Detrusor underactivity (DUA) is defined as a voiding contraction of reduced strength and/or duration, which prolongs urination and/or prevents complete emptying of the bladder within a 'normal' ...period of time. This issue is associated with voiding and postmicturition urinary symptoms, and can predispose to urinary infections and acute urinary retention. The aetiology of DUA is influenced by multiple factors, including ageing, bladder outlet obstruction, neurological disease, and autonomic denervation. The true prevalence of this condition remains unknown, as most data come from referral populations. Urodynamic testing is used to diagnose the condition, either by assessing the relationship between bladder pressures and urinary flow, or by interrupting voiding to measure detrusor pressure change under isovolumetric conditions. Current treatments for DUA have poor efficacy and tolerability, and often fail to improve quality of life; muscarinic receptor agonists, in particular, have limited efficacy and frequent adverse effects. Bladder emptying might be achieved through Valsalva straining, and intermittent or indwelling catheterization, although sacral nerve stimulation can reduce dependency on catheterization. Novel stem-cell-based therapies have been attempted; however, new drugs that increase contractility are currently largely conceptual, and the complex pathophysiology of DUA, difficulty achieving organ specificity of treatment, the limited availability of animal models, and the subjective nature of current outcome measures must be addressed to facilitate the development of such agents.
We report a 1-year update of functional urinary and sexual recovery, oncologic outcomes and postoperative complications in patients who completed a randomized controlled trial comparing posterior ...(Retzius sparing) with anterior robot-assisted radical prostatectomy.
A total of 120 patients with clinically low-intermediate risk prostate cancer were randomized to undergo robot-assisted radical prostatectomy via the posterior and anterior approach in 60 each. Surgery was performed by a single surgical team at an academic institution. An independent third party ascertained urinary and sexual function outcomes preoperatively, and 3, 6 and 12 months after surgery. Oncologic outcomes consisted of positive surgical margins and biochemical recurrence-free survival. Biochemical recurrence was defined as 2 postoperative prostate specific antigen values of 0.2 ng/ml or greater.
Median age of the cohort was 61 years and median followup was 12 months. At 12 months in the anterior vs posterior prostatectomy groups there were no statistically significant differences in the urinary continence rate (0 to 1 security pad per day in 93.3% vs 98.3%, p = 0.09), 24-hour pad weight (median 12 vs 7.5 gm, p = 0.3), erection sufficient for intercourse (69.2% vs 86.5%) or postoperative Sexual Health Inventory for Men score 17 or greater (44.6% vs 44.1%). In the posterior vs anterior prostatectomy groups a nonfocal positive surgical margin was found in 11.7% vs 8.3%, biochemical recurrence-free survival probability was 0.84 vs 0.93 and postoperative complications developed in 18.3% vs 11.7%.
Among patients with clinically low-intermediate risk prostate cancer randomized to anterior (Menon) or posterior (Bocciardi) approach robot-assisted radical prostatectomy the differences in urinary continence seen at 3 months were muted at the 12-month followup. Sexual function recovery, postoperative complication and biochemical recurrence rates were comparable 1 year postoperatively.
Abstract Background The clinical diagnosis of detrusor underactivity (DU) is hampered by the need for invasive pressure flow studies (PFS) in combination with a lack of knowledge of the associated ...signs and symptoms. This has contributed to a lack of awareness of DU and underactive bladder, and to the assumption that symptoms are always due to bladder outlet obstruction (BOO). Objective To investigate the signs and symptoms recorded in a large urodynamic database of patients who met the diagnoses of DU, BOO, and normal, to identify the clinical features associated with DU. Design, setting, and participants From the database of 28 282 adult PFS records, 1788 patients were classified into: (1) those with DU without BOO; (2) those with BOO without DU; and (3) those with normal PFS. Results Patients with DU reported a statistically significantly higher occurrence of decreased and/or interrupted urinary stream, hesitancy, feeling of incomplete bladder emptying, palpable bladder, and absent and/or decreased sensation compared with patients with normal PFS. Other differences were found between men with DU and BOO, and between women with DU and normal PFS. Conclusions There are signs and symptoms that can distinguish DU patients from patients with normal PFS and further distinguish between DU and BOO, which is traditionally invasively diagnosed. This is a first step to better understand the clinical presentation of DU patients, is consistent with the recent underactive bladder working definition, and justifies further exploration of the signs and symptoms of DU. Patient summary The clinical diagnosis of detrusor underactivity is hampered by the need for invasive urodynamics in combination with a lack of knowledge of the associated signs and symptoms. This study has shown that there are signs and symptoms that can distinguish men and women patients with DU from patients with either normal urodynamic studies or with BOO.
Background
Invasive urodynamic tests are used to investigate men with lower urinary tract symptoms (LUTS) and voiding dysfunction to determine a definitive objective diagnosis. The aim is to help ...clinicians select the treatment that is most likely to be successful. These investigations are invasive and time‐consuming.
Objectives
To determine whether performing invasive urodynamic investigation, as opposed to other methods of diagnosis such as non‐invasive urodynamics or clinical history and examination alone, reduces the number of men with continuing symptoms of voiding dysfunction. This goal will be achieved by critically appraising and summarising current evidence from randomised controlled trials related to clinical outcomes and cost‐effectiveness. This review is not intended to consider whether urodynamic tests are reliable for making clinical diagnoses, nor whether one type of urodynamic test is better than another for this purpose.
The following comparisons were made.
• Urodynamics versus clinical management.
• One type of urodynamics versus another.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, issue 10), MEDLINE (1 January 1946 to Week 4 October 2014), MEDLINE In‐Process and other non‐indexed citations (covering 27 November 2014; all searched on 28 November 2014), EMBASE Classic and EMBASE (1 January 2010 to Week 47 2014, searched on 28 November 2014), ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) (searched on 1 December 2014 and 3 December 2014, respectively), as well as the reference lists of relevant articles.
Selection criteria
Randomised and quasi‐randomised trials comparing clinical outcomes in men who were and were not investigated with the use of invasive urodynamics, or comparing one type of urodynamics against another, were included. Trials were excluded if they did not report clinical outcomes.
Data collection and analysis
Three review authors independently assessed trial quality and extracted data.
Main results
We included two trials, but data were available for only 339 men in one trial, of whom 188 underwent invasive urodynamic studies. We found evidence of risk of bias, such as lack of outcome information for 24 men in one arm of the trial.
Statistically significant evidence suggests that the tests did change clinical decision making. Men in the invasive urodynamics arm were more likely to have their management changed than men in the control arm (proportion with change in management 24/188 (13%) vs 0/151 (0%), risk ratio (RR) 39.41, 95% confidence interval (CI) 2.42 to 642.74). However, the quality of the evidence was low.
Low‐quality evidence indicates that men in the invasive urodynamics group were less likely to undergo surgery as treatment for voiding LUTS (164/188 (87%) vs 151/151 (100%), RR 0.87, 95% CI 0.83 to 0.92).
Investigators observed no difference in urine flow rates before and after surgery for LUTS (mean percentage increase in urine flow rate, 140% in invasive urodynamic group vs 149% in immediate surgery group, P value = 0.13). Similarly, they found no differences between groups with regards to International Prostate Symptom Score (IPSS) (mean percentage decrease in IPSS score, 58% in invasive urodynamics group vs 59% in immediate surgery group, P value = 0.22).
No evidence was available to demonstrate whether differences in management equated to improved health outcomes, such as relief of symptoms of voiding dysfunction or improved quality of life.
No evidence from randomised trials revealed the adverse effects associated with invasive urodynamic studies.
Authors' conclusions
Although invasive urodynamic testing did change clinical decision making, we found no evidence to demonstrate whether this led to reduced symptoms of voiding dysfunction after treatment. Larger definitive trials of better quality are needed, in which men are randomly allocated to management based on invasive urodynamic findings or to management based on findings obtained by other diagnostic means. This research will show whether performance of invasive urodynamics results in reduced symptoms of voiding dysfunction after treatment.
In Dysfunctional voiding, failure of the external sphincter-pelvic floor complex to relax during micturition results in bladder outflow obstruction with a spectrum of presentation from more benign ...lower urinary tract dysfunction including recurrent urinary tract infections, to significant upper tract pathology and end-stage renal failure. There is no underlying neurological or anatomical cause and the condition is postulated to be a largely learnt behavior. Diagnosis relies on non-invasive urodynamics and in particular uroflowmetry, plus or minus EMG, which is also used in biofeedback, the mainstay of treatment. The etiology, presentation, diagnosis, and treatment with particular emphasis on non-invasive urodynamics are covered.
Acyloxyacyl hydrolase regulates voiding activity Aguiniga, Lizath M; Searl, Timothy J; Rahman-Enyart, Afrida ...
American journal of physiology. Renal physiology,
04/2020, Letnik:
318, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Corticotropin-releasing factor (CRF) regulates diverse physiological functions, including bladder control. We recently reported that
expression is under genetic control of
, the locus encoding ...acyloxyacyl hydrolase (AOAH), suggesting that AOAH may also modulate voiding. Here, we examined the role of AOAH in bladder function. AOAH-deficient mice exhibited enlarged bladders relative to wild-type mice and had decreased voiding frequency and increased void volumes. AOAH-deficient mice had increased nonvoiding contractions and increased peak voiding pressure in awake cystometry. AOAH-deficient mice also exhibited increased bladder permeability and higher neuronal firing rates of bladder afferents in response to stretch. In wild-type mice, AOAH was expressed in bladder projecting neurons and colocalized in CRF-expressing neurons in Barrington's nucleus, an important brain area for voiding behavior, and
was elevated in Barrington's nucleus of AOAH-deficient mice. We had previously identified aryl hydrocarbon receptor (AhR) and peroxisome proliferator-activated receptor-γ as transcriptional regulators of
, and conditional knockout of AhR or peroxisome proliferator-activated receptor-γ in
-expressing cells restored normal voiding in AOAH-deficient mice. Finally, an AhR antagonist improved voiding in AOAH-deficient mice. Together, these data demonstrate that AOAH regulates bladder function and that the AOAH-
axis is a therapeutic target for treating voiding dysfunction.
Abstract Background No study has compared the bothersomeness of all lower urinary tract symptoms (LUTS) using a population-based sample of adults. Despite this lack of evidence, investigators have ...often cited their LUTS of interest as the “most bothersome” or “one of the most bothersome.” Objective To compare the population- and individual-level burden of LUTS in men and women. Design, setting, and participants In this population-based cross-sectional study, questionnaires were mailed to 6000 individuals (18–79 yr of age) randomly identified from the Finnish Population Register. Outcome measurements and statistical analysis The validated Danish Prostatic Symptom Score questionnaire was used for assessment of bother of 12 different LUTS. The age-standardized prevalence of at least moderate bother was calculated for each symptom (population-level burden). Among symptomatic individuals, the proportion of affected individuals with at least moderate bother was calculated for each symptom (individual-level bother). Results and limitations A total of 3727 individuals (62.4%) participated (53.7% female). The LUTS with the greatest population-level burden were urgency (7.9% with at least moderate bother), stress urinary incontinence (SUI) (6.5%), nocturia (6.0%), postmicturition dribble (5.8%), and urgency urinary incontinence (UUI) (5.0%). Burden from incontinence symptoms was higher in women than men, and the opposite was true for voiding and postmicturition symptoms. At the individual level, UUI was the most bothersome for both genders. Although the response proportion was high, approximately a third did not participate. Conclusions Both men and women with UUI report moderate or major bother more frequently than individuals with other LUTS. At the population level, the most prevalent bothersome symptoms are urgency, SUI, and nocturia. Patient summary Urinary urgency was the most common troubling symptom in a large population-based study; however, for individuals, urgency incontinence was the most likely to be rated as bothersome.
Investigators have for decades used mouse voiding patterns as end points for studying behavioral biology. It is only recently that mouse voiding patterns were adopted for study of lower urinary tract ...physiology. The spontaneous void spot assay (VSA), a popular micturition assessment tool, involves placing a mouse in an enclosure lined by filter paper and quantifying the resulting urine spot pattern. The VSA has advantages of being inexpensive and noninvasive, but some investigators challenge its ability to distinguish lower urinary tract function from behavioral voiding. A consensus group of investigators who regularly use the VSA was established by the National Institutes of Health in 2015 to address the strengths and weaknesses of the assay, determine whether it can be standardized across laboratories, and determine whether it can be used as a surrogate for evaluating urinary function. Here we leverage experience from the consensus group to review the history of the VSA and its uses, summarize experiments to optimize assay design for urinary physiology assessment, and make best practice recommendations for performing the assay and analyzing its results.
Late genitourinary (GU) toxicity after radiation therapy limits the quality of life of prostate cancer survivors; however, efforts to explain GU toxicity using patient and dose information have ...remained unsuccessful. We identified patients with a greater congenital GU toxicity risk by identifying and integrating patterns in genome-wide single nucleotide polymorphisms (SNPs).
We applied a preconditioned random forest regression method for predicting risk from the genome-wide data to combine the effects of multiple SNPs and overcome the statistical power limitations of single-SNP analysis. We studied a cohort of 324 prostate cancer patients who were self-assessed for 4 urinary symptoms at 2 years after radiation therapy using the International Prostate Symptom Score.
The predictive accuracy of the method varied across the symptoms. Only for the weak stream endpoint did it achieve a significant area under the curve of 0.70 (95% confidence interval 0.54-0.86; P = .01) on hold-out validation data that outperformed competing methods. Gene ontology analysis highlighted key biological processes, such as neurogenesis and ion transport, from the genes known to be important for urinary tract functions.
We applied machine learning methods and bioinformatics tools to genome-wide data to predict and explain GU toxicity. Our approach enabled the design of a more powerful predictive model and the determination of plausible biomarkers and biological processes associated with GU toxicity.
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