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.

Efficacy and safety of flexible dose fesoterodine in men and women with overactive bladder symptoms including nocturnal urinary urgency.

PURPOSE: Awakening from sleep to urinate is the hallmark of nocturia, a condition that impacts several facets of health related quality of life and for which current therapy is suboptimal. Given the paucity of prospective data on antimuscarinics for the management of nocturia, we investigated the efficacy and safety of flexible dose fesoterodine for the treatment of nocturnal urgency in subjects with nocturia and overactive bladder. MATERIALS AND METHODS: Subjects with 2 to 8 nocturnal urgency episodes per 24 hours began a 2-week, single-blind, placebo run-in followed by 1:1 randomization to 12 weeks of double-blind treatment with fesoterodine (4 mg daily for 4 weeks with an optional increase to 8 mg) or placebo using predefined criteria for nocturnal urgency episodes, nocturnal urine volume voided and total 24-hour urine volume voided. The primary end point was change from baseline to week 12 in the mean number of micturition related nocturnal urgency episodes per 24 hours. RESULTS: Overall 963 subjects were randomized from 2,990 screened, and 82% of subjects treated with fesoterodine and 84% of those treated with placebo completed the study. Significant improvements in the primary end point (-1.28 vs -1.07), in nocturnal micturitions per 24 hours (-1.02 vs -0.85) and in nocturnal frequency urgency sum (-4.01 vs -3.42) were observed with fesoterodine vs placebo (all p ≤0.01). Health related quality of life measures (overactive bladder questionnaire Symptom Bother -20.1 vs -16.5, sleep 22.3 vs 19.9 and other domains; all p <0.05) were improved with fesoterodine. CONCLUSIONS: To our knowledge this is the first prospective study to assess antimuscarinic efficacy for reducing nocturnal urgency. Flexible dose fesoterodine significantly reduced nocturnal urgency episodes vs placebo in subjects with overactive bladder.

Perioperative bowel habits of women undergoing gynecologic surgery: a pilot study.

OBJECTIVES: To describe perioperative bowel habits of women undergoing gynecologic surgery. METHODS: This prospective cohort study included women undergoing gynecologic surgery. Before surgery, participants completed the Bristol Stool Form Scale (BSFS), a validated instrument describing stool characteristics consistent with transit categories: slow (BSFS 1-2), normal (BSFS 3-5), and fast (BSFS 6-7). For 2 weeks after surgery, the participants recorded daily medications and bowel movements (BM), and completed BSFS. The χ(2) test, the Fisher exact test, analysis of variance, t tests, and ordinal regression were used. RESULTS: Preoperatively, most (70%) of 340 women had normal stool transit, with 15% having slow transit and 7% having fast transit. Complete postoperative data were available for 170 (50%). Mean ± SD time to first postoperative BM was 2.8 ± 1.4 days with transit classification: 48% normal, 32% slow, and 20% fast. CONCLUSIONS: Most women had normal stool transit both preoperatively and postoperatively. Time to first BM was longer after open surgery by approximately 3 days.

Reliability and responsiveness of the Urgency Severity and Life Impact Questionnaire (USIQ).

INTRODUCTION AND HYPOTHESIS: The aims of this study are (1) to assess the reliability (test-retest) of the Urgency Severity and Life Impact Questionnaire (USIQ) and (2) to test the effect of extended-release tolterodine on symptoms of urinary urgency using this validated instrument. METHODS: To measure reliability, women with overactive bladder (OAB) completed the USIQ on two separate occasions, prior to treatment for OAB. To assess the responsiveness, the USIQ participants completed the above-mentioned questionnaires prior to and following 4 weeks of treatment for OAB with extended-release tolterodine. RESULTS: USIQ-S and USIQ-QoL scores at the two visits did not differ significantly. Repeated measures of USIQ-S and USIQ-QoL demonstrated a moderate to excellent intraclass correlation coefficient (0.64-0.74; P < 0.0001 and 0.48-0.91, P < 0.0001, respectively). A significant decrease in mean USIQ-S and USIQ-QOL (71 ± 14 vs. 44 ± 19, P < 0.0001 and 51 ± 22 vs. 39 ± 10, P < 0.01, respectively) scores following treatment with tolterodine. CONCLUSIONS: This valid, reliable measure can be used in clinical practice and research trials to measure urgency severity.

Solifenacin objectively decreases urinary sensation in women with overactive bladder syndrome.

PURPOSE: To evaluate the test-retest reliability of a device that measures urinary sensation during cystometry, and to use that device to determine whether treatment of overactive bladder syndrome (OAB) with solifenacin is associated with a change in urinary sensation. METHODS: Overall 15 women were recruited for this study, ten women with OAB and urodynamically demonstrated detrusor overactivity and five controls without OAB underwent filling cystometry twice with contemporaneous, continuous recording of urinary sensation. Women with OAB received solifenacin 10 mg daily during the weeks between testing. We compared the areas under the initial and repeat sensation-volume curves. RESULTS: While taking solifenacin, the maximum cystometric capacity increased from 329 ± 168 ml to 464 ± 123 ml (P < 0.002), and the area under the bladder volume-sensation curve decreased (P < 0.0001). Untreated controls did not exhibit these changes. CONCLUSION: We present psychometric data demonstrating improved bladder sensation during the treatment of OAB with solifenacin. If clinical correlations are confirmed by future study, such urinary sensation measures may prove useful as assessment, treatment predictor, or outcome measures in OAB research and/or clinical care.

Perineal surface electromyography does not typically demonstrate expected relaxation during normal voiding.

AIMS: To describe perineal surface patch electromyography (EMG) activity during urodynamics (UDS) and compare activity between filling and voiding phases and to assess for a relationship between preoperative EMG activity and postoperative voiding symptoms. METHODS: 655 women underwent standardized preoperative UDS that included perineal surface EMG prior to undergoing surgery for stress urinary incontinence. Pressure-flow studies were evaluated for abdominal straining and interrupted flow. Quantitative EMG values were extracted from 10 predetermined time-points and compared between fill and void. Qualitative EMG activity was assessed for the percent of time EMG was active during fill and void and for the average amplitude of EMG during fill compared to void. Postoperative voiding dysfunction was defined as surgical revision or catheterization more than 6 weeks after surgery. Fisher's exact test with a 5% two-sided significance level was used to assess differences in EMG activity and postoperative voiding dysfunction. RESULTS: 321 UDS had interpretable EMG studies, of which 131 (41%) had EMG values at all 10 predetermined and annotated time-points. Quantitative and qualitative EMG signals during flow were usually greater than during fill. The prevalence of postoperative voiding dysfunction in subjects with higher preoperative EMG activity during void was not significantly different. Results were similar in the 42 subjects who had neither abdominal straining during void nor interrupted flow. CONCLUSIONS: Perineal surface patch EMG did not measure expected pelvic floor and urethral sphincter relaxation during voiding. Preoperative EMG did not predict patients at risk for postoperative voiding dysfunction.

Nonsteroidal antiinflammatory drug use and lower urinary tract symptoms: results from the Boston area community health survey.

There is evidence for a role of inflammation in the etiology of lower urinary tract symptoms (LUTS), raising the possibility that use of nonsteroidal antiinflammatory drugs (NSAIDs) may inhibit the development or progression of LUTS. The authors examined the association between use of prescription and over-the-counter NSAIDs and LUTS among 1,974 men and 2,661 women in the Boston Area Community Health Survey (2002-2005). Multivariable-adjusted logistic regression was used to estimate odds ratios and 95% confidence intervals for LUTS, voiding symptoms, storage symptoms, and nocturia. There was no clear association between use of prescription or over-the-counter NSAIDs (compared with no NSAID use) and overall LUTS, voiding symptoms, or nocturia in men or women. However, over-the-counter NSAID use was positively associated with storage symptoms in women (odds ratio = 1.37, 95% confidence interval: 1.03, 1.83), and there was a positive association between over-the-counter NSAID use and overall LUTS among women with a history of arthritis (odds ratio = 2.09, 95% confidence interval: 1.20, 3.64). These results do not provide strong support for an association between NSAIDs and LUTS. However, the associations between over-the-counter NSAID use and certain urologic symptoms, particularly among women with arthritis, and the potential mechanisms involved should be evaluated in future studies.

Early termination of a trial of mycophenolate mofetil for treatment of interstitial cystitis/painful bladder syndrome: lessons learned.

PURPOSE: We evaluated the efficacy and tolerability of mycophenolate mofetil in patients with treatment refractory interstitial cystitis/painful bladder syndrome. MATERIALS AND METHODS: A total of 210 patients with interstitial cystitis/painful bladder syndrome were to be randomized into a multicenter, placebo controlled trial using a 2:1 randomization. Participants in whom at least 3 interstitial cystitis/painful bladder syndrome specific treatments had failed and who had at least moderately severe symptoms were enrolled in a 12-week treatment study. The primary study end point was the global response assessment. Secondary end points were general and disease specific symptom questionnaires, and voiding diaries. RESULTS: Only 58 subjects were randomized before a black box warning regarding mycophenolate mofetil safety was issued by the manufacturer in October 2007. The trial was halted, and interim analysis was performed and presented to an independent data and safety monitoring board. Six of the 39 subjects (15%) randomized at study cessation were considered responders for mycophenolate mofetil compared to 3 of 19 controls (16%, p=0.67). Secondary outcome measures reflected more improvement in controls. CONCLUSIONS: In a randomized, placebo controlled trial that was prematurely halted mycophenolate mofetil showed efficacy similar to that of placebo to treat symptoms of refractory interstitial cystitis/painful bladder syndrome. The results of this limited study cannot be used to confirm or refute the hypothesis that immunosuppressive therapy may be beneficial to at least a subgroup of patients with interstitial cystitis/painful bladder syndrome. Despite study termination lessons can be gleaned to inform future investigations.

Size does matter: donor renal volume predicts recipient function following live donor renal transplantation.

PURPOSE: With the now routine use of computerized tomography angiography with 3-dimensional reconstruction in the donor evaluation, renal volume can be easily determined using volume calculating software. We evaluated whether donor renal volume could predict recipient renal function. MATERIALS AND METHODS: Clinical data of all donor and recipient pairs undergoing live donor kidney transplantation at our institution between January 2006 and October 2009 were reviewed. The volume of the kidney selected for transplant was determined using volume calculating software, and correlated to transplant recipient nadir and 1-year serum creatinine. Multivariate regression analysis was performed to adjust for demographic and clinical variables. RESULTS: During the study period 114 patients underwent live donor renal transplantation. Recipient nadir and 1-year serum creatinine levels were significantly correlated with the volume of donated kidney even after adjusting for age, body mass index, body surface area and donor creatinine clearance. Kidney volume also retained significance after excluding recipients from analysis who experienced acute rejection episodes. CONCLUSIONS: Larger kidney volumes calculated using 3-dimensional computerized tomography with volume calculating software are correlated with lower recipient nadir and 1-year serum creatinine levels.

Association of nocturia and mortality: results from the Third National Health and Nutrition Examination Survey.

PURPOSE: Nocturia, a common problem in men and women, has been associated with chronic illnesses such as heart disease and hypertension. Using data from the Third National Health and Nutrition Examination Survey we investigated the association of nocturia with subsequent mortality risk. MATERIALS AND METHODS: NHANES III is a national probability survey of the United States between 1988 and 1994. Mortality data were obtained by linkage of NHANES III to the National Death Index. Cox proportional hazards regression models were used to assess the association between nocturia and all cause mortality, controlling for potential confounders in a sample of 15,988 men and women 20 years old or older. RESULTS: The prevalence of nocturia, defined as 2 or more voiding episodes nightly, was 15.5% in men and 20.9% in women. Multivariate analyses showed a statistically significant trend of increased mortality risk with increased number of voiding episodes in men and women. The magnitude of the nocturia and mortality association was greater in those younger than 65 years with attenuated associations in the 65 years old or older age group. CONCLUSIONS: Nocturia is a strong predictor of mortality, more so in younger men and women than in the elderly, with a dose-response pattern in increased mortality risk with increasing number of voiding episodes nightly. Potential underlying mechanisms of the observed association of nocturia and increased mortality risk include sleep disruption and subsequent development of related comorbid conditions.

Patient expectations did not predict outcome of drug and behavioral treatment of urgency urinary incontinence.

OBJECTIVES: : This study aimed to determine whether expectations of treatment outcomes in women participating in a drug and behavioral treatment trial for urge urinary incontinence are related to patient factors, demographics, health-related locus of control, and treatment outcomes. METHODS: : Baseline assessments included expectations (improvement in bladder condition, time to improvement in bladder condition, and duration of improvement) and the Medical Health Locus of Control (MHLC) scale. Outcomes were measured by the Patient Global Impression of Improvement scale (PGI-I) at the end of active treatment (10 weeks) and 8 months after trial start. RESULTS: : At baseline among 173 subjects, 114 (66%) believed their incontinence would get "very much better," 94 (55%) expected improvement by 1 month, and 111 (66%) expected improvement would last for the rest of their lives. There were no significant associations between baseline expectations or MHLC with the Patient Global Impression of Improvement scale at 10 weeks or 8 months. CONCLUSIONS: : Expectations of treatment outcome and MHLC did not predict eventual patient-reported treatment outcome in this sample of women with urge-predominant urinary incontinence participating in a trial of drug and behavioral therapy.

Severe acidosis during laparoscopic repair of pelvic organ prolapse and incontinence.

The creation and maintenance of a carbon dioxide pneumoperitoneum to allow a laparoscopic approach to surgery for pelvic organ prolapse has been associated with hypercapnea and respiratory acidosis. We present a case report of a 68-year-old patient who developed severe acidosis during a robotic-assisted laparoscopic sacrocolpopexy and discuss a practical approach to surgical and anesthetic decision making.

Preoperative voiding detrusor pressures do not predict stress incontinence surgery outcomes.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to determine whether preoperative voiding detrusor pressures were associated with postoperative outcomes after stress incontinence surgery. METHODS: Opening detrusor pressure, detrusor pressure at maximum flow (p (det) Q(max)), and closing detrusor pressure were assessed from 280 valid preoperative urodynamic studies in subjects without advanced prolapse from a multicenter randomized trial comparing Burch and autologous fascia sling procedures. These pressures were compared between subjects with and without overall success, stress-specific success, postoperative detrusor overactivity, and postoperative urge incontinence using independent sample t tests. RESULTS: There were no clinically or statistically significant differences in mean preoperative voiding detrusor pressures in any comparison of postoperative outcomes. CONCLUSIONS: We found no evidence that preoperative voiding detrusor pressures predict outcomes in women with stress predominant urinary incontinence undergoing Burch or autologous fascial sling procedures.

Risk factors for recurrence following radical cystectomy for pathologic node negative bladder cancer.

BACKGROUND AND OBJECTIVES: To evaluate for risk factors associated with bladder cancer recurrence in patients with pathologically negative lymph nodes. METHODS: A retrospective review of 405 patients undergoing radical cystectomy for bladder cancer between 1996 and 2008 was performed. Patients with node-positive disease and <6 months of follow up were excluded. Clinical and pathological characteristics including stage, lymphadenectomy type (standard vs. extended), number of nodes removed, margin status, lymphovascular invasion (LVI), perineural invasion (PNI), presence of carcinoma in situ, and site of recurrence were evaluated. Kaplan-Meier analysis was used to calculate 5-year recurrence-free survival stratified by lymph node yield. RESULTS: Two hundred sixty patients met the inclusion criteria. Overall, 80 (30.8%) patients recurred within 5 years. Univariate analysis identified LVI, PNI, extravesical disease, positive margins, and lymph node yield <14 to be significant predictors of disease recurrence. On multivariate analysis LVI, PNI, and node yield <14 retained significance (P = 0.01, 0.037, 0.038, respectively). There was no difference in 5-year recurrence free survival when stratified by node yield using the Kaplan-Meier method (P = 0.138). CONCLUSIONS: We identified LVI, PNI, and lymph node yield <14 as three independent risk factors for bladder cancer recurrence in patients with node-negative bladder cancer.

Long-term outcomes of salvage radiotherapy for PSA-recurrent prostate cancer: validation of the Stephenson nomogram.

PURPOSE: Approximately one-third of patients who undergo radical prostatectomy for clinically localized prostate cancer will ultimately develop a biochemical recurrence. We report our long-term outcomes of salvage radiotherapy (SRT), and in so doing, validate a recently published prognostic nomogram. METHODS: A retrospective chart review was performed of all patients treated with SRT following radical prostatectomy for biochemical PSA recurrence at our institution between 1992 and 2003. We calculated the probability of 6-year biochemical progression-free survival following SRT and performed a goodness-of-fit test to ascertain whether the previously published nomogram correctly predicted our observations. RESULTS: During the study period, 96 patients were treated with SRT. At a median follow-up of 71 months, 44 (46%) had a durable PSA-free response. There was no significant difference between the observed progression-free survival and that predicted by the Stephenson nomogram (P = 0.7). Multivariate logistic regression analysis determined that PSA value at the initiation of SRT (P = 0.02) and pathologic Gleason Score (P = 0.04) were significantly associated with the probability of recurrence. CONCLUSIONS: During the study period, nearly half of patients treated with SRT for PSA recurrence following radical prostatectomy had a durable treatment response. We found the predictive nomogram developed by Stephenson, et al. to be valid when tested on our independent cohort of patients.

Nocturia research: current status and future perspectives.

This review summarizes the status of nocturia research, highlighting the condition's distinct nature, as well as areas where further studies are needed. Unlike other LUTS, nocturia has a specific and detrimental effect on the sleep period, and when >or=2 voids per night are experienced it is associated with various sequelae including reduced QoL and productivity, and increased morbidity and perhaps mortality. Many sources suggest that nocturia is associated with chronic medical illness, but little evidence demonstrates that successful treatment of these conditions results in normalization of nocturia, or that improvement in nocturia improves QoL and overall health. To date, management algorithms for LUTS have been based upon reasonable supposition and limited evidence, rather than controlled trials. Whilst a working clinical model is useful until conclusive research is available, a healthy scepticism should be maintained. It is likely that more than one contributory factor is responsible for nocturia, and management ought to better reflect this multifactorial pathophysiology. Indeed, traditional perspectives assuming nocturia to be part of the OAB or BPE symptom complex may have helped to propagate the misconception that therapy for these conditions is sufficient to improve nocturia. In reality, improvements in nocturia with anticholinergics, alpha-blockers and/or 5-alpha reductase inhibitors have been consistently disappointing. Antidiuretic therapy may represent a more tailored approach to management for many nocturia patients, given the high rates of nocturnal polyuria reported. Combination therapy may be required. Further high quality research on pathophysiology, management and patient-reported outcomes with treatment is needed to augment existing limited data.

Effect of amitriptyline on symptoms in treatment naïve patients with interstitial cystitis/painful bladder syndrome.

PURPOSE: Amitriptyline is frequently used to treat patients with interstitial cystitis/painful bladder syndrome. The evidence to support this practice is derived mainly from a small, single site clinical trial and case reports. MATERIALS AND METHODS: We conducted a multicenter, randomized, double-blind, placebo controlled clinical trial of amitriptyline in subjects with interstitial cystitis/painful bladder syndrome who were naïve to therapy. Study participants in both treatment arms received a standardized education and behavioral modification program. The drug dose was increased during a 6-week period from 10 up to 75 mg once daily. The primary outcome was a patient reported global response assessment of symptom improvement evaluated after 12 weeks of treatment. RESULTS: A total of 271 subjects were randomized and 231 (85%) provided a global response assessment at 12 weeks of followup. Study participants were primarily women (83%) and white (74%), with a median age of 38 years. In an intent to treat analysis (271) the rate of response of subjects reporting moderate or marked improvement from baseline in the amitriptyline and placebo groups was 55% and 45%, respectively (p = 0.12). Of the subgroup of subjects (207) who achieved a drug dose of at least 50 mg, a significantly higher response rate was observed in the amitriptyline group (66%) compared to placebo (47%) (p = 0.01). CONCLUSIONS: When all randomized subjects were considered, amitriptyline plus an education and behavioral modification program did not significantly improve symptoms in treatment naïve patients with interstitial cystitis/painful bladder syndrome. However, amitriptyline may be beneficial in persons who can achieve a daily dose of 50 mg or greater, although this subgroup comparison was not specified in advance.

Effects of colpocleisis on bowel symptoms among women with severe pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: Our objective was to evaluate bowel symptoms after colpocleisis. METHODS: This was a planned ancillary analysis of a prospective, colpocleisis cohort study of 152 women. Those with baseline and 1-year questionnaires (Colorectal-Anal Distress Inventory (CRADI) and the Colorectal-Anal Impact Questionnaire (CRAIQ)) were included. "Bothersome" CRADI symptoms (score>2("moderately", "quite a bit")) were identified. CRADI and CRAIQ scores were compared, and postoperative symptom resolution and new symptom development were measured. RESULTS: Of 121 (80%) subjects with complete data, mean age was 79.2 +/- 5.4 years and all had stage 3-4 prolapse. Procedures performed: partial colpocleisis (61%), total colpocleisis (39%), levator myorrhaphy (71%), and perineorrhaphy (97%). Bothersome bowel symptom(s) were present in 77% at baseline (obstructive (17-26%), incontinence (12-35%) and pain/irritation (3-34%)). All bothersome obstructive and most bothersome incontinence symptoms were less prevalent 1 year after surgery. CRADI and CRAIQ scores significantly improved. The majority of bothersome symptoms resolved (50-100%) with low rates of de novo symptoms (0-14%). CONCLUSIONS: Most bothersome bowel symptoms resolve after colpocleisis, especially obstructive and incontinence symptoms, with low rates of de novo symptoms.

Reflex testing of male urine specimens misses few positive cultures may reduce unnecessary testing of normal specimens.

OBJECTIVES: To determine the predictive values of leukocyte count for the presence of a positive urine culture in ambulatory male urology patients. Many institutions have adopted a practice of "reflex testing" urine samples, in which urine culture is only performed if a threshold number of leukocytes (WBCs [white blood cells]) is present. METHODS: We performed a retrospective chart review of all male patients who presented to our tertiary-care urology clinic in 2006. Only those with both a urinalysis and urine culture performed were included in this study. A urine culture was considered positive if at least 10,000 colonies of a uropathogen were present. Data were tabulated and analyzed using SPSS V15.0 software. RESULTS: Of 874 patients, 176 (20%) urine cultures were positive. WBCs were present at a concentration of at least 5/hpf (high power field) in 367 (42%) of all specimens and in 163 of 176 (93%) positive specimens, but were present at lower concentrations in 13 specimens with positive cultures. The presence of >5 WBC/hpf had a positive predictive value of 47%, and a negative predictive value of 97% for positive culture. CONCLUSIONS: Reflex urine testing, in which cultures are done on urine specimens with >5 WBC/hpf, would have missed 7% of positive urine cultures, while avoiding 69% of all cultures. Reflex testing may be appropriate in most ambulatory urology patients.