Clinical trial outcomes of high- and extra high-profile breast implants.

BACKGROUND: Clinical data concerning potential risks and benefits associated with the use of high- and extra high-profile breast implants are lacking. OBJECTIVES: The authors assess the risk of adverse events (AE) with high- and extra high-profile breast implants compared with low- to moderate-profile breast implants in patients enrolled in long-term clinical studies. METHODS: Relative risks (RR) of capsular contracture (CC), moderate to severe malposition, and secondary procedure were calculated using Cox proportional hazards regression, adjusting for patient, procedure, and device characteristics among patients enrolled in the primary augmentation cohorts of the Core (NCT00689871; round, silicone-filled implants) and 410 (NCT00690339; shaped, highly cohesive silicone-filled implants) clinical studies. Study pooling provided comparisons of implant shape and fill, as well as contributed to relative outcome. Analyses were also stratified by preoperative breast measures. RESULTS: In the Core study (N = 454; 907 implants; mean follow-up 7.2 years; 3669 person-years), and the combined Core and 410 studies (N = 4412; 8811 implants; mean follow-up 3.0 years; 14 528 person-years), risk of CC, secondary procedures, and mastopexy as a secondary procedure were reduced in high-profile versus low- to moderate-profile breast implants (P < .05). The risk of moderate to severe malposition was not significantly different between high-profile and low- to moderate-profile breast implants in the Core or combined studies (RR, 0.58 [95% confidence interval (CI), 0.22-1.51] and RR, 0.72 [95% CI, 0.31-1.70], respectively). Analyses stratified by preoperative breast measures did not indicate higher risk of CC, malposition, or secondary procedure among patients with either smaller (<17 cm) or larger (≥17 cm) preoperative measures. CONCLUSIONS: Among primary augmentation patients with round, silicone-filled, or shaped, highly cohesive silicone-filled implants, high- and extra high-profile implants were associated with lower risks of CC, secondary procedures, and mastopexy and were not associated with greater risks of moderate to severe malposition versus low- to moderate-profile implants. LEVEL OF EVIDENCE: 3.

National practice patterns for immediate postoperative instillation of chemotherapy in nonmuscle invasive bladder cancer.

PURPOSE: We assessed the use of intravesical postoperative chemotherapy among United States urologists in patients with nonmuscle invasive bladder cancer. MATERIALS AND METHODS: A national sample of United States based urologists (259) retrospectively assessed their practice patterns involving intravesical postoperative chemotherapy after transurethral resection in patients with nonmuscle invasive bladder cancer. These urologists reviewed the medical records of their last 4 patients with nonmuscle invasive bladder cancer, and completed a case report form for specific demographic, pathological and treatment information. Selection criteria included the pathological and patient factors of histologically confirmed diagnosis of nonmuscle invasive bladder cancer-transitional cell carcinoma, completion of initial treatment plan with ongoing observation, candidate for or recipient of intravesical therapy, and no ongoing initial intravesical induction therapy. RESULTS: Overall the participation rate among those sampled was 61%. Of the 1,010 eligible patients with nonmuscle invasive bladder cancer 59.6% received instillation therapy during the initial treatment, of whom 28.4% (16.9% of patients overall) received intravesical postoperative chemotherapy. Primary, low risk patients most often received intravesical postoperative chemotherapy and 90.4% of the time patients received immediate instillation within 12 hours of surgery. However, of the urologists surveyed 66% never used intravesical postoperative chemotherapy, 17% used intravesical postoperative chemotherapy half (50%) of the time and only 2% used intravesical postoperative chemotherapy all (100%) of the time. CONCLUSIONS: Wide variation in the use of intravesical postoperative chemotherapy exists among urologists in the United States. The reason for the great diversity in the use of intravesical postoperative chemotherapy is speculative. However, physician awareness, physician bias, recurrence risk, and local pharmacy and hospital practice factors are all likely contributing factors.

Economic and humanistic consequences of preventable bladder tumor recurrences in nonmuscle invasive bladder cancer cases.

PURPOSE: Perioperative intravesical chemotherapy following transurethral resection of bladder tumor has been underused despite level 1 evidence supporting its performance. The primary objective of this study was to estimate the economic and humanistic consequences associated with preventable recurrences in patients initially diagnosed with nonmuscle invasive bladder cancer. MATERIALS AND METHODS: Using population based estimates of nonmuscle invasive bladder cancer incidence, a 2-year model was developed to estimate the number of preventable recurrences in eligible patients untreated with perioperative intravesical chemotherapy. Therapy utilization rates were obtained from a retrospective database analysis and a chart review study of 1,010 patients with nonmuscle invasive bladder cancer. Recurrence rates of nonmuscle invasive bladder cancer were obtained from a randomized clinical trial comparing transurethral resection of bladder tumor with or without perioperative mitomycin C. Costs were estimated using prevailing Medicare reimbursement rates. Quality adjusted life-year estimates and disutilities for complications were obtained from the literature. RESULTS: The model estimated that 7,827 bladder recurrences could be avoided if all patients received immediate intravesical chemotherapy. It estimated an economic savings of $3,847 per avoidable recurrence, resulting in an aggregate savings of $30.1 million. The model also estimated that 1,025 quality adjusted life-years are lost every 2 years due to preventable recurrences, resulting in 0.13 quality adjusted life-years (48 quality adjusted days) lost per avoidable recurrence. This translates into 0.02 quality adjusted life-years (8.1 quality adjusted days) lost per patient not receiving immediate intravesical chemotherapy. CONCLUSIONS: Greater use of immediate intravesical chemotherapy in the United States has the potential to substantially decrease the economic and humanistic burdens of nonmuscle invasive bladder cancer.

The efficacy and tolerability of dapsone 5% gel in female vs male patients with facial acne vulgaris: gender as a clinically relevant outcome variable.

BACKGROUND: Gender differences in skin and acne have been reported. OBJECTIVE: To evaluate the effect of gender on the efficacy and tolerability of dapsone 5% gel. METHODS: This was a pooled analysis of data from 2 identical phase 3 randomized, double-blind, and vehicle-controlled trials (DAP0203 and DAP0204) of dapsone 5% gel conducted in the United States and Canada between November 2002 and September 2003. A total of 2,898 patients with acne vulgaris were included in the pooled analysis. Of these, 1,453 patients (753 female, 700 male) received dapsone 5% gel twice daily, and 1,445 patients (767 female, 678 male) received vehicle twice daily. End points included the mean percentage reduction from baseline in acne lesion counts and the proportion of patients achieving clinical success (Global Acne Assessment Scale score of 0, clear skin, or 1, almost clear skin). Assessments were performed at baseline and at weeks 2, 4, 6, 8, and 12. RESULTS: The mean percentage reduction in acne lesion counts at 12 weeks was significantly greater in females than males in both treatment groups. The mean reduction in total lesion counts in dapsone-treated females and males was, respectively, 46.6% vs 35.8% (P<.0001). Reductions in papulopustular and comedonal lesion counts were likewise significantly higher in female than male patients (each P<.0001). Significantly more dapsone-treated females than males achieved clinical success (48.6% vs 34.4%; P=.0003). CONCLUSION: The response to dapsone 5% gel appears to be influenced by gender, with female patients experiencing a significantly greater reduction in acne lesion counts and a significantly higher clinical success rate following 12 weeks of treatment. These data suggest that gender is a novel predictor of outcome that should be considered in acne clinical trial design and analysis.

Trospium chloride once-daily extended release is efficacious and tolerated in elderly subjects (aged ≥ 75 years) with overactive bladder syndrome.

OBJECTIVE: • To evaluate the safety and efficacy of once-daily trospium chloride extended release (ER) in overactive bladder syndrome (OAB) in subjects aged ≥ 75 years. SUBJECTS AND METHODS: • The analysis included subjects ≥ 75 years of age with OAB. • A subgroup analysis of pooled data was performed for subjects aged ≥ 75 years from two randomized, double-blind, multicenter studies of subjects with OAB receiving once-daily trospium 60 mg extended release (ER) or placebo for 12 weeks, followed by 9-month open-label extension periods during which all subjects received trospium ER. A total of 143 of the 1165 subjects from two phase III registration trials who were aged ≥ 75 years (85 trospium ER, 58 placebo; mean age 79 years and ranging up to 90 years; 73% female) were evaluated. • Dual primary efficacy variables were the changes from baseline in the average number of toilet voids per day and urge urinary incontinence episodes per day. RESULTS: • At week 12 of the double-blind period, trospium ER produced greater improvements from baseline than placebo in voiding diary parameters, OAB Patient Global Assessment, and quality of life. • Efficacy and tolerability persisted among subjects receiving open-label trospium ER for up to 1 year. CONCLUSIONS: • Once-daily trospium chloride 60 mg ER demonstrated efficacy vs placebo and was tolerated in subjects aged ≥ 75 years with OAB. • For subjects who continued into the open-label treatment period, efficacy and tolerability were observed for up to 1 year.

Once-daily administration of trospium chloride extended release provides 24-hr coverage of nocturnal and diurnal symptoms of overactive bladder: an integrated analysis of two phase III trials.

AIMS: Once-daily extended release (XR) trospium chloride, which provides therapeutic trospium plasma concentrations over 24 hours, has demonstrated efficacy in treating overactive bladder (OAB) symptoms as evaluated over a 24-hr period. This analysis examined the effects of trospium XR on diurnal and nocturnal OAB symptoms. METHODS: Pooled data were analyzed from two identically designed Phase III trials in which patients with OAB were randomized to receive trospium XR 60 mg or placebo once daily in the morning for 12 weeks. Efficacy was assessed using 3-day urinary diaries. Diurnal events were those occurring from arising from bed in the morning until retiring in the evening; nocturnal events were those occurring from retiring until arising. RESULTS: In total, 1,165 patients received trospium XR (N = 578) or placebo (N = 587). At Week 12 comparison of trospium XR versus placebo, a significantly greater mean reduction from baseline in nocturnal voids (-0.8 vs. -0.6; P = 0.006) and diurnal voids (-1.9 vs. -1.4; P < 0.0001) was noted. At Week 12, the mean percent reduction from baseline with trospium XR versus placebo in nocturnal urge urinary incontinence (UUI) episodes (-60.2% vs. -48.3%; P = 0.003) and mean absolute reduction in diurnal UUI episodes (-2.0 vs. -1.5; P < 0.0001) was significantly greater. Predictors of nocturnal response were duration (weeks) and type of therapy (trospium XR vs. placebo). Reductions in nocturnal toilet voids were accompanied by significant improvements in sleep-related quality of life (QoL) domains. CONCLUSIONS: Trospium XR significantly improved both nocturnal and diurnal OAB symptoms. Nocturnal improvements were associated with sleep-related QoL benefits. These results indicate that the XR formulation of trospium chloride provides effective 24-hr coverage of OAB symptoms.

Once-daily trospium chloride 60 mg extended-release provides effective, long-term relief of overactive bladder syndrome symptoms.

AIMS: Once-daily extended-release (XR) trospium chloride has been evaluated for the treatment of overactive bladder syndrome (OAB) in two 12-week randomized, double-blind, placebo-controlled studies. This pooled analysis of the 9-month open-label extensions to these studies evaluated the long-term efficacy and tolerability of trospium XR. METHODS: Following double-blind treatment, subjects with OAB could enter the open-label period, during which they received trospium 60 mg XR once daily for 36 weeks. The primary efficacy variables were changes from baseline in the number of toilet voids and urgency urinary incontinence (UUI) episodes per day at Week 48. Adverse events (AEs) were also recorded. RESULTS: Of the 1,027 subjects who completed double-blind treatment, 944 (92%) continued into the open-label period (placebo-to-trospium, N = 483; trospium-to-trospium, N = 461); 332 (68.7%) and 335 (72.7%), respectively, completed the open-label period. At Week 48, the mean change from baseline in the number of toilet voids/day was -3.21 in the placebo-to-trospium group and -3.35 in the trospium-to-trospium group, and the median change from baseline in the number of UUI episodes/day was -2.33 in both groups. Efficacy was maintained relative to Week 12 in trospium-to-trospium subjects, while improvement was seen following trospium initiation in placebo-to-trospium subjects. Improvement from baseline was also observed on secondary efficacy parameters at Week 48. Trospium was well tolerated; dry mouth and constipation were the most common class treatment-emergent AEs. Central nervous system AEs were rare and did not increase with long-term treatment. CONCLUSIONS: Long-term treatment of OAB with once-daily trospium 60 mg XR is effective and well tolerated.

Clinical evidence for the role of a topical anti-inflammatory agent in comedonal acne: findings from a randomized study of dapsone gel 5% in combination with tazarotene cream 0.1% in patients with acne vulgaris.

BACKGROUND: Acne pathogenesis is multifactorial and includes inflammation. Combining drugs targeting multiple components of acne pathogenesis is standard practice. OBJECTIVE: To assess the safety and efficacy of dapsone gel 5%, an anti-inflammatory agent, in combination with tazarotene cream 0.1% for treatment of acne vulgaris. METHODS: Patients were randomized to receive combination therapy (dapsone gel 5% twice-daily plus tazarotene cream 0.1% daily) or monotherapy (tazarotene cream 0.1% daily). Efficacy and safety data were collected after 1, 2, 4, 8, and 12 weeks of treatment. RESULTS: Patients in both arms (n=86, dapsone + tazarotene; n=85, tazarotene) showed significant reductions from baseline in inflammatory, noninflammatory and total lesion counts (P is less than .001 for all). At 12 weeks, patients treated with dapsone plus tazarotene showed a greater reduction from baseline in noninflammatory (comedonal) and total lesion counts than tazarotene-treated patients (noninflammatory, 59.7 percent vs. 46.5 percent, P=.01; total, 63.3% vs. 53.6%, P=.02). The percentage of patients achieving treatment success (an investigator subjective score of 0 [none] or 1 [minimal]) was greater in dapsone plus tazarotene?treated patients (42.2%) than in tazarotene-treated patients (21.8%;P=.01). Both treatments were well tolerated. CONCLUSION: Combination therapy with dapsone gel 5% plus tazarotene cream 0.1% was more effective than tazarotene monotherapy for treatment of comedonal acne. The results suggest that anti-inflammatory agents such as dapsone can effectively treat early stages of acne (both comedonal and noncomedonal) when used in combination with a retinoid.

Obesity is associated with a more severe overactive bladder disease state that is effectively treated with once-daily administration of trospium chloride extended release.

AIMS: Obesity is an established risk factor for urinary incontinence, yet no information exists as to the efficacy of antimuscarinic agents in this population. The goal of this study is to examine the efficacy of once daily trospium chloride (Sanctura) XR in overweight and obese patients with the overactive bladder syndrome. METHODS: The primary and secondary end-points of the 1,165 study subjects from the integrated trospium chloride XR pivotal trials were stratified by World Health Organization (WHO) obesity levels I and II. RESULTS: Obesity (WHO level I, II criteria) was associated with a more severe baseline OAB disease state (P < 0.01). Trospium chloride XR was more effective than placebo at reducing the primary endpoints (toilet voids, UUI, P < 0.0001) and at improving the secondary end-points (percent patients continent and urgency severity, P < 0.0001) for WHO obesity levels I and II. CONCLUSIONS: Obesity is associated with a more severe OAB disease state. Once daily trospium chloride XR is efficacious in the obese patient with the OAB syndrome.

Delayed presentation of urinoma after radiofrequency ablation-assisted laparoscopic partial nephrectomy.

PURPOSE: To examine the outcomes and complications of thermal ablation-assisted laparoscopic partial nephrectomy (LPN). PATIENTS AND METHODS: Radiofrequency ablation (RFA)-assisted laparoscopic partial nephrectomy was employed in 16 consecutive renal masses with a mean size of 3.0 cm over 12 months. The indications were primarily adjacent bowel, hilar location, or both. After RFA, the renal mass was laparoscopically excised and examined pathologically. RESULTS: The mean operative treatment time was 99 minutes. The estimated blood loss was 121 mL, and no patient required a blood transfusion. Urinoma was diagnosed in three patients at an average of 13 days postoperatively and resolved with conservative management or ureteral stent placement. CONCLUSIONS: Radiofrequency ablation-assisted LPN provides effective hemostasis and, in the short term, cancer control. In this setting, urinoma presents as ipsilateral flank pain 1 to 2 weeks after surgery. The proposed mechanism for the delayed presentation is thermal injury to the collecting system, although an unrecognized direct collecting-system injury is possible. Conservative management, ureteral stent placement, or both led to resolution of all of the urinomas.

Urologic manifestations of nonurologic diseases gastrointestinal disorders.

A variety of common, gastrointestinal diseases result in significant genitourinary tract pathology. In general, knowledge of these associated disease processes permit rapid and accurate diagnosis and treatment. The underlying thread is the recognition of one pathophysiological process to explain patterns of a single disease.

The impact of osteoporosis in men treated for prostate cancer.

Prostate cancer patients are at significant risk for SREs, with up to 50% of androgen-insensitive patients experiencing an SRE at 24 months. The risk increases with the duration and type of cancer treatment. SREs decrease HRQOL, increase the cost of care, and are associated negatively with overall survival. Screening men at greatest risk (slender white men and men with hormone refractory disease or metastatic disease) with BMD measurements, and initiating empiric therapy (vitamin D3, calcium, parenteral estrogens, bisphosphates) may be warranted.

Effect of concomitant administration of trospium chloride extended release on the steady-state pharmacokinetics of metformin in healthy adults.

BACKGROUND: Overactive bladder (OAB) is often associated with a number of co-morbid medical conditions, including diabetes mellitus. This may necessitate several concomitant treatments, thus creating the potential for drug-drug interactions (DDIs). Trospium is renally eliminated, not metabolized via cytochrome P450; therefore, cytochrome P450 DDIs are unlikely. However, coadministration with another renally eliminated drug (e.g., metformin) may theoretically result in a DDI. OBJECTIVE: The objective of this study was to evaluate the pharmacokinetics (plasma and urine) and safety/tolerability of the coadministration of trospium chloride extended release (XR) and metformin under steady-state conditions in healthy male and female subjects. METHODS: In a single-centre, randomized, open-label, two-group, two-period study in healthy males and females aged 18-45 years, 44 subjects received oral metformin 500 mg twice daily for 3.5 days during one period, and oral trospium chloride XR 60 mg once daily for 10 days, followed by trospium chloride XR 60 mg once daily for 4 days plus metformin 500 mg twice daily for 3.5 days during the other period. The two periods occurred in a crossover fashion, separated by a 3-day washout period. RESULTS: Trospium chloride XR coadministration did not alter metformin steady-state pharmacokinetics. Metformin coadministration reduced trospium steady-state maximum plasma concentration (by 34 %) and area under the concentration-time curve from 0-24 hours (by 29 %). Neither drug's renal clearance was affected. No safety/tolerability issues of concern were observed with coadministration. CONCLUSION: No dosage adjustment is necessary for metformin when coadministered with trospium chloride XR.

Primary breast augmentation clinical trial outcomes stratified by surgical incision, anatomical placement and implant device type.

BACKGROUND: Clinical evidence concerning the potential risks and benefits associated with surgical incision, anatomical pocket and implant device type in primary breast augmentation is lacking. OBJECTIVES: This study assesses relative risk (RR) of adverse events stratified by surgical incision, anatomical pocket and breast implant device in primary augmentation patients enrolled in Core (NCT00689871, round/silicone devices) and 410 (NCT00690339, anatomically shaped/highly cohesive silicone devices) long-term clinical trials. METHODS: RR for time-to-first-event of Baker grade 3-4 capsular contracture (CC), moderate-severe malposition, and secondary procedure were calculated using multivariate time-to-event regression analysis. RESULTS: Risk of CC was increased with periareolar (unadjusted model only) and with axillary (adjusted model) versus inframammary incision. Risk of CC was significantly reduced with subpectoral versus subglandular placement (adjusted model), and with textured surface/round/silicone-filled devices and textured surface/shaped/highly cohesive silicone-filled devices versus smooth surface/round/silicone-filled devices (adjusted model). Risk of CC was significantly reduced with textured surface devices independent of subpectoral or subglandular placement (adjusted model). In a number-needed-to-treat analysis, 7-9 patients needed to be treated with a textured surface device to prevent one Baker grade 3-4 CC over 10 years. Risk of moderate-severe malposition was significantly increased with periareolar (adjusted model) and axillary (adjusted model) versus inframammary incision; and significantly lower with textured surface/shaped/highly cohesive silicone-filled devices than with smooth surface/round/silicone-filled devices (adjusted model). Risk of secondary procedures was significantly increased with periareolar (adjusted model) and axillary (adjusted model) versus inframammary incision; and significantly reduced with textured surface/shaped/highly cohesive silicone-filled devices versus smooth surface/round/silicone-filled devices (adjusted model). CONCLUSIONS: In primary breast augmentation, surgical incision, anatomical pocket, and device were significant predictors of clinical outcomes: capsular contracture, malposition and secondary procedure.

Interim results at 48 weeks of LAP-BAND AP experience (APEX) study: prospective, multicenter, open-label longitudinal patient observational study.

BACKGROUND: The development of laparoscopic adjustable gastric banding marked a breakthrough in minimally invasive bariatric surgery. The unique features of gastric banding, including device adjustability, lack of malabsorption, and easy reversibility, have contributed to its widespread use. Since Food and Drug Administration approval of the first laparoscopic adjustable gastric band, the device design has undergone engineering improvements. The LAP-BAND AP (LBAP) system received Food and Drug Administration approval in 2006. Little is known about the safety and efficacy of this new system. Our objective was to prospectively assess the efficacy and safety of the LBAP system in real-world clinical settings at 50 clinical centers throughout the United States. METHODS: In an open-label 5-year evaluation, 508 severely or morbidly obese patients from 50 centers in the United States underwent surgery using the LBAP system. The present interim report describes the results from 323 patients after ≥ 48 weeks of follow-up. RESULTS: By week 48, the patients had experienced a mean percentage of excess weight loss of 46% and a mean ± standard deviation reduction in the body mass index of 8.4 ± 3.69 kg/m(2). Sixteen patients (3.1%) experienced a severe device- or procedure-related adverse event. There were no deaths. CONCLUSION: These 48-week interim data demonstrate that the LBAP system offers a safe and effective therapy to reduce weight in severely obese patients.