Pilot study to assess the feasibility of self-administered, low-dose methoxyflurane for cystoscopic procedures.

INTRODUCTION: Methoxyflurane (MEOF) (Penthrox™) is an inhaled, self-administered, non-opioid analgesic approved by Health Canada for the short-term relief of moderate to severe acute pain associated with trauma or interventional medical procedures. In this pilot study, we evaluated the feasibility of using MEOF as an anesthetic agent in 11 patients undergoing outpatient cystoscopic procedures. METHODS: The average duration of the procedure was 24 (range 20-35) minutes and this included 10 minutes of administration time of the drug and five minutes of wait time before the procedure. The average monitoring time from start to end of the procedure was 23 (range 20-35) minutes and this included 15 minutes of monitoring post-procedure. On a scale of 0-10, patients on average rated the pain 4/10 (standard deviation [SD] 2.6). RESULTS: Global performance was on average 3/4 (SD 1.3) for the patients and 3/4 (SD 1.1) for the operator. Of the 11 patients, four reported adverse events; two experienced euphoria, one experienced dizziness, and one was unable to tolerate the medication. Two patients noted their adverse events to be of moderate intensity, while the other two were of mild intensity. None of the adverse events was deemed serious. CONCLUSIONS: Our findings in this pilot study provide proof of principle for the design of a randomized control trial to evaluate MEOF as an anesthetic in an outpatient cystoscopic procedural setting. As more urologic procedures are being performed in an outpatient setting, this may offer significant clinical benefit.

Prevalence and repair patterns of vesicovaginal fistula: a large retrospective population-based cohort analysis.

PURPOSE: Vesicovaginal fistulae (VVF) have a significant negative impact on quality of life, with failed surgical repair resulting in ongoing morbidity. Our aim was to characterize the rate of VVF repair and repair failures over time, and to identify predictors of repair failure. METHODS: We completed a population-based, retrospective cohort study of all women who underwent VVF repair in Ontario, Canada, aged 18 and older between 2005 and 2018. Risk factors for repair failure were identified using multivariable cox proportional hazard analysis; interrupted time series analysis was used to determine change in VVF repair rate over time. RESULTS: 814 patients underwent VVF repair. Of these, 117 required a second repair (14%). Mean age at surgery was 52 years (SD 15). Most patients had undergone prior gynecological surgery (68%), and 76% were due to iatrogenic injury. Most repairs were performed by urologists (60%). Predictors of VVF re-repair included iatrogenic injury etiology (HR 2.1, 95% CI 1.3-3.45, p = 0.009), and endoscopic repair (HR 6.1, 95% CI 3.1-11.1, p < 0.05,); protective factors included combined intra-abdominal/trans-vaginal repair (HR 0.51, 95% CI 0.3-0.8, p = 0.009), and surgeon years in practice (21 + years-HR 0.5, 95% CI 0.3-0.9, p = 0.005). Age adjusted annual rate of VVF repair (ranging from 0.8 to 1.58 per 100,000 women) and re-repair did not change over time. CONCLUSIONS: VVF repair and re-repair rates remained constant between 2005 and 2018. Iatrogenic injury and endoscopic repair predicted repair failure; combined intra-abdominal/trans-vaginal repair, and surgeon years in practice were protective. This suggests surgeon experience may protect against VVF repair failure.

Analysis of British Columbia practice patterns in the management of female stress urinary incontinence with emphasis on mesh use.

INTRODUCTION: Female stress urinary incontinence (SUI) is common and has a profound impact on quality of life. Suburethral slings are the most common treatment for SUI in this population. These can be placed with synthetic mesh or autologous fascia. Mesh-related complications after midurethral sling procedures are documented in the literature but the risk of complications and reoperation is lower than the use of transvaginal mesh for pelvic organ prolapse repair. In this study, we sought to evaluate local practice patterns of management of female SUI with specific emphasis on mesh use. METHODS: A survey created by an expert panel was disseminated to respective provincial societies. RESULTS: Sixty-eight percent of respondents offer midurethral slings in their practice but only 60.6% of these respondents would offer surgical removal of the sling if there were complications, such as mesh erosion or pain. A large portion (39.4%) of respondents are performing transobturator slings as compared to retropubic midurethral slings (36.3%) and only 8.5% have removed the leg component associated with the transobturator sling in their practice. Furthermore, compared to most respondents offering midurethral slings (64.8%), only a minority of surgeons offer alternatives: 23.9% of respondents offer periurethral bulking agent injections, 15.5% offer pubovaginal slings, and 12.7% offer retropubic urethropexies. CONCLUSIONS: Our study supports that surgeons should continue to review surgical risks and alternative treatment options as part of the surgical consent process. As such, surgeons should be able to offer a variety of surgical approaches to manage female SUI.

The Use of Metformin in Overactive Bladder: A Retrospective Nested Case-control, Population-based Analysis.

OBJECTIVE: To determine if metformin use is associated with a lower rate of overactive bladder (OAB) medication use. Metformin facilitates the proliferation and migration of stem cells, which have been shown to improve bladder overactivity in animal models. METHODS: We conducted a retrospective nested case-control cohort study using population-based health-care administrative databases. Our cohort included patients with diabetes mellitus type 2 (DM2) ≥69years. Cases received a prescription for an OAB medication, matched with up to 4 controls based on age, sex, and DM2 diagnosis date. Exposure was a new prescription for metformin prior to receiving an OAB medication. Adjusted odds ratios were estimated using conditional logistic regression. Sensitivity analysis was done to assess the relationship between cumulative days' supply of metformin and use of OAB medications. RESULTS: Within our cohort of 2,233,084 patients with DM2, there were 16,549 case subjects who received a prescription for an OAB medication, and 64,171 matched controls. We found a positive association between OAB medication use and metformin use (adjusted odds ratios=1.07, 95% CI=1.03-1.12). Summed days' supply of metformin was also associated with OAB medication use, except when summed metformin days was >2220. CONCLUSION: Older patients with DM2 exposed to metformin had a slightly higher rate of OAB medication use, until 2220+ days' metformin supply, whereafter no association was found. This suggests no protective role for metformin in the prevention of OAB in this patient population.

Treatment Patterns in Men Prescribed Benign Prostatic Obstruction or Overactive Bladder Medications in Canada: A Retrospective Population-based Study.

OBJECTIVE: To characterize first therapeutic change and healthcare resource utilization in older men initiating an overactive bladder (OAB) or benign prostatic obstruction (BPO) medication. METHODS: A retrospective cohort study using health administrative data from ICES in Ontario, Canada (from April 01, 2010 to December 31, 2018) was conducted in men aged ≥66 years with ≥1 OAB (ß3 agonist, antimuscarinic) or BPO (α-blocker, 5-α-reductase inhibitor) prescription and ≥1-year postindex data (index=first observed dispensation). EXCLUSIONS: prescriptions for these drugs ≤1 year preindex, a related procedure ≤5 years. Patients were grouped by condition based on index prescription. Treatment changes in relation to OAB and BPO were characterized by type. Costs and healthcare resource utilization pre- and post-index were compared. RESULTS: Age, geographic region, and income were similar between groups. The most common initial treatments were antimuscarinics (78.1%) in the OAB group and alpha-blockers (86.4%) in the BPO group. The OAB group was more likely to experience a therapeutic change and had a shorter time to first change in therapy (78 [30,231] vs 104 [30,350] days) and higher mean healthcare costs both pre- ($12,354 vs $11,497) and postindex ($14,423 vs $12,852). The most common first therapeutic change in both groups was discontinuing treatment (OAB: 75.6%; BPO: 69.9%). CONCLUSION: Men initiating OAB medications changed therapy sooner than those initiating BPO medications. Most discontinued first-line therapy without initiating further treatment, suggesting unmet need in this population.

Predicting Mirabegron Treatment Response in Patients with Overactive Bladder: A Post Hoc Analysis of Data from Clinical Trials.

BACKGROUND: Many patients discontinue overactive bladder (OAB) treatment because of unmet treatment expectations and/or tolerability issues. OBJECTIVE: To develop a model for predicting the individual treatment response to mirabegron using patient baseline characteristics. DESIGN, SETTING, AND PARTICIPANTS: This was a post hoc analysis of data from eight global phase 2/3, double-blind, randomized, placebo- or active-controlled trials of mirabegron in adult patients with OAB. INTERVENTION: Mirabegron 50 mg once-daily monotherapy for ≥12 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary efficacy outcomes were the change in the mean number of micturitions and the number of incontinence episodes/24 h after 12 wk of treatment. Secondary efficacy outcomes were the change in the mean number of urgency episodes/24 h and the change in Symptom Bother score after 12 wk of treatment. Baseline demographic characteristics, OAB-related characteristics, and intrinsic and extrinsic factor variables were used to create multivariable linear regression models to predict the primary and secondary outcomes. RESULTS AND LIMITATIONS: Data for 3627 patients were included. The predicted effect of mirabegron 50 mg was an average of 2.5 fewer micturition episodes/24 h (95% confidence interval -2.85 to -2.14) and 0.81 fewer incontinence episodes/24 h (95% confidence interval -1.15 to -0.46) from baseline to week 12. A higher number of urgency episodes was predictive of a larger reduction in micturition episodes; body mass index (BMI) ≥30 kg/m2, OAB symptoms for ≥12 mo, and incontinence at baseline were predictive of a smaller reduction. Mixed stress/urgency incontinence and more than five urgency episodes per day were predictive of greater reductions in incontinence episodes. Reductions in urgency episodes and Symptom Bother score were also predicted with mirabegron. Limitations include the exclusion of placebo groups from the analysis and the use of clinical trial rather than real-world data. CONCLUSIONS: Data from the predictive models provide new insights into the effects of modifiable factors (such as BMI) and nonmodifiable factors on treatment outcomes with mirabegron 50 mg. PATIENT SUMMARY: This study aimed to identify factors that could predict how patients with overactive bladder respond to mirabegron treatment to help doctors effectively treat this condition. Mirabegron treatment was associated with a lower number of urinations and occurrences of urinary incontinence per day. Factors associated with worse responses to the medication included being obese.

Routine pediatric vaccinations during the COVID-19 pandemic: A review of the global impact.

The coronavirus disease 2019 (COVID-19) pandemic has put standard, routine childhood vaccinations at risk worldwide. The disruption in vaccine coverage has resulted in a negative impact on the health of children, with some races, ethnicities, age groups, areas of settlement, and parts of the world affected more than others. This literature review studied and examined the impact of COVID-19 on infant, child, and adolescent vaccinations. Retrospectively, the analysis showed a decline, delays, or interruptions in the coverage of vaccines during the pan-demic and a decline in some countries' pre-pandemic and post-pandemic eras. Necessary attempts and efforts should be made for these delayed and missed vaccinations, as failure to do so could put children's health at risk. Thus, priority should be directed at instituting catch-up programs to support vaccine uptake and decrease the probability of acquiring vaccine-preventable diseases.

International Continence Society (ICS) report on the terminology for sexual health in men with lower urinary tract (LUT) and pelvic floor (PF) dysfunction.

INTRODUCTION: The terminology for sexual health in men with lower urinary tract (LUT) and pelvic floor (PF) dysfunction has not been defined and organized into a clinically based consensus terminology report. The aim of this terminology report is to provide a definitional document within this context that will assist clinical practice and research. METHODS: This report combines the input of the members of sexual health in men with LUT and PF Dysfunction working group of the International Continence Society (ICS), assisted at intervals by external referees. Appropriate core clinical categories and a sub-classification were developed to give coding to definitions. An extensive process of 18 rounds of internal and external review was involved to exhaustively examine each definition, with decision-making by collective opinion (consensus). The Committee retained evidence-based definitions, identified gaps, and updated or discarded outdated definitions. Expert opinions were used when evidence was insufficient or absent. RESULTS: A terminology report for sexual health in men with LUT and PF dysfunction, encompassing 198 (178 NEW) separate definitions, 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 speciality groups involved. Conservative and surgical managements are major additions and appropriate figures have been included to supplement and clarify the text. Emerging concepts and measurements, in use in the literature and offering further research potential, but requiring further validation, have been included as an appendix. Interval (5-10 years) review is anticipated to keep the document updated. CONCLUSION: A consensus-based terminology report for sexual health in men with LUT and PF dysfunction has been produced to aid clinical practice and research. The definitions that have been adopted are those that are most strongly supported by the literature at this time or are considered clinical principles or consensus of experts' opinions.

A Retrospective Look at Term Outcomes After Definitive Surgical Repair for Traumatic Pelvic Fracture Urethral Injuries - Does Initial Management Make a Difference?

OBJECTIVE: To compare the long-term outcomes of initial management of pelvic fracture urethral injury (PFUI) in a large cohort of trauma patients undergoing urethral reconstruction. MATERIALS AND METHODS: 119 patients underwent urethral reconstruction by a single surgeon for PFUI at our center between 1998-2018. We compared initial PFUI management - primary realignment vs suprapubic tube (SPT) insertion alone. Multivariable Cox proportional hazard analysis was used to assess the association between primary intervention and the risk of having a complication. RESULTS: PFUI was initially managed with primary realignment (57%) or SPT alone (43%). Ultimately, all patients underwent a primary perineal urethral anastomosis after a median of 7 months (IQR: 5-14). Overall, 27 patients (23%) had 1 or more long-term complications after a median 25 months (IQR:7-66), including urethral stricture, de novo erectile dysfunction, and urinary incontinence. On multivariable analysis, initial PFUI management did not predict for complications. CONCLUSION: No difference was found in long-term outcomes after urethral reconstruction when comparing initial PFUI management of primary realignment vs SPT insertion.

Taking Advantage of the Teachable Moment at Initial Diagnosis of Prostate Cancer-Results of a Pilot Randomized Controlled Trial of Supervised Exercise Training.

BACKGROUND: Increased physical activity (PA) levels are associated with improved prostate cancer (PCa) outcomes. Sustainable PA has been linked to improved health-related quality of life (QoL) in cancer patients. The time of diagnosis of PCa may offer a critical time point when patients might be more likely to consider lifestyle changes. This, in turn, may contribute to sustainable PA and its likely benefits. OBJECTIVE: The aims of this study were to determine if a structured PA intervention introduced at the time of diagnosis can (1) lead to sustainable PA and (2) help improve psychosocial and QoL outcomes as compared with usual PA. INTERVENTIONS/METHODS: This was a pilot randomized controlled trial enrolling patients with intermediate-risk PCa into either arm A (supervised 8- to 12-week physical exercise program; n = 10) or control arm B (usual PA; n = 10). Primary outcome was PA at 6 months. Secondary outcomes were QoL, psychological well-being, physical fitness, and functional outcomes postintervention. Change over time was compared using a nonparametric Wilcoxon test. RESULTS: Demographic variables were the same between arms. Comparing parameters at the start and 6 months post-radical prostatectomy, PA significantly improved in arm A (self-reported Godin score 24.7 vs 42.8 units, P < .01, objective number of chair stands [14-19, P < .01]), but not in arm B. There were no significant differences between arms in QoL and psychosocial outcomes. CONCLUSIONS: A preoperative supervised exercise training program increases long-term PA. IMPLICATIONS FOR PRACTICE: Future trials should evaluate PA sustainability beyond 6 months and if this leads to improved psychosocial and QoL outcomes.

Morbidity and predictors of delayed recognition of iatrogenic ureteric injuries.

INTRODUCTION: Although intraoperative iatrogenic ureteric injuries (IUI) are rare, significant consequences can occur if they are unrecognized at the time. The focus of our study is to characterize the associated morbidity and identify predictors of delayed recognition of IUI. METHODS: Sunnybrook Health Sciences Centre Research Ethics Board approved the study. Patients with a diagnosis of IUI between 2002 and 2020 were identified through an institutional electronic medical record system. Data pertaining to the demographic characteristics, diagnosis, and management of IUI, as well as overall outcomes were collected retrospectively. RESULTS: Of the 103 patients identified, 83% were female, 52% had previous abdominal surgery, and 18% had previous radiation. The median age was 67 (range 21-88) years. Twenty percent were not recognized at the time of surgery. Although delayed recognition was not a significant predictor for poor outcome after subsequent repair (i.e., hydronephrosis, ureteric stricture/obstruction), it was associated with substantial morbidity to the patient (i.e., additional procedures) and increased cost to the healthcare system (i.e., longer hospital stay, re-admission to hospital). Patients who underwent laparoscopic surgery had an 11 times more likely chance of having an unrecognized IUI as compared to those who underwent open surgery (odds ratio 11.515, p=0.0001). CONCLUSIONS: Delayed recognition of IUI may be associated with considerable adverse effects. In this retrospective case series, we identified laparoscopic surgery as a significant predictor for delayed recognition of IUI. This information underscores the need for future studies to facilitate intraoperative identification of ureteric injuries, particularly during laparoscopic procedures.

Standing open magnetic resonance imaging improves detection and staging of pelvic organ prolapse.

INTRODUCTION: The role of imaging in pelvic organ prolapse (POP) assessment is unclear. Open magnetic resonance imaging (MRI) systems have a configuration that allows for imaging women with POP in different positions. Herein, we use a 0.5 Tesla open MRI to obtain supine, seated, and standing images. We then compare these images to evaluate the impact of posture on detection and staging of POP. METHODS: Women presenting with symptoms of POP at a tertiary care university hospital were asked to participate in this prospective cohort study. Symptom scores, POP-Q staging and three-position MRI imaging of the pelvis data were collected. The pubococcygeal line (PCL) was used to quantify within-patient changes in pelvic organ position as defined by: no displacement, <1 cm inferior to the PCL, mild (1-3 cm), moderate (3.1-6 cm), and severe (>6 cm) in the axial and sagittal T2-weighted images. Statistical analysis was completed (T-test; p<0.05 significant). RESULTS: A total of 42 women, age range 40-78 years, participated. There was a significant difference in the mean values associated with anterior prolapse in the supine (0.7±1.8), seated (2.4±3.4), and upright (4.2±1.6) positions (p=0.015). There was a significant difference in the mean values associated with apical prolapse in the supine (0.5±1.5), seated (1.5±1.4), and upright (2.1±1.5) positions (p=0.036). CONCLUSIONS: Our findings suggest that POP is more readily detected and upstaged with standing MRI images as compared to supine and seated positions. The developed two-minute standing MRI protocol may enable clinicians to better assess the extent of POP.

Characterizing the cortical pathways underlying visual trigger induced urinary urgency incontinence by functional MRI.

AIMS: Visual triggers have long been recognized clinically to stimulate urgency urinary incontinence (UUI). Current pathophysiology recognizes the importance of cortical control over micturition but there is no standardized methodology for clinicians to study the impact of visual triggers. Our aim was to develop an imaging protocol able to characterize the brain's response to personalized visual triggers, providing a methodology for evaluation on connectivity within the brain in patients with visually triggered urinary urgency. METHODS: A magnetic resonance imaging (MRI) methodology specific for urologic use was developed. A 3T-Elition Scanner was first used to acquire static structural images. These images were then used to define approximately 200 brain regions of interest (ROI) using a validated brain atlas. Then, real-time functional MRI (fMRI) scans were conducted during natural bladder filling, where study subjects were shown randomized block sequences of visual stimuli comprised of both subject-specific trigger images and neutral images. The fMRI scan data were merged to identify key ROI underlying UUI. RESULTS: Dynamic fMRI scans were conducted in 10 subjects, 4 with trigger-induced UUI, 2 with trigger-induced urgency, and 4 with no urgency or leakage to visual triggers. No subjects with UUI history lost continence during imaging, but all four subjects reported sensations of urgency in response to their own subject-specific trigger images. The ROI identified were the periaqueductal gray, anterior cingulate gyrus, pons, and prefrontal cortex. We found increased activity in the prefrontal cortex and limbic system ROI in response to subject-specific visual triggers of UUI. CONCLUSIONS: This information provides proof of principle for further exploration of subject-specific trigger image evaluation using fMRI to explore causation in patients with UUI.

Hemi-Kock Continent Stoma With Augmentation Cystoplasty: Modifications and Outcomes.

OBJECTIVE: To evaluate the long-term outcomes and impact of surgical modifications on the need for secondary surgery of the Hemi-Kock continent catheterizable stoma, comprising a detubularized ileal segment with an attached stapled ileoileal intussusception of the catheterizable channel, in patients with complex lower urinary tract disorders. The technique may be used for augmentation in patients with reduced bladder capacity who require a continent catheterizable channel. Compared to the flap and ileocecal valve procedures, the hemi-Kock technique has not been widely adopted. MATERIALS AND METHODS: This is a retrospective case series including all patients who underwent a hemi-Kock catheterizable channel with cystoplasty from a single institution. Surgical technique and modifications in valve construction and tapering of the catheterizable limb are described. RESULTS: A total of 109 patients, with a median age of 38 years (range 18-72), underwent the procedure. At a mean of 10.4 years, 98 patients (90%) reported that they were managing with clean intermittent catheterization ± pads; 11 (10%) were failures. A total of 70 (64.2%) patients underwent secondary interventions with >60% performed endoscopically or under local anesthesia, mainly for bladder stones. Fourteen patients (12.8%) required valve revisions. However, the rate decreased from 18.2% (8/44) to 9.3% (6/65) following incorporation of the surgical modifications. CONCLUSION: We present the largest cohort to date of patients managed with a Hemi-Kock catheterizable channel and cystoplasty. Valve revision rate improved with surgical modifications. We demonstrate long-term durability and maintenance of stomal catheterization in the vast majority of patients.

Management of high-grade renal traumas with collecting system injuries.

INTRODUCTION: Approximately 50% of all high-grade renal traumas (HGRT, American Association for the Surgery of Trauma [AAST] grade 4/5) have associated collecting system injuries. Although most of these collecting system injuries will heal spontaneously, approximately 20-30% of these injuries are managed with ureteric stents. The objective of the study was to review the management of HGRT with collecting system injuries in a level 1 trauma center. METHODS: This was a single-center, retrospective cohort study of trauma patients with HGRT and collecting system injuries from 1998-2019. RESULTS: We identified 147 patients with HGRT. Of the 105 patients who had trauma computed tomography (CT) imaging within 24 hours, 46 were found to have collecting system injuries. Seven of these patients underwent intervention based on initial CT findings; the remaining 39 patients with urinary extravasation were conservatively managed. Of the 37 patients who underwent reimaging, 22 (59%) demonstrated a stable or resolving collection and 15 (41%) demonstrated continued urinary extravasation. Resolution of extravasation on subsequent imaging was observed in 10 of those patients, while five patients (14%) required intervention (four stents, one percutaneous drain) for symptoms/signs of urinary extravasation. CONCLUSIONS: In this study, most patients with HGRT and collecting system injuries did not require intervention unless the patient became symptomatic. The majority of collecting system injuries resolved with no intervention. This study underscores the need for future prospective trials to investigate the necessity of intervening in HGRT collecting system injuries and, secondarily, the need for routine re-imaging in these asymptomatic patients.