INTERNATIONAL NEUROUROLOGY JOURNAL INTERNATIONAL INJ pISSN 2093-4777 eISSN 2093-6931 Review Article Int Neurourol J 2020;24(1):3-11 NEU INTERNATIONAL RO UROLOGY JOURNAL https://doi.org/10.5213/inj.2040010.005 pISSN 2093-4777 · eISSN 2093-6931 Volume 19 | Number 2 June 2015 Volume pages 131-210 Official Journal of Korean Continence Society / Korean Society of Urological Research / The Korean Children’s Continence and Enuresis Society / The Korean Association of Urogenital Tract Infection and Inflammation einj.org Mobile Web Underactive Bladder; Review of Progress and Impact From the International CURE-UAB Initiative Michael B. Chancellor, Sarah N. Bartolone, Laura E. Lamb, Elijah Ward, Bernadette M.M. Zwaans, Ananias Diokno Department of Urology, Beaumont Health System, Royal Oak, MI, USA There is a significant need for research and understanding of underactive bladder (UAB). The International Congress of Uro- logic Research and Education on Aging UnderActive Bladder (CURE-UAB) was organized by Doctors Michael Chancellor and Ananias Diokno in order to address these concerns. CURE-UAB was supported, in part, by the US National Institute of Aging and National Institute of Diabetes Digestive and Kidney. Since 2014, there have been 5 successful CURE-UAB con- gresses. They have brought together diverse stakeholders in the UAB field to identify areas of major scientific challenge and initiated a call to action among the medical community. In this review, we will highlight current and novel treatments under development for UAB and the progress and impact from the CURE-UAB initiative. Keywords: Underactive urinary bladder; Overactive urinary bladder; Urodynamics; Sarcopenia; Aging • Fund/Grant Support: Funding support was in parts sponsored by the NIA, NIDDK (R13AG047010) and the Aikens Center for Neurourology Research at Beaumont Health System (Royal Oak, MI, USA). • Conflict of Interest: Michael B Chancellor is one of the inventors of the autologous muscle-derived cell process and has received royalty pay- ments for the stem cell process and payments for consulting from Cook MyoSite. Except for that, no potential conflict of interest relevant to this article was reported. INTRODUCTION ued to improve, there are still no effective treatments for patients with this converse condition. UAB symptoms can include strain- Underactive bladder (UAB) is a complex constellation of symp- ing, incomplete bladder emptying, hesitancy, frequent urination, toms with few treatment options that can significantly diminish or leakage due to overflow incontinence. UAB can be caused by the quality-of-life (QoL) of those affected. Many UAB patients myogenic and neurogenic conditions, as well as aging and medi- feel helpless when they cannot void or are unable to adequately cation side effects. empty their bladder. UAB is prevalent, underdiagnosed, and The current management of UAB treatment for urinary re- represents an unmet medical need in elderly and other popula- tention is clean intermittent catheterization (CIC) or indwelling tions [1]. There are no outcome-validated effective therapeutics catheters to empty the bladder [3]. However, complications and for UAB and research on promising candidates has slowed due adverse effects can arise, especially during long-term use. Cur- to a lack of consensus and understanding regarding its diagno- rent research and treatment under consideration for UAB are sis and treatment [2]. described in detail in previous summary papers from Congress While treatments for overactive bladder (OAB) have contin- of Urologic Research and Education on Aging UnderActive Corresponding author: Michael B. Chancellor https://orcid.org/0000-0001-9480-8972 This is an Open Access article distributed under the terms of the Cre- Department of Urology, Beaumont Health System, 3811 West 13 Mile Road, Royal ative Commons Attribution Non-Commercial License (https://creative- Oak, MI 48073, USA commons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distri- E-mail: [email protected] bution, and reproduction in any medium, provided the original work is properly cited. Submitted: January 11, 2020 / Accepted after revision: January 29, 2020 Copyright © 2020 Korean Continence Society www.einj.org INJ Chancellor, et al. • CURE-UAB Bladder (CURE-UAB) [4,5]. to the international congresses. The UAB Foundation is a pa- tient advocacy group dedicated to encouraging, supporting, and THE INTERNATIONAL CURE-UAB monitoring action on the implementation of evidence-based ef- forts to promote global action on UAB. The UAB Foundation The purpose of the CURE-UAB conference series was to gather focuses on involving key stakeholders and representing UAB diverse stakeholders from multiple disciplines and backgrounds patients and their family and friends who care deeply about this together to address the unmet needs of UAB research and care. underrepresented disease. American Urological Association The first CURE-UAB, sponsored by the National Institute on (AUA), GUS, and SUNA are professional organizations for cli- Aging (NIA), National Institute of Diabetes and Digestive and nicians and researchers in the urology fields. Kidney Diseases (NIDDK), Aikens Center for Neurourology Research at Beaumont Health System, and The Underactive RETURN ON INVESTMENT OF THE Bladder Foundation was held in February 2014 in Washington, INTERNATIONAL COLLABORATIVE CURE-UAB DC. The second international meeting was December 2015 in GRANT Denver, CO; the third meeting was held in March 2017 in Washington, DC; the fourth meeting was held in November The United States National Institutes of Health (NIH) R13 2018 in Honolulu, HI; and the fifth meeting was held in De- grant mechanism supports high-quality scientific conferences cember 2019 in East Lansing, MI. to promote unmet medical needs, awareness, and engage public and private stakeholders. Starting in 2014, the NIA and NIDDK Public, Academic and Industry Stakeholders funded the R13 (R13AG047010) grant entitled CURE-UAB to CURE-UAB has received support from the following academic bring stakeholders together to educate and promote awareness and public stakeholders: The Aikens Center for Neurourology on the topic of UAB. We hereby report metric of the impact of Research, American Urological Association, Underactive Blad- this R13 on the medical and scientific community. der Foundation (https://www.underactivebladder.org), Geriatric A review of the impact on science, public awareness, and re- Urology Society (GUS), and Society of Urology Nursing Associ- search advances were completed by comparing publications ation (SUNA). Additional support and cosponsorships from and grants from the time-period prior to the 2014 R13 award public, academic and industry stakeholders significantly added and the 5 years since R13 funding. 18 70 60 700 16 No. of grants No. of grants No. of publications 60 50 No. of publications 600 14 publications of No. publications of No. UAB 50 OAB 500 12 40 10 40 400 30 8 30 300 No. of grants of No. 6 grants of No. 20 20 200 4 10 2 10 100 0 0 0 0 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 Year CURE-UAB A Year CURE-UAB B Fig. 1. The number of publications and grants on underactive bladder (UAB, A) and overactive bladder (OAB, B) over time (shown is 1998 to 2019). The CURE-UAB conference series started in 2014 and ended in 2019 (yellow box and shading). Publication count (UAB: orange line, right y-axis; OAB: blue line, right y-axis) is from PubMed.gov search of "underactive bladder" or “overactive blad- der” on 12/17/19. Prior to 1998, there are only 38 publications total for underactive bladder, with the earliest one from 1980. Grant count (UAB: blue bars, left y-axis; OAB: green bars, left y-axis) is from Grantome.com search of "underactive bladder” or “overactive bladder” on 12/17/19. There were no grants on UAB reported before 2007. CURE-UAB, Congress of Urologic Research and Educa- tion on Aging UnderActive Bladder. 4 www.einj.org Int Neurourol J March 31, 2020 Chancellor, et al. • CURE-UAB INJ Impact on Science with axonal degeneration demonstrated in unobstructed, aging To determine the impact on science, PubMed was searched for human bladders [3,5]. the terms OAB and UAB from 1998 to 2019 (Fig. 1). In the 5 The long-term effects of UAB may lead to significant compli- years prior to CURE-UAB (2009-2013), there were 2,391 OAB cations. Urine left behind in the bladder can lead to urinary tract and 35 UAB references in PubMed. In the 5 years after the first infections (UTIs) which, if become chronic, can lead to kidney CURE-UAB meeting (2015–2019), there were 2,698 OAB and damage and blood infections. In severe cases, urine left behind 204 UAB papers. OAB publications increased by 13% over the in the bladder can build up to a level that causes reflux up the 5-year period while UAB increased by 483%. ureters and may also cause kidney damage. Additionally, sedi- ments can accumulate in the bladder, forming bladder stones. Impact on Research UAB patients using catheters to empty their bladders also Prior to CURE-UAB, there was never a program announce- can face long-term medical difficulties, including inflammation ment specific for this disease. After the start of the CURE-UAB and discomfort, the potential for injury, and an increased risk series, the NIH issued UAB program announcements in 2015 of bacterial infection. For many individuals, the use of catheters (PA 15-049, 050, 051) and reissued in 2018 (PA-18-570, 571 can also be a cause for embarrassment and can negatively im- and 572: Underactive Bladder and Detrusor Activity in Aging). pact their work and home life. For older patients, it can have a We then further determined the impact of the CURE-UAB se- major impact on QoL.