L. Keith Lloyd

The hytrin community assessment trial study: A one-year study of terazosin versus placebo in the treatment of men with symptomatic benign prostatic hyperplasia*

OBJECTIVESnTo determine the clinical effectiveness and safety of alpha(1)-blockade therapy versus placebo in the treatment of men with moderate to severe symptoms of prostatism in a community-based population under usual care conditions.nnnMETHODSnThe Hytrin Community Assessment Trial is a prospective, placebo-controlled, randomized, double-blinded, 1-year clinical trial, conducted at 15 academic medical centers (regional sites) and 141 private urology practices (satellite sites). A total of 2084 men at least 55 years old with moderate to severe symptoms of benign prostatic hyperplasia (BPH) as determined by an American Urological Association (AUA) Symptom Score (AUA-SS) of 13 or more points and a bother score (AUA-BS) of 8 or more were enrolled. Randomized patients at regional sites were required to have a peak urinary flow rate less that 15 mL/s with voided volume of at least 150 mL. Treatment with terazosin was initiated with 1 mg daily for 3 days, followed by 2 mg daily for 25 days. Thereafter, patients were titrated stepwise to 5 or 10 mg if they failed to achieve a 35% or greater improvement in the AUA-SS. Primary outcome measures were AUA-SS, AUA-BS, BPH Impact Index (BII), disease-specific quality of life (QQL) score, and treatment failure as defined as discontinuation due to persistent or worsening symptoms or need for surgical intervention for BPH. Secondary outcome measures were peak urinary flow rate and postvoid residual urine volume.nnnRESULTSnAUA-SS (0 to 35 point scale) improved from a baseline mean of 20.1 points by 37.8% during terazosin (n=976) and by 18.4% during placebo (n=973) treatment (P<0.001). Similarly, statistically superior improvements were observed in regard to the AUA-BS, BII, and the QQL score in the terazosin-treated patients. Peak urinary flow rate improved from a baseline of 9.6 mL/s (both regional treatment groups) by 2.2 mL/s in the terazosin group (n=137) and by 0.7 mL/s in the placebo group (n=140) (P< or = 0.05). Treatment failure occurred in 11.2% of terazosin- and 25.4% of placebo-treated patients (P<0.001; Kaplan-Meier adjusted withdrawal rates of 365 days). Withdrawal from study drug treatment due to adverse events occurred in 19.7% of terazosin- and 15.2% of placebo-treated patients (P<0.001).nnnCONCLUSIONSnTerazosin given once daily in a dose ranging from 2 to 10 mg in community-based urology practices under conditions simulating usual care is effective in reducing the symptoms, perception of bother, and the impairment of QQL due to urinary symptoms in men with moderate to severe symptoms of prostatism. This effect is superior to placebo and maintained over 12 months of follow-up. Clinical research outcome studies in BPH can be conducted in community-based practices, thus simulating as closely as possible usual care conditions.

Short-term and long-term changes in renal function after donor nephrectomy

We retrospectively examined the effect of nephrectomy on renal function in 55 living related donors. Renal function was measured with 131iodine-orthoiodohippurate scans. All patients were studied preoperatively, and 1 week and 1 year postoperatively. In 20 patients 10-year followup was available. Compensatory hypertrophy was complete 1 week postoperatively: effective renal plasma flow of the remaining kidney was 32.5% higher than preoperatively. The increase remained stable for at least a year. The degree of compensatory hypertrophy was significantly greater in male patients (46.9% after 1 week) than in female patients (26.7%). Compensatory hypertrophy occurred in all age groups studied and it was most pronounced in patients less than 30 years old. In the patients followed for 10 years effective renal plasma flow decreased from 387.7 ml. per minute 1 week after nephrectomy to 367.4 ml. per minute at 10 years. This result is similar to the decrease seen in the normal population. According to our results, renal donation by living related persons does not lead to long-term decrease in renal function.

Urodynamic Measures Do Not Predict Stress Continence Outcomes After Surgery for Stress Urinary Incontinence in Selected Women

PURPOSEnWe determined the prognostic value of preoperative urodynamic results in patients with stress urinary incontinence.nnnMATERIALS AND METHODSnIn a 9-center surgical trial, women with stress urinary incontinence were randomized to a Burch or pubovaginal sling procedure. Women were eligible for the study if they had predominant stress urinary incontinence symptoms, a positive cough stress test, a bladder capacity more than 200 ml and urethral hypermobility. Preoperative free uroflowmetry, filling cystometry and pressure flow studies were performed in all. Overall treatment success required a negative pad test, no urinary incontinence on a 3-day diary, a negative stress test, no self-reported stress urinary incontinence symptoms and no re-treatment for stress urinary incontinence. Stress specific success required all of the last 3 criteria. We examined urodynamic measures, and whether the presence of urodynamic stress incontinence, the presence of detrusor overactivity and Valsalva leak point pressure would predict surgical success.nnnRESULTSnSubjects with urodynamic stress incontinence had a 2-fold greater odds of overall success when compared with the No urodynamic stress incontinence group, but this trend did not quite reach statistical significance (OR 2.26; 95% C.I. 0.99, 5.17). Odds of stress specific success did not differ by urodynamic stress incontinence status. Subjects with detrusor overactivity did not have significantly worse success rates. Stratifying by treatment group, there was no difference in mean Valsalva leak point pressure values between surgical successes and failures.nnnCONCLUSIONSnWe found a nearly statistically significant trend that women with urodynamic stress incontinence are twice as likely to have a successful overall outcome from surgical management of stress urinary incontinence as women without urodynamic stress incontinence. The level of Valsalva leak point pressure and the presence of detrusor overactivity do not predict the success outcomes after the Burch or autologous fascia sling procedures in women with pure or predominant stress urinary incontinence. The impact of urodynamic studies on surgical outcomes needs further investigation.

Behavioral Therapy With or Without Biofeedback and Pelvic Floor Electrical Stimulation for Persistent Postprostatectomy Incontinence: A Randomized Controlled Trial

CONTEXTnAlthough behavioral therapy has been shown to improve postoperative recovery of continence, there have been no controlled trials of behavioral therapy for postprostatectomy incontinence persisting more than 1 year.nnnOBJECTIVEnTo evaluate the effectiveness of behavioral therapy for reducing persistent postprostatectomy incontinence and to determine whether the technologies of biofeedback and pelvic floor electrical stimulation enhance the effectiveness of behavioral therapy.nnnDESIGN, SETTING, AND PARTICIPANTSnA prospective randomized controlled trial involving 208 community-dwelling men aged 51 through 84 years with incontinence persisting 1 to 17 years after radical prostatectomy was conducted at a university and 2 Veterans Affairs continence clinics (2003-2008) and included a 1-year follow-up after active treatment. Twenty-four percent of the men were African American; 75%, white.nnnINTERVENTIONSnAfter stratification by type and frequency of incontinence, participants were randomized to 1 of 3 groups: 8 weeks of behavioral therapy (pelvic floor muscle training and bladder control strategies); behavioral therapy plus in-office, dual-channel electromyograph biofeedback and daily home pelvic floor electrical stimulation at 20 Hz, current up to 100 mA (behavior plus); or delayed treatment, which served as the control group.nnnMAIN OUTCOME MEASUREnPercentage reduction in mean number of incontinence episodes after 8 weeks of treatment as documented in 7-day bladder diaries.nnnRESULTSnMean incontinence episodes decreased from 28 to 13 per week (55% reduction; 95% confidence interval [CI], 44%-66%) after behavioral therapy and from 26 to 12 (51% reduction; 95% CI, 37%-65%) after behavior plus therapy. Both reductions were significantly greater than the reduction from 25 to 21 (24% reduction; 95% CI, 10%-39%) observed among controls (P = .001 for both treatment groups). However, there was no significant difference in incontinence reduction between the treatment groups (P = .69). Improvements were durable to 12 months in the active treatment groups: 50% reduction (95% CI, 39.8%-61.1%; 13.5 episodes per week) in the behavioral group and 59% reduction (95% CI, 45.0%-73.1%; 9.1 episodes per week) in the behavior plus group (P = .32).nnnCONCLUSIONSnAmong patients with postprostatectomy incontinence for at least 1 year, 8 weeks of behavioral therapy, compared with a delayed-treatment control, resulted in fewer incontinence episodes. The addition of biofeedback and pelvic floor electrical stimulation did not result in greater effectiveness.nnnTRIAL REGISTRATIONnclinicaltrials.gov Identifier: NCT00212264.

Effect of pentosan polysulfate therapy on intravesical potassium sensitivity

OBJECTIVESnTo evaluate further the intravesical potassium sensitivity test (PST) as an indicator of the epithelial leak of interstitial cystitis (IC) and determine whether successful pentosan polysulfate (PPS; Elmiron) treatment is associated with a change in PST results. Most individuals with IC appear to have an abnormally permeable epithelium that allows urinary solutes such as potassium to penetrate to the bladder interstitium, provoking symptoms.nnnMETHODSnData were from an optimal dose trial of PPS in IC. Patients underwent a PST before and after a 32-week trial of 300, 600, or 900 mg PPS/day. The response to PPS treatment was measured using the Patient Overall Rating of Improvement in Symptoms scale. The before and after treatment PSTs and Patient Overall Rating of Improvement of Symptoms scores were compared.nnnRESULTSnOf 377 patients with IC at 28 centers, 302 (80%) had a positive PST at entry. Of the 198 patients who completed the study, 153 were PST positive at entry and 92 (60%) showed clinical improvement at exit. Clinically improved patients had significant improvement on the PST analog pain and urgency scales (3.2 to 1.3 and 3.6 to 1.9, respectively; P <0.0001). In contrast, patients with no clinical improvement had no significant change in pain (3.1 to 2.7) or urgency (3.6 to 3.2).nnnCONCLUSIONSnPST shows abnormal epithelial permeability in most patients with IC and a significant reduction in this permeability after successful PPS therapy. PST appears to be a valid indicator of epithelial abnormality and a reliable test in the diagnosis of IC.

Urodynamic changes associated with behavioral and drug treatment of urge incontinence in older women

OBJECTIVES: To describe changes in bladder function and voiding frequency associated with behavioral and drug treatment for urge incontinence and to examine whether these variables mediate the positive effects of treatment on the frequency of incontinence.

Comparison of long-term renal function after spinal cord injury using different urinary management methods☆☆☆

OBJECTIVEnTo determine the effect of different bladder management methods on long-term renal function in persons with spinal cord injury (SCI).nnnDESIGNnCohort study.nnnSETTINGnModel SCI care system within a large teaching hospital.nnnPATIENTSnConsecutive sample of 1,114 persons with SCI who were injured between 1969 and 1994.nnnMAIN OUTCOME MEASUREnTotal and individual kidney effective renal plasma flow (ERPF).nnnRESULTSnERPF was generally lower in persons with cervical injuries or kidneys that had a renal stone, older persons, and women. Overall, there was very little change in renal function as time postinjury increased, and there were no clinically meaningful differences in the change in renal function over time among persons using different bladder management methods.nnnCONCLUSIONnRenal function was adequately preserved in the great majority of persons and did not appear to be influenced to any great extent by method of bladder management.

Prolapse and Incontinence Surgery in Older Women

PURPOSEnPelvic floor disorders including urinary incontinence, pelvic organ prolapse and fecal incontinence are common problems encountered by the older woman. With the increasing population of older American women urologists and gynecologists can expect to provide evaluation and treatment of these conditions with increasing frequency. These conditions are amenable to medical and surgical therapies.nnnMATERIALS AND METHODSnContemporary articles (2003 to the present) that included older women undergoing urogynecological surgery were included in this review. Current data on morbidity, mortality and/or surgical outcomes are presented with evidence based preoperative, intraoperative and postoperative surgical management strategies.nnnRESULTSnOlder women undergoing pelvic floor surgery can expect operative risks as well as subjective and objective anatomical and quality-of-life outcomes similar to those of younger women.nnnCONCLUSIONSnThe decision for surgical intervention for the treatment of pelvic floor disorders should not be based on chronological age alone. Before selecting a specific surgical procedure, all existing pelvic floor defects should be evaluated. Further research is required to understand the impact that surgery for pelvic floor disorders has on anatomical, physiological and functional outcomes in older women.

An Endogenous Pain Control System is Altered in Subjects with Interstitial Cystitis

PURPOSEnMultiple studies have demonstrated that in healthy subjects, painful stimuli applied to one part of the body inhibit pain sensation in other parts of the body, a phenomenon referred to as conditioned pain modulation. Conditioned pain modulation is related to the presence of endogenous pain control systems. Studies have demonstrated deficits in conditioned pain modulation associated inhibition in many but not all chronic pain disorders. In this study we determine whether conditioned pain modulation is altered in subjects with interstitial cystitis/bladder pain syndrome.nnnMATERIALS AND METHODSnFemale subjects with and without the diagnosis of interstitial cystitis/bladder pain syndrome were studied psychophysically using quantitative cutaneous thermal, forearm ischemia and ice water immersion tests. Conditioned pain modulation was assessed by quantifying the effects of immersion of the hand in ice water (conditioning stimulus) on threshold and tolerance of cutaneous heat pain (test stimulus) applied to the contralateral lower extremity.nnnRESULTSnThe conditioned pain modulation responses of the subjects with interstitial cystitis/bladder pain syndrome were statistically different from those of healthy control subjects for cutaneous thermal threshold and tolerance measures. Healthy control subjects demonstrated statistically significant increases in thermal pain tolerance whereas subjects with the diagnosis of interstitial cystitis/bladder pain syndrome demonstrated statistically significant reductions in thermal pain tolerance.nnnCONCLUSIONSnAn endogenous pain inhibitory system normally observed with conditioned pain modulation was altered in subjects with interstitial cystitis/bladder pain syndrome. This finding identifies interstitial cystitis/bladder pain syndrome as similar to several other chronic pain disorders such as fibromyalgia and irritable bowel syndrome, and suggests that a deficit in endogenous pain inhibitory systems may contribute to such chronic pain disorders.

Recurrent kidney stone: a 25-year follow-up study in persons with spinal cord injury.

OBJECTIVESnTo document the recurrence rate of kidney stones in patients with spinal cord injury and to assess the potential contributing factors and long-term renal function outcome.nnnMETHODSnA consecutive sample of 77 patients with initial kidney stones followed up on a yearly basis between 1973 and 1999 was used to estimate stone recurrence, stratified by demographic and clinical characteristics. Longitudinal data analyses were performed to assess the change in renal function over time among various post-treatment outcomes.nnnRESULTSnDuring an average of 7 years (range 1 to 21) of follow-up after the initial stone episode, 19 patients with recurrence, 15 with residual stones, and 43 who were stone free were documented. It was estimated that approximately 34% of the patients with an initial stone would develop a second stone episode within 5 years. This figure did not significantly change during the past 25 years (P = 0.18). Stone recurrence was two or more times greater for men than for women, for whites than for blacks, and for tetraplegics than for paraplegics, but the differences were not statistically significant (P >0.05). Renal function did not significantly decline over time for any of the post-treatment outcomes of the initial stones.nnnCONCLUSIONSnDespite marked improvement in urologic rehabilitation, little progress has been made during the past 25 years in reducing stone recurrence in persons with spinal cord injury. Future studies are required to determine the critical components of the causal pathway to stone formation, which may lead to the establishment of effective prophylactic interventions.