Is the time right for a new initiative in mathematical modeling of the lower urinary tract? ICI-RS 2023.

INTRODUCTION: A session at the 2023 International Consultation on Incontinence - Research Society (ICI-RS) held in Bristol, UK, focused on the question: Is the time right for a new initiative in mathematical modeling of the lower urinary tract (LUT)? The LUT is a complex system, comprising various synergetic components (i.e., bladder, urethra, neural control), each with its own dynamic functioning and high interindividual variability. This has led to a variety of different types of models for different purposes, each with advantages and disadvantages. METHODS: When addressing the LUT, the modeling approach should be selected and sized according to the specific purpose, the targeted level of detail, and the available computational resources. Four areas were selected as examples to discuss: utility of nomograms in clinical use, value of fluid mechanical modeling, applications of models to simplify urodynamics, and utility of statistical models. RESULTS: A brief literature review is provided along with discussion of the merits of different types of models for different applications. Remaining research questions are provided. CONCLUSIONS: Inadequacies in current (outdated) models of the LUT as well as recent advances in computing power (e.g., quantum computing) and methods (e.g., artificial intelligence/machine learning), would dictate that the answer is an emphatic "Yes, the time is right for a new initiative in mathematical modeling of the LUT."

Detrusor contractility in post-menopausal women: Impact of ageing, complaint and urodynamic diagnosis.

INTRODUCTION: Detrusor contractility (DC) can have a considerable impact on the management oflower urinary tract symptoms (LUTS). However, it is currently impossible to predict, based on clinical data alone, which woman has an impaired DC. Our aim was to determine if DC, assessed by projected isovolumetric pressure-1 (PIP1) and VBN contractility parameter k, was associated with age, main complaint, and urodynamic diagnosis in a population of older women. METHODS: Pressure-flow studies of non-neurologic post menopausal women over 65 referred for investigation of LUTS were retrospectively analyzed. Associations between DC indices PIP1 and k, and age, main complaint and urodynamic diagnosis were assessed in univariate analysis. RESULTS: One hundred and ninety women were included (mean age 74.5 years). There was no significant association between detrusor contractility indices and age considered as a continuous or a categorical variable. Urge urinary incontinence was significantly associated with greater detrusor contractility regardless of age. Regarding urodynamic diagnoses, DC was greater when bladder outlet obstruction and detrusor overactivity were diagnoses vs. detrusor underactivity alone or associated with detrusor overactivity, regardless of age. CONCLUSION: PIP1 and k indices allow an easy evaluation of detrusor contractility. In that population of older, post menopausal women, no significant change in the value of the indices is observed with aging whatever the complaint or the urodynamic diagnosis. None of these indices has predominance. LEVEL OF EVIDENCE: 4.

Can we improve our diagnosis of impaired detrusor contractility in women? An ICI-RS 2019 proposal.

INTRODUCTION: Widely accepted consensus terminology and calculations of detrusor contractility in females do not exist but may be useful. We report the output of a proposal session at the International Consultation on Incontinence Research Society meeting 2019, addressing the title topic. METHODS: Three formal presentations and a lively discussion addressed several questions including: which is the optimal cutoff value of female bladder voiding efficiency during uroflow to suspect obstruction or detrusor underactivity? Is there a definition of pure underactive and pure obstructed voiding in females? Is there a place to distinguish those relatively obstructed from those relatively underactive females especially in those cases of equivocal obstruction? Current measures of contractility were reviewed for their usefulness in women. RESULTS: No recommendation for a specific index or calculation can be made based on current knowledge. "Contractility" may be context-dependent regarding clinical care, clinical prognostication, and physiologic research. CONCLUSIONS: This group proposes that context-sensitive definitions of "Contractility" deserve attention by international leadership. Cooperative clinical and physiologic expertise will be needed to achieve this goal. Following initial recommendations based on expert opinion, the development of final definitions and measures of contractility should be iterative, based upon validation studies to be considered as part of the definitional process.

How can we better manage drug-resistant OAB/DO? ICI-RS 2018.

AIMS: Botulinum toxin A (BTX-A), sacral nerve stimulation (SNM), and posterior tibial nerve stimulation (PTNS) are established treatments for idiopathic overactive bladder (OAB) refractory to oral drug therapy. At the ICI-RS meeting in Bristol in 2018 a think tank was convened to address the question of how to better manage drug-resistant OAB/DO (detrusor overactivity). METHODS: The think tank conducted a literature review and an expert consensus meeting focusing on the evidence for predicting response and adverse events (AEs) with the current therapies for drug-resistant idiopathic OAB. RESULTS: Several factors have been associated with poor outcomes using BTX-A including increasing age, body mass index, male sex, and frailty. Voiding dysfunction with BTX-A also appears to be more prevalent in those with increasing age, male sex, higher baseline postvoid residual and with poorer contractility as assessed by urodynamic parameters. SNM full implantation appears to be higher with the first stage tined lead placement procedure compared to percutaneous nerve evaluation. Urodynamics do not appear to predict outcomes with SNM. Patients with psychiatric comorbidity are more likely to experience AEs with SNM. Outcomes related to lead positioning and the number of active electrodes are mixed in predicting long term success. Patients with increased daytime frequency and lower first sensation of bladder filling were independent factors associated with success with PTNS. CONCLUSIONS: Further research is required to optimize these procedures and to better understand which patients will benefit from the various options available in managing refractory OAB.

Are there different patterns of detrusor overactivity which are clinically relevant? ICI-RS 2018.

INTRODUCTION: Different patterns of detrusor overactivity (DO) have been described and included in several standardization terminology documents. However, it is unclear if these different patterns have any clinical significance. METHODS: This is a report of the proceedings of Proposal 3: "Are there different patterns of detrusor overactivity which are clinically relevant?" from the annual International Consultation on Incontinence-Research Society (ICIRS) meeting, which took place from 14 to 16 June 2018, in Bristol, UK. RESULTS: We have collected and discussed, as a committee, the evidence about different urodynamic (UD) patterns of detrusor overactivity and their potential clinical significance. We reviewed the important previous basic research and clinical studies and compiled summaries. The discussion focused on clinical relevance of different UD patterns of DO and what further research is required. CONCLUSIONS: There are several UD definitions of patterns of detrusor overactivity, however the clinical relevance of these definitions remains unclear. Future research should concentrate on defining the pattern of DO in relation to clinical diagnosis, gender, age, and treatment outcomes.

Is the value of urodynamics undermined by poor technique?: ICI-RS 2018.

INTRODUCTION: The quality of urodynamic measurements in clinical practice has been debated as a matter of concern. It is considered plausible that this has a direct bearing on patient care and the perceived value of urodynamic testing. METHODS: This is a report of the proceedings of the Think Tank: "Is the value of urodynamics undermined by poor technique?" from the Annual International Consultation on Incontinence-Research Society, which took place in June 2018 in Bristol, UK. The Think Tank discussed the evidence for deficiencies in urodynamic test quality and considered the implications of improvements for clinical diagnosis and practice. RESULTS: There is evidence that technique affects urodynamic quality, and that urodynamic practice is variable. Factors such as team skill set, technologies used, and training received will also affect the quality of urodynamic service. Questions exist regarding the influence of technique on the utility and perceived value of urodynamics. CONCLUSIONS: We suggest research questions that will provide the necessary evidence on the link between technique, reporting, and outcome, and clarify the role of good practice in the utility of urodynamic testing.

What research is needed to validate new urodynamic methods? ICI-RS2017.

AIMS: In recent years urodynamic innovations, although well researched, have failed to follow a standardized development pathway specifically in terms of clinical trials undertaken to demonstrate efficacy. This was discussed at the International Consultation on Incontinence Research Society (ICI-RS) in Bristol, United Kingdom, 2017 with the aim of defining minimum standards for future urodynamic research. METHODS: The recent recommendations from the IDEAL (innovation, development, exploration, assessment, and long-term study) collaboration regarding surgical research were reviewed. Two examples of recent novel urodynamic technologies, the penile cuff test and air charged urodynamic catheters were used as case studies and the research programmes behind their development were critiqued. RESULTS: The rigorous and standardized model of surgical research proposed by the IDEAL collaboration was endorsed as an appropriate model for future urodynamic research. A methodical approach to research can fulfil a host of objectives including illustration of the clinical need, help with design and refinement of technique and proving efficacy for any new test or device. The penile cuff test is a novel urodynamic measurement technique that has been well researched and is now used in clinical practice. Further research is needed before air charged catheters can be recommended for widespread clinical use and the IDEAL framework provides a template for ongoing development. CONCLUSIONS: In the future, these recommendations should lead to a more standardized and uniform programme of urodynamic research and enable a thorough evaluation of new technologies prior to wider clinical uptake.

Comparison of bladder voiding efficiency in women when calculated from a free flow versus an intubated flow.

OBJECTIVES: To assess the reproducibility of bladder voiding efficiency (BVE, Void%) between free flow (FF) and intubated flow (IF) and to correlate BVE measurements with urinary incontinence (UI) complaints and urodynamic (UDS) findings in women. METHODS: UDS recordings of women referred for LUTD evaluation to our UDS center were reviewed. Each file included FF at arrival, filling cystometry, and IF. Post-void residual volumes (PVR) were measured by catheterization after FF and IF. Women unable to void during the study or who expelled the catheter during IF, as well as studies with voided volume < 100 ml were excluded. Data was sub-analyzed according to 3 age categories, and UI complaints and UDS findings. RESULTS: Over the past 3 years, 237 UDS studies for FF and IF met all criteria. There was significant difference between voided volumes (232 vs. 335 ml) and PVR (24 vs. 71 ml) respectively (P < 0.0001). For the whole population, BVE IF (79.8 ± 28.6) was significantly lower than BVE FF (90.7 ± 15.9) (P < 0.0001). A significant decrease of BVE during IF was only noted for UI. BVE IF was significantly different in women in the peri-menopause and older groups. PVR IF increased with age and was significantly higher than PVR FF for women older than 45 years (P < 0.0001). CONCLUSIONS: BVE measurement in women has a role, but is most reliable from a FF. BVE is influenced by age and urinary incontinence complaints as well as UDS findings.

Are nomograms based on free uroflows helpful to evaluate urethral obstruction in men?

AIMS: It was demonstrated earlier that reduced maximum flow-rate (Qmax ) during intubated flow (IF) in women may be the consequence of a urethral reflex. Over-estimation of outflow obstruction is the consequence. Our hypothesis, that a similar phenomenon could occur in men, is tested using results of a free uroflow (FF) preceding an IF to eventually correct the Abrams-Griffiths (AG) number. METHODS: Retrospectively, analysis of 441 urodynamic studies of men suspected of bladder outflow obstruction (BOO) was performed. The Valentini-Besson-Nelson model links outflow obstruction (parameter pucp) and the detrusor contractility (parameter k) to Qmax and detrusor pressure at Qmax (pdet.Qmax ). AG and pucp are strongly correlated. Contractility is described by a graphical representation (a nomogram) which numerical fitting is an algebraic equation f(Qmax ,pdet.Qmax ). Nomograms based on IF allowed computing a calculated AG (corr-AG) on the basis of free flow. RESULTS: Included files (N = 362) had filling volume during FF > 90 mL; corr-AG was compared to AG. When Qmax.FF > 1.5*Qmax.IF (N = 114), 61 patients (53.5%) were found less obstructed with corr-AG, no one more obstructed. Increased BOO could be the result of a urethral reflex during IF and AG gave an overestimation. When Qmax.FF < 1.5*Qmax.IF (N = 248), only 39 patients (12.1%) were found less obstructed with corr-AG and 28 (11.3%) more obstructed. CONCLUSION: To obtain a reliable evaluation of BOO in men, it is suitable to perform a FF before IF. A corrected AG (corr-AG) obtained from IF analysis and nomograms based on FF may be helpful for evaluation of BOO in men.

Can we define and characterize the aging lower urinary tract?-ICI-RS 2015.

The prevalence of lower urinary tract (LUT) symptoms increases with age but the etiology is unknown. This article aims to identify research directions that clarify the basis of this association. The initial question is whether biological age is the variable of interest or a time-dependent accumulation of factors that impact on LUT function at rates that differ between individuals. In particular, the accumulation of conditions or agents due to inflammatory states or tissue ischemia is important. Much of the above has been concerned with changes to bladder function and morphology. However, the outflow tract function is also affected, in particular changes to the function of external sphincter skeletal muscle and associated sacral motor nerve control. Nocturia is a cardinal symptom of LUT dysfunction and is more prevalent with aging. Urine production is determined by diurnal changes to the production of certain hormones as well as arterial blood pressure and such diurnal rhythms are blunted in subjects with nocturia, but the causal links remain to be elucidated. Changes to the central nervous control of LUT function with age are also increasingly recognized, whether in mid-brain/brainstem regions that directly affect LUT function or in higher centers that determine psycho-social and emotional factors impinging on the LUT. In particular, the linkage between increasing white matter hyperintensities and LUT dysfunction during aging is recognized but not understood. Overall, a more rational approach is being developed to link LUT dysfunction with factors that accumulate with age, however, the precise causal pathways remain to be characterized. Neurourol. Urodynam. 36:854-858, 2017. © 2017 Wiley Periodicals, Inc.

VBN-based nomograms provide critical voiding parameters which can be used for invasive or non-invasive flow interpretation of women at risk of obstruction over time.

AIMS: To design a simple office-based method to evaluate characteristic parameters from free uroflowmetries (FF) or pressure flow studies (PFs). This method can be applied by any physician to any recording, for instance in the follow-up of women at risk of developing outflow obstruction over time after surgical interventions. METHOD: Using pressure-flow studies (PFs), a reliable evaluation of urethral obstruction (U) and detrusor contractility (k) parameters could be obtained from the maximum flow rate and detrusor pressure at maximum flow rate. Nomograms for these parameters were derived from theoretical computations using the VBN model. Then, to allow an evaluation of the real urethral obstruction, a protocol was designed incorporating FF data in the follow-up of women suspected of urethral obstruction. RESULTS: Two nomograms were obtained: (1) A urethral obstruction nomogram allowing to define a Woman Obstruction Index (WOI = pdet.Qmax - 0.5*Qmax ) which has the same structure than the A-G number in men. (2) A detrusor contractility nomogram which was generalized to all initial bladder volumes. The curves were fitted by algebraic equations easily programmable on any handheld device. CONCLUSION: Using a mathematical model of micturition and data extracted from PFs, two nomograms on urethral obstruction and detrusor contractility were designed. This tool offers a rapid and practical method for the clinician to follow women at risk of obstruction over time. Its applications will be the purpose of further studies. Neurourol. Urodynam. 36:37-42, 2017. © 2015 Wiley Periodicals, Inc.

Recommendations for future development of contractility and obstruction nomograms for women. ICI-RS 2014.

AIMS: At present, existing bladder outlet obstruction (BOO) nomograms for women are still not universally accepted. Moreover, only limited information is available regarding bladder contractility in women. The aim is to present the discussions and recommendations from the think tank session "Can we construct and validate contractility and obstruction nomograms for women?" held at the 2014 International Consultation on Incontinence-Research Society (ICI-RS) meeting in Bristol, UK. METHODS: An overview of clinical significance, bladder mechanics and modelling, lack of existing nomograms for women, and development of new nomograms were presented and discussed in a multidisciplinary think tank session. This think tank session was based on a collaboration between physicians, engineers, and researchers and consensus was achieved on future research initiatives. RESULTS AND CONCLUSIONS: Based on the think tank discussion, the ICI-RS panel put forward the following recommendations: the need to acquire normative age-matched data in women to define "normal" and "pathological" values of urodynamic parameters; the inclusion of additional clinical data in new nomograms and the use of this extra dimension to develop clinically applicable nomograms for female BOO and contractility; and finally, the need to take into account the variability of BOO in women when developing female bladder contractility nomograms.

Detrusor after-contraction: a new insight.

AIMS: Detrusor after-contractions (DAC) are non-common in adults. Both definition (nothing in ICS reports) and significance (artefact, link with detrusor overactivity (DO) or bladder outlet obstruction (BOO)) remain discussed. Our purpose was to carry out an analysis of the urodynamic parameters during voidings with DAC and, using the VBN model, to simulate pathophysiological conditions able to explain both voiding phase and DAC. MATERIALS AND METHODS: From large urodynamic database of patients referred for evaluation of lower urinary tract dysfunction, DAC were observed in 60 patients (5.7%). Criteria for DAC were post-void residual <30mL and increase of detrusor pressure >10cmH(2)O. VBN model was used for analysis of both pressure and flow curves, and simulations of pathophysiological conditions. RESULTS: Onset of DAC (ODAC) occurred when Q=7.3±5.7mL/s and bladder volume=17.9±15.4mL. Urgency-frequency syndrome and urodynamic diagnosis of DO were the more frequent scenarios associated with DAC. ODAC was associated to an inversion of the slope of detrusor pressure curve without any perturbation in flow curve. Among tested pathophysiological hypothesis (great, abnormal, detrusor force, sphincter contraction), none allowed restoring all recorded curves (flow rate, voiding pressure and DAC). CONCLUSION: No urodynamic characteristic of the first part of voiding is an index of occurrence of DAC. ODAC is a significant phenomenon linked with the bladder collapse. DAC is not associated with BOO but more probably with DO and appears as the result of local conditions in an almost empty bladder (concentration of stresses around a transducer); thus DAC seems of weak clinical significance.

Detrusor after-contraction: a new insight

Detrusor after-contractions (DAC) are non-common in adults. Both definition (nothing in ICS reports) and significance (artefact, link with detrusor overactivity (DO) or bladder outlet obstruction (BOO)) remain discussed. Our purpose was to carry out an analysis of the urodynamic parameters during voidings with DAC and, using the VBN model, to simulate pathophysiological conditions able to explain both voiding phase and DAC.