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Lower Urinary Tract Symptoms and Incident Falls in Community Dwelling Older Men: The Concord Health and Ageing in Men Project
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Lower Urinary Tract Symptoms and Incident Falls in Community Dwelling Older Men: The Concord Health and Ageing in Men Project Naomi Noguchi,* Lewis Chan, Robert G. Cumming, Fiona M. Blyth, David J. Handelsman, Markus J. Seibel, Louise M. Waite, David G. Le Couteur and Vasi Naganathan EQ1
From the Centre for Education and Research on Ageing and Ageing and Alzheimer’s Institute (NN, RGC, FMB, LMWA, DGLC, VN), Department of Urology (LC) and ANZAC Research Institute (DJH, MJS, DGLC), Concord Hospital and School of Public Health (RGC), University of Sydney, New South Wales, Australia
Purpose: We sought to determine which lower urinary tract symptoms are associated with incident falls in community dwelling older men. Materials and Methods: The Concord Health and Ageing in Men Project involves a representative sample of community dwelling men 70 years old or older in a defined geographic region in Sydney, New South Wales, Australia. Included in analysis were 1,090 men without neurological diseases, poor mobility or dementia at baseline. Lower urinary tract symptoms were assessed using I-PSS (International Prostate Symptom Score) and incontinence was assessed using ICIQ (International Consultation on Incontinence Questionnaire) at baseline. I-PSS subscores were calculated for storage and voiding symptoms. Incident falls in 1 year were determined by telephone followup every 4 months. Results: I-PSS storage and voiding subscores were associated with falls. Urgency incontinence was associated with falls (adjusted incidence rate ratio 2.57, 95% CI 1.54e4.30). In addition, intermediate to high I-PSS storage subscores without urgency incontinence were associated with falls (adjusted incidence rate ratio 1.72, 95% CI 1.24e2.38). Other types of incontinence and urgency alone without urgency incontinence were not associated with falls. Conclusions: Lower urinary tract storage and voiding symptoms were associated with falls in community dwelling older men. Of the symptoms of overactive bladder urgency incontinence carried a high risk of falls. Storage symptoms also contributed to the fall risk independently of urgency incontinence. Circumstances of falls among men with lower urinary tract symptoms should be explored to understand how lower urinary tract symptoms increase the fall risk and generate hypotheses regarding potential interventions. Furthermore, trials to treat lower urinary tract symptoms in older men should include falls as an end point. Key Words: urinary bladder; lower urinary tract symptoms; elderly; male; accidental falls
FALLS are common among older people and often result in injuries.1 LUTS such as incontinence, urgency,
CHAMP ¼ Concord Health and Ageing in Men Project DBI ¼ Drug Burden Index I-PSS-S ¼ I-PSS Storage Subscore IRR ¼ incidence rate ratio LUTS ¼ lower urinary tract symptoms OAB ¼ overactive bladder Accepted for publication June 18, 2016. No direct or indirect commercial incentive associated with publishing this article. The corresponding author certifies that, when applicable, a statement(s) has been included in the manuscript documenting institutional review board, ethics committee or ethical review board study approval; principles of Helsinki Declaration were followed in lieu of formal ethics committee approval; institutional animal care and use committee approval; all human subjects provided written informed consent with guarantees of confidentiality; IRB approved protocol number; animal approved project number. Supported by the Australian National Health and Medical Research Council Project Grant 301916, the Ageing and Alzheimer’s Institute, Sydney Medical School Foundation, and Geoff and Elaine Penny Aging Research Unit. * Correspondence: Centre for Education and Research on Ageing and Ageing, and Alzheimer’s Institute, Building 25 Concord Hospital, Hospital Rd., Concord New South Wales 2139, Australia (telephone: þ61-2-9767-9170; FAX: þ61-2-97675419; e-mail: [email protected]).
frequency and nocturia have been associated with falls but evidence of the association is less extensive in
0022-5347/16/1966-0001/0 THE JOURNAL OF UROLOGY® Ó 2016 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.
Dochead: Adult Urology
Abbreviations and Acronyms
http://dx.doi.org/10.1016/j.juro.2016.06.085 Vol. 196, 1-6, December 2016 Printed in U.S.A.
www.jurology.com
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LOWER URINARY TRACT SYMPTOMS AND FALLS IN COMMUNITY DWELLING OLDER MEN
men than in women.2,3 The patterns of co-occurrence and severity of LUTS are different between men and women.4 In addition, there may be gender related behavioral differences in strategies to manage LUTS that could also influence fall risk. Moreover, because multiple LUTS often coexist in 1 person, it is unclear which LUTS may potentially be targeted in strategies to decrease falls. Looking at all of the important LUTS in 1 population would help identify which LUTS have stronger associations with falls. In particular, causally related symptoms such as urgency and urgency incontinence must be examined for an association with falls, stratified by both of these symptoms to determine whether urgency incontinence makes any additional contribution to the fall risk over that of urgency alone. The aim of our study was to determine which LUTS were associated with incident falls during 1 year in community dwelling older men. To explore this we examined each lower urinary tract symptom by frequency of occurrence, I-PSS,5 incontinence type and urgency by the presence or absence of urgency incontinence for associations with incident falls.
MATERIALS AND METHODS Study Participants CHAMP is a prospective cohort study of a wide range of health issues in older men. Baseline data were collected between January 2005 and June 2007. The study was approved by the Concord Hospital human research ethics committee. All participants provided written informed consent. CHAMP includes 1,705 men 70 years old or older living in a defined region of metropolitan Sydney, New South Wales, Australia. The sampling frame was the New South Wales electoral roll, on which registration is compulsory. The only exclusion criterion was living in a residential aged care facility. The participation rate was 47%. The details of the sample selection process have been described previously.6
Lower Urinary Tract Symptoms Information about LUTS was collected from a selfadministered questionnaire using I-PSS5 and ICIQ.7 Nocturia was categorized into zero to 1 time, 2 to 3 times and 4 times or more per night. Other symptoms in I-PSS were categorized as not at all, less than half the time and at least half the time. I-PSS total score was categorized into lowd0 to 7, intermediated8 to 19 and highd20 to 35 points.6 The storage subscore of I-PSS was calculated as the sum of questions number 2, 4 and 7 (frequency, urgency and nocturia),7 and categorized as lowd0 to 3, intermediated4 to 8 and highd9 to 15 points. I-PSS-S was calculated as the sum of questions number 1, 3,5 and 6 (incomplete emptying, intermittence, weak stream and
Dochead: Adult Urology
straining),8 and classified as lowd0 to 4, intermediated5 to 11 and highd12 to 20 points. For I-PSS-S and the I-PSS voiding subscore these cutoff points of low, intermediate and high scores were set at the same proportions as the conventional cutoff values of total I-PSS.5 Incontinence was first categorized according to frequency, including none or at most weekly, more than weekly but less than daily and at least daily. Also, incontinence more frequent than weekly was categorized by type, including incontinence without an urgency component (nonurgency incontinence, including stress and other incontinence), incontinence with an urgency component (urgency incontinence, including urgency and mixed incontinence) and incontinence that occurred at most once per week, which was classified as no incontinence. Type of incontinence was determined using question 4 of ICIQ (“When does urine leak?”) with the response “[urine] leaks before you can get to the toilet” indicating an urgency component. To determine the individual contribution of urgency and of urgency incontinence to fall risk the men were categorized as those with urgency incontinence, those with urgency without urgency incontinence and those with neither urgency nor urgency incontinence. For this analysis urgency was defined as urgency occurring at least half the time and urgency incontinence was defined as more than weekly incontinence with an urgency component. Lastly, post hoc analysis was performed to determine the contribution of storage symptoms as a whole to fall risk, accounting for urgency incontinence. This analysis was added because intermediate to high I-PSS storage subscores incorporating all OAB symptoms9 were related to falls, and urgency incontinence, which is the most severe form of OAB, was also associated with falls. For this analysis having storage symptoms was defined as intermediate to high I-PSS-S (4 to 15 points). Men were classified into those with urgency incontinence regardless of I-PSS-S, those with storage symptoms without urgency incontinence and those with neither storage symptoms nor urgency incontinence.
Fall Ascertainment Participants were telephoned every 4 months. They were asked whether they had fallen in the previous 4 months and if so, how many times they had fallen. When falls were reported, study staff excluded near falls by asking whether the body of the participant had hit the ground or an object. The first 3 telephone followups representing the first year of followup were used in this study.
Covariates Information on demographic characteristics, lifetime history of diagnosed medical conditions including Parkinson’s disease, stroke, epilepsy and arthritis, history of falls in the previous year and dizziness was gathered using a self-administered questionnaire. Medical conditions and dizziness were dichotomized into absence and presence. Country of birth was categorized
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LOWER URINARY TRACT SYMPTOMS AND FALLS IN COMMUNITY DWELLING OLDER MEN
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as Australia, Italy, Great Britain, Greece, China and other. Variables assessed at the clinic interviews by trained personnel included MMSE (Mini-Mental State Examination),10 functional disability (a modification of the Katz activities of daily living11), physical performance tests (repeat chair stands, usual pace walk and narrow balance walk) and visual impairment. Also, participants brought medications that they had ingested daily or almost daily for at least a month before the clinic visit. Poor mobility was defined as needing help with walking across a small room and/or transferring from a bed to a chair.12 Time spent for each physical performance test was dichotomized into slow and normal/fast at the slowest quartile. Men who did not complete the tasks were categorized into the slowest quartile. Poor visual acuity was defined as less than 20/63 on the Logmar Visual Acuity Test.13 DBI was calculated by adding the burden of drugs with anticholinergic and sedative properties.14 DBI was categorized as 0, greater than 0 to 0.5 and greater than 0.5. The median DBI in men exposed to these drugs was 0.5. IQCODE, an informant screening questionnaire to assess cognitive decline,15 was administered by telephone shortly after the clinic visit. Men with a MMSE score of 26 or less, or a IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly) score of 3.6 or higher
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underwent a detailed cognitive examination performed by a geriatrician. A diagnosis of dementia was reached using DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, fourth edition)16 criteria at a consensus meeting attended by 2 geriatricians, a neurologist and a neuropsychologist.
Statistical Analysis Participant characteristics were derived as the mean SD or as frequency distributions. Fall IRRs were estimated using negative binomial regression. Negative binomial regression is suitable for analyzing recurrent events such as falls because it fully uses the count data, in contrast to setting arbitrary cutoff values, which occurs when logistic regression is used to analyze fall data. Negative binomial regression is a generalization of Poisson regression, that can deal with over dispersed data and also control for different followup durations. Men with neurological diseases (stroke, Parkinson’s disease and epilepsy), poor mobility and dementia at baseline were excluded from analyses. These conditions are known to affect the fall risk and also to cause LUTS, including functional incontinence. Each symptom, I-PSS, urgency/urgency incontinence status and composite storage symptoms/urgency incontinence status were entered into separate multivariate models as
Table 1. Baseline characteristics of 1,390 men in CHAMP Baseline I-PSS (range) Overall* No. pts Mean SD age No. birth country (%): Australia Italy Great Britain Greece China Other† No. previous yr fall history (%): None 1 2 or More No. incontinence (%): 1/Wk or less Greater than 1/wk, less than 1/day Greater than 1/day No. dizziness (%): No Yes No. walking aid (%): No Yes No impaired vision (%): 20/60 or Greater Less than 20/60 No. psychotropic medication (%): No Yes No. antihypertensive medication (%): No Yes
1,390 76.3 5.2 686 273 62 59 43 267
(49) (20) (4) (4) (3) (19)
Low (0e7)
Intermediate (8e19)
840 76.1 5.1
381 76.5 5.3
90 76.8 5.0
426 156 39 33 27 159
200 65 19 14 13 70
35 28 3 5 0 19
(51) (19) (5) (4) (3) (19)
(52) (17) (5) (4) (3) (18)
(39) (31) (3) (6) (21)
1,162 (85) 140 (10) 73 (5)
738 (88) 65 (8) 33 (4)
300 (79) 55 (14) 26 (7)
71 (79) 12 (13) 7 (8)
1,181 (86) 99 (7) 91 (7)
787 (94) 33 (4) 20 (2)
297 (78) 43 (11) 41 (11)
47 (53) 18 (20) 23 (26)
1,035 (75) 339 (25)
672 (80) 165 (20)
260 (68) 120 (32)
56 (63) 33 (37)
1,351 (97) 39 (3)
817 (97) 23 (3)
375 (98) 6 (2)
84 (93) 6 (7)
1,311 (97) 38 (3)
795 (97) 24 (3)
361 (98) 7 (2)
85 (94) 5 (6)
1,234 (89) 156 (11)
758 (90) 82 (10)
327 (86) 54 (14)
75 (83) 15 (17)
622 (45) 768 (55)
380 (45) 460 (55)
166 (44) 215 (56)
38 (42) 52 (58)
* Values may not equal total because of missing data. † No other country contributed more than 3% of patients. Dochead: Adult Urology
High (20e35)
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LOWER URINARY TRACT SYMPTOMS AND FALLS IN COMMUNITY DWELLING OLDER MEN
Table 2. Fall IRR in 1,390 community dwelling older men in CHAMP IRR (95% CI) No. Pts
Univariate
Multivariate*
Storage symptoms Frequency: Not at all Less than half time Half time or greater Urgency: Not at all Less than half time Half time or greater No. nocturia: 0e1 2e3 4 or Greater
467 565 261
1.00 1.20 (0.85e1.70) 1.23 (0.80e1.87)
1.00 1.21 (0.85e1.73) 1.10 (0.71e1.70)
749 383 220
1.00 1.35 (0.95e1.90) 2.08 (1.40e3.09)
1.00 1.20 (0.84e1.71) 1.62 (1.08e2.42)
615 617 134
1.00 1.26 (0.92e1.74) 1.54 (0.93e2.57)
1.00 1.13 (0.82e1.55) 1.18 (0.71e1.97)
Voiding symptoms Straining: Not at all Less than half time Half time or greater Weak stream: Not at all Less than half time Half time or greater Intermittent: Not at all Less than half time Half time or greater Incomplete emptying: Not at all Less than half time Half time or greater
1097 191 62
1.00 1.32 (0.87e2.02) 1.23 (0.61e2.49)
1.00 1.36 (0.89e2.07) 1.22 (0.59e2.50)
754 344 245
1.00 1.31 (0.91e1.87) 1.62 (1.10e2.40)
1.00 1.37 (0.95e1.97) 1.47 (0.99e2.19)
858 318 174
1.00 1.36 (0.95e1.94) 1.93 (1.26e2.97)
1.00 1.43 (0.99e2.06) 1.87 (1.23e2.85)
863 314 175
1.00 1.05 (0.73e1.52) 1.35 (0.86e2.10)
1.00 1.17 (0.80e1.69) 1.29 (0.83e2.00)
840 381 90
1.00 1.38 (0.98e1.93) 2.44 (1.41e4.22)
1.00 1.29 (0.91e1.82) 2.06 (1.20e3.54)
702 461 148
1.00 1.99 (1.43e2.76) 2.43 (1.53e3.86)
1.00 1.73 (1.24e2.40) 1.81 (1.13e2.90)
973 264 74
1.00 1.41 (0.97e2.05) 1.87 (1.02e3.46)
1.00 1.41 (0.97e2.04) 1.98 (1.09e3.60)
I-PSS Total (range): Low (0e7) Intermediate (8e19) High (20e35) Storage (range): Low (0e3) Intermediate (4e8) High (9e15) Voiding (range): Low (0e4) Intermediate (5e11) High (12e20)
Incontinence Incontinence frequency: 1/Wk or less Greater than 1/wk, less than 1/day 1/Day or greater Incontinence type: No (1/wk or less) Nonurgency Urgency
1181 99
1.00 1.60 (0.93e2.75)
1.00 1.34 (0.77e2.32)
91
1.72 (0.99e3.00)
1.13 (0.65e1.99)
1181 83 107
1.00 0.49 (0.23e1.04) 2.56 (1.59e4.15)
1.00 0.45 (0.21e0.94) 1.87 (1.15e3.04)
Urgency incontinence þ other OAB symptoms Urgency/urgency incontinence: Neither Urgency, no urgency incontinence Urgency incontinence
1083 161
1.00 1.60 (1.03e2.48)
1.00 1.33 (0.85e2.06)
107
2.85 (1.76e4.63)
2.05 (1.25e3.36)
Dochead: Adult Urology
400 401 IRR (95% CI) 402 No. Pts Univariate Multivariate* 403 Storage symptoms/urgency 404 incontinence:† 405 Neither 689 1.00 1.00 406 Storage symptoms without 521 2.01 (1.46e2.76) 1.72 (1.24e2.38) urgency incontinence 407 Urgency incontinence 107 3.77 (2.29e6.22) 2.57 (1.54e4.30) 408 409 * Adjusted for age, birth country, dizziness, visual impairment, arthritis, psychotropic medication, antihypertensive medication and walking aid. 410 † Storage symptoms defined as intermediate to high IPSS-S (4 to 15 points). 411 412 413 the main explanatory variable. Risk factors for falls that 414 were previously identified were forced into the multi415 variate models regardless of a statistical contribution to 416 the model to ensure face validity, including age, country of birth,17 dizziness, visual impairment, arthritis, DBI, 417 repeat chair stands, usual pace walk and narrow balance 418 walk. All analyses were performed using SASÒ, 419 version 9.3. 420 421 422 RESULTS 423 Of the 1,705 participants at baseline 307 with 424 neurological disease, poor mobility or dementia at 425 baseline were excluded from analysis. After 426 applying these exclusion criteria an additional 8 427 men (0.6%) who withdrew from study or died before 428 the first telephone followup were excluded. The 429 remaining 1,390 men were included in analyses. 430 Mean SD followup was 11.8 1.0 months (range 431 4 to 12). The fall rate ranged from zero to 12 per 432 year. A total of 102 men (10%) had a fall rate of 1 per 433 year and 97 (7%) had a fall rate of greater than 1 434 per year. 435 Table 1 shows the baseline characteristics of the ½T1 436 included men. Mean age was 76.3 5.2 years. Of 437 the men 49% were born in Australia and 20% were 438 born in Italy. In the previous year 10% of the men 439 had experienced a single fall and 5% had experi440 enced 2 or more falls. I-PSS was low in 64% of 441 participants, 29% had intermediate I-PSS and 442 7% had high I-PSS. Incontinence was experienced 443 more than weekly but less than daily in 7% of 444 men and at least daily in 7%. A higher proportion 445 of men in higher I-PSS categories reported 2 446 or more falls in the last year, including 4% 447 with low, 7% with intermediate and 8% with high 448 I-PSS. 449 Table 2 shows associations of LUTS, I-PSS, ur- ½T2 450 gency/urgency incontinence status and composite 451 storage symptoms/urgency incontinence status with 452 fall rates. Results of multivariate analyses are 453 described. Of individual symptoms on I-PSS ur454 gency and intermittency that occurred at least half 455 the time were significantly associated with an 456 Table 2 (continued )
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increased fall rate. High total I-PSS, intermediate to high I-PSS-S and high I-PSS voiding subscores were associated with an increased fall rate. Urgency incontinence was significantly associated with an increased fall rate but nonurgency incontinence was not. Urgency incontinence was associated with an increased fall rate but urgency without urgency incontinence was not. With regard to the combination of urgency incontinence and composite storage symptoms (urgency, frequency and nocturia) storage symptoms were significantly associated with an increased fall rate even in the absence of urgency incontinence.
DISCUSSION This population based prospective study shows that lower urinary tract storage and voiding symptoms are associated with falls in community dwelling older men. The strongest association was found for urgency incontinence that occurred more than weekly. Also, storage symptoms (urgency, frequency and nocturia) as a whole, represented as intermediate to high I-PSS-S, were associated with falls independently of urgency incontinence. In a large, well performed, prospective study of 5,872 men Parsons et al examined a wide range of LUTS for associations with falls.18 Unlike in our study, they did not account for incontinence but found weak associations of I-PSS individual symptoms and total I-PSS with falls. In our study with a smaller sample size only urgency, intermittence and total I-PSS were associated with falls. In addition, we found that storage and voiding subscores were associated with falls and neither had an apparently stronger association than the other score. Urgency incontinence was associated with falls in our study but other types of incontinence were not. This is consistent with studies in women.19,20 Urgency has also been associated with falls in past studies in men and women2,3 but these studies did not assess urine leakage. In our series urgency was further examined for an association with falls by the presence of urgency incontinence to determine whether urine leakage would make an additional contribution to fall risk beyond that of urgency alone. We defined urgency and incontinence as those occurring half the time and more than weekly, respectively, which we considered clinically important. Urgency incontinence was moderately associated with falls but urgency without urgency incontinence was not. On post hoc analysis OAB symptoms as a whole, represented as I-PSS-S, were examined for an association with falls by the presence of urgency incontinence, which is the most severe form of Dochead: Adult Urology
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OAB. We found that intermediate to high I-PSS-S was associated with falls even in the absence of urgency incontinence. This indicates that storage symptoms collectively contribute to fall risk, although urgency alone without accounting for frequency and nocturia did not make an independent contribution to fall risk. Our study has a number of strengths. CHAMP includes a large representative sample of community dwelling, older Australian men. While the response rate was relatively low at 47%, the prevalence of major medical conditions and the distribution of responses to a question on self-rated health were similar to those in 915 men 70 years old or older in the nationally representative MATeS (Men in Australia Telephone Survey) study.21 Validated questionnaires were used to assess a whole range of LUTS, falls were ascertained prospectively and associations were adjusted for an extensive list of previously identified fall risk factors. A limitation of our study is inherent in the study design. Our results only apply to community dwelling men without conditions related to LUTS and falls, such as dementia, poor mobility and neurological disease. Another limitation is that ascertainment of falls relied on recall of the last 4 months without using fall diaries. Although this was not ideal, Mackenzie et al reported that recalls of falls in last 6 months were reliable in people 70 years old or older.22 Besides, the quality of responses are unlikely to have varied according to LUTS status. To determine LUTS we did not discriminate between nocturnal micturition with and without urgency.23 This could have masked the possible association between nocturnal urgency and falls. Lastly and most importantly, causality is unclear since we could not determine the circumstances of the falls. Therefore, it is uncertain whether medical, surgical or behavioral interventions for LUTS alone could decrease falls in community dwelling older people.24 Since falls are often multifactorial, other predisposing or precipitating factors for falls that were not fully adjusted for may have had a part in the increased fall risk. The circumstances of falls in men with LUTS should be investigated to generate hypotheses about what types of interventions may be incorporated into multidimensional fall prevention strategies. Also, future trials to treat LUTS should consider including falls as an end point.
CONCLUSIONS Lower urinary tract storage and voiding symptoms are associated with falls in community dwelling older men. In particular, urgency incontinence
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(incontinence with an urgency component, including mixed incontinence) carries a higher risk of falls. Also, storage symptoms are collectively associated with falls even in the absence of urgency incontinence. Other types of incontinence and urgency alone without urgency incontinence were not associated with falls. Evidence is lacking about whether
treatment of LUTS decreases the fall risk in community dwelling men. The circumstances of falls among men with LUTS should be explored to generate hypotheses regarding potential interventions. Furthermore, trials to treat LUTS in older men should consider including falls as an end point.
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Dochead: Adult Urology
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12. Branch LG and Jette AM: A prospective study of long-term care institutionalization among the aged. Am J Public Health 1982; 72: 1373. 13. Virgili G, Acosta R, Grover LL et al: Reading aids for adults with low vision. Cochrane Database Syst Rev 2013; 10: CD003303. 14. Gnjidic D, Le Couteur DG, Naganathan V et al: Effects of Drug Burden Index on cognitive function in older men. J Clin Psychopharmacol 2012; 32: 273.
21. Holden CA, McLachlan RI, Pitts M et al: Men in Australia Telephone Survey (MATeS): a national survey of the reproductive health and concerns of middle-aged and older Australian men. Lancet 2005; 366: 218. 22. Mackenzie L, Byles J and D’Este C: Validation of self-reported fall events in intervention studies. Clin Rehabil 2006; 20: 331.
15. Jorm AF, Scott R, Cullen JS et al: Performance of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) as a screening test for dementia. Psychol Med 1991; 21: 785.
23. Weiss JP, Jumadilova Z, Johnson TM et al: Efficacy and safety of flexible dose fesoterodine in men and women with overactive bladder symptoms including nocturnal urinary urgency. J Urol 2013; 189: 1396.
16. Task Force on DSM-IV: Diagnostic and Statistical Manual of Mental Disorders: DSM-IV. Washington, D.C.: American Psychiatric Association 1994.
24. Batchelor FA, Dow B and Low MA: Do continence management strategies reduce falls? A systematic review. Australas J Ageing 2013; 32: 211.
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Lower Urinary Tract Symptoms and Incident Falls in Community Dwelling Older Men: The Concord Health and Ageing in Men Project Naomi Noguchi,* Lewis Chan, Robert G. Cumming, Fiona M. Blyth, David J. Handelsman, Markus J. Seibel, Louise M. Waite, David G. Le Couteur and Vasi Naganathan EQ1
From the Centre for Education and Research on Ageing and Ageing and Alzheimer’s Institute (NN, RGC, FMB, LMWA, DGLC, VN), Department of Urology (LC) and ANZAC Research Institute (DJH, MJS, DGLC), Concord Hospital and School of Public Health (RGC), University of Sydney, New South Wales, Australia
Purpose: We sought to determine which lower urinary tract symptoms are associated with incident falls in community dwelling older men. Materials and Methods: The Concord Health and Ageing in Men Project involves a representative sample of community dwelling men 70 years old or older in a defined geographic region in Sydney, New South Wales, Australia. Included in analysis were 1,090 men without neurological diseases, poor mobility or dementia at baseline. Lower urinary tract symptoms were assessed using I-PSS (International Prostate Symptom Score) and incontinence was assessed using ICIQ (International Consultation on Incontinence Questionnaire) at baseline. I-PSS subscores were calculated for storage and voiding symptoms. Incident falls in 1 year were determined by telephone followup every 4 months. Results: I-PSS storage and voiding subscores were associated with falls. Urgency incontinence was associated with falls (adjusted incidence rate ratio 2.57, 95% CI 1.54e4.30). In addition, intermediate to high I-PSS storage subscores without urgency incontinence were associated with falls (adjusted incidence rate ratio 1.72, 95% CI 1.24e2.38). Other types of incontinence and urgency alone without urgency incontinence were not associated with falls. Conclusions: Lower urinary tract storage and voiding symptoms were associated with falls in community dwelling older men. Of the symptoms of overactive bladder urgency incontinence carried a high risk of falls. Storage symptoms also contributed to the fall risk independently of urgency incontinence. Circumstances of falls among men with lower urinary tract symptoms should be explored to understand how lower urinary tract symptoms increase the fall risk and generate hypotheses regarding potential interventions. Furthermore, trials to treat lower urinary tract symptoms in older men should include falls as an end point. Key Words: urinary bladder; lower urinary tract symptoms; elderly; male; accidental falls
FALLS are common among older people and often result in injuries.1 LUTS such as incontinence, urgency,
CHAMP ¼ Concord Health and Ageing in Men Project DBI ¼ Drug Burden Index I-PSS-S ¼ I-PSS Storage Subscore IRR ¼ incidence rate ratio LUTS ¼ lower urinary tract symptoms OAB ¼ overactive bladder Accepted for publication June 18, 2016. No direct or indirect commercial incentive associated with publishing this article. The corresponding author certifies that, when applicable, a statement(s) has been included in the manuscript documenting institutional review board, ethics committee or ethical review board study approval; principles of Helsinki Declaration were followed in lieu of formal ethics committee approval; institutional animal care and use committee approval; all human subjects provided written informed consent with guarantees of confidentiality; IRB approved protocol number; animal approved project number. Supported by the Australian National Health and Medical Research Council Project Grant 301916, the Ageing and Alzheimer’s Institute, Sydney Medical School Foundation, and Geoff and Elaine Penny Aging Research Unit. * Correspondence: Centre for Education and Research on Ageing and Ageing, and Alzheimer’s Institute, Building 25 Concord Hospital, Hospital Rd., Concord New South Wales 2139, Australia (telephone: þ61-2-9767-9170; FAX: þ61-2-97675419; e-mail: [email protected]).
frequency and nocturia have been associated with falls but evidence of the association is less extensive in
0022-5347/16/1966-0001/0 THE JOURNAL OF UROLOGY® Ó 2016 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION AND RESEARCH, INC.
Dochead: Adult Urology
Abbreviations and Acronyms
http://dx.doi.org/10.1016/j.juro.2016.06.085 Vol. 196, 1-6, December 2016 Printed in U.S.A.
www.jurology.com
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LOWER URINARY TRACT SYMPTOMS AND FALLS IN COMMUNITY DWELLING OLDER MEN
men than in women.2,3 The patterns of co-occurrence and severity of LUTS are different between men and women.4 In addition, there may be gender related behavioral differences in strategies to manage LUTS that could also influence fall risk. Moreover, because multiple LUTS often coexist in 1 person, it is unclear which LUTS may potentially be targeted in strategies to decrease falls. Looking at all of the important LUTS in 1 population would help identify which LUTS have stronger associations with falls. In particular, causally related symptoms such as urgency and urgency incontinence must be examined for an association with falls, stratified by both of these symptoms to determine whether urgency incontinence makes any additional contribution to the fall risk over that of urgency alone. The aim of our study was to determine which LUTS were associated with incident falls during 1 year in community dwelling older men. To explore this we examined each lower urinary tract symptom by frequency of occurrence, I-PSS,5 incontinence type and urgency by the presence or absence of urgency incontinence for associations with incident falls.
MATERIALS AND METHODS Study Participants CHAMP is a prospective cohort study of a wide range of health issues in older men. Baseline data were collected between January 2005 and June 2007. The study was approved by the Concord Hospital human research ethics committee. All participants provided written informed consent. CHAMP includes 1,705 men 70 years old or older living in a defined region of metropolitan Sydney, New South Wales, Australia. The sampling frame was the New South Wales electoral roll, on which registration is compulsory. The only exclusion criterion was living in a residential aged care facility. The participation rate was 47%. The details of the sample selection process have been described previously.6
Lower Urinary Tract Symptoms Information about LUTS was collected from a selfadministered questionnaire using I-PSS5 and ICIQ.7 Nocturia was categorized into zero to 1 time, 2 to 3 times and 4 times or more per night. Other symptoms in I-PSS were categorized as not at all, less than half the time and at least half the time. I-PSS total score was categorized into lowd0 to 7, intermediated8 to 19 and highd20 to 35 points.6 The storage subscore of I-PSS was calculated as the sum of questions number 2, 4 and 7 (frequency, urgency and nocturia),7 and categorized as lowd0 to 3, intermediated4 to 8 and highd9 to 15 points. I-PSS-S was calculated as the sum of questions number 1, 3,5 and 6 (incomplete emptying, intermittence, weak stream and
Dochead: Adult Urology
straining),8 and classified as lowd0 to 4, intermediated5 to 11 and highd12 to 20 points. For I-PSS-S and the I-PSS voiding subscore these cutoff points of low, intermediate and high scores were set at the same proportions as the conventional cutoff values of total I-PSS.5 Incontinence was first categorized according to frequency, including none or at most weekly, more than weekly but less than daily and at least daily. Also, incontinence more frequent than weekly was categorized by type, including incontinence without an urgency component (nonurgency incontinence, including stress and other incontinence), incontinence with an urgency component (urgency incontinence, including urgency and mixed incontinence) and incontinence that occurred at most once per week, which was classified as no incontinence. Type of incontinence was determined using question 4 of ICIQ (“When does urine leak?”) with the response “[urine] leaks before you can get to the toilet” indicating an urgency component. To determine the individual contribution of urgency and of urgency incontinence to fall risk the men were categorized as those with urgency incontinence, those with urgency without urgency incontinence and those with neither urgency nor urgency incontinence. For this analysis urgency was defined as urgency occurring at least half the time and urgency incontinence was defined as more than weekly incontinence with an urgency component. Lastly, post hoc analysis was performed to determine the contribution of storage symptoms as a whole to fall risk, accounting for urgency incontinence. This analysis was added because intermediate to high I-PSS storage subscores incorporating all OAB symptoms9 were related to falls, and urgency incontinence, which is the most severe form of OAB, was also associated with falls. For this analysis having storage symptoms was defined as intermediate to high I-PSS-S (4 to 15 points). Men were classified into those with urgency incontinence regardless of I-PSS-S, those with storage symptoms without urgency incontinence and those with neither storage symptoms nor urgency incontinence.
Fall Ascertainment Participants were telephoned every 4 months. They were asked whether they had fallen in the previous 4 months and if so, how many times they had fallen. When falls were reported, study staff excluded near falls by asking whether the body of the participant had hit the ground or an object. The first 3 telephone followups representing the first year of followup were used in this study.
Covariates Information on demographic characteristics, lifetime history of diagnosed medical conditions including Parkinson’s disease, stroke, epilepsy and arthritis, history of falls in the previous year and dizziness was gathered using a self-administered questionnaire. Medical conditions and dizziness were dichotomized into absence and presence. Country of birth was categorized
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LOWER URINARY TRACT SYMPTOMS AND FALLS IN COMMUNITY DWELLING OLDER MEN
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as Australia, Italy, Great Britain, Greece, China and other. Variables assessed at the clinic interviews by trained personnel included MMSE (Mini-Mental State Examination),10 functional disability (a modification of the Katz activities of daily living11), physical performance tests (repeat chair stands, usual pace walk and narrow balance walk) and visual impairment. Also, participants brought medications that they had ingested daily or almost daily for at least a month before the clinic visit. Poor mobility was defined as needing help with walking across a small room and/or transferring from a bed to a chair.12 Time spent for each physical performance test was dichotomized into slow and normal/fast at the slowest quartile. Men who did not complete the tasks were categorized into the slowest quartile. Poor visual acuity was defined as less than 20/63 on the Logmar Visual Acuity Test.13 DBI was calculated by adding the burden of drugs with anticholinergic and sedative properties.14 DBI was categorized as 0, greater than 0 to 0.5 and greater than 0.5. The median DBI in men exposed to these drugs was 0.5. IQCODE, an informant screening questionnaire to assess cognitive decline,15 was administered by telephone shortly after the clinic visit. Men with a MMSE score of 26 or less, or a IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly) score of 3.6 or higher
3
underwent a detailed cognitive examination performed by a geriatrician. A diagnosis of dementia was reached using DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, fourth edition)16 criteria at a consensus meeting attended by 2 geriatricians, a neurologist and a neuropsychologist.
Statistical Analysis Participant characteristics were derived as the mean SD or as frequency distributions. Fall IRRs were estimated using negative binomial regression. Negative binomial regression is suitable for analyzing recurrent events such as falls because it fully uses the count data, in contrast to setting arbitrary cutoff values, which occurs when logistic regression is used to analyze fall data. Negative binomial regression is a generalization of Poisson regression, that can deal with over dispersed data and also control for different followup durations. Men with neurological diseases (stroke, Parkinson’s disease and epilepsy), poor mobility and dementia at baseline were excluded from analyses. These conditions are known to affect the fall risk and also to cause LUTS, including functional incontinence. Each symptom, I-PSS, urgency/urgency incontinence status and composite storage symptoms/urgency incontinence status were entered into separate multivariate models as
Table 1. Baseline characteristics of 1,390 men in CHAMP Baseline I-PSS (range) Overall* No. pts Mean SD age No. birth country (%): Australia Italy Great Britain Greece China Other† No. previous yr fall history (%): None 1 2 or More No. incontinence (%): 1/Wk or less Greater than 1/wk, less than 1/day Greater than 1/day No. dizziness (%): No Yes No. walking aid (%): No Yes No impaired vision (%): 20/60 or Greater Less than 20/60 No. psychotropic medication (%): No Yes No. antihypertensive medication (%): No Yes
1,390 76.3 5.2 686 273 62 59 43 267
(49) (20) (4) (4) (3) (19)
Low (0e7)
Intermediate (8e19)
840 76.1 5.1
381 76.5 5.3
90 76.8 5.0
426 156 39 33 27 159
200 65 19 14 13 70
35 28 3 5 0 19
(51) (19) (5) (4) (3) (19)
(52) (17) (5) (4) (3) (18)
(39) (31) (3) (6) (21)
1,162 (85) 140 (10) 73 (5)
738 (88) 65 (8) 33 (4)
300 (79) 55 (14) 26 (7)
71 (79) 12 (13) 7 (8)
1,181 (86) 99 (7) 91 (7)
787 (94) 33 (4) 20 (2)
297 (78) 43 (11) 41 (11)
47 (53) 18 (20) 23 (26)
1,035 (75) 339 (25)
672 (80) 165 (20)
260 (68) 120 (32)
56 (63) 33 (37)
1,351 (97) 39 (3)
817 (97) 23 (3)
375 (98) 6 (2)
84 (93) 6 (7)
1,311 (97) 38 (3)
795 (97) 24 (3)
361 (98) 7 (2)
85 (94) 5 (6)
1,234 (89) 156 (11)
758 (90) 82 (10)
327 (86) 54 (14)
75 (83) 15 (17)
622 (45) 768 (55)
380 (45) 460 (55)
166 (44) 215 (56)
38 (42) 52 (58)
* Values may not equal total because of missing data. † No other country contributed more than 3% of patients. Dochead: Adult Urology
High (20e35)
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LOWER URINARY TRACT SYMPTOMS AND FALLS IN COMMUNITY DWELLING OLDER MEN
Table 2. Fall IRR in 1,390 community dwelling older men in CHAMP IRR (95% CI) No. Pts
Univariate
Multivariate*
Storage symptoms Frequency: Not at all Less than half time Half time or greater Urgency: Not at all Less than half time Half time or greater No. nocturia: 0e1 2e3 4 or Greater
467 565 261
1.00 1.20 (0.85e1.70) 1.23 (0.80e1.87)
1.00 1.21 (0.85e1.73) 1.10 (0.71e1.70)
749 383 220
1.00 1.35 (0.95e1.90) 2.08 (1.40e3.09)
1.00 1.20 (0.84e1.71) 1.62 (1.08e2.42)
615 617 134
1.00 1.26 (0.92e1.74) 1.54 (0.93e2.57)
1.00 1.13 (0.82e1.55) 1.18 (0.71e1.97)
Voiding symptoms Straining: Not at all Less than half time Half time or greater Weak stream: Not at all Less than half time Half time or greater Intermittent: Not at all Less than half time Half time or greater Incomplete emptying: Not at all Less than half time Half time or greater
1097 191 62
1.00 1.32 (0.87e2.02) 1.23 (0.61e2.49)
1.00 1.36 (0.89e2.07) 1.22 (0.59e2.50)
754 344 245
1.00 1.31 (0.91e1.87) 1.62 (1.10e2.40)
1.00 1.37 (0.95e1.97) 1.47 (0.99e2.19)
858 318 174
1.00 1.36 (0.95e1.94) 1.93 (1.26e2.97)
1.00 1.43 (0.99e2.06) 1.87 (1.23e2.85)
863 314 175
1.00 1.05 (0.73e1.52) 1.35 (0.86e2.10)
1.00 1.17 (0.80e1.69) 1.29 (0.83e2.00)
840 381 90
1.00 1.38 (0.98e1.93) 2.44 (1.41e4.22)
1.00 1.29 (0.91e1.82) 2.06 (1.20e3.54)
702 461 148
1.00 1.99 (1.43e2.76) 2.43 (1.53e3.86)
1.00 1.73 (1.24e2.40) 1.81 (1.13e2.90)
973 264 74
1.00 1.41 (0.97e2.05) 1.87 (1.02e3.46)
1.00 1.41 (0.97e2.04) 1.98 (1.09e3.60)
I-PSS Total (range): Low (0e7) Intermediate (8e19) High (20e35) Storage (range): Low (0e3) Intermediate (4e8) High (9e15) Voiding (range): Low (0e4) Intermediate (5e11) High (12e20)
Incontinence Incontinence frequency: 1/Wk or less Greater than 1/wk, less than 1/day 1/Day or greater Incontinence type: No (1/wk or less) Nonurgency Urgency
1181 99
1.00 1.60 (0.93e2.75)
1.00 1.34 (0.77e2.32)
91
1.72 (0.99e3.00)
1.13 (0.65e1.99)
1181 83 107
1.00 0.49 (0.23e1.04) 2.56 (1.59e4.15)
1.00 0.45 (0.21e0.94) 1.87 (1.15e3.04)
Urgency incontinence þ other OAB symptoms Urgency/urgency incontinence: Neither Urgency, no urgency incontinence Urgency incontinence
1083 161
1.00 1.60 (1.03e2.48)
1.00 1.33 (0.85e2.06)
107
2.85 (1.76e4.63)
2.05 (1.25e3.36)
Dochead: Adult Urology
400 401 IRR (95% CI) 402 No. Pts Univariate Multivariate* 403 Storage symptoms/urgency 404 incontinence:† 405 Neither 689 1.00 1.00 406 Storage symptoms without 521 2.01 (1.46e2.76) 1.72 (1.24e2.38) urgency incontinence 407 Urgency incontinence 107 3.77 (2.29e6.22) 2.57 (1.54e4.30) 408 409 * Adjusted for age, birth country, dizziness, visual impairment, arthritis, psychotropic medication, antihypertensive medication and walking aid. 410 † Storage symptoms defined as intermediate to high IPSS-S (4 to 15 points). 411 412 413 the main explanatory variable. Risk factors for falls that 414 were previously identified were forced into the multi415 variate models regardless of a statistical contribution to 416 the model to ensure face validity, including age, country of birth,17 dizziness, visual impairment, arthritis, DBI, 417 repeat chair stands, usual pace walk and narrow balance 418 walk. All analyses were performed using SASÒ, 419 version 9.3. 420 421 422 RESULTS 423 Of the 1,705 participants at baseline 307 with 424 neurological disease, poor mobility or dementia at 425 baseline were excluded from analysis. After 426 applying these exclusion criteria an additional 8 427 men (0.6%) who withdrew from study or died before 428 the first telephone followup were excluded. The 429 remaining 1,390 men were included in analyses. 430 Mean SD followup was 11.8 1.0 months (range 431 4 to 12). The fall rate ranged from zero to 12 per 432 year. A total of 102 men (10%) had a fall rate of 1 per 433 year and 97 (7%) had a fall rate of greater than 1 434 per year. 435 Table 1 shows the baseline characteristics of the ½T1 436 included men. Mean age was 76.3 5.2 years. Of 437 the men 49% were born in Australia and 20% were 438 born in Italy. In the previous year 10% of the men 439 had experienced a single fall and 5% had experi440 enced 2 or more falls. I-PSS was low in 64% of 441 participants, 29% had intermediate I-PSS and 442 7% had high I-PSS. Incontinence was experienced 443 more than weekly but less than daily in 7% of 444 men and at least daily in 7%. A higher proportion 445 of men in higher I-PSS categories reported 2 446 or more falls in the last year, including 4% 447 with low, 7% with intermediate and 8% with high 448 I-PSS. 449 Table 2 shows associations of LUTS, I-PSS, ur- ½T2 450 gency/urgency incontinence status and composite 451 storage symptoms/urgency incontinence status with 452 fall rates. Results of multivariate analyses are 453 described. Of individual symptoms on I-PSS ur454 gency and intermittency that occurred at least half 455 the time were significantly associated with an 456 Table 2 (continued )
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increased fall rate. High total I-PSS, intermediate to high I-PSS-S and high I-PSS voiding subscores were associated with an increased fall rate. Urgency incontinence was significantly associated with an increased fall rate but nonurgency incontinence was not. Urgency incontinence was associated with an increased fall rate but urgency without urgency incontinence was not. With regard to the combination of urgency incontinence and composite storage symptoms (urgency, frequency and nocturia) storage symptoms were significantly associated with an increased fall rate even in the absence of urgency incontinence.
DISCUSSION This population based prospective study shows that lower urinary tract storage and voiding symptoms are associated with falls in community dwelling older men. The strongest association was found for urgency incontinence that occurred more than weekly. Also, storage symptoms (urgency, frequency and nocturia) as a whole, represented as intermediate to high I-PSS-S, were associated with falls independently of urgency incontinence. In a large, well performed, prospective study of 5,872 men Parsons et al examined a wide range of LUTS for associations with falls.18 Unlike in our study, they did not account for incontinence but found weak associations of I-PSS individual symptoms and total I-PSS with falls. In our study with a smaller sample size only urgency, intermittence and total I-PSS were associated with falls. In addition, we found that storage and voiding subscores were associated with falls and neither had an apparently stronger association than the other score. Urgency incontinence was associated with falls in our study but other types of incontinence were not. This is consistent with studies in women.19,20 Urgency has also been associated with falls in past studies in men and women2,3 but these studies did not assess urine leakage. In our series urgency was further examined for an association with falls by the presence of urgency incontinence to determine whether urine leakage would make an additional contribution to fall risk beyond that of urgency alone. We defined urgency and incontinence as those occurring half the time and more than weekly, respectively, which we considered clinically important. Urgency incontinence was moderately associated with falls but urgency without urgency incontinence was not. On post hoc analysis OAB symptoms as a whole, represented as I-PSS-S, were examined for an association with falls by the presence of urgency incontinence, which is the most severe form of Dochead: Adult Urology
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OAB. We found that intermediate to high I-PSS-S was associated with falls even in the absence of urgency incontinence. This indicates that storage symptoms collectively contribute to fall risk, although urgency alone without accounting for frequency and nocturia did not make an independent contribution to fall risk. Our study has a number of strengths. CHAMP includes a large representative sample of community dwelling, older Australian men. While the response rate was relatively low at 47%, the prevalence of major medical conditions and the distribution of responses to a question on self-rated health were similar to those in 915 men 70 years old or older in the nationally representative MATeS (Men in Australia Telephone Survey) study.21 Validated questionnaires were used to assess a whole range of LUTS, falls were ascertained prospectively and associations were adjusted for an extensive list of previously identified fall risk factors. A limitation of our study is inherent in the study design. Our results only apply to community dwelling men without conditions related to LUTS and falls, such as dementia, poor mobility and neurological disease. Another limitation is that ascertainment of falls relied on recall of the last 4 months without using fall diaries. Although this was not ideal, Mackenzie et al reported that recalls of falls in last 6 months were reliable in people 70 years old or older.22 Besides, the quality of responses are unlikely to have varied according to LUTS status. To determine LUTS we did not discriminate between nocturnal micturition with and without urgency.23 This could have masked the possible association between nocturnal urgency and falls. Lastly and most importantly, causality is unclear since we could not determine the circumstances of the falls. Therefore, it is uncertain whether medical, surgical or behavioral interventions for LUTS alone could decrease falls in community dwelling older people.24 Since falls are often multifactorial, other predisposing or precipitating factors for falls that were not fully adjusted for may have had a part in the increased fall risk. The circumstances of falls in men with LUTS should be investigated to generate hypotheses about what types of interventions may be incorporated into multidimensional fall prevention strategies. Also, future trials to treat LUTS should consider including falls as an end point.
CONCLUSIONS Lower urinary tract storage and voiding symptoms are associated with falls in community dwelling older men. In particular, urgency incontinence
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571 572 573 574 575 576 577 578 579 580 581 582 583 584 585 586 587 588 589 590 591 592 593 594 595 596 597 598 599 600 601 602 603 604 605 606 607 608 609 610 611 612 613 614 615 616 617 618 619 620
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(incontinence with an urgency component, including mixed incontinence) carries a higher risk of falls. Also, storage symptoms are collectively associated with falls even in the absence of urgency incontinence. Other types of incontinence and urgency alone without urgency incontinence were not associated with falls. Evidence is lacking about whether
treatment of LUTS decreases the fall risk in community dwelling men. The circumstances of falls among men with LUTS should be explored to generate hypotheses regarding potential interventions. Furthermore, trials to treat LUTS in older men should consider including falls as an end point.
REFERENCES 1. Tinetti M, Speechley M and Ginter S: Risk factors for falls among elderly persons living in the community. N Engl J Med 1988; 319: 1701. 2. Chiarelli P, Mackenzie L and Osmotherly P: Urinary incontinence is associated with an increase in falls: a systematic review. Aust J Physiother 2009; 55: 89. 3. Noguchi N, Chan L, Cumming RG et al: A systematic review of the association between lower urinary tract symptoms and falls, injuries and fractures in community-dwelling older men. Aging Male 20167; doi: 10.3109/13685538.2016. 1169399. 4. Chapple CR, Wein AJ, Abrams P et al: Lower urinary tract symptoms revisited: a broader clinical perspective. Eur Urol 2008; 54: 563. 5. Barry MJ, Fowler FJ Jr, O’Leary MP et al: Correlation of the American Urological Association symptom index with self-administered versions of the Madsen-Iversen, Boyarsky and Maine Medical Assessment Program Symptom indexes. J Urol 1992; 148: 1558. 6. Cumming RG, Handelsman D, Seibel MJ et al: Cohort profile: the Concord Health and Ageing in Men Project (CHAMP). Int J Epidemiol 2009; 38: 374. 7. Avery K, Donovan J, Peters TJ et al: ICIQ: a brief and robust measure for evaluating the symptoms and impact of urinary incontinence. Neurourol Urodyn 2004; 23: 322. 8. Liao CH, Chung SD and Kuo HC: Diagnostic value of International Prostate Symptom Score voiding-to-storage subscore ratio in male lower
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