ContextStress urinary incontinence (SUI) and urgency urinary incontinence (UUI) are associated with physical and psychological morbidity, and large societal costs. The long-term effects of delivery modes on each kind of incontinence remain uncertain.ObjectiveTo investigate the long-term impact of delivery mode on SUI and UUI.Evidence acquisitionWe searched Medline, Scopus, CINAHL, and relevant major conference abstracts up to October 31, 2014, including any observational study with adjusted analyses or any randomized trial addressing the association between delivery mode and SUI or UUI ≥1 yr after delivery. Two reviewers extracted data, including incidence/prevalence of SUI and UUI by delivery modes, and assessed risk of bias.Evidence synthesisPooled estimates from 15 eligible studies demonstrated an increased risk of SUI after vaginal delivery versus cesarean section (adjusted odds ratio [aOR]: 1.85; 95% confidence interval [CI], 1.56–2.19; I2 = 57%; risk difference: 8.2%). Metaregression demonstrated a larger effect of vaginal delivery among younger women (p = 0.005). Four studies suggested no difference in the risk of SUI between spontaneous vaginal and instrumental delivery (aOR: 1.11; 95% CI, 0.84–1.45; I2 = 50%). Eight studies suggested an elevated risk of UUI after vaginal delivery versus cesarean section (aOR: 1.30; 95% CI, 1.02–1.65; I2 = 37%; risk difference: 2.6%).ConclusionsCompared with cesarean section, vaginal delivery is associated with an almost twofold increase in the risk of long-term SUI, with an absolute increase of 8%, and an effect that is largest in younger women. There is also an increased risk of UUI, with an absolute increase of approximately 3%.Patient summaryIn this systematic review we looked for the long-term effects of childbirth on urinary leakage. We found that vaginal delivery is associated with an almost twofold increase in the risk of developing leakage with exertion, compared with cesarean section, with a smaller effect on leakage in association with urgency.

ObjectiveFamily studies and twin studies demonstrate that lower urinary tract symptoms and pelvic organ prolapse are heritable. This review aimed to identify genetic polymorphisms tested for an association with lower urinary tract symptoms or prolapse, and to assess the strength, consistency, and risk of bias among reported associations.Study DesignPubMed and HuGE Navigator were searched up to May 1, 2014, using a combination of genetic and phenotype key words, including “nocturia,” “incontinence,” “overactive bladder,” “prolapse,” and “enuresis.” Major genetics, urology, and gynecology conference abstracts were searched from 2005 through 2013. We screened 889 abstracts, and retrieved 78 full texts. In all, 27 published and 7 unpublished studies provided data on polymorphisms in or near 32 different genes. Fixed and random effects metaanalyses were conducted using codominant models of inheritance. We assessed the credibility of pooled associations using the interim Venice criteria.ResultsIn pooled analysis, the rs4994 polymorphism of the ADRB3 gene was associated with overactive bladder (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.7–3.6; n = 419). The rs1800012 polymorphism of the COL1A1 gene was associated with prolapse (OR, 1.3; 95% CI, 1.0–1.7; n = 838) and stress urinary incontinence (OR, 2.1; 95% CI, 1.4–3.2; n = 190). Other metaanalyses, including those for polymorphisms of COL3A1,LAMC1,MMP1,MMP3, and MMP9 did not show significant effects. Many studies were at high risk of bias from genotyping error or population stratification.ConclusionThese metaanalyses provide moderate epidemiological credibility for associations of variation in ADRB3 with overactive bladder, and variation of COL1A1 with prolapse. Clinical testing for any of these polymorphisms cannot be recommended based on current evidence.

Purpose: Nocturia (waking from sleep at night to void) is a common cause of sleep disruption associated with increased comorbidity and impaired quality of life. However, its impact on mortality remains unclear. We performed a systematic review and meta-analysis to evaluate the association of nocturia with mortality as a prognostic factor and a causal risk factor. Materials and Methods: We searched PubMedÒ, ScopusÒ, CINAHLÒ (Cumulative Index of Nursing and Allied Health Literature) and major conference abstracts up to December 31, 2018. Random effects meta-analyses were done to address the adjusted RR of mortality in people with nocturia. Metaregression was performed to explore potential determinants of heterogeneity, including the risk of bias. We applied the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) framework to rate the

AEP)Purpose: Although nocturia is associated with various comorbidities, its impact on falls and fractures remains unclear. We performed a systematic review and meta-analysis to evaluate the association between nocturia and falls and fractures as a prognostic and as a causal risk factor. Materials and Methods: We searched PubMedÒ, ScopusÒ, CINAHL (Cumulative Index to Nursing and Allied Health Literature) and abstracts of major urological meetings up to December 31, 2018. We conducted random effects meta-analyses of adjusted relative risks of falls and fractures. We applied the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence for nocturia as a prognostic and causal factor of falls and fractures. Results: Among 5,230 potential reports 9 observational longitudinal studies provided data on the association between nocturia and falls or fractures (1 for both, 4 for falls, 4 for fractures). Pooled estimates demonstrated a risk ratio of 1.20 (95% CI 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.

ContextAlthough family studies have shown that male lower urinary tract symptoms (LUTS) are highly heritable, no systematic review exists of genetic polymorphisms tested for association with LUTS.ObjectiveTo systematically review and meta-analyze studies assessing candidate polymorphisms/genes tested for an association with LUTS, and to assess the strength, consistency, and potential for bias among pooled associations.Evidence acquisitionA systematic search of the PubMed and HuGE databases as well as abstracts of major urologic meetings was performed through to January 2013. Case-control studies reporting genetic associations in men with LUTS were included. Reviewers independently and in duplicate screened titles, abstracts, and full texts to determine eligibility, abstracted data, and assessed the credibility of pooled associations according to the interim Venice criteria. Authors were contacted for clarifications if needed. Meta-analyses were performed for variants assessed in more than two studies.Evidence synthesisWe identified 74 eligible studies containing data on 70 different genes. A total of 35 meta-analyses were performed with statistical significance in five (ACE, ELAC2, GSTM1, TERT, and VDR). The heterogeneity was high in three of these meta-analyses. The rs731236 variant of the vitamin D receptor had a protective effect for LUTS (odds ratio: 0.64; 95% confidence interval, 0.49–0.83) with moderate heterogeneity (I2 = 27.2%). No evidence for publication bias was identified. Limitations include wide-ranging phenotype definitions for LUTS and limited power in most meta-analyses to detect smaller effect sizes.ConclusionsFew putative genetic risk variants have been reliably replicated across populations. We found consistent evidence of a reduced risk of LUTS associated with the common rs731236 variant of the vitamin D receptor gene in our meta-analyses.Patient summaryCombining the results from all previous studies of genetic variants that may cause urinary symptoms in men, we found significant variants in five genes. Only one, a variant of the vitamin D receptor, was consistently protective across different populations.

Background: The usefulness of lower urinary tract symptoms (LUTS) as mortality risk factors remains unclear. Repeated assessments are required to take into account symptom fluctuation and de novo symptom appearance. The study objective was to evaluate mortality in relation to three urinary storage symptoms-urgency, daytime frequency and nocturia-in middle-aged and elderly men, considering also other time-varying factors during follow-up. Methods: A mail survey of a population-based cohort of men initially aged 50, 60 and 70 years was conducted in Finland in 1994, 1999, 2004 and 2009. The questionnaire included assessments of LUTS based on the Danish Prostatic Symptom Score and comorbidities. The men were followed up for mortality through the population registry through 2014. LUTS-related hazard ratios (HR) were analyzed with timedependent Cox regression adjusted for the year of birth and comorbidities using variable values updated every five years. Sensitivity analyses were conducted using values of all variables fixed to the baseline assessment of 1994. Results: Of the 1332 eligible men with data on LUTS from each preceding survey, 514 (38.6%) died during the 21-year follow-up. In time-dependent analyses, daytime frequency and nocturia were significantly associated with increased mortality: the adjusted HR was 1.42 (95%CI 1.11-1.83) for daytime frequency, 1.38 (1.07-1.79) for nocturia and 1.19 (0.94-1.50) for urgency. In sensitivity analyses with fixed baseline characteristics, only nocturia was suggestively associated with an increased risk of death: the adjusted HR was 1.09 (0.84-1.42) for daytime frequency, 1.41 (0.99-2.02) for nocturia and 0.94 (0.52-1.68) for urgency. Conclusions: Among aging men, LUTS are more accurate predictors of short-term than longer-term mortality risk. Repeated assessments are needed to detect clinically 3 ill health. Accordingly, men relevant and persistent symptoms, often associated with with daytime frequency or nocturia exhibit a 1.4-fold risk of death and therefore, should be evaluated for underlying comorbidity.

Purpose:The utility of male lower urinary tract symptoms (LUTS) as mortality risk factors remains unclear. We explored LUTS-associated mortality among Finnish men, evaluating the association of symptom severity and bother with risk of death.Materials and Methods:A questionnaire including the Danish Prostatic Symptom Score was mailed to a population-based cohort of 3,143 men aged 50, 60 and 70 years in 1994, with repeat surveys in 1999, 2004, 2009 and 2015. The men were followed until the end of 2018. Mortality associated with LUTS was analyzed using time-dependent Cox regression adjusted for age and comorbidity, updating symptom data every 5 years, including interaction terms between symptoms and associated bother.Results:Of the 1,167 men in the analysis, 591 (50.6%) died during the 24-year followup. In analyses of moderate and severe symptoms disregarding bother, overall voiding and storage LUTS, daytime frequency and urgency incontinence were associated with increased mortality: the multivariable-adjusted hazard ratios were 1.19 (95% CI 1.00–1.40), 1.35 (1.13–1.62), 1.31 (1.09–1.58) and 2.19 (1.42–3.37), respectively. In analyses disregarding symptom severity and bother, voiding LUTS were associated with decreased mortality, while daytime frequency and nocturia were associated with increased mortality: the HRs were 0.82 (95% CI 0.67–1.00), 1.31 (95% CI 1.09–1.58) and 1.52 (95% CI 1.21–1.91), respectively. Excess mortality associated with bothersome daytime frequency and nocturia tended to be slightly higher: the HRs were 1.86 (95% CI 1.41–2.47) and 1.88 (95% CI 1.38–2.58), respectively. No significant interactions were found between symptoms and associated bother, however.Conclusions:Moderate and severe LUTS are potential risk factors for mortality, independently of their bother.

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