Evaluation of toxicities for intravesical drugs in phase 1 bladder cancer trials.

BACKGROUND: Improving clinical trial design is important for optimizing approval of safe and effective drugs. Phase 1 clinical trials seek to determine phase 2 doses by investigating predefined dose-limiting toxicities. Traditional definitions of dose-limiting toxicity may not be applicable to intravesical therapies for bladder cancer. This study compared the frequency of dose-limiting toxicities and serious adverse events in bladder cancer trials for intravesical therapies to other routes of administration. METHODS: Studies were abstracted from ClinicalTrials.gov and reconciled with a PubMed search. Primary and secondary end points were predefined before data abstraction, and the primary end point was subject-level dose-limiting toxicity rate. Fisher exact tests were performed with p < .05 designated as significant. RESULTS: Eighteen intravesical studies and 24 studies with other routes of administration (the per os/intravenous/intramuscular [PO/IV/IM] group) were identified. Dose-limiting toxicities were reported in 38.9% of intravesical studies, affecting 3.29% of subjects, compared with 30.0% of PO/IV/IM studies representing 4.19% of subjects (p = .52 for study-level and p = .60 for subject-level comparisons). Serious adverse events occurred in 53.9% of intravesical studies in 10.3% of subjects versus 91.0% of studies reporting serious adverse events affecting 41.4% of subjects in the PO/IV/IM group (p = .03 for subject-level and p < .0001 for study-level comparisons). CONCLUSIONS: There was no difference in subject-level dose-limiting toxicity rate between intravesical and PO/IV/IM bladder cancer trials. The serious adverse event rate was lower in the intravesical group. Heterogeneity of dose-limiting toxicity definition may affect interpretation of toxicity in phase 1 bladder cancer clinical trials studying different routes of administration. LAY SUMMARY: Bladder cancer is a common cancer type that may be treated with therapies that are instilled into the bladder and act locally, called intravesical therapies. This study used publicly available regulatory data from early phase clinical trials to determine whether measures of tolerability used in clinical trials are applicable to intravesical therapies for bladder cancer.

Large reduction in opioid prescribing by a multipronged behavioral intervention after major urologic surgery.

BACKGROUND: Surgeons play a pivotal role in combating the opioid crisis that currently grips the United States. Changing surgeon behavior is difficult, and the degree to which behavioral science can steer surgeons toward decreased opioid prescribing is unclear. METHODS: This was a single-institution, single-arm, pre- and postintervention study examining the prescribing of opioids by urologists for adult patients undergoing prostatectomy or nephrectomy. The primary outcome was the quantity of opioids prescribed in oral morphine equivalents (OMEs) after hospital discharge. The primary exposure was a multipronged behavioral intervention designed to decrease opioid prescribing. The intervention had 3 components: 1) formal education, 2) individual audit feedback, and 3) peer comparison performance feedback. There were 3 phases to the study: a pre-intervention phase, an intervention phase, and a washout phase. RESULTS: Three hundred eighty-two patients underwent prostatectomy, and 306 patients underwent nephrectomy. The median OMEs decreased from 195 to 19 in the prostatectomy patients and from 200 to 0 in the nephrectomy patients (P < .05 for both). The median OMEs prescribed did not increase during the washout phase. Prostatectomy patients discharged with opioids had higher levels of anxiety than patients discharged without opioids (P < .05). Otherwise, prostatectomy and nephrectomy patients discharged with and without opioids did not differ in their perception of postoperative pain management, activity levels, psychiatric symptoms, or somatic symptoms (P > .05 for all). CONCLUSIONS: Implementing a multipronged behavioral intervention significantly reduced opioid prescribing for patients undergoing prostatectomy or nephrectomy without compromising patient-reported outcomes.

Clinical Trials in Urology: Predictors of Successes and Failures.

PURPOSE: Clinical trials serve as a critical source of information to guide evidence-based practices in urology. Conversely, trials that are abandoned consume significant resources and results are underreported in the literature. MATERIALS AND METHODS: ClinicalTrials.gov was queried for urology trials from 2006 to 2016. Trials were screened by 2 screeners for applicability to urology and disputes were resolved by a third independent reviewer. Overall 1,340 trials met final inclusion criteria (722 successful trials, 618 failed trials). Univariable analysis used Fisher's exact, chi-squared and Wilcoxon rank sum tests. Trial characteristics, including AUA (American Urological Association) section, phase, subspecialty, intervention type, source of funding and randomization were examined for association with failure using multivariable logistic regression. RESULTS: Trial failure is associated with oncology subspecialty (adjusted odds ratio 2.25, 95% CI 1.60-3.18), infertility/andrology subspecialty (AOR 4.99, CI 1.60-17.61), device trials (AOR 1.64, CI 1.00-2.70) and combination funding by industry/government/grants (AOR 3.13, CI 2.21-4.48). Clinical trials in AUA sections were less likely to fail than international and multisectional trials. Among trials that failed, poor accrual was the primary reason for trial failure, comprising 41% of all failures. Other reasons for failure include inadequate budget (9%), sponsor cancellation (7%), poor interim results (7%) and toxicity (3%). CONCLUSIONS: Despite their significance, many urological trials fail prematurely due to poor accrual. Complex features inherent to oncology, andrology/infertility, devices and multisectional trials pose significant barriers to success.

Discrepancies in Self-Reported and Actual Conflicts of Interest for Robotic Pediatric Urological Surgery.

PURPOSE: Transparency of conflicts of interest is essential when assessing publications that address the benefits of robotic surgery over traditional laparoscopic and open operations. We assessed discrepancies between self-reported and actual conflicts of interest as well as whether conflicts of interest are associated with favorable endorsement of robotic surgery. MATERIALS AND METHODS: We searched the Embase® and MEDLINE® databases for articles on robotic surgery within pediatric urology. We included English language articles published since 2013, when data in the Open Payments program (Centers for Medicare and Medicaid Services, Baltimore, Maryland) became available. For all United States based authors Open Payments was used to identify the total amount of financial payment received from Intuitive Surgical®. Chi-square test was used to assess the association between conflicts of interest and favorable endorsement of robotic surgery. RESULTS: A total of 191 articles were initially identified. After exclusion criteria were applied 107 articles remained (267 distinct authors). Of the articles 86 (80.4%) had at least 1 author with a history of payment from Intuitive Surgical, with 79 (91.9%) having at least 1 author who did not declare a conflict of interest despite history of payment. A total of 44 authors (16.5%) had a history of payment from Intuitive Surgical, with an average payment of $3,594.15. Articles with a first and/or last author with a history of payment were more likely to contain a favorable endorsement of robotic surgery compared to articles without a history of payment (85.1% vs 63.6%, p = 0.0124). CONCLUSIONS: Nondisclosure of conflict of interest with Intuitive Surgical is extremely common within pediatric urology. Steps to ensure accurate reporting of conflicts of interest are essential. There appears to be an association between a history of payment and favorable endorsement of robotic surgery.

Risk of Radiation from Computerized Tomography Urography in the Evaluation of Asymptomatic Microscopic Hematuria.

PURPOSE: The AUA (American Urological Association) guidelines for asymptomatic microscopic hematuria recommend that patients undergo computerized tomography urography, which is associated with high doses of ionizing radiation. To our knowledge the associated risk of secondary malignancy and mortality remains unknown. We modeled the risk of malignancy and associated mortality due to ionizing radiation from computerized tomography urography relative to the additional diagnostic benefit offered over renal ultrasound. MATERIALS AND METHODS: We performed a PubMed® based literature search to identify model inputs. We obtained estimates of age and gender specific radiation induced secondary malignancy and mortality rates from the BEIR (Biologic Effects of Ionizing Radiation) VII Phase 2 report with dose extrapolation using the linear no threshold model. RESULTS: Patients with asymptomatic microscopic hematuria had a 0.053% and 0.48% prevalence of upper tract urothelial carcinoma and renal cell carcinoma, respectively. Ultrasound had 77% sensitivity for upper tract urothelial carcinoma and 82% sensitivity for renal cell carcinoma. The effective radiation dose of computerized tomography urography was 31.7 mSv. Based on these inputs a population of 100,000 patients with asymptomatic microscopic hematuria would include 53.1 and 478 patients with upper tract urothelial carcinoma and renal cell carcinoma, respectively. On ultrasound alone 98.2 cases of upper urinary tract malignancy would be missed. An additional 149 cases of secondary malignancy would be caused by computerized tomography urography associated radiation with 101 fatalities. A total of 1,018.3 computerized tomography urography studies would need to be performed to detect an additional case of upper tract malignancy. CONCLUSIONS: Based on current risk models computerized tomography urography for asymptomatic microscopic hematuria may be associated with a small but significant risk of secondary malignancy relative to the additional diagnostic benefit offered.

The lack of a relationship between physician payments from drug manufacturers and Medicare claims for abiraterone and enzalutamide.

BACKGROUND: Interactions between industry and prescribers have raised concerns regarding conflicts of interest. To the best of the authors' knowledge, quantitative data measuring these interactions have been limited until recently. In the current study, the authors sought to determine whether an association exists between industry payments and prescriber behavior with regard to abiraterone and enzalutamide. METHODS: Two Centers for Medicare and Medicaid Services databases were combined to analyze oncologists and urologists who received industry payments and/or prescribed abiraterone and enzalutamide. Correlation analysis was constructed on prescription count and industry payments. Multivariable median regression examined predictors of change in prescription count per dollar of industry payment. Stratifying prescribers by quantile evaluated threshold effects on prescribers. RESULTS: The number of prescriptions was similar between prescribers who did and those who did not receive industry payment for both drugs. The median industry payment amount to prescribers differed between prescribers and nonprescribers for abiraterone ($72 vs $56) and enzalutamide ($59 vs $31). Although no statistical association was found to exist between industry payment amount and prescription count for abiraterone prescribers, an association was found to exist for enzalutamide prescribers (rho = 0.31). A small change was found with regard to prescription count per dollar of industry payment for abiraterone (0.0007 prescriptions) and enzalutamide (0.0006 prescriptions). The amount of industry payment needed to predict one additional prescription was found to be lower in the fourth and fifth quantiles compared with the first through third quantiles. CONCLUSIONS: No difference in prescription count was found to exist between prescribers who received industry payments and those who did not. A positive correlation was noted between industry payments and prescription count for enzalutamide. Ease of adoption may affect differences between the 2 drugs. Cancer 2017;123:4356-62. © 2017 American Cancer Society.

Comparative effectiveness in urology: a state of the art review utilizing a systematic approach.

PURPOSE OF REVIEW: Comparative effectiveness research plays a vital role in healthcare delivery by guiding evidence-based practices. We performed a state-of-the-art review of comparative effectiveness research in the urology literature for 2016, utilizing a systematic approach. Seven high-impact papers are reviewed in detail. RECENT FINDINGS: Across the breadth of urology, there were several important studies in comparative effectiveness research, of which we will highlight two randomized controlled trials and five observational trials: radiotherapy, prostatectomy, and active monitoring have equivalent mortality outcomes in patients with localized prostate cancer; the ideal modality of patient education is yet to be determined, and written education has minimal effect on patient perception of prostate specific antigen screening; robotic prostatectomy is associated with higher perioperative complication rates on a population basis; racial disparities exist in incontinence rates after treatment for localized prostate cancer, but not in irritative, bowel, or sexual function; androgen deprivation therapy is associated with higher fracture, peripheral artery disease, and cardiac-related complications than bilateral orchiectomy; robotic and open cystectomy offer comparable cancer-specific mortality and perioperative outcomes; and bonuses for low-cost hospitals can inadvertently reward low-quality hospitals. SUMMARY: There have been major advancements in comparative effectiveness research in urology in 2016.

Lumbosacral spinal segmental contributions to tibial and pudendal neuromodulation of bladder overactivity in cats.

AIMS: To determine the spinal segmental afferent contributions to tibial and pudendal inhibition of bladder overactivity. METHODS: Intravesical infusion of 0.5% acetic acid was used to irritate the bladder and induce bladder overactivity in anesthetized cats. Tibial or pudendal nerve stimulation was used to suppress the bladder overactivity and increase bladder capacity during cystometry. L5-S3 dorsal roots ipsilateral to the stimulation were exposed by a laminectomy and transected sequentially during the experiments to determine the role of individual dorsal roots in tibial or pudendal neuromodulation. RESULTS: Transection of L5 dorsal root had no effect. Transection of L6 dorsal root in four cats produced an average 18% reduction in tibial inhibition, which is not a significant change when averaged in the group of 10 cats. Transection of L7 dorsal root completely removed the tibial inhibition without changing reflex bladder activity or pudendal inhibition. Transection of S1 dorsal root reduced the pudendal inhibition, after which transection of S2 dorsal root completely removed the pudendal inhibition. Transection of S3 dorsal root had no effect. The control bladder capacity was increased only by transection of S2 dorsal root. CONCLUSIONS: This study in cats revealed that tibial and pudendal neuromodulation of reflex bladder overactivity depends on activation of primary afferent pathways that project into different spinal segments. This difference may be related to the recent observation in cats that the two types of neuromodulation have different mechanisms of action.

Sacral neuromodulation of nociceptive bladder overactivity in cats.

AIMS: To investigate the effects of electrical stimulation of sacral dorsal/ventral roots on irritation-induced bladder overactivity, reveal possible different mechanisms under nociceptive bladder conditions, and establish a large animal model of sacral neuromodulation. METHODS: Intravesical infusion of 0.5% acetic acid (AA) was used to irritate the bladder and induce bladder overactivity in cats under α-chloralose anesthesia. Electrical stimulation (5, 15, or 30 Hz) was applied to individual S1-S3 dorsal or ventral roots at or below motor threshold intensity. Repeated cystometrograms (CMGs) were performed with/without the stimulation to determine the inhibition of bladder overactivity. RESULTS: AA irritation induced bladder overactivity and significantly (P < 0.05) reduced the bladder capacity to 62.6 ± 11.7% of control capacity measured during saline CMGs. At threshold intensity for inducing reflex twitching of the anal sphincter or toe, S1/S2 dorsal root stimulation at 5 Hz but not at 15 or 30 Hz inhibited bladder overactivity and significantly (P < 0.05) increased bladder capacity to 187.3 ± 41.6% and 155.5 ± 9.7% respectively, of AA control capacity. Stimulation of S3 dorsal root or S1-S3 ventral roots was not effective. Repeated stimulation of S1-S3 dorsal root did not induced a post-stimulation inhibition. CONCLUSIONS: This study established a cat model of sacral neuromodualation of nociceptive bladder overactivity. The results revealed that the mechanisms underlying sacral neuromodulation are different for nociceptive and non-nociceptive bladder activity.

Neurotransmitter Mechanisms Underlying Sacral Neuromodulation of Bladder Overactivity in Cats.

OBJECTIVE: To determine the role of opioid, ß-adrenergic, and metabotropic glutamate 5 receptors in sacral neuromodulation of bladder overactivity. MATERIAL AND METHODS: In α-chloralose anesthetized cats, intravesical infusion of 0.5% acetic acid (AA) irritated the bladder and induced bladder overactivity. Electric stimulation (5 Hz, 0.2 ms, 0.16-0.7V) of S1 or S2 sacral dorsal roots inhibited the bladder overactivity. Naloxone, propranolol, or MTEP were given intravenously (i.v.) to determine different neurotransmitter mechanisms. RESULTS: AA significantly (p < 0.05) reduced bladder capacity to 7.7 ± 3.3 mL from 12.0 ± 5.0 mL measured during saline infusion. S1 or S2 stimulation at motor threshold intensity significantly (p < 0.05) increased bladder capacity to 179.4 ± 20.0% or 219.1 ± 23.0% of AA control, respectively. Naloxone (1 mg/kg) significantly (p < 0.001) reduced the control capacity to 38.3 ± 7.3% and the bladder capacity measured during S1 stimulation to 106.2 ± 20.8% of AA control, but did not significantly change the bladder capacity measured during S2 stimulation. Propranolol (3 mg/kg) significantly (p < 0.01) reduced bladder capacity from 251.8 ± 32.2% to 210.9 ± 33.3% during S2 stimulation, but had no effect during S1 stimulation. A similar propranolol effect also was observed in naloxone-pretreated cats. In propranolol-pretreated cats during S1 or S2 stimulation, MTEP (3 mg/kg) significantly (p < 0.05) reduced bladder capacity and naloxone (1 mg/kg) following MTEP treatment further reduced bladder capacity. However, a significant inhibition could still be induced by S1 or S2 stimulation after all three drugs were administered. CONCLUSIONS: Neurotransmitter mechanisms in addition to those activating opioid, ß-adrenergic, and metabotropic glutamate 5 receptors also are involved in sacral neuromodulation.

Contribution of GABAA, Glycine, and Opioid Receptors to Sacral Neuromodulation of Bladder Overactivity in Cats.

In α-chloralose-anesthetized cats, we examined the role of GABAA, glycine, and opioid receptors in sacral neuromodulation-induced inhibition of bladder overactivity elicited by intravesical infusion of 0.5% acetic acid (AA). AA irritation significantly (P < 0.01) reduced bladder capacity to 59.5 ± 4.8% of saline control. S1 or S2 dorsal root stimulation at threshold intensity for inducing reflex twitching of the anal sphincter or toe significantly (P < 0.01) increased bladder capacity to 105.3 ± 9.0% and 134.8 ± 8.9% of saline control, respectively. Picrotoxin, a GABAA receptor antagonist administered i.v., blocked S1 inhibition at 0.3 mg/kg and blocked S2 inhibition at 1.0 mg/kg. Picrotoxin (0.4 mg, i.t.) did not alter the inhibition induced during S1 or S2 stimulation, but unmasked a significant (P < 0.05) poststimulation inhibition that persisted after termination of stimulation. Naloxone, an opioid receptor antagonist (0.3 mg, i.t.), significantly (P < 0.05) reduced prestimulation bladder capacity and removed the poststimulation inhibition. Strychnine, a glycine receptor antagonist (0.03-0.3 mg/kg, i.v.), significantly (P < 0.05) increased prestimulation bladder capacity but did not reduce sacral S1 or S2 inhibition. After strychnine (0.3 mg/kg, i.v.), picrotoxin (0.3 mg/kg, i.v.) further (P < 0.05) increased prestimulation bladder capacity and completely blocked both S1 and S2 inhibition. These results indicate that supraspinal GABAA receptors play an important role in sacral neuromodulation of bladder overactivity, whereas glycine receptors only play a minor role to facilitate the GABAA inhibitory mechanism. The poststimulation inhibition unmasked by blocking spinal GABAA receptors was mediated by an opioid mechanism.

24-Hour Urinary Parameters in Overweight and Obese Children with Urolithiasis.

PURPOSE: The increasing incidence of pediatric nephrolithiasis is a growing concern and its association with obesity continues to be an area of debate. We present data on urine chemistries of overweight/obese children compared to those with a normal body mass index and history of urolithiasis treated at a single institution in the United States, and assess risk factors. MATERIALS AND METHODS: We retrospectively identified 110 stone forming patients who underwent 24-hour urine collection and stratified them according to the Centers for Disease Control and Prevention definitions of overweight/obese (body mass index above 85th/95th percentile). Absolute urine collection quantities were compared between groups. Stone risk factors were analyzed according to Litholink® specified reference ranges. RESULTS: Compared to patients with low or normal body mass index, overweight and obese patients had lower body surface area adjusted citrate (242 mg/1.73 m(2) vs 315 mg/1.73 m(2), p = 0.03), lower urine phosphate (12 mg/kg vs 14 mg/kg, p = 0.04), lower urine magnesium (1.2 mg/kg vs 1.6 mg/kg, p = 0.01) and increased incidence of hypercalciuria (31% vs 11%, p = 0.02). Differences in urine citrate, phosphate and magnesium were not apparent when analyzing stone risk factors. There was no association between body mass index and urine pH. CONCLUSIONS: Overweight and obese stone forming children have decreased levels of urine citrate, phosphate and magnesium compared to patients with normal body mass index. The incidence of hypercalciuria is increased in overweight/obese patients. In contrast to findings in adults, there is no association between urine pH and body mass index.

Renal biopsy for medical renal disease: indications and contraindications.

INTRODUCTION: Percutaneous renal biopsy (PRB) is a safe and effective modality for sampling kidney tissue. In limited circumstances, alternative methods for kidney biopsy may be indicated. Historical contraindications for PRB such as bleeding diathesis, morbid obesity and solitary kidney have been called into question in the literature. We present a review of the literature on PRB and the risks and benefits associated with alternatives. MATERIALS AND METHODS: A review of the literature was performed through MEDLINE and PubMed. A total of 726 articles exist under the query, "percutaneous renal biopsy." Large series describing indications, contraindications, procedural methods, and complications were extracted. To further investigate the risks of percutaneous renal biopsy on solitary kidneys, the literature on percutaneous nephrolithotomy (PCNL) and biopsy of transplant kidneys were queried. Summaries of the data were compiled and synthesized in the body of the text. RESULTS: Percutaneous renal biopsy is safe and effective in the majority of kidney units for the evaluation of medical renal disease. Rates of bleeding range from 0.3%-7.4%, and nephrectomy rates are exceedingly low (0.1%-0.5%). Bleeding rates in open and laparoscopic approaches are comparable and range from 0%-7.0%, with major complications ranging from 0%-6.1%. CONCLUSIONS: The successes of percutaneous methods have called into question traditional contraindications such as solitary kidney, bleeding diathesis, and morbid obesity. In limited cases, alternative methods may be appropriate. We present a review of the literature for the various approaches and their associated complication rates.

Enhancing the Management of Benign Prostatic Hyperplasia: The Role of Electronic Health Record Patient Portal Distribution of the International Prostate Symptom Score.

INTRODUCTION: Recent AUA guidelines for the management of benign prostatic hyperplasia (BPH) recommend routine collection of the International Prostate Symptom Score (IPSS) data, but routine collection can be challenging to fully implement. We investigated the impact of distributing the IPSS by electronic patient portal (EPP) on IPSS completion and its impact on BPH management. METHODS: We performed a retrospective, longitudinal study of men undergoing a new patient visit (NPV) for BPH at our academic medical center. From September 2019 to November 2022, we identified patients undergoing an NPV for BPH. Prior to January 2021, the IPSS was collected in person at NPVs via paper forms; afterwards, the IPSS was distributed before the NPV using the EPP. Our primary outcome was IPSS completion; secondary outcomes were new BPH medications and BPH surgery ordered within 6 months. RESULTS: We identified 485 patients who underwent an NPV for BPH. EPP implementation significantly increased IPSS questionnaire completion (36.5% vs 56.9%, P < .0001). Following EPP implementation, we found that new BPH medications ordered at time of NPV decreased (10.4% vs 4.7%, P = .02). Although BPH surgery ordered within 6 months was similar, patients following EPP implementation had shorter time to BPH surgery compared to prior. CONCLUSIONS: Our study revealed that EPP distribution of the IPSS improves IPSS collection compliance, aligning our practice closer with AUA guidelines. Routine collection of the IPSS may impact clinical practice through the detection of more severe BPH, which reduces medical BPH management and time to definitive BPH therapy. Further work is needed to confirm findings.

The Changing Roles of Urologists, Radiologists, and Advanced Practice Providers in Uroradiology Procedures.

INTRODUCTION: Urology has seen shifts in the management of many urologic conditions with the advent of noninvasive procedures that rely on multidisciplinary radiological modalities. This study seeks to analyze changes in urologists, radiologists, and advanced practice providers (APPs) performing uroradiology procedures over time. METHODS: The Centers for Medicare & Medicaid Services Physician/Procedure Summary data from 2010 to 2021 were utilized to examine uroradiology Current Procedural Terminology codes billed by urologists, radiologists, and APPs. Percent of total reimbursement and higher volume procedure count (after excluding providers with <11 procedures by per year) by each provider field was calculated and analyzed for changes in distribution from 2010 to 2021. RESULTS: There were significant changes in all procedures when examining procedure reimbursement distribution in 2010 to 2021 (P < .001). During the period, urology saw decreases in reimbursement proportion as large as 28.7% for kidney cryoablation and increases as large as 14.2% for nephrostomy tube removals. Radiology saw the largest decreases in reimbursement proportion with an 18.9% decrease for nephrostograms, while the largest increase was 23.6% for suprapubic tube placements. APPs saw the largest increase in suprapubic tube changes reimbursement proportion, which rose 14.2% from 2010 to 2021. There were significant changes in proportion in all procedures, except for antegrade stent, renal cryoablation, renal biopsy, and renal thermoablation. CONCLUSIONS: Uroradiology procedures have seen shifts in the distribution of which provider type performs each procedure. Most large changes in reimbursement and procedure proportion were shifted between urology and radiology, with APPs seeing smaller changes.

Use of Placebo in Urologic Oncology Randomized Controlled Trials.

INTRODUCTION: Use of placebo in oncology randomized controlled trials (RCT) is ethically controversial. Placebo may introduce bias, as toxicity profiles of treatment arms can inadvertently unblind subjects and investigators. We investigated the use of placebo in urologic oncology RCTs, hypothesizing that most placebo-controlled trials are effectively unblinded, either explicitly with open-label design or implicitly due to large differences in adverse events (AE) or oncologic outcomes. METHODS: Urologic oncology RCTs utilizing placebo were identified via ClinicalTrials.gov. Interventional prostate, bladder/urothelial, and renal cancer trials from 2014 to 2024 were included. Subject incompletion, all-cause mortality, AE rates, and serious AE (SAE) rates were identified and compared between placebo and active arms using χ2 and Fisher's exact tests. RESULTS: Sixty studies met inclusion criteria and included 66 placebo arms with 12,918 subjects and 81 active arms with 16,098 subjects. There was no significant difference in incompletion rates between placebo and active arms. Subjects enrolled in active arms reported statistically significant higher SAE and AE rates compared to those in placebo arms across the majority of physiological domains, including 18/24 domains for SAEs and 13/24 for AEs. This relationship persisted in sensitivity analyses where unblinded trials were excluded. CONCLUSIONS: In urologic oncology placebo-controlled RCTs, active arms are associated with significantly higher rates of AEs and SAEs compared with placebo arms. These findings indicate a strong possibility that true blinding is not possible in oncology RCTs, even with optimal study design, and serve to better inform future clinical trial design and implementation challenges in employing placebo control.

Changes in Billing and Reimbursement for Urology Office Visits Before and After Medicare Payment Reforms.

INTRODUCTION: The impact of Medicare reimbursement changes on urology office visit reimbursements has not been fully examined. This study aims to analyze the impact of urology office visit Medicare reimbursements from 2010 to 2021, with a focus on 2021 Medicare payment reforms. METHODS: The Centers for Medicare and Medicaid Services Physician/Procedure Summary data from 2010-2021 were utilized to examine office visit CPT (Current Procedural Terminology) new patient visit codes 99201-99205 and established patient visit codes 99211-99215 by urologists. Mean office visit reimbursements (2021 USD), CPT specific reimbursements, and proportion of level of service were compared. RESULTS: The 2021 mean visit reimbursement was $110.95, up from $99.42 in 2020 and $94.44 in 2010 (both P < .001). From 2010 to 2020, all CPT codes, except for 99211, had a decrease in mean reimbursement. From 2020 to 2021, there was an increase in mean reimbursement for CPT codes 99205, 99212-99215 and decreases in 99202, 99204 and 99211 (P < .001). New and established patient urology office visits had significant migration of billing codes from 2010 to 2021 (P < .001). New patient visits were most commonly as 99204, which increased from 47% in 2010 to 65% in 2021 (P < .001). The most commonly billed established patient urology visit was 99213 until 2021 when 99214 became the most common at 46% (P < .001). CONCLUSIONS: Urologists have seen increases in mean reimbursements for office visits both before and after the 2021 Medicare payment reform. Contributing factors consist of increased established patient visit reimbursements despite decreased new patient visit reimbursements, and changes in level of CPT code billings.

Surfacing safety hazards using standardized operating room briefings and debriefings at a large regional medical center.

BACKGROUND: Briefings and debriefings, previously shown to be a practical and feasible strategy to improve interdisciplinary communication and teamwork in the operating room (OR), was then assessed as a strategy to prospectively surface clinical and operational defects in surgical care--and thereby prevent patient harm. METHODS: A one-page, double-sided briefing and debriefing tool was used by surgical teams during cases at the William Beaumont Hospital Royal Oak (Royal Oak, Michigan) campus to surface clinical and operational defects during the study period (October 2006-May 2010). Defects were coded into six categories (with each category stratified by briefing or debriefing period) during the first six months, and refinement of coding resulted in expansion to 16 defect categories and no further stratification. A provider survey was used in January 2008 to interview a sample of 40 caregivers regarding the perceived effectiveness of the tool in surfacing defects. FINDINGS: The teams identified a total of 6,202 defects--an average of 141 defects per month--during the entire study period. Of 2,760 defects identified during the six-defect coding period, 1,265 (46%) surfaced during briefings, and the remaining 1,495 (54%) during debriefings. Equipment (48%) and communication (31%) issues were most prominent. Of 3,442 defects identified during the 16-defect coding period, the most common were Central Processing Department (CPD) instrumentation (22%) and Communication/Safety (15%). Overall, 70 (87%) of the 80 responses were in agreement that briefings were effective for surfacing defects, as were 59 (76%) of the 78 responses for debriefings. CONCLUSIONS: Briefings and debriefings were a practical and effective strategy to surface potential surgical defects in the operating rooms of a large medical center.