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Biomedical subjects

Roger Dmochowski

Publications and source records attributed to Roger Dmochowski.

At least 19 recordsLinked to original sources
PubMed2006

Oxybutynin transdermal system improves the quality of life in adults with overactive bladder: a multicentre, community-based, randomized study.

OBJECTIVE: To assess health-related quality-of-life (HRQoL) and safety with the oxybutynin transdermal system (OXY-TDS) (Oxytrol), Watson Pharma, Corona, CA, USA) in the Multicentre Assessment of Transdermal Therapy in Overactive Bladder With Oxybutynin (MATRIX) study, as HRQoL measurements are increasingly important in evaluating pharmacotherapy for overactive bladder (OAB). PATIENTS AND METHODS: This randomized, open-label, community-based study enrolled 2878 participants aged >/=18 years who had been given a diagnosis of OAB. The 327 study sites were representative of various practice types. All participants were treated with OXY-TDS 3.9 mg/day for </=6 months. HRQoL was assessed using the King's Health Questionnaire (KHQ); the primary endpoint was the change in KHQ scores from baseline to study end. RESULTS: Most enrolees (2052/2625; 78.2%) had moderate to severe OAB at baseline (Patient Perception of Bladder Condition score >/= 4 on a scale of 1-6), and most (1632/2859; 57.1%) had been given previous drug treatment for OAB. Of 2592 with evaluable baseline KHQ scores, 92.2% reported urgency and 88.2% reported urge urinary incontinence. The most impaired domains at baseline were Incontinence Impact (69.3), Symptom Severity (55.9), and Sleep/Energy (54.2). There were clinically meaningful and statistically significant improvements in nine of 10 domains at the study end; the greatest improvements were in Incontinence Impact (-13.5), Symptom Severity (-12.4), and Role Limitations (-13.3). The treatment was well tolerated, with low incidences of drug-related anticholinergic adverse effects such as dry mouth (75; 2.6%), constipation (44; 1.5%), and dizziness (21; 0.7%). There were drug-related application-site reactions, including pruritus, erythema, dermatitis and irritation, in 14.0% of participants. CONCLUSIONS: OXY-TDS treatment was well tolerated in this diverse, community-based population, and resulted in clinically significant improvements in HRQoL, regardless of baseline characteristics.

Administration, Cutaneous↗
PubMed2006

Efficacy and tolerability of tolterodine extended release in male and female patients with overactive bladder.

OBJECTIVES: To evaluate the efficacy and tolerability of tolterodine extended release (ER) in men and women with overactive bladder (OAB). METHODS: We analyzed data from two 12-wk, placebo-controlled trials of tolterodine ER (4mg QD). Patients completed 7-d bladder diaries and rated the urgency sensation associated with each micturition on a 5-point urgency rating scale. Micturitions were categorized by urgency rating: total (1-5), non-OAB (1-2), OAB (3-5), or severe OAB (4-5). Changes in micturitions during 24-h, daytime, and nocturnal intervals were assessed. RESULTS: At baseline, 73% (547 of 745) of men and 57% (539 of 953) of women were continent. By week 12, tolterodine ER (n=848) reduced OAB and severe OAB micturitions during 24-h, daytime, and nocturnal intervals in both sexes compared with placebo (n=850). Adverse event rates were low and similar across treatment and gender. CONCLUSIONS: In men and women with OAB, tolterodine ER reduced OAB and severe OAB micturitions, and was well tolerated.

Benzhydryl Compounds↗
PubMed2006

Antimuscarinic therapy in men with lower urinary tract symptoms: what is the evidence?

Lower urinary tract symptoms (LUTS) in men have, until recently, been assumed to arise from bladder outlet obstruction (BOO) caused by benign prostatic hyperplasia. Given this presumption, all manifestations (obstructive and irritative) of LUTS have been presumed to be responsive to therapy for prostatic disorders such as alpha-blockade (with or without the relatively recent addition of 5alpha-reductase inhibitors) or surgical intervention for benign prostatic hyperplasia. However, evidence demonstrates that persistence of irritative urinary symptoms is often encountered in men despite presumed adequate management of their obstructive complaints. Although antimuscarinic drugs have been found to be effective for irritative urinary symptoms attributed to the overactive bladder syndrome, concern regarding the use of this class of drugs in men with even potential coexistent BOO has limited the use of these drugs. Data are now accumulating that suggest that the antimuscarinic class may be used in men with bothersome, irritative symptoms, despite the presence of BOO (as defined by symptoms and urodynamics) and with a reasonable expectation of efficacy and little added risk. Critical evaluation of this evidence suggests that a role may exist for the antimuscarinic class in management of LUTS in men. However, areas of incomplete knowledge, including the risk associated with long-term (greater than 3 months) use of these drugs and the value of the antimuscarinic class as monotherapy in men with LUTS, still remain to be investigated.

Humans↗
PubMed2006

Pathophysiology of overactive bladder.

Overactive bladder (OAB) is a complex of symptoms frequently encountered in the primary care setting. Impediments to optimal management of OAB include inaccurate perceptions on the part of patients and primary care providers, e.g., that the symptoms of OAB represent a natural progression of aging and are beyond the scope of treatment or that diagnosis and treatment are specialist concerns. Complicating the physician's task is the reluctance of many patients to initiate discussion of their OAB symptoms and the fact that patients often develop disruptive coping strategies rather than seek medical treatment, possibly because of a belief that OAB is a normal part of aging rather than an actual medical condition. In most cases, OAB may be managed quite well by the primary care physician who has an understanding of the pathophysiology of OAB. This article reviews normal bladder function and then explores pathophysiologic changes that likely cause the symptoms of OAB.

Aging↗
PubMed2006

Management of incontinence for family practice physicians.

Family practice physicians are likely to encounter urinary incontinence and overactive bladder (OAB) in their patients. An informed family practice physician can generally accurately diagnose the cause and type of incontinence in patients with a properly focused physical examination and, if necessary, auxiliary testing. Accurate diagnosis can lead to effective treatment when physicians are familiar with available treatment options, including pharmacologic, surgical, behavioral therapies, and catheterization.

Family Practice↗
PubMed2006

Multicenter phase III trial studying trospium chloride in patients with overactive bladder.

OBJECTIVES: To study the efficacy and safety of trospium chloride in treating overactive bladder. Trospium chloride is an anticholinergic agent with predominantly peripheral nonselective antimuscarinic activity and thus has potential therapeutic value in treating patients with overactive bladder. METHODS: Patients with overactive bladder were randomized on a 1:1 basis to either placebo or trospium chloride 20 mg twice daily in this 12-week, multicenter, parallel, double-blind, placebo-controlled study. The primary endpoint was the change in the average number of toilet voids per 24 hours. The secondary efficacy variables were changes in the average void urgency severity, volume per toilet void, urge frequency, number of daily urge urinary incontinence episodes, and daytime sleepiness. RESULTS: A total of 658 patients were randomized at 52 sites. Trospium chloride significantly decreased the average number of daily toilet voids, average urgency severity, urge frequency, and urge urinary incontinence episodes and increased the average volume per void at weeks 1, 4, and 12. All effects occurred by the end of week 1 and all improved and were sustained throughout the 12-week study. Adverse events included dry mouth and constipation. CONCLUSIONS: Trospium chloride had significant and sustained effectiveness beginning at the end of week 1 and continuing through 12 weeks of treatment. Trospium chloride was also safe and generally well tolerated.

Benzilates↗
PubMed2006

Tolterodine extended release improves overactive bladder symptoms in men with overactive bladder and nocturia.

OBJECTIVES: To evaluate the efficacy and safety of nighttime dosing with tolterodine extended release (TER) in men with overactive bladder (OAB) and nocturia. METHODS: This was a post hoc analysis of data from two 12-week, double-blind, placebo-controlled trials of nighttime (<4 hours before bedtime) TER (4 mg daily) dosing. Men with a mean micturition frequency of eight or more times in 24 hours, including a mean of 2.5 or more nocturia episodes/night, were included. For each micturition, patients used 7-day diaries to record urinary urgency on a 5-point urgency rating scale (1, none; 2, mild; 3, moderate; 4, severe; 5, urgency urinary incontinence). Micturitions were analyzed post hoc by urgency rating categories: total (1 to 5), non-OAB (1 to 2), OAB (3 to 5), and severe OAB (4 to 5). Adverse events were recorded throughout the study. RESULTS: A total of 745 men (mean age 64 years) were randomized to placebo (n = 374) or TER (n = 371). Of the 745 men, 73% reported no incontinence episodes in a 7-day diary at baseline. At week 12, the weekly values for nighttime severe OAB micturitions and 24-hour and daytime total, OAB, and severe OAB micturitions were significantly reduced in the TER group versus the placebo group. The TER-treated men also reported a significant reduction in the mean urgency rating versus placebo. Adverse events associated with TER were low and comparable to those in the placebo group, with the exception of dry mouth (11% versus 4%). Withdrawals because of adverse events were infrequent (3% TER, 4% placebo). Five men were withdrawn for symptoms suggestive of urinary retention (3 TER, 2 placebo). CONCLUSIONS: Nighttime TER dosing reduced urgency-related micturitions and was well tolerated in men with OAB and nocturia.

Benzhydryl Compounds↗
PubMed2006

Time to onset of improvement in symptoms of overactive bladder using antimuscarinic treatment.

OBJECTIVE: To evaluate the time to onset of statistically significant and clinically meaningful effects of trospium chloride in patients with an overactive bladder (OAB). PATIENTS AND METHODS: Data from a recent Phase III clinical study of trospium chloride were obtained, in which 658 patients with OAB were randomized (1 : 1) to placebo or trospium chloride 20 mg twice daily for 12 weeks. Original study safety endpoints consisting of adverse events, vital signs, electrocardiograms, and laboratory changes were collected, while original efficacy endpoints included number of toilet voids/day, urgency severity per toilet void, urge urinary incontinence (UUI), and volume voided per toilet void at weeks 1, 4, and 12. Results were also analysed using the OAB Symptom Composite Score (OAB-SCS). The efficacy analysis focused on changes from baseline in these endpoints from 1 to 7 days of treatment to establish the earliest point at which there was statistical significance or clinical efficacy. RESULTS: There were statistically significant improvements in efficacy over placebo in endpoints (toilet voids, urgency severity/void, UUI episodes, OAB-SCS) within a few days of treatment, with improvements in symptoms continuing to 7 days of treatment. There were clinically meaningful improvements in most endpoints by the end of the first week. CONCLUSIONS: The time to onset of the clinical effect should be studied more extensively to identify when patients might expect a clinically meaningful improvement in their OAB-related symptoms.

Adult↗
PubMed2006

Efficacy and tolerability of tolterodine extended-release in continent patients with overactive bladder and nocturia.

OBJECTIVE: To evaluate the clinical efficacy and tolerability of tolterodine extended-release (ER) in continent patients with overactive bladder (OAB) and nocturia. PATIENTS AND METHODS: A post hoc analysis was conducted of data from a 12-week, double-blind study of 850 patients randomized to tolterodine ER (4 mg once daily) or placebo, taken within 4 h of going to bed. Patients with a mean of > or = 8 voids/24 h were enrolled, including a mean of > or = 2.5 voids/night. Patients completed 7-day voiding diaries, and for each void an urgency rating was assessed using a 5-point scale (1, none; 5, urgency incontinence); 24-h voids were categorized by urgency rating: total (1-5), non-OAB (1-2), OAB (3-4), and severe OAB (4-5) voids. All adverse events were recorded. RESULTS: The post hoc analysis included 513 patients (243 placebo; 270 tolterodine ER; 58% men) who were continent at baseline; 47% of 24-h voids were classed as non-OAB, and 12% as severe OAB. After 12 weeks of treatment, tolterodine ER significantly reduced mean urgency rating and 24-h OAB, severe OAB, and total voids vs placebo. Tolterodine ER did not affect normal, non-OAB voids, and there were no significant adverse events related to voiding. Other than dry mouth (tolterodine ER, 9% vs placebo, 2%), all the adverse events were reported in <3% of patients; <2% of patients receiving tolterodine ER withdrew because of adverse events. CONCLUSIONS: In continent patients with OAB, tolterodine ER significantly improved urgency rating and reduced 24-h OAB, severe OAB, and total voids, suggesting that it is an effective and well-tolerated treatment option for this subpopulation. More studies are needed to better understand the clinical efficacy of tolterodine ER in this under evaluated group of OAB patients without incontinence.

Adult↗
PubMed2005

The Q-T interval and antimuscarinic drugs.

Antimuscarinic drugs form the mainstay of pharmacotherapy for the treatment of overactive bladder. The primary sites of activity of the agents for the desired therapeutic effect are the M3 and M2 receptors of the bladder. Drug interaction with other non-vesical muscarinic receptors produces a range of undesired adverse events. In general, certain adverse effects associated with antimuscarinic agents such as dry mouth (salivary) and constipation (colon) may be considered only bothersome, and somnolence and confusion (central nervous system) may be considered more serious in nature. However, effects on the myocardium are considered to be more significant safety issues and increased awareness and understanding of the effect of drugs on the myocardium, including the additional effects of drug-drug interaction, has increased a need for the evaluation of new drugs for cardiac safety. The role of genetics (and the identification of populations at risk) in the causation of congenital dysrhythmias has received specific attention in this area. New drugs now must undergo more intense scrutiny and cardiac testing to evaluate their effects on cardiac rate and rhythm, especially the QT interval. The recently approved agents (trospium, solifenacin, darifenacin) used for the treatment of overactive bladder have been rigorously evaluated for these effects.

Electrophysiology↗
PubMed2005

Stress incontinence injection therapy: what is best for our patients?

OBJECTIVE: Urethral injection (periurethral/intraurethral bulking) is an established, minimally invasive therapy for stress urinary incontinence (SUI). This review aims to determine which women should potentially benefit from, and be considered as candidates for, injection therapy and to elucidate what we are trying to achieve. METHODS: Based on MEDLINE database searches, all aspects of urethral injection were examined, including patient selection, safety, injection technique, efficacy, quality of life, goals and cost. RESULTS: Such therapy has a low complication rate, improves or cures about 3 out of 4 women, as shown in mainly short-term studies, and improves patients' quality of life. It can be used in the majority of patients with uncomplicated SUI. Therefore, injection therapy may be considered as a first-line treatment option for patients who have failed conservative therapy such as pelvic floor exercises and who decline or have a contraindication for pharmacological treatment. However, the decision of whether to use this type of treatment must be based on an informed discussion between the physician and patient--this dialogue should incorporate questions about patients' own treatment goals. Injection therapy appears to have the profile required to meet patients' goals, based on the findings that a procedure with an improvement in incontinence, minimal short-term risk, no long-term risk, and performed in a clinic, would be acceptable. CONCLUSION: Investigating and trying to achieve patients' own treatment goals will ultimately enable us to do what is best for our patients, but current evidence suggests that injection therapy is a valid option worth discussing with many patients.

Biocompatible Materials↗
PubMed2005

The overactive bladder-symptom composite score: a composite symptom score of toilet voids, urgency severity and urge urinary incontinence in patients with overactive bladder.

PURPOSE: To our knowledge there is no index in urology that yields a single, quantifiable and clinically interpretable measure of overactive bladder (OAB) symptoms, including urgency, 24-hour voiding frequency and urge urinary incontinence (UUI). Urgency is the most difficult of these symptoms to measure. The Indevus Urgency Severity Scale (Indevus Pharmaceuticals, Lexington, Massachusetts) was recently developed and validated to capture urgency severity per toilet void. The scale has been combined with 24-hour frequency and UUI episodes to create the OAB Symptom Composite Score (OAB-SCS). We present this composite score. MATERIALS AND METHODS: Two multicenter trials were performed to determine the effects of trospium chloride given as 20 mg tablets vs placebo. A total of 1,157 patients, including 581 who received placebo and 576 who received trospium, were randomly assigned to treatment. Daily OAB-SCS totals were obtained for each patient for each day during the 7-day diary collection period for every visit. RESULTS: The average baseline OAB-SCS value was 36. The mean change from baseline in the trospium and placebo groups was 5 and 1 OAB-SCS points in patients with mild OAB, 10 and 5 in patients with moderate OAB, and 13 and 9 in patients with severe OAB, respectively. CONCLUSIONS: The OAB-SCS discriminated between placebo and pharmacologically treated (trospium chloride) patients with OAB in this study. The OAB-SCS is an improvement over individual symptoms alone. It is easy to implement and interpret and it will prove to be a clinically relevant tool in clinical trials in which patient diary data are captured.

Benzilates↗
PubMed2005

Mixed incontinence: definitions, outcomes, and interventions.

PURPOSE OF REVIEW: Mixed incontinence remains a problematic issue in clinical practice. Interventions designed to benefit one of the contributory symptoms often do no benefit the other constituent symptom. Recent evolution in the taxonomy of mixed incontinence as well as the increased reporting of standardized results has produced a better understanding of the response of this entity to clinical interventions. RECENT FINDINGS: Three main areas of development have occurred in the analysis of mixed incontinence. The advancements in definitional and taxonomic changes have clarified the concept and presentation of mixed incontinence. In light of these changes, results reported from pharmacologic or surgical interventions have improved. Several new studies have demonstrated the efficacy of these interventions in selected groups of patients using either pharmacologic or operative modalities. SUMMARY: In well selected and symptomatically characterized patients, therapy directed at mixed incontinence can provide efficacious results. The implications of these positive outcomes suggest that therapy founded on appropriate symptomatic appraisal can produce generally salubrious outcomes. These outcomes must, however, be assessed with tools that allow adequate differentiation of symptomatic changes including methods that delineate not only cure but also symptom improvement.

Adult↗
PubMed2005

Effect of the proton pump inhibitor omeprazole on the pharmacokinetics of extended-release formulations of oxybutynin and tolterodine.

This study assessed the effect of the proton pump inhibitor omeprazole on the bioavailability of the extended-release formulations of oxybutynin and tolterodine. Forty-four healthy volunteers received each of 4 treatments in a 4-period crossover design. The treatments consisted of osmotically controlled extended-release oxybutynin chloride tablets at 10 mg/d or extended-release tolterodine tartrate capsules at 4 mg/d, with and without preceding treatment with 20 mg omeprazole daily for 4 days. Blood samples collected predose and at scheduled time points for 36 hours postdose were analyzed for oxybutynin and its active metabolite, N-desethyloxybutynin, or tolterodine and its active 5-hydroxymethyl metabolite, as appropriate. The AUCinfinity ratios for oxybutynin and its metabolite with and without prior omeprazole fell within the 80% to 125% range (accepted as the criterion for bioequivalence), as did those for tolterodine and its active moiety. The peak concentration ratios for oxybutynin and metabolite also conformed to this range; those for tolterodine did not. Increasing gastric pH with omeprazole does not substantially alter the pharmacokinetic properties of extended-release oxybutynin but may alter those of extended-release tolterodine.

Adolescent↗
PubMed2005

Improving the tolerability of anticholinergic agents in the treatment of overactive bladder.

Pharmacological treatment for overactive bladder has centred around the interruption of the detrusor activity that is central to urge and incontinence symptoms. The majority of patients with this disorder are treated with antimuscarinic agents. These drugs have been demonstrated to improve urgency, frequency of micturition and urge incontinence, all of which are primary symptoms of overactive bladder; however, they are also commonly associated with anticholinergic adverse effects, most notably dry mouth. Attempts to increase tolerability have included the development of advanced formulations that regulate release of the active ingredient and the development of pharmacological agents that target the desired bladder receptors more specifically and accurately. Although all agents provide good efficacy, tolerability is greatly affected by the formulation used to deliver the active pharmacological agent, as well as the specificity of the targeted receptors. Clinical trials involving a transdermal formulation of oxybutynin have shown that this delivery method may be associated with a lower incidence of anticholinergic adverse events compared with both the immediate-release and the extended-release oral formulations of traditional agents, as well as the most recently approved agents - trospium chloride, solifenacin and darifenacin. Much is still being learned about the function and specificity of muscarinic receptors, which will support the development of agents with sustained efficacy and enhanced tolerability compared with the available formulations to date. These include the S-isomer of oxybutynin, as well as selective muscarinic M2 receptor antagonists.

Administration, Oral↗
PubMed2003

Advancements in minimally invasive treatments for female stress urinary incontinence: radiofrequency and bulking agents.

Continuous advancements in materials technology have provided the possibility that multiple new urethral bulking agents will be available soon. Experience continues to accrue in clinical trials for urethral bulking with these agents. Parallel use for the indication of pediatric vesicourethral reflux also has provided evidence of biologic activity related to these compounds. All of the agents closest to complete analysis are synthetic and represent a variety of material types and characteristics. As these materials evolve, understanding of the preferential injection technique is being gained. Delivery methods and sites may prove to alter the biologic activity of these compounds substantially. Emphasis on other minimally invasive options for the surgical treatment of stress incontinence also has resulted in the development of radiofrequency vesicourethral suspension. Improved understanding of thermal application to tissue, acute and chronic tissue response to this application, and accumulating human experience with this method of therapy has provided an acceptable tolerability profile for this therapy. This profile may provide application of this method of therapy to an in-office treatment setting, precluding hospitalization and substantially decreasing convalescence times.

Administration, Intravaginal↗