Factors that influence the urodynamic results of botulinum toxin in the treatment of neurogenic hyperactivity | Actas Urológicas Españolas (English Edition)

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In patients with NLUTD, the main objective is to prevent kidney damage, so urodynamic results turn out to be much more important than the symptoms or impact of neurogenic dysfunction on the quality of life of patients.<a class="elsevierStyleCrossRef" href="#bib0110">1</a>Neurogenic detrusor overactivity (NDO) is a common NLUTD in patients with spinal cord injury.<a class="elsevierStyleCrossRef" href="#bib0115">2</a> This dysfunction is the leading cause of urinary incontinence in these patients.<a class="elsevierStyleCrossRef" href="#bib0120">3</a> Furthermore, if it is associated with periurethral detrusor-sphincter dyssynergia (PDSD), it poses a risk of renal impairment due to the functional obstruction it causes.<a class="elsevierStyleCrossRef" href="#bib0125">4</a> Therefore, proper treatment is essential.The initial treatment of NDO is with anticholinergic agents acting on bladder muscarinic receptors.<a class="elsevierStyleCrossRef" href="#bib0130">5</a> However, this treatment is not always effective. Moreover, it is associated with the occurrence of significant side effects, particularly dry mouth and constipation, resulting in abandonment in about 20% of patients.<a class="elsevierStyleCrossRef" href="#bib0135">6</a>Intradetrusorian injection of botulinum toxin type A (BTX-A) has been proposed as a treatment in patients with NDO in whom anticholinergic therapy has been ineffective or poorly tolerated.<a class="elsevierStyleCrossRef" href="#bib0110">1</a> BTX-A has demonstrated both clinical and urodynamic efficacies in patients with NDO not responding to oral treatment with anticholinergics.<a class="elsevierStyleCrossRef" href="#bib0140">7</a> However, this treatment is not as effective in all patients. To date there is no study that analyzes the prognostic factors of the treatment outcome of NDO with BTX-A.The main objective of our study is to determine which factors influence the urodynamic result of treatment with BTX-A in a series of patients with spinal cord injury and NDO. As secondary objectives we set to confirm the urodynamic efficacy of BTX-A and the duration of its therapeutic effect in patients with spinal cord injury and NDO.Material and methodsA retrospective study of a cohort of 70 patients with SCI undergoing intradetrusorian BTX-A injection was performed for the treatment of NDO.The criteria for the injection of botulinum toxin were urodynamic demonstration of NDO, refractory to anticholinergic treatment at high doses (oxybutynin 15mg/day) (55 cases) or patient intolerance to anticholinergic treatment due to side effects (15 cases). In all cases, botulinum toxin injection was performed for the first time, and anticholinergic therapy was maintained in patients who were receiving it. In 33 cases, anticholinergics were associated with intermittent bladder catheterization and in 22 cases with permanent bladder catheter.All patients signed an informed consent. Botulinum toxin being a licensed treatment as compassionate use for NDO, and not being a clinical trial, the study was not submitted to the approval of the scientific committee.The patients included in the study underwent a medical history where the level and degree of spinal cord injury as well as their evolution time were determined, and then a urodynamic study with a Solar polygraph (MMS, Enschede, The Netherlands), according to the specifications of the ICS<a class="elsevierStyleCrossRef" href="#bib0145">8</a> and the protocols of the Good Urodynamic Practice.<a class="elsevierStyleCrossRef" href="#bib0150">9</a> In short, patients were placed in the supine position and we proceeded to bladder filling through a two-way 8Fr catheter, inserted transurethrally, with saline at room temperature and a speed of 20ml/s. The abdominal pressure was recorded using a catheter with transrectal balloon. The filling phase ended when there was an involuntary detrusor contraction.In this study, the following parameters were determined: cystomanometric bladder capacity (CBC), the bladder volume at which the first involuntary contraction (ICV) took place, the maximum pressure of the involuntary contraction (IC maxP), the filling pressure (fillP), maximum detrusor voiding pressure (maxP), maximum urinary flow (Qmax), post-void residual (PVR), and the index of urethral resistance (BOOI).From February 2008 to December 2012, a total of 70 patients were treated, of 39±13.3 years of age (mean±standard deviation). The sample consisted of 40 males and 30 females. The age of the SCI was 167±13.3 months.The botulinum toxin injection was performed with a dose of 300IU of onabotulinum toxin A (Botox® Allergan, Inc., Irving, CA, U.S.A.) spread over 30 locations with respect to the trigone.The patients underwent a second study at 6±4.3 months, after injection of botulinum toxin. After treatment, patients were followed with new urodynamic studies to observe the evolution of urodynamic data for an average of 16±12.2 months (range 3–45 months).The results were stored in an ACCES® database and exported to the statistical program SPSS® for their analysis. The statistical analysis consisted in applying the Fisher exact test for dichotomous variables, the mean comparison test of Student's “t”-test for parametric variables, both independent and paired, the Pearson correlation coefficient, and a survival analysis according to the Kaplan–Meier method. The significance level was set at 95% bilateral. 10% bilateral was considered a trend toward significance. The values were expressed as mean±standard deviation.ResultsThe distribution by level and degree of spinal cord injury is shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>The variation of urodynamic parameters following injection of botulinum toxin is shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. We observed a significant increase of the CBC, bladder volume at the first involuntary contraction, and PR.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> analyzed the influence of clinical parameters on CBC after injection of botulinum toxin. It was noted that the only significant difference was the presence of permanent bladder catheter.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Survival analysis showed that the median regarding the time taken for the CBC to return to baseline was 32 months (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>DiscussionIn our study, we observed that injection of BTX-A significantly increased both CBC and ICV, in addition to an increase in PR after 6 months of treatment. However, we observed no statistically significant differences from the fillP, CI maxP, Qmax, maxP, or BOOI.In randomized clinical trials (RCTs) on the effectiveness of botulinum toxin in patients with NDO, a significant increase in both CBC and ICV is also observed.<a class="elsevierStyleCrossRef" href="#bib0155">10</a> Moreover, a decrease in detrusor pressure is also demonstrated both during filling (bladder compliance) and during urination.<a class="elsevierStyleCrossRefs" href="#bib0160">11–13</a> These results have been corroborated by means of the meta-analysis conducted by Mehta et al.<a class="elsevierStyleCrossRef" href="#bib0140">7</a> Only in two observational studies a significant decrease in detrusor pressure was not evidenced during filling.<a class="elsevierStyleCrossRefs" href="#bib0175">14,15</a> In our study, we also observed a decrease in maximum detrusor pressure during voiding and peak urinary flow, although not reaching the proposed level of statistical significance (5% bilateral); in both cases it was below 10% bilateral (p<0.1), indicating a tendency of significance, which possibly with an increased sample size would have resulted in statistical significance.Reduction in the maximum flow and maximum detrusor pressure during the voiding phase, along with increased postvoid residue, clinically confirmed that the mechanism of action of botulinum toxin is exerted on detrusor contractile activity.<a class="elsevierStyleCrossRef" href="#bib0185">16</a> In our study, we also observed that the rate of urethral resistance did not vary significantly after 6 months of treatment, so it follows that the effects of botulinum toxin on the voiding phase are not due to an increase in urethral resistance.Regarding the predictors of outcome of botulinum toxin in our study, we observed that both patient age and sex, the age of the injury, or anticholinergic therapy did not influence the outcome of treatment with BTX-A at 6 months on bladder capacity. In an RCT conducted by Neel<a class="elsevierStyleCrossRef" href="#bib0190">17</a> et al. anticholinergic administration after injection of BTX-A did not significantly improve urodynamic results with respect to patients who were not administered. The efficacy of BTX-A treatment is associated with the elimination or reduction of anticholinergic therapy,<a class="elsevierStyleCrossRefs" href="#bib0160">11,17</a> so in those patients who need to continue this medication, we should suspect lack of efficacy or partial efficacy of botulinum toxin treatment.In our study, the only prognostic outcome regarding bladder volume (CBC) of treatment with BTX-A observed was the presence of permanent bladder catheter. This information has not been evaluated in other studies because, in most cases, among the criteria of inclusion, the need for patients to perform or the will to perform ICV is included. The presence of permanent bladder catheter is a known risk factor for the development of urological complications such as infections<a class="elsevierStyleCrossRef" href="#bib0195">18</a> and urinary stones.<a class="elsevierStyleCrossRef" href="#bib0200">19</a> Furthermore, it was found that its presence causes a progressive decrease in bladder capacity.<a class="elsevierStyleCrossRef" href="#bib0205">20</a>Our study shows that the effect of BTX-A on bladder capacity is maintained in 50% of patients up to 32 months. Most follow-up studies focus on the effectiveness of repeated treatment doses. Schurch et al.<a class="elsevierStyleCrossRef" href="#bib0165">12</a> calculate that the time after treatment in which bladder capacity remains above that of the control group is more than 24 weeks (6 months). Grise et al.<a class="elsevierStyleCrossRef" href="#bib0210">21</a> estimate that the median with regard to the reoccurrence of urinary incontinence in patients achieving continence after treatment with BTX-A is 168 days (approximately 6 months). It is possible that the urodynamic effect of BTX-A is longer than its clinical effect. In any case, it would be interesting to design a study to confirm our data.Among the limitations of our study, there is the fact that it is retrospective, so there could be some bias in information. The absence of a control group has less effect on the main objective, since the study of prognostic factors involves analyzing only the population under treatment. Its main strength is that it is the first study that analyzes the prognostic factors of treatment with BTX-A in patients with NDO.Conflict of interestThe authors declare that they have no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres485642" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec507912" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres485641" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec507911" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Material and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-09-29" "fechaAceptado" => "2014-11-18" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec507912" "palabras" => array:5 [ 0 => "Botulinum toxin" 1 => "Urodynamics" 2 => "Detrusor hyperactivity" 3 => "Neurogenic bladder" 4 => "Spinal cord injury" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec507911" "palabras" => array:5 [ 0 => "Toxina botulínica" 1 => "Urodinámica" 2 => "Hiperactividad del detrusor" 3 => "Vejiga neurógena" 4 => "Lesión medular" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectivesTo determine the urodynamic efficacy and factors that influence the urodynamic results of treatment of neurogenic detrusor hyperactivity with intradetrusor injection of botulinum toxin type A (BTX-A) in patients with spinal cord injury (SCI). Material and methodsA retrospective study was conducted with a cohort of 70 patients composed of 40 men and 30 women with stable SCI (mean age, 39±13.3 years) who underwent an intradetrusor injection of 300 IUs of BTX-A. A urodynamic study was conducted prior to the injection and 6±4.3 months after the treatment. New urodynamic studies were subsequently performed up to an interval of 16±12.2 months. ResultsThe BTX-A significantly increased (p<.05) the cystomanometric bladder capacity, the bladder volume of the first involuntary contraction of the detrusor and the postvoid residue. We observed a decrease that tended toward statistical significance (p<.1) of the maximum detrusor pressure and the maximum urine flow. Neither the bladder accommodation nor the urethral resistance index (bladder outlet obstruction index) varied significantly. The increase in vesical capacity was maintained in 50% of the sample for more than 32 months. Age, sex, anticholinergic treatment and lesion age showed no influence in terms of the increase in bladder capacity. The indwelling urinary catheter (IUC) was the only statistically significant negative factor. ConclusionsThe urodynamic effect of BTX-A is maintained for a considerable time interval. The IUC negatively influences the result of the treatment." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivosDeterminar la eficacia urodinámica y los factores que influyen en los resultados urodinámicos del tratamiento de la hiperactividad neurógena del detrusor con inyección intradetrusoriana de toxina botulínica tipo A (TXB-A) en pacientes con lesión medular (LM). Material y métodosSe realizó un estudio retrospectivo en una cohorte de 70 pacientes formada por 40 varones y 30 mujeres con LM estable de 39±13,3 años de edad (media±desviación típica), sometidos a inyección intradetrusoriana de 300UI de TXB-A. Se realizó un estudio urodinámico previo y otro a los 6±4,3 meses del tratamiento. Posteriormente se realizaron nuevos estudios urodinámicos hasta un intervalo de 16±12,2 meses. ResultadosLa TXB-A aumentó significativamene (p<0,05) la capacidad vesical cistomanométrica, el volumen vesical de la primera contracción involuntaria del detrusor y el residuo posmiccional. Se observó una disminución con tendencia hacia la significación estadística (p<0,1) de la presión máxima miccional del detrusor y el flujo miccional máximo. No varió significativamente la acomodación vesical ni el índice de resistencia uretral (BOOI). El aumento de la capacidad vesical se mantuvo en el 50% de la muestra más de 32 meses. La edad, el sexo, el tratamiento anticolinérgico y la antigüedad de la lesión no mostraron influencia respecto del aumento de la capacidad vesical. La sonda a permanencia (SVP) fue el único factor negativo estadísticamente significativo. ConclusionesEl efecto urodinámico de la TXB-A se mantiene durante un considerable intervalo de tiempo. La SVP influye negativamente en el resultado del tratamiento." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Gutiérrez-Martín P, Vírseda-Chamorro M, Salinas Casado J, Gómez-Rodríguez A, Esteban-Fuertes M. Factores que influyen en los resultados urodinámicos de la toxina botulínica en el tratamiento de la hiperactividad neurógena. Actas Urol Esp. 2015;39:217–221." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1455 "Ancho" => 1183 "Tamanyo" => 68295 ] ] "descripcion" => array:1 [ "en" => "Probability of recovery of basal cystomanometric bladder capacity in terms of follow-up." ] ] 1 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col">Level \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Degree</th><th class="td" title="table-head " align="left" valign="top" scope="col">Total \t\t\t\t\t\t\n \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Incomplete \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Complete \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">C1–C8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">D1–D4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">D5–L1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">28 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">L2-cauda equina \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab769293.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Distribution of the level and degree of spinal cord injury." ] ] 2 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "BOOI: urethral resistance index." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Parameter \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Baseline \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post treatment \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Significance \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Cystomanometric capacity (ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">188±110.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">247±144.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.002<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Filling pressure (cm H2O) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8±12.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7±8.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.580 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Volume 1st contraction (ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">121±70.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">196±117.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.003<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Maximum contraction pressure (cm H2O) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">56±25.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">52±25.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.496 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Peak flow (ml/s) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4±6.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2±3.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.057<a class="elsevierStyleCrossRef" href="#tblfn0010">**</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Maximum voiding pressure of the detrusor (cm H2O) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">68±36.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">52±36.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.066<a class="elsevierStyleCrossRef" href="#tblfn0010">**</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Post-void residual (ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">168±106.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">236±149.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.002<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">BOOI (cm H2O) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35±39.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37±26.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.851 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab769294.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "Significant differences (p<0.05)." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "**" "nota" => "Trend to significance (p<0.1)." ] ] ] "descripcion" => array:1 [ "en" => "Comparison of the distribution of urodynamic parameters before and after the first follow-up following injection of botulinum toxin." ] ] 3 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Parameter \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Ratio</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Significance \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Age (completed years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">r=−0.125 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.334 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Sex \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male244±158.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Female250±130.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.865 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Age of SCI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">r=−0.075 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.596 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Permanent catheter \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Present155±103.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Absent286±143.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.001<a class="elsevierStyleCrossRef" href="#tblfn0015">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Anticholinergic therapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Present246±140.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Absent251±176.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.920 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab769295.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "*" "nota" => "Significant differences." ] ] ] "descripcion" => array:1 [ "en" => "Relationship between previous clinical parameters and cystomanometric bladder capacity (ml) after the first follow-up after injection of botulinum toxin." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:21 [ 0 => array:3 [ "identificador" => "bib0110" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chapter 4: Guidelines for the diagnosis and treatment of overactive bladder (OAB) 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Factors that influence the urodynamic results of botulinum toxin in the treatment of neurogenic hyperactivity

Factores que influyen en los resultados urodinámicos de la toxina botulínica en el tratamiento de la hiperactividad neurógena

P. Gutiérrez-Martína,

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plgmartin@yahoo.co.uk

Corresponding author.

, M. Vírseda-Chamorrob, J. Salinas Casadoc, A. Gómez-Rodrígueza, M. Esteban-Fuertesb

a Servicio de Urología, Hospital Virgen de la Salud, Toledo, Spain

b Servicio de Urología, Hospital Nacional de Parapléjicos, Toledo, Spain

c Servicio de Urología, Hospital Clínico de san Carlos, Universidad Complutense, Madrid, Spain

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refractory to anticholinergic treatment at high doses &#40;oxybutynin 15<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41; &#40;55 cases&#41; or patient intolerance to anticholinergic treatment due to side effects &#40;15 cases&#41;&#46; In all cases&#44; botulinum toxin injection was performed for the first time&#44; and anticholinergic therapy was maintained in patients who were receiving it&#46; In 33 cases&#44; anticholinergics were associated with intermittent bladder catheterization and in 22 cases with permanent bladder catheter&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">All patients signed an informed consent&#46; Botulinum toxin being a licensed treatment as compassionate use for NDO&#44; and not being a clinical trial&#44; the study was not submitted to the approval of the scientific committee&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The patients included in the study underwent a medical history where the level and degree of spinal cord injury as well as their evolution time were determined&#44; and then a urodynamic study with a Solar polygraph &#40;MMS&#44; Enschede&#44; The Netherlands&#41;&#44; according to the specifications of the ICS<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">8</span></a> and the protocols of the Good Urodynamic Practice&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">9</span></a> In short&#44; patients were placed in the supine position and we proceeded to bladder filling through a two-way 8Fr catheter&#44; inserted transurethrally&#44; with saline at room temperature and a speed of 20<span class="elsevierStyleHsp" style=""></span>ml&#47;s&#46; The abdominal pressure was recorded using a catheter with transrectal balloon&#46; The filling phase ended when there was an involuntary detrusor contraction&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">In this study&#44; the following parameters were determined&#58; cystomanometric bladder capacity &#40;CBC&#41;&#44; the bladder volume at which the first involuntary contraction &#40;ICV&#41; took place&#44; the maximum pressure of the involuntary contraction &#40;IC maxP&#41;&#44; the filling pressure &#40;fillP&#41;&#44; maximum detrusor voiding pressure &#40;maxP&#41;&#44; maximum urinary flow &#40;Qmax&#41;&#44; post-void residual &#40;PVR&#41;&#44; and the index of urethral resistance &#40;BOOI&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">From February 2008 to December 2012&#44; a total of 70 patients were treated&#44; of 39<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;3 years of age &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation&#41;&#46; The sample consisted of 40 males and 30 females&#46; The age of the SCI was 167<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;3 months&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The botulinum toxin injection was performed with a dose of 300<span class="elsevierStyleHsp" style=""></span>IU of onabotulinum toxin A &#40;Botox<span class="elsevierStyleSup">&#174;</span> Allergan&#44; Inc&#46;&#44; Irving&#44; CA&#44; U&#46;S&#46;A&#46;&#41; spread over 30 locations with respect to the trigone&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The patients underwent a second study at 6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;3 months&#44; after injection of botulinum toxin&#46; After treatment&#44; patients were followed with new urodynamic studies to observe the evolution of urodynamic data for an average of 16<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;2 months &#40;range 3&#8211;45 months&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The results were stored in an ACCES<span class="elsevierStyleSup">&#174;</span> database and exported to the statistical program SPSS<span class="elsevierStyleSup">&#174;</span> for their analysis&#46; The statistical analysis consisted in applying the Fisher exact test for dichotomous variables&#44; the mean comparison test of Student&#39;s &#8220;<span class="elsevierStyleItalic">t</span>&#8221;-test for parametric variables&#44; both independent and paired&#44; the Pearson correlation coefficient&#44; and a survival analysis according to the Kaplan&#8211;Meier method&#46; The significance level was set at 95&#37; bilateral&#46; 10&#37; bilateral was considered a trend toward significance&#46; The values were expressed as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0075" class="elsevierStylePara elsevierViewall">The distribution by level and degree of spinal cord injury is shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">The variation of urodynamic parameters following injection of botulinum toxin is shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; We observed a significant increase of the CBC&#44; bladder volume at the first involuntary contraction&#44; and PR&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> analyzed the influence of clinical parameters on CBC after injection of botulinum toxin&#46; It was noted that the only significant difference was the presence of permanent bladder catheter&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Survival analysis showed that the median regarding the time taken for the CBC to return to baseline was 32 months &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0095" class="elsevierStylePara elsevierViewall">In our study&#44; we observed that injection of BTX-A significantly increased both CBC and ICV&#44; in addition to an increase in PR after 6 months of treatment&#46; However&#44; we observed no statistically significant differences from the fillP&#44; CI maxP&#44; Qmax&#44; maxP&#44; or BOOI&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">In randomized clinical trials &#40;RCTs&#41; on the effectiveness of botulinum toxin in patients with NDO&#44; a significant increase in both CBC and ICV is also observed&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a> Moreover&#44; a decrease in detrusor pressure is also demonstrated both during filling &#40;bladder compliance&#41; and during urination&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">11&#8211;13</span></a> These results have been corroborated by means of the meta-analysis conducted by Mehta et al&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">7</span></a> Only in two observational studies a significant decrease in detrusor pressure was not evidenced during filling&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">14&#44;15</span></a> In our study&#44; we also observed a decrease in maximum detrusor pressure during voiding and peak urinary flow&#44; although not reaching the proposed level of statistical significance &#40;5&#37; bilateral&#41;&#59; in both cases it was below 10&#37; bilateral &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;1&#41;&#44; indicating a tendency of significance&#44; which possibly with an increased sample size would have resulted in statistical significance&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Reduction in the maximum flow and maximum detrusor pressure during the voiding phase&#44; along with increased postvoid residue&#44; clinically confirmed that the mechanism of action of botulinum toxin is exerted on detrusor contractile activity&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">16</span></a> In our study&#44; we also observed that the rate of urethral resistance did not vary significantly after 6 months of treatment&#44; so it follows that the effects of botulinum toxin on the voiding phase are not due to an increase in urethral resistance&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Regarding the predictors of outcome of botulinum toxin in our study&#44; we observed that both patient age and sex&#44; the age of the injury&#44; or anticholinergic therapy did not influence the outcome of treatment with BTX-A at 6 months on bladder capacity&#46; In an RCT conducted by Neel<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">17</span></a> et al&#46; anticholinergic administration after injection of BTX-A did not significantly improve urodynamic results with respect to patients who were not administered&#46; The efficacy of BTX-A treatment is associated with the elimination or reduction of anticholinergic therapy&#44;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">11&#44;17</span></a> so in those patients who need to continue this medication&#44; we should suspect lack of efficacy or partial efficacy of botulinum toxin treatment&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">In our study&#44; the only prognostic outcome regarding bladder volume &#40;CBC&#41; of treatment with BTX-A observed was the presence of permanent bladder catheter&#46; This information has not been evaluated in other studies because&#44; in most cases&#44; among the criteria of inclusion&#44; the need for patients to perform or the will to perform ICV is included&#46; The presence of permanent bladder catheter is a known risk factor for the development of urological complications such as infections<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">18</span></a> and urinary stones&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">19</span></a> Furthermore&#44; it was found that its presence causes a progressive decrease in bladder capacity&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">20</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Our study shows that the effect of BTX-A on bladder capacity is maintained in 50&#37; of patients up to 32 months&#46; Most follow-up studies focus on the effectiveness of repeated treatment doses&#46; Schurch et al&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">12</span></a> calculate that the time after treatment in which bladder capacity remains above that of the control group is more than 24 weeks &#40;6 months&#41;&#46; Grise et al&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">21</span></a> estimate that the median with regard to the reoccurrence of urinary incontinence in patients achieving continence after treatment with BTX-A is 168 days &#40;approximately 6 months&#41;&#46; It is possible that the urodynamic effect of BTX-A is longer than its clinical effect&#46; In any case&#44; it would be interesting to design a study to confirm our data&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Among the limitations of our study&#44; there is the fact that it is retrospective&#44; so there could be some bias in information&#46; The absence of a control group has less effect on the main objective&#44; since the study of prognostic factors involves analyzing only the population under treatment&#46; Its main strength is that it is the first study that analyzes the prognostic factors of treatment with BTX-A in patients with NDO&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflict of interest</span><p id="par0130" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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            0 => "Botulinum toxin"
            1 => "Urodynamics"
            2 => "Detrusor hyperactivity"
            3 => "Neurogenic bladder"
            4 => "Spinal cord injury"
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            0 => "Toxina botul&#237;nica"
            1 => "Urodin&#225;mica"
            2 => "Hiperactividad del detrusor"
            3 => "Vejiga neur&#243;gena"
            4 => "Lesi&#243;n medular"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To determine the urodynamic efficacy and factors that influence the urodynamic results of treatment of neurogenic detrusor hyperactivity with intradetrusor injection of botulinum toxin type A &#40;BTX-A&#41; in patients with spinal cord injury &#40;SCI&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A retrospective study was conducted with a cohort of 70 patients composed of 40 men and 30 women with stable SCI &#40;mean age&#44; 39<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;3 years&#41; who underwent an intradetrusor injection of 300 IUs of BTX-A&#46; A urodynamic study was conducted prior to the injection and 6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;3 months after the treatment&#46; New urodynamic studies were subsequently performed up to an interval of 16<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;2 months&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The BTX-A significantly increased &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41; the cystomanometric bladder capacity&#44; the bladder volume of the first involuntary contraction of the detrusor and the postvoid residue&#46; We observed a decrease that tended toward statistical significance &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;1&#41; of the maximum detrusor pressure and the maximum urine flow&#46; Neither the bladder accommodation nor the urethral resistance index &#40;bladder outlet obstruction index&#41; varied significantly&#46; The increase in vesical capacity was maintained in 50&#37; of the sample for more than 32 months&#46; Age&#44; sex&#44; anticholinergic treatment and lesion age showed no influence in terms of the increase in bladder capacity&#46; The indwelling urinary catheter &#40;IUC&#41; was the only statistically significant negative factor&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The urodynamic effect of BTX-A is maintained for a considerable time interval&#46; The IUC negatively influences the result of the treatment&#46;</p></span>"
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            "titulo" => "Material and methods"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Determinar la eficacia urodin&#225;mica y los factores que influyen en los resultados urodin&#225;micos del tratamiento de la hiperactividad neur&#243;gena del detrusor con inyecci&#243;n intradetrusoriana de toxina botul&#237;nica tipo A &#40;TXB-A&#41; en pacientes con lesi&#243;n medular &#40;LM&#41;&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; un estudio retrospectivo en una cohorte de 70 pacientes formada por 40 varones y 30 mujeres con LM estable de 39<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#44;3 a&#241;os de edad &#40;media<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>desviaci&#243;n t&#237;pica&#41;&#44; sometidos a inyecci&#243;n intradetrusoriana de 300<span class="elsevierStyleHsp" style=""></span>UI de TXB-A&#46; Se realiz&#243; un estudio urodin&#225;mico previo y otro a los 6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;3 meses del tratamiento&#46; Posteriormente se realizaron nuevos estudios urodin&#225;micos hasta un intervalo de 16<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#44;2 meses&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La TXB-A aument&#243; significativamene &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41; la capacidad vesical cistomanom&#233;trica&#44; el volumen vesical de la primera contracci&#243;n involuntaria del detrusor y el residuo posmiccional&#46; Se observ&#243; una disminuci&#243;n con tendencia hacia la significaci&#243;n estad&#237;stica &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;1&#41; de la presi&#243;n m&#225;xima miccional del detrusor y el flujo miccional m&#225;ximo&#46; No vari&#243; significativamente la acomodaci&#243;n vesical ni el &#237;ndice de resistencia uretral &#40;BOOI&#41;&#46; El aumento de la capacidad vesical se mantuvo en el 50&#37; de la muestra m&#225;s de 32 meses&#46; La edad&#44; el sexo&#44; el tratamiento anticolin&#233;rgico y la antig&#252;edad de la lesi&#243;n no mostraron influencia respecto del aumento de la capacidad vesical&#46; La sonda a permanencia &#40;SVP&#41; fue el &#250;nico factor negativo estad&#237;sticamente significativo&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El efecto urodin&#225;mico de la TXB-A se mantiene durante un considerable intervalo de tiempo&#46; La SVP influye negativamente en el resultado del tratamiento&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Please cite this article as&#58; Guti&#233;rrez-Mart&#237;n P&#44; V&#237;rseda-Chamorro M&#44; Salinas Casado J&#44; G&#243;mez-Rodr&#237;guez A&#44; Esteban-Fuertes M&#46; Factores que influyen en los resultados urodin&#225;micos de la toxina botul&#237;nica en el tratamiento de la hiperactividad neur&#243;gena&#46; Actas Urol Esp&#46; 2015&#59;39&#58;217&#8211;221&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Probability of recovery of basal cystomanometric bladder capacity in terms of follow-up&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col">Level&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Degree</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Incomplete&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Complete&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">C1&#8211;C8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">D1&#8211;D4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">D5&#8211;L1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">L2-cauda equina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Distribution of the level and degree of spinal cord injury&#46;</p>"
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        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "tabla" => array:3 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">BOOI&#58; urethral resistance index&#46;</p>"
          "tablatextoimagen" => array:1 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Parameter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Baseline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Significance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Cystomanometric capacity &#40;ml&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">188<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>110&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">247<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>144&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;002<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Filling pressure &#40;cm H<span class="elsevierStyleInf">2</span>O&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;580&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Volume 1st contraction &#40;ml&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">121<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>70&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">196<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>117&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;003<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Maximum contraction pressure &#40;cm H<span class="elsevierStyleInf">2</span>O&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">56<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>25&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">52<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>25&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;496&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Peak flow &#40;ml&#47;s&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;057<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Maximum voiding pressure of the detrusor &#40;cm H<span class="elsevierStyleInf">2</span>O&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>36&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">52<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>36&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;066<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Post-void residual &#40;ml&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">168<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>106&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">236<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>149&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;002<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">BOOI &#40;cm H<span class="elsevierStyleInf">2</span>O&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>39&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>26&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;851&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Comparison of the distribution of urodynamic parameters before and after the first follow-up following injection of botulinum toxin&#46;</p>"
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        "tabla" => array:2 [
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Parameter&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;334&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Male244<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>158&#46;0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;865&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Age of SCI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;596&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Permanent catheter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Present155<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>103&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Absent286<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>143&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;001<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Anticholinergic therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Present246<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>140&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Absent251<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>176&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;920&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Relationship between previous clinical parameters and cystomanometric bladder capacity &#40;ml&#41; after the first follow-up after injection of botulinum toxin&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:21 [
            0 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chapter 4&#58; Guidelines for the diagnosis and treatment of overactive bladder &#40;OAB&#41; and neurogenic detrusor overactivity &#40;NDO&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46; Nambiar"
                            1 => "M&#46; Lucas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/nau.22631"
                      "Revista" => array:7 [
                        "tituloSerie" => "Neurourol Urodyn"
                        "fecha" => "2014"
                        "volumen" => "33"
                        "numero" => "Suppl&#46; 3"
                        "paginaInicial" => "S21"
                        "paginaFinal" => "S25"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25042139"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Systematic review of the epidemiology of urinary incontinence and detrusor overactivity among patients with neurogenic overactive bladder"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Ruffion"
                            1 => "D&#46; Castro-Diaz"
                            2 => "H&#46; Patel"
                            3 => "K&#46; Khalaf"
                            4 => "A&#46; Onyenwenyi"
                            5 => "D&#46; Globe"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000353274"
                      "Revista" => array:6 [
                        "tituloSerie" => "Neuroepidemiology"
                        "fecha" => "2013"
                        "volumen" => "41"
                        "paginaInicial" => "146"
                        "paginaFinal" => "155"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23942583"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chapter 2&#58; Pathophysiology of neurogenic detrusor overactivity and the symptom complex of overactive bladder"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "C&#46; Chapple"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/nau.22635"
                      "Revista" => array:7 [
                        "tituloSerie" => "Neurourol Urodyn"
                        "fecha" => "2014"
                        "volumen" => "33"
                        "numero" => "Suppl&#46; 3"
                        "paginaInicial" => "S6"
                        "paginaFinal" => "S13"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25042142"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "4"
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Article information

ISSN: 21735786
Original language: English

DOI:10.1016/j.acuroe.2015.03.004

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