RESUMEN
PURPOSE: We studied the effect of repeat detrusor botulinum neurotoxin type A injections on urinary symptoms, health and quality of life in patients with refractory neurogenic detrusor overactivity secondary to multiple sclerosis. MATERIALS AND METHODS: This was a prospective, open label, single center study in 137 patients with multiple sclerosis treated with detrusor injections of botulinum neurotoxin type A with observations made from 2002 to 2009. A minimally invasive outpatient technique was used for injection. Patients were asked to contact the department if and when they required repeat treatment. Recurrent detrusor overactivity was then identified on urodynamics. The primary outcomes measured were the change in symptoms and quality of life, as assessed by the Urogenital Distress Inventory, Incontinence Impact Questionnaire and EuroQol-5 Dimensions questionnaires (www.ion.ucl.ac.uk/departments/repair/themes/uroneurology) before and 4 weeks after botulinum treatment. Continence status, the need for clean intermittent self-catheterization before and after injections, and interinjection intervals were also analyzed. RESULTS: Mean Urogenital Distress Inventory and Incontinence Impact Questionnaire 7 scores showed considerable improvement 4 weeks after each treatment even when repeated 6 times. Almost all patients relied on clean intermittent self-catheterization after treatment. Before the first treatment 83% of patients were incontinent but 4 weeks after the first treatment 76% (104 of 137) became completely dry. This efficacy was sustained with repeat injections. The median interval between re-treatments remained constant at 12 to 13 months. CONCLUSIONS: Repeated detrusor botulinum neurotoxin type A injections for refractory neurogenic detrusor overactivity in patients with multiple sclerosis have a consistent effect on bladder control, resulting in sustained improvement in quality of life.
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Toxinas Botulínicas Tipo A/administración & dosificación , Fármacos Neuromusculares/administración & dosificación , Calidad de Vida , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Administración Intravesical , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Estudios Prospectivos , Retratamiento , Factores de Tiempo , Vejiga Urinaria Hiperactiva/etiología , Adulto JovenRESUMEN
STUDY TYPE: Therapy (case series). LEVEL OF EVIDENCE: 4. What's known on the subject? and What does the study add? We know that repeated injections of botulinum toxin A are effective in treating refractory detrusor overactivity particularly in NDO. This study shows that in both NDO and IDO repeated injections of the toxin improve quality of life as assessed by three validated questionnaires. The effect is most marked after the first injection in NDO patients but thereafter similar in both groups. OBJECTIVE: To compare the effect of repeated detrusor injections of botulinum toxin (BoNT-A) on health-related quality of life (HRQL) in patients with idiopathic (IDO) or neurogenic detrusor overactivity (NDO). PATIENTS AND METHODS: Between 2003 and 2009, 151 patients (109 with NDO and 42 with IDO) were treated by BoNT-A (Botox®, Allergan Inc., Irvine, CA, USA). Changes in HRQL were assessed using the validated short forms of Urogenital Distress Inventory (UDI-6), the Incontinence Impact Questionnaire (IIQ-7) and EuroQOL-5D (EQ-5D) before and 4 weeks after BoNT-A. RESULTS: The maximum number of repeated injections was five (mean±sd, 2.8±1.05). Mean±sd follow-up was 27.49±17.01 months. The UDI-6 and IIQ-7 questionnaires showed a consistent improvement after repeated injections in both groups with detrusor overactivity. The EQ-5D was not statistically different before and after each injection in either the NDO or IDO population. After repeated injections, no statistical differences in the change on the UDI-6 and IIQ-7 scores were found between NDO and IDO, except after the first treatment, when the decrease in UDI-6 was higher in NDO than in IDO. The EQ-5D anxiety and depression subscore improved in both groups after each injection and with the number of injections. In IDO, after the second injection, no patient reported extreme anxiety or depression and, after the fourth injection, none had anxiety or depression. The inter-injection interval was shorter after the first injection in those with NDO than in IDO but was similar thereafter. CONCLUSIONS: Intradetrusor injections of BoNT-A improved the HRQL of both NDO and IDO patients. Although improvement in HRQL was greater and the duration of efficacy shorter in NDO patients after the first injection, there was no significant difference after subsequent injections. Mean inter-injection interval in IDO and in NDO patients was similar from the second injection onwards and improvements in HRQL score were the same.
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Toxinas Botulínicas Tipo A/uso terapéutico , Calidad de Vida , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Adulto , Distribución de Chi-Cuadrado , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intralesiones , Masculino , Satisfacción del Paciente , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Reino Unido , Vejiga Urinaria Neurogénica/diagnóstico , Vejiga Urinaria Neurogénica/tratamiento farmacológico , Vejiga Urinaria Neurogénica/psicología , Vejiga Urinaria Hiperactiva/diagnóstico , Vejiga Urinaria Hiperactiva/psicología , UrodinámicaRESUMEN
PURPOSE: We documented the effects of intradetrusor injections of botulinum neurotoxin type A (Botox(R)) for refractory idiopathic detrusor overactivity so that prospective patients maybe properly informed about possible improvement in quality of life, the duration of interinjection intervals and the risk of clean intermittent self-catheterization. MATERIALS AND METHODS: A total of 81 consecutive patients with refractory idiopathic detrusor overactivity treated with intradetrusor injections of 200 U botulinum neurotoxin type A at 20 sites per injection course were evaluated in this prospective, nonrandomized, open label cohort study. The primary outcome was changes in quality of life, as assessed by the short form of the Urogenital Distress Inventory and the Incontinence Impact Questionnaire before and after treatment. Secondary outcomes were the interinjection interval and the need for clean intermittent self-catheterization. RESULTS: After intradetrusor botulinum neurotoxin type A injections there was significant improvement in quality of life, which was sustained after repeat injections. Mean Urogenital Distress Inventory and Incontinence Impact Questionnaire scores decreased from 56 to 26 and 59 to 21 after injection 1 in 81 patients, from 52 to 30 and 51 to 24 after injection 2 in 24, from 40 to 19 and 43 to 17 after injection 3 in 13, from 44 to 17 and 61 to 15 after injection 4 in 6 and from 51 to 17 and 63 to 14 after injection 5 in 4, respectively. The median interinjection interval was 15, 12, 14 and 13 months between injections 1 and 2, 2 and 3, 3 and 4, and 4 and 5, respectively. Considering a post-void residual urine of greater than 100 ml with lower urinary tract symptoms as the indication for clean intermittent self-catheterization, the overall clean intermittent self-catheterization rate after treatment was 43%. CONCLUSIONS: Intradetrusor botulinum neurotoxin type A injections for refractory idiopathic detrusor overactivity significantly improved quality of life. This effect was sustained after repeat injection. More than 2 of 5 patients with refractory idiopathic detrusor overactivity required clean intermittent self-catheterization after botulinum neurotoxin type A injections and all prospective patients should be informed about this.
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Toxinas Botulínicas Tipo A/administración & dosificación , Neurotoxinas/administración & dosificación , Educación del Paciente como Asunto , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Adulto JovenRESUMEN
OBJECTIVE: To assess whether incomplete bladder emptying and the need for clean intermittent self-catheterization (CISC) is predictable, by analysing urodynamic and detrusor contractility variables in patients treated with botulinum toxin-A (BTX-A) for refractory idiopathic detrusor overactivity (IDO). PATIENTS AND METHODS: Sixty-seven patients (mean age 50.3) with IDO, from two centres, had bladder injections of 200 U BTX-A. Patients with difficulty in emptying their bladder and/or persistent overactive bladder symptoms, with postvoid residual volumes (PVR) of >150 mL after treatment were started on CISC. Urodynamics were conducted at baseline, 4 and 12-16 weeks after injection with BTX-A. Detrusor contractility was assessed using the projected isovolumetric pressure (PIP1) in women and bladder contractility index (BCI) in men. RESULTS: There were improvements in the mean maximum cystometric capacity, bladder compliance and maximum detrusor pressures during filling cystometry after BTX-A injections. The PVR was significantly increased at 4 but not at 12 weeks. Nineteen patients required CISC and when compared with those not needing CISC their pretreatment maximum flow rate (15 vs 22 mL/s, P = 0.003), PIP1 (43 vs 58, P = 0.02) and BCI (113 vs 180, P = 0.001) were lower. Receiver operator characteristic curve analysis suggested that a PIP1 of < or =50 in women (sensitivity 0.83; specificity 0.70; area under the curve 0.822) and BCI < or =120 (sensitivity 0.7; specificity 0.79; area 0.879) might predict the need for CISC. CONCLUSION: The maximum flow rate, PIP1 and BCI were significantly lower in patients who required CISC after BTX-A treatment than in those who did not. A PIP1 of < or =50 in women and a BCI of < or =120 might be predictive of a need for CISC in this setting, and might help when counselling patients.
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Toxinas Botulínicas Tipo A/uso terapéutico , Fármacos Neuromusculares/uso terapéutico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Vejiga Urinaria/fisiopatología , Urodinámica/fisiología , Adolescente , Adulto , Anciano , Toxinas Botulínicas Tipo A/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Fármacos Neuromusculares/efectos adversos , Sensibilidad y Especificidad , Resultado del Tratamiento , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria Hiperactiva/fisiopatología , Cateterismo Urinario , Adulto JovenRESUMEN
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.
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Toxinas Botulínicas Tipo A/administración & dosificación , Conexina 43/metabolismo , Fármacos Neuromusculares/administración & dosificación , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Vejiga Urinaria Hiperactiva/patología , Adulto , Anciano , Biomarcadores/metabolismo , Biopsia con Aguja , Conexina 43/efectos de los fármacos , Cistoscopía , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Inyecciones Intramusculares , Persona de Mediana Edad , Valores de Referencia , Medición de Riesgo , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Vejiga Urinaria Hiperactiva/metabolismo , Urodinámica/efectos de los fármacos , Urotelio/efectos de los fármacos , Urotelio/metabolismoRESUMEN
Health economic aspects are crucial in arguing the feasibility of setting up a new service using an unlicensed treatment. Overall, the costs of intradetrusor botulinum neurotoxin-A treatment appear to be modest relative to the improvement in quality of life. However, in managing the overactive bladder, there is a need for a widely accepted definition of 'clinical improvement' or a common outcome measure to direct future clinical and health economic research.
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Toxinas Botulínicas Tipo A/economía , Fármacos Neuromusculares/economía , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Administración Intravesical , Toxinas Botulínicas Tipo A/uso terapéutico , Análisis Costo-Beneficio , Costos de los Medicamentos/estadística & datos numéricos , Humanos , Fármacos Neuromusculares/uso terapéutico , Calidad de Vida , Resultado del Tratamiento , Vejiga Urinaria Hiperactiva/economíaRESUMEN
BACKGROUND: We examined, for the first time in a prospective study, the histological changes in the urothelium and suburothelium of patients with neurogenic (NDO) or idiopathic detrusor overactivity (IDO) after one or repeat treatments with intradetrusor BoNTA. METHODS: Flexible cystoscopic bladder biopsies were obtained from patients with urodynamically proven intractable spinal NDO or IDO before and 4 and 16 wk after one or repeat treatments with intradetrusor injections of BOTOX1 (NDO 300 U, IDO 200 U). Specimens were stained for haematoxylin-eosin and analysed blindly for inflammatory changes, fibrosis, hyperplasia, and dysplasia in the urothelium and suburothelium. Statistical comparisons were significant at p values less than 0.05. RESULTS: Signs of chronic inflammation were found in 59.1% of baseline biopsies (65.6% of NDO vs. 50% of IDO, p=0.049), 67.6% of post-first biopsies and 86.4% after repeat injections. The two groups were comparable for degree of baseline inflammation, which did not change significantly after first injection and up to 16 wk after a third injection. Mild fibrosis was found in 2.2% of biopsies examined, equally before and after treatment, but not after repeat injections. No dysplasia or hyperplasia was identified. Eosinophils were identified more frequently in biopsies taken after repeat injections compared with the post-first injection and baseline biopsies (chi2=8.23, p=0.018). No difference existed between NDO and IDO bladders. CONCLUSIONS: BoNTA injections do not appear to be producing significant inflammatory changes, fibrosis, or dysplastic changes in human bladder urothelium/suburothelium after a single injection and in a limited number of repeat treatment biopsies. The presence of eosinophils might be treatment-related, because they were mostly found in post-treatment biopsies.
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Toxinas Botulínicas Tipo A/administración & dosificación , Fármacos Neuromusculares/administración & dosificación , Vejiga Urinaria Neurogénica/tratamiento farmacológico , Vejiga Urinaria Neurogénica/patología , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Vejiga Urinaria Hiperactiva/patología , Administración Intravesical , Toxinas Botulínicas Tipo A/farmacología , Humanos , Fármacos Neuromusculares/farmacología , Estudios Prospectivos , Urotelio/efectos de los fármacos , Urotelio/patologíaRESUMEN
OBJECTIVES: Limited studies to date have reported on the onset of effect of intradetrusor botulinum neurotoxin type A (BoNTA) injections when used to treat the symptoms of the overactive bladder (OAB). Furthermore, few studies have examined the effect of BoNTA on urgency and nocturia, now recognised as the most bothersome symptoms of the OAB syndrome. We studied the immediate effect of BoNTA on the OAB symptoms by recording the daily changes during the week after treatment of patients with neurogenic or idiopathic detrusor overactivity (NDO/IDO). METHODS: Twenty-four patients (16 NDO, 8 IDO) treated with 300mu BOTOX((R)) (NDO) or 200mu (IDO) completed a 4-d voiding diary before and 4 wk after treatment and a 7-d diary starting the day immediately after injections. Data were analysed for intragroup daily changes during the first week and for further changes at 4 wk. Parametric t tests were used for statistical analysis (significance at p<0.05). RESULTS: The two groups were comparable at baseline for all studied variables. In NDO, significant improvements in urgency, frequency, and nocturia were seen at day 2 post injection and in incontinence at day 3, and were sustained at 4 wk. In IDO, the first significant change in urgency, frequency, and incontinence was seen at day 4, with urgency showing the most consistent changes thereafter. All parameters significantly improved at 4 wk. CONCLUSIONS: Intradetrusor BoNTA ameliorates all OAB symptoms within the first week after treatment, but urgency is most rapidly and consistently affected, suggesting an early effect on bladder afferent pathways. Differences in the toxin dose or possibly underlying pathophysiology may account for an earlier trend for symptomatic improvement in the NDO patients.
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Toxinas Botulínicas Tipo A/administración & dosificación , Fármacos Neuromusculares/administración & dosificación , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Adulto , Femenino , Humanos , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Trastornos Urinarios/tratamiento farmacológicoRESUMEN
OBJECTIVE: Our objective was to demonstrate the efficacy and impact on quality of life of detrusor injections of botulinum neurotoxin type A in the treatment of bladder dysfunction in patients with multiple sclerosis. METHODS: Forty-three patients with multiple sclerosis suffering from severe urgency incontinence were treated with detrusor injections of botulinum neurotoxin type A. Data from cystometric assessment of the bladder, voiding diaries, quality-of-life questionnaires, and procontinence medication usage were collected before treatment and 4 and 16 weeks after injection. The same data were also collected after repeat treatments. RESULTS: Highly significant improvements (p < 0.0001) in incontinence episodes and urinary urgency, daytime frequency and nocturia, were the symptomatic reflection of the significant improvements in urodynamically demonstrated bladder function. Although 98% of patients had to perform self-catheterization after treatment, there were sustained improvements in all quality-of-life scores. The mean duration of effect was 9.7 months. Similar results were seen with repeat treatments. INTERPRETATION: Minimally invasive injections of botulinum neurotoxin type A have been shown to be exceptionally effective in producing a prolonged improvement in urinary continence in patients with multiple sclerosis. This treatment is likely to have a major impact on future management.
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Toxinas Botulínicas Tipo A/administración & dosificación , Esclerosis Múltiple/tratamiento farmacológico , Incontinencia Urinaria/tratamiento farmacológico , Administración Intravesical , Adulto , Animales , Femenino , Humanos , Inyecciones Intramusculares , Masculino , Ratones , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/fisiopatología , Estudios Prospectivos , Resultado del Tratamiento , Incontinencia Urinaria/etiología , Incontinencia Urinaria/fisiopatologíaRESUMEN
BACKGROUND: Patients with neurogenic bladder represent a small fraction of the total overactive bladder population. As a consequence, development of new therapies in this area has largely focused on idiopathic urinary incontinence. The absence of data for patients with neurological disease has far-reaching implications, affecting reimbursement and physicians' willingness to prescribe therapies, and limiting access of potential valuable treatments to patients whose lives are significantly impaired by inadequately managed bladder symptoms. SCOPE: The range of new therapies is increasing. Although many reviews of the overall safety, efficacy and mode of action of such treatments are available, there is limited information on how these treatments will best be used in clinical practice. We considered the current benefits and limitations of the various new licensed and unlicensed therapies and what role each would have in the future management of neurogenic urinary incontinence. CONCLUSIONS: A wide range of new treatments have been investigated for the management of overactive bladder; few, however, have been evaluated extensively in neurogenic urinary incontinence. Further studies are required to determine the optimal dosing regimes and formulations for individual sub-populations of neurogenic bladder patients and to determine the cost-effectiveness of these interventions. With the current experience available, two treatment algorithms for a subset of patients with neurological disease have also been proposed, which suggest at which stage of management and in which patients individual therapies for neurogenic urinary incontinence could be used.
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Vejiga Urinaria Neurogénica/tratamiento farmacológico , Incontinencia Urinaria/tratamiento farmacológico , Algoritmos , Toxinas Botulínicas Tipo A/farmacología , Toxinas Botulínicas Tipo A/uso terapéutico , Cannabinoides/farmacología , Cannabinoides/uso terapéutico , Capsaicina/farmacología , Capsaicina/uso terapéutico , Antagonistas Colinérgicos/farmacología , Antagonistas Colinérgicos/uso terapéutico , Diterpenos/farmacología , Diterpenos/uso terapéutico , Humanos , Antagonistas Muscarínicos/farmacología , Antagonistas Muscarínicos/uso terapéutico , Resultado del Tratamiento , Vejiga Urinaria Neurogénica/complicaciones , Incontinencia Urinaria/etiologíaRESUMEN
BACKGROUND: The management of urinary incontinence in patients with neurological disease is complex. Physicians face a multitude of challenges related to progression of the primary condition, the presence of a diversity of other related and unrelated symptoms, the safety, efficacy and tolerability issues associated with multiple therapies being required and the changing need for collaboration with other specialities. SCOPE: Current guidelines produced by the urological communities, as well as the disease-focused organizations, aim to standardize care in their specific group of patients. A passive approach to implementation, however, means that guidelines produced are all too frequently not readily available to, read by or followed by the wider audience. In addition, each speciality has its own guidelines and a different view of the primary focus of care in neurological patients, which may lead to variations in recommendations and, subsequently, in clinical practice. A review of current urological and disease specific guidelines was made to evaluate differences between the published guidance between the specialities and within urology itself. CONCLUSIONS: Although availability of effective therapies remains a cornerstone of neurogenic bladder treatment, consideration must also be given to the non-pharmacological and surgical issues related to the global management of this population. Improved cross-speciality interactions and development of patient-specific treatment and follow-up plans, which are in keeping with the current guidelines of each speciality involved, may serve to enhance physicians' understanding of the importance of effective urinary incontinence treatment as well as the overall management of the patient.
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Guías de Práctica Clínica como Asunto/normas , Vejiga Urinaria Neurogénica/tratamiento farmacológico , Europa (Continente) , Humanos , Calidad de la Atención de Salud , Vejiga Urinaria Neurogénica/fisiopatología , Incontinencia UrinariaRESUMEN
OBJECTIVE: Little published data exist on the effect of intradetrusor botulinum neurotoxin type A (BoNT/A) on the quality of life (QOL) of patients with overactive bladder. We examined post-BoNT/A QOL changes of patients with neurogenic detrusor overactivity (NDO) in comparison to those with idiopathic detrusor overactivity (IDO), and their correlations with respective changes in lower urinary tract symptoms (LUTS) and urodynamic parameters. METHODS: Patients with urodynamically proven intractable DO were assessed for changes in QOL 4 and 16 wk after treatment with intradetrusor BOTOX injections (NDO 300U; IDO 200U) using the short forms of the Urinary Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7). Percent changes in total QOL score were correlated to respective changes in clinical parameters recorded by bladder diaries and voiding cystometry. RESULTS: Forty-eight treated patients (32 NDO, 16 IDO) had QOL data in at least one follow-up. Highly significant decreases (p < 0.0001) in mean +/- standard error QOL score at 4 wk were maintained at 16 wk for both the NDO and IDO subgroups. Percent improvement in QOL score was similar for NDO versus IDO at 4 (67.6 +/- 4.5 versus 70.3 +/- 7.7, p = 0.74) and 16 wk (65.2 +/- 5.5 versus 71.9 +/- 8.8, p = 0.51). Percent changes in QOL score of the whole patient group correlated with changes in 24-h micturition frequency, number of voids associated with urgency, and number of urge incontinence episodes, but not with urodynamic parameters. CONCLUSIONS: Intradetrusor BoNT/A produces comparable, significant improvements in the QOL of patients with either NDO or IDO at least up to 16 wk after treatment. In contrast to urodynamic parameters, changes in LUTS appear to be the major determinants of improvements in the patients' QOL.
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Toxinas Botulínicas Tipo A/uso terapéutico , Fármacos Neuromusculares/administración & dosificación , Calidad de Vida , Vejiga Urinaria Neurogénica/tratamiento farmacológico , Incontinencia Urinaria/tratamiento farmacológico , Trastornos Urinarios , Adulto , Toxinas Botulínicas Tipo A/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intramusculares , Masculino , Encuestas y Cuestionarios , UrodinámicaRESUMEN
OBJECTIVE(S): This study aimed to assess the resource utilisation, health benefits and cost-effectiveness of intra-detrusor injections of botulinum neurotoxin-A (BoNT/A) in patients with overactive bladder (OAB). METHODS: 101 patients with urodynamically-proven detrusor overactivity of either neurogenic (NDO; n = 63) or idiopathic (IDO; n = 38) origin received intra-detrusor injections of 200-300 units of BoNT/A in 20-30 ml saline as part of a research protocol. Twenty-nine patients received repeat injections after 7-26 months. Symptom severity and urodynamic parameters were assessed at 0, 4 and 16 weeks. The cost of therapy was quantified based on the NHS resources used by typical patients and was used to calculate the cost-effectiveness of BoNT/A compared with standard care from the perspective of the UK NHS. RESULTS: In an intent-to-treat analysis, 82% of patients showed a 25% or greater improvement in at least two out of five parameters (urinary frequency, urgency, urgency incontinence episodes, maximum cystometric capacity and maximum detrusor pressure) four weeks after treatment, reducing to 65% after 16 weeks. A 50% or greater improvement in the frequency of micturition, urgency or urgency incontinence was seen in 73% of patients at four weeks and 54% at 16 weeks. There were no significant differences between IDO and NDO patients in the proportion meeting these endpoints. Therapy cost pounds 826 per patient, with a cost-effectiveness ratio of pounds 617 per patient-year with > or = 25% clinical improvement. CONCLUSION(S): This study demonstrates that intra-detrusor BoNT/A is an effective treatment for OAB that is highly likely to be cost-effective in both idiopathic and neurogenic disease.
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Toxinas Botulínicas Tipo A/uso terapéutico , Fármacos Neuromusculares/uso terapéutico , Incontinencia Urinaria/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas Tipo A/economía , Análisis Costo-Beneficio , Femenino , Humanos , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , Músculo Liso/efectos de los fármacos , Reino Unido , Incontinencia Urinaria/economíaRESUMEN
PURPOSE: Several studies have shown that intradetrusor injections of botulinum neurotoxin type A (BoNT/A) may effectively treat intractable spinal neurogenic detrusor overactivity (NDO), but fewer reports exist on the use of BoNT/A in patients with idiopathic detrusor overactivity (IDO). The purpose of this study was to investigate whether comparable efficacy could be displayed in the response of patients with IDO to those with NDO. MATERIALS AND METHODS: In a prospective, open label study, patients with urgency, and/or urgency incontinence due to urodynamically proven intractable detrusor overactivity received 300 units (NDO) or 200 units (IDO) of Botox injected into the bladder with a minimally invasive outpatient technique. Urodynamic maximum cystometric capacity and maximum detrusor pressure during filling, frequency of voids (frequency), number of incontinence episodes (leak) and number of voids associated with urgency per 24 hours (urgency) from 4-day voiding diaries were compared between the 2 groups at baseline and for changes at 4 and 16 weeks after treatment. RESULTS: A total of 44 patients with spinal NDO and 31 with IDO were treated. At 16 weeks, mean +/- standard error maximum cystometric capacity increased from 229.1 +/- 24.8 to 427.0 +/- 26.9 ml, p <0.0001 in NDO and from 193.6 +/- 24.0 to 327.1 +/- 36.1 ml, p=0.0008 in IDO. Maximum detrusor pressure during filling decreased from 60.7 +/- 6.8 to 26.1 +/- 3.7 cm H2O, p <0.0001 in NDO and from 62.1 +/- 10.8 to 45.1 +/- 8.1 cm H2O, p=0.027 in IDO. Frequency decreased from 12.3 +/- 0.7 to 6.6 +/- 0.6 voids per 24 hours, p <0.0001 in NDO and from 13.6 +/- 1.1 to 8.3 +/- 0.7, p=0.0002 in IDO. Leak decreased from 3.9 +/- 0.5 to 0.7 +/- 0.2 incontinence episodes per 24 hours, p <0.0001 in NDO and from 3.2 +/- 0.8 to 0.6 +/- 0.3, p=0.0017 in IDO, and urgency decreased from 7.5 +/- 0.6 to 1.44 +/- 0.3 episodes per 24 hours, p <0.0001 in NDO and from 10.9 +/- 1.7 to 4.9 +/- 1.1, p <0.0001 in IDO. The 2 groups were comparable for baseline data, but percent improvement in urgency was greater in patients with NDO at 4 weeks (78.2% vs 56.3%, p=0.019) and 16 weeks (78.3% vs 50.7%, p=0.013). Of patients with NDO 69% required self-catheterization de novo posttreatment compared with 19.3% of those with IDO. CONCLUSIONS: Patients with intractable IDO respond to intradetrusor BoNT/A with equally significant improvements in urodynamic and lower urinary tract symptom parameters as those with spinal NDO, despite the lower dose of toxin used.
Asunto(s)
Toxinas Botulínicas Tipo A/administración & dosificación , Hipertonía Muscular/tratamiento farmacológico , Fármacos Neuromusculares/administración & dosificación , Vejiga Urinaria Neurogénica/tratamiento farmacológico , Incontinencia Urinaria/tratamiento farmacológico , Adulto , Anciano , Biopsia , Toxinas Botulínicas Tipo A/efectos adversos , Cistoscopía , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Presión Hidrostática , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , Hipertonía Muscular/diagnóstico , Hipertonía Muscular/patología , Fármacos Neuromusculares/efectos adversos , Estudios Prospectivos , Resultado del Tratamiento , Vejiga Urinaria/inervación , Vejiga Urinaria/patología , Vejiga Urinaria Neurogénica/diagnóstico , Vejiga Urinaria Neurogénica/patología , Incontinencia Urinaria/diagnóstico , Incontinencia Urinaria/patología , Urodinámica/efectos de los fármacosRESUMEN
Bladder dysfunction is a common problem for patients with multiple sclerosis. The severity of symptoms often correlate with the degree of spinal cord involvement and, hence, the patient's general level of disability. The emphasis of management is now mainly medical and is increasingly offered by nonurologists. Treatments can be highly effective, relieving patients of what are otherwise very troublesome symptoms that would compound their neurological disability. This article gives an overview of the neural control of the bladder, followed by an explanation of the pathophysiology of detrusor overactivity secondary to neurological disease. A review of methods available for treating bladder dysfunction in multiple sclerosis then follows. The treatment options for this disorder are largely medical and include established first-line measures such as anticholinergics, clean intermittent self-catheterization and the use of desmopressin, as well as potential second-line agents, such as cannabinoids, intravesical vanilloids and intradetrusor botulinum neurotoxin type A. The diminishing role of surgical intervention is also discussed.