The use of botulinum toxin type A in the treatment of HTLV-1-associated overactive bladder refractory to conventional therapy

Urinary symptoms occur in 19% of human T-cell lymphotropic virus type 1 (HTLV-1)-infected patients who do not fulfill criteria for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and in almost 100% of HAM/TSP patients. Few studies have evaluated therapies for overactive bladder (OAB) caused by HTLV-1 infection. This case report describes the effect of onabotulinum toxin A on the urinary manifestations of three patients with HAM/TSP and OAB symptoms. The patients were intravesically administered 200 units of Botox®. Their incontinence episodes improved, and their OAB symptoms scores (OABSS) reduced significantly. These data indicate that Botox® should be a treatment option for OAB associated with HTLV-1 infection.

Evaluation and treatment of the overactive bladder

The overactive bladder is characterized by symptoms of frequency, urgency, and urge incontinence, substantially affecting the quality of life of millions of people throughout the world. The symptoms are associated with significant social, psychological, occupational, domestic, physical, and sexual problems. Despite the considerable impact of this condition on quality of life, sufferers are often unwilling to discuss their problem with family members or health care professionals. This situation is unfortunate, for much can be done to alleviate the symptoms of this distressing condition. It is therefore of utmost importance that medical education about symptoms of the overactive bladder and other related problems be improved to help health care professionals identify and treat patients who will benefit from therapy. This article reviews current thinking regarding definition, epidemiology, quality of life effects, evaluation, and management of the overactive bladder.

A prospective randomised double-blind controlled trial evaluating the effect of trans-sacral magnetic stimulation in women with overactive bladder.

Overactive bladder (OAB) is a prevalent condition with 16% of adults having one or more symptoms that significantly affect quality of life. Transcutaneous electrical nerve stimulation and neuromodulators have had success in treating OAB but are expensive, invasive, and sometimes cumbersome. We developed an alternative neuromodulatory technique that involves electromagnetic stimulation of the sacral nerve roots with a portable electromagnetic device to produce trans-sacral stimulation of the S3 and S4 sacral nerve roots. The aim of this study was to evaluate the impact of this device on OAB symptoms in women with a prospectively randomised double-blind controlled study. Following a power analysis, women with symptoms of OAB were prospectively recruited with ethical approval for randomisation to an active treatment (n = 33) or placebo group (n = 30) in a double-blind trial. The patient, at home, used the belt device daily for 20 min over 12 weeks. Outcome measures included a 3-day voiding diary, 1 h pad test, visual analogue score (VAS) for symptom impact (0-100%), Kings Health Questionnaire (KHQ) and Australian Quality of Life questionnaire (AQOL) at baseline, 6 and 12 weeks. Overall, no difference was found between groups for any of the research questions. Specifically, we were unable to demonstrate any difference between the active and sham device groups in frequency, nocturia, urinary leakage, or quality of life, nor was there any evidence of a placebo effect. The quality of the data was high with the number of missing observations (especially for disease specific KHQ and general AQOL) being few. This attempt to promote trans-sacral electromagnetic neuromodulation with a specially created device was ineffective on the symptoms of OAB.

The family school : the impact of a group training programme on overactive hard-to-manage preschool children and their parents

Föräldraskap upplevs som en utmanande uppgift i dag och det påstås att föräldrar oftare än förr skulle var i behov av råd och stöd beträffande barnuppfostran. Denna uppgift kan ytterligare försvåras om det i familjen finns ett hyperaktivt okoncentrerat barn att uppfostra. Detta arbete undersökte effekterna av ett kortvarigt gruppbaserat interventionsprogram benämnt Familjeskolan POP (Preschool Overactivity Programme). Familjeskolan är avsedd för familjer med barn i lekåldern, som visar beteendesvårigheter såsom ADHD (Attention Deficit Hyperactivity Disorder), ODD (Oppositional Deficit Disorder) eller CD (Conduct Disorder). Målet för Familjeskolan är att öka föräldrarnas kunskaper och självförtroende då de har ett krävande svårhanterligt barn att uppfostra. Familjeskolan strävar också till att reducera barns icke-önskvärda beteenden genom att öka deras sociala färdigheter och koncentrationsförmåga. Familjeskolan verkställdes i Helsingfors vid ADHD- centrets lokaliteter. 45 mödrar och deras barn från huvudstadsregionen deltog i denna undersökning. Av dessa deltog 33 i Familjeskola-programmet medan de 12 övriga bildade den s.k. kontrollgruppen. Undersökningsresultaten tyder på förbättringar beträffande både moderns och faderns föräldrakunskaper efter Familjeskola-interventionen. Det är att lägga märke till att enbart mödrar deltog i interventionsprogrammet. Efter programmet klarade mödrar enligt egen utsaga vardagen bättre. Speciellt hade de blivit bättre på att hantera barnens beteendesvårigheter och hyperaktivt okoncentrerat beteende. Resultaten påvisade också att programmet var effektivast för de mödrar som före Familjeskolan upplevde sig besitta ringa föräldrakunskaper. Mödrarna rapporterade en signifikant minskning i barnens totala beteendesvårigheter. Efter interventionen ansåg mödrarna att deras barn var mindre olydiga, hyperaktiva samt att deras beteendesvårigheter var lindrigare. Enligt dagvårdspersonalen hade barnens totala beteendesvårigheter och problem med koncentration och hyperaktivitet också minskat. Motsvarande förbättringar uppnåddes inte i kontrollgruppen. Resultaten från uppföljningsintervjun, visade också att barnens beteendeförändringar var bestående både hemma och i daghemmet. Både föräldrar och dagvårdspersonalen rapporterade en signifikant minskning i barnens totala svårigheter jämfört med innan familjerna påbörjade interventionen. Föräldrarna rapporterade en marginell minskning i barnens ADHD-liknande beteende, beteendesvårigheter och i svårigheter med kamrater, dagvårdspersonalen däremot rapporterade en signifikant minskning i barnens beteendesvårigheter, hyperaktivt/okoncentrerat beteende samt i svårigheter med kamrater mellan innan familjerna påbörjade interventionen och uppföljningen ett år efter. Resultaten av denna undersökning stödjer hypotesen att kortvariga gruppbaserade interventionsprogram kan åstadkomma permanenta förbättringar i föräldrakunskaper och barns beteende. Detta gäller främst hyperaktivitet, koncentrationssvårigheter och trotsighet.

Validação do International Consultation on Incontinence Questionnaire Overactive Bladder (ICIQ-OAB) para a língua portuguesa

OBJETIVOS: traduzir, adaptar culturalmente e validar o questionário International Consultation on Incontinence Questionnaire Overactive Bladder (ICIQ-OAB) para a língua portuguesa. MÉTODOS: dois tradutores brasileiros, cientes dos objetivos da pesquisa, traduziram o ICIQ-OAB para o português e as duas traduções geradas foram retrotraduzidas por outros dois tradutores ingleses. As diferenças entre as versões foram harmonizadas e pré-testadas em um estudo piloto. A versão final do ICIQ-OAB foi aplicada junto com a versão já traduzida e validada do questionário International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) em 142 pacientes, entre homens e mulheres, com sintomas miccionais irritativos. Para validação do ICIQ-OAB foram testadas propriedades psicométricas: confiabilidade (consistência interna e teste-reteste) e validade de construto. O reteste foi realizado quatro semanas após a primeira entrevista. RESULTADOS: a confiabilidade do instrumento foi avaliada por meio do Coeficiente α Cronbach, tendo como resultado geral 0,7. O teste-reteste avaliou a estabilidade do instrumento por meio do coeficiente de correlação intraclasse e apresentou resultado de 0,91 e 0,95, quando comparados aos questionários ICIQ-OAB e ICIQ-SF, respectivamente. Comparando os instrumentos por meio do coeficiente de correlação de Pearson foi encontrado 0,7 (p=0,0001), o que confirma a validade de critério do estudo. A validade concorrente foi avaliada pela correlação entre algumas variáveis sociodemográficas e clínicas e o escore final do ICIQ-OAB. CONCLUSÃO: a versão em português do ICIQ-OAB traduzida e adaptada culturalmente para o português do Brasil apresentou confiabilidade e validade de constructo satisfatórias e foi considerada válida para avaliação dos sintomas miccionais irritativos de pacientes brasileiros de ambos os sexos.

Relationship between anxiety and overactive bladder syndrome in older women

PURPOSE: The objective of this study was to investigate the relationship between overactive bladder syndrome and anxiety in older women.METHODS: Of the 198 older women who were invited, 29 were excluded and 166 were then divided into two groups according to the Advanced Questionnaire of Overactive Bladder (OAB-V8): one group with overactive bladder symptoms (OAB-V8≥8) and the other without the symptoms of an overactive bladder (OAB-V8<8). The purpose was to conduct a frequency analysis and to investigate the relation of the social demographic data and anxiety in the two groups. The Beck Anxiety Inventory (BAI) was used to evaluate the level of anxiety. The Kolmogorov-Smirnov test was used to determine the distribution of the data. The differences between the two groups for the continuous variables were analyzed by the Mann-Whitney U test, the differences for the categorical variables were analyzed by the Chi-Square test and the association between the continuous variables was analyzed by the Spearman Correlation test. The tests were two-tailed with a confidence level of 5%.RESULTS: Overall, the frequency of an overactive bladder was present in 117 (70.5%) of the participants. The body mass index (BMI) of the group with overactive bladder symptoms was significantly higher than the BMI of those without these symptoms (p=0.001). A higher prevalence of mild, moderate and severe anxiety was observed among older women with overactive bladder symptoms. In addition, the overactive bladder symptoms group presented a positive low correlation with anxiety symptoms (r=0.345) and with BMI (r=0.281). There was a small correlation between BMI and anxiety symptoms (r=0.164).CONCLUSIONS: Overactive bladder syndrome was prevalent among older women and the existence of these symptoms was linked to the presence of mild, moderate and/or severe anxiety symptoms.

Bryophyllum pinnatum inhibits detrusor contractility in porcine bladder strips--a pharmacological study towards a new treatment option of overactive bladder

A broad spectrum of synthetic agents is available for the treatment of overactive bladder. Anti-cholinergic drugs show a poor compliance due to side effects. There is an increasing use of plant extracts in medicine. We have therefore investigated the inhibitory effects of leaf press juice from Bryophyllum pinnatum (Lam.) Oken (Kalanchoe pinnata L.) on bladder strips and compared the effects to that of oxybutynin.

Cadherin-11 up-regulation in overactive bladder suburothelial myofibroblasts

PURPOSE: We investigated whether the adherens junction proteins cadherin-11 and beta-catenin can be immunohistochemically visualized in the human bladder using commercially available antibodies and, if so, whether there are differences between patients with overactive bladder and refractory detrusor overactivity, and controls without lower urinary tract symptoms. MATERIALS AND METHODS: In a prospective, nonrandomized single center study 32 patients with overactive bladder and refractory detrusor overactivity, and 8 controls without lower urinary tract symptoms underwent cystoscopic bladder biopsy. Quantitative immunohistochemistry was performed. The primary outcome was cadherin-11 and beta-catenin expression in the human bladder using commercially available antibodies. The secondary outcome was differences in cadherin-11 and beta-catenin in patients with overactive bladder and refractory detrusor overactivity, and controls. RESULTS: Double labeling experiments showed co-localization of cadherin-11 and connexin 43 in the suburothelium. There was also strong co-localization of cadherin-11 and beta-catenin in the suburothelium and detrusor. Significant 2-fold up-regulation of cadherin-11 was found in the suburothelium of patients with overactive bladder compared with that in controls (p = 0.018), whereas beta-catenin was similar in the groups (p = 0.6). In the detrusor cadherin-11 and beta-catenin expression was comparable in patients with overactive bladder and controls (each p = 0.5). No difference was observed in cadherin-11 and beta-catenin in patients with overactive bladder with idiopathic vs neurogenic detrusor overactivity in the suburothelium and the detrusor (p >0.3 and >0.2, respectively). CONCLUSIONS: Using commercially available antibodies cadherin-11 and beta-catenin expression in human bladder suburothelial myofibroblasts and detrusor smooth muscle cells was noted. Cadherin-11 up-regulation in suburothelial myofibroblasts in patients with overactive bladder may be significant in overactive bladder pathogenesis.

Suburothelial myofibroblasts in the human overactive bladder and the effect of botulinum neurotoxin type A treatment

BACKGROUND: An increasing body of evidence suggests a possible role of suburothelial myofibroblasts (MFs) in bladder mechanosensation and in the pathophysiology of detrusor overactivity (DO). OBJECTIVE: To determine whether markers of MFs, including gap junction protein connexin43 (Cx43) and c-kit have altered immunohistochemical expression in the suburothelium of patients with neurogenic DO (NDO) or idiopathic DO (IDO) and whether this is affected by successful treatment of DO with botulinum neurotoxin type A (BoNTA). DESIGN, SETTING, AND PARTICIPANTS: Patients with NDO (n=10) or IDO (n=11) were treated in a single-centre, open-label study of intradetrusor BoNTA injections. Control tissue was obtained from 10 patients undergoing pelvic-floor repair procedures who had no overactive bladder (OAB) symptoms. This study is registered with ClinicalTrials.gov, number NCT00662064. INTERVENTIONS: Bladder biopsies performed with flexible cystoscopes were obtained from control subjects and from NDO and IDO patients before BoNTA treatment and at 4 wk and 16 wk after treatment. They were studied with quantitative immunofluorescence using antibodies to connexin 43 (Cx43), vimentin, and c-kit. MEASUREMENTS: Differences in Cx43, vimentin, and c-kit immunoreactivity between control subjects and NDO or IDO patients (primary outcomes). Changes in NDO or IDO, Cx43 immunoreactivity, and c-kit immunoreactivity after BoNTA treatment (secondary outcomes). RESULTS AND LIMITATIONS: Cx43 immunoreactivity was increased in both IDO and NDO patients compared to controls, but remained unchanged after BoNTA treatment. C-kit immunoreactivity was similar in NDO/IDO patients and controls and remained unchanged after BoNTA treatment. CONCLUSIONS: Increased gap junction formation in the suburothelium has been demonstrated in biopsies from humans with DO. It is hypothesised that this change could have a significant role in the pathogenesis of the detrusor abnormality. Successful treatment of NDO or IDO does not appear to be associated with changes in the expression of Cx43 or c-kit on suburothelial MFs.

Transcutaneous electrical nerve stimulation: an effective treatment for refractory non-neurogenic overactive bladder syndrome?

PURPOSE: To assess the effect of transcutaneous electrical nerve stimulation (TENS) for treating refractory overactive bladder syndrome (OAB). PATIENTS AND METHODS: A consecutive series of 42 patients treated with TENS for refractory OAB was prospectively investigated at an academic tertiary referral centre. Effects were evaluated using bladder diary for at least 48 h and satisfaction assessment at baseline, after 12 weeks of TENS treatment, and at the last known follow-up. Adverse events related to TENS were also assessed. RESULTS: Mean age of the 42 patients (25 women, 17 men) was 48 years (range, 18-76). TENS was successful following 12 weeks of treatment in 21 (50 %) patients, and the positive effect was sustained during a mean follow-up of 21 months (range, 6-83 months) in 18 patients. Following 12 weeks of TENS treatment, mean number of voids per 24 h decreased significantly from 15 to 11 (p < 0.001) and mean voided volume increased significantly from 160 to 230 mL (p < 0.001). In addition, TENS completely restored continence in 7 (39 %) of the 18 incontinent patients. Before TENS, all 42 patients were dissatisfied or very dissatisfied; following 12 weeks of TENS treatment, 21 (50 %) patients felt satisfied or very satisfied (p < 0.001). No adverse events related to TENS were noted. CONCLUSIONS: TENS seems to be an effective and safe treatment for refractory OAB warranting randomized, placebo-controlled trials.

Electrical stimulation with non-implanted electrodes for overactive bladder in adults

External sources The National Institute for Health Research (NIHR), UK. This project was supported byNIHR via Cochrane Infrastructure, Cochrane Programme Grant or Cochrane Incentive funding to the Incontinence Group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, National Health Service (NHS) or the Department of Health. NHS Grampian Endowment Research Grants, UK. This project was also supported by NHS Grampian Endowment Research Grants.