Statin medications and the risk of gynecomastia.

OBJECTIVE: Case reports have suggested an increased risk of gynecomastia with HMG-CoA reductase inhibitors (ie, statins). A recent meta-analysis also found that statins decrease circulating testosterone levels in men. We investigated whether statin use was associated with an increased risk of gynecomastia. DESIGN: Case-control study. PATIENTS: A cohort of patients from a random sample of 9 053 240 US subjects from the PharMetrics Plus™ health claims database from 2006 to 2016 was created. MEASUREMENTS: New cases of gynecomastia requiring at least two ICD-9 codes were identified from the cohort and matched to 10 controls by follow-up time and age using density-based sampling. Rate ratios (RRs) for users of statins were computed using conditional logistic regression adjusting for alcoholic cirrhosis, hyperthyroidism, testicular cancer, Klinefelter syndrome, obesity, hypogonadism, hyperprolactinemia and use of spironolactone, ketoconazole, H2 receptor antagonists (H2 blockers), risperidone, testosterone and androgen deprivation therapy. RESULTS: Our cohort included 6147 cases of gynecomastia and 61 470 corresponding matched controls. The adjusted RR for current, recent and past statin use with respect to gynecomastia was 1.19 (1.04-1.36), 1.38 (1.15-1.65) and 1.20 (1.03-1.40), respectively. CONCLUSIONS: Statin use is associated with an increased risk of developing gynecomastia. Clinicians should be cognizant of this effect and educate patients accordingly.

The Cardiovascular Safety of Dutasteride.

PURPOSE: Randomized controlled trials suggest an increased risk of heart failure with dutasteride, which inhibits both the type 1 and type 2 isoforms of 5α-reductase. In contrast, no such association has been suggested for finasteride, which selectively inhibits the type 2 isoform. We investigated the risk of cardiovascular events among patients receiving dutasteride relative to finasteride. MATERIALS AND METHODS: We performed a population based cohort study of Ontario men 66 years old or older who commenced treatment with dutasteride or finasteride between October 1, 2005 and March 31, 2015. For each individual treated with dutasteride, we identified 1 treated with finasteride, matching on a propensity score and calendar quarter of treatment initiation to account for temporal changes in prescribing. The primary outcome was hospitalization for heart failure. Secondary analyses were done to examine acute myocardial infarction and stroke. Cox proportional hazards regression was used to adjust for differences between groups. RESULTS: We studied 36,311 men who commenced dutasteride and 36,311 treated with finasteride. In the primary analysis, we found no difference in the risk of heart failure among patients receiving dutasteride relative to those receiving finasteride (adjusted HR 0.98, 95% CI 0.88-1.08). Similarly, we found no difference in the risk of acute myocardial infarction (HR 0.94, 95% CI 0.82-1.08) or stroke (HR 1.03, 95% CI 0.88-1.20). CONCLUSIONS: In this population based cohort study of more than 72,000 older men, dutasteride was not associated with an increased risk of cardiovascular events relative to finasteride.

Erectile Dysfunction Medications and Treatment for Cardiometabolic Risk Factors: A Pharmacoepidemiologic Study.

BACKGROUND: Erectile dysfunction (ED) can be a sentinel marker for future cardiovascular disease and has been described as providing a "window of curability" for men to receive targeted cardiovascular risk assessment. AIM: To determine whether the prescription of phosphodiesterase type 5 inhibitors (PDE5is) for ED leads to the detection and treatment of previously undiagnosed cardiometabolic risk factors. METHODS: We performed a retrospective population-based cohort study of residents of British Columbia, Canada using linked health care databases from 2004 to 2011. An individual-level time series analysis with switching replications was used to determine changes in drug use for hypertension, hypercholesterolemia, and diabetes in men 40 to 59 years old. The observation window for each patient was 720 days before and 360 days after the index date. OUTCOMES: The primary outcome was changes in prescriptions for antihypertensive, statin, and oral antidiabetic drugs, with secondary outcomes being laboratory tests for plasma cholesterol and glucose. RESULTS: 5,858 men 40 to 59 years old newly prescribed a PDE5i were included in the analysis. We found a sudden increase in prescriptions for antihypertensive drugs (40 per 1,000; P < .001), statins (10 per 1,000; P = .001), and antidiabetic drugs (17 per 1,000; P = .002) in the 90 days after a new prescription for a PDE5i. For hypercholesterolemia and diabetes, most of this change was observed in men with relevant screening tests performed in the 30 days after their PDE5i prescription. Only 15% and 17% of men who did not have a screening test for cholesterol and glucose, respectively, in the year before their PDE5i prescription went on to have one in the subsequent 30 days. CLINICAL IMPLICATIONS: The paucity of screening tests observed in our study after PDE5i prescriptions suggests that physicians should be educated on the recommended screening guidelines for men newly diagnosed with ED. STRENGTHS AND LIMITATIONS: The number of men who were ordered a laboratory test or written a prescription but chose not to complete or fill it, respectively, is unknown. CONCLUSION: Treatment for ED with PDE5is can be a trigger or "gateway drug" for the early detection and treatment of cardiometabolic risk factors provided physicians perform the requisite screening investigations. Skeldon SC, Cheng L, Morgan SG, et al. Erectile Dysfunction Medications and Treatment for Cardiometabolic Risk Factors: A Pharmacoepidemiologic Study. J Sex Med 2017;14:1597-1605.

The effect of competing direct-to-consumer advertising campaigns on the use of drugs for benign prostatic hyperplasia: time series analysis.

BACKGROUND: Direct-to-consumer advertising (DTCA) remains a controversial issue, with concerns that it leads to unnecessary and inappropriate prescribing. Whether DTCA shifts prescribing from first-line (guideline-recommended) therapy to second-line drugs has not been studied. OBJECTIVE: The purpose of this study was to determine the impact of sequential DTCA campaigns for two drugs used to treat benign prostatic hyperplasia (BPH): one newer agent, dutasteride (Avodart(®)), and one older first-line agent, tamsulosin (Flomax(®)). DESIGN: Interrupted time series analysis was used to assess the impact of each DTCA campaign using data on consumer "response" from Google Trends and dispensed prescriptions from IMS Health. PARTICIPANTS: We analyzed data for the United States from January 2003 to December 2007. INTERVENTION: DTCA for dutasteride and tamsulosin commenced on July, 2005 and April, 2006, respectively. MAIN MEASURES: Monthly Internet search volume (scaled from 0 to 100) for the advertised trade name of each drug and monthly U.S. prescription rates per 1,000 population were analyzed. KEY RESULTS: The dutasteride campaign was associated with an increase in Internet searches for both "Avodart" (level change +31.3 %, 95 % CI: 27.2-35.4) and "Flomax" (level change +8.3 %, 95 % CI: 0.9-15.7), whereas the tamsulosin campaign was associated with increased "Flomax" searches (level change +25.3 %, 95 % CI: 18.7-31.8). The dutasteride campaign was associated with an increase in the prescription of dutasteride (trend = 0.45/month, 95 % CI: 0.33-0.56), but a larger impact was observed with tamsulosin prescriptions (trend = 0.76/month, 95 % CI: 0.02-1.50). Similarly, the tamsulosin campaign was associated with an immediate fourfold increase in the prescribing of tamsulosin (level change +5.76 units, 95 % CI: 1.79-9.72) compared to dutasteride (level change +1.47 units, 95 % CI: 0.79-2.14). CONCLUSIONS: DTCA was associated with the utilization of drugs to treat symptomatic BPH. However, both campaigns were associated with greater increases in the use of the guideline-recommended first-line agent. DTCA campaigns may increase the overall levels of guideline-recommended treatments to a greater extent than the specific advertised agents.

Erectile Dysfunction and Undiagnosed Diabetes, Hypertension, and Hypercholesterolemia.

PURPOSE: We investigated whether erectile dysfunction, a marker for future cardiovascular disease, is associated with undiagnosed cardiometabolic risk factors among US men. Identifying the presence of these risk factors could lead to earlier initiation of treatment for primary prevention of cardiovascular disease. METHODS: We analyzed cross-sectional data from men aged 20 years and older who participated in the National Health and Nutrition Examination Survey during 2001-2004. Erectile dysfunction was determined by a single, validated survey question. We used logistic regression analyses to investigate the relationship between erectile dysfunction and undiagnosed hypertension, hypercholesterolemia, and diabetes. RESULTS: After multivariate adjustment, men with erectile dysfunction had more than double the odds of having undiagnosed diabetes (odds ratio = 2.20; 95% CI, 1.10-4.37), whereas no association was seen for undiagnosed hypertension or undiagnosed hypercholesterolemia. For the average man aged 40 to 59 years, the predicted probability of having undiagnosed diabetes increased from 1 in 50 in the absence of erectile dysfunction to 1 in 10 in the presence of erectile dysfunction. CONCLUSIONS: Our results underscore the importance of erectile dysfunction as a marker of undiagnosed diabetes. Erectile dysfunction should be a trigger to initiate diabetes screening, particularly among middle-aged men.

Loss of androgen receptor expression is not associated with pathological stage, grade, gender or outcome in bladder cancer: a large multi-institutional study.

OBJECTIVE: • To investigate androgen receptor (AR) expression in a large series of patients with bladder cancer (BC) because data on a limited number of patients showed that loss of AR expression was associated with invasive BC. PATIENTS AND METHODS: • A total of 472 patients with urothelial bladder carcinoma (UBC) from two institutional centres (Toronto and Dallas) were analysed. Tissue microarrays comprising both non-muscle-invasive UBC (n= 167) and muscle-invasive UBC (n= 305) were accrued and immunohistochemical staining for AR was performed. • We used bright-field microscopy imaging coupled with advanced colour detection software to detect, classify and count stained cellular objects and manual scoring. • Results obtained in Dallas were blindly reviewed and validated in Toronto and samples randomly chosen were further analysed in Rochester, NY, USA. RESULTS: • The AR were positively expressed in 61/472 (12.9%) bladder tumours. No statistically significant difference in AR expression between men and women was observed. • Only 9.0% of non-muscle-invasive BC expressed the AR compared with 15.1% of muscle-invasive tumours (P= 0.059). The highest percentage of AR positivity (28.9% of cases) was found in T2 tumours. • There was no statistically significant difference in death from BC, time to death, or time to recurrence between AR-positive and AR-negative cases. CONCLUSION: • In contrast to previous reports, based on our large BC series, we did not observe a decrease in AR protein expression in bladder tumours with increased pathological stage. Our data do not suggest that loss of AR expression is gender-related nor is it associated with invasive BC.

Testosterone therapy: Prescribing and monitoring patterns of practice in British Columbia.

INTRODUCTION: Guidelines recommend that testosterone therapy (TTh) be restricted to men with a biochemical diagnosis of hypogonadism, and that therapeutic responses be titrated within the normal range. METHODS: Using four provincial longitudinal databases in British Columbia, we identified men prescribed TTh from 1997-2013. We characterized the prescribing and monitoring practices of TTh in the context of serum testosterone levels drawn prior to and following initiation of TTh in a population-based setting. RESULTS: In our analysis of 37 741 men who received at least one TTh prescription, 48% received injectable testosterone and the vast majority were treated by general practitioners. The number of prescriptions for men increased annually, particularly after 2008; 40% discontinued their treatment after their first or second prescription, while 27% received more than 10 repeats. The absolute percentage of pre- and post-serum testosterone levels ordered increased by 16% and 31% during the study period, respectively. However, after initiating TTh, only 36% of all the men had a followup serum testosterone level drawn. Of those with low serum testosterone levels prior to TTh, 49% remained biochemically hypogonadal following TTh, suggesting non-compliance or inadequate dosing. CONCLUSIONS: Many men prescribed TTh did not continue beyond a short trial. While the practice of checking pre-and post-TTh testosterone levels improved over the study period, it is concerning that only one-third had a followup serum testosterone level and half remained biochemically low. Further education is required around TTh prescribing, dose titration, and monitoring to ensure both effective and safe prescribing practice.

Learning from the learning curve: factors associated with successful endoscopic correction of vesicoureteral reflux using dextranomer/hyaluronic acid copolymer.

PURPOSE: Conflicting reports exist regarding the parameters guiding successful correction of vesicoureteral reflux using dextranomer/hyaluronic acid copolymer. We performed logistic regression analysis to evaluate the effect of injected volume while adjusting for other factors potentially associated with success following dextranomer/hyaluronic acid copolymer injection. MATERIALS AND METHODS: Between July 2003 and June 2006, 126 consecutive patients (34 boys and 92 girls) with a mean +/- SD age of 6.5 +/- 3.7 years with primary vesicoureteral reflux (196 refluxing ureters) underwent injection for febrile urinary tract infections. Success was defined as complete reflux resolution. Age, gender, laterality, preoperative vesicoureteral reflux grade, surgeon experience, dextranomer/hyaluronic acid copolymer volume, time to surgery from initial presentation and preoperative treatment for lower urinary tract symptoms were analyzed. RESULTS: Vesicoureteral reflux grade was I to V in 7 (3.5%), 53 (27%), 91 (46.4%), 30 (15.3%) and 15 renal units (7.6%), respectively. The success rate after 1 injection was 50% by patient and 59.2% by ureter. Mean injected volume was 0.9 +/- 0.27 ml in those who had a successful injection vs 0.67 +/- 0.24 ml in those in whom injection failed (p <0.001). The success rate after 1 injection was 78.9% using 0.8 ml or greater dextranomer/hyaluronic acid copolymer compared to 31.7% with less than 0.8 ml. Multivariate analysis confirmed that higher dextranomer/hyaluronic acid copolymer volume (p = 0.001), lower preoperative grade (p = 0.013), surgeon experience (p = 0.025) and treatment for lower urinary tract symptoms (p = 0.009) were associated with successful correction of vesicoureteral reflux. CONCLUSIONS: Our analysis strengthens the previously reported association of surgeon experience and vesicoureteral reflux grade with successful endoscopic vesicoureteral reflux correction. The data also revealed an association between injected volume and vesicoureteral reflux correction even while controlling for other variables, highlighting its importance as a true success modifier.

Failed pyeloplasty in children: comparative analysis of retrograde endopyelotomy versus redo pyeloplasty.

PURPOSE: We compared retrograde endopyelotomy to redo pyeloplasty for the treatment of failed pyeloplasty in children. MATERIALS AND METHODS: Of 32 patients with recurrent ureteropelvic junction obstruction retrograde endopyelotomy was performed in 18 and redo pyeloplasty was performed in 14. Patient age, gender, side, stent placement at initial pyeloplasty, presentation of secondary ureteropelvic junction obstruction, hospital stay, complications and success rates were compared. Success was defined as radiographic relief of obstruction as determined by ultrasound or diuretic renography at latest followup. RESULTS: Median patient age was 6 years (range 2 to 14) at retrograde endopyelotomy and 7.2 years (1 to 17) at redo pyeloplasty. Retrograde endopyelotomy technique consisted of holmium laser in 10 patients and cautery/balloon dilation in 8. Redo pyeloplasty was performed through a flank incision in 12 patients and by laparoscopy in 2. Retrograde endopyelotomy was successful in 39% of the patients, while redo pyeloplasty had a 100% success rate (p = 0.002). Of the patients with failed retrograde endopyelotomy 5 had a stricture greater than 1 cm and 7 were younger than 4 years. Mean length of the narrowed ureteral segment was 10.1 mm in the failed retrograde endopyelotomy group vs 5.8 mm in the successful group (p <0.01). Only 1 of 8 children (13%) had a successful retrograde endopyelotomy using cautery followed by balloon dilation. Hospital stay was 1.3 days for the retrograde endopyelotomy group and 2.9 days for the redo pyeloplasty group (p <0.01). Mean followup was 47 months (range 15 to 132) after retrograde endopyelotomy and 33.1 months (12 to 78) after redo pyeloplasty. CONCLUSIONS: Retrograde endopyelotomy had a significantly lower success rate than redo pyeloplasty for correction of recurrent ureteropelvic junction obstruction after failed pyeloplasty in children. Patient age less than 4 years and narrowed ureteral segment greater than 10 mm were associated with a poor outcome after retrograde endopyelotomy.

Prostate-specific antigen testing for prostate cancer screening: A national survey of Canadian primary care physicians' opinions and practices.

INTRODUCTION: In 2014, the Canadian Task Force on Preventive Health Care (CTFPHC) recommended against routine prostate cancer screening with the prostate-specific antigen (PSA) blood test. We surveyed Canadian primary care physicians (PCPs) to understand their opinions and attitudes towards prostate cancer screening in 2016. METHODS: Twenty PCPs piloted the survey to assess its accessibility. We distributed a flyer to 19 633 PCPs as an insert in a large mailed package inviting them to attend a national meeting, and later promoted the survey at the meeting. Multinomial logistic regression models examined factors associated with agreement of key guideline statements and the overall benefit of PSA screening. RESULTS: A total of 1254 PCPs responded (rate of 6.4%); 54.7% of physicians aware of the CTFPHC recommendations report screening less often as a result. Overall, 55.6% of PCPs feel that the risks of PSA screening outweigh the benefits. On multivariable analysis, physicians who did not read the guidelines, did not have an academic appointment, or were in practice for over 20 years were significantly more likely to disagree with the statement that men 55-69 years old should not be screened for prostate cancer with PSA. CONCLUSIONS: Our national survey found that the prostate cancer screening practices of Canadian PCPs varies widely across physician demographic groups, with almost equal numbers for or against. This has significant ethical, medical, and legal implications. The poor response rate to highly incentivized survey request may suggest a reluctance or general apathy towards this subject because of the Task Force recommendations. Future efforts should provide physicians with objective guidance around PSA screening, incorporating input from all stakeholders, including PCPs, urologists, and patients.

Bladder cancer: a portal into men's health.

Bladder cancer is the fourth most common cancer among men in the United States, with a 3-fold higher incidence than women. Globally, tobacco smoking remains significantly more common in men, contributing to half of all cases of bladder cancer. To prevent bladder cancer, urologists should promote smoking cessation to patients presenting at earlier ages with concerns such as sexual dysfunction, infertility, pelvic pain, or vasectomy. Bladder cancer also provides an entry point for men into the healthcare system, at which time, urologists can discuss and coordinate attention to other male health issues such as cardiovascular illness, depression, or addiction. By assuming the role of men's health physicians, urologists can have a significant benefit on men's urologic and overall health by targeting risk factors and behaviors.

Testosterone therapy and risk of myocardial infarction: a pharmacoepidemiologic study.

BACKGROUND: Recent studies have provided conflicting and controversial results about the risk of cardiovascular events, including myocardial infarction (MI), with testosterone replacement therapy (TRT). The potential adverse effects of different TRT formulations and duration of therapy on MI risk are unknown. METHODS: We performed a case-control study within a cohort of 934,283 men aged 45-80 from the IMS LifeLink Health Plan Claims Database. For each case of MI, four controls were identified using density-based sampling. Rate ratios (RRs) were computed for current and past TRT users. As a sensitivity analysis, the risk of MI before and after the start of a first-time TRT prescription in the same patient was also computed. RESULTS: We identified 30,066 MI cases and 120,264 corresponding controls. Current use of TRT was not associated with an increased risk of MI (RR 1.01, 95% confidence interval [CI] 0.89-1.16); first-time users did show an increased risk (RR 1.41, 95% CI 1.06-1.87; number needed to harm 305). There was no association between MI and past TRT users and no differences among the different formulations. The RRs for current use and first-time use of TRT in men with a previous history of coronary artery disease were 1.05 (95% CI 0.79-1.41) and 1.78 (95% CI 0.93-3.40), respectively. CONCLUSION: In this large observational study, an association between MI and past or current TRT use was not found. However, a statistically significant association was observed between first-time TRT exposure and MI, although the absolute risk was low.

Urological complications of illicit drug use.

Illicit drug use is prevalent worldwide; over 24 million people are estimated to have used recreational drugs during the past month in the UK and USA alone. Illicit drug use can result in a wide spectrum of potential medical complications that include many urological manifestations. To ensure optimal care and treatment, urologists need to be cognizant of these complications in their patients, particularly among youths. Ketamine uropathy is thought to affect over one-quarter of ketamine users and can lead to severe lower urinary tract symptoms, as well as upper tract obstruction. Cannabis use has been associated with an increased risk of bladder cancer, prostate cancer and nonseminomatous germ cell tumours in case-control studies. Fournier's gangrene has been reported following injection of heroin and cocaine into the penis. Excessive use of cough medicines can lead to the development of radiolucent stones composed of ephedrine, pseudoephedrine and guaifenesin. As the current evidence is mostly limited to case reports and case series, future epidemiological studies are needed to fully address this issue.

Do patients know their nerve-sparing status after radical prostatectomy?

OBJECTIVE: To determine patients' knowledge regarding their nerve-sparing status (NSS) after radical prostatectomy (RP) and what factors during their clinical treatment are associated with this. METHODS: One hundred consecutive patients attending an erectile dysfunction clinic in Toronto, Canada, with a prior RP were surveyed from December 2010 to June 2011. Patients were questioned whether they had undergone a nerve-sparing procedure and, if so, whether it was unilateral or bilateral. Patients were assessed on both knowledge (known vs unknown) and accuracy (correct vs incorrect) regarding their NSS. Operative reports were used to determine the true NSS of each patient. RESULTS: Thirty-nine percent of patients had no knowledge of their NSS. Forty-five percent of patients were able to correctly identify their NSS, including only 19% of patients undergoing a non-nerve-sparing procedure. On univariate analysis, factors associated with patients correctly knowing their NSS were age, having a nerve-sparing strategy dictated in the preoperative clinic note, nerve sparing included in the surgical consent form, and type of nerve-sparing procedure performed. On multivariate analysis, planned nerve-sparing approach dictated in the preoperative note (odds ratio [OR], 4.86), nerve sparing included in surgical consent (OR, 3.76), time since surgery (OR, 0.99), and having a bilateral nerve-sparing procedure (OR, 5.91) were associated with correctly identifying one's NSS. CONCLUSION: After RP, a significant proportion of patients with erectile dysfunction have no knowledge of whether they underwent a nerve-sparing procedure. By discussing with patients the planned nerve-sparing technique preoperatively and counseling them on their NSS postoperatively, urologists may be able to improve on patient recollection of their NSS.

Striated muscle in the prostatic apex: does the amount in radical prostatectomy specimens predict postprostatectomy urinary incontinence?

OBJECTIVE: To investigate whether the amount of striated muscle (SM) removed with the apical aspect of the prostate at prostatectomy can be predictive of postprostatectomy urinary incontinence (UI). METHODS: The records of 61 consecutive patients seen in follow-up after prostatectomy were reviewed. Complete clinical data were collected. Two uropathologists reviewed the hematoxylin and eosin sections of the apical margin to semiquantitatively assess the amount of SM according to the following scheme: 0 = no SM, 1 = 1%-10% SM (of total tissue), 2 = 11%-30% SM, and 3 = >30% SM. Continence status was determined based on the last clinical visit, with UI considered as any reported leakage. RESULTS: Patients had a median age of 62 years at surgery (interquartile range, 58-66 years) and had a median follow-up after surgery of 100 weeks (interquartile range, 50-176 weeks). Both prostate weight and SM score (P = .045 for both) were statistically significant predictors of incontinence on multivariate analysis. The odds of a patient with an average SM score of ≥2 being incontinent was 11.7 times that of a patient with an average score of <2. Using an SM score of ≥2 had a specificity of 98% and a sensitivity of 19% for detecting incontinence in patients after radical prostatectomy. CONCLUSION: The amount of SM seen in the pathology specimen after radical prostatectomy has a significant effect on postoperative UI.

Lean methodology improves efficiency in outpatient academic uro-oncology clinics.

OBJECTIVE: To determine if lean methodology, an industrial engineering tool developed to optimize manufacturing efficiency, can successfully be applied to improve efficiencies and quality of care in a hospital-based high-volume uro-oncology clinic. METHODS: Before the lean initiative, baseline data were collected on patient volumes, wait times, cycle times (patient arrival to discharge), nursing assessment time, patient teaching, and physician ergonomics (via spaghetti diagram). Value stream analysis and a rapid improvement event were carried out, and significant changes were made to patient check-in, work areas, and nursing face time. Follow-up data were obtained at 30, 60, and 90 days. The Student t test was used for analysis to compare performance metrics with baseline. RESULTS: The median cycle time before the lean initiative was 46 minutes. This remained stable at 46 minutes at 30 days but improved to 35 minutes at 60 days and 41 minutes at 90 days. Shorter wait times allowed for increased nursing and physician face time. The average length of the physician assessment increased from 7.5 minutes at baseline to 10.6 minutes at 90 days. The average proportion of value-added time compared with the entire clinic visit increased from 30.6% at baseline to 66.3% at 90 days. CONCLUSION: Using lean methodology, we were able to shorten the patient cycle time and the time to initial assessment as well as integrate both an initial registered nurse assessment and registered nurse teaching to each visit. Lean methodology can effectively be applied to improve efficiency and patient care in an academic outpatient uro-oncology clinic setting.

Tamsulosin treatment for benign prostatic hyperplasia and risk of severe hypotension in men aged 40-85 years in the United States: risk window analyses using between and within patient methodology.

OBJECTIVE: To characterize risk of hypotension requiring admission to hospital in middle aged and older men treated with tamsulosin for benign prostatic hyperplasia. DESIGN: Population based retrospective cohort study (between patient methodology) and self controlled case series (within patient methodology). SETTING: Healthcare claims data from the IMS Lifelink database in the United States. PARTICIPANTS: Men aged 40-85 years with private US healthcare insurance entering the cohort at their first dispensing for tamsulosin or for a 5α reductase inhibitor (5ARI) between January 2001 and June 2011 after a minimum of six months' enrolment. MAIN OUTCOMES MEASURES: Hypotension requiring admission to hospital. Cox proportional hazards models estimated rate ratios at time varying intervals during follow-up: weeks 1-4, 5-8, and 9-12 after tamsulosin initiation; weeks 1-4, 5-8, and 9-12 after restarting tamsulosin (after a four week gap); and maintenance tamsulosin treatment (remaining exposed person time). Covariates included age, calendar year, demographics, antihypertensive use, healthcare use, and a Charlson comorbidity score. A self controlled case series, having implicit control for time invariant covariates, was additionally conducted. RESULTS: Among 383,567 new users of study drugs (tamsulosin 297,596; 5ARI 85,971), 2562 admissions to hospital for severe hypotension were identified. The incidence for hypotension was higher for tamsulosin (42.4 events per 10,000 person years) than for 5ARIs (31.3 events per 10,000 person years) or all accrued person time (29.1 events per 10,000 person years). After tamsulosin initiation, the cohort analysis identified an increased rate of hypotension during weeks 1-4 (rate ratio 2.12 (95% confidence interval 1.29 to 3.04)) and 5-8 (1.51 (1.04 to 2.18)), and no significant increase at weeks 9-12. The rate ratio for hypotension also increased at weeks 1-4 (1.84 (1.46 to 2.33)) and 5-8 (1.85 (1.45 to 2.36)) after restarting tamsulosin, as did maintenance tamsulosin treatment (1.19 (1.07 to 1.32)). The self controlled case series gave similar results as the cohort analysis. CONCLUSIONS: We observed a temporal association between tamsulosin use for benign prostatic hyperplasia and severe hypotension during the first eight weeks after initiating treatment and the first eight weeks after restarting treatment. This association suggests that physicians should focus on improving counseling strategies to warn patients regarding the "first dose phenomenon" with tamsulosin.

Patients with Lynch syndrome mismatch repair gene mutations are at higher risk for not only upper tract urothelial cancer but also bladder cancer.

BACKGROUND: Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer, is caused by mutations in mismatch repair (MMR) genes. An increased risk for upper tract urothelial carcinoma (UTUC) has been described in this population; however, data regarding the risk for bladder cancer (BCa) are sparse. OBJECTIVE: To assess the risk of BCa in MMR mutation carriers and suggest screening and management recommendations. DESIGN, SETTING, AND PARTICIPANTS: Cancer data from 1980 to 2007 were obtained from the Familial Gastrointestinal Cancer Registry in Toronto for 321 persons with known MMR mutations: mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) (MLH1); mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) (MSH2); mutS homolog 6 (E. coli) (MSH6); and PMS2 postmeiotic segregation increased 2 (S. cerevisiae) (PMS2). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Standardized incidence ratios from the Ontario Cancer Registry, using the Surveillance Epidemiology and End Results public database, were used to compare cancer risk in patients with MMR mutations with the Canadian population. Microsatellite instability analysis and immunohistochemistry (IHC) of the MMR proteins were also performed and the results compared with matched sporadic bladder tumors. RESULTS AND LIMITATIONS: Eleven of 177 patients with MSH2 mutations (6.21%, p<0.001 compared with the Canadian population) were found to have BCa, compared with 3 of 129 patients with MLH1 mutations (2.32%, p>0.05). Of these 11 tumors, 81.8% lacked expression of MSH2 on IHC, compared with the matched sporadic cases, which all displayed normal expression of MSH2 and MLH1. The incidence of UTUC among MSH2 carriers was 3.95% (p<0.001), and all tumors were found to be deficient in MSH2 expression on IHC. Mutations in the intron 5 splice site and exon 7 of the MSH2 gene increased the risk of urothelial cancer. Limitations include possible inflated risk estimates due to ascertainment bias. CONCLUSIONS: LS patients with MSH2 mutations are at an increased risk for not only UTUC but also BCa and could be offered appropriate screening.

Comparative analysis of tubularized incised plate versus onlay island flap urethroplasty for penoscrotal hypospadias.

PURPOSE: Despite being the dominant technique for repair of distal hypospadias, application of the tubularized incised plate approach for penoscrotal hypospadias remains controversial. We report our experience with severe hypospadias, comparing tubularized incised plate to transverse island flap onlay urethroplasty. MATERIALS AND METHODS: We retrospectively reviewed consecutive patients with penoscrotal hypospadias presenting between 1998 and 2006. Based on surgeon preference 35 children underwent tubularized incised plate and 40 underwent onlay urethroplasty. Penoscrotal transposition and degree of ventral curvature, type of ventral curvature repair, complication rate, postoperative uroflowmetry pattern in toilet trained patients and number of reoperations were compared between the 2 groups. RESULTS: Mean patient age at surgery was 17 months (range 9 to 91) for tubularized incised plate urethroplasty and 17.8 months (10 to 58) for the onlay procedure. Urethroplasty was performed over an 8Fr catheter in all patients. With mean followups of 30 months (range 6 to 74) and 38.8 months (16 to 80) the overall complication rates were 60% and 45% for the tubularized incised plate and onlay procedures, respectively. Fistula occurred in 15 patients and repair breakdown in 3 patients (total 51.4%) treated with tubularized incised plate repair, compared to 8 and 2 patients, respectively (25%), treated with onlay repair (p = 0.01). Fistula location also differed significantly between the 2 groups, with proximal fistulas occurring in 11 of 15 tubularized incised plate repairs (73.3%) vs 2 of 8 onlay repairs (25%, p = 0.02). Recurrent ventral curvature was more frequent after onlay urethroplasty (5.7% vs 12.5%, not significant). At a mean age of 5.1 years a plateau uroflow curve (vs normal bell curve) was observed in 16 of 24 children (66.7%) who underwent tubularized incised plate repair and in 7 of 21 (33.3%) who underwent onlay repair (p <0.01). CONCLUSIONS: In this series the overall complication rate was similar for tubularized incised plate and onlay urethroplasty. Despite similar urethroplasty calibers, the uroflow curves and fistula positions in patients undergoing tubularized incised plate repair suggest that the neourethra distal to the fistula may be relatively narrow, creating flow resistance and leading to proximal fistula. Longer followup and close monitoring are needed before embracing one approach over the other.