posed by winter weather are greater for individuals who use scooters, manual and power wheelchairs (wheeled mobility devices [WMDs]) than for the general ambulatory population, and to determine what WMD users identify as the most salient environmental barriers to community participation during the winter. DESIGN Cross-sectional survey organized around 5 environmental domains: technological, natural, physical, social/attitudinal, and policy. SETTING Urban community in Canada. PARTICIPANTS Convenience sample of WMD users or their proxy (N=99). INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Not applicable. RESULTS Forty-two percent identified reduced outing frequency in winter months, associated with increased age (χ(3)=6.4, P=.04), lack of access to family/friends for transportation (χ(2)=8.1, P=.04), and primary type of WMD used in the winter (scooter χ(2)=8.8, P=.003). Most reported tires/casters becoming stuck in the snow (95%) or slipping on the ice (91%), difficulty ascending inclines/ramps (92%), and cold hands while using controls or pushing rims (85%); fewer identified frozen wheelchair/scooter batteries, seat cushions/backrests, or electronics. Sidewalks/roads were reported to be problematic by 99%. Eighty percent reported needing additional help in the winter. Limited community access in winter led to a sense of loneliness/isolation, and fear/anxiety related to safety. Respondents identified policies that limited participation during winter. CONCLUSIONS People who use WMDs decrease their community participation in cold weather because of multiple environmental barriers. Clinicians, researchers, and policymakers can take a multidimensional approach to mitigate these barriers in order to enhance community participation by WMD users in winter.

The effects of sildenafil on the cardiovascular response in men with spinal cord injury at or above the sixth thoracic level.

Abstract Background: Sildenafil is efficacious for erectile dysfunction in men with spinal cord injury (SCI), but can induce hypotension in neurologically intact people. Those with SCI at or above the sixth thoracic level (T6) often have pre-existing hypotension, yet the cardiovascular response to sildenafil has not been studied in this group. Objective: To evaluate the effect of sildenafil on the cardiovascular response in men with complete SCI at or above T6. Methods: This was a randomized, double-blind, placebo-controlled, cross-over study. Twenty-three SCI participants were each randomly given placebo; sildenafil, 50 mg; and sildenafil, 1 00 mg; separated by at least 1 week. The following were measured before administration, and hourly for 4 hours afterward: (a) blood pressure (BP) and heart rate (HR) , both supine and sitting; and (b) perceived dizziness on a visual analog scale upon sitting. Results: Analysis was done using a 4-way repeated-measures analysis of variance. No significant changes occurred with placebo. Sildenafil caused the following changes. Systolic BP changed little in thoracic spinal cord-injured (TSCI) participants, but decreased significantly (P < 0.005) in cervical spinal cord-injured (CSCI) participants. Diastolic BP decreased in all participants (P < 0.005). HR increased in the TSCI participants for 1 hour (P < 0.05), but was not altered in the CSCI participants. Dizziness increased in the TSCI participants after administration of 100 mg (P < 0.05) and in the CSCI participants after administration of 50 mg (P < 0.05). There were no adverse events or outcomes. Conclusion: Sildenafil induces significant hypotension in people with cervical-level injuries-more so than in thoracic-level injuries-and can cause dizziness in both populations. It should be prescribed with caution and informed consent from the patient.