Complete genome sequence of Pseudomonas aeruginosa strain NCTR 501 isolated from the inner ear of a laboratory mouse (Mus musculus) diagnosed with otitis media.

We report the circularized 6,427,509-bp genome of Pseudomonas aeruginosa isolated from the inner ear of a laboratory mouse (Mus musculus) diagnosed with otitis media. The genome of P. aeruginosa NCTR 501 has a circular chromosome of 6,420,288 bp and two plasmids of 4,042 and 3,179 bp, respectively.

Mirabegron Vs Placebo Add-on Therapy in Men With Overactive Bladder Symptoms Receiving Tamsulosin for Underlying Benign Prostatic Hyperplasia: A Safety Analysis From the Randomized, Phase 4 PLUS Study.

OBJECTIVE: To analyze the safety of mirabegron add-on therapy in men with overactive bladder symptoms concurrently receiving tamsulosin for lower urinary tract symptoms associated with benign prostatic hyperplasia. METHODS: The Phase 4 PLUS study comprised a 4-week run-in period (tamsulosin [0.4 mg]) and a 12-week randomized treatment period (add-on treatment: mirabegron [25 mg] or placebo). Doses were increased to mirabegron 50 mg or matched placebo after 4 weeks. Safety assessments: treatment-emergent adverse events (TEAEs), vital signs, 12-lead electrocardiograms, and changes in postvoid residual volume and maximum urinary flow (Qmax). RESULTS: The safety analysis set included 352 tamsulosin plus mirabegron (TAM + MIRA) and 354 tamsulosin plus placebo (TAM + PL) patients. The frequency of overall TEAEs was higher with TAM + PL, although a higher incidence of drug-related TEAEs was observed with TAM + MIRA. Most TEAEs were mild or moderate in severity. Drug-related serious TEAEs were reported for 3 patients (2 TAM + MIRA patients: acute myocardial infarction with cerebral infarction and angina pectoris, 1 TAM + PL patient: lacunar stroke). Hypertension, headache, and nasopharyngitis were the most common TEAEs. Special interest TEAEs were infrequently reported. The most common was urinary retention and 2 TAM + MIRA patients required catheterization (neither led to discontinuation). No major changes in blood pressure or pulse rate were noted and similar electrocardiogram parameters were observed for both groups. Changes in mean postvoid residual volume and Qmax were not clinically meaningful. CONCLUSION: No unexpected safety concerns were noted in men receiving tamsulosin for lower urinary tract symptoms associated with benign prostatic hyperplasia who subsequently received mirabegron add-on therapy.

Efficacy and Safety of Mirabegron versus Placebo Add-On Therapy in Men with Overactive Bladder Symptoms Receiving Tamsulosin for Underlying Benign Prostatic Hyperplasia: A Randomized, Phase 4 Study (PLUS).

PURPOSE: PLUS investigated the efficacy and safety of mirabegron add-on therapy in men with overactive bladder symptoms receiving tamsulosin for underlying lower urinary tract symptoms attributable to benign prostatic hyperplasia. MATERIALS AND METHODS: In this phase 4 study a 4-week 0.4 mg tamsulosin run-in period was followed by a 12-week, randomized, double-blind, treatment period in which patients initially received 25 mg mirabegron or placebo add-on therapy. At 4 weeks doses were titrated to 50 mg mirabegron or placebo equivalent. Efficacy end points were changes from baseline to end of treatment in mean number of micturitions per day (primary), mean volume voided per micturition, number of urgency episodes per day, total urgency and frequency score, and total International Prostate Symptom Score (secondary). Safety assessments included treatment emergent adverse events, and post-void residual volume, and maximum urinary flow measurements. RESULTS: Of the 676 men most were 65 years old or older (380, 56.2%). Tamsulosin plus mirabegron was statistically superior to tamsulosin plus placebo in reducing the mean number of micturitions per day (-2.00 vs -1.62; adjusted difference -0.39; 95% CI -0.76, -0.02). Statistically superior results were noted for tamsulosin plus mirabegron in mean volume voided per micturition, urgency episodes per day, and total urgency and frequency score (not International Prostate Symptom Score). Higher overall treatment emergent adverse event rates were observed with tamsulosin plus placebo, although higher rates of drug related treatment emergent adverse events were noted with tamsulosin plus mirabegron. Urinary retention rates were higher in the tamsulosin plus mirabegron group. Post-void residual volume and maximum urinary flow results were not clinically meaningful. CONCLUSIONS: The results of PLUS underscore the utility of mirabegron add-on therapy to treat men with overactive bladder symptoms receiving tamsulosin for benign prostatic hyperplasia.

Preliminary outcomes of the European multicentre experience with the ZSI 375 artificial urinary sphincter for treatment of stress urinary incontinence in men.

INTRODUCTION: The ZSI 375 is a new artificial urinary sphincter utilised in men suffering from stress urinary incontinence (SUI). We present the first European multicentre study on the effectiveness of ZSI 375. MATERIAL AND METHODS: This study was conducted in a retrospective, non-randomized format in centres across Europe. Between May 2009 and December 2014, ZSI 375 was fitted in 109 SUI patients following radical prostatectomy, transurethral resection of prostate (TURP), rectal surgery and high intensity focused ultrasound (HIFU). Patients with history of pelvic radiotherapy or previous surgical treatment for incontinence or stricture were excluded from the series. Follow-up was completed by December 2016. The key outcome measures included overall improvement and complication rates. RESULTS: A total of 109 patients in 10 European centres were recruited and had the ZSI 375 device implanted. The average patient age was 72 years old. The indication for the majority of patients was incontinence following radical prostatectomy (100/109 patients, 91.74%). On average, patients were incontinent for 48.6 months prior to treatment. All patients used ≥4 pads daily at baseline and thus were classified as suffering from 'severe incontinence'. The average follow-up until the final visit was 43 months. The pad usage decreased to 0.84 on average by the last visit. There were no reported cases of device infection. A total of 9 patients had urethral cuff erosion (8.25%),which was the most common complication in this series. A further 3 men (2.75%) experienced mechanical failure requiring subsequent device reimplantation. The implantation of the ZSI 375 device was considered successful in 92.66% of patients. CONCLUSIONS: The ZSI 375 is an effective surgical treatment option in men with severe stress urinary incontinence.

Clinical and Patient-reported Outcome Measures in Men Referred for Consideration of Surgery to Treat Lower Urinary Tract Symptoms: Baseline Results and Diagnostic Findings of the Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods (UPSTREAM).

BACKGROUND: Clinical evaluation of male lower urinary tract symptoms (MLUTS) in secondary care uses a range of assessments. It is unknown how MLUTS evaluation influences outcome of therapy recommendations and choice, notably urodynamics (UDS; filling cystometry and pressure flow studies). OBJECTIVE: To report participants' sociodemographic and clinical characteristics, and initial diagnostic findings of the Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods (UPSTREAM). UPSTREAM is a randomised controlled trial evaluating whether symptoms are noninferior and surgery rates are lower if UDS is included. DESIGN, SETTING, AND PARTICIPANTS: A total of 820 men (≥18 yr of age) seeking treatment for bothersome LUTS were recruited from 26 National Health Service hospital urology departments. INTERVENTION: Care pathway based on routine, noninvasive tests (control) or routine care plus UDS (intervention arm). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome is International Prostate Symptom Score (IPSS) and the key secondary outcome is surgery rates 18 mo after randomisation. International Consultation on Incontinence Questionnaires were captured for MLUTS, sexual function, and UDS satisfaction. Baseline clinical and patient-reported outcome measures (PROMs), and UDS findings were informally compared between arms. Trends across age groups for urinary and sexual PROMs were evaluated with a Cuzick's test, and questionnaire items were compared using Pearson's correlation coefficient. RESULTS AND LIMITATIONS: Storage LUTS, notably nocturia, and impaired sexual function are prominent in men being assessed for surgery. Sociodemographic and clinical evaluations were similar between arms. Overall mean IPSS and quality of life scores were 18.94 and 4.13, respectively. Trends were found across age groups, with older men suffering from higher rates of incontinence, nocturia, and erectile dysfunction, and younger men suffering from increased daytime frequency and voiding symptoms. Men undergoing UDS testing expressed high satisfaction with the procedure. CONCLUSIONS: Men being considered for surgery have additional clinical features that may affect treatment decision making and outcomes, notably storage LUTS and impaired sexual function. PATIENT SUMMARY: We describe initial assessment findings from a large clinical study of the treatment pathway for men suffering with bothersome urinary symptoms who were referred to hospital for further treatment, potentially including surgery. We report the patient characteristics and diagnostic test results, including symptom questionnaires, bladder diaries, flow rate tests, and urodynamics.

Vesomni improves the quality of life in men with lower urinary tract symptoms in routine clinical practice in Europe.

AIM: To evaluate the impact of Vesomni/Urizia/Volutsa, a fixed-dose combination tablet containing 6 mg solifenacin (antimuscarinic) and 0.4 mg tamsulosin (α-blocker), on health-related quality of life (HRQoL) and treatment satisfaction in men with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) in routine clinical practice. METHODS: EUROPA was a noninterventional study of men with LUTS/BPH not responding to monotherapy who were prescribed Vesomni in routine clinical practice. Data were collected retrospectively (1 year) and prospectively (1 year). Assessments were performed at baseline, weeks 4 to 8, weeks 9 to 18 (optional), weeks 19 to 39 (optional), and Weeks 40 to 52. The primary endpoint was change from baseline in HRQoL, as assessed by the Overactive Bladder Questionnaire (OAB-q) symptom bother subscale score. Change from baseline in OAB-q total and coping, sleep, and social interaction subscale scores, treatment satisfaction-visual analog scale (TS-VAS), International Prostate Symptom Score (IPSS), and European Quality of Life 5-Dimension-5-Level (EQ-5D-5L) questionnaire were also evaluated. RESULTS: Five hundred and eighty-nine patients were enrolled. The mean changes in adjusted mean (95% confidence interval [CI]) OAB-q symptom bother subscale scores were -16.40 (-24.31, -8.49) at weeks 4 to 8 and -19.59 (-28.26, -10.92) at weeks 40 to 52; at weeks 40 to 52, changes were clinically meaningful in 84.6% of patients. Adjusted mean (95% CI) change from baseline to weeks 40 to 52 were 15.02 (7.35, 22.69), 19.37 (10.86, 27.89), 18.65 (7.44, 29.86), 9.85 (3.90, 15.81), and 16.09 (9.07, 23.11) for concern, coping, sleep, social interaction, and total, respectively. TS-VAS, IPSS, and EQ-5D-5L all improved, and treatment persistence at weeks 40 to 52 was 77.1%. Urinary retention was reported in four (0.7%) patients. CONCLUSIONS: Vesomni was well-tolerated and improved HRQoL and treatment satisfaction in patients with LUTS/BPH.

Mirabegron improves quality-of-life, treatment satisfaction, and persistence in patients with overactive bladder: a multi-center, non-interventional, real-world, 12-month study.

OBJECTIVE: Observational studies can provide evidence about patient outcomes in routine clinical practice. This prospective, non-interventional study (BELIEVE) is the largest real-world European study to date to assess quality-of-life, treatment satisfaction, resource utilization, and persistence in patients with overactive bladder (OAB) who were prescribed mirabegron as part of routine clinical practice. METHODS: The primary objective was to evaluate change from baseline in quality-of-life based on overactive bladder questionnaire (OAB-q) sub-scales. Secondary objectives included evaluation of treatment persistence, patient satisfaction, healthcare resource utilization and adverse events (AEs). Follow-up was for 12 months with visit windows at 2-4 and 10-12 months. Median change from baseline in total OAB-q and its sub-scales (Health-related quality-of-life [HRQoL] and symptom bother scale) were assessed. RESULTS: Overall, 862 patients were enrolled from eight European countries. In the Full Analysis Set (FAS), 73.7% were female, mean age was 61.2 years; 47.7% ≥65 years. At baseline, 41.3% had switched from other OAB treatments, 42.2% were treatment naïve, 10.1% were lapsed, and 6.4% were on combination treatment. Symptom bother and HRQoL total scores improved from baseline to 2-4 and 10-12 months. There was a notable improvement in dry rate, increasing from 34.9% at baseline to 43.7% at 10-12 months in the FAS, and a reduction in pad use. Persistence was high, with 53.8% of FAS patients remaining on mirabegron at 10-12 months. Overall, no unexpected safety issues were observed and AEs were consistent with the known safety profile of mirabegron. CONCLUSION: Patients receiving mirabegron in a real-world setting reported meaningful improvements in QoL and health status, with a persistence rate of 53.8% at 12 months for the FAS. No unexpected safety issues were observed, and AEs were consistent with the known safety profile of mirabegron.

Persistence and adherence with mirabegron vs antimuscarinics in overactive bladder: Retrospective analysis of a UK General Practice prescription database.

INTRODUCTION AND OBJECTIVES: Persistence with antimuscarinic (AM) drugs prescribed for overactive bladder (OAB) is poor. This study aimed to compare persistence and adherence with the beta-3-adrenoceptor agonist mirabegron (MIR) vs AMs over 12 months. PATIENTS AND METHODS: This retrospective cohort analysis included patients aged ≥18 years who were prescribed MIR, or any AM. A 12-month look-back was used to assess inclusion eligibility. The primary end-point was persistence, defined as time to first discontinuation of index drug, during 1 year follow-up. The secondary end-point was adherence, estimated by medication possession ratio (MPR). RESULTS: Inclusion criteria were met by 6189 patients. Those prescribed AMs were mostly treatment-naïve (range 72.9%-95.3%) vs 54.4% of MIR patients. There was greater persistence with MIR vs AM. The median number of days on therapy with MIR was 101, vs 27-56 for AMs. Patients receiving AMs were significantly more likely to discontinue than those receiving MIR (hazard ratio [HR] range 1.24-2.05, P < .01 for each AM vs MIR. In treatment-naïve patients, HRs ranged from 1.25 (solifenacin, P = .012) to 2.07 (oxybutynin IR, P < .001). In treatment-experienced patients, they ranged from 1.10 (fesoterodine, P = NS) to 2.12 (oxybutynin IR, P < .001). Adherence was greater with MIR (mean MPR 48.4%) than with AMs (range 27.6%-40.4%, P < .001). Treatment-experienced patients were significantly less likely to discontinue treatment (HR 0.87, P = .006). DISCUSSION AND CONCLUSION: MIR was associated with a significantly longer time to discontinuation, greater persistence and better adherence than AMs. However, there was a steep decline in persistence with all drugs after 1 month. This is unlikely to be wholly explained by anticholinergic adverse events, as it was also seen with MIR. The lower proportion of MIR patients who were treatment-naive reflects current prescribing guidelines whereby MIR is prescribed after an initial generic AM trial. The study was limited by the small number of MIR patients. Study identifier: ISN 178-MA-3059.

Postprandial changes in small bowel water content in healthy subjects and patients with irritable bowel syndrome.

BACKGROUND & AIMS: Postprandial symptoms are common in patients with irritable bowel syndrome with diarrhea (IBS-D) and could be diet related. We studied postprandial changes in distribution of water in the upper gastrointestinal tract of healthy volunteers (HVs) and patients with IBS-D after contrasting meals. METHODS: In study 1, 11 HVs consumed 350-mL test meals with 5% mannitol (unabsorbable) or 5% glucose (readily absorbed). In study 2, 17 HVs consumed a 331-kcal meal, with or without 15 g bran. In study 3, 26 patients with IBS-D consumed the study 2 diet with bran meal. All subjects underwent serial magnetic resonance imaging analysis. RESULTS: In study 1, subjects' small bowel water content (SBWC) increased after the mannitol but not glucose meals, reaching 381 mL (interquartile range, 343-491 mL) and 47 mL (18-78 mL), respectively, 40 minutes after eating (P < .001). In study 2, SBWC initially decreased after both meal types and then increased, plateauing at 180-405 minutes and was greater after the bran meal (P = .02). In study 3, fasting and postprandial SBWC was lower in IBS-D than in HVs (P < .05 and P < .0001, respectively). Patients with IBS-D had faster orocecal transit times (135 minutes; 90-180 minutes) compared with HVs (225 minutes; 203-293 minutes; P < .0001) and reduced terminal ileum diameter (P < .003). CONCLUSIONS: Postprandial SBWC initially decreases, because of rapid, nutrient-driven fluid absorption, and then increases after a mixed liquid/solid meal. Patients with IBS-D have reduced fasting and postprandial SBWC with faster transit, possibly indicating increased small intestinal tone.