Publications by authors named "Matthias Oelke"

140 Publications

Development of a Management Algorithm for Acute and Chronic Radiation Urethritis and Cystitis.

Urol Int 2021 Jun 15:1-12. Epub 2021 Jun 15.

Department of Urology, St. Antonius Hospital, Gronau, Germany.

Objective: The purpose of this review was to summarize the current literature on the assessment and treatment of radiation urethritis and cystitis (RUC) for the development of an evidenced-based management algorithm.

Material And Methods: The PubMed/MEDLINE database was searched by a multidisciplinary group of experts in January 2021.

Results: In total, 48 publications were identified. Three different types of RUC can be observed in clinical practice: inflammation-predominant, bleeding-predominant, and the combination of inflammation- and bleeding-RUC. There is no consensus on the optimal treatment of RUC. Inflammation-predominant RUC should be treated symptomatically based on the existence of bothersome storage or voiding lower urinary tract symptom as well as on pain. When bleeding-predominant RUC has occurred, hydration and hyperbaric oxygen therapy (HOT) should be used first and, if HOT is not available, oral drugs instead (sodium pentosane polysulfate, aminocaproic acid, immunokine WF 10, conjugated estrogene, or pentoxifylline + vitamin E). If local bleeding persists, focal therapy of bleeding vessels with a laser or electrocoagulation is indicated. In case of generalized bleeding, intravesical installation should be initiated (formalin, aluminium salts, and hyaluronic acid/chondroitin). Vessel embolization is a less invasive treatment with potentially less complications and good clinical outcomes. Open- or robot-assisted surgery is indicated in patients with permanent, life-threatening bleeding, or fistulae.

Conclusions: Treatment of RUC, if not self-limiting, should be done according to the type of RUC and in a stepwise approach. Conservative/medical treatment (oral and topic agents) should primarily be used before invasive (transurethral) treatments.
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http://dx.doi.org/10.1159/000515716DOI Listing
June 2021

What are the chances of improvement or cure from overactive bladder? A pooled responder analysis of efficacy and treatment emergent adverse events following treatment with fesoterodine.

Neurourol Urodyn 2021 Aug 26;40(6):1559-1568. Epub 2021 May 26.

Department of Urology, St. Antonius-Hospital, Gronau, Germany.

Aim: This study describes patients with different degrees and combinations of symptom resolution in response to fesoterodine exposure to aid physicians in counselling patients with overactive bladder (OAB) on the likelihood of treatment success.

Methods: Data came from 12-week fixed-dose studies of fesoterodine. The proportions of patients experiencing symptom resolution and change in patient-reported outcome measures (PROM) at 4, 8, and 12 weeks were calculated. Treatment-emergent adverse events (TEAE) were reported according to response in urinary urgency episodes (UUE). The relationship between PROM and response was examined.

Results: Out of 6689 patients, 81.6% female, urgency urinary incontinence (UUI) episodes/24 h were more responsive to fesoterodine than UUE; with roughly 50% of patients reporting a 50% reduction and fewer than 10% reporting absence of UUE at 12 weeks compared to approximately 40%-50% reporting absence of UUI. TEAE was numerically lower in patients with greater response. There was a statistically significant relationship between improvement in urinary urgency and associated change in OAB-q symptom bother scores, r = 0.54, p < 0.001. At Week 4, 64.0%-76.7% of patients who had achieved a significant change in Patient Perception of Bladder Condition (PPBC) had a 50% reduction in UUI. At Week 12 this proportion was between 80% and 87.9%, with those being exposed to fesoterodine treatment reporting response in PPBC at numerically higher rates.

Conclusion: These data provide clinicians with information from which they may usefully communicate the likelihood of symptom resolution in response to pharmacotherapy for OAB and answer a key clinical question posed by many care providers. Roughly ⅓ of fesoterodine treated patients reported a 50% reduction urgency and ¾ reported 50% resolution of incontinence at 12 weeks. Total resolution of all symptoms was seldom achieved.
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http://dx.doi.org/10.1002/nau.24706DOI Listing
August 2021

Reply By Authors.

J Urol 2021 08 7;206(2):317-318. Epub 2021 May 7.

Prostate Center Northwest, Department of Urology, Pediatric Urology and Uro-Oncology, St. Antonius-Hospital, Gronau, Germany.

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http://dx.doi.org/10.1097/JU.0000000000001776.02DOI Listing
August 2021

Perioperative and Postoperative Outcomes of Robot-Assisted Radical Prostatectomy in Prostate Cancer Patients with Prior Transurethral Subvesical Deobstruction: Results of a High-Volume Center.

J Urol 2021 Aug 27;206(2):308-318. Epub 2021 Apr 27.

Prostate Center Northwest, Department of Urology, Pediatric Urology and Uro-Oncology, St. Antonius-Hospital, Gronau, Germany.

Purpose: Prostate cancer patients who are scheduled for robot-assisted radical prostatectomy often have a history of transurethral resection or laser enucleation of the prostate as treatment of benign prostatic hyperplasia. We examined if these patients have impaired surgical, functional and oncologic outcomes compared to those who have no symptom burden of moderate to severe benign prostatic hyperplasia and no previous transurethral resection or laser enucleation of the prostate.

Materials And Methods: We compared 368 robot-assisted radical prostatectomy patients with previous transurethral resection or laser enucleation of the prostate (group A) to 4,945 robot-assisted radical prostatectomy patients without transurethral resection or laser enucleation of the prostate and without moderate or severe benign prostatic hyperplasia symptoms (group B) at a high-volume robot-assisted radical prostatectomy center. Multivariable Cox regression analyses assessed impact of transurethral resection or laser enucleation of the prostate on erectile function and urinary continence recovery, biochemical recurrence or metastatic progression. Analyses were repeated after propensity score matching.

Results: No relevant differences in surgical outcomes, such as surgical margin and 30-day complications rates, were observed. Urinary continence recovery rates at 12 months were 67% vs 74% (group A vs B; p <0.001). Erectile function recovery rates at 24 months were 52% vs 62% (p <0.001). Biochemical recurrence-free rates at 36 months were identical, at 87.3% vs 87.8%. Before and after propensity score matching, transurethral resection or laser enucleation of the prostate negatively affected erectile function recovery (matched HR 0.68, 95% CI 0.53-0.88; p=0.003) in multivariable Cox regression analyses. Similarly, transurethral resection or laser enucleation of the prostate had negative effect on urinary continence recovery (HR 0.84, 95% CI 0.73-0.97; p=0.015) but no effect on biochemical recurrence or metastatic progression.

Conclusions: Previous transurethral resection or laser enucleation of the prostate does not negatively impact surgical, complication-related, and oncologic outcomes if the robot-assisted radical prostatectomy is performed by highly experienced surgeons. However, transurethral resection or laser enucleation of the prostate negatively affects erectile function and urinary continence recovery.
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http://dx.doi.org/10.1097/JU.0000000000001776DOI Listing
August 2021

The impact of age on pathological insignificant prostate cancer rates in contemporary robot-assisted prostatectomy patients despite active surveillance eligibility.

Minerva Urol Nephrol 2021 Apr 22. Epub 2021 Apr 22.

Prostate Center Northwest, Department of Urology, Pediatric Urology and Uro-Oncology, St. Antonius-Hospital, Gronau, Germany.

Background: To assess insignificant prostate cancer(iPCa) rates after robot-assisted radical prostatectomy (RARP) in contemporary patients who were preoperatively eligible for active surveillance(AS). IPCa indicates no risk of PCa progression.

Methods: We retrospectively analysed 2,837 RARP patients (2010-2019) who fulfilled at least one AS entry criteria set - Prostate Cancer Research International - Active Surveillance(PRIAS), University of California San Francisco(UCSF), National Comprehensive Cancer Network(NCCN) or University of Toronto. We utilized four different iPCa definitions, (1) based on pT2 and Gleason score ≤6 and also cumulative tumor-volume (2) ≤2.5mL, (3) ≤0.7mL or (4) ≤0.5mL. For each AS set we tested the rates of iPCa and compared between age <70 vs. ≥70 yrs. This was complemented by multivariable logistic regression(LRM) predicting iPCa, adjusted for age and clinical AS variables. Finally, within the subgroup, who had iPCa, we tested rate of those, who were deemed preoperatively AS ineligible.

Results: Between most(PRIAS) and least stringent(TORONTO) AS sets, iPCa(1) was correctly predicted in 70-57%. Similarly, for iPCa definitions 2-4, rates were (2)59-42%, (3)34-19% and (4)27-14%. Senior patients harbored decreased proportions of iPCa. LRM confirmed that advanced age is associated with a lower chance of iPCa. More stringent AS sets lead to higher rates of AS ineligibility, e.g. 53% for PRIAS, despite iPCa.

Conclusions: AS sets show limited accuracy for stricter iPCa definitions, which further declined with advanced age. Greater AS stringency resulted in more AS ineligible patients despite harboring iPCa. In consequence, patients are at risk for overtreatment. Clinicians must consider age and different AS sets that result in highly variable detection rates of iPCa.
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http://dx.doi.org/10.23736/S2724-6051.21.04174-4DOI Listing
April 2021

Factors Associated with Decisions for Initial Dosing, Up-Titration of Propiverine and Treatment Outcomes in Overactive Bladder Syndrome Patients in a Non-Interventional Setting.

J Clin Med 2021 Jan 15;10(2). Epub 2021 Jan 15.

Department of Pharmacology, Johannes Gutenberg University, 55131 Mainz, Germany.

Two doses of propiverine ER (30 and 45 mg/d) are available for the treatment of overactive bladder (OAB) syndrome. We have explored factors associated with the initial dosing choice (allocation bias), the decision to adapt dosing (escalation bias) and how dosing relative to other factors affects treatment outcomes. Data from two non-interventional studies of 1335 and 745 OAB patients, respectively, receiving treatment with propiverine, were analyzed post-hoc. Multivariate analysis was applied to identify factors associated with dosing decisions and treatment outcomes. Several parameters were associated with dose choice, escalation to higher dose or treatment outcomes, but only few exhibited a consistent association across both studies. These were younger age for initial dose choice and basal number of urgency and change in incontinence episodes for up-titration. Treatment outcome (difference between values at 12 weeks vs. baseline) for each OAB system was strongly driven by the respective baseline value, whereas no other parameter exhibited a consistent association. Patients starting on the 30 mg dose and escalating to 45 mg after 4 weeks had outcomes comparable with those staying on a starting dose of 30 or 45 mg. We conclude that dose escalation after 4 weeks brings OAB patients with an initially limited improvement to a level seen in initially good responders. Analysis of underlying factors yielded surprisingly little consistent insight.
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http://dx.doi.org/10.3390/jcm10020311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830207PMC
January 2021

Beyond Antimuscarinics: A Review of Pharmacological and Interventional Options for Overactive Bladder Management in Men.

Eur Urol 2021 Apr 2;79(4):492-504. Epub 2021 Jan 2.

Department of Urology, Clinic Favoriten and Sigmund Freud Private University, Vienna, Austria.

Context: The role of overactive bladder (OAB) treatment in women beyond antimuscarinics has been evaluated extensively. Beta-3 agonists, botulinum toxin-A (BTX-A), and nerve stimulation are indicated in these patients. However, data on male patients in this clinical scenario are scarce.

Objective: The aim of this systematic review was to evaluate the evidence on treatment options beyond antimuscarinics in men with OAB.

Evidence Acquisition: A search of PubMed, EMBASE, Scopus, Web of science, Cochrane Central Register of Controlled Trials, and Cochrane Central Database of Systematic Reviews databases was performed for relevant articles published between January 2000 and October 2020, using the following Medical Subject Headings: "male/man," "LUTS," "overactive bladder," "storage symptoms," "urgency," "nocturia," "incontinence," "beta-3 agonist," "PDE-5 inhibitors," "botulinum toxin," "sacral nerve stimulation/neurostimulation," "percutaneous/transcutaneous tibial nerve stimulation," "PTENS," and "combination therapy." Evidence acquisition was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. PROSPERO registration number is CRD42020201223.

Evidence Synthesis: Overall, 24 studies were retrieved. In male OAB, mirabegron (MIRA) is the most intensively investigated pharmacological option. A pooled analysis of five randomized clinical trials (RCTs), including 1187 patients, concluded that MIRA 50 mg was associated with a greater reduction in frequency versus placebo (-0.37, 95% confidence interval [CI]: -0.74, -0.01, p <  0.05). A pooled analysis of three RCTs, including 1317 male patients, has also shown that the addition of MIRA 50 mg in men receiving the α-blocker tamsulosin improved the mean number of micturitions per day (-0.27, 95% CI: -0.46 to -0.09, p <  0.05), urgency episodes (-0.50, 95% CI: -0.77 to -0.22, p <  0.05), total OAB symptom score (-0.66, 95% CI: -1.00 to -0.38, p <  0.05), and mean volume voided (+10.76 ml, 95% CI: 4.87-16.64, p <  0.05). MIRA treatment is well tolerated in men. Other pharmacological treatment options, such as phosphodiesterase-5 (PDE-5) inhibitors, should be considered investigational. BTX-A seems to be effective as third-line treatment in male OAB patients. A higher rate of intermittent self-catheterization (5-42%) is observed in male than in female patients. Data on nerve stimulation are scarce.

Conclusions: MIRA has the most robust data in terms of safety and efficacy in this patient population. Preliminary data in men suggest that BTX-A is indicated as an interventional treatment. Evidence for PDE-5 inhibitors and nerve stimulation is too limited to provide recommendations. Future studies in this population should aim to better define the best treatment sequence and to identify predictors for treatment response and failure, to determine a therapeutic approach tailored to patients' characteristics.

Patient Summary: Overactive bladder is highly prevalent in men. Mirabegron 50 mg is the treatment option supported by the highest level of evidence when antimuscarinics failed. Botulinum toxin A injections seems to be an effective treatment as interventional option. Roles of nerve stimulation and phosphodiesterase inhibitors in male OAB patients are still to be defined.
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http://dx.doi.org/10.1016/j.eururo.2020.12.032DOI Listing
April 2021

Impact of early vs. delayed initiation of dutasteride/tamsulosin combination therapy on the risk of acute urinary retention or BPH-related surgery in LUTS/BPH patients with moderate-to-severe symptoms at risk of disease progression.

World J Urol 2020 Dec 18. Epub 2020 Dec 18.

Clinical Pharmacology and Therapeutics Group, University College London, BMA House, Tavistock Square, London, WC1H 9JP, UK.

Purpose: To evaluate the effect of delayed start of combination therapy (CT) with dutasteride 0.5 mg and tamsulosin 0.4 mg on the risk of acute urinary retention or benign prostatic hyperplasia (BPH)-related surgery (AUR/S) in patients with moderate-to-severe lower urinary tract symptoms (LUTS) at risk of disease progression.

Methods: Using a time-to-event model based on pooled data from 10,238 patients from Phase III/IV dutasteride trials, clinical trial simulations (CTS) were performed to assess the risk of AUR/S up to 48 months in moderate-to-severe LUTS/BPH patients following immediate and delayed start of CT for those not responding to tamsulosin monotherapy. Simulation scenarios (1300 subjects/arm) were investigated, including immediate start (reference) and alternative delayed start (six scenarios 1-24 months). AUR/S incidence was described by Kaplan-Meier survival curves and analysed using log-rank test. The cumulative incidence of events as well as the relative and attributable risks were summarised stratified by treatment.

Results: Survival curves for patients starting CT at month 1 and 3 did not differ from those who initiated CT immediately. By contrast, significant differences (p < 0.001) were observed when switch to CT occurs ≥ 6 months from the initial treatment. At month 48, AUR/S incidence was 4.6% vs 9.5%, 11.0% and 11.3% in patients receiving immediate CT vs. switchers after 6, 12 and 24 months, respectively.

Conclusions: Start of CT before month 6 appears to significantly reduce the risk of AUR/S compared with delayed start by ≥ 6 months. This has implications for the treatment algorithm for men with LUTS/BPH at risk of disease progression.
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http://dx.doi.org/10.1007/s00345-020-03517-0DOI Listing
December 2020

Which drugs are best for overactive bladder? From patients' expectations to physicians' decisions.

Int J Clin Pract 2021 Apr 11;75(4):e13870. Epub 2020 Dec 11.

Department of Urology, Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Sheffield, United Kingdom.

Aim: In order to help physicians determine which drugs are the best for treating overactive bladder (OAB) symptoms, this review considered three questions: what are the patient's expectations? What information is generated by the Multicriteria Decision Analysis (MCDA) model? What can physicians expect from medical treatments?

Methods: A comprehensive literature search was undertaken on these three topics in order to assist physicians regarding the optimum treatment modality for OAB.

Results: Patients' difficulties in reporting symptoms and their expectations of treatment outcomes interfere with the success of treatment. To assist physicians in meeting patients' expectations and to choose the most appropriate treatment, a new approach, recognised by the European Medicines Agency, the MCDA model was used to compare the benefits and safety of OAB treatments.

Conclusion: The MCDA model is useful for comparing the benefit-safety profiles of OAB drugs in order to equip clinicians with information on the drug that might best meet their patient's needs. Flexibly dosed fesoterodine appeared to be most efficacious in resolving urgency and urgency incontinence compared with other drugs, and resolution of urinary urgency appears to be associated with a reduced number of reported adverse events.
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http://dx.doi.org/10.1111/ijcp.13870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047881PMC
April 2021

Model-based meta-analysis of the time to first acute urinary retention or benign prostatic hyperplasia-related surgery in patients with moderate or severe symptoms.

Br J Clin Pharmacol 2021 Jul 19;87(7):2777-2789. Epub 2021 Jan 19.

Clinical Pharmacology & Therapeutics Group, University College London, London, WC1H 9JP, UK.

Aims: Combination therapy of 5α-reductase inhibitor and α-blocker is a guideline-endorsed therapeutic approach for patients with moderate-to-severe lower urinary tract symptoms or benign prostatic hyperplasia (LUTS/BPH) who are at risk of disease progression. We aimed to disentangle the contribution of clinical and demographic baseline characteristics affecting the risk of acute urinary retention or BPH-related surgery (AUR/S) from the effect of treatment with drugs showing symptomatic and disease-modifying properties.

Methods: A time-to-event model was developed using pooled data from patients (n = 10 238) enrolled into six clinical studies receiving placebo, tamsulosin, dutasteride or tamsulosin-dutasteride combination therapy. A parametric hazard function was used to describe the time to first AUR/S. Covariate model building included the assessment of relevant clinical and demographic factors on baseline hazard. Predictive performance was evaluated by graphical and statistical methods.

Results: An exponential hazard model best described the time to first AUR/S in this group of patients. Baseline International Prostate Symptom Score, prostate-specific antigen, prostate volume and maximum urine flow were identified as covariates with hazard ratio estimates of 1.04, 1.08, 1.01 and 0.91, respectively. Dutasteride monotherapy and tamsulosin-dutasteride combination therapy resulted in a significant reduction in the baseline hazard (56.8% and 66.4%, respectively). By contrast, the effect of tamsulosin did not differ from placebo.

Conclusions: Our analysis showed the implications of disease-modifying properties of dutasteride and tamsulosin-dutasteride combination therapy for the risk of AUR/S. It also elucidated the contribution of different baseline characteristics to the risk of these events. The use of tamsulosin monotherapy (symptomatic treatment) has no impact on individual long-term risk.
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http://dx.doi.org/10.1111/bcp.14682DOI Listing
July 2021

The International Continence Society (ICS) report on the terminology for male lower urinary tract surgery.

Neurourol Urodyn 2020 11 12;39(8):2072-2088. Epub 2020 Oct 12.

Department of Urology, Paediatric Urology and Uro-Oncology, St. Antonius Hospital, Gronau, Germany.

Introduction: In the development of terminology of the lower urinary tract (LUT), due to its increasing complexity, the terminology for male LUT surgery needs to be updated using a male-specific approach and via a clinically-based consensus report.

Methods: This report combines the input of members of the Standardization Committee of the International Continence Society in a Working Group with recognized experts in the field, assisted by many external referees. Appropriate core clinical categories and a subclassification were developed to give a numeric coding to each definition. An extensive process of 14 rounds of internal and external review was developed to exhaustively examine each definition, with decision-making by collective opinion (consensus).

Results: A Terminology Report for male LUT and pelvic floor surgery, encompassing 149 separate definitions/descriptors, has been developed. It is clinically-based with the most common diagnoses defined. Clarity and user-friendliness have been key aims to make it interpretable by practitioners and trainees in male LUT surgery. Figures have not been included to avoid any preference or bias towards a specific procedure.

Conclusions: A consensus-based Terminology Report for male LUT surgery has been produced aimed at being a significant aid to clinical practice and a stimulus for research.
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http://dx.doi.org/10.1002/nau.24509DOI Listing
November 2020

The role of novel minimally invasive treatments for lower urinary tract symptoms associated with benign prostatic hyperplasia.

BJU Int 2020 09 3;126(3):317-326. Epub 2020 Aug 3.

Department of Urology, St. Antonius Hospital, Gronau, Germany.

Objectives: To provide an update on novel minimally invasive lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) treatments in a non-systematic review. To define potential target populations for the various new minimally invasive treatments.

Methods: Recent literature, meta-analyses and guideline recommendations for aquablation (AquaBeam ; PROCEPT BioRobotics, Redwood City, CA, USA), water vapour thermal therapy (Rezūm ; Boston Scientific, Natick, MA, USA), prostate artery embolisation (PAE), prostatic urethral lift (UroLift ; NeoTract-Teleflex, Pleasanton, CA, USA) and the temporary implantable nitinol device [i-TIND (nitinol butterfly-like stent ); Medi-Tate Ltd., Or-Akiva, Israel] were reviewed.

Results: Procedures that can be performed on an outpatient basis (Rezūm, PAE, UroLift and i-TIND) are not an alternative for the standard patient requiring BPH surgery. Their effect on urinary flow, post-void residual urine volume or bladder outlet obstruction is less pronounced than that of transurethral resection of the prostate (TURP). Yet, these options appear to be valuable for those patients unfit for surgery, men who want to avoid medical therapy in general, or those who want to avoid sexual side-effects associated with medical therapy or standard BPH surgery (e.g. TURP). Aquablation is the first successfully operationalised robotic resection system, especially for patients with prostates >50 g. Nevertheless, long-term data are necessary for all novel, minimally invasive treatments.

Conclusions: Better designed clinical trials, a clearer definition of target populations and a more realistic marketing allow a better characterisation of novel minimally invasive therapies for LUTS/BPH. It is hoped that some of these novel devices will stand the test of time, in contrast to the vast majority of their predecessors.
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http://dx.doi.org/10.1111/bju.15154DOI Listing
September 2020

Prevalence of female urinary incontinence in the developing world: A systematic review and meta-analysis-A Report from the Developing World Committee of the International Continence Society and Iranian Research Center for Evidence Based Medicine.

Neurourol Urodyn 2020 04 3;39(4):1063-1086. Epub 2020 Apr 3.

Department of Urology, Pediatric Urology and Urologic Oncology, St. Antonius Hospital, Gronau, Germany.

Aims: The prevalence of urinary incontinence (UI) in the developing world varies widely. Factors influencing prevalence rates are a key area of interest, and knowledge of these would provide appropriate planning for preventive primary and secondary health care programs. The objective of this report was to synthesize the best available evidence to determine UI prevalence rates in adult women in a population setting.

Methods: A comprehensive search strategy was employed to find published and unpublished studies. Databases searched included PubMed, Embase, Scopus, Web of Science, and Google Scholar. We used the standardized Joanna Briggs Institute Meta-Analysis of Statistics, Assessment, and Review Instrument to appraise the included studies.

Results: In total, 54 studies with 138,722 women aged 10 to 90 years were included in this meta-analysis. Prevalence of UI ranged from 2.8% in Nigeria to 57.7% in Iran. The total prevalence of UI was 25.7% (95% CI: 22.3-29.5) and the prevalence rates for stress, urgency, and mixed UI were 12.6% (95% CI: 10.3-15.4), 5.3% (95% CI: 3.4-8.3), and 9.1% (95% CI: 7.0-11.8), respectively. When we excluded the elderly population, UI prevalence only slightly changed (26.2%; 95% CI: 22.6-30.2). Prevalence rates varied considerably during different recall periods, ranging from 15.6% for UI during the last 12 months to 41.2% for UI during the last 3 months. However, the study quality and use of validated vs nonvalidated questionnaires only had a minor impact on the prevalence rates.

Conclusions: The prevalence, methodology, and definition of UI vary widely. A large-scale multinational study with a homogeneous methodology is necessary to correctly calculate and compare the prevalence rates to improve health policies in the developing world.
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http://dx.doi.org/10.1002/nau.24342DOI Listing
April 2020

[The Alken stages-a German-French affair].

Urologe A 2020 Oct;59(10):1208-1216

Klinik für Urologie, Kinderurologie und Urologische Onkologie, St. Antonius-Hospital GmbH, Gronau, Deutschland.

Anatomy and pathophysiology of the prostate have gained increasing attention of anatomists and surgeons at the beginning of the 19th century. It was only around 1900 that French and German authors discussed staging of clinical benign prostatic hyperplasia (BPH) in order to group therapy. From 1970 to the 1990s, staging of the clinical course of BPH was associated with the name of Carl-Erich Alken, a leading figure within the German urological society at that time, although Alken never researched or focused on disease staging. He only presented the three traditional clinical stages originally described in 1888 by Jean Casimir Felix Guyon in a short and often edited and translated student's textbook (1955).
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http://dx.doi.org/10.1007/s00120-020-01173-1DOI Listing
October 2020

Model-based meta-analysis of individual International Prostate Symptom Score trajectories in patients with benign prostatic hyperplasia with moderate or severe symptoms.

Br J Clin Pharmacol 2020 08 14;86(8):1585-1599. Epub 2020 Apr 14.

Clinical Pharmacology and Therapeutics Group, University College London, London, UK.

Aims: International Prostate Symptom Score (IPSS) is a marker of lower urinary tract symptoms (LUTS) deterioration or improvement in benign prostate hyperplasia (BPH). Whereas changes in IPSS relative to baseline have been used as endpoints in clinical trials, little attention has been given to the time course of symptoms. The current investigation aimed to develop a drug-disease model to describe individual IPSS trajectories in moderate and severe BPH patients.

Methods: A model-based meta-analytical approach was used including data from 10 238 patients enrolled into Phase III and IV studies receiving placebo, tamsulosin, dutasteride or combination therapy over a period of up to 4 years. Model predictive performance was assessed using statistical and graphical criteria. Subsequently, simulations were performed to illustrate the implications of treatment with drugs showing symptomatic and disease-modifying properties in patients with varying disease progression rates.

Results: Improvement and worsening of IPSS could be characterized by a model including a sigmoid function which disentangles drug effects from placebo and varying disease progression rates on IPSS. Mean estimate (95% confidence intervals) for the disease progression rate was 0.319 (0.271-0.411) month . Treatment effect on IPSS (DELTA) was found to be 0.0605, 0.0139 and 0.0310 month for placebo, tamsulosin and combination therapy, respectively. In addition, it appears that individual trajectories can be clustered together into different phenotypes describing the underlying disease progression rate (i.e. slow, moderate and fast progressors).

Conclusions: The availability of a drug-disease model enables the evaluation of interindividual differences in disease progression rate, deterioration of symptoms and treatment effects on LUTS/BPH.
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http://dx.doi.org/10.1111/bcp.14268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373698PMC
August 2020

Development and validation of a patient decision aid for prostate Cancer therapy: from paternalistic towards participative shared decision making.

BMC Med Inform Decis Mak 2019 07 11;19(1):130. Epub 2019 Jul 11.

Department of Radiation Oncology (MAASTRO Clinic), GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Dr. Tanslaan 12, 6229, ET, Maastricht, The Netherlands.

Background: Patient decision aids (PDAs) can support the treatment decision making process and empower patients to take a proactive role in their treatment pathway while using a shared decision-making (SDM) approach making participatory medicine possible. The aim of this study was to develop a PDA for prostate cancer that is accurate and user-friendly.

Methods: We followed a user-centered design process consisting of five rounds of semi-structured interviews and usability surveys with topics such as informational/decisional needs of users and requirements for PDAs. Our user-base consisted of 8 urologists, 4 radiation oncologists, 2 oncology nurses, 8 general practitioners, 19 former prostate cancer patients, 4 usability experts and 11 healthy volunteers.

Results: Informational needs for patients centered on three key factors: treatment experience, post-treatment quality of life, and the impact of side effects. Patients and clinicians valued a PDA that presents balanced information on these factors through simple understandable language and visual aids. Usability questionnaires revealed that patients were more satisfied overall with the PDA than clinicians; however, both groups had concerns that the PDA might lengthen consultation times (42 and 41%, respectively). The PDA is accessible on http://beslissamen.nl/ .

Conclusions: User-centered design provided valuable insights into PDA requirements but challenges in integrating diverse perspectives as clinicians focus on clinical outcomes while patients also consider quality of life. Nevertheless, it is crucial to involve a broad base of clinical users in order to better understand the decision-making process and to develop a PDA that is accurate, usable, and acceptable.
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http://dx.doi.org/10.1186/s12911-019-0862-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624887PMC
July 2019

Impact of disease progression on individual IPSS trajectories and consequences of immediate versus delayed start of treatment in patients with moderate or severe LUTS associated with BPH.

World J Urol 2020 Feb 11;38(2):463-472. Epub 2019 May 11.

Clinical Pharmacology and Therapeutics Group, University College London, London, UK.

Purpose: Despite superiority of tamsulosin-dutasteride combination therapy versus monotherapy for lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH), patients at risk of disease progression are often initiated on α-blockers. This study evaluated the impact of initiating tamsulosin monotherapy prior to switching to tamsulosin-dutasteride combination therapy versus immediate combination therapy using a longitudinal model describing International Prostate Symptom Score (IPSS) trajectories in moderate/severe LUTS/BPH patients at risk of disease progression.

Methods: Clinical trial simulations (CTS) were performed using data from 10,238 patients from Phase III/IV dutasteride trials. The effect of varying disease progression rates was explored by comparing profiles on- and off-treatment. CTS scenarios were investigated, including a reference (immediate combination therapy) and six alternative virtual treatment arms (delayed combination therapy of 1-24 months). Clinical response (≥ 25% IPSS reduction relative to baseline) was analysed using log-rank test. Differences in IPSS relative to baseline at various on-treatment time points were assessed by t tests.

Results: Delayed combination therapy initiation led to significant (p < 0.01) decreases in clinical response. At month 48, clinical response rate was 79.7% versus 74.1%, 70.3% and 71.0% and IPSS was 6.3 versus 7.6, 8.1 and 8.0 (switchers from tamsulosin monotherapy after 6, 12 and 24 months, respectively) with immediate combination therapy. More patients transitioned from severe/moderate to mild severity scores by month 48.

Conclusions: CTS allows systematic evaluation of immediate versus delayed combination therapy. Immediate response to α-blockers is not predictive of long-term symptom improvement. Observed IPSS differences between immediate and delayed combination therapy (6-24 months) are statistically significant.
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http://dx.doi.org/10.1007/s00345-019-02783-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994451PMC
February 2020

What uro-gynecologists should know about sacral neuromodulation (SNM) for the treatment of refractory overactive bladder.

Arch Gynecol Obstet 2019 05 2;299(5):1243-1252. Epub 2019 Apr 2.

Department of Obstetrics and Gynecology, University Hospital Tübingen, Tübingen, Germany.

Purpose: To inform uro-gynecologists about the current standards and latest developments of sacral neuromodulation (SNM) in women with overactive bladder (OAB).

Methods: Literature search in the PubMed database for articles published between 1988 and 2019 on SNM for OAB in women.

Results: In total, 361 articles were identified and 51 articles retrieved for the review. SNM shows an objective success rate of 70-80%, OAB cure rate of 17-47% and a subjective satisfaction rate of 80-90%. These benefits have to be weighed against an adverse event rate of approx. 40%. SNM is significantly more successful than switching to another antimuscarinic after failed antimuscarinic drug therapy. Efficacy of SNM is slightly lower compared to bladder wall injections with 200 U botulinum toxin in the first months but efficacy of both treatments appears to be similar after 24 months. MRI examinations of patients with a sacral neurostimulator should only be performed after radiologist consultation. Sacral neurostimulators in patients with another pacemaker system should only be implanted after interdisciplinary consultation. The sacral neuromodulator should be turned off during pregnancy and delivery. SNM for OAB in patients with concomitant female sexual dysfunction or fecal incontinence seems to be beneficial.

Conclusions: SNM is a successful and recommended second-line treatment of OAB. Sacral neurostimulators should preferably be implanted in SNM-centers because complications and the frequency of revisions are significantly reduced with increasing experience of the surgeon.
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http://dx.doi.org/10.1007/s00404-019-05127-7DOI Listing
May 2019

A Comprehensive Review of Overactive Bladder Pathophysiology: On the Way to Tailored Treatment.

Eur Urol 2019 06 26;75(6):988-1000. Epub 2019 Mar 26.

Department of Urology, University Hospital of Rouen, Rouen, France.

Context: Current literature suggests that several pathophysiological factors and mechanisms might be responsible for the nonspecific symptom complex of overactive bladder (OAB).

Objective: To provide a comprehensive analysis of the potential pathophysiology underlying detrusor overactivity (DO) and OAB.

Evidence Acquisition: A PubMed-based literature search was conducted in April 2018, to identify randomised controlled trials, prospective and retrospective series, animal model studies, and reviews.

Evidence Synthesis: OAB is a nonspecific storage symptom complex with poorly defined pathophysiology. OAB was historically thought to be caused by DO, which was either "myogenic" (urgency initiated from autonomous contraction of the detrusor muscle) or "neurogenic" (urgency signalled from the central nervous system, which initiates a detrusor contraction). Patients with OAB are often found to not have objective evidence of DO on urodynamic studies; therefore, alternative mechanisms for the development of OAB have been postulated. Increasing evidence on the role of urothelium/suburothelium and bladder afferent signalling arose in the early 2000s, emphasising an afferent "urotheliogenic" hypothesis, namely, that urgency is initiated from the urothelium/suburothelium. The urethra has also recently been regarded as a possible afferent origin of OAB-the "urethrogenic" hypothesis. Several other pathophysiological factors have been implicated, including metabolic syndrome, affective disorders, sex hormone deficiency, urinary microbiota, gastrointestinal functional disorders, and subclinical autonomic nervous system dysfunctions. These various possible mechanisms should be considered as contributing to diagnostic and treatment algorithms.

Conclusions: There is a temptation to label OAB as "idiopathic" without obvious causation, given the poorly understood nature of its pathophysiology. OAB should be seen as a complex, multifactorial symptom syndrome, resulting from multiple potential pathophysiological mechanisms. Identification of the underlying causes on an individual basis may lead to the definition of OAB phenotypes, paving the way for personalised medical care.

Patient Summary: Overactive bladder (OAB) is a storage symptom syndrome with multiple possible causes. Identification of the mechanisms causing a patient to experience OAB symptoms may help tailor treatment to individual patients and improve outcomes.
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http://dx.doi.org/10.1016/j.eururo.2019.02.038DOI Listing
June 2019

The development of the ICIQ-UAB: A patient reported outcome measure for underactive bladder.

Neurourol Urodyn 2019 03 22;38(3):996-1004. Epub 2019 Feb 22.

Bristol Urological Institute, Bristol, UK.

Aims: To present the development of the International Consultation on Incontinence Questionnaire-underactive bladder (ICIQ-UAB) as the first patient reported outcome measure for the assessment of the symptoms and impact on the health-related quality of life of UAB developed in-line with the Food and Drug Administration Guidance for Industry.

Methods: Draft items were developed following 44 semi-structured concept elicitation interviews in the UK and refined using 36 cognitive interviews. A pilot study was designed to assess the draft ICIQ-UAB's initial psychometric properties with 54 patients recruited from European hospitals. Further concept elicitation interviews were also carried out with 11 patients in the US and 10 patients in Japan. All participants had a prior urodynamic diagnosis of detrusor underactivity.

Results: The cognitive interviews confirmed the initial items to be understood and interpreted as intended. Pilot testing showed that both internal consistency (Cronbach's α ≥ 0.85) and test-retest reliability (stable patients; intraclass correlation coefficient ≥ 0.88) were high. The interviews in the US and Japan elicited symptoms and impacts that support previous findings in the UK and provided further insight into the experiences of patients in those countries. The developmental ICIQ-UAB was refined using the evidence from all substudies.

Conclusions: The validity and reliability of the ICIQ-UAB were supported in a pilot study setting and the wider cultural applicability by the additional interviews in the US and Japan. Following further validation in future clinical trials, the developmental ICIQ-UAB is envisaged as an important tool for the monitoring of future UAB treatment strategies.
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http://dx.doi.org/10.1002/nau.23947DOI Listing
March 2019

The International Continence Society (ICS) report on the terminology for adult male lower urinary tract and pelvic floor symptoms and dysfunction.

Neurourol Urodyn 2019 02 25;38(2):433-477. Epub 2019 Jan 25.

University of Toronto, Ontario, Canada.

Introduction: In the development of terminology of the lower urinary tract, due to its increasing complexity, the terminology for male lower urinary tract and pelvic floor symptoms and dysfunction needs to be updated using a male-specific approach and via a clinically-based consensus report.

Methods: This report combines the input of members of the Standardisation Committee of the International Continence Society (ICS) in a Working Group with recognized experts in the field, assisted by many external referees. Appropriate core clinical categories and a subclassification were developed to give a numeric coding to each definition. An extensive process of 22 rounds of internal and external review was developed to exhaustively examine each definition, with decision-making by collective opinion (consensus).

Results: A Terminology Report for male lower urinary tract and pelvic floor symptoms and dysfunction, encompassing around 390 separate definitions/descriptors, has been developed. It is clinically-based with the most common diagnoses defined. Clarity and user-friendliness have been key aims to make it interpretable by practitioners and trainees in all the different specialty groups involved in male lower urinary tract and pelvic floor dysfunction. Male-specific imaging (ultrasound, radiology, CT, and MRI) has been a major addition whilst appropriate figures have been included to supplement and help clarify the text.

Conclusions: A consensus-based Terminology Report for male lower urinary tract and pelvic floor symptoms and dysfunction has been produced aimed at being a significant aid to clinical practice and a stimulus for research.
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http://dx.doi.org/10.1002/nau.23897DOI Listing
February 2019

Intradetrusor onabotulinumtoxinA injections are significantly more efficacious than oral oxybutynin for treatment of neurogenic detrusor overactivity: results of a randomized, controlled, 24-week trial.

Einstein (Sao Paulo) 2018 Aug 6;16(3):eAO4207. Epub 2018 Aug 6.

Centro de Reabilitação e Readaptação Dr. Henrique Santillo, Goiânia, GO, Brazil.

Objective: To prospectively compare the results of intradetrusor onabotulinumtoxinA injections and oral oxybutynin for urinary continence, urodynamic parameters and quality of life in patients with neurogenic detrusor overactivity due to spinal cord injury.

Methods: Adult patients under intermittent catheterization were randomized 1:1 to receive one injection of onabotulinumtoxinA 300U or oxybutynin 5mg, per oris, three times/day. Primary study endpoint was change in urinary incontinence episodes/24 hours and secondary study endpoints were maximum cystometric capacity, maximum detrusor pressure, bladder compliance and quality of life before randomization and at week 24.

Results: Sixty-eight patients participated in the trial. Significant improvements in urinary incontinence per 24 hours, all investigated urodynamic parameters and quality of life were observed in both groups. Compared with oral oxybutynin, onabotulinumtoxinA was significantly more efficacious for all parameters investigated. Non-response to treatment was higher for oral oxybutynin (23.5%) than onabotulinumtoxinA (11.8%). Dry mouth was the most common adverse in patients with oral oxybutynin (72%) and transient macroscopic hematuria in patients with onabotulinumtoxinA (28%). Only one patient with oral oxybutynin dropped out the study because of adverse effects.

Conclusion: The comparison of the two study drugs showed that onabotulinumtoxinA was significantly more efficacious than oral oxybutynin with regard to continence, urodynamic parameters and quality of life. Clinicaltrials.gov: NCT:01477736.
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http://dx.doi.org/10.1590/S1679-45082018AO4207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6080704PMC
August 2018

[Nocturia in men with benign prostatic hyperplasia].

Aktuelle Urol 2018 Aug 7;49(4):319-327. Epub 2018 Aug 7.

Urologie, St. Antonius Hospital, Gronau.

Nocturia, defined as nocturnal micturition with a frequency of at least once per night, is one of the most frequent lower urinary tract symptoms in men with benign prostatic hyperplasia (BPH) and often causes them to consult a physician. Nocturia is often bothersome and responsible for increased morbidity and mortality. Nocturia can be caused by increased fluid intake, increased diuresis or decreased bladder capacity, either alone or in combination. The underlying pathophysiology of nocturia can only be detected by methodical evaluation of the patient. Bladder diaries for 3 days are an essential part of the assessment. Treatment goals include reducing the nocturnal voiding frequency to less than 2 episodes per night, increasing the duration of undisturbed sleep to more than 4 hours, restoring quality of life, and reducing morbidity as well as mortality. In patients with reduced functional bladder capacity, α-blockers, 5α-reductase inhibitors, phosphodiesterase type-5 inhibitors, plant extracts or prostate operations (e. g. TURP) have shown to significantly reduce nocturnal voiding frequency. If nocturnal polyuria causes or contributes to nocturia, as shown in up to 80 % of BPH patients with nocturia, the treatment goal is to reduce urine production during the night. Low nocturnal serum concentration of the antidiuretic hormone can be treated with desmopressin to be taken at bedtime. The risk of hyponatremia is reduced with the new low-dose desmopressin formulation, which can be used even in men older than 65 years of age. Drug combinations may be useful in men with a mixed pathophysiology of nocturia.
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http://dx.doi.org/10.1055/a-0650-3700DOI Listing
August 2018

Renal cell cancer after kidney transplantation.

Langenbecks Arch Surg 2018 Aug 12;403(5):631-641. Epub 2018 Jul 12.

Department of General, Visceral and Transplant Surgery, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.

Purpose: This study aims to identify modifiable risk factors for de novo renal cell carcinoma (RCC) after kidney transplantation in a matched-pair approach matching for unmodifiable factors.

Patients And Methods: One thousand six hundred fifty-five adults who underwent kidney transplantation in the period 1 January 2000 to 31 December 2012 were analyzed. Patients with RCC after kidney transplantation were matched in a 1:2 ratio with those without RCC using the indication for transplantation, age at transplantation (± 10 years), recipient sex (male/female), number of received transplants, living organ donor transplantation (yes/no), and time of follow-up in days as matching criteria. The paired t test was used to compare continuous variables and the Cochran-Mantel-Haenszel test for categorical variables. Multivariable conditional logistic regression modeling was used to identify independent risk factors for RCC.

Results: In matched-pair analysis, a total number of 26 incident cases with RCC after kidney transplantation could be matched. Post-transplant RCC was significantly associated with longer durations of pre-transplant hemodialysis (p = 0.007) and post-transplant immunosuppression with cyclosporine (p = 0.029) and/or mycophenolate mofetil (p = 0.020) and with larger proportions of post-transplant time on mycophenolate mofetil (p = 0.046) and/or prednisolone medication (p = 0.042). Multivariable conditional logistic regression modeling revealed a significant risk increasing multiplicative factor interaction between the duration of pre-transplant dialysis (years) and the time of prednisolone usage (percent/100). Cyclosporine A usage and mycophenolate mofetil usage were also revealed as independent, significant risk factors for RCC development.

Conclusions: Longer pre-transplant dialysis, cyclosporine-based protocols and/or intensified immunosuppression with additional mycophenolate mofetil, and larger proportions of time of prednisolone treatment during follow-up increase de novo RCC risk.
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http://dx.doi.org/10.1007/s00423-018-1694-xDOI Listing
August 2018

Do patient characteristics predict which patients with overactive bladder benefit from a higher fesoterodine dose?

Int Urogynecol J 2019 Feb 29;30(2):239-244. Epub 2018 Mar 29.

Pfizer Inc, New York, NY, USA.

Introduction And Hypothesis: We sought to determine whether baseline characteristics predict which overactive bladder (OAB) patients benefit from fesoterodine 8 mg versus 4 mg.

Methods: In double-blind, placebo-controlled, flexible-dose trials, baseline characteristics of OAB patients with ≥ 1 urgency urinary incontinence (UUI) episodes/24 h who escalated from fesoterodine 4 mg to 8 mg were evaluated. Possible dose-escalation predictors (age; sex; previous antimuscarinic use; UUI, micturitions, and urgency episodes/24 h; race; body mass index; time to dose escalation; OAB duration) were compared in escalators versus non-escalators. Patients from fixed-dose trials with dose-escalator characteristics were identified (matched dose-escalator sample) to assess changes from baseline with fesoterodine 4 mg, 8 mg, and placebo.

Results: In flexible-dose trials, significant predictors of fesoterodine dose escalation were younger age (≤ 65.8 years), greater number of baseline micturitions (≥ 13.1) and urgency episodes/24 h (≥ 10.9), greater OAB duration (≥ 9.1 years), and more frequent previous antimuscarinic use (58.3%), but not baseline UUI episodes/24 h. In the matched dose-escalator sample (fesoterodine 4 mg: n = 215; 8 mg: n = 198; placebo: n = 217), change from baseline in UUI episodes significantly improved with fesoterodine 8 mg versus 4 mg (P = 0.043) and with both doses versus placebo (P < 0.001). Dry mouth and constipation rates were higher with fesoterodine 8 mg.

Conclusions: Dose-escalator patients had a significantly greater UUI response with fesoterodine 8 mg versus 4 mg. Given the potential for adverse events, fesoterodine 4 mg is recommended to start; however, patients with UUI and identified predictors may benefit from initial treatment with fesoterodine 8 mg or rapid dose escalation.
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http://dx.doi.org/10.1007/s00192-018-3640-4DOI Listing
February 2019

A practical approach to the management of nocturia.

Int J Clin Pract 2017 Nov 5;71(11). Epub 2017 Oct 5.

Department of Urology, Ghent University Hospital, Ghent, Belgium.

Aim: To raise awareness on nocturia disease burden and to provide simplified aetiologic evaluation and related treatment pathways.

Methods: A multidisciplinary group of nocturia experts developed practical advice and recommendations based on the best available evidence supplemented by their own experiences.

Results: Nocturia is defined as the need to void ≥1 time during the sleeping period of the night. Clinically relevant nocturia (≥2 voids per night) affects 2%-18% of those aged 20-40 years, rising to 28%-62% for those aged 70-80 years. Consequences include the following: lowered quality of life; falls and fractures; reduced work productivity; depression; and increased mortality. Nocturia-related hip fractures alone cost approximately €1 billion in the EU and $1.5 billion in the USA in 2014. The pathophysiology of nocturia is multifactorial and typically related to polyuria (either global or nocturnal), reduced bladder capacity or increased fluid intake. Accurate assessment is predicated on frequency-volume charts combined with a detailed patient history, medicine review and physical examination. Optimal treatment should focus on the underlying cause(s), with lifestyle modifications (eg, reducing evening fluid intake) being the first intervention. For patients with sustained bother, medical therapies should be introduced; low-dose, gender-specific desmopressin has proven effective in nocturia due to idiopathic nocturnal polyuria. The timing of diuretics is an important consideration, and they should be taken mid-late afternoon, dependent on the specific serum half-life. Patients not responding to these basic treatments should be referred for specialist management.

Conclusions: The cause(s) of nocturia should be first evaluated in all patients. Afterwards, the underlying pathophysiology should be treated specifically, alone with lifestyle interventions or in combination with drugs or (prostate) surgery.
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http://dx.doi.org/10.1111/ijcp.13027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698733PMC
November 2017

Efficacy and safety of daily mirabegron 50 mg in male patients with overactive bladder: a critical analysis of five phase III studies.

Ther Adv Urol 2017 Dec 10;9(6):137-154. Epub 2017 May 10.

Department of Urology, Academic Medical Hospital, University of Maastricht, The Netherlands.

Background: Oral pharmacotherapies to treat overactive bladder (OAB) are used less in men despite a similar prevalence of storage symptoms as women. The efficacy and safety of once-daily mirabegron 50 mg was evaluated in male OAB patients from five phase III studies that included placebo or antimuscarinic (tolterodine ER 4 mg or solifenacin 5 mg) as a comparator.

Methods: Three pooled 12-week placebo-controlled studies (mirabegron 50 mg placebo) and one 12-week non-inferiority phase IIIb study (BEYOND; mirabegron 50 mg solifenacin 5 mg) were used for efficacy (daily micturition frequency, urgency and incontinence episodes) and safety analyses. An additional 52-week active-controlled phase III safety study (mirabegron 50 mg tolterodine ER 4 mg) was included in the safety analysis. Male patients aged ⩾18 years with OAB for ⩾3 months were included in the analyses. Patients may also have a history of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH)/benign prostatic enlargement (BPE) or concomitant use of α-blockers.

Results: In the pooled studies, mirabegron 50 mg demonstrated superiority placebo (treatment difference: -0.37 [95% confidence interval (CI): -0.74, -0.01]) for reducing micturition frequency; improvements in urgency and incontinence were not significantly different between mirabegron 50 mg and placebo. In BEYOND, mirabegron 50 mg was comparable with solifenacin 5 mg for reducing micturition frequency, urgency, and incontinence episodes. Mirabegron was well tolerated at 12 and 52 weeks and overall treatment-emergent adverse events (AEs) were similar to those with placebo.

Conclusions: In a male OAB population with or without LUTS associated with BPH/BPE, mirabegron 50 mg provided similar improvements in urgency, frequency, and incontinence as solifenacin 5 mg, and is a well-tolerated alternative to antimuscarinics. In the three pooled 12-week studies, significant differences were not seen for urgency and incontinence placebo, although mirabegron 50 mg did demonstrate significant improvements placebo for frequency.
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http://dx.doi.org/10.1177/1756287217702797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444577PMC
December 2017

Incidence of urinary retention during treatment with single tablet combinations of solifenacin+tamsulosin OCAS™ for up to 1 year in adult men with both storage and voiding LUTS: A subanalysis of the NEPTUNE/NEPTUNE II randomized controlled studies.

PLoS One 2017 6;12(2):e0170726. Epub 2017 Feb 6.

Maastricht University Medical Center, Maastricht, The Netherlands.

Introduction: The emergence of urinary retention (UR), specifically acute urinary retention (AUR), has been a concern when treating men with lower urinary tract symptoms (LUTS) with antimuscarinic drugs.

Materials And Methods: In NEPTUNE (12-week, double-blind), men (≥45 years) with LUTS were randomized to receive tamsulosin oral-controlled absorption system (TOCAS) 0.4 mg, fixed-dose combination (FDC) of solifenacin (Soli) 6 mg + TOCAS 0.4 mg, FDC Soli 9 mg + TOCAS 0.4 mg, or placebo. In NEPTUNE II (40-week, open-label extension of NEPTUNE), continuing patients received 4-week FDC Soli 6 mg + TOCAS, then FDC Soli 6 mg or 9 mg + TOCAS for the remainder of the study, switchable every 3 months.

Results: Across both studies, 1208 men received ≥1 dose of FDC Soli 6 mg or 9 mg + TOCAS for up to 52 weeks; 1199 men completed NEPTUNE and 1066 received ≥1 dose in NEPTUNE II. In total, 13 men (1.1%; 95% CI, 0.6%-1.8%) reported a UR event while receiving FDC, eight of which were AUR (0.7%; 95% CI, 0.3%-1.3%, incidence 7/1000 man-years). Six men reported UR events while taking Soli 6 mg + TOCAS (three AUR), and seven men reported a UR event while taking Soli 9 mg + TOCAS (five AUR). One man developed AUR while taking TOCAS alone and four reported UR (three AUR) during placebo run-in. Most AUR/UR events occurred within 4 months of treatment initiation.

Conclusions: FDC Soli and TOCAS was associated with a low rate of UR and AUR in men with LUTS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0170726PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293258PMC
August 2017
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