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.

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.

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.

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.

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.

Blood-brain barrier permeation and efflux exclusion of anticholinergics used in the treatment of overactive bladder.

Overactive bladder (OAB) is a common condition, particularly in the elderly. Anticholinergic agents are the mainstay of pharmacological treatment of OAB; however, many anticholinergics can cross the blood-brain barrier (BBB) and may cause central nervous system (CNS) effects, including cognitive deficits, which can be especially detrimental in older patients. Many anticholinergics have the potential to cause adverse CNS effects due to muscarinic (M(1)) receptor binding in the brain. Of note, permeability of the BBB increases with age and can also be affected by trauma, stress, and some diseases and medications. Passive crossing of a molecule across the BBB into the brain is dependent upon its physicochemical properties. Molecular characteristics that hinder passive BBB penetration include a large molecular size, positive or negative ionic charge at physiological pH, and a hydrophilic structure. Active transport across the BBB is dependent upon protein-mediated transporter systems, such as that of permeability-glycoprotein (P-gp), which occurs only for P-gp substrates, such as trospium chloride, darifenacin and fesoterodine. Reliance on active transport can be problematic since genetic polymorphisms of P-gp exist, and many commonly used drugs and even some foods are P-gp inhibitors or are substrates themselves and, due to competition, can reduce the amount of the drug that is actively transported out of the CNS. Therefore, for drugs that are preferred not to cross into the CNS, such as potent anticholinergics intended for the bladder, it is optimal to have minimal passive crossing of the BBB, although it may also be beneficial for the drug to be a substrate for an active efflux transport system. Anticholinergics demonstrate different propensities to cross the BBB. Darifenacin, fesoterodine and trospium chloride are substrates for P-gp and, therefore, are actively transported away from the brain. In addition, trospium chloride has not been detected in cerebrospinal fluid assays and does not appear to have significant CNS penetration. This article reviews the properties of anticholinergics that affect BBB penetration and active transport out of the CNS, discusses issues of increased BBB permeability in patients with OAB, and examines the clinical implications of BBB penetration on adverse events associated with anticholinergics.

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.

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.

Safety and tolerability profiles of anticholinergic agents used for the treatment of overactive bladder.

Anticholinergics are the mainstay of pharmacotherapy for overactive bladder (OAB). The anticholinergics used to treat OAB differ in their pharmacological profiles, which may affect their propensity for causing commonly observed adverse effects. The purpose of this is review is to use published clinical data to evaluate the safety and tolerability of commonly prescribed anticholinergics for OAB, provide a context for safety and tolerability in terms of drug pharmacology, summarize the impact of adverse effects on adherence, and discuss the influence of study design on safety and tolerability outcomes. A MEDLINE search was conducted for the period 1990-2010 to identify studies evaluating mechanisms of action, pharmacological profiles, safety issues and adverse events pertaining to anticholinergics used in the treatment of OAB. Compared with immediate-release preparations, the extended-release, once daily and transdermal formulations are associated with lower rates of anticholinergic adverse effects, due to improved consistency in serum levels. The most significant adverse effects in terms of affecting the use of anticholinergics agents are CNS and cardiac disturbances. CNS issues are associated with pharmacological properties such as serum concentration, blood-brain barrier permeability and active transport, and receptor binding affinity. Cardiac safety (corrected QT interval) is more dependent on specific molecular attributes. However, more common but less bothersome adverse effects associated with systemic blockade of the muscarinic receptors include dry mouth, constipation, headache and blurred vision. A high potential for interaction between anticholinergics and drugs that compete with the same pathways for hepatic metabolism via cytochrome P450 and renal excretion increases the risk of adverse effects for both antimuscarinic and associated medications, especially in the elderly, who are more likely to be taking multiple drugs. This literature review demonstrates that all OAB anticholinergics are effective in reducing symptoms of OAB; however, important pharmacodynamic/pharmacokinetic differences between these agents may influence their efficacy and incidence of associated adverse effects. Because OAB is a chronic disease requiring long-term therapy, careful assessment of the pharmacological differences is needed in order to tailor therapy to the individual patient's clinical needs, and thereby maximize the chance of treatment success and long-term adherence to therapy. Since anticholinergic adverse effects are known to affect treatment adherence and persistence, the potential for adverse effects should be considered when selecting treatment for an individual patient.

Anaplastic large T-cell lymphoma and breast implants: a review of the literature.

BACKGROUND: Anecdotal reports and one case-control study suggested an association, without evidence of causation, between breast implants and anaplastic lymphoma kinase-negative anaplastic large T-cell lymphoma (ALCL), a rare non-Hodgkin's lymphoma. This review summarizes the published evidence, including case reports and epidemiologic studies. METHODS: A PubMed search limited to English language articles was conducted using the search terms "breast implant" and "lymphoma," "primary T-cell breast lymphoma," or "breast implant and ALCL" to identify all published cases of breast-associated ALCL. RESULTS: A total of 18 publications were retrieved describing 27 cases of ALCL in breast implant recipients. Breast-associated ALCL occurred in women with and without implants. Approximately 78 percent of cases (21 of 27) were CD30 anaplastic lymphoma kinase-negative, with an indolent clinical course. Both saline- and silicone-filled devices were identified; however, implant style and surface texture were largely unreported. The tumor stage at diagnosis was I in 16 of 27, II or higher in seven of 27, or unreported in four of 27. No prospective epidemiologic study has linked implants and ALCL; however, a single case-control study in Dutch women reported increased odds of association between ALCL and implants, and an estimated frequency of one in 1 million women with and without breast implants. CONCLUSIONS: An association, without evidence of causation, was reported between breast implants and ALCL. Further study is required to confirm this association. Breast-associated ALCL occurred rarely in women with and without breast implants and had a primarily indolent clinical course, which may provoke a revision of the World Health Organization nomenclature for lymphoma; however, aggressive clinical behavior was also reported. The cases of ALCL were not confined to a specific type of implant. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, V.

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.

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.

Managing late periprosthetic fluid collections (seroma) in patients with breast implants: a consensus panel recommendation and review of the literature.

BACKGROUND: The goal of this consensus is to establish an algorithm for the management of patients who develop a late or delayed periprosthetic fluid collection. A work group of practicing plastic surgeons and device industry physicians met periodically by teleconference and discussed issues pertinent to the diagnosis and management of late periprosthetic fluid collections in patients with breast implants. Based on these meetings, treatment recommendations and a treatment algorithm were prepared in association with an editorial assistant. METHOD: The work group participants discussed optimal care approaches developed in their private practices and from evidence in the literature. RESULTS: The consensus algorithm and treatment and management recommendations represent the consensus of the group. CONCLUSIONS: The group concluded that late periprosthetic fluid collection (arbitrarily defined as occurring ≥ 1 year after implant) is an infrequently reported occurrence (0.1 percent) after breast implant surgery and that, at a minimum, management should include clinically indicated ultrasound-guided aspiration of fluid, with appropriate cultures and cytologic testing. Further evaluation and additional treatment is recommended for recurrence of periprosthetic fluid collection after aspiration, or clinical suspicion of infection or neoplasia.

Once-daily trospium chloride 60 mg extended release in subjects with overactive bladder syndrome who use multiple concomitant medications: Post hoc analysis of pooled data from two randomized, placebo-controlled trials.

BACKGROUND: Overactive bladder syndrome (OAB) is associated with various co-morbidities; treatment of these frequently results in multiple medication use (MMU) and the potential for drug-drug interactions, which may lead to adverse events and altered efficacy. With the aging population, the prevalence of MMU is likely to increase in the overall population, an increase due in part to treatment of co-morbidities that are more common in the elderly. OBJECTIVE: To assess safety and efficacy outcomes with once-daily trospium chloride 60 mg extended release (XR) in subjects with OAB who were taking multiple concomitant medications. STUDY DESIGN: Post hoc analysis of pooled data from two 12-week randomized, placebo-controlled studies. SETTING: Urology, urogynaecology, and primary care offices/clinics. PATIENTS: Subjects aged ≥18 years with OAB for ≥6 months who had baseline urinary frequency of ≥30 toilet voids/3 days; ≥1 'severe' urgency severity rating/3 days (on the Indevus Urgency Severity Scale); and pure urge urinary incontinence (UUI) or mixed incontinence with predominant UUI, with ≥3 UUI episodes/3 days. This analysis utilized data from subjects taking concomitant medications, focusing on those taking seven or more. INTERVENTION: Once-daily trospium chloride 60 mg XR or placebo. MAIN OUTCOME MEASURE: Predictors of treatment-emergent adverse events (TEAEs) identified by multivariate logistic regression analysis. RESULTS: Concomitant medications were being taken by 1135 subjects (placebo, n = 576; trospium chloride XR, n = 559); 427 were taking seven or more (placebo, n = 199; trospium XR, n = 228). Among subjects taking seven or more concomitant medications, there was no significant difference between trospium chloride XR and placebo in the proportion of subjects experiencing one or more TEAEs (64.5% vs 58.3%). Logistic regression analysis indicated that the odds of experiencing a TEAE were influenced by concomitant medication use, but not by randomization assignment to trospium chloride XR or to placebo, suggesting that concomitant drugs contribute more to TEAEs than trospium chloride XR. Compared with subjects taking one to two concomitant medications, the adjusted odds ratio (OR) for experiencing any TEAE was 3.39 (95% CI 2.39, 4.80; p < 0.0001) for subjects taking seven or more concomitant medications. The adjusted OR for experiencing any TEAE for subjects randomized to active treatment compared with placebo was 1.19 (95% CI 0.85, 1.67; p = 0.31). Efficacy in subjects taking seven or more concomitant medications was similar to that in the overall pooled study population. CONCLUSIONS: Trospium chloride XR does not increase the likelihood of a TEAE compared with placebo. The probability of experiencing a TEAE was significantly influenced by use of multiple concomitant medications. Trospium chloride XR was as effective in subjects with OAB taking seven or more concomitant medications as in the overall pooled study population. The data support the conclusion that trospium chloride XR is safe and effective in patients with OAB taking multiple concomitant medications.