Victor Andreev - Academia.edu (original) (raw)
Papers by Victor Andreev
Contemporary Clinical Trials, 2018
The Neuroimaging and Sensory Testing (NIST) Study of the Symptoms of Lower Urinary Tract Dysfunct... more The Neuroimaging and Sensory Testing (NIST) Study of the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) is a cross-sectional, case-control study designed to investigate whether disrupted brain connectivity and sensory processing are associated with abnormal lower urinary tract symptoms (LUTS) in patients with overactive bladder syndrome (OAB). The NIST Study tests the hypotheses that patients with urinary urgency will demonstrate: (1) abnormal functional and structural connectivity of brain regions involved in urinary sensation
Neurourology and Urodynamics, 2019
Aims: Lower urinary tract symptoms (LUTS) are diverse in type and variable in severity. We examin... more Aims: Lower urinary tract symptoms (LUTS) are diverse in type and variable in severity. We examined symptom change within the Symptoms of the Lower Urinary Tract Dysfunction Research Network (LURN) Observational Cohort study identified clusters over time and tested associations with treatments received. Methods: Patient-reported LUTS and treatment data were collected at multiple time points between baseline and 12 months from the LURN Observational Cohort study. LUTS severity scores were calculated to summarize changes in symptom reporting over time in previously identified LURN clusters. Repeated measures linear regression models tested adjusted associations between cluster membership and severity scores. Results: Four-hundred seventeen men and 396 women were classified into improved, unchanged, and worsened symptoms between baseline and 12 months (men: 44.1%, 40.5%, and 15.3%; women: 55.8%, 33.1%, 11.1%, respectively). Improvement in LUTS severity scores varied by cluster (estimated adjusted mean change from baseline range: −.04 change in standard deviations of severity scores (ΔSD) to −.67 ΔSD). Prostate surgery was associated with improved severity scores (−.63 ΔSD) in men, while stress incontinence surgery was associated with improved severity scores (−.88 ΔSD) in women. Conclusion: Symptom improvement varied by cluster indicating response to therapy differs amongst subtypes of patients with LUTS. The differential improvement of patients in clusters suggests mechanistic differences between clusters and may aid in selecting more targeted treatments in the future.
Neurourology and Urodynamics, 2019
AimsThe aims of this study were to assess the completeness of voiding diaries in a research conte... more AimsThe aims of this study were to assess the completeness of voiding diaries in a research context and to correlate diary data with patient‐reported questionnaires.MethodsMen and women enrolled in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) were given a 3‐day voiding and fluid‐intake diary to fill‐out. Diaries were assessed for completeness and intake‐output imbalances. They were assigned to one of four categories based on a percentage of missing data and fluid imbalance: no diary submitted, unusable (>40% missing void or intake volumes, or unphysiological fluid imbalance), usable but not complete, and complete.ResultsA total of 1064 participants were enrolled and 85% (n = 902) returned the bladder diary. Of the diaries returned, 94% (n = 845) had data on three separate days, 87% (n = 786) had no missing intake volumes, 61% (n = 547) had no missing voided volumes, and 70% (n = 635) had a fluid imbalance within 3 L across the 3‐day time period, resulti...
Journal of Urology, 2019
Purpose-Conventional classification of patients with lower urinary tract symptom (LUTS) into diag... more Purpose-Conventional classification of patients with lower urinary tract symptom (LUTS) into diagnostic categories based on a pre-defined symptom complex or predominant symptom appears inadequate, as patients frequently present with multiple urinary symptoms that could not be perfectly categorized into traditional diagnostic groups. We used a novel clustering method to identify male LUTS patient subtypes, based on detailed multi-symptom information. Materials and Methods-Baseline data from 503 care-seeking men in the LURN Observational Cohort study was analyzed. Symptoms and their severity were assessed using the LUTS Tool and AUA Symptom Index (52 questions total). A resampling-based consensus clustering algorithm identified patient subtypes with distinct symptom signatures. Results-Four distinct symptom clusters were identified. Patients in cluster M1 (n=166) had predominant symptoms of frequency, nocturia, hesitancy, straining, weak stream, intermittency and incomplete bladder emptying, suggestive of bladder outlet obstruction. Patients in cluster M2 (n=93) mainly endorsed post-micturition symptoms (e.g., post-void dribbling, post-void leakage), with some weak stream. Patients in cluster M3 (n=114) reported mostly urinary frequency without incontinence. Patients in cluster M4 (n=130) reported severe frequency, urgency and urgency incontinence. The majority of other urinary symptoms were statistically different between pairs of
Journal of Urology, 2019
Purpose-Despite management, some patients continue to have bothersome lower urinary tract symptom... more Purpose-Despite management, some patients continue to have bothersome lower urinary tract symptoms (LUTS). We examined characteristics associated with LUTS bother in a prospective cohort. Materials and Methods-Data were obtained from care-seeking patients with LUTS at six US tertiary-care centers in a one-year prospective, observational cohort study. Participants answered the American Urological Association Symptom Index global urinary bother question at study entry and 12 months later. Multiple linear and logistic regressions were used to identify factors associated with 12-month urinary bother. Results-Of 756 participants, 121 (16%) had worsened LUTS bother over the study period. Baseline factors associated with more severe bother at 12 months among men included non-white race, hypertension, worse urinary frequency and incontinence, and higher levels of stress (all p<0.05). Among women, more severe bother at baseline, urinary urgency and frequency, and worse physical function were associated with more severe bother at 12 months. Adjusted for other variables, worsened LUTS were more likely among men who were non-white (OR [95% CI]=1.79 [0.95-3.39]) or diabetic (OR=1.68 [0.86-3.26]) and among women with diabetes (OR=1.
Biological, ecological, social, and technological systems are complex structures with multiple in... more Biological, ecological, social, and technological systems are complex structures with multiple interacting parts, often represented by networks. Correlation matrices describing interdependency of the variables in such structures provide key information for comparison and classification of such systems. Classification based on correlation matrices could supplement or improve classification based on variable values, since the former reveals similarities in system structures, while the latter relies on the similarities in system states. Importantly, this approach of clustering correlation matrices is different from clustering elements of the correlation matrices, because our goal is to compare and cluster multiple networks, not the nodes within the networks. A novel approach for clustering correlation matrices, named snakes-and-dragons, is introduced and illustrated by examples from neuroscience, human microbiome, and macroeconomics.
Journal of Urology, 2019
INTRODUCTION AND OBJECTIVES: Interpersonal trauma, including physical and emotional abuse, has th... more INTRODUCTION AND OBJECTIVES: Interpersonal trauma, including physical and emotional abuse, has the potential to contribute to urinary tract dysfunction through multiple mechanisms. We examined associations between interpersonal trauma exposures, post-traumatic stress disorder (PTSD) symptoms, and urinary tract symptoms in a communitybased population of ethnically-diverse midlife and older women. METHODS: We analyzed data from a multiethnic, communitybased cohort study of 2,016 women aged 40-80 years enrolled in an integrated healthcare system in California (the Reproductive Risks of Incontinence Study at Kaiser). Lifetime history of traumatic exposures, current PTSD symptoms, and current urinary tract symptoms were assessed using structured questionnaires in 2008-2012. Multivariableadjusted logistic regression models examined associations between interpersonal trauma exposures and PTSD symptoms with: 1) any weekly incontinence, 2) weekly stress-type incontinence, 3) weekly urgency-type incontinence, and 4) nocturia !2 times/night. RESULTS: Of the 1,999 participants analyzed, 36% were Caucasian, 22% Black, 23% Latina, and 20% Asian. Twenty-seven percent reported at least one lifetime interpersonal trauma exposure, and 23% reported clinically significant PTSD (by PTSD Checklist-Civilian Version score !30). Overall, 45% reported any weekly incontinence, 23% weekly stress-type incontinence, 23% weekly urgency-type incontinence, and 35% nocturia. In multivariable models adjusting for age, race/ethnicity, education, body mass index, parity, menopausal status, pelvic surgery, and selected medications, women with a history of emotional abuse were more likely to report any weekly incontinence (adjusted odds ratio [AOR] [1.3, 95% confidence interval [CI][1.0-1.7) and nocturia (AOR[1.7, CI[1.4-2.2). Physical abuse was associated with nocturia (AOR [1.4, CI[1.0-1.8) but not incontinence. PTSD was associated with any weekly incontinence (AOR[1.5, CI[1.2-1.9), stress-type incontinence (AOR[1.7, CI[1.3-2.2), urgency-type incontinence (AOR [1.6, CI[1.2-2.1), and nocturia (AOR[2.0, CI-1.6-2.5). CONCLUSIONS: Over 20% of midlife and older women in this community-based cohort had a history of physical or emotional interpersonal trauma, which contributed to their risk of urinary tract symptoms. Findings point to interpersonal trauma as a potentially under-recognized risk factor for urinary tract dysfunction and highlight the need for trauma-informed care of women presenting with urinary symptoms in community settings.
Journal of Urology, 2019
Purpose: Lower urinary tract symptoms are prevalent and burdensome, yet methods to enhance diagno... more Purpose: Lower urinary tract symptoms are prevalent and burdensome, yet methods to enhance diagnosis and appropriately guide therapies are lacking. We systematically reviewed the literature for human studies of biomarkers associated with lower urinary tract symptoms. Materials and Methods: PubMedÒ, EMBASEÒ and Web of ScienceÒ were searched from inception to February 13, 2018. Articles were included if they were in English, performed in benign urological populations without neurological disorders or interstitial cystitis/bladder pain syndrome, and assessed a biomarker's association with or ability to predict specific lower urinary tract symptoms or urological conditions. Bioinformatic pathway analyses were conducted to determine whether individual biomarkers associated with symptoms are present in unifying pathways. Results: Of 6,150 citations identified 125 met the inclusion criteria. Most studies (93.6%) assessed biomarkers at 1 time point and were crosssectional in nature. Few studies adjusted for potentially confounding clinical variables or assessed biomarkers in an individual over time. No individual biomarkers are currently validated as diagnostic tools for lower urinary tract symptoms. Compared to controls, pathway analyses identified multiple immune response pathways that were enriched in overactive bladder
Journal of Urology, 2019
Purpose: To improve the potential for finding clinically important subtypes of patients with lowe... more Purpose: To improve the potential for finding clinically important subtypes of patients with lower urinary tract symptoms (LUTS), we describe the development of the Comprehensive Assessment of Self-reported Urinary Symptoms (CASUS)-and use it to present data on the experiences of LUTS in treatment-seeking women and men from a prospective observational cohort. Materials and Methods: An initial list of LUTS as confirmed in 22 qualitative interviews with providers and 88 qualitative interviews with care-seeking and non-care-seeking women and men with LUTS. Items from extant measures were adopted and revised and new items were developed, and all were evaluated for understanding in 64 cognitive interviews. Items were administered to a prospective cohort of female and male LUTS patients seeking care and analyses were conducted to describe item response distributions and correlations among item responses separately for women and men. Results: A total of 444 males and 372 females provided responses to CASUS. There were several sets of items that had different relationships for women compared to men. In particular, the associations between sensation-related items and incontinence-related items were generally positive among females, but were often negative among males. Conclusions: Using an intensive development process, the CASUS addresses a wide range of LUTS. It should help to identify clinically important subtypes of patients. Further, the collection of items can provide the foundation for shorter measures for use in the clinic and as trial endpoints.
The Journal of Urology, 2018
bladder volume (BV: voided volumeþPVR). IPSS was also stratified in three classes of LUTS severit... more bladder volume (BV: voided volumeþPVR). IPSS was also stratified in three classes of LUTS severity: 0-7 moderate, 8-19 fair, 20-35 severe. Patients satisfaction was measured by VAS and a simple question. Q-square and T-Student tests were used for statistical analysis. RESULTS: IPSS class showed improvement in both groups, higher when BOO was associated to DU (p¼0.037). In both groups no statistical difference was documented regarding improvement of IPSS mean score (p¼0.68), mean peak flow (p¼0.052), and mean PVR/PVR ratio (p¼0.49). Subjective satisfaction was high in both groups. Patients characteristic and outcomes are reported in Table 1 and Table 2. CONCLUSIONS: In patients with detrusor underactivity TURP leads to a significant improvement in functional outcomes. Males with DU and BOO had better results but with no statistical difference. Thus, the lack of BOO in patients with DU should not be excluding from surgical indications.
The Journal of Urology, 2018
increased risk of urinary tract infections (UTI) and may be considered an indication for clinical... more increased risk of urinary tract infections (UTI) and may be considered an indication for clinical intervention. We sought to describe the associations between measured PVR and self-reported symptoms and UTI in patients seeking treatment for lower urinary tract symptoms (LUTS). METHODS: Data were obtained from the LURN Observational Cohort Study. PVR and self-reported history of UTIs were collected at the baseline clinic visit. Women were asked if they had ever had more than two UTIs while men were asked if they had ever had any UTIs. Lower urinary tract symptoms (LUTS) were collected using the AUA-SI and the LUTS Tool. Comparisons by sex were made using Wilcoxon two-sample and chi-square tests. RESULTS: 48% of women reported more than 2 UTIs and 22% of men reported having had a UTI (Table). Median measured PVR was not different by UTI status for males or females (median PVR [ml] for UTI vs. no UTI: 29.5 vs. 27 for males and 26 vs. 25.5 for females). There was no difference in elevated PVR (>200ml) by UTI in either sex (11.1% vs. 7.7% in males and 2.7% vs. 2.1% in females). Self-reported symptoms of incomplete emptying were slightly higher in females who had more than 2 UTIs compared to those that did not (median LUTS Tool score 2 [sometimes] vs. 1 [rarely], p¼0.004; median AUA score 2 [< half the time] vs. 1 [<1 time in 5], p¼0.006), but these scores did not differ between men with any previous UTIs compared to men no previous UTIs. CONCLUSIONS: The PVR in care-seeking people is not associated with the self-reported incidence of recurrent UTI, despite some association with retention symptoms in females. Our results suggest that an elevated PVR may not be associated with recurrent urinary tract infections.
The Journal of Urology, 2018
Lower urinary tract symptoms are common in women and presumably relate to four recognized domains... more Lower urinary tract symptoms are common in women and presumably relate to four recognized domains of toileting behaviors, including 1) place, 2) timing, 3) position, and 4) style. However, little is still known about the associations between abnormal or dysfunctional toileting behaviors and urinary symptoms. Our aim was to investigate whether increased lower urinary tract symptoms, specifically overactive bladder (OAB), are correlated with increased self-report of dysfunctional toileting behaviors in a community-based sample of women. METHODS: In this cross-sectional study, we recruited 2,215 community women to complete online, validated questionnaires, including the Toileting Behavior Scale (TBS) and International Consultation on Incontinence Questionnaire-Overactive bladder (ICIQ-OAB). Dysfunctional behavior questions were grouped by premature voiding (voiding without the need to urinate), delayed voiding, and straining to void. Pearson correlation was used to examine the strength of associations between ICIQ-OAB and dysfunctional toileting behavior scores. RESULTS: The average age was 47.3 (range: 18-89). All except 3 women (99.9%) reported a place preference for voiding, with 10.5% (n¼233) always avoiding public restrooms. Overall, 79.9% (n¼1,770) reported premature voiding, 64.5% (n¼1,429) straining to void, and 97.8% (n¼2,166) delayed voiding. Reasons for delaying urination at least sometimes were 00 busy 00 (84.5%, n¼ 1,873) or 00 at work 00 (37.6%, n¼ 832). There were significant positive correlations between ICIQ-OAB scores and all dysfunctional toileting behaviors, with the strongest correlation being premature voiding (r¼0.364, p<0.001). CONCLUSIONS: Nearly all women in our sample endorsed dysfunctional toileting behaviors with voiding. There was correlation of toileting behaviors and lower urinary tract symptoms. Women with worse OAB symptoms were most likely to void pre-emptively, in the absence of desire, although many also reported straining to void and delaying voiding. Further study is needed to explore the effects of dysfunctional toileting behaviors on the development or worsening of lower urinary tract symptoms in adult women.
The Journal of Urology, 2018
associated with the decreased prevalence of BPH in men !60 years. Amount of drinking was negative... more associated with the decreased prevalence of BPH in men !60 years. Amount of drinking was negatively associated with the BPH prevalence in all age groups except for men < 50 years. Among metabolic syndrome-related components, decreased HDL-cholesterol was the most powerful variable associated with the prevalence of BPH in all age categories although all components of metabolic syndrome were related with increased prevalence of BPH, especially in male !50 years. CONCLUSIONS: Metabolic syndrome and its components, especially decreased HDL-cholesterol, increased the prevalence of BPH and appropriate alcohol intake plays a role in preventing BPH. In addition, from the viewpoint of BPH, social and medical attention to male with low-income thought to be needed.
The Journal of Urology, 2018
baseline, as evidenced by 95% CIs, was achieved with each treatment. Drug-related adverse events ... more baseline, as evidenced by 95% CIs, was achieved with each treatment. Drug-related adverse events (AEs) were reported in 16.4% of all pts; with higher incidence observed with Tol4 and V100 þ Tol4. Dry mouth was more common with Tol4 (7.1%) vs V50mg (3.6%); V100 mg (2.4%); V100 þ Tol4 (4.5%). Discontinuation due to AEs was also higher with Tol4 (6.3%) vs V50mg (2.7%); V100 mg (2.8%); V100þTol4 (3.7%). Changes in heart rate and blood pressure were minimal with V50 or V100 mg and similar to Tol4. CONCLUSIONS: Vibegron 50mg and 100 mg once daily are well tolerated and provide durable efficacy in OAB pts during longterm use.
The Journal of Urology, 2018
ABSTRACTWe present a novel methodology for subtyping of persons with a common clinical symptom co... more ABSTRACTWe present a novel methodology for subtyping of persons with a common clinical symptom complex by integrating heterogeneous continuous and categorical data. We illustrate it by clustering women with lower urinary tract symptoms (LUTS), who represent a heterogeneous cohort with overlapping symptoms and multifactorial etiology. Identifying subtypes within this group would potentially lead to better diagnosis and treatment decision-making. Data collected in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN), a multi-center prospective observational cohort study, included self-reported urinary and non-urinary symptoms, bladder diaries, and physical examination data for 545 women. Heterogeneity in these multidimensional data required thorough and non-trivial preprocessing, including scaling by controls and weighting to mitigate data redundancy, while the various data types (continuous and categorical) required novel methodology using a weighted Tanimoto indic...
Urology, 2019
Objectives: To assess the feasibility of a novel proteomics approach to identify biomarkers assoc... more Objectives: To assess the feasibility of a novel proteomics approach to identify biomarkers associated with LUTS within serum and urine, because many clinical factors contribute to lower urinary tract symptoms (LUTS) in men and women. These factors confound clinicians' abilities to reliably evaluate and treat LUTS. Previous studies identified candidate LUTS biomarkers, but none are clinically utilized. Methods: Eighteen male and 18 female Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) Observational Cohort Study participants with LUTS (measured on the LUTS Tool questionnaire) were randomly selected. Twelve male and 12 female controls with minimal or no LUTS were recruited and matched for clinico-demographic characteristics. The SomaScan Assay (SomaLogic) was used to measure the abundance of 1305 proteins contained within urine and serum. Statistical analyses were performed to evaluate reproducibility of assays, compare protein abundances, and estimate effect size.
<p>Results of the computer simulation of electric potential, electric field and electroosmo... more <p>Results of the computer simulation of electric potential, electric field and electroosmotic flow velocity in the axisymmetric model of the cell (cylinder of 10 µm radius and 10 µm height, nucleus–sphere of 3 µm radius, located in the center of the cylinder). Mathematical model is described by eqs. (1–6); parameters are presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061884#pone-0061884-t001" target="_blank">Table 1</a>. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061884#pone-0061884-g001" target="_blank">Figure 1A</a> represents electric potential (color map) and electric field strength (arrows) in the model of the polarized cell; inward current enters through the top of the cylinder and leaves the cell through the bottom of the cylinder (eq. 2). Electric potential is in the range −0.007÷−0.059 V; strong component of electric field parallel to the cylindrical surface is present. For comparison, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061884#pone-0061884-g001" target="_blank">Figure 1B</a> presents electric potential and field in the non-polarized cell (zero inward and outward current); here the component of electric field parallel to the surface is practically absent. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061884#pone-0061884-g001" target="_blank">Figure 1C</a> demonstrates electroosmotic flow circulation (color represents magnitude of the velocity, arrows represent direction) caused by electric field distribution in the polarized cell (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061884#pone-0061884-g001" target="_blank">Fig. 1A</a>), maximum value of fluid velocity 120 µm/s is in the vicinity of the cylindrical wall, while the average magnitude of the fluid velocity across the cytoplasm is 20 µm/s. Fluid circulates, moving downwards near the cylindrical wall and upwards near the nucleus. For comparison, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061884#pone-0061884-g001" target="_blank">Figure 1D</a> demonstrates that electroosmotic flow is practically absent (except the filleted corners) in the model of a non-polarized cylindrical cell, where electric field parallel to the surface is absent.</p
Contemporary Clinical Trials, 2018
The Neuroimaging and Sensory Testing (NIST) Study of the Symptoms of Lower Urinary Tract Dysfunct... more The Neuroimaging and Sensory Testing (NIST) Study of the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) is a cross-sectional, case-control study designed to investigate whether disrupted brain connectivity and sensory processing are associated with abnormal lower urinary tract symptoms (LUTS) in patients with overactive bladder syndrome (OAB). The NIST Study tests the hypotheses that patients with urinary urgency will demonstrate: (1) abnormal functional and structural connectivity of brain regions involved in urinary sensation
Neurourology and Urodynamics, 2019
Aims: Lower urinary tract symptoms (LUTS) are diverse in type and variable in severity. We examin... more Aims: Lower urinary tract symptoms (LUTS) are diverse in type and variable in severity. We examined symptom change within the Symptoms of the Lower Urinary Tract Dysfunction Research Network (LURN) Observational Cohort study identified clusters over time and tested associations with treatments received. Methods: Patient-reported LUTS and treatment data were collected at multiple time points between baseline and 12 months from the LURN Observational Cohort study. LUTS severity scores were calculated to summarize changes in symptom reporting over time in previously identified LURN clusters. Repeated measures linear regression models tested adjusted associations between cluster membership and severity scores. Results: Four-hundred seventeen men and 396 women were classified into improved, unchanged, and worsened symptoms between baseline and 12 months (men: 44.1%, 40.5%, and 15.3%; women: 55.8%, 33.1%, 11.1%, respectively). Improvement in LUTS severity scores varied by cluster (estimated adjusted mean change from baseline range: −.04 change in standard deviations of severity scores (ΔSD) to −.67 ΔSD). Prostate surgery was associated with improved severity scores (−.63 ΔSD) in men, while stress incontinence surgery was associated with improved severity scores (−.88 ΔSD) in women. Conclusion: Symptom improvement varied by cluster indicating response to therapy differs amongst subtypes of patients with LUTS. The differential improvement of patients in clusters suggests mechanistic differences between clusters and may aid in selecting more targeted treatments in the future.
Neurourology and Urodynamics, 2019
AimsThe aims of this study were to assess the completeness of voiding diaries in a research conte... more AimsThe aims of this study were to assess the completeness of voiding diaries in a research context and to correlate diary data with patient‐reported questionnaires.MethodsMen and women enrolled in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) were given a 3‐day voiding and fluid‐intake diary to fill‐out. Diaries were assessed for completeness and intake‐output imbalances. They were assigned to one of four categories based on a percentage of missing data and fluid imbalance: no diary submitted, unusable (>40% missing void or intake volumes, or unphysiological fluid imbalance), usable but not complete, and complete.ResultsA total of 1064 participants were enrolled and 85% (n = 902) returned the bladder diary. Of the diaries returned, 94% (n = 845) had data on three separate days, 87% (n = 786) had no missing intake volumes, 61% (n = 547) had no missing voided volumes, and 70% (n = 635) had a fluid imbalance within 3 L across the 3‐day time period, resulti...
Journal of Urology, 2019
Purpose-Conventional classification of patients with lower urinary tract symptom (LUTS) into diag... more Purpose-Conventional classification of patients with lower urinary tract symptom (LUTS) into diagnostic categories based on a pre-defined symptom complex or predominant symptom appears inadequate, as patients frequently present with multiple urinary symptoms that could not be perfectly categorized into traditional diagnostic groups. We used a novel clustering method to identify male LUTS patient subtypes, based on detailed multi-symptom information. Materials and Methods-Baseline data from 503 care-seeking men in the LURN Observational Cohort study was analyzed. Symptoms and their severity were assessed using the LUTS Tool and AUA Symptom Index (52 questions total). A resampling-based consensus clustering algorithm identified patient subtypes with distinct symptom signatures. Results-Four distinct symptom clusters were identified. Patients in cluster M1 (n=166) had predominant symptoms of frequency, nocturia, hesitancy, straining, weak stream, intermittency and incomplete bladder emptying, suggestive of bladder outlet obstruction. Patients in cluster M2 (n=93) mainly endorsed post-micturition symptoms (e.g., post-void dribbling, post-void leakage), with some weak stream. Patients in cluster M3 (n=114) reported mostly urinary frequency without incontinence. Patients in cluster M4 (n=130) reported severe frequency, urgency and urgency incontinence. The majority of other urinary symptoms were statistically different between pairs of
Journal of Urology, 2019
Purpose-Despite management, some patients continue to have bothersome lower urinary tract symptom... more Purpose-Despite management, some patients continue to have bothersome lower urinary tract symptoms (LUTS). We examined characteristics associated with LUTS bother in a prospective cohort. Materials and Methods-Data were obtained from care-seeking patients with LUTS at six US tertiary-care centers in a one-year prospective, observational cohort study. Participants answered the American Urological Association Symptom Index global urinary bother question at study entry and 12 months later. Multiple linear and logistic regressions were used to identify factors associated with 12-month urinary bother. Results-Of 756 participants, 121 (16%) had worsened LUTS bother over the study period. Baseline factors associated with more severe bother at 12 months among men included non-white race, hypertension, worse urinary frequency and incontinence, and higher levels of stress (all p<0.05). Among women, more severe bother at baseline, urinary urgency and frequency, and worse physical function were associated with more severe bother at 12 months. Adjusted for other variables, worsened LUTS were more likely among men who were non-white (OR [95% CI]=1.79 [0.95-3.39]) or diabetic (OR=1.68 [0.86-3.26]) and among women with diabetes (OR=1.
Biological, ecological, social, and technological systems are complex structures with multiple in... more Biological, ecological, social, and technological systems are complex structures with multiple interacting parts, often represented by networks. Correlation matrices describing interdependency of the variables in such structures provide key information for comparison and classification of such systems. Classification based on correlation matrices could supplement or improve classification based on variable values, since the former reveals similarities in system structures, while the latter relies on the similarities in system states. Importantly, this approach of clustering correlation matrices is different from clustering elements of the correlation matrices, because our goal is to compare and cluster multiple networks, not the nodes within the networks. A novel approach for clustering correlation matrices, named snakes-and-dragons, is introduced and illustrated by examples from neuroscience, human microbiome, and macroeconomics.
Journal of Urology, 2019
INTRODUCTION AND OBJECTIVES: Interpersonal trauma, including physical and emotional abuse, has th... more INTRODUCTION AND OBJECTIVES: Interpersonal trauma, including physical and emotional abuse, has the potential to contribute to urinary tract dysfunction through multiple mechanisms. We examined associations between interpersonal trauma exposures, post-traumatic stress disorder (PTSD) symptoms, and urinary tract symptoms in a communitybased population of ethnically-diverse midlife and older women. METHODS: We analyzed data from a multiethnic, communitybased cohort study of 2,016 women aged 40-80 years enrolled in an integrated healthcare system in California (the Reproductive Risks of Incontinence Study at Kaiser). Lifetime history of traumatic exposures, current PTSD symptoms, and current urinary tract symptoms were assessed using structured questionnaires in 2008-2012. Multivariableadjusted logistic regression models examined associations between interpersonal trauma exposures and PTSD symptoms with: 1) any weekly incontinence, 2) weekly stress-type incontinence, 3) weekly urgency-type incontinence, and 4) nocturia !2 times/night. RESULTS: Of the 1,999 participants analyzed, 36% were Caucasian, 22% Black, 23% Latina, and 20% Asian. Twenty-seven percent reported at least one lifetime interpersonal trauma exposure, and 23% reported clinically significant PTSD (by PTSD Checklist-Civilian Version score !30). Overall, 45% reported any weekly incontinence, 23% weekly stress-type incontinence, 23% weekly urgency-type incontinence, and 35% nocturia. In multivariable models adjusting for age, race/ethnicity, education, body mass index, parity, menopausal status, pelvic surgery, and selected medications, women with a history of emotional abuse were more likely to report any weekly incontinence (adjusted odds ratio [AOR] [1.3, 95% confidence interval [CI][1.0-1.7) and nocturia (AOR[1.7, CI[1.4-2.2). Physical abuse was associated with nocturia (AOR [1.4, CI[1.0-1.8) but not incontinence. PTSD was associated with any weekly incontinence (AOR[1.5, CI[1.2-1.9), stress-type incontinence (AOR[1.7, CI[1.3-2.2), urgency-type incontinence (AOR [1.6, CI[1.2-2.1), and nocturia (AOR[2.0, CI-1.6-2.5). CONCLUSIONS: Over 20% of midlife and older women in this community-based cohort had a history of physical or emotional interpersonal trauma, which contributed to their risk of urinary tract symptoms. Findings point to interpersonal trauma as a potentially under-recognized risk factor for urinary tract dysfunction and highlight the need for trauma-informed care of women presenting with urinary symptoms in community settings.
Journal of Urology, 2019
Purpose: Lower urinary tract symptoms are prevalent and burdensome, yet methods to enhance diagno... more Purpose: Lower urinary tract symptoms are prevalent and burdensome, yet methods to enhance diagnosis and appropriately guide therapies are lacking. We systematically reviewed the literature for human studies of biomarkers associated with lower urinary tract symptoms. Materials and Methods: PubMedÒ, EMBASEÒ and Web of ScienceÒ were searched from inception to February 13, 2018. Articles were included if they were in English, performed in benign urological populations without neurological disorders or interstitial cystitis/bladder pain syndrome, and assessed a biomarker's association with or ability to predict specific lower urinary tract symptoms or urological conditions. Bioinformatic pathway analyses were conducted to determine whether individual biomarkers associated with symptoms are present in unifying pathways. Results: Of 6,150 citations identified 125 met the inclusion criteria. Most studies (93.6%) assessed biomarkers at 1 time point and were crosssectional in nature. Few studies adjusted for potentially confounding clinical variables or assessed biomarkers in an individual over time. No individual biomarkers are currently validated as diagnostic tools for lower urinary tract symptoms. Compared to controls, pathway analyses identified multiple immune response pathways that were enriched in overactive bladder
Journal of Urology, 2019
Purpose: To improve the potential for finding clinically important subtypes of patients with lowe... more Purpose: To improve the potential for finding clinically important subtypes of patients with lower urinary tract symptoms (LUTS), we describe the development of the Comprehensive Assessment of Self-reported Urinary Symptoms (CASUS)-and use it to present data on the experiences of LUTS in treatment-seeking women and men from a prospective observational cohort. Materials and Methods: An initial list of LUTS as confirmed in 22 qualitative interviews with providers and 88 qualitative interviews with care-seeking and non-care-seeking women and men with LUTS. Items from extant measures were adopted and revised and new items were developed, and all were evaluated for understanding in 64 cognitive interviews. Items were administered to a prospective cohort of female and male LUTS patients seeking care and analyses were conducted to describe item response distributions and correlations among item responses separately for women and men. Results: A total of 444 males and 372 females provided responses to CASUS. There were several sets of items that had different relationships for women compared to men. In particular, the associations between sensation-related items and incontinence-related items were generally positive among females, but were often negative among males. Conclusions: Using an intensive development process, the CASUS addresses a wide range of LUTS. It should help to identify clinically important subtypes of patients. Further, the collection of items can provide the foundation for shorter measures for use in the clinic and as trial endpoints.
The Journal of Urology, 2018
bladder volume (BV: voided volumeþPVR). IPSS was also stratified in three classes of LUTS severit... more bladder volume (BV: voided volumeþPVR). IPSS was also stratified in three classes of LUTS severity: 0-7 moderate, 8-19 fair, 20-35 severe. Patients satisfaction was measured by VAS and a simple question. Q-square and T-Student tests were used for statistical analysis. RESULTS: IPSS class showed improvement in both groups, higher when BOO was associated to DU (p¼0.037). In both groups no statistical difference was documented regarding improvement of IPSS mean score (p¼0.68), mean peak flow (p¼0.052), and mean PVR/PVR ratio (p¼0.49). Subjective satisfaction was high in both groups. Patients characteristic and outcomes are reported in Table 1 and Table 2. CONCLUSIONS: In patients with detrusor underactivity TURP leads to a significant improvement in functional outcomes. Males with DU and BOO had better results but with no statistical difference. Thus, the lack of BOO in patients with DU should not be excluding from surgical indications.
The Journal of Urology, 2018
increased risk of urinary tract infections (UTI) and may be considered an indication for clinical... more increased risk of urinary tract infections (UTI) and may be considered an indication for clinical intervention. We sought to describe the associations between measured PVR and self-reported symptoms and UTI in patients seeking treatment for lower urinary tract symptoms (LUTS). METHODS: Data were obtained from the LURN Observational Cohort Study. PVR and self-reported history of UTIs were collected at the baseline clinic visit. Women were asked if they had ever had more than two UTIs while men were asked if they had ever had any UTIs. Lower urinary tract symptoms (LUTS) were collected using the AUA-SI and the LUTS Tool. Comparisons by sex were made using Wilcoxon two-sample and chi-square tests. RESULTS: 48% of women reported more than 2 UTIs and 22% of men reported having had a UTI (Table). Median measured PVR was not different by UTI status for males or females (median PVR [ml] for UTI vs. no UTI: 29.5 vs. 27 for males and 26 vs. 25.5 for females). There was no difference in elevated PVR (>200ml) by UTI in either sex (11.1% vs. 7.7% in males and 2.7% vs. 2.1% in females). Self-reported symptoms of incomplete emptying were slightly higher in females who had more than 2 UTIs compared to those that did not (median LUTS Tool score 2 [sometimes] vs. 1 [rarely], p¼0.004; median AUA score 2 [< half the time] vs. 1 [<1 time in 5], p¼0.006), but these scores did not differ between men with any previous UTIs compared to men no previous UTIs. CONCLUSIONS: The PVR in care-seeking people is not associated with the self-reported incidence of recurrent UTI, despite some association with retention symptoms in females. Our results suggest that an elevated PVR may not be associated with recurrent urinary tract infections.
The Journal of Urology, 2018
Lower urinary tract symptoms are common in women and presumably relate to four recognized domains... more Lower urinary tract symptoms are common in women and presumably relate to four recognized domains of toileting behaviors, including 1) place, 2) timing, 3) position, and 4) style. However, little is still known about the associations between abnormal or dysfunctional toileting behaviors and urinary symptoms. Our aim was to investigate whether increased lower urinary tract symptoms, specifically overactive bladder (OAB), are correlated with increased self-report of dysfunctional toileting behaviors in a community-based sample of women. METHODS: In this cross-sectional study, we recruited 2,215 community women to complete online, validated questionnaires, including the Toileting Behavior Scale (TBS) and International Consultation on Incontinence Questionnaire-Overactive bladder (ICIQ-OAB). Dysfunctional behavior questions were grouped by premature voiding (voiding without the need to urinate), delayed voiding, and straining to void. Pearson correlation was used to examine the strength of associations between ICIQ-OAB and dysfunctional toileting behavior scores. RESULTS: The average age was 47.3 (range: 18-89). All except 3 women (99.9%) reported a place preference for voiding, with 10.5% (n¼233) always avoiding public restrooms. Overall, 79.9% (n¼1,770) reported premature voiding, 64.5% (n¼1,429) straining to void, and 97.8% (n¼2,166) delayed voiding. Reasons for delaying urination at least sometimes were 00 busy 00 (84.5%, n¼ 1,873) or 00 at work 00 (37.6%, n¼ 832). There were significant positive correlations between ICIQ-OAB scores and all dysfunctional toileting behaviors, with the strongest correlation being premature voiding (r¼0.364, p<0.001). CONCLUSIONS: Nearly all women in our sample endorsed dysfunctional toileting behaviors with voiding. There was correlation of toileting behaviors and lower urinary tract symptoms. Women with worse OAB symptoms were most likely to void pre-emptively, in the absence of desire, although many also reported straining to void and delaying voiding. Further study is needed to explore the effects of dysfunctional toileting behaviors on the development or worsening of lower urinary tract symptoms in adult women.
The Journal of Urology, 2018
associated with the decreased prevalence of BPH in men !60 years. Amount of drinking was negative... more associated with the decreased prevalence of BPH in men !60 years. Amount of drinking was negatively associated with the BPH prevalence in all age groups except for men < 50 years. Among metabolic syndrome-related components, decreased HDL-cholesterol was the most powerful variable associated with the prevalence of BPH in all age categories although all components of metabolic syndrome were related with increased prevalence of BPH, especially in male !50 years. CONCLUSIONS: Metabolic syndrome and its components, especially decreased HDL-cholesterol, increased the prevalence of BPH and appropriate alcohol intake plays a role in preventing BPH. In addition, from the viewpoint of BPH, social and medical attention to male with low-income thought to be needed.
The Journal of Urology, 2018
baseline, as evidenced by 95% CIs, was achieved with each treatment. Drug-related adverse events ... more baseline, as evidenced by 95% CIs, was achieved with each treatment. Drug-related adverse events (AEs) were reported in 16.4% of all pts; with higher incidence observed with Tol4 and V100 þ Tol4. Dry mouth was more common with Tol4 (7.1%) vs V50mg (3.6%); V100 mg (2.4%); V100 þ Tol4 (4.5%). Discontinuation due to AEs was also higher with Tol4 (6.3%) vs V50mg (2.7%); V100 mg (2.8%); V100þTol4 (3.7%). Changes in heart rate and blood pressure were minimal with V50 or V100 mg and similar to Tol4. CONCLUSIONS: Vibegron 50mg and 100 mg once daily are well tolerated and provide durable efficacy in OAB pts during longterm use.
The Journal of Urology, 2018
ABSTRACTWe present a novel methodology for subtyping of persons with a common clinical symptom co... more ABSTRACTWe present a novel methodology for subtyping of persons with a common clinical symptom complex by integrating heterogeneous continuous and categorical data. We illustrate it by clustering women with lower urinary tract symptoms (LUTS), who represent a heterogeneous cohort with overlapping symptoms and multifactorial etiology. Identifying subtypes within this group would potentially lead to better diagnosis and treatment decision-making. Data collected in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN), a multi-center prospective observational cohort study, included self-reported urinary and non-urinary symptoms, bladder diaries, and physical examination data for 545 women. Heterogeneity in these multidimensional data required thorough and non-trivial preprocessing, including scaling by controls and weighting to mitigate data redundancy, while the various data types (continuous and categorical) required novel methodology using a weighted Tanimoto indic...
Urology, 2019
Objectives: To assess the feasibility of a novel proteomics approach to identify biomarkers assoc... more Objectives: To assess the feasibility of a novel proteomics approach to identify biomarkers associated with LUTS within serum and urine, because many clinical factors contribute to lower urinary tract symptoms (LUTS) in men and women. These factors confound clinicians' abilities to reliably evaluate and treat LUTS. Previous studies identified candidate LUTS biomarkers, but none are clinically utilized. Methods: Eighteen male and 18 female Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) Observational Cohort Study participants with LUTS (measured on the LUTS Tool questionnaire) were randomly selected. Twelve male and 12 female controls with minimal or no LUTS were recruited and matched for clinico-demographic characteristics. The SomaScan Assay (SomaLogic) was used to measure the abundance of 1305 proteins contained within urine and serum. Statistical analyses were performed to evaluate reproducibility of assays, compare protein abundances, and estimate effect size.
<p>Results of the computer simulation of electric potential, electric field and electroosmo... more <p>Results of the computer simulation of electric potential, electric field and electroosmotic flow velocity in the axisymmetric model of the cell (cylinder of 10 µm radius and 10 µm height, nucleus–sphere of 3 µm radius, located in the center of the cylinder). Mathematical model is described by eqs. (1–6); parameters are presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061884#pone-0061884-t001" target="_blank">Table 1</a>. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061884#pone-0061884-g001" target="_blank">Figure 1A</a> represents electric potential (color map) and electric field strength (arrows) in the model of the polarized cell; inward current enters through the top of the cylinder and leaves the cell through the bottom of the cylinder (eq. 2). Electric potential is in the range −0.007÷−0.059 V; strong component of electric field parallel to the cylindrical surface is present. For comparison, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061884#pone-0061884-g001" target="_blank">Figure 1B</a> presents electric potential and field in the non-polarized cell (zero inward and outward current); here the component of electric field parallel to the surface is practically absent. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061884#pone-0061884-g001" target="_blank">Figure 1C</a> demonstrates electroosmotic flow circulation (color represents magnitude of the velocity, arrows represent direction) caused by electric field distribution in the polarized cell (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061884#pone-0061884-g001" target="_blank">Fig. 1A</a>), maximum value of fluid velocity 120 µm/s is in the vicinity of the cylindrical wall, while the average magnitude of the fluid velocity across the cytoplasm is 20 µm/s. Fluid circulates, moving downwards near the cylindrical wall and upwards near the nucleus. For comparison, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0061884#pone-0061884-g001" target="_blank">Figure 1D</a> demonstrates that electroosmotic flow is practically absent (except the filleted corners) in the model of a non-polarized cylindrical cell, where electric field parallel to the surface is absent.</p