The impact of urinary incontinence on falls: A systematic review and meta-analysis

Shinje Moon; Hye Soo Chung; Yoon Jung Kim; Sung Jin Kim; Ohseong Kwon; Young Goo Lee; Jae Myung Yu; Sung Tae Cho

doi:10.1371/journal.pone.0251711

. 2021 May 19;16(5):e0251711. doi: 10.1371/journal.pone.0251711

The impact of urinary incontinence on falls: A systematic review and meta-analysis

Shinje Moon ¹, Hye Soo Chung ¹, Yoon Jung Kim ¹, Sung Jin Kim ², Ohseong Kwon ², Young Goo Lee ², Jae Myung Yu ¹, Sung Tae Cho ^2,^*

Editor: Peter FWM Rosier³

PMCID: PMC8133449 PMID: 34010311

Abstract

Objective

Previous studies on the association between urinary incontinence (UI) and falls have reported conflicting results. We, therefore, aimed to evaluate and clarify this association through a systematic review and meta-analysis of relevant studies.

Methods

We performed a literature search for relevant studies in databases including PubMed and EMBASE from inception up to December 13, 2020, using several search terms related to UI and falls. Based on the data reported in these studies, we calculated the pooled odds ratios (ORs) for falls and the corresponding 95% confidence intervals (CIs) using the Mantel–Haenszel method.

Results

This meta-analysis included 38 articles and a total of 230,129 participants. UI was significantly associated with falls (OR, 1.62; 95% CI, 1.45–1.83). Subgroup analyses based on the age and sex of the participants revealed a significant association between UI and falls in older (≥65 years) participants (OR, 1.59; 95% CI, 1.31–1.93), and in both men (OR, 1.88; 95% CI, 1.57–2.25) and women (OR, 1.41; 95% CI, 1.29–1.54). Subgroup analysis based on the definition of falls revealed a significant association between UI and falls (≥1 fall event) (OR, 1.61; 95% CI, 1.42–1.82) and recurrent falls (≥2 fall events) (OR, 1.63; 95% CI, 1.49–1.78). According to the UI type, a significant association between UI and falls was observed in patients with urgency UI (OR, 1.76; 95% CI, 1.15–1.70) and those with stress UI (OR, 1.73; 95% CI, 1.39–2.15).

Conclusions

This meta-analysis, which was based on evidence from a review of the published literature, clearly demonstrated that UI is an important risk factor for falls in both general and older populations.

Introduction

The proportion of adults aged ≥65 years is increasing more rapidly than that of people in other age groups because of the global increase in life expectancy. However, this increase in life expectancy also increases the risk of geriatric syndromes, which are defined as the set of multifactorial conditions affecting older adults who are vulnerable to the changing circumstances [1]. Inouye et al. reported a high prevalence of five geriatric syndromes, namely, falls, incontinence, pressure ulcers, delirium, and functional decline, which are associated with high morbidity and poor quality of life [1].

Of these geriatric syndromes, falls represent one of the most important and increasing public health problems affecting older adults because these events often require medical attention. The World Health Organization (WHO) defines falls as “events that result in a person coming to rest inadvertently on the ground or floor or other lower-level.” These events are often recurrent, and approximately half of the affected individuals experience another fall within 1 year [2]. According to the WHO, 28–35% of people older than 65 years of age fall each year, and this prevalence increases with age [3]. Another study determined that more than 30% of older (>65 years) home-dwelling individuals fall at least once per year [4]. Consequently, a substantial proportion of these individuals develop serious injuries, pain, depression, and other comorbidities. Even a slight fall can cause a fracture, which increases the risk of institutionalization and the associated economic burden. Falls also instill a source of fear in caregivers and negatively affect the healthcare systems [3]. In summary, falls result in negative health outcomes and limit the quality of life of older individuals, and strategies to prevent this geriatric syndrome should be established.

Assessing the association between falls and other geriatric syndromes [1] is clinically important in preventing falls. This syndrome is highly prevalent in the general population and affects men and women of all ages. Of the other geriatric syndromes, urinary incontinence (UI) is more common in women than in men; however, and the prevalence increases with age. Current estimates suggest that approximately 20 million women and 6 million men in the United States experience UI during their lives. This condition has been shown to affect 11–34% of men and 13–50% of women older than 60 years and 43–80% of all older nursing home residents [5]. UI is associated with not only a decreased quality of life but also a longer hospital stay and a reduced chance of hospital discharge [5]. However, many patients, particularly older individuals, avoid or do not receive treatment for UI due to the social stigma attached to the condition.

Although several epidemiological studies have evaluated the effects of UI on falls, the results of analyses based on age, sex, and the definition of falls have been inconclusive. Although some studies reported that UI is positively associated with falls [6–8], others indicated no association [9–11]. Hence, a meta-analysis was warranted to clarify our understanding of the role of UI in falls. We, therefore, performed a meta-analysis to provide evidence and determine the effect of UI on the risk of falls based on a comprehensive investigation of the literature. Furthermore, we conducted subgroup analyses based on patients’ mean age, sex, the definition of falls, and type of UI.

Methods

Search strategy

A literature search was conducted in adherence to the principles outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses—PRISMA (S1 Table). The study protocol was registered in PROSPERO (CRD42021225038). Two independent investigators (S.M. and S.T.C.) searched citation databases (PubMed, EMBASE, and Web of Science) for relevant studies. The search terms were a combination of “urinary incontinence” and “fall.” The search was limited to original articles written in English and published between database inception and December 13, 2020 (S2 Table).

Study selection

The inclusion criteria were as follows: 1) population: studies with participants aged ≥ 50 years or mean age ≥ 60 years; 2) exposure: the presence of UI; 3) comparators: participants without UI; 4) outcomes: incidence of falls; and 5) study design: case-control or cohort studies.

The exclusion criteria were as follows: 1) articles published as experimental studies, containing only abstracts, and published as non-original articles, including expert opinions or reviews; 2) studies that enrolled young adults aged <40 years; 3) observational studies without a control group.

Data extraction

Data of the following variables were extracted independently by two investigators using the same criteria: name of the first author, year of publication, country, demographic characteristics of the participants, mean age of the participants, number of study participants, number of cases of falls, and odds ratios (OR) with 95% confidence intervals (CI).

Risk of bias assessment

We used the Risk Of Bias In Non-randomized Studies—of Exposures (ROBINS-E), a modified form of ROBINS—of Interventions (ROBINS-I), to assess the methodological quality of the included studies [12, 13]. Discrepancies were resolved by discussion with a third investigator (J.M.Y).

Data analyses and statistical methods

The overall ORs and 95% CIs of all studies were computed using the Mantel–Haenszel method. Heterogeneity among the studies was tested using the Higgins I² statistic, where an I² of ≥50% indicated heterogeneity. We computed the ORs using the random-effects model. Publication bias was calculated using a funnel plot and Egger’s test. Sensitivity analysis was also performed.

Subgroup analysis

All analyses were conducted using the Comprehensive Meta-Analysis software version 3 (Biostat, Englewood, NJ, USA).

Results

Study characteristics

In total, 1,427 studies were identified from the literature search (PubMed: 286, EMBASE: 439, and Web of Science: 702). After excluding 250 duplicate studies, we reviewed the remaining studies. Next, 1,177 studies were excluded during primary screening. After reviewing the texts of 107 articles, we excluded 73 studies, resulting in the inclusion of 34 articles [2, 7–11, 14–40]. In addition, we found four eligible studies from a previous review [41]. Finally, a total of 38 studies with 230,129 participants were included in this meta-analysis (Fig 1).

The main characteristics of the studies are summarized in Table 1 [2, 7–11, 14–40, 42–46]. The meta-analysis revealed that, overall, 27.6% of participants (n = 63,618) experienced falls. The definitions of falls varied across the reviewed studies. Twenty-nine studies defined a fall as ≥1 fall event [7–9, 11, 17, 18, 20, 22, 23, 26–40, 42–46], four studies defined a fall as ≥2 fall events [14, 15, 21, 25], and five studies defined a fall as ≥1 fall event and recurrent falls as ≥2 fall events [2, 10, 16, 19, 24].

Table 1. Summary of the 38 studies included in the present meta-analysis.

Study [Reference]	Country	Source of sample	Population characteristics	No. of total participants	Definition of falls/ No. of participants with falls	Definition and type of UI/ No. of participants with UI	Relative risk (95% CI)	Risk of bias
Tinetti ME et al. 1995 [14]	USA	Community dwelling adults, aged 72 years and older	Mean age: 79.7 Women:73%	927	At least two falls in 1 year	At least one UI / week in 1 year	Crude OR: 1.9 (95% CI, 1.2–2.9)	Critical
Tinetti ME et al. 1995 [14]	USA	Community dwelling adults, aged 72 years and older	Mean age: 79.7 Women:73%	927	96	146	Crude OR: 1.9 (95% CI, 1.2–2.9)	Critical
Luukinen H et al. 1996 [15]	Finland	Community dwelling adults, aged 70 years and older	Mean age: 76.1	1,016	At least two falls in 1 year	UI during the past 2 years	Adjusted ^a OR: 1.70 (95% CI, 1.03–2.89)	Serious
Luukinen H et al. 1996 [15]	Finland	Community dwelling adults, aged 70 years and older	Men: 396 Women: 620	1,016	88	158	Adjusted ^a OR: 1.70 (95% CI, 1.03–2.89)	Serious
Johansson C et al. 1996 [9]	Sweden	Community dwelling women, aged 85 year old	Mean age: 85	658	At least one falls	UI monthly, weekly, several/week, daily, several/day.	Crude OR: 1.00 (95% CI, 0.75–1.33)	Critical
			Women:100%		286	urge type (46%),
						stress (21%), mixed (33%)
						384
Brown JS et al. 2000 [7]	USA	Community-dwelling women, aged 65 years and older	Mean age: 78.5	6,049	At least one falls in 1 year	UI during the past 1 year.	Adjusted ^b OR:	Moderate
			Women:100%		1,927	At least one UI:2,818 (46.6%),	-Stress type: 1.06 (95% CI, 0.95–1.19)
			Women:100%		1,927	At least weekly urge type: 1,493 (24.7%), At least weekly stress type: 1,137(18.8%), Both type: 708(11.7%).	-Urge type: 1.26 (95% CI, 1.14–1.40)
Tromp AM et al. 2001 [16]	Netherlands	Community-dwelling adults, aged 65 years and older	Mean age: 72.6	1,469	At least one falls in 1 year	Self- reported UI 24%	Adjusted ^c OR: 1.6 (95% CI, 1.2–2.1)	Serious
			Men: 705 Women: 764		464		Adjusted ^c OR: 1.6 (95% CI, 1.2–2.1)
			Men: 705 Women: 764		464		Recurrent fall: Adjusted OR: 1.7 (95% CI, 1.2–2.5)
de Rekeneire N et al. 2003 [17]	USA	Community-dwelling adults, aged 70 to 79 years	Age (70–79) Men: 1,447		At least one falls in 1 year	Self- reported UI1,175	Adjusted ^d OR:	Serious
			Women: 1,515	2,962	652		- Men 1.5 (95% CI, 1.1–2.0)
			Women: 1,515	2,962	652		- Women: 1.5 (95% CI, 1.2–1.9)
Takazawa K et al. 2005 [10]	Japan	Women in a day care service at geriatric health facility	Median age: 81	118	At least one falls in 1 year	At least once a week during the past 1 year	Crude OR: 1.12 (95% CI, 0.54–2.32)	Critical
			Women:100%		56	At least once a week during the past 1 year
			Women:100%		56	Stress type: 25 (49.0%), Urge type: 46(90.2%) 52
Teo JS et al. 2006 [18]	Australia	Community-dwelling women	Mean age: 79.1	782	At least one falls in 1 year	Self- reported UI (regardless of amount and frequency)	Adjusted ^e OR: -Stress type: 1.06 (95% CI, 0.77–1.45)	Serious
			Women:100%		275		Adjusted ^e OR: -Stress type: 1.06 (95% CI, 0.77–1.45)
							-Urge type: 1.96 (95% CI, 1.45–2.65)
						Stress type: 69.4% (pure 36.8%)
						Urge type: 36.3% (pure 3.7%), both type: 32.6%.
						73.1%
Hasegawa J et al. 2010 [19]	Japan	Disabled older people who were admitted to facilities	Mean age: 82.5	1,082	At least one falls	UI events during placement 180	Adjusted ^f OR: 2.14 (95% CI, 1.03–2.89)	Serious
			Mean age: 82.5		264
			Men: 327
			Women: 755
Foley AL et al. 2012 [8]	UK	Community-dwelling adults aged 70 years or Over	Median age: 76	5,474	At least one falls in 1 year	Self- reported UI	Crude OR:	Critical
			Men: 2,245		1,813	Stress type: 16.5%, urge type: 24.9%	-Stress type: 3.56 (95% CI, 3.06–4.15)
			Women: 2,917		26.7%	-Urge type: 2.19 (95% CI, 1.92–2.49)
Allain TJ et al. 2014 [20]	Malawi	Community-dwelling adults aged 60 years or Over	Mean age: 72	98	At least one falls in 1 year	Self- reported UI	Crude OR: 3.27 (95% CI, 1.26–8.50)	Critical
			Men: 29		At least one falls in 1 year	Self- reported UI
			Women: 69		40	25%
Huang LK et al. 2015 [21]	Taiwan	Community-dwelling adults aged 65 years or Over	Age ≥65 years	187	At least two falls in 1 year	UI in the past 1 year and 1week.	Adjusted ^g OR: 1.86 (95% CI, 0.86–4.02)	Serious
			Men: 65		At least two falls in 1 year	UI in the past 1 year and 1week.
			Women: 122		53	29.9%
Kim H et al. 2015 [22]	Japan	Community-dwelling women aged 75–84 years	Mean age: 78.5	1,399	At least one falls	UI over once a week	Crude OR: 1.57 (95% CI, 1.14–2.16)	Critical
			Women:100%		269	Stress type: 29.2% (76/260), Urge type: 25.0% (65/260), and Mixed type:45.8% (119/260)
			Women:100%		269	260
Sakushima K et al. 2016 [11]	Japan	Ambulatory patients with Parkinson’s disease in an outpatient clinic of an academic hospital	Mean age: 71.5	97	At least one falls in 6 months	Mild: less than once a day, severe: once a day or more past 1 week.	Crude OR: 2.05 (95% CI, 0.88–4.73)	Critical
			Men: 40		44
			Women: 57
						Mild 27
						Severe 17
Schluter PJ et al. 2018 [23]	New Zealand	Community-dwelling adults aged 65 years or Over	Mean age: 82.7	67,288	At least one falls in 90 days	UI in the last 3 days	Adjusted ^h OR:	Moderate
			Mean age: 82.7		At least one falls in 90 days	Occasional UI: less than daily, frequently UI: daily	Adjusted ^h OR:
			Men: 25,257		27,213		-Men
			Women: 42,032				Occasional UI 1.53 (95% CI, 1.43–1.64)
						Men 34.3%
						Women 42.6%
							Frequent UI 1.69 (95% CI, 1.57–1.82)
							-Women
							Occasional UI
							1.33 (95% CI, 1.26–1.39)
							Frequent UI 1.39 (95% CI, 1.32–1.46)
Agudelo-Botero M et al. 2018 [24]	Mexico	Community-dwelling adults aged 60 years or Over	Age ≥60 years	9,598	At least one falls in 2 years	UI during the last 2 years	Adjusted ⁱ OR: -Occasional falls	Moderate
			Men: 4,271		At least one falls in 2 years	UI during the last 2 years
			Men: 4,271		4,466 (46%, one fall 16%, recurrent falls 30%))	3,021
			Women: 5,327				1.12 (95% CI, 0.98–1.28)
			Women: 5,327				-Recurrent falls 1.52 (95% CI, 1.37–1.69)
Kang J et al. 2018 [25]	Korea	Patients older than 65 who visited the geriatric clinic	Mean age: 73	404	At least two falls in 6 months	UI during the last 1 month	Crude OR: 2.07 (95% CI, 1.23–3.35)	Critical
			Men: 114		At least two falls in 6 months	UI during the last 1 month
			Men: 114		89	133
			Women: 290		89	133
Kim HJ et al. 2018 [26]	Korea	Community-dwelling adults aged 66 years or over in nationwide cohort study	Age (66–80) Men: 20,943	39,854	At least one falls in 6 months	Self- reported UI	Crude OR: 5.29 (95% CI, 4.87–5.73)	Critical
			Age (66–80) Men: 20,943		At least one falls in 6 months	5,703
			Women: 18,911		2,802	5,703
Sohn K et al. 2018 [27]	Korea	Community-dwelling women aged 65 years or over in Korean Longitudinal Study of Ageing	Age ≥65 years	2,418	At least one falls in 2 years	UI in the past 1 year	Crude OR: 1.29 (95% CI, 0.92–1.79)	Critical
			Women:100%		At least one falls in 2 years	UI in the past 1 year
			Women:100%		204	506
Singh DKA et al. 2019 [28]	Malaysia	Community-dwelling adults aged 60 years or Over	Mean age: 68.9	3,901	At least one falls in 1 year	Self- reported UI	Adjusted ^j OR: 1.35 (95% CI, 1.07–1.69)	Serious
Singh DKA et al. 2019 [28]	Malaysia	Community-dwelling adults aged 60 years or Over	Men: 1,807 Women: 2,127	3,901	804	615	Adjusted ^j OR: 1.35 (95% CI, 1.07–1.69)	Serious
Peeters G et al. 2019 [29]	Australia, Netherlands, Great Britain Ireland	Community-dwelling adults from four cohort (ALSWH, LASA, NSHD, TILDA)	Mean age:	ALSWH: 10,641	At least one falls in 1 year	Self- reported UI	Adjusted ^a OR:	Serious
			-ALSWH: 55.0–63.1.	ALSWH: 10,641	At least one falls in 1 year	-ALSWH: 45.6–59.0%	Adjusted ^a OR:
				LASA: 802	-ALSWH: 2,352	-ALSWH: 45.6–59.0%	-ALSWH:
				LASA: 802	-ALSWH: 2,352	-LASA: 16.7%	1.53 (95% CI, 1.44–1.63) -LASA:
			Women:100%-LASA: 59.7	NSHD: 2,987	-LASA: 201	-NSHD: 32.2%	1.53 (95% CI, 1.44–1.63) -LASA:
			Women:100%-LASA: 59.7	NSHD: 2,987	-NSHD: 520	-TILDA: 10.3–12.6%	1.62 (95% CI, 0.95–2.78)
			Women:51.6%	TILDA: 4663	-TILDA: 820		1.62 (95% CI, 0.95–2.78)
			Women:51.6%				-NSHD: 1.68 (95% CI,
			-NSHD: 53.5–63.4				-NSHD: 1.68 (95% CI,
			-NSHD: 53.5–63.4				1.22–2.31) -TILDA: 2.09 (95% CI, 1.75–2.49)
			Women:50.9–52.2%
			-TILDA: 56.7–58.6
			Women:55.5–57.3
Giraldo-Rodriguez L et al. 2019 [30]	Mexico	Community-dwelling adults aged 50 years or Over	Aged ≥ 50	13,626	At least one falls in 2 years	UI during the past 2 years	Crude OR:	Critical
			Aged ≥ 50		At least one falls in 2 years	UI during the past 2 years	- Men: 1.42	Critical
			Men: 5,843		5,341	-Men: 730 (12.5%)	(95% CI, 1.18–1.71)
			Women: 7,783			Stress type:141(2.4%), urge type:317(5.4%), mixed type:272(4.7%)
						-Women: 2,155
						(27.7%)
							- Women:
							1.22 (95% CI, 1.06–1.39)

						Stress type:731(9.4%), urge
						type:488(6.3%), mixed type:936(12%)
Huang MH et al. 2019 [31]	USA	Men aged 65 years or over who had prostate cancer or breast cancer	74.5(men)	1097	At least one falls in 1 years	UI during the past 6 months	- Men Adjusted ^k	Serious
			75.1(women)	1097	At least one falls in 1 years	UI during the past 6 months	- Men Adjusted ^k
			Men: 660		231	285(men)	OR:
			Women: 437			219 (women)	1.69 (95% CI, 1.08–2.65)
							-Women
							Crude OR: 2.27 (0.89–5.80)
Abbs E et al. 2020 [32]	USA	Homeless adults aged 50 years or Over	Median age: 58	350	At least one falls in the past 6 months	UI during the past 6 months 167	Adjusted ^l OR: 1.40 (95% CI, 1.07–1.81)	Moderate
			Men: 270		At least one falls in the past 6 months	UI during the past 6 months 167
			Women: 80		118
Abell JG et al. 2020 [33]	UK	Community-dwelling adults aged 60 years or Over	Mean age: 69.6	3,783	At least one falls in 1 year	UI during the past 12 months	Adjusted ^m HR:: 1.49 (95% CI, 1.14–1.95)	Moderate
			Men: 1,791		315	574
			Women: 1,992
Britting S et al. 2020 [34]	Austria	Community-dwelling adults aged 75 years or over from SCOPE cohort	Median age: 79.5	2,256	At least one falls in 1 year	UI during the last 1 month	Adjusted ⁿ OR: 1.33 (95% CI, 1.09–1.63)	Moderate
	Germany		Median age: 79.5	2,256	At least one falls in 1 year	UI during the last 1 month
	Israel		Men: 1,000		746	653
	Italy		Women: 1,256
	Netherlands
	Poland
	Spain
Dokuzlar O et al. 2020 a [35]	Turkey	Women aged 65 years or over	Mean age: 74.4	682	At least one falls in 1 year	UI during the past 12 months	Adjusted ^o OR: 1.61 (p value: 0.006)	Serious
Dokuzlar O et al. 2020 a [35]	Turkey	Women aged 65 years or over	Women:100%		215	55.4%	Adjusted ^o OR: 1.61 (p value: 0.006)	Serious
Dokuzlar O et al. 2020 b [36]	Turkey	Men aged 65 years or over	Mean age: 75.0	334	At least one falls in 1 year	UI during the past 12 months	Adjusted ^o OR: 2.468 (p-value: 0.001)	Serious
Dokuzlar O et al. 2020 b [36]	Turkey	Men aged 65 years or over	Men:100%		85	33.2%	Adjusted ^o OR: 2.468 (p-value: 0.001)	Serious
Lee K et al. 2020 [37]	USA	Community-dwelling adults aged 65 years or over	Mean age: 70.4	17,712	At least one falls in 2 year	UI during the past 12 months	Adjusted ^p OR: 1.96 (95% CI, 1.59–2.40)	Serious
			Mean age: 70.4		4,779	3,340
			Men: 7,626
			Women: 10,086
Magnuszewski L et al. 2020 [38]	Poland	Patients admitted to the department of geriatrics	Mean age: 85	358	At least one falls in 1 year	Self- reported UI	Adjusted ^q OR: 1.37 (95% CI, 0.75–2.49)	Serious
			Men:80		At least one falls in 1 year	146
			Women: 278		157	146
Moon S et al. 2020 [2]	Korea	Community-dwelling women aged 65 years or over	Mean age: 74.5	6,134	At least one falls in 1 year	Self- reported UI	Adjusted ^r OR: 1.33(95% CI, 1.00−1.76)	Moderate
			Mean age: 74.5	6,134	At least one falls in 1 year	281
			Women:100%		1,152	281
Savas S et al. 2020 [39]	Turkey	Community-dwelling adult	Mean age: 65	1176	At least one falls in 1 year	Self- reported UI	Crude OR:	Critical
			Men:592	1176	At least one falls in 1 year	346	1.21 (95% CI, 0.79–1.87)
			Women: 584		276	346	1.21 (95% CI, 0.79–1.87)
Tsai YJ et al. 2020 [40]	Taiwan	Community-dwelling adults aged 65 years or over (NHIS 2005, 2009, 2013)	Men:4,142	8,822	At least one falls in 1 year	Self- reported UI	Adjusted ^s OR: 1.09 (0.80–1.49), 1.29 (0.90–1.84), 1.42 (1.04–1.94)	Serious
			Women: 4,680		At least one falls in 1 year	1,573
			Women: 4,680		1,672	1,573
Cesari M et al.2002 [42]	Italy	Community-dwelling adults admitted to national home care program	Mean age: 77.2	5,570	At least one falls in 90 days	Self- reported UI	Adjusted ^t OR: 1.06 (0.93–1.20),	Serious
				5,570	1,997	1,744
				Men: 2,290
				Women: 3,280
Hedman AM et al. 2013 [43]	Sweden	Community-dwelling adults aged 75 years or over	Median age: 81	1,243	At least one falls in 1 year	Self- reported UI 1,139	Adjusted ^u OR: 1.53 (1.23–1.91),	Serious
			Men: 471		434	425(men)	Adjusted ^u OR: 1.53 (1.23–1.91),
			Women: 772			714(women)	- Men: 1.67 (1.13–2.47),
			Women: 772			714(women)	- Women: 1.53 (1.16–2.00)
Moreira MD et al. 2007 [46]	Brazil	Community-dwelling adults aged 60 years or over	Mean age: 79	490	At least one falls in 1 year	Self- reported UI 86	p <0,025	Critical
			Men: 116		At least one falls in 1 year	Self- reported UI 86
			Men: 116		137
			Women: 374		137
Stenhagen M et al. 2013 [44]	Sweden	Community-dwelling adults aged 60 years or over	Men: 264	1,736	At least one falls in 6 months	Self- reported UI	Crude OR: 1.89 (1.38–2.58)	Serious
			Women: 394 (3-year follow up)	555 (3-year follow up)	At least one falls in 6 months	267
				555 (3-year follow up)	106(3-year follow up)
				1,542(6-year follow up)	106(3-year follow up)		With UI: 267 (67 with falls)
			Men: 784	1,542(6-year follow up)	205(6-year follow up)
			Women: 963 (6-year follow up)
							Without UI: 1453 (219 with falls)
							Adjusted ^a OR: 1.31 (0.94–1.82)
van Helden S et al. 2007 [45]	Netherland	Patients older than 50 who visited the geriatric clinic	Mean age: 67.1	277	At least one falls in 3 months	Self- reported UI	Crude OR: 2.07 (0.98–4.41)	Critical
			Men: 77		42	50
			Women: 200		42	50

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OR, odds ratios; HR, hazard ratios; UI, urinary incontinence; CI, confidence intervals; ALSWH, The Australian Longitudinal Study on Women’s Health; LASA, The Longitudinal Ageing Study Amsterdam; NSHD, The MRC National Survey of Health and Development; TILDA, The Irish Longitudinal Study on Ageing.

^a adjusted for age and sex,

^b adjusted for age, living situation, overall frailty, number of falls in the previous year, whether she walked for exercise, alcohol and caffeine consumption, medical history, medication use, grip strength, gait speed, whether she used her arms to stand from chair, and performance of 10-second tandem balance.

^c adjusted for age, gender, educational level, urbanization level, chronic diseases, physical function, level of activity and mobility, previous falls, fear of falling

^d adjusted for age, race, study site, and body mass index.

^e adjusted for age, central nervous system drug and cardiovascular system drugs.

^f adjusted for age, gender, physical function, behavioral symptom, and medication use.

^g adjusted for gender, depressive mood, and activities involving lower limb.

^h adjusted for: age, ethnicity, marital status, living arrangements, body mass index, cognitive performance, dementia, congestive heart failure, Chronic obstructive pulmonary disease, depression, diabetes mellitus, alcohol consumption, smoking status, hearing status, vision status, fatigue, mobility, stability, dizziness, wandering, season, bisphosphonates, vitamin D, and calcium.

ⁱ adjusted for sociodemographic, medical and functional covariables.

^j adjusted for age, sex, educational level and ethnicity.

^k adjusted for age at prostate cancer diagnosis, time since cancer diagnosis, history of falls, marital status, physical summary score of Veterans RAND 12-Item Health Survey.

^l adjusted for age, sex, race, stroke, Activities of Daily Living (ADL) impairment, use of an assistive device., marijuana use, opioid use, history of physical assault, any nights spent in unsheltered settings.

^m adjusted for age, sex, chronic conditions (coronary heart disease, diabetes, Stroke, Arthritis, Osteoporosis, Parkinson’s Disease), BMI, Smoking status, Alcohol consumption, The Short Physical Performance Battery (SPPB), and history of severe fall.

ⁿ adjusted for age, gender, geriatric depression score (GDS), chronic kidney disease (CKD), instrumental activities of daily living (IADL) score and Euro-Qol 5D Score.

^o adjusted for age, education level, and living environment.

^p adjusted for age, sex, race/ethnicity, and spouse/partner status.

^q adjusted for age, multimorbidity, chronic diseases (cardiac heart failure, peripheral arterial disease, history of stroke/ transient ischemic attack, Parkinson’s disease, and chronic osteoarthritis, Performance Oriented Mobility Assessment, Barthel Index, IADL score, gait speed, Clinical Frailty Scale, Mini Nutritional Assessment Short Form, albumin value, vitamin B12 level and taking certain medications (quetiapine, vitamin D, diuretics, benzodiazepines and selective serotonin reuptake inhibitor).

^r adjusted for age, smoking status, alcohol consumption, body mass index, hypertension, dyslipidemia, and diabetes mellitus, cognitive impairment, ADL and IADL disability, visual and hearing impairment, and lower limb weakness.

^s adjusted for age, sex, developing difficulty in performing ADLs or IADLs, use of sleeping pills, vision, comorbidities, depressive symptoms, and frequency of exercise.

^t adjusted for age, gender, activities of daily living impairment, foot problems, gait problems, fear of falling, visual impairment, wandering, depression, parkinsonism, and environmental hazards.

^u Poor self-rated health, Pain in neck and shoulders, Back pain, sciatica or hip pain, Pain in hands, elbows, legs or knees, Headache or migraine, Anxiety, Tiredness, Sleeping disorders, Tinnitus, Recurring stomach problems, Overweight/Underweight.

Fig 2 summarizes the quality assessment results of the studies and shows that the major source of bias in the studies bias was the lack of adjustment for potential confounders. Among the 38 studies, 14 studies did not adjust for confounding factors and were classified as studies with a critical risk of bias [8–11, 14, 20, 22, 25–27, 30, 39, 45, 46]. Seventeen studies had a serious risk of bias since more than one critically important confounding factor, namely age, sex, and physical function, was not appropriately adjusted or UI was not properly defined [15–19, 21, 28, 29, 31, 35–38, 40, 42–44]. Seven studies, which were appropriately adjusted for confounding factors, had a moderate risk of bias [2, 7, 23, 24, 32–34].

Impact of UI on falls

According to the random-effects model, the overall OR for falls was 1.62 (95% CI, 1.45–1.83). An overall I² of 96.0% indicated heterogeneity among the studies (Fig 3). The funnel plot and Egger’s test did not reveal any publication bias (p = 0.477, Fig 4A). The sensitivity analysis revealed consistently significant ORs between 1.55 and 1.67, even after excluding the results of each included study (Fig 4B). After excluding 14 studies with a critical risk of bias, the OR was 1.46 (95% CI, 1.38–1.56; I², 76.5%).

Fig 3 — OR, odds ratio; CI, confidence interval. *Study that defined falls as at least two falls within 1 year.

Fig 4 — A. Funnel plot of publication bias in studies comparing the odds ratios of urinary incontinence for falls. B. Sensitivity analysis of the meta-analysis of studies comparing the odds ratios of urinary incontinence for falls. *Study that defined falls as at least two falls within 1 year.

Analyses of subgroups stratified by age, sex, the definition of falls, and type of UI

Subgroup analyses were performed according to the age and sex of the participants (Table 2). A significant association between UI and falls was observed in older adults (≥65 years; OR, 1.59; 95% CI, 1.31–1.93) [2, 7–10, 14–17, 21–23, 25–27, 31, 34–37, 40, 43], and in both men (OR, 1.88; 95% CI, 1.57–2.25) [17, 23, 29–31, 36] and women (OR, 1.41; 95% CI, 1.29–1.54) [2, 7, 9, 10, 17, 18, 22, 23, 27, 29–31, 35, 45]. In a subgroup analysis of 34 studies that defined falls as ≥1 fall event, the OR for the association between UI and falls was 1.61 (95% CI, 1.42–1.82; I², 96.3%; Table 2) [2, 7–11, 16–20, 22–24, 26–40, 42–46]. In a subgroup analysis of nine studies that defined recurrent falls as ≥2 fall events, the OR for the association between UI and falls was 1.63 (95% CI, 1.49–1.78; I², 40.6%; Table 2) [2, 10, 14–16, 19, 21, 24, 25]. In a subgroup analysis according to the type of UI, a significant association between UI and falls was observed in patients with urgency UI (OR, 1.76; 95% CI, 1.15–1.70) [7, 8, 10, 18, 30] and in those with stress UI (OR, 1.73; 95% CI, 1.39–2.15) [7, 8, 10, 18, 30].

Table 2. Subgroup analysis of the association between urinary incontinence and falls.

Subgroup	No. of studies [Reference]	OR (95% CI)	Heterogeneity (I²), %
Age, ≥ 65 years	22 [2, 7–10, 14–17, 21–23, 25–27, 31, 34–37, 40, 43]	1.59 (1.31–1.93)	97.6%
Sex
Men	6 [17, 23, 29–31, 36]	1.88 (1.57–2.25)	75.2%
Women	14 [2, 7, 9, 10, 17, 18, 22, 23, 27, 29–31, 35, 45]	1.41 (1.29–1.54)	79.5%
Definition of falls
Falls ≥ 1	34 [2, 7–11, 16–20, 22–24, 26–40, 42–46]	1.61 (1.42–1.82)	96.3%
Falls ≥ 2	9 [2, 10, 14–16, 19, 21, 24, 25]	1.63 (1.49–1.78)	40.6%
Type of urinary incontinence
Urgency incontinence	5 [7, 8, 10, 18, 30]	1.76 (1.15–1.70)	97.1%
Stress incontinence	5 [7, 8, 10, 18, 30]	1.73 (1.39–2.15)	90.2%

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Discussion

Although UI is a known risk factor for falls, the strength of the association between these conditions remains unclear because of variability in the study designs and populations used in previous risk estimations. This systematic review and meta-analysis conducted to evaluate the association between falls and UI revealed that UI was associated with overall falls. Our analysis identified a probable excess OR of 65% for at least one fall among people with UI relative to those without UI. An analysis of participants with recurrent falls yielded a similar trend and a higher risk magnitude. The overall OR for recurrent falls was 63% among people with UI relative to those without UI.

In a subgroup analysis, we determined that the OR for falls increased by 59% in older adults (≥65 years) with UI relative to those without UI. These findings exceed those of older systematic reviews that considered a more limited range of fall-related outcomes and consistently reported an increased risk of falls and fractures among participants with UI [47]. UI is of significant concern to older adults and can lead to isolation and reduced self-worth. Previous studies have identified various risk factors for falls, such as old age, female sex, visual disturbances, cognitive disorders, low body mass index, and UI.

We conducted another subgroup analysis according to the type of UI. A previous review highlighted a predominant association of falls with urgency UI, rather than with other types of UI [47]. This association is attributed to the urgent need to use the toilet and the anxiety associated with a failure to reach the toilet. Several studies have shown that behavioral changes induced by UI can affect the likelihood of falls [48, 49]. Our analysis also showed a higher risk of falls in patients with urgency UI than in those with stress UI. Falls related to this condition have been generally reported to occur in the toilet [7, 47]. Despite this relationship, however, the commonly held assumption that urgency leads to falls while rushing to the toilet has not been confirmed yet [6].

Few studies have investigated the relationship between UI and falls [47], and the causality between UI and falls remains unexplained [6]. However, one hypothesis is that a strong desire to void could change gait parameters and thus, increase the risk of falls [50]. The reduced velocity and stride width during strong desire to void conditions (i.e., urgency) in the UI group could explain their high fall rate [50]. The other hypothesis is that women with impaired mobility probably take a longer time to reach the toilet; hence, if there is a high degree of urgency, then impaired mobility can increase the risk of UI [51]. Therefore, the causality between UI and falls could probably be explained by a strong desire to void and physical impairments in mobility and balance [50, 51]. However, although these hypotheses could explain the relationship between the urgency-type UI and falls, they are rather insufficient to explain the association between stress-type UI and falls. Since the symptoms of urgency UI and stress UI are clinically different, the association between stress UI and falls may indicate a general alteration in the striated muscle physiology in the aging population [8]. In addition, restricted mobility in older women may limit their ability to change positions to prevent stress UI [22].

There is a well-recognized association between falls and lower urinary tract symptoms (LUTS) in older adults [7, 8, 47, 52, 53]. Older people with urgency or urgency UI are significantly more likely to fall than age-matched controls, with ORs for falls ranging between 1.5 and 2.3 [6, 47, 54, 55]. However, the reason for this association is not understood and has not been thoroughly studied [6].

In a recent systemic review on the association between falls and LUTS conducted by Noguchi et al., none of the identified studies had investigated the potential causes of these associations. In addition, the categorization of UI and degree of accounting for confounding variables were inconsistent across the studies [56]. Although the data identified were suitable only for qualitative synthesis, UI and storage symptoms among LUTS have been consistently reported to have a weak to moderate association with falls [6, 56].

As our findings suggest that this association is significant, the identification and treatment of UI may be an effective intervention for reducing the risk of falls, especially in older adults. Bladder training, timed or prompt voiding, and environmental modifications (e.g., a bedside commode) may decrease the incidence of falls [7].

Concerning the impact of UI on the risk of falling, many falls are related to a person’s physical condition or medical problems, such as multimorbidities, polypharmacy, neurological diseases, and sarcopenia, as well as urological comorbidities [57]. Especially, multiple medications, such as blood pressure-lowering drugs causing orthostatic hypotension, psychotropics, anticonvulsants, and sedatives, can contribute to falls [57]. In addition, the geriatric syndrome has a multifactorial etiology, with the factors being closely related to each other [1]. Among them, UI and falls are very important for the older population, and both are associated with sarcopenia [8, 58, 59]. Therefore, an appropriate statistical approach to decrease the impact of such confounding variables is necessary for correct analysis of the association between UI and falls.

The strengths of this study include the collection of evidence through a rigorous systematic review and meta-analysis. This study also included a comprehensive search of both published and unpublished studies. Multiple measurements of falls were considered, consistent with multiple types of risk estimates. Although many studies have included UI as a risk factor for falls, only a few studies have identified UI as an individual risk factor [47]. Therefore, this is the first systematic review and meta-analysis to evaluate UI as an individual risk factor for falls.

Despite these strengths, our study was limited largely by the included studies, particularly the significant heterogeneity, quality of the study designs, and reporting scope of the original articles. However, when studies with a critical risk of bias were excluded, significant results were observed. In addition, no publication bias was observed, and the results were not changed by specific studies in the sensitivity analysis. Furthermore, although we conducted subgroup analyses based on age, sex, and type of UI, we did not perform analyses according to the severity of UI. Finally, the paucity of evidence regarding the severity of UI limits the applicability of our current findings with regard to an accurate correlation between UI and falls.

In conclusion, the continued increase in the proportion of older adults globally will lead to continued increases in the clinical and economic impacts of serious falls. Based on evidence from the published literature and a meta-analysis, we demonstrate here that UI is a predictor of more frequent falls in both general and older adults. Clinicians should, therefore, be aware that UI predicts an increased risk of falls that could lead to fractures and should, therefore, provide appropriate precautions and care. Future studies are needed to address the impact of UI treatment on the incidence of falls.

Supporting information

S1 Table. PRISMA checklist.

(DOCX)

Click here for additional data file.^{(28.7KB, docx)}

S2 Table. Electronic search strategy.

(DOCX)

Click here for additional data file.^{(16.3KB, docx)}

S1 Data. PubMed: 286 studies.

(DOCX)

Click here for additional data file.^{(134.2KB, docx)}

Abbreviations

CI: confidence interval
LUTS: lower urinary tract symptoms
OR: odds ratio
UI: urinary incontinence
WHO: World Health Organization

Data Availability

The literature search was conducted in adherence to the principles outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Funding Statement

The authors declare that they have no relevant financial interests. (no funding).

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PLoS One. doi: 10.1371/journal.pone.0251711.r001

Decision Letter 0

Peter FWM Rosier

5 Nov 2020

PONE-D-20-28464

The Impact of Urinary Incontinence on Falls: A Systematic Review and Meta-Analysis

PLOS ONE

Dear Dr. Cho,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a

ACADEMIC EDITOR:

In addition to the reviewers' comments, I have a comment. The populations in the studies you have selected are quite different. Some studies have included elderly people with Parkinson's disease or multiple sclerosis, and others elderly people diagnosed with frailty. These people with impaired mobility and / or strength might have a different starting risk if incontinence (or frequent micturition) is present, or develops than in the cohorts without these disorders. Doesn't this require a separate paragraph in the discussion on how this (confounder?) is handled in the manuscripts? You also mention the term 'prompt voiding', the standard term for this strategy is 'prompted voiding', I think.

Please ensure that your decision is justified on PLOS ONE’s publication criteria and not, for example, on novelty or perceived impact.

==============================

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PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: In this systematic review with meta-analysis, the authors focused on the relationship between urinary incontinence and falls. Although the subject is fascinating, the study is penalized by an incomplete submission (tables 1 to 3 are missing) and the absence of subgroup analysis concerning the type of urinary incontinence (urgency vs. stress). It is therefore possible to improve this manuscript by taking into account these 2 points and those that follow:

General comment: Authors should avoid the term "elderly" or "elder" and prefer "older"

1. Abstract: There is a difference between the abstract and the methods in the dates of literature search (october 2019 in the abstract and april 2020 in the methods)

2. Methods:

a. Why did the authors choose as an eligibility criteria studies with population over 20 years? The introduction is developed around the ageing of the population and the fact that both urinary incontinence and falls are geriatric syndromes. I do know that the definition of older age varies widely among countries but 20 years old is definitely not old…

b. Results of the study selection process should be included in the results and not in the methods

c. Data extraction: there is no information on urinary incontinence, its type or severity.

d. Quality assessment. This section should be renamed as: risk of bias assessment. Unfortunately, there is no validation study of the Newcastle Ottawa tool, and no validation of the cut-off used to assess the risk of bias (what is the reference for this cut-off?) Could the authors discuss the choice of this tool and use a more appropriate one?

e. Why the authors did not register their systematic review and meta-analysis protocol? It is well known that the absence of a published protocol can lead to bias (10.1001/jama.287.21.2831).

f. Regarding the search strategy, there is no full electronic search strategy available as it is stated in the PRISMA checklist. Authors should provide it as a supplementary data.

3. Results:

a. The results section is uncomplete since tables 1 to 3 are missing (problem during the submission process?). It is difficult to judge this work without these tables, and I cannot make much more comments without these tables.

b. It seems that there is a problem with the figure 3 (“omitting” in front of each study name). Did the authors proofread their manuscript?

c. The study by Peeters et al in 2019 was included 4 times in the meta-analysis. Could the authors provide an explanation? Are they sure that it was not conducted in the same population?

4. Discussion:

Since we do not have any tables, it is difficult to understand why the authors did not discuss a critical point. I think that the association between UI and falls is rather known and admitted, but the remaining question is “is there any causality between UI and falls”? As the authors said, UI and falls are probably more related to “frailty” and the significant association that many studies highlight may not exist as such.

o Do we have any prospective data to answer this question?

o Do we have some biological hypothesis to support this? (rather not, the authors started to discuss this point but not enough to my opinion, they forgot to include in there discussion the studies published by Dumoulin et al. on gait and urge to void, by Fritel et al. on urinary incontinence subtypes and mobility impairment, etc. )

o Were the studies adjusted on potential confounders? (neurological pathologies? Comorbidities? Polypharmacy?)

o Was the association different if stress or urgency urinary incontinence were considered?

Reviewer #2: I want to congratulate the authors for the idea and development of this manuscript. The paper adds valuable information about the link of falls and UI in terms of higher level of evidence after this systematic review.

I suggest some comments in order to improve quality and understanding of the manuscript:

1. Figure 4 can be omitted, from my view it does not add important information for the reader

2. Please describe acronyms TE/seTE in figure 2.

3. There is a significative statistical heterogeneity in the studies included. This is reflected in the results section, but it is a limitation of the study and need to be commented in the discussion. Probably this point and the quality of the study designs and the reporting scope of the original articles is the main limitation of this meta-analysis.

4. Some studies have shown association between type of UI (specially UUI) and severity (more number of UUI episodes per week). The authors don’t clarify why they don’t include this subgroup analysis. It would be very interesting to have this information in this kind of systematic review.

5. There is a previous systematic review on LUTS and falls that the authors has not mentioned [Noguchi, N., 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, 2016: p. 1-7.]. In this SR none of the identified studies examined potential causes for these associations; the categorisation of continence or not and degree of accounting for confounding variables was inconsistent across the included studies. This point should be discussed and compared with results with your SR.

6. From the point of view of the reader is not clear the categorization in the definition of falls (≥1, ≥2, ≥2 recurrent falls). It would be very helpful to provide a definition of falls (within which time lapse?, what is the definition of recurrent falls?).

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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Reviewer #1: Yes: Rebecca Haddad

Reviewer #2: No

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PLoS One. 2021 May 19;16(5):e0251711. doi: 10.1371/journal.pone.0251711.r002

Author response to Decision Letter 0

1 Feb 2021

PLOS ONE - Decision on Manuscript PONE-D-20-28464

Peter F.W.M. Rosier, M.D. PhD

Academic Editor

PLOS ONE

Dear Dr. Rosier:

On behalf of all of the authors for this manuscript, we really appreciate your meticulous comments as they refine this manuscript. Regarding these comments, the reviewer’s suggestions were implemented in the revised manuscript.

The changes are summarized below in red.

Authors tried to revise the manuscript following their opinions as far as we can. We hope the revised manuscript will better meet the requirements of your journal for publication. We thank the editor and the reviews of PLOS ONE once again for the constructive review of our paper.

Sincerely yours,

Sung Tae Cho, MD, Ph.D.

Professor, Dept. of Urology,

Kangnam Sacred Heart Hospital

Hallym University College of Medicine

Attachment

Submitted filename: Response to Reviewers_rev.docx

Click here for additional data file.^{(1.4MB, docx)}

PLoS One. doi: 10.1371/journal.pone.0251711.r003

Decision Letter 1

Peter FWM Rosier

11 Mar 2021

PONE-D-20-28464R1

The Impact of Urinary Incontinence on Falls: A Systematic Review and Meta-Analysis

PLOS ONE

Dear Dr. Cho,

==============================

ACADEMIC EDITOR:

Your manuscript has been greatly improved, but, apart from the reviewers comments, I believe I am still missing the answer and / or the processing of my questions to the authors in my earlier letter. Therefore more or less again, in addition to the question of the reviewer to clarify the choice of age categories, I would also like to add some clarification regarding the studies that included persons with a disorder. This is to make it clearer how generalizable your conclusions can be, or how specific they should be. You may therefore have to check, in any case, whether your conclusion is not too general.

==============================

Please submit your revised manuscript by Apr 25 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

We look forward to receiving your revised manuscript.

Kind regards,

Peter F.W.M. Rosier, M.D. PhD

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Reviewer #1: Thank you to the authors for taking our remarks into account and for modifying the manuscript accordingly, which has been considerably improved. Please find additional comments.

Methods

- It is still not clear why this age (≥40 years) was chosen in a study about an essentially geriatric problem. Authors must explain it. Why did they not choose ≥ 60 years old? I only found 2 studies in the results with a possible mean age under 60 (Giraldo Rodriguez L et al. 2019 [29] and Abbs E et al. 2020 [31]). This remark does not mean that I want the authors to remove these studies, but I really want to know the reason behind this selection criteria.

- Study selection: rather use “exposure” than “intervention”

Results

- In table 1, there are some missing informations:

* population characteristics: sex ratio (Tinetti, Johansson etc.), age (de Rekeneire, Huang, etc.) or both (Kim) are missing for some of the studies. Please fill in the missing informations.

* exposition: there is no information on the definition/type/prevalence of UI. Please fill in the missing informations.

* I would merge the 2 columns “definition of falls” and “no. of participants with falls” so that you can add a “UI” column.

* for adjusted OR, I would add, as a footnote under the table, the variables of adjustment.

* when OR is not available, please give the prevalence in the two groups.

* footnotes: missing explanation of the abbreviations: ALSWH, LASA, NSHD, TILDA, UI, CI

* For the study by Stenhagen et al., were the OR calculated on the 6 years or 3 years data? Please indicate the number of participants according to the OR calculation

- Risk of bias assessment

*Figure 2 risk of bias: The authors forgot to adapt the ROBINS-I template to the ROBINS-E tool. For example, D3 bias in classification of interventions is not applicable to the ROBINS-E tool and should be replace by “Bias in classification of exposures”. Please check every single item to be in accordance with the ROBINS-E tool.

*In the manuscript, I think you should explain a little bit more the risk of bias. At least write the major source of bias (bias due to confounding) and highlight the studies who correctly address confounding factors in the relationship between UI and falls.

- Figures 3 et 4 B

The “favours A/favours B” footnote does not work here since authors assess the effect of an exposure and not an intervention. Please modify to something more adequate to this analysis

Discussion

The authors have made some changes regarding the hypotheses to explain of the association between urge UI and falls. But the authors did not make any hypotheses to explain the association between stress UI and falls. To my opinion it is important, and it is one of the most interesting findings of this meta-analysis. Clinicians will remember that urinary incontinence of any type is a factor associated with falls. But authors must make some hypotheses. Is UI just a marker of poor health? Or is UI a real causal factor? Here authors should discuss a little bit more the studies that correctly address confounding factors, especially the ones that could lead to both UI and falls (for example multimorbidity, polypharmacy, neurological diseases, sarcopenia, etc.).

Reviewer #2: I have reviewed this new version of the manuscript. Reviewer's comments and questions have been fully addressed, and the manuscript has increased significantly its quality and understanding.

I am satisfied with the final result. No more comments to add.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Rébecca Haddad

Reviewer #2: Yes: Salvador Arlandis

PLoS One. 2021 May 19;16(5):e0251711. doi: 10.1371/journal.pone.0251711.r004

Author response to Decision Letter 1

25 Apr 2021

PLOS ONE - Decision on Manuscript PONE-D-20-28464R1

Peter F.W.M. Rosier, M.D. PhD

Academic Editor

PLOS ONE

Dear Dr. Rosier:

We are pleased to re-submit our revised manuscript to the PLOS ONE. We express our sincere appreciation for your thoughtful comments. Following your suggestions, we describe answers about the issues raised by reviewers. In addition, we designate any changes by highlighting with red color in the revised manuscript.

Reviewers' comments:

Reviewer #1: Thank you to the authors for taking our remarks into account and for modifying the manuscript accordingly, which has been considerably improved. Please find additional comments.

Methods

Response: Thank you for careful comments. Considering the heterogeneous characteristics between young adults and older adults, we excluded the studies with young adults to remove their confounding effect on the results. However, considering several cohort studies often included middle aged people in their baseline survey, we thought that tight age criterion might miss large population based cohort studies such as Giraldo‐Rodríguez et al. Therefore, we chose the broad criterion (≥40 years) to screen as many studies as possible. In addition, we thought the heterogeneous effect of middle aged people could be solved by subgroup analysis stratified by age and conducted a subgroup analysis with studies in older adults (≥65 years). Nevertheless, we agreed the reviewer’ comment that this criterion could not explain enough of the aim of our study. Therefore, we modified this criterion as follow:

1) population: studies with participants aged ≥ 50 years or mean age ≥ 60 years

- Study selection: rather use “exposure” than “intervention”

Response: As reviewer’s comment, we revised the manuscript.

Results

- In table 1, there are some missing informations:

* population characteristics: sex ratio (Tinetti, Johansson etc.), age (de Rekeneire, Huang, etc.) or both (Kim) are missing for some of the studies. Please fill in the missing informations.

* exposition: there is no information on the definition/type/prevalence of UI. Please fill in the missing informations.

* I would merge the 2 columns “definition of falls” and “no. of participants with falls” so that you can add a “UI” column.

* for adjusted OR, I would add, as a footnote under the table, the variables of adjustment.

* when OR is not available, please give the prevalence in the two groups.

* footnotes: missing explanation of the abbreviations: ALSWH, LASA, NSHD, TILDA, UI, CI

* For the study by Stenhagen et al., were the OR calculated on the 6 years or 3 years data? Please indicate the number of participants according to the OR calculation

Response: We agree with the reviewer. For all studies, we have checked again to find if there was any information missing. Then, we have added the missing data and modified the table 1. as the reviewer pointed out.

- Risk of bias assessment

Response: As reviewer’s comment, we revised figure 2.

Thank you for careful comments. We explained more details about the risk of bias in manuscript.

- Figures 3 et 4 B

The “favours A/favours B” footnote does not work here since authors assess the effect of an exposure and not an intervention. Please modify to something more adequate to this analysis

Response: As reviewer’s comment, we revised figure 3 and 4 as follow:

favours A/favours B � Decreased risk of falls/Increased risk of falls

Discussion

Response: We agree with the reviewer that the hypothesis of stress UI is different to those of urgency UI. Thus, we have added the sentence in the discussion section as the reviewer pointed out (page 24, lines 13-19).

Is UI just a marker of poor health? Or is UI a real causal factor? Here authors should discuss a little bit more the studies that correctly address confounding factors, especially the ones that could lead to both UI and falls (for example multimorbidity, polypharmacy, neurological diseases, sarcopenia, etc.).

Response: Thank you for your comments. Thus, we have performed the updated literature search and added the sentence about confounding factors such as multimorbidity, polypharmacy, neurological diseases and sarcopenia in the discussion section as the reviewer pointed out (page 25, lines 12-22).

We hope this revised work is impressive to your editor, reviewers, and readers. We thank the editor and the reviews of PLOS ONE once again for the warm review of our paper and look forward to hearing from you.

Sincerely yours,

Sung Tae Cho, MD, Ph.D.

Professor, Dept. of Urology,

Kangnam Sacred Heart Hospital

Hallym University College of Medicine

Attachment

Submitted filename: Response to Reviewers_0425.docx

Click here for additional data file.^{(21.7KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0251711.r005

Decision Letter 2

Peter FWM Rosier

3 May 2021

The Impact of Urinary Incontinence on Falls: A Systematic Review and Meta-Analysis

PONE-D-20-28464R2

Dear Dr. Cho,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

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Kind regards,

Peter F.W.M. Rosier, M.D. PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

none

Reviewers' comments:

PLoS One. doi: 10.1371/journal.pone.0251711.r006

Acceptance letter

Peter FWM Rosier

6 May 2021

PONE-D-20-28464R2

The Impact of Urinary Incontinence on Falls: A Systematic Review and Meta-Analysis

Dear Dr. Cho:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

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Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Peter F.W.M. Rosier

Academic Editor

PLOS ONE

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

S1 Table. PRISMA checklist.

(DOCX)

Click here for additional data file.^{(28.7KB, docx)}

S2 Table. Electronic search strategy.

(DOCX)

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S1 Data. PubMed: 286 studies.

(DOCX)

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Data Availability Statement

The literature search was conducted in adherence to the principles outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

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PERMALINK

The impact of urinary incontinence on falls: A systematic review and meta-analysis

Shinje Moon

Hye Soo Chung

Yoon Jung Kim

Sung Jin Kim

Ohseong Kwon

Young Goo Lee

Jae Myung Yu

Sung Tae Cho

Roles

Abstract

Objective

Methods

Results

Conclusions

Introduction

Methods

Search strategy

Study selection

Data extraction

Risk of bias assessment

Data analyses and statistical methods

Subgroup analysis

Results

Study characteristics

Fig 1. Schematic diagram of the search strategy.

Table 1. Summary of the 38 studies included in the present meta-analysis.

Fig 2. Quality assessment of the risk of bias in the 33 studies included in this meta-analysis.

Impact of UI on falls

Fig 3. Forest plots of the risk ratio of the association between urinary incontinence and falls.

Fig 4. Funnel plot and sensitivity analysis.

Analyses of subgroups stratified by age, sex, the definition of falls, and type of UI

Table 2. Subgroup analysis of the association between urinary incontinence and falls.

Discussion

Supporting information

Abbreviations

Data Availability

Funding Statement

References

Decision Letter 0

Peter FWM Rosier

Roles

Author response to Decision Letter 0

Decision Letter 1

Peter FWM Rosier

Roles

Author response to Decision Letter 1

Decision Letter 2

Peter FWM Rosier

Roles

Acceptance letter

Peter FWM Rosier

Roles

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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