Renal & Urology News September 2014 Issue

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VOLUME 13, ISSUE NUMBER 9

Tighter BP Control Not Always Best Stricter blood pressure targets may not improve outcomes, according to new study findings

BY JODY A. CHARNOW OPTIMAL BLOOD pressure targets in patients with hypertension may need to be reconsidered in light of the findings of recently published studies.

In one study, researchers led by Csaba P. Kovesdy, MD, chief of nephrology at the Memphis VA Medical Center in Memphis, found that stricter control of systolic blood pressure (SBP) is associated with higher all-cause mortality in patients with chronic kidney disease (CKD). The other study, led by John J. Sim, MD, area research chair, Kaiser

IN THIS ISSUE 9 14

Hypothyroidism may increase risk of diabetic nephropathy CKD found to raise risk of surgical complications

14

Visceral fat area predicts subtypes of renal cell carcinoma

15

Alcohol may protect against renal function decline in men

21

Stents may benefit some patients with renal artery stenosis Experts offer advice on how to measure physician productivity in a practice.

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Permanente Los Angeles Medical Center, demonstrated that systolic and diastolic pressures higher and lower than 130–139 mm Hg systolic and 60–79 diastolic are associated with an increased risk of death and development of end-stage renal disease (ESRD) in patients with and without CKD. In a study using a nationwide cohort of U.S. veterans, Dr. Kovesdy and his colleagues analyzed data from 77,765 CKD patients with uncontrolled hypertension who then received 1 or more additional antihypertensive med-

ESRD Clusters in Families, Study Finds END-STAGE renal disease (ESRD) clusters in families, including ESRD without known hereditary causes, a Norwegian study found.

The study, by Rannveig Skrunes, MD, of Haukeland University Hospital in Bergen, and colleagues, included 5,119,134 individuals recorded in the Norwegian Population Registry. These were people born in Norway and who were alive in 1980, when the Norwegian Renal Registry started registering all individuals developing ESRD requiring chronic renal replacement therapy.

ESRD developed in 8,203 subjects during follow-up; 27,046 had a continued on page 8

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LOWER BP MAY RAISE DEATH RISK Lower blood pressure (BP) targets in hypertensive patients with chronic kidney disease may increase their death risk, a study found. Below are the death rates per 1,000 patient-years in patients in the following BP ranges: 100

Death rate per 1,000 patient-years

S E P T E M B E R 2 014

80

80.9

Blood pressure (mm Hg)

60 40

Less than 120

41.8

120 –139

20 0

Source: Kovesdy CP et al. Observational modeling of strict vs conventional blood pressure control in patients with chronic kidney disease. JAMA Intern Med (published online ahead of print).

ications with evidence of a decrease in SBP. Of the 77,765 patients, 5,760 had a treated SBP of less than 120 mm Hg and 72,005 patients had SBP of 120–139 mm Hg at follow-up. During a median follow-up of 6 years, 19,517

died. The death rate was 80.9 per 1,000 patient-years in the SBP below 120 mm Hg group compared with 41.8 per 1,000 patient-years in the SBP 120–139 mm Hg group, Dr. Kovesdy’s continued on page 8

DKTs May Improve Kidney Use

BY JODY A. CHARNOW SAN FRANCISCO—Dual kidney transplants (DKTs) using organs from marginal donors that might otherwise be discarded are a viable option that could help counteract the growing shortage of acceptable single kidneys, researchers reported at the 2014 World Transplant Congress.

Robert J. Stratta, MD, and colleagues at Wake Forest School of Medicine in Winston-Salem, N.C., studied 72 DKTs performed over a 12-year period, including 45 (62.5%) using expanded criteria donor (ECD) kidneys, 17 (23.6%) using kidneys donated after cardiac death (DCD), and 10 (13.9%)

CME FEATURE

using standard criteria donor (SCD) kidneys. After a mean follow-up time of 58 months, the actual patient and graft survival rates were 85%, and 71%, respectively. The 1-year and death-censored graft survival rates were 90% and 80%. The outcomes did not differ by donor source or recipient age. Delayed graft function (DGF) and primary non-function occurred in 24% and 2.8% of recipients, respectively.

“The increasing disparity between organ supply and demand challenges the transplant community to maximize and optimize the use of organs from all consented deceased donors,” continued on page 8

Earn 1 CME credit in this issue

Shared Decision Making in Managing Idiopathic and Neurogenic OAB PAGE 26

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Focal PCa Therapy Safe, Feasible TARGETED FOCAL therapy (TFT) in carefully selected patients is a feasible and practical option for treating low-risk prostate cancer (PCa) with minimal impact on quality of life, researchers concluded.

Al B. Barqawi, MD, and colleagues at the University of Colorado Denver School of Medicine in Aurora prospectively evaluated the use of focal cryotherapy in 62 patients with organconfined low-risk PCa, defined as a Gleason score of 7 or less, a tumor burden of 50% or less, and a PSA

IN THIS ISSUE 9 14

Advanced prostate cancer linked to low melatonin Obesity increases the risk of urinary and other cancers

14

Visceral fat area found to predict subtypes of renal cell carcinoma

15

Post-brachytherapy erectile function preserved in most men

21

Stents may benefit some patients with renal artery stenosis Experts offer advice on how to measure physician productivity in a practice.

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level below 10 ng/dL. At 1 year, repeat biopsy results were negative in 50 (81%) patients. All 12 men with positive repeat biopsies had a Gleason score of 6 with 1 or 2 positive cores. The cohort overall had a significant median 3.0 ng/dL decrease in PSA level and a significant median 1.5 point decrease in American Urological Association symptom score.

None of the patients experienced post-operative erectile dysfunction or urinary incontinence. The investigators observed no significant change in Sexual Health Inventory for Men.

PCa Urine Test Shows Promise RESEARCHERS HAVE reported promising results using fluorescence microscopy and a photodynamic agent to detect shed prostate cancer (PCa) cells in voided urine, according to a recent report.

Their results show that the technique—which involves treating voided urine specimens with the photodynamic agent 5-aminolevulinic acid (5-ALA) following by imaging with fluorescence microscopy (PPIX)— has a greater sensitivity for detecting PCa than digital rectal examination (DRE) and transrectal ultrasound and a greater specificity than PSA and PSA continued on page 8

© IMAGE COURTESY OF AL B. BARQAWI, MD

Researchers report promising results using 3D mapping biopsies and cryotherapy

RESEARCHERS USED 3D mapping biopsies to identify cancer foci for cryoablation.

Study findings appear in The Journal of Urology (2014;192:749-753), where Dr. Barqawi’s group noted that most patients never see symptoms associated with PCa, but men newly diagnosed with the malignancy fear that they may be among the minority with aggressive disease.

Retrospective studies have shown that patients who are candidates for active surveillance (AS) at the time of radical prostatectomy have experienced disease upgrading and upstaging. In addition, they cited a study published in the continued on page 8

AKI Linked To Antipsychotics NEW FINDINGS may explain the observed association between atypical antipsychotic drug use and an elevated risk for acute kidney injury (AKI) and other adverse outcomes in elderly patients, researchers reported.

A team led by Amit X. Garg, MD, PhD, of professor of medicine and epidemiology at Western University in London, Ontario, and a researcher at the Institute for Clinical and Evaluative Sciences (ICES), studied almost 100,000 patients aged 65 years and older who received a new outpatient prescription for an oral atypical antipsychotic drug and an equal number of matched patients who did not receive

CME FEATURE

such a prescription. Atypical antipsychotic drug use was associated with a nearly 2-fold higher 90-day risk of hospitalization for AKI—the primary outcome of the study—compared with non-use, according to the researchers. In addition, 5.5% of patients prescribed the drug were hospitalized with AKI compared with 3.3% of nonusers. Antipsychotic drug use was associated with other adverse outcomes that may explain the observed association with AKI, with use of the medications associated with a nearly 2-fold increased 90-day risk of hypotension and acute urinary retention, and 2.3 continued on page 8

Earn 1 CME credit in this issue

Shared Decision Making in Managing Idiopathic and Neurogenic OAB PAGE 26

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www.renalandurologynews.com SEPTEMBER 2014

Renal & Urology News 5

FROM THE EDITOR EDITORIAL ADVISORY BOARD

The Ebola Threat: Why Not an Outbreak Here?

T

hanks to air travel, the separation of continents by thousands of miles of ocean no longer provides a secure buffer against the spread of communicable diseases from far-flung places.

Passengers from Africa, Asia, or South America who are infected with highly virulent bacteria or viruses can arrive in the heart of a bustling American city in less than a day. Given the numbers of people traveling between countries, the international dispersal of potentially lethal pathogens seems inevitable.

One of those pathogens could be Ebola virus, which kills up to 90% of people infected with it. The World Health Organization (WHO) recently declared the Ebola outbreak in West Africa (namely Guinea, Liberia, Sierra Leone, and Nigeria) a global emergency. According to WHO, confirmed, probable, or suspected Ebola disease has been documented in 2,240 individuals as of August 16, and 1,229 have died from it.

The U.S. has no guaranteed immunity from an Ebola outbreak, even though we may have an edge in containing the virus compared with the nations now beset by a severe Ebola outbreak.

Complacency here could set the stage for an outbreak. A patient sickened with the virus could seek care in an emergency department, where medical staff might not immediately suspect Ebola infection and the usual precautions taken to prevent pathogen transmission may not be enough. Paramedics could respond to a 911 call for somebody who collapsed, bleeding, on a city street and never give a thought to the possibility of Ebola.

Complacency is understandable. Many exotic diseases are endemic to distant countries afflicted by poverty and squalid living conditions. Additionally, we trust that our modern medical and public health infrastructure would rapidly contain the spread of a contagious disease before a major outbreak results.

Travel-related dispersal of potentially deadly infectious diseases across great distances is not new. Europeans traveling by ship brought smallpox to the New World in the late 1400s and early 1500s, and it decimated the susceptible Native American populations. In those days, a ship’s journey from Europe to the New World took a few months. Now, millions of people traverse oceans in travel times measured in hours, crisscrossing the globe relatively quickly by jet as they make countless visits to various destinations. Under the right set of circumstances, it would take just one of these individuals to be infectious with Ebola or something just as bad—or worse—to start an outbreak. Medical personnel, especially those on the frontlines, must be vigilant.

Jody A. Charnow Editor

Medical Director, Urology

Medical Director, Nephrology

Robert G. Uzzo, MD, FACS G. Willing “Wing” Pepper Chair in Cancer Research Professor and Chairman Department of Surgery Fox Chase Cancer Center Temple University School of Medicine Philadelphia

Kamyar Kalantar-Zadeh, MD, MPH, PhD Medical Director, Nephrology Professor & Chief Division of Nephrology & Hypertension University of California, Irvine School of Medicine Orange, Calif.

Nephrologists

Urologists

Anthony J. Bleyer, MD, MS Professor of Internal Medicine/Nephrology Wake Forest University School of Medicine Winston-Salem, N.C.

Christopher S. Cooper, MD Director, Pediatric Urology Children’s Hospital of Iowa Iowa City

Suphamai Bunnapradist, MD Director of Research Department of Nephrology Kidney Transplant Research Center The David Geffen School of Medicine at UCLA

R. John Honey, MD Head, Division of Urology, Endourology/Kidney Stone Diseases St. Michael’s Hospital University of Toronto Stanton Honig, MD Department of Urology Yale University School of Medicine New Haven, CT J. Stephen Jones, MD, FACS Vice President Regional Medical Operations Professor & Horvitz/Miller Distinguished Chair in Urological Oncology Cleveland Clinic Regional Hospitals Jaime Landman, MD Professor of Urology and Radiology Chairman, Department of Urology University of California Irvine

Csaba P. Kovesdy, MD Chief of Nephrology Memphis VA Medical Center Fred Hatch Professor of Medicine University of Tennessee Health Science Center, Memphis Edgar V. Lerma, MD, FACP, FASN, FAHA Clinical Associate Professor of Medicine Section of Nephrology Department of Medicine University of Illinois at Chicago College of Medicine, Chicago Allen Nissenson, MD Emeritus Professor of Medicine The David Geffen School of Medicine at UCLA, Chief Medical Officer, DaVita Inc.

James M. McKiernan, MD Assistant Professor of Urology Columbia University College of Physicians and Surgeons New York City

Rulan Parekh, MD, MS Associate Professor of Pediatrics and Medicine University of Toronto

Kenneth Pace, MD, MSc, FRCSC Assistant Professor Division of Urology St. Michael’s Hospital University of Toronto

Robert Provenzano, MD Chief, Section of Nephrology St. John Hospital and Medical Center, Detroit Robert S. Rigolosi, MD Director, Regional Hemodialysis Center Holy Name Hospital, Teaneck, N.J.

Ryan F. Paterson, MD, FRCSC Assistant Professor Division of Urologic Sciences University of British Columbia Vancouver, Canada

Lynda Anne Szczech, MD, MSCE Medical Director, Pharmacovigilence and Global Product Development, PPD, Inc. Morrisville, N.C.

Renal & Urology News Staff

Editor Jody A. Charnow Production editor Kim Daigneau Web editor

Stephan Cho

Group art director, Haymarket Medical Jennifer Dvoretz

Production manager Krassi Varbanov

Production director Kathleen Millea Grinder Circulation manager Paul Silver National accounts manager William Canning Publisher Dominic Barone Editorial director

Jeff Forster

Senior VP, medical journals & digital products

Jim Burke, RPh

Senior VP, clinical communications group

John Pal

CEO, Haymarket Media Inc.

Lee Maniscalco

Renal & Urology News (ISSN 1550-9478) Volume 13, Number 9. Published monthly by Haymarket Media, Inc., 114 West 26th Street, 4th Floor, New York, NY 10001. Periodicals postage paid at New York, NY, and an additional mailing office. The subscription rates for one year are, in the U.S., $75.00; in Canada, $85.00; all other foreign countries, $110.00. Single issues, $20.00. www.renalandurologynews.com. Postmaster: Send address changes to Renal & Urology News, c/o DMD Data Inc., 2340 River Road, Des Plaines, IL 60018. For reprints, contact Wright’s Reprints at 1.877.652.5295. Copyright: All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means (electronic, mechanical, photocopying, recording, or otherwise) without the prior written permission of Haymarket Media, Inc. Copyright © 2014.

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SEPTEMBER 2014

www.renalandurologynews.com

Contents

SEPTEMBER 2014

■

VOLUME 13, ISSUE NUMBER 9

Nephrology 7

ONLINE

this month at renalandurologynews.com Clinical Quiz

Take our latest quiz at renalandurologynews.com /clinical-quiz/. Answer correctly and you will be entered to win a $50 American Express gift card.

Congratulations to our July winner: Bruce Lippmann, MD

Videos

Some of our recent postings include: • A-Fib After Surgery Increases Stroke Risk • Bladder Cancer vs. Smoking, Obesity • Renal Mass Biopsy Underused in U.S.

Drug Showcase

Read up on recently-approved pharmaceuticals. Our latest include: • Adempas (riociguat), for chronic hypertension • Farxiga (dapagliflozin), for type 2 diabetes • Fortesta (testosterone gel), for hypogonadism

News Coverage

Visit our website for timely reports from upcoming meetings.

9

15

21

CALENDAR

Hypothyroidism May Raise Diabetic Nephropathy Risk In a study of diabetics, subclinical hypothyroidism was associated with a 3.5 times increased odds of nephropathy compared with euthyroid patients.

International Continence Society Annual Meeting Rio de Janeiro October 20–24

CKD May Worsen Surgery Outcomes New studies demonstrate increased risks of major perioperative and postoperative complications and death.

Annual Dialysis Conference New Orleans January 31–February 3

Alcohol May Reduce eGFR Loss in Men Heavy alcohol drinkers and binge drinkers had a significant 86% and 58% decreased odds of renal dysfunction compared with abstainers.

Genitourinary Cancers Symposium Orlando, Fla. February 26–28 European Association of Urology Madrid March 20–24

Panel: Stents May Help Some RAS Patients A new consensus statement states that renal artery stenting may benefit patients with renal artery stenosis who historically have been excluded from modern clinical trials.

Urology 9

14

Low Melatonin Found to Raise Advanced PCa Risk Urinary levels of a melatonin metabolic below the median were associated with a 4-fold increased risk versus levels above the median.

Hydronephrosis, UTUC Outcomes Linked Moderate or severe hydronephrosis predicts worse oncologic outcomes in patients with high-grade upper tract urothelial carcinoma.

15

Post-Brachytherapy Erectile Function Preserved in Most PCa Patients Preservation rates are better younger men and those without medical comorbidities, according to an Australian study.

21

MRI Can Accurately Detect Significant Prostate Cancer Diffusion-weighted magnetic resonance imaging noninvasively detects significant prostate tumors with a high probability and without contrast medium or an endorectal coil.

“With all of these advantages DW-MRI has

the potential to rapidly disseminate into clinical practice for PCa management.

See our story on page 21

006_Neph_RUN0914.indd 6

Kidney Week Philadelphia November 11–16

26

CME Feature 26

Shared Decision Making in Managing Idiopathic and Neurogenic OAB Michael B. Chancellor, MD, David A. Ginsberg, MD, and Victor W. Nitti, MD, discuss how to improve outcomes by communicating effectively about appropriate options and eliciting patient input.

Departments 5

From the Editor The Ebola Threat: Why Not an Outbreak Here?

7

News in Brief BRCA2 mutation increases PCa death risk

20

Practice Management Advice for measuring practice productivity

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6 Renal & Urology News

SEPTEMBER 2014

www.renalandurologynews.com

Contents

SEPTEMBER 2014

■

VOLUME 13, ISSUE NUMBER 9

Urology

ONLINE

this month at renalandurologynews.com

9

Low Melatonin Found to Raise Advanced PCa Risk Urinary levels of a melatonin metabolic below the median were associated with a 4-fold increased risk versus levels above the median.

14

Hydronephrosis, UTUC Outcomes Linked Moderate or severe hydronephrosis predicts worse oncologic outcomes in patients with high-grade upper tract urothelial carcinoma.

15

Clinical Quiz

Take our latest quiz at renalandurologynews.com /clinical-quiz/. Answer correctly and you will be entered to win a $50 American Express gift card.

Congratulations to our July winner: Bruce Lippmann, MD

Videos

Some of our recent postings include: • A-Fib After Surgery Increases Stroke Risk • Bladder Cancer vs. Smoking, Obesity • Renal Mass Biopsy Underused in U.S.

21

News Coverage

Visit our website for timely reports from upcoming meetings.

Post-Brachytherapy Erectile Function Preserved in Most PCa Patients Preservation rates are better younger men and those without medical comorbidities, according to an Australian study.

MRI Can Accurately Detect Significant Prostate Cancer Diffusion-weighted magnetic resonance imaging noninvasively detects significant prostate tumors with a high probability and without contrast medium or an endorectal coil.

7

9

Hypothyroidism May Raise Diabetic Nephropathy Risk In a study of diabetics, subclinical hypothyroidism was associated with a 3.5 times increased odds of nephropathy compared with euthyroid patients.

CKD May Worsen Surgery Outcomes New studies demonstrate increased risks of major perioperative and postoperative complications and death.

15

Alcohol May Reduce eGFR Loss in Men Heavy alcohol drinkers and binge drinkers had a significant 86% and 58% decreased odds of renal dysfunction compared with abstainers.

21

Panel: Stents May Help Some RAS Patients A new consensus statement states that renal artery stenting may benefit patients with renal artery stenosis who historically have been excluded from modern clinical trials.

“With all of these advantages DW-MRI has

the potential to rapidly disseminate into clinical practice for PCa management.

See our story on page 21

006_Uro_RUN0914.indd 6

International Continence Society Annual Meeting Rio de Janeiro October 20–24 Kidney Week Philadelphia November 11–16 Annual Dialysis Conference New Orleans January 31–February 3 Genitourinary Cancers Symposium Orlando, Fla. February 26–28 European Association of Urology Madrid March 20–24

Nephrology

Drug Showcase

Read up on recently-approved pharmaceuticals. Our latest include: • Adempas (riociguat), for chronic hypertension • Farxiga (dapagliflozin), for type 2 diabetes • Fortesta (testosterone gel), for hypogonadism

CALENDAR

26

CME Feature 26

Shared Decision Making in Managing Idiopathic and Neurogenic OAB Michael B. Chancellor, MD, David A. Ginsberg, MD, and Victor W. Nitti, MD, discuss how to improve outcomes by communicating effectively about appropriate options and eliciting patient input.

Departments 5

From the Editor The Ebola Threat: Why Not an Outbreak Here?

7

News in Brief BRCA2 mutation increases PCa death risk

20

Practice Management Advice for measuring practice productivity

8/21/14 4:40 PM

www.renalandurologynews.com

SEPTEMBER 2014

Renal & Urology News 7

News in Brief

Please visit us at www.renalandurologynews.com for the latest news updates from the fields of urology and nephrology

Short Takes BRCA2 Mutation Ups PCa Death Risk

controlled by treatment that includes

Prostate cancer (PCa) patients with a

who are already being treated with

BRCA2 mutation are more likely to die

both drugs separately.

either canagliflozin or metformin or

The product will be available in tablets

from the malignancy than those without the mutation, researchers reported

containing canagliflozin 50 mg or

online in the British Journal of Cancer.

150 mg and metformin 500 mg or

Mohammad R. Akbari, MD, of the

1000 mg. The recommended dosing is

Women’s College Research Institute

twice daily. The prescribing information

in Toronto, and colleagues identified

has a boxed warning for lactic acidosis.

4,187 men who underwent a PCa of an elevated PSA level or abnormal

PCa Found in One Fifth Of Men Undergoing RCP

digital rectal examination. They

French researchers who studied 2,424

screened the BRCA2 gene for mutations

men undergoing radical cystopros-

and followed the men for death from

tatectomy (RCP) for muscle-invasive

PCa until December 2012. The 12-year

bladder cancer found that 518 of

PCa-specific survival rate was 61.8% for

them (21.4%) also had prostate can-

men with a BRCA2 mutation compared

cer (PCa), according to study findings

with 94.3% for men without a mutation.

published online ahead of print in BJU

biopsy from 1998 to 2010 as a result

International.

Two-Drug Pill Okayed for Treating Diabetes

MD, of Paris XI University, showed that

The FDA has granted marketing ap-

the incidence of PCa varied by age,

proval to Janssen Pharmaceuticals,

ranging from 5.2% in patients younger

Inc., for Invokamet, a fixed-dose combi-

than 50 years to 30.5% in those old-

nation of canagliflozin and metformin.

er than 75 years. Most tumors were

The study, led by Géraldine Pignot,

organ-confined and well-differentiated.

Invokamet is indicated as an adjunct to diet and exercise to improve

At the end of follow-up, 9 patients

glycemic control in adults with type

(1.7%) experienced biochemical recur-

2 diabetes who are not adequately

rence of PCa.

Patient Access to Lab Reports In a recent online poll, Renal & Urology News asked readers, “Is allowing patients direct access lab results a good idea?” Here are the results based on 207 responses.

Yes: 68.6%

No: 27.05%

Do not know: 4.35%

0

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20

30

40

50

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Hypothyroidism May Raise Diabetic Nephropathy Risk S

ubclinical hypothyroidism (SCH) may be independently associated with diabetic nephropathy in patients with diabetes mellitus, according to a Japanese study.

Shinya Furukawa, MD, PhD, of Ehime University Graduate School of Medicine in Ehime, and collaborators studied 414 patients with type 2 diabetes and no history of thyroid disease. The prevalence of diabetic nephropathy was significantly greater in the SCH than the euthyroid group (16.7% vs. 6.1%). On multivariate analysis, SCH was associated with a 3.5 times increased odds of diabetic nephropathy and a 4.6 times increased odds of hypertension, the researchers reported online ahead of print in the Endocrine Journal.

“These findings imply that SCH may be a new therapeutic target to prevent the development and progression of renal disease in diabetes patients,” the authors concluded. “Thyroid function screening should be offered to diabetes patients with diabetic nephropathy.”

PCa Patients Are At Higher Risk of Secondary Cancers P

rostate cancer (PCa) patients are at increased risk for secondary primary malignancies compared with the general population, a study found.

In a study of 20,558 PCa patients in Zurich, Switzerland, 1,718 developed a second primary tumor after their PCa diagnosis, mostly frequently lung and colon cancer (15% and 13%, respectively). Overall, the likelihood for a secondary primary cancer was 1.11 times greater in PCa patients compared with the general population of men, Mieke Van Hemelrijck, MD, of King’s College London in the U.K., and colleagues reported online in PLoS One (2014;9:e102596). PCa patients were twice as likely as men in the general population to develop kidney and bladder cancer. They also were 2.9 times and 1.7 times more likely to develop primary thyroid and colon cancer, respectively.

“Increased diagnostic activity after PCa diagnosis may partly explain increased risks within the first years of diagnosis, but time-stratified analyses indicated that increased risks remained and even increased over time,” the authors concluded.

Antibiotic Lock Shown to Reduce Infection Risk T

he use of a prophylactic antibiotic lock solution in hemodialysis (HD) patients is associated with significant reductions in catheter-related infections and mortality, according to a study published online ahead of print in the Clinical Journal of the American Society of Nephrology.

Carol Moore, PharmD, and colleagues from Henry Ford Hospital in Detroit found that a locking solution of gentamicin and citrate lowered catheter-related bloodstream infections by 73% and mortality by 68% compared with heparin. The study evaluated a cross-over from heparin (1,000 units/mL) to a low-dose gentamicin/citrate solution (0.32 mg/mL gentamicin in 4% trisodium citrate) in 555 chronic HD patients using permanent tunneled cuffed catheters in three outpatient centers in the Detroit metropolitan area.

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Hypertension revisited

continued from page 1

team reported online ahead of print in JAMA Internal Medicine. After adjusting for propensity scores, the SBP less than 120 mm Hg group had a 70% increased risk of death compared with the SBP 120–139 mm Hg group.

“Our goal was to model a clinical trial, capitalizing on the availability of a very large clinical database that allowed us to select patients whose blood pressure trajectory suggested a change from uncontrolled level to different BP goals using pharmacologic intervention,” Dr. Kovesdy told Renal & Urology News.

“The observational nature of the study does not allow us to claim that the higher mortality was a direct result of the lower observed BP. Nevertheless, our results are similar to those reported by other studies done in the CKD population, and suggest that blood pressure has a J-shaped association with mortality, and that it may be advisable to avoid over-treating hypertension in patients with kidney disease.”

In clinical practice, Dr. Kovesdy pointed out, this would mean that targeting an SBP range of about 120–140 mm Hg rather than an SBP of below 140 mm Hg may be more beneficial.

ESRD study

continued from page 1

first-degree relative with ESRD. The researchers defined first-degree relatives as parents, siblings, or children.

Subjects who had a first-degree relative with ESRD had a 7.2 times higher risk of ESRD compared with individuals who did not. In separate analyses that excluded known hereditary nephropathies, individuals with a firstdegree relative with ESRD had a 3.7 times increased risk of ESRD.

The risk of ESRD is higher in persons with a first-degree relative with ESRD. Dr. Skrunes’ team looked at the relative risk of ESRD according to its cause. As expected, the investigators noted, those who had a first-degree relative with ESRD due to hereditary renal disease had a significant 36 times higher risk of ESRD and a 5.2, 4.7, 2.6, and 2.6 times higher risk of ESRD if a first degree relative was diagnosed

Cover_012_RUN0914_V2.indd 8

The approach may require the tapering of antihypertensive regimens in patients whose SBP is less than 120 mm Hg, especially if they display symptoms or signs of organ hypo-perfusion, such as lightheadedness or an increase in serum creatinine.

Direct extrapolation of these results to ESRD patients is not possible, he said, although observational data in dialysis patients also suggests the presence of a J-shaped curve. In dialysis patient the situation is, however, more complex due to differences in pre-, post-, and interdialytic blood pressures.

The study by Dr. Sim’s team, which was published in the Journal of the American College of Cardiology (2014;64:588-597), included 398,419 treated hypertensive patients (30% of whom had diabetes mellitus) in the Kaiser Permanenete Southern California health system. Of these, 25,182 (6.3%) died and ESRD developed in 4,957 (1.2%). Compared with an SBP of 130–139 mm Hg, an SBP below 110 mm Hg was associated with a 4-fold increased risk of a composite outcome of death or ESRD. An SBP of 110–119 mm Hg was associated with a 1.8 times increased risk. Patients with an SBP of 150–159, 160-169, and 170 mm Hg or higher had a 2.3, 3.3, and

with glomerular disease, interstitial nephritis, diabetic nephropathy, or hypertensive nephropathy respectively, compared with subjects who did not have a first-degree relative with ESRD. “In our opinion, the findings of higher risks of hypertensive and diabetic nephropathy argue for the importance of multifactorial genetic risk factors that also could include potentially modifiable risk factors for more rapid progression of renal fibrosis,” the authors concluded in a paper published online ahead of print in the Clinical Journal of the American Society of Nephrology.

The researchers pointed out that individuals who share genetic risk factors often also share environmental risk factors. The higher risk of ESRD among individuals with first-degree relatives with ESRD may be monogenic or multifactorial, they noted.

“It has not been possible to quantify environmental factors or the interplay between genes and environment,” they wrote. “The take-home messages are, nevertheless, that ESRD clusters in families and that screening of firstdegree relatives of patients with ESRD with regard to renal dysfunction might be considered.” n

4.9 times increased risk. Diastolic BP of 60–79 mm Hg was associated with the lowest risk. The nadir systolic and diastolic pressures associated with the lowest risk were 137 and 71 mm Hg, respectively.

An SBP target of about 120–140 rather than below 140 mm Hg may be more beneficial.

“Controlling hypertension is the priority,” Dr. Sim said. “As a nation, we have been able to steadily improve our hypertension treatment and subsequent control rates to the degree that now we have to better establish the ideal treatment ranges. Our Kaiser Permanente study suggests that ‘the lower the better’

Dual kidney transplants continued from page 1

Dr. Stratta told Renal & Urology News.

“Growing acceptance and use of marginal donor kidneys, defined as having limited renal functional capacity, have been tempered by concerns that these kidneys have inferior outcomes.”

At a mean 36 months post-DKT, 11 patients died, 8 with a functioning graft. Graft survival and function were comparable to that of concurrent single SCD kidney recipients and superior to that of concurrent single ECD kidney recipients.

Results also showed that in the absence of DGF or acute rejection, the proportion of renal function transplanted from donor to DKT recipients was 77% compared with 55%-58% among patients receiving single kidneys from SCD, ECD, or DCD donors.

“Medium term outcomes, similar to concurrent SCD single kidney recipients, can be achieved and waiting times can be reduced in a predominantly older recipient population with primarily ECD kidneys,” the authors concluded in their poster presentation.

Both donors and recipients had a mean age of 60 years; 29 donors and

approach is not ideal and that there may be a subpopulation where clinicians may be adding risk with aggressive treatment.

For those individuals, clinicians should consider down titration and withdrawal of medications in order to achieve more appropriate blood pressures.”

In an editorial accompanying the report by Dr. Sim’s team (pp.598–600), Charlotte Andersson, MD, of Gentofte Hospital in Hellerup, Denmark, and Ramachandran S. Vasan, MD, of Boston University School of Medicine, noted that available randomized trials have not convincingly demonstrated improved mortality rates with aggressive antihypertensive treatment.

“Ultimately, we need further studies to establish the optimal BP treatment target for patients with various comorbidities,” the authors wrote. “It may make sense to treat younger people with less comorbidity more aggressively than older patients or people with a large burden of comorbidity, but the exact numerical BP targets are yet to be determined.”

Drs. Andersson and Vasan added that truly uncontrolled hypertension remains a challenge, “and we still must be concerned about undertreatment of hypertension, even as we sort out the optimal treatment target.” n

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8 Renal & Urology News

26 recipients were aged 65 years and older. Nearly all of the transplanted kidneys were refused by multiple centers, with many targeted for discard in the absence of DKT utilization.

The recipients had mean pre-­transplant waiting and dialysis vintage times of 12 months and 25 months, respectively.

In an effort to use marginal donor kidneys not considered suitable for single kidney transplants, for whatever reasons, the application of DKT has evolved in lieu of organ discard, said Dr. Stratta, who is a transplant surgeon and a professor of surgery.

“At present, the decision to perform a DKT versus either 2 single kidney transplants or discarding both kidneys is multifactorial and usually occurs when both kidneys have been refused for single kidney transplantation by multiple centers and have accrued prolonged cold ischemia time,” he explained. “In addition to donor organ quality and excessive cold ischemia, the greatest potential risk factor for inferior outcomes in DKT is poor recipient selection.”

Outcomes are optimized when a systematic approach based on careful assessment of donor and kidney quality as well as appropriate recipient selection is implemented, he said. n

8/21/14 4:31 PM

SEPTEMBER 2014 www.renalandurologynews.com

Focal PCa Therapy continued from page 1

Journal of Clinical Oncology (2009;28:126131) showing that up to 26% of men on AS protocols who later elected to undergo radical treatment experienced a 50% rate of biochemical recurrence after a median of 6.8 years of follow-up.

“The short-term benefits of surveillance may not outweigh the long-term cancer

AKI and antipsychotics continued from page 1

times increased risk all-cause mortality compared with non-use of the drugs.

The mortality findings support FDA’s “black box” warnings that these drugs cause an increased risk of death in elderly patients [a warning based on the analyses of randomized, placebo-controlled trials averaging 10 weeks in duration]. The Committee on the Safety of Medicines in the United Kingdom has also issued a warning that these drugs should not be given to elderly patients with dementia.

Writing in a report published in Annals of Internal Medicine (2014;161:242248), Dr. Garg and his colleagues noted that AKI resulting from the use of atypical antipsychotic drugs is described in some case reports.

The drugs, which include quetiapine

outcomes of treatment in these patients,” Dr. Barqawi’s group wrote.

The problem faced by clinicians is determining the group to which patients belong: men for whom AS may be ideal but undesirable or those in whom quietly aggressive cancer should be treated despite seeming candidacy for observation, Dr. Barqawi and colleagues stated.

“TFT is an intervention that may be beneficial to patients in each group,” the

(Seroquel), risperidone (Risperdal), and olanzapine (Zyprexa), continue to be used in older adults to manage behavioral symptoms of dementia (tens of millions of prescriptions each year worldwide, Dr. Garg pointed out), despite being an unapproved indication for these medications.

In an ICES-issued press release, Dr. Garg said the study “calls for a careful reevaluation of prescribing atypical antipsychotic drugs in older adults, especially for the unapproved indication of managing behavioral symptoms of dementia. The drugs should be used after other approaches have been exhausted; when prescribed, patients and their families must be warned about potential adverse effects, and patients should be monitored for early warning signs of potential adverse effects. Also, when patients present with AKI, atypical antipsychotic drugs

ESRD Risk Lower with Partial Nephrectomy, Study Finds PARTIAL NEPHRECTOMY is associ-

the rate of ESRD, but in the modern

ated with a lower risk of end-stage

cohort, PN was associated with a

renal disease (ESRD) requiring renal

significant 53% decreased risk of ESRD

replacement therapy compared with

in a propensity-score-matched analysis

radical nephrectomy, according to a

and a significant 56% decreased risk in

new study.

a multivariable analysis, the research-

Stanley A. Yap, MD, of the University

ers reported online ahead of print in

of California San Diego, and col-

BJU International. PN also was associ-

leagues studied 11,937 patients who

ated with a significant 52% and 50%

underwent surgery for pathologically

lower risk of new-onset chronic kidney

confirmed RCC. Of these, 2,107 under-

disease (CKD), respectively, based on

went partial nephrectomy (PN) and

propensity-score-matching and multi-

9,830 underwent radical nephrectomy

variable analyses.

(RN). Separately, the researchers ana-

“Although it is well-known that RN is

lyzed a “modern cohort” of patients

associated with more CKD than PN, we

who had surgery during the period

provide the first direct evidence that PN

2003–2010.

is associated with less ESRD requiring

The median follow-up was 57 months.

renal replacement therapy than RN in a

In the study population overall, the type

modern cohort of patients with RCC,”

of surgery was not associated with

the authors concluded. n

Cover_URO_RUN0914.indd 8

researchers wrote. “Serving as a middle ground between observational strategies and aggressive treatment, TFT holds great promise for localized PCa.” The researchers identified cancer foci by performing 3D mapping biopsies (3DMB) using triplane transrectal ultrasonography. They placed gold fiducial markers as orientation landmarks for subsequent TFT. “These markers, which are commonly used

Seniors taking atypical antipsychotic drugs are at higher risk of acute kidney injury.

should be considered a potential cause and promptly discontinued if possible.”

He and his colleagues noted that, to their knowledge, their study is first

PCa urine test continued from page 1

density, the investigators noted.

“To our knowledge, this is the first successful demonstration of PPIX in urine sediments treated with 5-ALA used to detect PCa in a noninvasive yet highly sensitive manner,” the authors wrote in an online report in BMC Urology. “However, further studies are warranted to determine the role of PPIX-PPD for PCa detection.”

Yashushi Nakai, MD, and colleagues at Nara Medical University in Nara, Japan, tested the approach in 138 men with an abnormal DRE and/or elevated PSA levels. Needle prostate biopsies revealed PCa in 81 (58.7%).

Of these 81 patients, 60 were PPIXpositive, for a sensitivity of 74.1%.

Although 57 patients did not have PCa by conventional diagnostic procedures, 17 of these at-risk patients were PPIXpositive, for a specificity of 70.2%.

Dr. Nakai’s group noted that the positivity rate of their approach did not increase with increasing total PSA or tumor stage, but did increase with

in radiotherapy, allow the surgeon to precisely target specific areas of the prostate during TFT that were found to have cancer foci on 3DMB.” They defined TFT as complete ablation of all clinically detected cancer foci in the prostate using a minimally invasive technique, with preservation of the sphincter, normal gland tissue, and neurovascular bundle, according to the report. n

population-based investigation of AKI resulting from the use of antipsychotic drugs. Population-based studies, they observed, complement information generated from clinical trials by providing an opportunity to study uncommon but important adverse drug reactions with adequate statistical power. Populationbased studies also include vulnerable groups not enrolled in clinical trials and allow effects “to be studied in routine practice, where treatments and monitoring are less regimented than in trials.”

The authors indicate that the findings should not be generalized to younger patients who may take these drugs for mental health reasons. Younger patients are less prone to adverse drug effects than the elderly. Also, if an older adult is taking one of these medications, if they or their families have any concerns they should first speak to their physician before discontinuing the drug. n

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8 Renal & Urology News

increasing Gleason score, although the trend was not statistically significant.

“These results showed a possibility that PCa detection with PPIX-PPD [photodynamic diagnosis] identified more clinically significant PCa compared with PCa detected by other reported methods.”

The sensitivity and specificity of the new assay were 74.1% and 70.2%, respectively.

The authors stated that although their findings were “quite compelling,” the study had limitations. For example, they obtained limited pathologic data on the patients with positive PPIX-PDD results and positive prostate biopsy results who proceeded to undergo radical prostatectomy.

In addition, with a limited follow-up (mean 27 months), they noted that the false-positive PPIX-PDD results must be interpreted cautiously. n

8/21/14 4:39 PM

www.renalandurologynews.com SEPTEMBER 2014

Renal & Urology News 9

CKD May Worsen Surgery Outcomes PREOPERATIVE chronic kidney disease (CKD) may increase the likelihood of adverse surgical outcomes, according to new studies.

In a study of patients who underwent urologic surgery, Marianne Schmid, MD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues found that patients with CKD are at elevated risk for poor perioperative outcomes. Another study, which was led by Kenji Minakata, MD, PhD, of Kyoto University Graduate School of Medicine in Kyoto, Japan, demonstrated that severe CKD is associated a higher risk of in-hospital death and development of acute kidney injury (AKI) following coronary artery bypass grafting (CABG).

The study by Dr. Schmid’s group, which was published online ahead of print in the International Journal of Urology, analyzed data from the National Surgical Quality Improvement Program (NSQIP) dataset. The researchers identified 13,168 patients who underwent either radical prostatectomy (65.4% of the cohort), partial nephrectomy (10.7%), radical nephrectomy (16.1%), and radical cystectomy (7.8%). Of the evaluable patients, 64.3% had reduced kidney function (estimated

In a study, severe CKD raised the risk of in-hospital death after CABG surgery.

glomerular filtration rate [eGFR] of 89 mL/min/1.73 m2 or less).

Compared with no CKD, CKD stages 3 and 4 were independently associated with a significant 1.6 and 2.2 times increased odds of any 30-day major postoperative complication, respectively. CKD stage 3 was associated with a significant 2.1 times increased odds of requiring a blood transfusion.

CKD stages 3, 4, and 5 were associated with a significant 2.6, 3.3, and 1.7 times increased odds of a prolonged length of

hospital stay, respectively, and a significant 4.2, 10.1, and 17.1 times increased odds of 30-day mortality, respectively.

Prior to major urologic surgery, the authors concluded, it is crucial to assess renal function and recognize CKD for perioperative risk stratification to improve postoperative outcomes. “Better perioperative management of CKD in this population will require coordination among urologists and nephrologists with a preoperative risk assessment.”

In a discussion of the study’s noteworthy findings, the researchers underscored the fact that 64.3% of the study cohort had reduced eGFR, with 14.2% of patients classified as CKD stage 3 or worse. More importantly, 17% of the initial cohort had to be excluded due to lack of available data for eGFR calculation.

“To our knowledge, this is the first estimate of the prevalence of CKD in a mixed urological oncological surgery patient cohort,” they wrote.

Dr. Schmid and her colleagues said the main strength of their study was the large sample size and its populationbased nature, “with good-quality prospectively collected clinical information provided by the NSQIP dataset.”

Nevertheless, the study had limitations that hinder the generalizability of the

findings. For example, the NSQIP does not account for various clinical, tumor, and surgical confounders, such as preoperative hydronephrosis, radiology findings, and tumor size, stage, grade, the researchers pointed out.

The study by Dr. Minakata’s group, which was published online in the Circulation Journal, included 1,522 who underwent CABG. The researchers classified subjects according to preoperative eGFR: greater than 90 mL/ min/1.73 m 2 (normal); 60–90 mL/ min/1.73 m2 (mild CKD); 30–59 mL/ min/1.73 m2 (moderate CKD); and less than 30 mL/min/1.73 m2 (severe CKD).

Of the 1,522 subjects, 121 (8%) had normal renal function, 713 (47%) had mild CKD, 515 (34%) had moderate CKD, and 169 (11%) had severe CKD. In multivariate analysis, patients with severe CKD had a significant 3.3-fold increased risk of in-hospital death compared with patients who had no or mild CKD. Patients with moderate and severe CKD had a significant 5.1 and 14.8 times increased risk of AKI, respectively, compared with those who had no or mild CKD. Patients with severe CKD had a 2.5 times increased risk of postoperative infection. n

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New studies demonstrate increased risks of major perioperative and postoperative complications, death

Low Melatonin Found to Raise Advanced PCa Risk LOW URINARY LEVELS of melatonin are associated with an increased risk of advanced prostate cancer (PCa), new findings suggest.

In a prospective study, researchers measured first morning void urinary levels of 6-sulfatoxymelatonin (6-STM), the primary melatonin metabolite, in a cohort of 928 Icelandic men who did not have PCa. During the study period, 111 men were diagnosed with PCa, including 24 with advanced disease. Men with morning 6-STM levels below the median had a significant 4-fold increased risk for advanced PCa compared with men with levels above the median, according to findings published online ahead of print in European Urology. The median follow-up time from urine collection to PCa diagnosis was 2.3 years.

Men who reported sleep problems at baseline had lower morning 6-STM levels compared with those who reported no sleep problems.

009_RUN0914.indd 9

“The study adds to accumulating epidemiologic data investigating associations between circadian disruption or sleep loss and PCa, and provides a potential mechanism and framework for understanding prior results,” the authors noted.

The researchers, led by Sarah C. Markt, ScD, of the Harvard School of Public Health in Boston, noted that the International Agency for Research on Cancer categorized night-shift work as a probable human carcinogen based primarily on breast cancer data. Night-shift work disrupts circadian rhythms and suppresses melatonin secretion through nocturnal exposure to artificial light, they explained. Previous studies have demonstrated that night-shift work is associated with an increased risk of PCa and elevated PSA among men without PCa. For example, a study by Marie-Élise Parent, PhD, of INRS-Institut ArmandFrappier, a component of the University of Quebec in Laval, found that men

who had ever worked at night had a 2.8 times increased PCa risk compared with men who never worked at night, after adjusting for potential confounders.

The study, published in the American Journal of Epidemiology (2012;176:751759), examined data from a population-

New study adds to data linking circadian disruption or sleep loss and prostate cancer. based, case-control study conducted in Montreal that elicited information about job histories—including work hours—from 3,137 men with various incident cancers and 512 controls.

Dr. Markt’s group acknowledged some study limitations. Their study results rest on a single morning urinary 6-STM

measurement, which may not represent long-term levels, they noted. Other limitations included the small number of cases of advanced PCa that were diagnosed and a short follow-up. In addition, men may have had underlying disease at the time of exposure assessment and the study was restricted to elderly men in Iceland. Melatonin levels in this population may differ from those of other populations. Despite the study’s limitations, the researchers said “it is unlikely that underlying biologic impact on PCa pathogenesis would differ.”

Men in the study were participants in the Age, Gene/Environment Susceptibility-Reykjavik study, which collected information by physical examination, questionnaire, and biologic specimens during a 2-day assessment from 2002 to 2006. PCa diagnoses and causes of death were ascertained by linkage with the Icelandic Cancer Registry and Statistics Iceland. n

8/21/14 4:43 PM

14 Renal & Urology News

SEPTEMBER 2014 www.renalandurologynews.com

HHD Has Benefits, Disadvantages DAILY HOME hemodialysis (HHD) is associated with a lower risk of cardiovascular-related hospitalizations but a higher risk of infection-related hospitalizations than convention thrice-weekly in-center hemodialysis (HD), according to a study. Both modalities are associated with a similar risk of all-cause hospitalization.

Eric D. Weinhandl, MS, and colleagues at the Chronic Disease Research Group, Minneapolis Medical Research Foundation in Minneapolis, Minn., studied 3,480 daily HHD and 17,400 matched thrice-weekly in-center HD patients. In an intention-to-treat follow-up, the cumulative incidence of cardiovascular-related admissions after 1 year was 24.1% for the daily HHD patients compared with 26.7% for the conventional HD patients, the researchers reported online ahead of print in the American Journal of Kidney Diseases. This difference translated into an 11% decreased likelihood of cardiovascular-related admissions in the daily HHD versus the conventional HD group. The daily HHD group had an 8% and 13% decreased risk of a first

Visceral Fat Area Predicts RCC Subtype PATIENTS with localized renal cell carcinoma (RCC) are more likely to have clear-cell rather than non-clear-cell RCC if they have a greater visceral fat area (VFA), according to a study published online ahead of print in BJU International.

The study, by Hong-Kai Wang, MD, of Fudan University Shanghai

admission and readmission for cardiovascular causes, respectively, compared with the conventional HD group.

The cumulative incidence of infectionrelated admissions in the intention-totreat follow-up at 1 year was 29.5% in the daily HHD group versus 22.9% in the conventional HD group, a difference that translated into an 18% increased risk of infection-related admissions in the daily HHD group relative to the conventional HD group. Patients in the daily HHD group had a 35% and 3% increased risk of a first admission and readmission for infection-related causes, respectively, compared with those in the conventional HD group.

Weinhandl’s team noted that the cardiovascular benefits of intensive HD have been reported previously. These include reductions in left ventricular mass and both systolic and diastolic blood pressure, decreased use of antihypertensive medications, and increased left ventricular ejection fraction.

The investigators noted that more frequent dialysis might directly increase infection risk. They cited a study of Australian patients undergoing HHD for

New findings confirm the cardiovascular advantages of daily home hemodialysis.

24 hours or more weekly demonstrating that each additional session per week was associated with a 56% increased risk of a first access-related adverse event, with 59% of events involving infection. In addition, HHD may engender risks not present with in-center HD. “Medicare Conditions for Coverage require ESRD [end-stage renal disease] facilities to implement infection control practices,”

they wrote. “At home, no such structure exists. The dialysis area and equipment may become contaminated and patients and care partner may not follow procedures taught during training.”

Weinhandl and his colleagues pointed out that a higher prevalence of catheter use in daily HHD patients could account for increased infection risk, although the prevalence of catheter access among daily HHD patients in the U.S. in 2009 was 24%, which is comparable to contemporary prevalence estimates among U.S. in-center HD patients.

The authors concluded that because cardiovascular disease (CVD) is the leading cause of death in HD patients, the protective association of daily HHD with CVD is important. “The adverse association of daily HHD with infection constitutes a safety concern that requires attention to infection control practices in the home, promptness of infection treatment, and cannulation technique,” they wrote.

“The clinical success of daily HHD likely depends on patients and providers recognizing the advantages and challenges of this increasingly popular modality,” they concluded. n

© PHANIE / SCIENCE SOURCE

It lowers the risk of cardiovascular events, but raises the risk of serious infections, study finds

Hydronephrosis, UTUC Outcomes Linked MODERATE or severe hydronephrosis predicts worse oncologic outcomes in patients with high-grade (HG) upper tract urothelial carcinoma (UTUC), according to a new study.

In these patients, moderate or severe hydronephrosis (HN) is associated with a significant 5.5 times greater likelihood of local or systemic cancer recurrence and 5.2 times greater likelihood of cancer-related death compared with no or mild HN, researchers led by Vitaly Margulis, MD, of the University of Texas Southwestern Medical Center in Dallas,

reported online ahead of print in Urologic Oncology. Moderate or severe HN also is associated with a significant 9.3 times increased risk of muscle-invasive cancer and 4.5 times increased risk of nonorgan-confined cancer.The researchers found no association between degree of HN and oncologic outcomes among patients with low-grade disease.

The study, which was retrospective, included 141 patients who underwent extirpative surgery for localized upper tract urothelial carcinomas. Of these, 113 had HG disease (80%), 49 (35%) had

muscle-invasive disease and 41 (29%) had non-organ-confined disease. At a median follow-up of 34 months, 49 patients (35%) had intravesical recurrence, 28 (20%) experienced local or systemic recurrence, and 24 (17%) died from their cancer.

“Because preoperative imaging is a routinely available diagnostic tool, HN may serve as a surrogate parameter for advanced disease and may be used to help counsel patients with HG tumors toward neoadjuvant chemotherapy and radical surgical treatment,” the investigators concluded. n

Cancer Center in Shanghai, China, and colleagues included 487 patients with localized RCC. Of these, 418 had clear-cell and 69 had non-clearcell RCC. The mean VFA was 25 cm2 greater in the clear-cell than the nonclear-cell patients. In patients with a normal BMI, those in a higher quartile of VFA were more likely to harbor clear-cell RCC than patients with in lower quartile. n

018_RUN0914.indd 14

Obesity Ups Risk of Urinary, Other Cancers HIGH BODY MASS index (BMI) is associated with an elevated risk of urinary and other cancers, according to a recent report.

In a study of a prospective cohort of 54,725 Finns aged 24–74 years and cancer-free at enrollment, increasing BMI was associated with increasing

risk of cancers of the kidney, bladder, liver, colon, and all sites combined in men, and of cancers of the stomach, colon, gallbladder, and ovary in women, researchers Xin Song, a PhD student at the University of Helsinki in Finland, and colleagues reported in the European Journal of Epidemiology

(2014;29:477-487). Results also showed that increasing BMI was associated with decreasing risk of lung cancer in men and lung and breast cancers in women.

Additionally, high BMI in women was associated with an increased overall cancer risk in never smokers but a decreased risk in smokers. n

8/21/14 4:28 PM

www.renalandurologynews.com

SEPTEMBER 2014

Post-Brachytherapy Erectile Function Is Preserved in Most PCa Patients Factors Affecting Erectile Function Preservation

Percent

In a study of prostate cancer patients treated with brachytherapy, a lower Gleason score and lower biologically effective dose of radiation were associated with significantly better 5-year actuarial erectile function preservation rates, as shown here.

80 70 60 50 40 30 20 10 0

Gleason score

Biologically effective dose

73%

18%

74%

52%

Less than 7

7

Less than 150 Gy

150 Gy or higher

Source: Ong WL et al. Long-term erectilefunction following permanent seed brachytherapy treatment for localized prostate cancer. Radiother Oncol (2014;published online ahead of print).

THREE-FIFTHS of men receiving permanent seed brachytherapy (BT) for localized prostate cancer (PCa) have preserved erectile function (EF) 5 years after seed implantation, a study found.

A team led by Jeremy L. Millar, MBChB, associate professor of surgery and public health at Monash University in Melbourne, Australia, conducted a prospective, longitudinal single-center study of 366 patients who underwent BT. All patients completed the International Index of Erectile Function 5-item questionnaire before

treatment and at regular follow-up post-treatment. Of the 366 patients, 277 (76%) reported normal erectile function and 89 (24%) reported mild erectile dysfunction prior to treatment.

The patients were followed up for a median of 41 months. The 5-year actuarial rate of EF preservation was 59%, the investigators reported online ahead of print in Radiotherapy and Oncology.

The 5-year actuarial EF preservation rate was significantly higher in patients with a Gleason score below 7 than in those with a Gleason score of 7 (73%

vs. 18%). The rate also was significantly higher among patients younger than 60 years than older patients (69% vs. 50%) and significantly lower in patients with than without medical comorbidities (47% vs. 64%). In addition, patients who received a biologically effective dose (BED) of radiation below 150 Gy had a significantly higher 5-year actuarial rate of EF preservation than those who had a BED of 150 Gy or greater (74% vs. 52%).

On multivariate analysis, Gleason score was the strongest predictor of EF preservation, with a score below 7 associated with a 3.7 increased likelihood of EF preservation compared with a Gleason score of 7. A BED below 150 Gy was associated with a 60% increased likelihood of EF preservation compared with a BED of 150 Gy or higher.

Dr. Millar told Renal & Urology News that, overall, the results are consistent with a large amount of previous work suggesting good rates of EF preservation with BT for PCa. He noted that the follow-up in the current study was longer than in most previous studies of EF after PCa treatment, and the rates of long-term preservation of EF contrast with the widely-held belief that EF after BT rapidly and materially gets worse after 1 or 2 years. ■

Renal & Urology News 15

Alcohol May Reduce eGFR Loss in Men ALCOHOL consumption may protect against kidney function decline in men.

Researchers at The Catholic University of Korea in Seoul led

by Sang-Wook Song, MD, PhD, studied 5,251 participants in the Korean National Health and Nutrition Examination Survey, a crosssectional survey of Korea civilians.

Among men, heavy alcohol drinkers and binge drinkers had a significant 86% and 58% decreased odds of renal dysfunction (estimated glomerular filtration rate [eGFR] below 60 mL/min/1.73 m2) compared with abstainers after adjusting for age, smoking status, body mass index, and other potential confounders. The investigators observed no significant association between alcohol consumption and eGFR among women.

In addition, in both men and women, the study found no significant association between alcohol consumption and urine albumin to creatinine ratio.

In a report published in Kidney & Blood Pressure Research (2014;39:4049), Dr. Song’s group noted that heavy alcohol consumption or binge drinking may lead to increases in other chronic

Substance Abuse Worsens PCa Outcomes

disease and social problems, including

SUBSTANCE USE disorders may adversely affect outcomes in men with advanced prostate cancer (PCa), researchers reported online ahead of print in Cancer.

In a study of 14,277 men with advanced PCa, those who were diagnosed with a substance use disorder were 2.3 times more likely to be hospitalized, 2.6 times more likely to make an outpatient hospital visit, and 1.7 times more likely to make an emergency department visit than patients without a such a disorder.

For the study, Sumedha Chhatre, PhD, and colleagues at the University of Pennsylvania in Philadelphia, analyzed Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data for men aged at least 66 years who were diagnosed with advanced PCa from 2001 to 2004. They identified individuals who had a claim for substance use disorder in the year before their

considered cautiously, given the other

015_RUN0914.indd 15

cancer diagnosis (pretreatment phase), 1 year after the diagnosis (treatment phase), and an additional 4 years after diagnosis (follow-up phase). Of the 14,277 men, 1,509 (10.6%) had a substance use disorder as defined using the International Classification of Diseases (ICD-9). These disorders included alcoholic psychosis and related, drug psychoses and related, alcohol dependence syndrome, drug dependence, and nondependent use of drugs.

Substance abuse disorder in the followup phase was associated with a 2-fold greater likelihood of hospitalization or hospital outpatient visit and a 1.7-fold greater likelihood of an emergency department visit. In addition, compared with men who did not have a substance use disorder, those who did had 70% higher costs. During the follow-up phase, they had 60% higher costs.

The authors concluded that substance use disorder among Medicare patients

with PCa “can pose unique challenges to the delivery of effective and efficient care. Substance use disorder can be multifaceted and chronic; therefore, it demands intense management similar to that for cancer.” Dr. Chhatre’s group added that there is an urgent need to ascertain the missed opportunities for identifying and treating substance use disorder among elderly PCa patients.

“As a first step, guidelines for prostate cancer care can incorporate screening for substance use disorder as a recommendation,” they wrote.

Compared with men who did not have a substance use disorder, those who did had a significantly lower mean age (72.4 vs. 74.5 years), a significantly greater proportion of African Americans (17.6% vs. 11.2%), and a significantly lower proportion of married men (59.6% vs. 70.8%) and men living in a metropolitan area (79.8% vs. 87.7%). ■

accidents and intentional injuries, and death. “Thus, our results should be harmful effects related to alcohol consumption,” the authors concluded.

The researchers classified mean daily alcohol intake into 3 categories: abstinence (no alcohol-containing drinks within the past year); moderate drinking (men and women: 0.1-39.99 grams and 0.1-19.99 grams of pure alcohol per day, respectively); and heavy drinking (40 grams or more of pure alcohol for men and 20 grams or more per day for women).

For men, the researchers defined binge drinking as consuming 5 or more standard drinks consecutively on a single occasion; for women, it was 4 or more standard drinks. They used the Korean definition of a “standard drink,” which is any drink containing 12 grams of pure alcohol. ■

8/21/14 4:44 PM

20 Renal & Urology News

SEPTEMBER 2014 www.renalandurologynews.com

Practice Management RVUs are a useful gauge of doctors’ productivity, but caseloads and reimbursements are other potentially valuable measures. BY TAMMY WORTH

How RVUs can be used Both small and large practices can use RVUs for various reasons, Burnett said.

Large groups likely use these numbers to create compensation packages.

Small groups can use them when negotiating managed care contracts. They can look at an RVU for a procedure and find out if all of their payers are reimbursing enough for the treatment.

If not, they can use that as a starting point for contract negotiations.

RVUs can also be used to determine the capacity of an organization that might be considering expansion, said Ric Perry, also a director with Navigant. Perry said that RVUs are an objective way to understand how much work physicians should be doing and how much is done in the practice overall. If there is a discrepancy, it may be

PM_RUN0914.indd 20

time to hire another physician to handle some of the load.

If a small group is considering selling to a hospital or negotiating as part of an Accountable Care Organization, RVUs are a good bargaining tool in those discussions, said William Allen, executive medical director of the health solutions practice at FTI Consulting. Proving the group has a high productivity level is invaluable in contract negotiations.

While RVUs are valuable in the feefor-service world, Allen said, they may also be useful as the system moves toward paying for quality as well. One way quality is determined is by the amount of good care delivered per dollar spent. Value can also be highlighted if the quality and productivity measures align.

© THINKSTOCK

W

hether in a small, independent practice where the doctors “eat what they kill” or a large group owned by a hospital, it is important to know the productivity of the providers. For some time, relative value units (RVUs) have been the key way to measure productivity, but they can also be used to gain a better understanding of the practice on the whole.

Some experts say groups should look beyond RVUs to other measurements as well.

RVUs are a marker created by the Centers for Medicare and Medicaid Services to measure the productivity of physicians. An RVU is tabulated for CPT codes by calculating things like the time it takes for an office visit or procedure and the technical skill and training needed to perform a service.

Geographical differences are also taken into account.

“Work RVUs certainly aren’t perfect, but they are still the only systematic way to measure a doctor’s work,” said Jimmy Burnett, a director with Navigant Healthcare’s Physician Performance Improvement Practice.

Proving high productivity may be helpful for small groups considering selling to a hospital.

Surgical yield Tom Ferkovic, managing director of SS&G Healthcare, said RVUs are a good way to measure productivity, but offices can also use simple measures like collections per doctor or number of patients seen.

“The most important thing to determine about what to measure is how the practice makes money,” Ferkovic said.

“What are the key indicators that will make you successful?”

A urology practice’s success, for instance, may be driven by surgical procedures. It would be good to know the surgical yield: how many patients have to be seen to get a patient who needs a procedure. A goal could be to lower that number. If a physician has to see 8 patients for every one surgery, a goal can be set to reduce it to 4 patients for every 1 procedure.

Resource use Another important measurement to understand is whether or not physicians are bringing in new patients and doing new procedures to make sure they are helping the practice grow. It also is important to know

how physicians are using the group’s resources.

“You can have someone with a lot of revenue who is also eating up a lot of expense, so that’s not good either,” he said. “None of this should be looked at in a vacuum.”

One measurement that the most successful practices use is denial percentages, Ferkovic said. This is something that not all groups evaluate, but they should, he said. “If you are tracking RVUs, you have to see if they are

reimbursed,” he said. “If claims are denied, they will get credit for those, but not get paid.”

Ferkovic also offered 2 important points relevant to any kind of measurement. The measurement has to provide information in an extremely timely manner and it should not take hours to put together. The data should be fairly easy for the staff to obtain and evaluate.

Tammy Worth is a freelance medical journalist based in Blue Springs, Mo.

Measuring Productivity In addition to measuring relative value units to determine a doctor’s productivity, practice managers might want to try to answer the following questions: • How many patients does a doctor see?

• What is the surgical yield, the number of patients who have to be seen to identify one who needs a procedure?

• What is a doctor’s collections?

• Are physicians bringing in new patients and doing new procedures to make sure they are helping the practice grow?

• How are physicians using a practice’s resources?

8/21/14 4:46 PM

www.renalandurologynews.com

SEPTEMBER 2014

Renal & Urology News 21

BP Rises As Sodium Intake Increases The association is strongest in consumers of high-sodium diets, hypertensives, and older individuals

Panel: Stents May Help Some RAS Patients RENAL ARTERY STENTING may benefit patients with renal artery stenosis (RAS) who have historically been excluded from modern clinical trials, according to a consensus statement issued by the Society for Cardiovascular Angiography and Interventions (SCAI).

The recent Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial failed to demonstrate benefit from renal stenting over optimal medical therapy, but patients whose condition might be improved by stenting were excluded from the trial.

The recommendations, which are contained in a paper titled, “SCAI Expert Consensus Statement for Renal Artery Stenting Appropriate Use,” were published online in Catheterization and Cardiovascular Interventions. The recommendations are based on an expert panel review of scientific data. The panel concluded that patients most likely to benefit from renal artery stent-

021_RUN0914.indd 21

0.74 mm Hg per gram among those with a sodium excretion of less than 3 grams per day.

In addition, the researchers, led by Andrew Mente, PhD, of McMaster University in Hamilton, Ont., observed a more pronounced effect of sodium excretion on SBP among individuals with hypertension than those without it. SBP increased by 2.49 mm Hg per gram of sodium excretion in hypertensives compared with 1.30 mm Hg per gram in non-hypertensives.

SBP increased by 2.97 mm Hg per gram among individuals aged 55 years and older, 2.43 mm Hg per gram among subjects aged 45–55 years, and 1.96 mm Hg per gram among those younger than 45 years.

Potassium excretion was inversely associated with SBP, significantly more so in individuals with hypertension than in those without it. Each 1-gram increment in potassium excretion per day was associated with a 0.75 mm Hg decrement in SBP and a 0.06 mm Hg decrement in DBP.

ing are those with cardiac disturbance syndrome or “flash” pulmonary edema; patients whose high blood pressure (BP) has not been controlled by 3 or more medications at maximal tolerated doses; and those with blockages in both kidneys or severe blockages in a single functioning kidney where BP or renal dysfunction cannot be managed medically.

Patients with mild or moderate blockages (less than 70%), those with longstanding loss of blood flow and those with complete blockage of the renal artery are typically not good candidates for renal artery stenting, according to the panel.

“The CORAL trial answered many of our questions about renal artery stenting, but some patients who are seeking treatment today were not included in CORAL, including patients in whom optimal medical therapy failed,” the paper’s lead author, Sahil A. Parikh, MD, said in an SCAI press release.

“The new recommendations were developed to help physicians evaluate treatment options for the broad range of patients with renal artery disease.”

Dr. Parikh is assistant professor of medicine at Case Western Reserve University School of Medicine in Cleveland. ■

Sodium’s Effect on Blood Pressure Increasing sodium excretion is associated with increasing blood pressure, according to a new study of 102,216 adults from 18 countries. Individuals who consume a high-sodium diet are among those in whom the association is particularly strong. Shown here are the increments in systolic blood pressure per gram of urinary sodium according to subjects’ 24-hour sodium excretion.

3.0

24-hour sodium excretion

2.5

2.58 mm Hg

2.0

mm Hg

INCREASING urinary sodium concentrations—a surrogate for sodium intake—are associated with increasing blood pressure, particularly among individuals consuming high-sodium diets, those with hypertension, and older people, according to a new report in The New England Journal of Medicine (2014;371:601-611).

In a study of 102,216 adults from 18 countries, researchers found that each 1-gram increment in estimated sodium excretion was associated with a 2.11 mm Hg increment in systolic blood pressure (SBP) and a 0.78 mm Hg increment in diastolic blood pressure (DBP).

The association was most pronounced among subjects with a sodium excretion greater than 5 grams per day. In these individuals, each 1-gram increment in sodium excretion was associated with a 2.58 mm Hg increment in SBP. Among those with a sodium excretion of 3–5 grams per day, each 1-gram increment in sodium excretion was associated with a significant 1.74 mm Hg increment in SBP. SBP increased by a non-significant

1.74 mm Hg

1.5 1.0 0.5 0.0

0.74 mm Hg Less than 3 grams

3-5 grams

More than 5 grams

Source: Mente A et al. Association of urinary sodium and potassium excretion with blood pressure. N Engl J Med 2014;371:601-611.

In a separate report published in the same journal issue (pp.624-634), researchers reported the findings of a study suggesting that 1.65 million deaths from cardiovascular causes that occurred globally in 2010 were attributable to sodium consumption above a reference level of 2.0 grams

per day. Of these deaths, 61.9% occurred in men and 38.1% occurred in women. The researchers, led by Dariush Mozaffarian, MD, DrPH, of the Harvard School of Public Health in Boston, noted that these deaths accounted for nearly 1 of every 10 cardiovascular-related deaths. ■

MRI Can Accurately Detect Significant Prostate Cancer DIFFUSION-WEIGHTED magnetic reso-

Of the 111 men, 93 had PCa, which

nance imaging (DW-MRI) noninvasively

was significant in 80 cases and insignifi-

detects significant prostate tumors

cant in 13, the investigators reported in

with a high probability and without

The Journal of Urology (2014;192:737-

contrast medium or an endorectal coil,

742). The researchers defined sig-

according to a new study.

nificant PCa as any tumor with a 1 cm

Lauren J. Bains, MD, and colleagues

or greater diameter, extraprostatic

at the University of Bern in Switzerland

extension, or a Gleason score of 7 or

prospectively studied 111 men with

greater. The sensitivity and specificity

prostate and/or bladder cancer who

of DW-MRI for detecting significant PCa

underwent DW-MRI of the pelvis without

was 89%–91% and 77%–81%, respec-

an endorectal coil prior to radical prosta-

tively, for the 3 readers. The median

tectomy (78 patients) or cystoprostatec-

reading time was 13–18 minutes, with

tomy (33 patients). based on qualitative

good interreader agreement.

imaging analysis, 3 independent readers

“With all of these advantages DW-MRI

blinded to clinical and pathologic data

has the potential to rapidly disseminate

assigned a prostate cancer (PCa) suspi-

into clinical practice for PCa manage-

cion grade. The final pathology served

ment,” the authors concluded.

as the reference standard. “For study

It may improve patient stratification

purposes only the largest tumor focus

for individualized treatment options,

of the prostate (index lesion) was con-

such as by discriminating tumors

sidered since it is postulated by some

requiring curative treatment from those

investigators to dictate PCa prognosis,”

that may benefit from expectant man-

the researchers noted.

agement, Dr. Bain’s group noted. ■

8/21/14 4:46 PM

26 Renal & Urology News

SEPTEMBER 2014 www.renalandurologynews.com

CME FEATURE

Shared Decision Making in Managing Idiopathic and Neurogenic OAB Communicating effectively about appropriate options and eliciting patient input can improve outcomes through better efficacy, tolerability, and adherence.

Release Date: September 15, 2014 Expiration Date: September 15, 2015 Estimated time to complete the educational activity: 1 hour This activity is provided by Global Education Group in collaboration with Haymarket Medical Education (HME), and is supported by an educational grant from Allergan, Inc., and Astellas Pharma US, Inc. STATEMENT OF NEED: Data suggest that physicians often fail to communicate adequately with patients to select individualized therapy. Along with the prevalence of overactive bladder (OAB) and the frequent failure of initial therapy, this points to the need for urology specialists to heighten their diagnostic acuity for OAB and its comorbidities, and to strengthen their ability to communicate with patients to individualize treatment, improving efficacy, safety, and adherence.

TARGET AUDIENCE: This activity has been designed to meet the educational needs of urologists, urogynecologists, and other health care providers who treat patients with bladder dysfunction.

EDUCATIONAL OBJECTIVES: After completing the activity, the participant should be better able to: • Assess idiopathic overactive bladder (OAB), particularly in patients with comorbid diseases, recognizing the impact on quality of life • Assess treatment options for OAB based on the patient’s needs, considering efficacy, safety, and improved adherence • Implement diagnostic strategies to identify patients with neurogenic detrusor overactivity (NDO) to more efficiently individualize treatment • Select, assess, and modify treatment for NDO to provide optimal individualized therapy • Discuss how to improve patient communication regarding current and emerging therapies and the impact of adherence ACCREDITATION STATEMENT: Global Education Group is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT: Global Education Group designates this enduring educational activity for a maximum of 1.0 AMA PRA Category 1 Credit TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

DISCLOSURE OF CONFLICTS OF INTEREST: Global Education Group (Global) requires instructors, planners, managers, and other individuals and their spouse/ life partner who are in a position to control the content of this activity to disclose any real or apparent conflict of interest they may have as related to the content of this activity. All identified conflicts of interest are thoroughly vetted by Global for fair balance, scientific objectivity of studies mentioned in the materials or used as the basis for content, and appropriateness of patient care recommendations.

The faculty reported the following financial relationships or relationships to products or devices they or their spouse/life partner have with commercial interests related to the content of this activity: Name of Faculty Reported Financial Relationship Michael B. Chancellor, MD Consultant/Independent Contractor: Allergan, Targacept Inc., Lipella Pharmaceuticals Inc., Cook Group Incorporated.

Grant/Research Support: Cook Group Incorporated, Medtronic, Inc. Honoraria: Allergan.

David A. Ginsberg, MD

Consultant/Independent Contractor: Allergan.

Honoraria: Allergan, Medtronic, Inc.

Victor W. Nitti, MD

Consultant/Independent Contractor: Allergan, Astellas, AMS, Coloplast, Ono Pharmaceutical Co., Ltd., Pneumoflex Systmes, LLC, Serenity Pharmaceuticals, LLC, Theracoat.

MICHAEL B. CHANCELLOR, MD; DAVID A. GINSBERG, MD; VICTOR W. NITTI, MD

F

or patients with symptoms of idiopathic and neurogenic overactive bladder (OAB), challenges facing the clinician include determining what they hope to gain from treatment. The answers can help formulate a treatment plan that patients find acceptable, increasing adherence, and circumvent treatment failure.

In shared decision making, clinicians and patients share the best available evidence when making decisions, and patients are supported to consider options to achieve informed preferences.1,2 Patients should be proactive in describing concerns and preferences in choosing treatment and the physician should elicit this information from the patient and consider it, integrating good communication skills and using patient decision support tools.1

To view examples of shared decision making in 3 actual patient-clinician videos (with excerpts of faculty discussions) cited in this article, go to myCME.com.

For either idiopathic OAB or neurogenic detrusor overactivity (NDO), eliciting patient feedback and sharing the best available evidence when describing relevant options are important in achieving patient satisfaction (see Patient-Clinician Video A with Dr. Nitti on myCME.com).

Speakers Bureau: Allergan.

Stock Shareholder: Serenity Pharmaceuticals, LLC. The planners and managers, Ashley Marostica, RN, MSN, Amanda Glazar, PhD, Andrea Funk, and Stacey Hansen of Global Education Group, have disclosed that they have no relevant financial relationships or conflicts of interest.

The content managers, Debra A. Hughes, MS, Mary Jo Krey, Lori Marrese, and Jody A. Charnow of Haymarket Medical Education, have disclosed that they have no relevant financial relationships or conflicts of interest.

METHOD OF PARTICIPATION: There are no fees for participating in and receiving CME credit for this activity. During the period September 15, 2014 through September 15, 2015, participants must: 1) read the learning objectives and faculty disclosures, 2) study the educational activity, 3) complete the posttest and submit it online. Physicians may register at www.myCME.com/renalandurologynews, and 4) complete the evaluation form online.

A statement of credit will be issued only upon receipt of a completed activity evaluation form and a completed post-test with a score of 70% or better.

Provided by lobal Education Group G

W14-124 OAB_RUN_Sept2014 v10.indd 26

In collaboration with Haymarket Medical Education

Supported by an educational grant from Allergan, Inc. and Astellas Pharma US, Inc.

Michael B. Chancellor, MD, (left) Professor, Oakland University; William Beaumont School of Medicine, Director of Neurourology Program; Department of Urology, Beaumont Hospital, Royal Oak, Royal Oak, Michigan David A. Ginsberg, MD, (center) Associate Professor of Clinical Urology, Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California; Chief of Urology, Rancho Los Amigos National Rehabilitation Center, Downey, California Victor W. Nitti, MD, (right) Vice Chairman of Urology; Professor of Urology, New York University Langone Medical Center, New York, New York

8/21/14 4:48 PM

www.renalandurologynews.com SEPTEMBER 2014

OAB is defined as urgency, with or without urgency urinary incontinence (UUI), usually with frequency and nocturia, in the absence of pathologic or metabolic conditions that might explain these symptoms.3 Evaluation of urinary incontinence (UI) should include a history to delineate other causes (Table 1).

The American Urological Association (AUA) and the Society of Urodynamics, Female Pelvic Medicine, & Urogenital Reconstruction (SUFU) guideline offers a diagnosis and treatment algorithm for non-neurogenic OAB in adults.4 Minimum requirements are a history, examination, and urinalysis. To confirm a diagnosis of OAB and exclude other disorders, a urine culture, postvoid residual volume, and bladder diaries may be necessary. In the uncomplicated patient, urodynamics, cystoscopy, and renal/bladder ultrasound should not be used initially.

First-Line Treatments for OAB

Behavioral therapy. This approach has reduced the frequency of incontinence by 50% to 80%5,6 in both men7 and women.6 It may comprise bladder training, incremental voiding schedules, dietary modification, and/or pelvic floor muscle training.

Weight loss can also improve UI.8 A 6-month program that resulted in a weight loss of 8.0% in obese women reduced overall incontinence episodes Table 1. Urinary Incontinence Evaluation: Other Causes of Symptoms Local pathology Infection Bladder stones Bladder tumor Interstitial cystitis Outlet obstruction Metabolic Diabetes Polydipsia Medications Diuretics Antidepressants Antihypertensives Hypnotics and sedatives Analgesics and narcotics Other factors Pregnancy Psychological Estrogen deficiency

W14-124 OAB_RUN_Sept2014 v10.indd 27

by 47% vs. 28% in the control group.

UUI episodes were reduced by 42% and 26%, respectively.

The combination of behavioral therapy plus antimuscarinics has also been explored. In elderly women, behavioral therapy alone reduced UI by 58% vs.

89% when behavioral therapy was combined with oxybutynin. In contrast, oxybutynin alone reduced UI by 73%, vs. 84% when oxybutynin was combined with behavioral therapy.9 Tolterodine combined with behavioral therapy resulted in a greater decrease in UI and patient satisfaction than behavioral therapy alone.10 Antimuscarinics alone, as well as antimuscarinics plus behavioral therapy, were more effective than behavioral therapy alone. However, it is unclear if antimuscarinics plus behavioral therapy are more effective than antimuscarinics alone.11 One challenge noted with behavioral therapy is adherence appears to diminish over time.12

Second-Line Treatments for OAB

Antimuscarinics. In adults, the AUA/ SUFU guideline recommends the following oral antimuscarinics (listed in alphabetical order, no hierarchy implied): darifenacin (Enablex), fesoterodine (Toviaz), oxybutynin (Ditropan, Ditropan XL), solifenacin (Vesicare), Table 2. AUA/SUFA Guideline for OAB (Non-Neurogenic): Precautions When Using Antimuscarinics Do not use antimuscarinics in patients with narrow-angle glaucoma unless approved by the treating ophthalmologist.

tolterodine (Detrol LA), and trospium (Sanctura). Extended-release (ER) formulations are preferred over immediate-release (IR) due to a lower rate of dry mouth. Transdermal oxybutynin may also be offered. To improve outcomes in patients with issues related to efficacy or tolerability, the dose may be modified or a different antimuscarinic prescribed.4 Antimuscarinics have comparable efficacy and safety.4,13 The choice of medication depends on the patient’s history of prior antimuscarinic use, adverse events (AEs), patient preferences, comorbidities, use of other medications, and the availability of specific medications.4 AEs, particularly dry mouth and constipation, are commonly cited as the reason for the common discontinuation of antimuscarinics, warranting precaution (Table 2).

Frailty in elderly patients may encompass mobility deficits, weight loss, weakness, and cognitive deficits.4,14 Medications in older people can have a lower therapeutic index and a higher AE profile, and the effects of polypharmacy should be considered.4 The elderly are more prone to the cognitive deficits of antimuscarinics.15 In patients with dementia, antimuscarinics are contraindicated or must be used with extreme caution.16 Beta 3 -agonists. Selective beta 3 agonists for OAB avoid activation of the ß1- and ß2-adrenergic receptor as well as undesirable AEs such as increased heart rate and muscle tremors. 4 The ß 3 -agonist mirabegron (Myrbetriq 25 mg and 50 mg) was approved for OAB in the United States in 2012 for once-daily use (after the

Use antimuscarinics with extreme caution in patients with impaired gastric emptying or a history of urinary retention.

Manage constipation and dry mouth before abandoning effective antimus­ carinic therapy.

Use caution in prescribing antimuscarinics in patients who are using other medications with anticholinergic properties.

Use caution in prescribing antimuscarinics in the frail OAB patient.

Patients refractory to therapy should be evaluated by an appropriate specialist if they desire additional therapy.

Mean change from baseline

OAB

Renal & Urology News 27

initial AUA/SUFU guideline was published; included in the newly revised Guideline) (Figure 1). No dry mouth or constipation is seen, but patients should be monitored for hypertension (see Patient-Clinician Video B with Dr. Ginsberg on myCME.com).

Pooled analysis of phase 3 studies showed mean change from baseline in the number of incontinence episodes per 24 hours was better with mirabegron 50 mg vs. placebo (-1.48 vs. -1.09); also reduced was mean number of micturitions per 24 hours, -1.77 vs.

-1.18, respectively; the number of severe urgency episodes (grade 3 or 4) per 24 hours (-1.93 vs. -1.20); and number of UUI episodes per 24 hours (-1.28 vs. -0.93; all P<0.05). Patients in all mirabegron groups combined had approximately twice the rate of hypertension as those receiving placebo.17

Third-Line Treatments for OAB

Sacral neuromodulation (InterStim®).

This device stimulates the S3 nerve to “modulate” inappropriate reflexes.

Following first-stage stimulation, if patients show >50% improvement, a permanent implant involving minor surgery may be considered.

Patients 5 years postimplant18,19 have shown >50% improvement in 68% of patients with UI and >50% improvement in the 56% of those with urgencyfrequency.19 The success rate for refractory UUI was 87% at 1 month and 62% at 5 years, with 80% of patients still using sacral neuromodulation at 5 years.18 In a prospective, randomized, multicenter trial evaluating the 6-month success rate of sacral neuromodulation

0.00

Placebo (n=415)

-0.25

Mirabegron 25 mg (n=410)

-0.50

Mirabegron 50 mg (n=426)

-0.75 -1.00 -1.25 -1.50 -1.75 -2.00 -2.25 Baseline

4 Week

8 12

http://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/ 202611Orig1s000TOC.cfm

Gormley EA, Lightner DJ, Burgio KL, et al; AUA/SUFU. J Urol. 2012;188(6 Suppl):2455-2463.

Figure 1. Mirabegron: Mean (SE) Change from Baseline in Mean Number of Micturitions per 24 Hours – Study 3

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28 Renal & Urology News

SEPTEMBER 2014 www.renalandurologynews.com

vs. standard medical therapy in 147 patients with mild-to-moderate OAB symptoms, the sacral neuromodulation group showed significant improvements in quality of life (QoL) vs. the standard medical therapy group (all P < 0.001).

Also, 86% of sacral neuromodulation subjects reported improved or greatly improved urinary symptom interference score at 6 months vs. 44% for standard medical therapy subjects.20 Percutaneous Tibial Nerve Stim­ ulation (PTNS). The only approved PTNS system (Urgent® PC) is a minimally invasive neuromodulation system that provides retrograde electrical stimulation of the sacral nerve plexus.

The system targets specific neural tissue and “jams” the pathways transmitting unwanted signals. The OrBIT (Overactive Bladder Innovative Therapy) trial found both PTNS and tolterodine ER to be equally effective in 100 patients.21 PTNS responders in the OrBIT trial were treated for an additional 9 months, with improved efficacy seen at 12 months.22 Botulinum toxins. Although several botulinum toxin compounds are in clinical use, the doses among them are not interchangeable: • OnabotulinumtoxinA (OnaBoNTA) – Botox • AbobotulinumtoxinA (AboBoNTA) – Dysport • IncobotulinumtoxinA (IncoBoNTA) – Xeomin • RimabotulinumtoxinB (RimaBoNTB) – Myobloc/ NeuroBloc OnaBoNTA is the only botulinum toxin approved to treat OAB in the US (approved after the initial AUA/SUFU guideline was published, now in the revised Guideline), and is the main botulinum toxin with any published clinical data in OAB. At 12 weeks, onaBoNTA significantly reduced UUI vs. placebo (60.8% vs.

29.2%23; 62.8% vs. 26.8%24), with mean percent change from baseline favoring onaBoNTA in daily episodes of incontinence (-47.9 vs. -12.5 23; -53.1 vs.

-16.824), urgency (-31.6 vs. -10.0 23; -41.1 vs. -8.424), micturitions (-16.9 vs. 4.123; -19.7 vs. -6.0 24), and nocturia (-20.2 vs.

0.223; -25.1 vs -8.8 24). All patients studied were refractory to prior therapy with antimuscarinics. Patients also reported greater improvement in the

W14-124 OAB_RUN_Sept2014 v10.indd 28

QoL measures. A higher percentage of patients on the onaBoNTA arm, compared with placebo, initiated clean intermittent catheterization (6.1% vs.

0 23; 6.9% vs. 0.7%24) and tested positive for a urinary tract infection (UTI) (24.5% vs. 9.2%23; 24.1% vs. 9.6%24).

The duration of effect of onaBoNTA was defined by patient request for retreatments; they were eligible for retreatment if they requested it, had a minimum of 12 weeks from the previous treatment, had at least 2 UUI episodes on a 3-day diary, and had a postvoid residual (PVR) of <100 mL.23,24 Median time to retreatment request was 166 days (~24 weeks). Efficacy was sustained for up to 5 treatments,25 and maintained efficacy with repeat injection has been observed in the literature for both OAB and NDO.26,27 Augmentation cystoplasty. Reserved for patients refractory to conservative management and other therapies,4 this surgery carries a significant risk profile, including bladder stones, mucus, small-bowel obstruction, surgical complications, and perforation.28

NDO Neurogenic bladder dysfunction can impact upper urinary tract function, affecting renal function, and can cause urinary incontinence, stones, and UTIs. It can also affect QoL, skin care problems, and sexual function. A significant number of patients with neurogenic bladder dysfunction may be both incontinent and require a wheelchair.

Bladder management goals include preserving the upper urinary tract, treating symptoms (incontinence, urgency), preventing UTIs, avoiding bladder overdistention, maintaining adequate bladder capacity with low compliance, promoting low-pressure micturition, minimizing use of indwelling catheter, and selecting therapy that minimizes risks to the patient while maximizing social, emotional, and vocational acceptability.29 Table 3 summarizes the evaluation of bladder function in patients with neurologic disease.

Comprehensive History History taking should cover a patient’s life span, with a special focus on pain, infection, hematuria, and fever that may point to the need for additional diagnostic testing. History should include:30

© BIGSTOCK

CME FEATURE

In shared decision making, clinicians and patients share the best available evidence and patients are supported to consider options to achieve informed preferences.

• Specific urinary history —— Mode/type of voiding (eg, catheterization); relief after voiding —— Bladder sensation —— Enuresis —— Initiation of micturition (normal, precipitate, reflex, strain, Credé) —— Interruption of micturition (normal, paradoxical, passive) —— Voiding/bladder diary where appropriate • Bowel history —— Rectal sensation, fecal incontinence —— Desire to defecate; defecation pattern; initiation of defecation • Sexual history —— Genital sensation —— Genital or sexual dysfunction symptoms • Past and present general, medical, social factors —— Hereditary/familial risk factors —— History of diabetes, stroke; history of accidents or surgeries, especially involving the spine or central nervous system —— QoL, social history (smoking, alcohol, drug use), life expectancy

Physical Examination Physical examination should include a focused neurourologic evaluation. In addition to standard evaluation of the abdomen, back, rectum, pelvis, and genitalia, clinicians need to evaluate the dermatomes of spinal cord levels L2-S4 and urogenital and other reflexes in the lower spinal cord.30

Sensations to S2-S5 nerves on both sides should be assessed to determine their presence, type of sensation, and whether the bulbocavernous, perianal, and knee and ankle reflexes are increased, normal, reduced, or absent.

Plantar responses (Babinski) should also be tested. The presence of anal sphincter tone will predict voluntary contractions of anal sphincter and pelvic muscles. A prostate examination in men and a pelvic prolapse examination in women should be done.30 Urgency and other urinary symptoms in neurologic patients may stem from non-neurologic etiologies. Conditions that should be ruled out include Table 3. Evaluating Bladder Function in Patients With Neurologic Disease History and physical examination1 Neurologic examination1 Urinalysis, blood chemistry 1-3 Bladder and renal ultrasound (if indicated)3 Urodynamic testing • Uroflow1,2 • Postvoid residual volume2 • Cystometrogram with or without electromyogram1,2 • Multichannel urodynamic testing1 1. P annek J, et al. European Association of Urology (EAU); 2011 Mar. http://www.uroweb.org/gls/ pdf/19_Neurogenic_LR%20II.pdf. Accessed July 18, 2014.

2. Rackley R, et al. Neurogenic bladder. http:// emedicine.medscape.com/article/453539-overview.

Updated November 23, 2011. Accessed July 18, 2014.

3. Abrams P, et al. Neurourol Urodyn. 2010;29:213-240.

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Renal & Urology News 29

CME FEATURE bladder abnormalities arising from bladder cancer, calculus, or interstitial cystitis; prostate or urethral abnormalities, prostate cancer or urethral stones in men/pelvic prolapse in women; and urogenital infections.

Urodynamic Studies

Urodynamic studies (see Table 3) can help guide management because symptoms and physical examination do not always correlate with type, extent, or level of injury or risk to renal function; in patients with spinal cord injury, the level of injury does not always correlate with urodynamic findings.31 The incidence of bladder dysfunction is among the highest in patients with spinal cord injury (68%).

However, there are a variety of other neurologic disorders where bladder dysfunction is commonly seen, including multiple sclerosis (incidence of 37%-72%), myelodysplasia (50%72%), Parkinson’s disease (35%-70%), diabetes (9%-33%), and cerebrovascular disease (12%-19%).32

Treatment Options for NDO Treatment options for NDO include, for failure to empty: behavioral modification (ie, pelvic floor exercises), clean intermittent catheterization (CIC), botulinum toxin A injection into the sphincter, suprapubic catheter, indwelling catheter, sphincterotomy, urethral stent, and urinary diversion. For failure to store, treatment options include: behavioral therapy (ie, diet and fluid intake, timed voiding), antimuscarinics, beta3-agonist, botulinum toxin A injections into the detrusor, indwelling catheter, and reconstruction.

Behavioral therapy. Treatment includes behavioral therapy that may be combined with antimuscarinics.33 Behavioral modifications comprise moderating fluid intake, reducing or eliminating caffeine, pelvic floor muscle exercises, biofeedback, timed voiding, toileting assistance, bladder education/retraining, and weight loss.

Pharmacologic approaches. These include the oral antimuscarinic/anticholinergic agents listed previously.

The beta3-agonist mirabegron as well as some other agents also may be tried; however, none of these pharmacologic agents are approved for NDO. Botulinum toxin. This approach may be appropriate for some patients with NDO (see Patient-Clinician Video C with Dr. Chancellor on myCME.com).

OnabotulinumtoxinA. Two phase 3 randomized, placebo-controlled, pivotal studies in patients with incontinence due to detrusor overactivity associated with a neurologic condition (eg, spinal cord injury or multiple sclerosis) who were either spontaneously voiding or using catheterization found that onaBoNTA significantly reduced weekly incontinence episodes and increased incontinence QoL. 34,35 OnaBoNTA at a dose of 200 U in 135 patients (Figure 2) and 300 U in 132 patients decreased mean urinary incontinence at week 6 by 21 and 23 episodes per week, respectively, vs. 9 episodes per week in 149 patients on placebo (each dose P<0.001). Also, maximum cystometric capacity, maximum detrusor pressure during the first involuntary detrusor contraction (PdetmaxIDC), and Incontinence-Quality of Life (I-QoL) score were significantly

Study 11 Week 2 Week 6†

Study 22 Week 12

Week 2 Week 6†

-5

31%

-10 -15 -20 P<0.05*

65% P<0.001*

-25

-10

36%

-15

P<0.001*

67% P<0.05*

-25

OnaBoNTA 200 U, n=135

Placebo, n=149

Mean baseline UI frequency: OnaBoNTA 200 U = 32.3/wk Placebo = 28.3/wk

OnaBoNTA 200 U, n=92

Placebo, n=92

Mean baseline UI frequency: OnaBoNTA 200 U = 32.5/wk Placebo = 36.7/wk

† Primary end point = mean change from baseline in weekly frequency of UI episodes at week 6. *Pairwise comparison vs. placebo 1. Ginsberg D, et al. J Urol. 2012;187:2131–2139; 2. Adapted from Cruz F, et al. Eur Urol. 2011;60:742–750.

Figure 2. OnaBoNTA Significant Reduction in Weekly Incontinence Episodes

W14-124 OAB_RUN_Sept2014 v10.indd 29

AbobotulinumtoxinA. A study of the efficacy and dose dependency of aboBoNTA in 13 men and 9 women with NDO who received successive doses injected repeatedly into the bladder showed a constant effect following 4 injections. Both doses—500 U (in 12 patients) and 1000 U (in 10 patients)— showed similar duration and efficacy, which was slightly better, although nonsignificant, with 1000 U.36

Surgical Procedures for NDO

-5

-20

• The need for CIC is temporary.

• If CIC must be used, it does not mean that all voids involve CIC. • The risk of CIC at 100 U for OAB is ~5%.

• The risk of CIC at 200 U for NDO is ~20%.

• If a patient has neurogenic bladder dysfunction and is spontaneously voiding, consider using the 100 U dose to decrease the risk of postinjection need for CIC.

Week 12

0

Mean change from baseline (episodes/week)

Mean change from baseline (episodes/week)

0

improved over values in the placebo group (each dose P<0.001).34 In patients with multiple sclerosis (n=154) or spinal cord injury (n=121), at week 6, onaBoNTA 200 U and 300 U significantly reduced UI episodes per week (-21.8 and -19.4, respectively) vs. placebo (-13.2; P<0.01); onaBoNTA benefit was observed by the first posttreatment study visit at week 2.

Improvements in maximum cystometric capacity, PdetmaxIDC, and I-QoL total score at week 6 were significantly greater with both onaBoNTA doses than with placebo (P<0.001).35 The approved dose of onaBoNTA is 200 U. The most frequent AEs were UTI, urinary retention, hematuria, fatigue, and insomnia.34,35 With regard to retention, clinicians should keep in mind:

Sacral neuromodulation. When sacral neuromodulation is considered, patients who respond to neuromodulation during the test phase proceed to full implantation of pulse generators and leads. Programming is required.37 Sacral neuromodulation is not approved for NDO. Patients with defined neurologic abnormalities such as multiple sclerosis or spinal cord injury may benefit from sacral neuromodulation, but studies in this population of patients have been few38,39 and sacral neuromodulation for NDO is an off-label use.

Augmentation cystoplasty. This reconstruction may be indicated for patients with refractory symptoms and those with risk or progression of upper tract deterioration. There is a high likelihood that lifelong intermittent catheterization will ultimately be required.

Risks such as stones, metabolic and nutritional abnormalities, renal insufficiency, and malignancy are best treated through early recognition and prompt therapy.40,41

Evaluating Outcomes For OAB, clinicians should use a voiding diary and global response for QoL to determine effect of treatment as well as validated OAB-specific questionnaires, and should query patients about AEs. Although global response scales for QoL and a voiding diary to determine effect of treatment for NDO are important, the clinician also may need to know urodynamic testing outcomes, especially in patients with elevated detrusor pressures, to assess that there is no risk of future upper tract damage.

Conclusion “Treatment success” is complex and based on individual patient expectations. Communicating with and explaining all appropriate options to the patient, based on the differing efficacy and AE profiles of the treatments available for OAB and NDO as well as eliciting patient input, can enhance outcomes. n

References 1. Elwyn G, Frosch D, Thomson R, et Al. Shared decision making: a model for clinical practice.

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2. Elwyn G, Laitner S, Coulter A, et al. Implementing shared decision making in the NHS. BMJ. 2010;341:C5146.

3. Abrams P, Cardozo L, Fall M, et al. The standardization of terminology in lower urinary tract function: report of the standardisation sub-committee of the International Continence Society. Urology.

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4. Gormley EA, Lightner DJ, Burgio KL, et al; American Urological Association; Society of Urodynamics, Female Pelvic Medicine, & Urogenital Reconstruction. Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline. J Urol. 2012;188(6 Suppl):2455-2463.

5. Fantl JA, Wyman JF, McClish DK, et al. Efficacy of bladder training in older women with urinary incontinence. JAMA. 1991;265(5):609-613.

6. Jarvis GJ. A controlled trial of bladder drill and drug therapy in the management of detrusor instability.

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7. Burgio KL, Goode PS, Johnson TM, et al. Behavioral versus drug treatment for overactive bladder in men: the Male Overactive Bladder Treatment in Veterans (MOTIVE) trial. J Am Geriatr Soc. 2011;59(12):2209-2216.

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CME FEATURE 8. Vissers D, Neels H, Vermandel A, et al. The effect of non-surgical weight loss interventions on urinary incontinence in overweight women: a systematic review and meta-analysis. Obes Rev. 2014 Apr 22. doi: 10.1111/obr.12170.

9. Burgio KL, Locher JL, Goode PS. Combined behavioral and drug therapy for urge incontinence in older women. J Am Geriatr Soc. 2000;48(4):370-374.

10. Burgio KL, Kraus SR, Menefee S, et al; Urinary Incontinence Treatment Network. Behavioral therapy to enable women with urge incontinence to discontinue drug treatment: a randomized trial. Ann Intern Med. 2008;149(3):161-169.

11. Rai BP, Cody JD, Alhasso A, Stewart L. Anticholinergic drugs versus non-drug active therapies for non-neurogenic overactive bladder syndrome in adults. Cochrane Database Syst Rev. 2012 Dec 12;12:CD003193. doi: 10.1002/14651858.CD003193.pub4.

12. Borello-France D, Burgio KL, Goode PS, et al.

Adherence to behavioral interventions for urge incontinence when combined with drug therapy: adherence rates, barriers, and predictors. Phys Ther.

2010;90(10):1493-1505.

13. Chapple CR, Khullar V, Gabriel Z, et al. The effects of antimuscarinic treatments in overactive bladder: an update of a systematic review and meta-analysis.

Eur Urol. 2008;54(3):543-562.

14. Sternberg SA, Wershof Schwartz A, Karunananthan S, et al. The identification of frailty: a systematic literature review. J Am Geriatr Soc. 2011;59(11):2129-2138.

15. Donnellan CA, Fook L, McDonald P, Playfer JR. Oxybutynin and cognitive dysfunction. BMJ. 1997;315(7119):1363-1364.

16. Tsao JW, Heilman KM. Transient memory impairment and hallucinations associated with tolterodine use.

N Engl J Med. 2003;349(23):2274-2275.

17. Nitti VW, Khullar V, van Kerrebroeck P, et al.

Mirabegron for the treatment of overactive bladder: a prespecified pooled efficacy analysis and pooled safety analysis of three randomized, double-blind, placebo-controlled, phase III studies. Int J Clin Pract.

2013;67(7):619-632.

18. Groen J, Blok BF, Bosch JL. Sacral neuromodulation as treatment for refractory idiopathic urge urinary incontinence: 5-year results of a longitudinal study in 60 women. J Urol. 2011;186(3):954-959.

19. van Kerrebroeck PE, van Voskuilen AC, Heesakkers JP, et al. Results of sacral neuromodulation therapy for urinary voiding dysfunction: outcomes of a prospective, worldwide clinical study. J Urol.

2007;178(5):2029-2034.

20. Siegel S, Noblett K, Mangel J, et al. Results of a prospective, randomized, multicenter study evaluating sacral neuromodulation with InterStim therapy compared to standard medical therapy at 6-months in subjects with mild symptoms of overactive bladder. Neurourol Urodyn. 2014 Jan 10. doi: 10.1002/ nau.22544. [Epub ahead of print] 21. Peters KM, MacDiarmid SA, Wooldridge LS, et al.

Randomized trial of percutaneous tibial nerve stimulation versus extended-release tolterodine: results from the overactive bladder innovative therapy trial.

J Urol. 2009;182(3):1055-1061.

22. MacDiarmid SA, Peters KM, Shobeiri SA, et al. Longterm durability of percutaneous tibial nerve stimulation for the treatment of overactive bladder. J Urol.

2010;183(1):234-240.

23. Nitti VW, Dmochowski R, Herschorn S, et al; EMBARK Study Group. OnabotulinumtoxinA for the treatment of patients with overactive bladder and urinary incontinence: results of a phase 3, randomized, placebo controlled trial. J Urol. 2013;189(6):2186-2193.

24. Chapple C, Sievert KD, MacDiarmid S, et al.

OnabotulinumtoxinA 100 U significantly improves all idiopathic overactive bladder symptoms and quality of life in patients with overactive bladder and urinary incontinence: a randomised,

double-blind, placebo-controlled trial. Eur Urol.

2013;64(2):249-256.

25. Reitz A, Denys P, Fermanian C, et al. Do repeat intradetrusor botulinum toxin type a injections yield valuable results? Clinical and urodynamic results after five injections in patients with neurogenic detrusor overactivity. Eur Urol. 2007;52(6):1729-1735.

26. Duthie JB, Vincent M, Herbison GP, et al. Botulinum toxin injections for adults with overactive bladder syndrome. Cochrane Database Syst Rev. 2011 Dec 7;(12):CD005493. doi: 10.1002/14651858.

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27. Sahai A, Cortes E, Seth J, et al. Neurogenic detrusor overactivity in patients with spinal cord injury: evaluation and management. Curr Urol Rep. 2011;12(6):404-412.

28. Campbell JD, Gries KS, Watanabe JH, et al.

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29. Kennelly MJ, Devoe WM. Overactive bladder: pharmacologic treatments in the neurogenic population.

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30. Pannek J, et al. Guidelines on neurogenic lower urinary tract dysfunction. European Association of Urology (EAU); 2011 Mar. http://www.uroweb.org/ gls/pdf/19_Neurogenic_LR%20II.pdf. Accessed March 28, 2012.

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32. Wein AJ, Dmochowski RR. Neuromuscular dysfunction of the lower urinary tract. In: Wein AJ, Kavoussi LR, Novick AC, et al (eds). Campbell-Walsh Urology.

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33. Yamaguchi O, Nishizawa O, Takeda M, et al; Neurogenic Bladder Society. Clinical guidelines for overactive bladder. Int J Urol. 2009;16(2):126-142.

34. Ginsberg D, Gousse A, Keppenne V, et al. Phase 3 efficacy and tolerability study of onabotulinumtoxinA for urinary incontinence from neurogenic detrusor overactivity. J Urol. 2012;187(6):2131-2139.

35. Cruz F, Herschorn S, Aliotta P, et al. Efficacy and safety of onabotulinumtoxinA in patients with urinary incontinence due to neurogenic detrusor overactivity: a randomised, double-blind, placebo-controlled trial. Eur Urol. 2011;60(4):742-750.

36. Ghalayini IF, Al-Ghazo MA, Elnasser ZA. Is efficacy of repeated intradetrusor botulinum toxin type A (Dysport) injections dose dependent? Clinical and urodynamic results after four injections in patients with drug-resistant neurogenic detrusor overactivity.

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37. Leong RK, De Wachter SG, van Kerrebroeck PE. Current information on sacral neuromodulation and botulinum toxin treatment for refractory idiopathic overactive bladder syndrome: a review. Urol Int. 2010;84(3):245-253.

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39. Hassouna M, Siegel S, Nyeholt A, et al. Sacral neuromodulation in the treatment of urgencyfrequency symptoms: a multicenter study on efficacy and safety. J Urol. 2000:163;1849-1854.

40. Obermayr F, Szavay P, Schaefer J, Fuchs J. Outcome of augmentation cystoplasty and bladder substitution in a pediatric age group. Eur J Pediatr Surg.

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CME Post-test Expiration Date: September 2015 Global Education Group designates this educational activity for a maximum of 1.0 AMA PRA Category 1 Credit ™. Participants should claim only the credit commensurate with the extent of their participation in the activity. Physician post-tests must be completed and submitted online. Physicians may register at no charge at www.myCME.com/renalandurologynews. You must receive a score of 70% or better to receive credit.

1. For a 67-y/o woman with symptoms of incontinence who has not had any previous therapy, what testing would you do? a. Patient history, physical exam, and urinalysis b. Urinalysis, postvoid residual (PVR), and bladder diaries c. Urodynamics, cystoscopy, and renal/bladder ultrasound d. None of the above 2. For a 49-y/o man with advanced multiple sclerosis and urgency urinary incontinence (UUI), what testing would you do? a. Urinalysis only b. Renal/bladder ultrasound only c. Urodynamics d. Cystoscopy 3. For a 58-y/o man with advanced diabetes and severe hypertension, Sjögren’s syndrome, and UUI who does not want an implantable therapy, what options would you recommend? a. Antimuscarinic b. Beta3-agonist c. Sacral neuromodulation d. Botulinum toxin injection 4. For a 73-y/o woman with UUI who has failed physical treatment and antimuscarinics, is not concerned about tolerable adverse events, and does not want surgery, which of the following would you first consider? a. Beta3-agonist b. Botulinum toxin injection c. Sacral neuromodulation d. Augmentation cystoplasty 5. Shared decision making involves: a. The clinician making decisions on behalf of the patient. b. Effective communication skills to elicit and consider relevant information from the patient and explain how various treatments work. c. The clinician giving explanations only when the patient asks for them. d. Encouraging the patient to choose treatment based on handouts they have been given.

6. For a 72-y/o man with symptoms of incontinence who has dry mouth and moderate dementia, which of the following factors would you consider when recommending therapy? a. Either antimuscarinics or beta3-agonist plus physical therapy would be helpful. b. Antimuscarinics can increase hypertension. c. Antimuscarinics can negatively affect cognition. d. Beta3-agonist can increase dry mouth.

7. Which one of the following statements is true? a. Neurogenic detrusor overactivity (NDO) affects only spinal cord-injured patients. b. Hydronephrosis and renal failure can result from NDO. c. Bladder overdistention is not a concern with NDO. d. Assessing PVR but not urodynamics is essential in evaluating the patient with NDO. 8. Which one of the following statements is correct? a. Mirabegron has its primary effect on the beta3-receptor of the bladder detrusor muscle. b. The dosing units of available botulinum toxins are not bioequivalent. c. The choice of pharmacologic medication depends mainly on the patient’s history of prior antimuscarinic use. d. All of the above.

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