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Sič A, Stojanović B, Đorđević M. Neurogenic Bladder in Children with Myelomeningocele. Diseases 2025; 13:117. [PMID: 40277827 PMCID: PMC12025530 DOI: 10.3390/diseases13040117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Revised: 04/11/2025] [Accepted: 04/15/2025] [Indexed: 04/26/2025] Open
Abstract
Myelomeningocele (MMC), a severe congenital anomaly resulting from neural tube closure defects, poses significant urological challenges necessitating specialized care. This review explores the intricate landscape of MMC within urological practice, advocating for a multidisciplinary approach to optimize patient outcomes. By surveying diverse treatment modalities, this review aims to offer insights into enhancing urological management strategies for MMC and guiding future research directions. At the heart of the conversation lies the pathophysiology of neurogenic bladder dysfunction in children with MMC, with a particular focus on the complexities of diagnosis and the various paradigms guiding urological management. Common complications such as recurrent urinary tract infections are examined alongside non-surgical interventions like intermittent catheterization (CIC) and pharmacotherapy, notably oxybutynin. Additionally, surgical options including botulinum toxin injection and reconstructive procedures are explored to enhance urological outcomes for affected children. By unpacking the complexities of neurogenic bladder dysfunction in MMC, this review emphasizes the imperative of a collaborative, multidisciplinary approach in urological care, ultimately aiming to enhance patient well-being and functional outcomes.
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Affiliation(s)
- Aleksandar Sič
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (B.S.); (M.Đ.)
| | - Borko Stojanović
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (B.S.); (M.Đ.)
- Department of Urology, University Children’s Hospital, 11000 Belgrade, Serbia
| | - Miroslav Đorđević
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (B.S.); (M.Đ.)
- Department of Urology, University Children’s Hospital, 11000 Belgrade, Serbia
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
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Unal B, Pisirici P, Koseoglu Kurt A, Tugtepe H. Comparison of the efficiency of transcutaneous electrical nerve stimulation and manual therapy in children with cerebral palsy with lower urinary system dysfunction- a randomized prospective trial. J Pediatr Urol 2025; 21:260-267. [PMID: 38641452 DOI: 10.1016/j.jpurol.2024.03.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Revised: 03/21/2024] [Accepted: 03/22/2024] [Indexed: 04/21/2024]
Abstract
INTRODUCTION Neurological defects in children with cerebral palsy (CP) not only affect their motor skills but also lead to bladder and bowel problems. Although most children with CP have achieved urinary control, more than 50% of cases experience lower urinary tract symptoms (LUTS). Common LUTS complaints observed in CP include delayed toilet training, urinary incontinence, increased frequency of urination, urgency, urinary hesitancy, and recurrent urinary tract infections. OBJECTIVE This study aimed to prospectively evaluate and compare the effectiveness of two different physiotherapy approaches, sacral Transcutaneous Electrical Nerve Stimulation (TENS) and massage, on lower urinary tract dysfunction in children with CP. METHOD A total of 54 children with CP who had the Dysfunctional Voiding Scoring System (DVISS) of 8.5 or higher were included in the study. Children were randomized to the TENS (TG; n = 27) and Manual Therapy (MG; n = 27) groups. TENS application was performed 2 sessions in a week for 20 min for a total of 12 weeks. The electrodes used during the application were adhered bilaterally to the parasacral region (S2-S4). 4 electrodes of 5 × 5 cm were used. Classical bowel massage was applied to the MG with the friction massage technique twice a week for 12 weeks. Manual therapy applications were performed in the form of abdominal, colon, and friction massage, twice a week for 20 min by the physiotherapist. Massage was applied to the abdominal region between the lower subcostal border and the anterior superior iliac spine. Questionnaires were applied before and after treatment interventions: DVISS, functional bladder capacity (FBC), frequency of voiding, and urinary incontinence episodes evaluated by bladder diary, Bristol Gaita Scale, and Pediatric Incontinence Quality of Life Scale (PIN-Q) used. RESULTS The decrease in the episodes of incontinence was higher in the TG (p = 0.037; p < 0.05). FBC increased after treatment in both groups, but there was no statistically significant difference between the groups (p = 0.683; p > 0.05). Manual therapy was more effective in improving constipation symptoms. In both groups, DVISS and PIN-Q values decreased after treatment, but the decrease in TG was statistically significant in the evaluation made between groups (p = 0.001; p < 0.01). CONCLUSION Both parasacral TENS and massage provided a significant improvement in LUTS, constipation, and quality of life but TENS showed a bigger improvement. We suggest adding these interventions to the treatment of bladder and bowel problems in CP children.
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Affiliation(s)
- Betul Unal
- Bahçeşehir University, Graduate Education Institute, Physiotherapy and Rehabilitation Doctoral Program, Istanbul, Turkiye
| | - Pelin Pisirici
- Bahçeşehir University, Faculty of Health Sciences, Department of Physiotherapy and Rehabilitation, Istanbul, Turkiye.
| | - Aygul Koseoglu Kurt
- Bahçeşehir University, Graduate Education Institute, Physiotherapy and Rehabilitation Doctoral Program, Istanbul, Turkiye
| | - Halil Tugtepe
- Private Tugtepe Pediatric Urology Center, Division of Bladder and Bowel Dysfunction, Istanbul, Turkiye
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Izumi N, Kitta T, Mitsui T. Importance of Regular Examination and Follow-up in Pediatric Patients with Neurogenic Bladder: 24-Month Follow-up Study Using a Japanese Health Insurance Database. Adv Ther 2023; 40:5519-5535. [PMID: 37843724 PMCID: PMC10611833 DOI: 10.1007/s12325-023-02692-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 09/19/2023] [Indexed: 10/17/2023]
Abstract
INTRODUCTION Data on the long-term management of neurogenic bladder (NGB) are scarce. We evaluated the current status of NGB management in Japanese children over 24-month follow-up using the JMDC database. METHODS In this descriptive, observational, retrospective cohort study, patients (≤ 17 years) with NGB were included. Patient characteristics and their management status were investigated. A multivariate analysis evaluating the potential risk factors for the development of urinary tract infection (UTI) was performed. The diagnosis of spina bifida, demographics, baseline comorbidities, and early use of clean intermittent catheterization (CIC) and/or overactive bladder (OAB) drugs were used as independent variables. RESULTS Of 883 eligible children, 39.3% had spina bifida. Over 12/24-month post-index periods, renal urinary tract ultrasound and urinalysis were performed at least once in > 35%/> 45% patients, respectively, while specific tests (urodynamics, cystourethrography, scintigraphy) were performed in substantially fewer (< 11%/< 13%) patients. Over 24 months, 21.5% patients used OAB medications (mostly anticholinergics) and 10.8% underwent CIC, alone or with medications; 1.2% patients underwent surgery. Lower UTI (23.3%), urinary incontinence (9.7%), and hydronephrosis (7.0%) were the most common incident complications. Multivariate analysis evaluating risk factors for UTI showed significantly higher odds ratios with point estimates of ≥ 2 for CIC (5.70), presence of spina bifida (2.86), and constipation (2.07). Overall, urodynamic assessments were inadequately performed. CONCLUSION Patients with use of CIC and/or having spina bifida and constipation had a higher risk of UTI, suggesting the need for careful follow-up. More guideline-compliant and diligent patient management is necessary in Japanese children with NGB.
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Affiliation(s)
- Naoko Izumi
- Internal Medicine and Hospital Medical Affairs, Pfizer Japan, Inc., 3-22-7 Yoyogi, Shibuya-ku, Tokyo, 151-8589, Japan.
| | - Takeya Kitta
- Department of Renal and Urologic Surgery, Asahikawa Medical University, Asahikawa, 078-8510, Japan
| | - Takahiko Mitsui
- Department of Urology, University of Yamanashi Graduate School of Medical Sciences, Chuo, 409-3898, Japan
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Sano Y, Shoji S, Shahin M, Sweeney K, Darekar A, Malhotra BK. Population Pharmacokinetic and Pharmacodynamic Modeling of Fesoterodine in Pediatric Patients with Neurogenic Detrusor Overactivity. Eur J Drug Metab Pharmacokinet 2023; 48:257-269. [PMID: 36892754 PMCID: PMC10175358 DOI: 10.1007/s13318-023-00818-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/06/2023] [Indexed: 03/10/2023]
Abstract
BACKGROUND AND OBJECTIVE Fesoterodine is a muscarinic receptor antagonist approved for the treatment of overactive bladder (OAB) in adults and neurogenic detrusor overactivity (NDO) in pediatric patients. This work aimed to characterize the population pharmacokinetics of 5-hydroxymethyl tolterodine (5-HMT, the active metabolite of fesoterodine) and its pharmacokinetic/pharmacodynamic relationship in pediatric patients with OAB or NDO following administration of fesoterodine. METHODS 5-HMT plasma concentrations from 142 participants of age ≥ 6 years were analyzed, and a nonlinear mixed-effects model was developed. Weight-based simulations of 5-HMT exposure and maximum cystometric capacity (MCC) were conducted using the final models. RESULTS A one-compartment model with first-order absorption and a lag time, which included the effects of body weight, sex, cytochrome (CYP) 2D6 metabolizer status and fesoterodine formulation on pharmacokinetic parameters, best described the 5-HMT pharmacokinetics. An Emax model described the exposure-response relationship adequately. The median maximum concentration at steady state for pediatric patients weighing 25-35 kg and receiving 8 mg once daily (QD) was estimated to be 2.45 times greater than that in adults receiving 8 mg QD. Furthermore, simulation results showed dosing with fesoterodine 4 mg QD to pediatric patients weighing 25-35 kg and 8 mg QD to pediatric patients weighing >35 kg would achieve adequate exposure to demonstrate a clinically meaningful change from baseline (CFB) MCC. CONCLUSIONS Population models were developed for 5-HMT and MCC in pediatric patients. Weight-based simulations indicated that 4 mg QD for pediatric patients weighing 25-35 kg and 8 mg QD for those weighing > 35 kg provided similar exposures to those in adults following 8 mg QD and a clinically meaningful CFB MCC. CLINICAL TRIAL NUMBERS NCT00857896, NCT01557244.
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Xiang L, Li H, Xie QQ, Siau CS, Xie Z, Zhu MT, Zhou B, Li ZP, Wang SB. Rehabilitation care of patients with neurogenic bladder after spinal cord injury: A literature review. World J Clin Cases 2023; 11:57-64. [PMID: 36687186 PMCID: PMC9846973 DOI: 10.12998/wjcc.v11.i1.57] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 11/15/2022] [Accepted: 12/15/2022] [Indexed: 01/04/2023] Open
Abstract
This article reviews the research progress of rehabilitation treatment and nursing care of patients with neurogenic bladder after spinal cord injury, in order to provide reference for the rehabilitation treatment and nursing care of patients. We reviewed recent medical literature on patients with neurogenic bladder, focusing on neurogenic bladder caused by spinal cord injury. We analyzed 30 recent of publications in patients with neurogenic bladder after spinal cord injury, in addition to reviewing and evaluating the commonly used rehabilitation nursing methods for neurogenic bladder. Psychological counseling is a vital aspect which cannot be neglected in the process of neurogenic bladder rehabilitation. Hitherto, the commonly used drug and surgical treatments may have negatively impacted the mental health of patients in varying degrees. However, in clinical practice, applying intermittent catheterization in patients who have neurogenic bladder with spinal cord injury may help improve patients' life quality, mitigate psychological burden, and reduce negative emotions.
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Affiliation(s)
- Lei Xiang
- Centre for Community Health Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia
- Department of Rehabilitation Medicine, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Han Li
- School of Medicine, Taizhou University, Taizhou 318000, Zhejiang Province, China
| | - Qi-Qi Xie
- School of Medicine, Taizhou University, Taizhou 318000, Zhejiang Province, China
| | - Ching Sin Siau
- Centre for Community Health Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia
| | - Zhi Xie
- College of Biology & Pharmacy, Three Gorges University, Yichang 443002, Hubei Province, China
| | - Meng-Ting Zhu
- School of Medicine, Taizhou University, Taizhou 318000, Zhejiang Province, China
| | - Bo Zhou
- School of Medicine, Taizhou University, Taizhou 318000, Zhejiang Province, China
| | - Zhi-Peng Li
- School of Medicine, Taizhou University, Taizhou 318000, Zhejiang Province, China
| | - Shuai-Bin Wang
- Department of Urology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang Province, China
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Kutzenberger J, Angermund A, Domurath B, Möhr S, Pretzer J, Soljanik I, Kirschner-Hermanns R. [Short version of the S2k guideline on drug therapy of neurogenic lower urinary tract dysfunction (NLUTD)]. UROLOGIE (HEIDELBERG, GERMANY) 2023; 62:41-52. [PMID: 36271186 DOI: 10.1007/s00120-022-01950-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 09/12/2022] [Indexed: 11/07/2022]
Abstract
BACKGROUND In Germany about one million patients suffer from neurogenic lower urinary tract dysfunction (NLUTD). If left untreated, various forms of NLUTD can lead to secondary damage of the lower and upper urinary tract. Thus, the guideline was developed for the drug therapy of patients with NLUTD, who frequently require lifelong care and aftercare. METHODS The guideline was developed in a consensus process with several meetings and online reviews, and final recommendations were decided on in online consensus meetings. Ballots were sent to elected officials of the contributing professional societies. Level of consensus was given for each coordinated recommendation ( https://www.awmf.org/leitlinien/detail/ll/043-053.html ). RESULTS/MOST IMPORTANT RECOMMENDATIONS: (Video)urodynamic classification of the NLUTD should be conducted before the use of antimuscarinic drugs (84.2%). Approved oral antimuscarinics should be used as first choice. Contraindications must be respected (100%). If oral treatment is ineffective or in the case of adverse drug reaction (ADRs) alternatively instillation of oxybutynin solution intravesically (83%) or onabotulinumneurotoxine (OBoNT) injection should be offered (89.5%). In case of failure or ADRs of antimuscarinics, β3 sympathomimetic mirabegron can be used to treat neurogenic detrusor overactivity (NDO) (off-label use) (100%). In case of paraplegia below C8 or multiple sclerosis with an expanded disability status scale (EDSS) of ≤ 6.5, OBoNT injection can be offered as an alternative (89.5%). Drug therapy for NDO should be started early in newborns/young children (84.2%). Conservative, nondrug therapy should be considered in frail elderly (94.7%). No parasympathomimetic therapy should be used to treat neurogenic detrusor underactivity (94.7%). CONCLUSION Precise knowledge of the neurological underlying disease/sequence of trauma and the exact classification of the NLUTD are required for development of individualized therapy.
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Affiliation(s)
- J Kutzenberger
- Departement Neuro-Urologie, Kliniken Hartenstein - UKR, Bad Wildungen, Deutschland.
- , Fontanestr. 16, 34596, Bad Zwesten, Deutschland.
| | - A Angermund
- Neuro-Urologie, Schön Klinik Vogtareuth, Vogtareuth, Deutschland
| | - B Domurath
- Zentrum für Neuro-Urologie, Kliniken Beelitz, Beelitz-Heilstätten, Deutschland
| | - S Möhr
- Neuro-Urologie, REHAB Basel, Klinik für Neurorehabilitation und Paraplegiologie, Basel, Schweiz
| | - J Pretzer
- Klinik für Urologie und Neuro-Urologie, Unfallkrankenhaus Berlin, Berlin, Deutschland
| | - I Soljanik
- Klinik für Paraplegiologie, Department für Orthopädie, Unfallchirurgie und Paraplegiologie, Universität Heidelberg, Heidelberg, Deutschland
| | - R Kirschner-Hermanns
- Universitätsklinikum Bonn, Sektion Neuro-Urologie/, Klinik für Urologie und Kinderurologie und Neuro-Urologie, Johanniter Neurologisches Rehabilitationszentrum Godeshöhe e. V., Bonn, Deutschland
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Kitta T, Darekar A, Malhotra B, Shahin MH, Jones P, Lindsay M, Mallen S, Nieto A, Crook TJ. Fesoterodine treatment of pediatric patients with neurogenic detrusor overactivity: A 24-week, randomized, open-label, phase 3 study. J Pediatr Urol 2022; 19:175.e1-175.e10. [PMID: 36504158 DOI: 10.1016/j.jpurol.2022.11.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 11/11/2022] [Accepted: 11/20/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND Neurogenic detrusor overactivity (NDO) can damage the upper urinary tract leading to chronic renal impairment. Antimuscarinic therapy is used to improve urinary incontinence and protect the upper urinary tract in patients with NDO. OBJECTIVE This study investigated safety and efficacy of fesoterodine, a muscarinic receptor antagonist, in 6‒<18-year-old patients with NDO (NCT01557244). STUDY DESIGN This open-label phase 3 study included 2 pediatric cohorts. Patients in Cohort 1 (bodyweight >25 kg) were randomized to fesoterodine 4 or 8 mg extended-release tablets or oxybutynin XL tablets administered over the 12-week active comparator-controlled phase. The safety extension phase evaluated fesoterodine 4 and 8 mg for a further 12 weeks, with patients in the oxybutynin arm allocated to fesoterodine 4 or 8 mg. Patients in Cohort 2 (bodyweight ≤25 kg) were randomized to fesoterodine 2 or 4 mg extended-release beads-in-capsule (BIC) administered over a 12-week efficacy phase and 12-week safety extension phase. Patients with stable neurologic disease and clinically or urodynamically proven NDO were included. The primary endpoint was change from baseline to Week 12 in maximum cystometric bladder capacity (MCC). Secondary efficacy endpoints included detrusor pressure at maximum bladder capacity, bladder volume at first involuntary detrusor contraction, bladder compliance, and incontinence episodes. Safety endpoints included adverse event incidence, and specific assessments of cognition, behavior and vision. The pharmacokinetics of 5-hydroxymethyl tolterodine (5-HMT; fesoterodine's active metabolite) was determined using population-pharmacokinetic analysis. RESULTS In Cohort 1 (n = 124), fesoterodine 4 and 8 mg treatment resulted in significant increases from baseline in the primary endpoint of MCC at Week 12. In Cohort 2 (n = 57), fesoterodine 2 and 4 mg BIC treatment resulted in improvements in MCC from baseline. Fesoterodine 4 and 8 mg and fesoterodine 4 mg BIC led to improvements in some secondary efficacy endpoints. The most common treatment-related adverse reactions were gastrointestinal effects, such as dry mouth, which occurred more frequently with oxybutynin than fesoterodine. No detrimental effects on visual accommodation or acuity, or on cognitive function or behavior were observed. DISCUSSION These safety and efficacy results are consistent with limited published data on fesoterodine treatment in pediatric populations with overactive bladder or NDO. Study limitations include the lack of placebo control and the small sample size, which limits the ability to make formal efficacy comparisons and detect rare adverse reactions. CONCLUSION Fesoterodine has a favorable benefit-risk profile in 6‒<18-year-old patients with NDO and may represent an additional option for pediatric NDO treatment.
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Affiliation(s)
- Takeya Kitta
- Department of Renal and Urologic Surgery, Asahikawa Medical University Hospital, Asahikawa, Japan.
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Abstract
Mirabegron (MYRBETRIQ®), a beta-3 adrenergic agonist developed by Astellas Pharma Inc., is well established as a treatment for overactive bladder in adults and is available as extended-release (ER) tablets administered once daily. More recently, mirabegron has been investigated in pediatric patients with neurogenic detrusor overactivity (NDO) and received its first approval in this indication in pediatric patients aged ≥ 3 years on 25 March 2021 in the USA. In addition to mirabegron ER tablets (which can be used in pediatric patients weighing ≥ 35 kg), mirabegron is available as an ER oral suspension (MYRBETRIQ® Granules) for pediatric patients; in those weighing < 35 kg, only the ER oral suspension formulation should be used. The ER tablet and ER oral suspension formulations are not substitutable on a mg-by-mg basis. This article summarizes the milestones in the development of mirabegron for NDO leading to this pediatric first approval.
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Affiliation(s)
- Susan J Keam
- Springer Nature, Mairangi Bay, Private Bag 65901, Auckland, 0754, New Zealand.
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Baka-Ostrowska M, Bolong DT, Persu C, Tøndel C, Steup A, Lademacher C, Martin N. Efficacy and safety of mirabegron in children and adolescents with neurogenic detrusor overactivity: An open-label, phase 3, dose-titration study. Neurourol Urodyn 2021; 40:1490-1499. [PMID: 34058027 PMCID: PMC8361978 DOI: 10.1002/nau.24657] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 03/04/2021] [Accepted: 03/05/2021] [Indexed: 12/13/2022]
Abstract
Aims To evaluate the efficacy and safety of mirabegron in children and adolescents (aged 3 to <18 years) with neurogenic detrusor overactivity (NDO) using clean intermittent catheterization. Methods In this open‐label, multicenter, baseline‐controlled, Phase III study (NCT02751931), participants received once‐daily mirabegron at an adult dose equivalent of 25 mg. Dose was increased to 50 mg equivalent unless there were safety/tolerability concerns. The primary efficacy endpoint was change from baseline to Week 24 in maximum cystometric capacity (MCC). Secondary urodynamic assessments, Pediatric Incontinence Questionnaire (PIN‐Q), Patient Global Impression of Severity (PGI‐S), Clinician Global Impression of Change (CGI‐C), and Acceptability questionnaires were included. Results Overall, 86 participants (55 aged 3 to <12 years, 31 aged 12 to <18 years) received treatment; 68 were included in efficacy assessments. A statistically significant increase in MCC from baseline to Week 24 was observed (87.20 ml, 95% confidence interval: 66.07, 108.33; p < .001); this increase was apparent from Week 4. Significant increases in bladder compliance, bladder volume until first detrusor contraction, average volume per catheterization, maximum daytime catheterized volume and number of dry days per week. Significant decreases in detrusor pressure and number of leakage episodes per day were also observed. Significant improvement in PGI‐S but not PIN‐Q was observed. Most participants reported their condition had either much or very much improved using the CGI‐C. Mirabegron was well tolerated in this population with a profile aligned with that in adults. Conclusions Mirabegron was effective and well‐tolerated in the treatment of pediatric patients with NDO.
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Affiliation(s)
| | - David T Bolong
- Section of Pediatric Urology, Philippine Children's Medical Centre, Manila, Philippines
| | - Cristian Persu
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Camilla Tøndel
- Department of Pediatrics, Haukeland University Hospital, Bergen, Norway
| | - Achim Steup
- Astellas Pharma US, Inc., Northbrook, Illinois, USA
| | | | - Nancy Martin
- Astellas Pharma US, Inc., Northbrook, Illinois, USA
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Moussa M, Papatsoris AG, Chakra MA, Fares Y, Dabboucy B, Dellis A. Perspectives on urological care in spina bifida patients. Intractable Rare Dis Res 2021; 10:1-10. [PMID: 33614369 PMCID: PMC7882087 DOI: 10.5582/irdr.2020.03077] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 10/04/2020] [Accepted: 12/12/2020] [Indexed: 02/05/2023] Open
Abstract
Spina bifida (SB) is a neurogenetic disorder with a complex etiology that involves genetic and environmental factors. SB can occur in two major forms of open SB or SB aperta and closed SB or SB occulta. Myelomeningocele (MMC), the most common neural tube defects (NTDs), occurs in approximately 1 in 1,000 births. Considering non-genetic factors, diminished folate status is the best-known factor influencing NTD risk. The methylenetetrahydrofolate reductase (MTHFR) gene has been implicated as a risk factor for NTDs. The primary disorder in the pathogenesis of MMC is failed neural tube closure in the embryonic spinal region. The clinical manifestation of SB depends on clinical type and severity. SB can be detected in the second trimester using ultrasound which will reveal specific cranial signs. The management of MMC traditionally involves surgery within 48 h of birth. Prenatal repair of MMC is recommended for fetuses who meet maternal and fetal Management of Myelomeningocele Study (MOMS) specified criteria. Urological manifestations of SB include urinary incontinence, urolithiasis, sexual dysfunction, renal dysfunction, and urinary tract infection. Renal failure is among the most severe complications of SB. The most important role of the urologist is the management of neurogenic bladder. Medical management with clean intermittent catheterization and anticholinergic treatment is generally considered the gold standard of therapy. However, when this therapy fails surgical reconstruction become the only remaining option. This review will summarize the pathogenesis, risk factors, genetic contribution, diagnostic test, and management of SB. Lastly, the urologic outcomes and therapies are reviewed.
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Affiliation(s)
- Mohamad Moussa
- Urology Department, Zahraa Hospital, University Medical Center, Lebanese University, Beirut, Lebanon
| | - Athanasios G. Papatsoris
- 2nd Department of Urology, School of Medicine, Sismanoglio Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Mohamad Abou Chakra
- Department of Urology, Faculty of Medicine, Lebanese University, Beirut, Lebanon
| | - Youssef Fares
- Department of Neurosurgery, Neuroscience Research Center, Faculty of Medical Sciences, Lebanese University, Beirut, Lebanon
| | - Baraa Dabboucy
- Department of Neurosurgery, Faculty of Medicine, Lebanese University, Beirut, Lebanon
| | - Athanasios Dellis
- Department of Urology/General Surgery, Areteion Hospital, Athens, Greece
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Ma L, Tang JY, Zhou JY, Zhu C, Zhang X, Zhou P, Yu Q, Wang Y, Gu XJ. Fluoxetine, a selective serotonin reuptake inhibitor used clinically, improves bladder function in a mouse model of moderate spinal cord injury. Neural Regen Res 2021; 16:2093-2098. [PMID: 33642399 PMCID: PMC8343320 DOI: 10.4103/1673-5374.308667] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
After spinal cord injury, the upward conduction of the spinal cord is lost, resulting in the loss of micturition control, which manifests as detrusor sphincter dyssynergia and insufficient micturition. Studies have shown that serotonergic axons play important roles in the control of the descending urination tract. In this study, mouse models of moderate spinal cord contusions were established. The serotonin agonists quipazine (0.2 mg/kg), 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DAPT, 0.1 mg/kg), buspirone (1 mg/kg), sumatriptan (1 mg/kg), and rizatriptan (50 mg/kg), the serotonin reuptake inhibitors fluoxetine (20 mg/kg) and duloxetine (1 mg/kg), and the dopamine receptor agonist SKF-82197 (0.1 mg/kg) were intraperitoneally administered to the model mice 35 days post-injury in an acute manner. The voided stain on paper method and urodynamics revealed that fluoxetine reduced the amount of residual urine in the bladder and decreased bladder and external urethral sphincter pressure in a mouse model of moderate spinal cord injury. However, fluoxetine did not improve the micturition function in a mouse model of severe spinal cord injury. In contrast, the other serotonergic drugs had no effects on the micturition functions of spinal cord injury model mice. This study was ethically approved by the Institutional Animal Care and Use Committee of Jiangsu Province Hospital of Chinese Medicine (approval No. 2020DW-20-02) on September 11, 2020.
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Affiliation(s)
- Long Ma
- Department of Urology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Jing-Yuan Tang
- Department of Urology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Jin-Yong Zhou
- Department of Central Laboratory, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Chen Zhu
- Department of Urology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Xin Zhang
- Department of Urology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Ping Zhou
- Department of Urology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Qiu Yu
- Department of Urology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Yan Wang
- Department of Urology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Xiao-Jian Gu
- Department of Urology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
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Mostafaei H, Shariat SF, Salehi-Pourmehr H, Janisch F, Mori K, Quhal F, Hajebrahimi S. The clinical pharmacology of the medical treatment for overactive bladder in adults. Expert Rev Clin Pharmacol 2020; 13:707-720. [PMID: 32500759 DOI: 10.1080/17512433.2020.1779056] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Abstract
INTRODUCTION Overactive bladder is a prevalent symptom complex that affects the patient's quality of life. Any disruption between the neuronal micturition pathway can lead to bladder overactivity. Neurogenic causes, myogenic causes, aging, bladder outlet obstruction, sex, and psychological factors are some of the factors contributing to bladder overactivity. The complaint of any symptoms of OAB, which is highly prevalent and affects overall QOL, often needs therapeutic interventions. When conservative therapy methods fail, the addition of medications is recommended. The most commonly used agents for the treatment of OAB are antimuscarinic drugs. New classes of drugs, such as beta-3 agonists, have enriched our pharmacologic armamentarium. AREAS COVERED In this review, with a special focus on oral pharmacological treatments, we discussed the definition, etiology, symptoms, diagnosis, and management of OAB. EXPERT OPINION OAB is a multifactorial condition with every patient presenting with a different collection of symptoms and signs. Medical therapies should be given in conjunction with behavioral therapies. Using high or low doses, flexible doses, and stopping or changing the medications are interchangeable strategies based on the level of treatment efficacy and patient satisfaction.
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Affiliation(s)
- Hadi Mostafaei
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna , Vienna, Austria.,Research Center for Evidence Based Medicine, Tabriz University of Medical Sciences , Tabriz, Iran
| | - Shahrokh F Shariat
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna , Vienna, Austria.,Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University , Moscow, Russia.,Department of Urology, University of Texas Southwestern Medical Center , Dallas, TX, USA.,Department of Urology, Second Faculty of Medicine, Charles University , Prague, Czech Republic.,Department of Urology, Weill Cornell Medical College , New York, NY, USA.,Karl Landsteiner Institute of Urology and Andrology , Vienna, Austria.,Department of Urology, University of Jordan , Amman, Jordan
| | - Hanieh Salehi-Pourmehr
- Research Center for Evidence Based Medicine, Tabriz University of Medical Sciences , Tabriz, Iran.,Student Research Committee, Tabriz University of Medical Sciences , Tabriz, Iran
| | - Florian Janisch
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna , Vienna, Austria.,Department of Urology, Medical University of Hamburg , Hamburg, Germany
| | - Keiichiro Mori
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna , Vienna, Austria.,Department of Urology, The Jikei University School of Medicine , Tokyo, Japan
| | - Fahad Quhal
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna , Vienna, Austria.,King Fahad Specialist Hospital-Dammam , Saudi Arabia
| | - Sakineh Hajebrahimi
- Research Center for Evidence Based Medicine, Tabriz University of Medical Sciences , Tabriz, Iran
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13
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Ferrafiat V, Soleimani M, Chaumette B, Martinez A, Guilé JM, Keeshin B, Gerardin P. Use of Prazosin for Pediatric Post-Traumatic Stress Disorder With Nightmares and/or Sleep Disorder: Case Series of 18 Patients Prospectively Assessed. Front Psychiatry 2020; 11:724. [PMID: 32774309 PMCID: PMC7388897 DOI: 10.3389/fpsyt.2020.00724] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Accepted: 07/09/2020] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVES Few studies have investigated pharmacologic treatment for pediatric post-traumatic stress disorder (PTSD). Prazosin, an alpha-1 adrenergic receptor antagonist, has been studied and demonstrated to be efficacious in an adult population for PTSD related sleep disturbances; however, in the pediatric population, data is limited to case reports and retrospective case series. This study prospectively assessed the safety and effects of Prazosin on PTSD symptoms in a pediatric sample. METHODS Since 2016, 18 patients with PSTD under the age of 15 admitted in a child and adolescent psychiatric unit were challenged with prazosin as part of a treatment protocol. PTSD symptoms and adverse effects were collected weekly and prospectively assessed each month with validated clinical scales. All data were retrospectively analyzed. This treatment protocol and the evaluation of clinical data were approved by our Ethical committee for research on preexisting data at the University Teaching Hospital of Rouen. RESULTS Among the 18 patients (10 girls and 8 boys), 13 (72%) had experienced sexual abuse and 5 (28%) family violence. After 1 month of treatment with a mean prazosin dose of 2.16 ( ± 0.6) mg/day, the CGI-S score significantly decreased from 5.3 ( ± 0.9) to 2.9 ( ± 0.7) (improvement of 43%). The mean total UCLA-PTSD-RI score significantly decreased 11.4 points ( ± 5.4) during the first week and 37.9 ( ± 16) during the first month, leading to an improvement of 20% and 67%, respectively. The improvement was significant irrespective of trauma exposure or sex. No adverse effects were reported except for one patient (hypotension). CONCLUSION Consistent with prior case reports and retrospective reviews, our retrospective analysis of data prospectively and systematically assessed among 18 patients suggests that prazosin is well-tolerated and associated with improvement in symptoms for pediatric PTSD.
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Affiliation(s)
- Vladimir Ferrafiat
- Child and Adolescent Psychiatric Unit, URHEA, CHSR Sotteville les Rouen, Rouen, France.,Child and Adolescent Psychiatric Department, CHU Charles Nicolle, Rouen, France
| | - Maryam Soleimani
- Child and Adolescent Psychiatric Unit, URHEA, CHSR Sotteville les Rouen, Rouen, France.,Child and Adolescent Psychiatric Department, CHU Charles Nicolle, Rouen, France
| | - Boris Chaumette
- Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada
| | - Audrey Martinez
- Child and Adolescent Psychiatric Department, CHU Charles Nicolle, Rouen, France
| | - Jean-Marc Guilé
- Child and Adolescent Psychiatry Services, Amiens University Hospital, Picardie Jules Verne University, Amiens, France.,Department of Psychiatry, McGill University, Montreal, QC, Canada.,INSERM U1105 Research Group for Analysis of the Multimodal Cerebral Function, University of Picardie-Jules Verne (UPJV), Amiens, France
| | - Brooks Keeshin
- Department of Pediatrics, University of Utah, Salt Lake City, UT, United States
| | - Priscille Gerardin
- Child and Adolescent Psychiatric Unit, URHEA, CHSR Sotteville les Rouen, Rouen, France.,Child and Adolescent Psychiatric Department, CHU Charles Nicolle, Rouen, France
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Ladi-Seyedian SS, Sharifi-Rad L, Nabavizadeh B, Kajbafzadeh AM. Traditional Biofeedback vs. Pelvic Floor Physical Therapy-Is One Clearly Superior? Curr Urol Rep 2019; 20:38. [PMID: 31147796 DOI: 10.1007/s11934-019-0901-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
PURPOSE OF REVIEW Pelvic floor physical therapy is a worldwide accepted therapy that has been exclusively used to manage many pelvic floor disorders in adults and children. The aim of this review is to suggest to clinicians an updated understanding of this therapeutic approach in management of children with non-neuropathic voiding dysfunction. RECENT FINDINGS Today, pelvic floor muscle training through biofeedback is widely used as a part of a voiding retraining program aiming to help children with voiding dysfunction which is caused by pelvic floor overactivity. Biofeedback on its own, without a pelvic floor training component, is not an effective treatment. Biofeedback is an adjunct to the pelvic floor training. In the current review, we develop the role of pelvic floor physical therapy in management of children with non-neuropathic voiding dysfunction and compare it with biofeedback therapy alone.
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Affiliation(s)
- Seyedeh-Sanam Ladi-Seyedian
- Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, No. 62, Dr. Qarib St, Keshavarz Blvd, Tehran, 14194 33151, Iran
| | - Lida Sharifi-Rad
- Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, No. 62, Dr. Qarib St, Keshavarz Blvd, Tehran, 14194 33151, Iran.,Department of Physical Therapy, Children's Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran
| | - Behnam Nabavizadeh
- Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, No. 62, Dr. Qarib St, Keshavarz Blvd, Tehran, 14194 33151, Iran
| | - Abdol-Mohammad Kajbafzadeh
- Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, No. 62, Dr. Qarib St, Keshavarz Blvd, Tehran, 14194 33151, Iran.
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Lucas E. Medical Management of Neurogenic Bladder for Children and Adults: A Review. Top Spinal Cord Inj Rehabil 2019; 25:195-204. [PMID: 31548786 PMCID: PMC6743750 DOI: 10.1310/sci2503-195] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Neurogenic bladder is a chronic condition affecting patients of all ages with significant medical and quality of life implications. Goals of treatment consist of protection of the upper urinary tract and promotion of reliable urinary continence. Successful management involves medications and most often bladder drainage via clean intermittent catheterization. This article reviews current literature on medical management to achieve goals of treatment.
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Bioengineering Approaches for Bladder Regeneration. Int J Mol Sci 2018; 19:ijms19061796. [PMID: 29914213 PMCID: PMC6032229 DOI: 10.3390/ijms19061796] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Revised: 06/06/2018] [Accepted: 06/10/2018] [Indexed: 12/25/2022] Open
Abstract
Current clinical strategies for bladder reconstruction or substitution are associated to serious problems. Therefore, new alternative approaches are becoming more and more necessary. The purpose of this work is to review the state of the art of the current bioengineering advances and obstacles reported in bladder regeneration. Tissue bladder engineering requires an ideal engineered bladder scaffold composed of a biocompatible material suitable to sustain the mechanical forces necessary for bladder filling and emptying. In addition, an engineered bladder needs to reconstruct a compliant muscular wall and a highly specialized urothelium, well-orchestrated under control of autonomic and sensory innervations. Bioreactors play a very important role allowing cell growth and specialization into a tissue-engineered vascular construct within a physiological environment. Bioprinting technology is rapidly progressing, achieving the generation of custom-made structural supports using an increasing number of different polymers as ink with a high capacity of reproducibility. Although many promising results have been achieved, few of them have been tested with clinical success. This lack of satisfactory applications is a good reason to discourage researchers in this field and explains, somehow, the limited high-impact scientific production in this area during the last decade, emphasizing that still much more progress is required before bioengineered bladders become a commonplace in the clinical setting.
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Ladi-Seyedian SS, Nabavizadeh B, Sharifi-Rad L, Kajbafzadeh AM. Pharmacological treatments available for the management of underactive bladder in neurological conditions. Expert Rev Clin Pharmacol 2017; 11:193-204. [DOI: 10.1080/17512433.2018.1411801] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- Seyedeh-Sanam Ladi-Seyedian
- Pediatric Urology and Regenerative Medicine Research Center, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Behnam Nabavizadeh
- Pediatric Urology and Regenerative Medicine Research Center, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Lida Sharifi-Rad
- Pediatric Urology and Regenerative Medicine Research Center, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- Department of Physical Therapy, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Abdol-Mohammad Kajbafzadeh
- Pediatric Urology and Regenerative Medicine Research Center, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
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