Bladder Antimuscarinics and Cognitive Decline in Elderly Patients

Introduction: The evidence on the impact of bladder antimuscarinics initiation on cognitive function in older adults is inconsistent. Methods: A retrospective analysis of data from the National Alzheimer\u27s Coordinating Center (NACC) on enrollees 65 years and older evaluated the association between antimuscarinic initiation and cognitive decline. We defined decline from baseline (yes/no) for cognitive assessments included in the NACC Uniform Data Set 2.0 battery. New users were matched on year of enrollment and time in the cohort to randomly selected nonusers. Analyses were conducted using inverse probability of treatment weights based on baseline propensity scores. Results: Our analyses included 698 new users and 7037 nonusers. The odds ratio (OR) and 95% confidence interval for cognitive decline in users as compared to nonusers was 1.4 (1.19–1.65) for Mini–Mental State Examination (MMSE), and 1.21 (1.03–1.42) for Clinical Dementia Rating; in addition, the odds of decline were 20% higher in users compared to nonusers for semantic memory/language and executive function. The effect estimate for MMSE was 1.94 (1.3–2.91) for those with mild cognitive impairment, 1.26 (0.99–1.62) in those with normal cognition, and 1.44 (1.04–1.99) in those with dementia at baseline. Discussion: Our results show that antimuscarinic initiation is associated with cognitive decline and raise questions about their use, especially in those with impaired cognition

A Comparative Study on the Efficacy of Solifenacin Succinate in Patients with Urinary Frequency with or without Urgency

OBJECTIVES: Patients with overactive bladder (OAB) often have trouble perceiving urgency because of difficulties in distinguishing between urgency and desire to void. Empirical antimuscarinic treatment of patients with frequency only may be reasonable if conservative management has failed. We compared the efficacy of solifenacin in patients with frequency with or without urgency. MATERIALS AND METHODS: This multicenter, 12-week, open-label, comparative, non-inferiority clinical trial assessed whether the solifenacin efficacy for frequency without urgency is non-inferior to its efficacy for frequency with urgency. All patients had micturition frequency ≥ 8 voids/day with or without urgency. Primary efficacy variable: daily frequency change at 12 weeks relative to baseline. Secondary efficacy variables: change at 12 weeks relative to baseline in Patients' Perception of Bladder Condition (PPBC), OAB Symptom Score (OABSS), and Benefit, Satisfaction, Willingness to continue (BSW) questionnaire. RESULTS: Of the 286 enrolled patients, 240 (83.9%) completed the study (without urgency n = 115with urgency n = 125). Full dataset analysis revealed that the groups without and with urgency exhibited significant reductions in daily micturition frequency of -2.49 ± 0.35 (mean ± standard error) and -2.63 ± 0.37, respectively. The lower limit of the 95% two-sided CI of the comparison of the two group means was -1.14, which is smaller than the -0.8 margin of clinical equivalence. The two groups did not differ in improvement in PPBC, OABSS, or BSW scores. Both tolerated the treatment well. CONCLUSIONS: It was not possible to verify that the solifenacin efficacy for frequency alone was non-inferior to its efficacy for OAB. Nevertheless, solifenacin tended to be effective for frequency regardless of urgency

Modeling dose-response relationships of the effects of fesoterodine in patients with overactive bladder

<p>Abstract</p> <p>Background</p> <p>Fesoterodine is an antimuscarinic for the treatment of overactive bladder, a syndrome of urgency, with or without urgency urinary incontinence (UUI), usually with increased daytime frequency and nocturia. Our objective was to develop predictive models to describe the dose response of fesoterodine.</p> <p>Methods</p> <p>Data from subjects enrolled in double-blind, placebo-controlled phase II and III trials were used for developing longitudinal dose-response models.</p> <p>Results</p> <p>The models predicted that clinically significant and near-maximum treatment effects would be seen within 3 to 4 weeks after treatment initiation. For a typical patient with 11 micturitions per 24 hours at baseline, predicted change was -1.2, -1.7, and -2.2 micturitions for placebo and fesoterodine 4 mg and 8 mg, respectively. For a typical patient with 2 UUI episodes per 24 hours at baseline, predicted change was -1.05, -1.26, and -1.43 UUI episodes for placebo and fesoterodine 4 mg and 8 mg, respectively. Increase in mean voided volume was estimated at 9.7 mL for placebo, with an additional 14.2 mL and 28.4 mL for fesoterodine 4 mg and 8 mg, respectively.</p> <p>Conclusions</p> <p>A consistent dose response for fesoterodine was demonstrated for bladder diary endpoints in subjects with overactive bladder, a result that supports the greater efficacy seen with fesoterodine 8 mg in post hoc analyses of clinical trial data. The dose-response models can be used to predict outcomes for doses not studied or for patient subgroups underrepresented in clinical trials.</p> <p>Trial Registration</p> <p>The phase III trials used in this analysis have been registered at ClinicalTrials.gov (NCT00220363 and NCT00138723).</p

EXTRACTIVE-SPECTROPHOTOMETRIC DETERMINATION OF SOME ANTIMUSCARINIC ANTAGONIST IN TABLET FORMULATIONS USING ERIOCHROME CYANINE R

Objective: To develop and validate simple, rapid and sensitive spectrophotometric method for the assay of four antimuscarinic antagonists, namely oxybutynin (OXB), solifenacin (SOL), tolterodine (TOL) and fesoterodine (FES) in bulk and pharmaceutical formulations.Methods: The proposed method is based on the reaction of the selected drugs with eriochrome cyanine R (ECR) in buffered aqueous solution at pH 1.0. The formed ion-pair complexes were extracted with dichloromethane and measured quantitatively with maximum absorption at 464 nm. All variables that affect on color intensity such as pH, buffer volume and concentration of ECR and extractive solvents were studied and optimized.Results: The calibration graphs were linear over the concentration range of 4–24, 4–32, 4–32 and 2–22 mg/ml for OXB, SOL, TOL and FES, respectively. The stoichiometry of the reaction was found to be 1:1 in all cases. Molar absorptivity values were found to be 2.043×104, 1.856×104, 1.798×104 and 2.856×104 l/mol/cm for OXB, SOL, TOL and FES, respectively. Excipients which used as an additive in commercial formulations did not interfere in the analysis.Conclusion: The developed method was successfully applied to determine OXB, SOL, TOL and FES in pharmaceutical preparations. The developed method can be used for quality control and routine analysis where time, cost effectiveness and high specificity of analytical technique are of great importance

Men’s preferences for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia : a discrete choice experiment

HERU is supported by the Chief Scientist Office (CSO) at the Scottish Government Health and Social Care Directorate. Sebastian Heidenreich acknowledges financial support from the Institute of Applied Health Science, University of Aberdeen. Medical writing support was provided by Tyrone Daniel from Bioscript Medical, and was funded by Astellas Pharma Europe Ltd. Presented in part as a poster at the ISPOR 17th Annual European Congress, November 8–12, 2014, Amsterdam, The Netherlands. The poster’s abstract was published in Value in Health. 2014;17 (7):A472. Open Access JournalPeer reviewedPublisher PD

Lung cancer in Sweden : incidence, diagnosis and survival

Globally, lung cancer is the most commonly diagnosed form of cancer, as well as the number one cancer-related cause of death. This thesis includes four population-based studies that considered different aspects of lung cancer, covering incidence, diagnosis and survival. Study I considered the incidence of lung cancer in relation to use of antimuscarinic medications to treat overactive bladder. We identified first-time users of antimuscarinic medications and matched them with individuals not exposed to antimuscarinic medications. Exposed individuals had lower incidence of lung cancer than those unexposed. The inverse association became more pronounced over time from the start of treatment and with the amount of medication from filled prescriptions. Our finding of an inverse association generates hypotheses regarding the prevention of cancer and new treatment strategies for patients with cancer. In study II, we identified individuals with incident non-small cell lung cancer and compared characteristics and survival by smoking status at diagnosis. We found that women, adenocarcinoma, and epidermal growth factor receptor mutation were overrepresented among never-smokers. Furthermore, compared to current smokers, survival was longer for never-smokers. Our findings emphasise the need for an improved understanding of lung cancer among never-smokers that may help to prevent lung cancer and improve survival. Patients with incident lung cancer were identified in study III and matched with individuals free of lung cancer. We investigated patterns of recent use of antibiotics as an indicator of early symptoms of lung cancer. We found that a diagnosis of lung cancer was associated with increased likelihood of recent pre-diagnostic use of antibiotics. The likelihood became more pronounced with the number of filled prescriptions and with proximity to the diagnosis. Our findings further emphasise the importance of ruling out lung cancer following pneumonia treatment. In study IV, we identified patients with incident adenocarcinoma or squamous cell carcinoma of the lung and investigated temporal trends in relative survival. We found that relative survival increased between 1995 and 2016. The increase was most pronounced among women, patients with stage III cancer, patients with adenocarcinoma, and never-smokers. These findings corroborate results from other countries. The increase in relative survival for patients with lung cancer in recent decades can probably be attributed to the improvements in diagnostic procedures and new treatments

The prevention and management of hospital admissions for urinary tract infection in patients with multiple sclerosis

Introduction Urinary tract infections (UTIs) are one of the commonest reasons for patients with multiple sclerosis (PwMS) presenting to hospital. Management of recurrent UTIs in PwMS can be challenging and characteristics of such patients are not well described. Aims To describe the neurological and urological features of PwMS presenting to hospital for UTIs and identify areas of management that could be improved to reduce UTI frequency. Methods Health episode statistics data were used to identify PwMS presenting to a tertiary hospital with UTI over a 5-year period. Medical records were reviewed for demographic, MS and urological history. The seven PwMS with the highest numbers of encounters were seen in a multidisciplinary clinic to enable detailed assessments. Results 52 PwMS (25 female, 27 male) with mean age of 60 had 112 emergency department presentations and 102 inpatient admissions for UTI. 24 presented multiple times and were more likely to be older and male with progressive MS. Almost two-thirds were using a urinary catheter. Less than half were under current urological and neurological follow-up. Escherichia coli and Pseudomonas spp were the commonest organisms cultured. Resistance to antibiotics was more frequent in patients with multiple presentations. Conclusions PwMS presenting to hospital for UTIs are more often male, older, with progressive MS and high levels of disability. A small group of PwMS accounted for a large number of encounters. Preventative and management strategies can be applied in primary and secondary care settings, with an emphasis on bladder, catheter and general physical care

New medical treatments for lower urinary tract symptoms due to benign prostatic hyperplasia and future perspectives

Background: Lower Urinary Tract Symptoms (LUTS) in men are a common clinical problem in urology and have been historically strictly linked to benign prostatic hyperplasia (BPH), which may lead to bladder outlet obstruction (BOO). New molecules have been approved and have entered the urologists' armamentarium, targeting new signaling pathways and tackling specific aspects of LUTS. Objective of this review is to summarize the evidence regarding the new medical therapies currently available for male non-neurogenic LUTS, including superselective α1-antagonists, PDE-5 inhibitors, anticholinergic drugs and intraprostatic onabotulinum toxin injections. Methods: The National Library of Medicine Database was searched for relevant articles published between January 2006 and December 2015, including the combination of "BPH", "LUTS", "medical" and "new". Each article's title, abstract and text were reviewed for their appropriateness and their relevance. One hundred forty eight articles were reviewed. Results: Of the 148 articles reviewed, 92 were excluded. Silodosin may be considered a valid alternative to non-selective α1-antagonists, especially in the older patients where blood pressure alterations may determine major clinical problems and ejaculatory alterations may be not truly bothersome. Tadalafil 5 mg causes a significant decrease of IPSS score with an amelioration of patients' QoL, although with no significant increase in Qmax. Antimuscarinic drugs are effective on storage symptoms but should be used with caution in patients with elevated post-void residual. Intraprostatic injections of botulinum toxin are well-tolerated and effective, with a low rate of adverse events; however profound ameliorations were seen also in the sham arms of RCTs evaluating intraprostatic injections. Conclusion: New drugs have been approved in the last years in the medical treatment of BPH-related LUTS. Practicing urologists should be familair with their pharmacodynamics and pharmacokinetics