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Sökning: L773:0733 2467 OR L773:1520 6777 > (2020-2023)

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  • Andersson, Karl Erik, et al. (författare)
  • Are there relevant animal models to set research priorities in LUTD? ICI-RS 2019
  • 2020
  • Ingår i: Neurourology and Urodynamics. - : John Wiley & Sons Inc.. - 0733-2467 .- 1520-6777. ; 39:S3, s. 9-15
  • Forskningsöversikt (refereegranskat)abstract
    • Aim: To discuss animal models of lower urinary tract disorders (LUTD) and their translational impact. Methods: Report of discussions based on presented literature-search based reviews relevant for the purpose. Results: Animal models can be used to investigate fundamental biological mechanisms, but also as tools to elucidate aspects of the pathogenesis of disease and to provide early evidence of any safety risk. Several different models may be required to obtain information that can have a translational impact. The term “translational research” covers not only the process of directly transferring knowledge from basic sciences to human trials to produce new drugs, devices, and treatment options for patients (T1 type translation) but also the implementation of early clinical research findings (phases I-III) into practice to improve care for patients (T2 type). Direct transfer of animal data to T2 is rarely possible, and the process often does not continue after the first trials in humans (phase I). It should be emphasized that many preclinical observations do not have (and do not need to have) immediate translational impact. Conclusions: No single animal model can mimic the complexity of the human disease. Still, animal models can be useful for gaining information on LUT function in humans, for elucidating pathophysiological mechanisms, and for the definition of targets for future drugs to treat LUT disorders.
  • Carlsson Farrelly, Elisabeth, et al. (författare)
  • One treatment with onabotulinumtoxinA relieves symptoms of overactive bladder in patients refractory to one or more oral medications
  • 2023
  • Ingår i: Neurourology and Urodynamics. - : John Wiley & Sons. - 0733-2467 .- 1520-6777. ; 42:6, s. 1203-1213
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction and Hypothesis: Patients with overactive bladder (OAB) often undergo prolonged treatment with one or more oral OAB medications. OnabotulinumtoxinA (onabotA), a type A botulinum toxin, may provide an appropriate alternative to oral treatments in patients intolerant of or refractory to one or more oral OAB medications. The GRACE study demonstrated real-world benefits of onabotA treatment for OAB in patients refractory to oral medications. This exploratory post hoc analysis of data from the GRACE study aims to determine if treatment history impacts benefit from treatment with onabotA.Methods: This is a subanalysis of the GRACE study, a prospective observational study (NCT02161159) that enrolled patients with symptomatic OAB inadequately managed by at least one oral OAB medication. Patients had a treatment history of one or more anticholinergics (AC) and/or β-3 adrenoreceptor agonists (β-3) for relief of OAB; results were stratified according to treatment history. Patients in this analysis elected to discontinue oral medications upon treatment with onabotA. Safety was followed for 12 months in all patients that received at least 1 dose of onabotA; efficacy was determined over a 12-week period.Results: Compared to baseline levels, significant reductions in urinary incontinence (UI), urgency, micturition, and nocturia were noted as early as 1 week and were sustained at 12 weeks, regardless of the type and number of oral medications taken before treatment with onabotA. At 12 weeks post-onabotA, the mean change from baseline UI episodes/day for those with a treatment history of only one AC was −2.4 (n = 43, p ≤ 0.001); more than one AC, −2.4 (n = 52, p ≤ 0.001); one β-3, −3.3 (n = 12, p < 0.05); at least one AC and at least one β-3, −3.2 (n = 56, p ≤ 0.001). Pad and liner use was significantly decreased at 12 weeks post-onabotA across all treatment history groups. Reductions in diaper pant use varied, with less of a reduction in patients with a treatment history of more than one AC compared to patients with a history of at least one AC and one β-3 (p < 0.05) or those with a history of only one AC (p < 0.05). Overall, a total of 253/288 of patients (88%) reported improvements on the treatment benefit scale 12 weeks after treatment with onabotA, regardless of type and number of prior oral medications. In the population of patients that received at least one dose of onabotA (N = 504), 57 adverse events were reported in 38 patients (7.5%); 9 were serious (1.8%). Urinary retention was reported in 5 patients (1.0%); 1 was severe (0.2%). Symptomatic urinary tract infection was reported in 2 patients (0.4%).Conclusions: In this exploratory post hoc analysis of real-world data from the GRACE study, there were few significant differences in outcomes based on the type and number of prior oral medications. Thus, patients who are refractory to one or more oral OAB medications may benefit from earlier treatment with onabotA.
  • Ehrén, Ingrid, et al. (författare)
  • Cognitive challenges in persons with spina bifida : Bearing on urological dysfunctions?
  • 2020
  • Ingår i: Neurourology and Urodynamics. - : John Wiley & Sons. - 0733-2467 .- 1520-6777. ; 39:8, s. 2139-2145
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: To evaluate if adult persons with spina bifida (SB) who have urinary tract complications have cognitive difficulties that can be identified by neuropsychological tests.METHODS: All individuals with SB ≥ 18 years of age registered at a regional outpatient clinic (n = 219) were invited, of which, 154 persons were included. Neuropsychological assessment of their cognitive status was performed with Wechsler Adult Intelligence Scale®-Fourth Edition: Coding, Block design, Arithmetic's, FAS (word generation), Rey Auditory Verbal Test for learning, and delayed recall 30 min. Bladder and bowel function were assessed with questions used by the Nordic Spinal Cord Injury Registry (NSCIR) in structured interviews, by questionnaires, and by chart reviews.RESULTS: Average neuropsychological test results for this SB population was shown to be approximately 1 SD under the median for the general population. The Coding test showed significantly lower test results as compared with the whole SB group in persons with urinary tract complications, especially urinary tract infections, reduced kidney function, dependent emptying of the bladder, and the bowel and accidental bowel leakage. The Arithmetic's test showed a significant difference between subgroups in all parameters except reduced kidney function whereas the other neuropsychological tests were significantly correlated with some but not all urological parameters.CONCLUSION: We propose neuropsychological testing with primarily two tests to find those persons with SB who, due to cognitive challenges, might need extra support to minimize urological complications.
  • Ehrén, Ingrid, et al. (författare)
  • Voiding conditions, renal and bowel function in a cohort of adults with spina bifida
  • 2020
  • Ingår i: Neurourology and Urodynamics. - : Wiley. - 0733-2467 .- 1520-6777. ; 39:6, s. 1796-1802
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: To map voiding patterns, degree of continence, use of drugs for voiding disorders, kidney function and surgical interventions but also the bowel function in a near-total regional cohort of adults with spina bifida aged more than or equal to 18 years.METHODS: All individuals more than or equal to 18 years of age with spina bifida registered at a regional outpatient clinic (n = 219) were invited to participate, of which 196 persons were included. Bladder and bowel function were assessed according to questions used by the Nordic Spinal Cord Injury Registry by structured interviews and questionnaires in combination with review of patient charts including kidney function.RESULTS: Twenty percent of the patients voided spontaneously. Fifty-four percent used clean intermittent catherization (CIC) and of these, 14% had also undergone augmentation of the bladder and/or implantation of an artificial sphincter or sling, 23% had undergone major urological surgery, and 3% had an indwelling catheter. Seventeen percent of patients voiding spontaneously or using CIC reported total continence but as many as 36% reported daily leakage. Anticholinergics was the most common drug, used by 21% in the total cohort. About 13% of the patients had a reduced kidney function but only 1.5% had end stage renal failure. Seventy-three percent had problems emptying the bowel and 18% experienced fecal leakage weekly or even daily.CONCLUSION: We found a large variation in problems with bladder and bowel function in this adult group of persons with spina bifida. A structured customized program for follow-up seems necessary to optimize their health status in these areas.
  • Fraser, Matthew O., et al. (författare)
  • Best practices for cystometric evaluation of lower urinary tract function in muriform rodents
  • 2020
  • Ingår i: Neurourology and Urodynamics. - : John Wiley & Sons Inc.. - 0733-2467 .- 1520-6777. ; 39:6, s. 1868-1884
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Rodent cystometry has provided valuable insights into the impact of the disease, injury, and aging on the cellular and molecular pathways, neurologic processes, and biomechanics of lower urinary tract function. The purpose of this white paper is to highlight the benefits and shortcomings of different experimental methods and strategies and to provide guidance on the proper interpretation of results. Methods: Literature search, selection of articles, and conclusions based on discussions among a panel of workers in the field. Results: A range of cystometric tests and techniques used to explore biological phenomena relevant to the lower urinary tract are described, the advantages and disadvantages of various experimental conditions are discussed, and guidance on the practical aspects of experimental execution and proper interpretation of results are provided. Conclusions: Cystometric evaluation of rodents comprises an extensive collection of functional tests that can be performed under a variety of experimental conditions. Decisions regarding which approaches to choose should be determined by the specific questions to be addressed and implementation of the test should follow standardized procedures.
  • Fry, Christopher Henry, et al. (författare)
  • New targets for overactive bladder—ICI-RS 2109
  • 2020
  • Ingår i: Neurourology and Urodynamics. - : John Wiley & Sons Inc.. - 0733-2467 .- 1520-6777. ; 39:S3, s. 113-121
  • Forskningsöversikt (refereegranskat)abstract
    • Aim: To review evidence for novel drug targets that can manage overactive bladder (OAB) symptoms. Methods: A think tank considered evidence from the literature and their own research experience to propose new drug targets in the urinary bladder to characterize their use to treat OAB. Results: Five classes of agents or cellular pathways were considered. (a) Cyclic nucleotide–dependent (cyclic adenosine monophosphate and cyclic guanosine monophosphate) pathways that modulate adenosine triphosphate release from motor nerves and urothelium. (b) Novel targets for β3 agonists, including the bladder wall vasculature and muscularis mucosa. (c) Several TRP channels (TRPV1, TRPV4, TRPA1, and TRPM4) and their modulators in affecting detrusor overactivity. (d) Small conductance Ca2+-activated K+ channels and their influence on spontaneous contractions. (e) Antifibrosis agents that act to modulate directly or indirectly the TGF-β pathway—the canonical fibrosis pathway. Conclusions: The specificity of action remains a consideration if particular classes of agents can be considered for future development as receptors or pathways that mediate actions of the above mentioned potential agents are distributed among most organ systems. The tasks are to determine more detail of the pathological changes that occur in the OAB and how the specificity of potential drugs may be directed to bladder pathological changes. An important conclusion was that the storage, not the voiding, phase in the micturition cycle should be investigated and potential targets lie in the whole range of tissue in the bladder wall and not just detrusor.
  • Speich, John E., et al. (författare)
  • Are oxidative stress and ischemia significant causes of bladder damage leading to lower urinary tract dysfunction? Report from the ICI-RS 2019
  • 2020
  • Ingår i: Neurourology and Urodynamics. - : John Wiley & Sons Inc.. - 0733-2467 .- 1520-6777. ; 39:S3, s. 16-22
  • Tidskriftsartikel (refereegranskat)abstract
    • Several studies indicate that pelvic ischemia and oxidative stress may play a significant role in lower urinary tract dysfunction (LUTD), including detrusor overactivity (DO)/overactive bladder (OAB) and detrusor underactivity (DU)/underactive bladder (UAB). The present article addresses proposal 1: “Are oxidative stress and ischemia significant causes of bladder damage leading to LUTD?” from the 2019 International Consultation on Incontinence—Research Society (ICI-RS) meeting. Bladder ischemia in animals and humans is briefly described, along with the proposed progression from ischemia to LUTD. Bladder ischemia is compared with ischemia of other organs, and the ongoing development of pelvic ischemia animal models is discussed. In addition, the distribution of blood within the bladder during filling and voiding and the challenges of quantification of blood flow in vivo are described. Furthermore, oxidative stress, including potential biomarkers and treatments, and challenges regarding antioxidant therapy for the treatment of LUTD are discussed. Finally, seven critical research questions and proposed studies to answer those questions were identified as priorities that would lead to major advances in the understanding and treatment of lower urinary tract symptoms (LUTS)/LUTD associated with pelvic ischemia and oxidative stress.
  • Wadensten, Towe, et al. (författare)
  • App-based self-management of urgency and mixed urinary incontinence in women : One-year follow-up
  • 2022
  • Ingår i: Neurourology and Urodynamics. - : John Wiley & Sons. - 0733-2467 .- 1520-6777. ; 41:4, s. 945-954
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: To evaluate the long-term effect of the Tät®II app for treatment of urgency (UUI) and mixed urinary incontinence (MUI).Methods: Long-term follow-up of a randomized controlled trial, including 123 women ≥18 years old with UUI or MUI, without red-flag symptoms, and ≥2 leakages per week. All participants, regardless of group, had received the intervention, a treatment app, at the long-term follow-up. Long-term data were collected through web-based questionnaires 15 months after participants received the intervention. The app included pelvic floor muscle training, bladder training, psychoeducation, lifestyle advice, an exercise log, reminders, reinforcement messages, and tailored advice. The primary outcome was a change in incontinence symptoms (International Consultation on Incontinence Questionnaire [ICIQ]—Urinary Incontinence Short Form [ICIQ-UI SF]), from baseline to follow-up. Other outcomes were urgency symptoms (ICIQ—Overactive Bladder Module (ICIQ-OAB)), quality of life (ICIQ—Lower Urinary Tract Symptoms Quality of Life Module [ICIQ-LUTSqol]), and improvement (Patient's Global Impression of Improvement [PGI-I]).Results: Of the 123 women, 102 (83%) completed the long-term follow-up. The ICIQ-UI SF mean score improved from 11.5 to 7.6 (mean difference 4.0, 95% CI 3.2–4.7). The ICIQ-OAB improved from 6.7 to 5.5 (mean difference 1.3, 95% CI 0.9–1.6) and the ICIQ-LUTSqol improved from 38.0 to 30.9 (mean difference 7.1, 95% CI 5.7–8.5). Of the 102 women, 74 (73%) reported improvement.Conclusions: Self-management with the Tät®II app for UUI and MUI had a significant effect across all outcome measures also long-term and might serve as an alternative first-line treatment for these conditions.
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