Rodney U. Anderson

Once daily controlled versus immediate release oxybutynin chloride for urge urinary incontinence

PURPOSE We compared the efficacy and safety of once daily controlled and immediate release oxybutynin for incontinence. MATERIALS AND METHODS This multicenter, randomized, double-blind, active control, parallel study was designed to evaluate urge urinary incontinence episodes using a 7-day diary. RESULTS A total of 97 women and 8 men 34 to 76 years old with urge incontinence or mixed incontinence with a clinically significant urge component were enrolled in the study. The number of weekly urge incontinence episodes decreased from 27.4 to 4.8 after controlled and from 23.4 to 3.1 after immediate release oxybutynin (p = 0.56), and total incontinence episodes decreased from 29.3 to 6 and from 26.3 to 3.8, respectively (p = 0.6). Weekly urge incontinence episodes from baseline to end of study also decreased to 84% after controlled and 88% after immediate release oxybutynin (p = 0.7). Continence was achieved in 41% of the controlled and 40% of the immediate release group (p = 0.9). Dry mouth of any severity was reported by 68 and 87% of the controlled and immediate release groups, respectively (p = 0.04), and moderate or severe dry mouth occurred in 25 and 46%, respectively (p = 0.03). CONCLUSIONS Participants taking a single daily does of controlled release oxybutynin had similar reductions in urge incontinence and total incontinence episodes compared to those taking oxybutynin 1 to 4 times daily. A lower incidence of dry mouth was reported for controlled release oxybutynin.

Prospective Randomized Controlled Trial of Extended-Release Oxybutynin Chloride and Tolterodine Tartrate in the Treatment of Overactive Bladder: Results of the OBJECT Study

OBJECTIVE To compare the efficacy and tolerability of extended-release oxybutynin chloride and tolterodine tartrate at 12 weeks in participants with overactive bladder. SUBJECTS AND METHODS The OBJECT (Overactive Bladder: Judging Effective Control and Treatment) study was a prospective, randomized, double-blind, parallel-group study conducted between March and October 2000 at 37 US study sites. Participants who had between 7 and 50 episodes of urge incontinence per week and 10 or more voids in 24 hours received extended-release oxybutynin, 10 mg/d, or tolterodine, 2 mg twice daily. The outcome measures were the number of episodes of urge incontinence, total incontinence, and micturition frequency at 12 weeks adjusted for baseline. RESULTS A total of 315 women and 63 men were randomized and treated, and 332 participants (276 women, 56 men) completed the study. At the end of the study, extended-release oxybutynin was significantly more effective than tolterodine in each of the main outcome measures: weekly urge incontinence (P=.03), total incontinence (P=.02), and micturition frequency episodes (P=.02) adjusted for baseline. Both drugs improved symptoms of overactive bladder significantly from baseline to the end of the study as assessed by the 3 main outcome measures (P<.001). Dry mouth, the most common adverse event, was reported by 28.1% and 33.2% of participants taking extended-release oxybutynin and tolterodine, respectively (P=.32). Rates of central nervous system and other adverse events were low and similar in both groups. CONCLUSIONS Extended-release oxybutynin was more effective than tolterodine as measured by end-of-study urge incontinence, total incontinence, and micturition frequency episodes. Both groups had similar rates of dry mouth and other adverse events.

Randomized Multicenter Feasibility Trial of Myofascial Physical Therapy for the Treatment of Urological Chronic Pelvic Pain Syndromes

PURPOSE We determined the feasibility of conducting a randomized clinical trial designed to compare 2 methods of manual therapy (myofascial physical therapy and global therapeutic massage) in patients with urological chronic pelvic pain syndromes. MATERIALS AND METHODS We recruited 48 subjects with chronic prostatitis/chronic pelvic pain syndrome or interstitial cystitis/painful bladder syndrome at 6 clinical centers. Eligible patients were randomized to myofascial physical therapy or global therapeutic massage and were scheduled to receive up to 10 weekly treatments of 1 hour each. Criteria to assess feasibility included adherence of therapists to prescribed therapeutic protocol as determined by records of treatment, adverse events during study treatment and rate of response to therapy as assessed by the patient global response assessment. Primary outcome analysis compared response rates between treatment arms using Mantel-Haenszel methods. RESULTS There were 23 (49%) men and 24 (51%) women randomized during a 6-month period. Of the patients 24 (51%) were randomized to global therapeutic massage, 23 (49%) to myofascial physical therapy and 44 (94%) completed the study. Therapist adherence to the treatment protocols was excellent. The global response assessment response rate of 57% in the myofascial physical therapy group was significantly higher than the rate of 21% in the global therapeutic massage treatment group (p = 0.03). CONCLUSIONS We judged the feasibility of conducting a full-scale trial of physical therapy methods and the preliminary findings of a beneficial effect of myofascial physical therapy warrants further study.

Alfuzosin and Symptoms of Chronic Prostatitis–Chronic Pelvic Pain Syndrome

BACKGROUND In men with chronic prostatitis-chronic pelvic pain syndrome, treatment with alpha-adrenergic receptor blockers early in the course of the disorder has been reported to be effective in some, but not all, relatively small randomized trials. METHODS We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of alfuzosin, an alpha-adrenergic receptor blocker, in reducing symptoms in men with chronic prostatitis-chronic pelvic pain syndrome. Participation in the study required diagnosis of the condition within the preceding 2 years and no previous treatment with an alpha-adrenergic receptor blocker. Men were randomly assigned to treatment for 12 weeks with either 10 mg of alfuzosin per day or placebo. The primary outcome was a reduction of at least 4 points (from baseline to 12 weeks) in the score on the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) (range, 0 to 43; higher scores indicate more severe symptoms). A 4-point decrease is the minimal clinically significant difference in the score. RESULTS A total of 272 eligible participants underwent randomization, and in both study groups, 49.3% of participants had a decrease of at least 4 points in their total NIH-CPSI score (rate difference associated with alfuzosin, 0.1%; 95% confidence interval, -11.2 to 11.0; P=0.99). In addition, a global response assessment showed similar response rates at 12 weeks: 33.6% in the placebo group and 34.8% in the alfuzosin group (P=0.90). The rates of adverse events in the two groups were also similar. CONCLUSIONS Our findings do not support the use of alfuzosin to reduce the symptoms of chronic prostatitis-chronic pelvic pain syndrome in men who have not received prior treatment with an alpha-blocker. (ClinicalTrials.gov number, NCT00103402.)

Pharmacotherapy for neurogenic detrusor overactivity.

Chancellor MB, Anderson RU, Boone TB: Pharmacotherapy for neurogenic detrusor overactivity. Am J Phys Med Rehabil 2006;85:536–545. Patients with neurogenic detrusor overactivity are a heterogeneous group with voiding dysfunction secondary to neurologic injury or disease. The neurogenic detrusor overactivity syndrome, which may include urinary frequency, urgency, and incontinence, frequently contributes to a loss of independence, or even institutionalization. Urodynamic assessment provides the best method of quantifying and classifying neurogenic detrusor overactivity dysfunction in patients with primary diagnoses as diverse as Parkinson’s disease, cerebral palsy, multiple sclerosis, spinal cord injury, and spina bifida. For many patients, management of urinary symptoms includes pharmacotherapy with an anticholinergic agent. Several novel approaches to managing neurogenic detrusor overactivity, including intravesical instillation of anticholinergic agents, vanilloids, and neurotoxins, are being investigated. For most patients, however, flexible dosing with an anticholinergic agent, with clean intermittent catheterization when indicated, has been shown to reduce the risks of urologic complications, improve levels of continence, and enhance patient quality of life in both children and adults.

Prophylaxis of Bacteriuria During Intermittent Catheterization of the Acute Neurogenic Bladder

A randomized prospective study of bacteriuria control during early intermittent bladder catheterization was performed on a spinal cord injury service. The 64 male subjects underwent 16,620 catheterizations and had 83 significant episodes of infection. The infection rates among various groups were compared: 1) control patients, 2) patients treated with intravesical neomycin/polymyxin-B, 3) patients given low dose daily macrocrystals of nitrofurantoin and 4) patients given intravesical treatment and oral nitrofurantoin. There was significant reduction in infection rates when oral and intravesical antibiotics were used.

Painful Myofascial Trigger Points and Pain Sites in Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome

PURPOSE A combination of manual physiotherapy and specific relaxation training effectively treats patients with chronic prostatitis/chronic pelvic pain syndrome. However, little information exists on myofascial trigger points and specific chronic pelvic pain symptoms. We documented relationships between trigger point sites and pain symptoms in men with chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS We randomly selected a cohort of 72 men who underwent treatment with physiotherapy and relaxation training from 2005 to 2008. Patients self-reported up to 7 pelvic pain sites before treatment and whether palpation of internal and external muscle trigger points reproduced the pain. Fishers exact test was used to compare palpation responses, ie referral pain, stratified by reported pain site. RESULTS Pain sensation at each anatomical site was reproduced by palpating at least 2 of 10 designated trigger points. Furthermore, 5 of 7 painful sites could be reproduced at least 50% of the time (p <0.05). The most prevalent pain sites were the penis in 90.3% of men, the perineum in 77.8% and the rectum in 70.8%. Puborectalis/pubococcygeus and rectus abdominis trigger points reproduced penile pain more than 75% of the time (p <0.01). External oblique muscle palpation elicited suprapubic, testicular and groin pain in at least 80% of the patients at the respective pain sites (p <0.01). CONCLUSIONS This report shows relationships between myofascial trigger points and reported painful sites in men with chronic prostatitis/chronic pelvic pain syndrome. Identifying the site of clusters of trigger points inside and outside the pelvic floor may assist in understanding the role of muscles in this disorder and provide focused therapeutic approaches.

Prostatic Secretion Leukocyte Studies in Non-Bacterial Prostatitis (Prostatosis)

Non-bacterial prostatitis is a common affliction among men and lacks objective criteria for clear identification. We studied 43 consecutive patients and 20 normal controls for the presence of bacteria and quantitation of prostatic secretion leukocytes. Significantly greater numbers of macrophages per volume of prostatic secretion were found in the patients. Multiple observations of such increased leukocyte proliferation could be used to establish true prostatic inflammation.

Delivery of antitumor drug to bladder cancer by use of phase transition liposomes and hyperthermia.

It has been proposed that liposomes (phospholipid bilayer vesicles) could be used to entrap enzymes or drugs and then be administered intravenously to patients as a natural molecule to be metabolized. After liposome degradation, the entrapped molecules would be released at higher concentrations in target tissues. In 1979, it was shown that liposomes containing a chemotherapeutic agent could preferentially release the agent at the transition temperature of the lipids. In an effort to deliver high dose methotrexate (MTX) to animal transitional cell carcinomas (TCC), we used liposomes with phase transition temperature a few degrees above 37 C. Experimentally induced bladder TCC tumors (induced with N-(4-(5-nitro-2-furyl)-2 thiazolyl) formamide) were transplanted into hind legs of C3H/Bi mice. These animals received tritiated MTX encapsulated in phase transition liposomes. Tumors were heated to 42 +/- 0.5 C (by ultrasound) before receiving the liposomes containing tritiated molecules of MTX. After an appropriate time sequence the tumors were removed and MTX uptake of each tumor was noted and compared to the controls having unheated tumors. Heated TCC tumors accumulated 11.9-fold more MTX than nonheated tumors receiving the same dose. Animals receiving free MTX did not exhibit a temperature dependent difference. This indicates that the phase transition temperature of specifically engineered liposome may be used to increase delivery of high dose methotrexate to transitional cell carcinomas.

Pregabalin for the treatment of men with chronic prostatitis/chronic pelvic pain syndrome: A randomized controlled trial

BACKGROUND Evidence suggests that the urogenital pain of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) may be neuropathic. METHODS This randomized, double-blind, placebo-controlled trial was conducted across 10 tertiary care centers in North America to determine whether pregabalin, which has been proved effective in other chronic pain syndromes, is effective in reducing CP/CPPS symptoms. In 2006-2007, 324 men with pelvic pain for at least 3 of the previous 6 months were enrolled in this study. Men were randomly assigned to receive pregabalin or placebo in a 2:1 ratio and were treated for 6 weeks. Pregabalin dosage was increased from 150 to 600 mg/d during the first 4 weeks. The primary outcome was a 6-point decrease in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score. Multiple secondary outcomes were assessed. RESULTS Of 218 men assigned to receive pregabalin, 103 (47.2%) reported at least a 6-point decrease in the NIH-CPSI total score at 6 weeks compared with 35.8% (38 of 106 men) assigned to receive placebo (P = .07, exact Mantel-Haenszel test, adjusting for clinical sites). Compared with the placebo group, men assigned to receive pregabalin experienced reductions in the NIH-CPSI total score and subscores (P < .05), a higher Global Response Assessment response rate (31.2% and 18.9%; P = .02), and improvement in total McGill Pain Questionnaire score (P = .01). Results for the other outcomes did not differ between groups. CONCLUSION Pregabalin therapy for 6 weeks was not superior to placebo use in the rate of a 6-point decrease (improvement) in the NIH-CPSI total score in men with CP/CPPS. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00371033.