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array:23 [ "pii" => "S2173578616300026" "issn" => "21735786" "doi" => "10.1016/j.acuroe.2016.02.012" "estado" => "S300" "fechaPublicacion" => "2016-05-01" "aid" => "772" "copyright" => "AEU" "copyrightAnyo" => "2014" "documento" => "article" "crossmark" => 1 "subdocumento" => "ssu" "cita" => "Actas Urol Esp. 2016;40:203-8" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 18 "formatos" => array:2 [ "HTML" => 10 "PDF" => 8 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0210480615001679" "issn" => "02104806" "doi" => "10.1016/j.acuro.2015.04.008" "estado" => "S300" "fechaPublicacion" => "2016-05-01" "aid" => "772" "copyright" => "AEU" "documento" => "article" "crossmark" => 1 "subdocumento" => "ssu" "cita" => "Actas Urol Esp. 2016;40:203-8" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 227 "formatos" => array:3 [ "EPUB" => 2 "HTML" => 157 "PDF" => 68 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Artículo de revisión</span>" "titulo" => "Vacuna oral (OM-89) en la profilaxis de infección urinaria recurrente: una revisión sistemática realista con metaanálisis" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "203" "paginaFinal" => "208" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Oral vaccine (OM-89) in the recurrent urinary tract infection prophylaxis: a realistic systematic review with meta-analysis" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figura 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 904 "Ancho" => 3219 "Tamanyo" => 290382 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Disuria a los 6 meses.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "K.A. Taha Neto, L. Nogueira Castilho, L.O. Reis" "autores" => array:3 [ 0 => array:2 [ "nombre" => "K.A." "apellidos" => "Taha Neto" ] 1 => array:2 [ "nombre" => "L." "apellidos" => "Nogueira Castilho" ] 2 => array:2 [ "nombre" => "L.O." "apellidos" => "Reis" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173578616300026" "doi" => "10.1016/j.acuroe.2016.02.012" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173578616300026?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210480615001679?idApp=UINPBA00004N" "url" => "/02104806/0000004000000004/v1_201604260021/S0210480615001679/v1_201604260021/es/main.assets" ] ] "itemSiguiente" => array:18 [ "pii" => "S2173578616300038" "issn" => "21735786" "doi" => "10.1016/j.acuroe.2016.02.013" "estado" => "S300" "fechaPublicacion" => "2016-05-01" "aid" => "805" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Actas Urol Esp. 2016;40:209-16" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 16 "formatos" => array:2 [ "HTML" => 11 "PDF" => 5 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Treatment trends for clinically localized prostate cancer. National population analysis: GESCAP group" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "209" "paginaFinal" => "216" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tendencias de tratamiento en el cáncer de próstata clínicamente localizado. Análisis poblacional a nivel nacional: grupo GESCAP" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "B. Miñana, A. Rodríguez-Antolín, F. Gómez-Veiga, C. Hernández, J.F. Suárez, J.M. Fernández-Gómez, M. Unda, J. Burgos, A. Alcaraz, P. Rodríguez, C. Moreno, E. Pedrosa, J.M. Cózar" "autores" => array:14 [ 0 => array:2 [ "nombre" => "B." "apellidos" => "Miñana" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Rodríguez-Antolín" ] 2 => array:2 [ "nombre" => "F." "apellidos" => "Gómez-Veiga" ] 3 => array:2 [ "nombre" => "C." "apellidos" => "Hernández" ] 4 => array:2 [ "nombre" => "J.F." "apellidos" => "Suárez" ] 5 => array:2 [ "nombre" => "J.M." "apellidos" => "Fernández-Gómez" ] 6 => array:2 [ "nombre" => "M." "apellidos" => "Unda" ] 7 => array:2 [ "nombre" => "J." "apellidos" => "Burgos" ] 8 => array:2 [ "nombre" => "A." "apellidos" => "Alcaraz" ] 9 => array:2 [ "nombre" => "P." "apellidos" => "Rodríguez" ] 10 => array:2 [ "nombre" => "C." "apellidos" => "Moreno" ] 11 => array:2 [ "nombre" => "E." "apellidos" => "Pedrosa" ] 12 => array:2 [ "nombre" => "J.M." "apellidos" => "Cózar" ] 13 => array:1 [ "colaborador" => "representing the Spanish Prostate Cancer Group (GESCAP)" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0210480615002454" "doi" => "10.1016/j.acuro.2015.09.005" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210480615002454?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173578616300038?idApp=UINPBA00004N" "url" => "/21735786/0000004000000004/v1_201604260030/S2173578616300038/v1_201604260030/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review article</span>" "titulo" => "Oral vaccine (OM-89) in the recurrent urinary tract infection prophylaxis: A realistic systematic review with meta-analysis" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "203" "paginaFinal" => "208" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "K.A. Taha Neto, L. Nogueira Castilho, L.O. Reis" "autores" => array:3 [ 0 => array:3 [ "nombre" => "K.A." "apellidos" => "Taha Neto" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "L." "apellidos" => "Nogueira Castilho" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:4 [ "nombre" => "L.O." "apellidos" => "Reis" "email" => array:1 [ 0 => "reisleo.l@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Faculty of Medicine, Center of Life Sciences, Pontifical Catholic University of Campinas, PUC-Campinas, Campinas, São Paulo, Brazil" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Radium Institute, Campinas, São Paulo, Brazil" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Vacuna oral (OM-89) en la profilaxis de infección urinaria recurrente: una revisión sistemática realista con metaanálisis" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 844 "Ancho" => 3240 "Tamanyo" => 218921 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Urinary tract infection at 6 months.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The urinary tract infection (UTI) is considered to be the most common bacterial infection and also is one of the most frequent pathologies in the world accounting for much of the infectious process, especially in women, ranging from asymptomatic bacteriuria to severe cases of pyelonephritis.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Recently, UTI accounted for nearly 7 million office visits and 1 million emergency department visits, resulting in 100,000 hospitalizations/year.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> Approximately 33% of women aged 20–40 years reported at least one episode of treatment for UTI and 10% of women reported an episode of recurrent infection during their lives.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Escherichia coli</span> is the most common pathogen in the UTI, involving the upper and lower urinary tract, accounting for over 85% cystitis and for more than 60% of recurrent cystitis. UTI is defined as recurrent if there are at least two episodes in 6 months or 3 episodes in 12 months.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">3,4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Due to the enormous incidence of UTI, with major socio-economic implications, there is a concern to prevent recurrences in various ways such as: antibiotic prophylaxis (increasing the risk of bacterial resistance), natural ingredients (cranberry juice, probiotics), and immunization.</p><p id="par0025" class="elsevierStylePara elsevierViewall">While for antibiotic prophylaxis and natural ingredients, once discontinued, new episodes of recurrent UTI are common,<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">5</span></a> immunization confers a striking rational with durable protection.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">6</span></a> Among the different forms of immunoprophylaxis available, the oral immunostimulant OM-89 is the most studied in the literature, providing placebo-controlled studies for a potential meta-analysis.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">Escherichia coli</span> extract (OM-89), whose active ingredient is the bacterial lysate acts as a vaccine, stimulating T-lymphocytes, inducing interferon production, increasing the endogenous level of IgA in the urine and activating the monocyte derived dendritic cells.<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">7,8</span></a> Several studies have shown to decrease the recurrence of UTI, especially cystitis, as well as improvement in laboratory parameters and symptoms with the use of oral OM-89; however, there are only a few prospective randomized studies on the issue, dated from over 10 years.<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">9,10</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The main objective of this study is to evaluate the efficacy of oral OM-89 in the prophylaxis of recurrent uncomplicated UTI through a focused contemporary systematic review and meta-analysis.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><p id="par0040" class="elsevierStylePara elsevierViewall">This systematic review included double-blind randomized trials associating the use of extract of <span class="elsevierStyleItalic">E. coli</span> with prevention of recurrent uncomplicated UTI. All studies utilized orally administrated OM-89, 6<span class="elsevierStyleHsp" style=""></span>mg daily.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Research strategy</span><p id="par0045" class="elsevierStylePara elsevierViewall">Research in English scientific publications related to “oral OM-89”, and “urinary tract infection” and “immune-stimulation” or “bacterial vaccine” or “antibiotic prophylaxis”, including the following databases: PubMed, MEDLINE and Cochrane Collaboration. Publications from key references were also consulted.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Selection criteria for studies</span><p id="par0050" class="elsevierStylePara elsevierViewall">We have identified 15 double-blind randomized trials related to recurrent urinary tract infection and use of OM-89.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Inclusion criteria were double-blind randomized trials using orally administered OM-89, 6<span class="elsevierStyleHsp" style=""></span>mg daily, during three months with a minimum of three months of follow-up. Outcomes were the frequency of bacteriuria in 3 and 6 months, dysuria in 6 months, and acute cystitis in 6 months.</p><p id="par0060" class="elsevierStylePara elsevierViewall">After methodological analysis, 10 papers were excluded due to poor quality, characterized by not attending at least three of the following criteria: randomization method, allocation concealment, masking of evaluators, masking of patients, masking of researchers, description of “drop-outs”, predetermined sample size, analysis by intention to treat (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">After selection criteria, five double blinding studies, with description of “drop-outs” were used for data analysis according to PRISMA flow chart diagram<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">11</span></a> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Data extraction</span><p id="par0070" class="elsevierStylePara elsevierViewall">Three independent reviewers extracted the data from all studies. The outcomes analyzed were the frequency of bacteriuria in 3 and 6 months, dysuria in 6 months, and acute cystitis in 6 months. The name of the authors and the years of publication of the article were used for identification purposes.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0075" class="elsevierStylePara elsevierViewall">All meta-analyses were performed using Review Manager 5 (RevMan 5; The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) with random effects model. Dichotomous data were compared using odds ratio (OR).</p><p id="par0080" class="elsevierStylePara elsevierViewall">Confidence intervals of 95% (CI) were calculated for each estimate and presented in forest plots. The OR symbolized by a solid diamond at the bottom of the plot of the forest (the width of which represents the 95% CI) is the best estimate of the result (pooled) true.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Data were combined into a pre-determined subgroup and sensitivity analyses were performed to test the stability of our conclusions. The heterogeneity of the groups in the results was assessed using the Chi-square test and was expressed by the <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> index, as described by Higgins and colleagues.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">12</span></a> When a significant heterogeneity was detected (<span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>35%), a possible explanation for this was pursued.</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0090" class="elsevierStylePara elsevierViewall">Of the 5 selected studies, we observed that the date of publication ranged from 1985 to 2005: Frey (1986),<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">3</span></a> Tammen (1990),<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">14</span></a> Schulman (1993),<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">13</span></a> Magasi (1994)<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">8</span></a> and Bauer (2005).<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">1</span></a> We studied 396 patients in the OM-89 group and 392 in the control group. Overall there were 61 dropouts in the control group and 76 in the OM-89 group.</p><p id="par0095" class="elsevierStylePara elsevierViewall">As a major limitation, there was no appropriate description of their methodologies and none of the studies presented related term describing conflict of interest or commitment to the pharmaceutical industry.</p><p id="par0100" class="elsevierStylePara elsevierViewall">All studies were multi-centric and described dropouts, except for Magasis's and Tammen's study, which show no clarity on allocation concealment (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Bacteriuria at 3 months</span><p id="par0105" class="elsevierStylePara elsevierViewall">Regarding the maintenance of bacteriuria at 3 months through urinalysis, according to the number of bacteria per mL in urine samples, only Frey's, Schulman's and Magasi's works could be included.</p><p id="par0110" class="elsevierStylePara elsevierViewall">Comparing OM-89 and control groups, maintenance of bacteriuria at 3 months occurred in 18.4% (29/157) and 45.7% (70/153), respectively; showing benefit with the use of the extract of <span class="elsevierStyleItalic">E. coli</span>, odds ratio of 0.28.</p><p id="par0115" class="elsevierStylePara elsevierViewall">However, taking into account the heterogeneity of the groups, we obtained an <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span>: 78%, denoting high diversity (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Bacteriuria at 6 months</span><p id="par0120" class="elsevierStylePara elsevierViewall">Regarding the maintenance of bacteriuria at 6 months through urinalysis, according to the number of bacteria per mL in urine samples, representing the consolidation period of protection; again, only Frey's, Schulman's and Magasi's works could be included.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Comparing OM-89 and control groups, maintenance of bacteriuria at 6 months occurred in 13.2% (21/159) and 29.4% (45/153), respectively; odds ratio 0.36, in favor of OM-89, with high heterogeneity, <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span>: 41% (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Dysuria at 6 months</span><p id="par0130" class="elsevierStylePara elsevierViewall">All studies could be included in the analysis of dysuria at 6 months (Frey, Tammen, Schulman, Magasi and Bauer).</p><p id="par0135" class="elsevierStylePara elsevierViewall">Comparing OM-89 and control groups, dysuria at 6 months occurred in 7.5% (29/385) and 18.9% (73/385), respectively; odds ratio 0.35, in favor of OM-89, with low heterogeneity, <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span>: 0% (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Acute cystitis at 6 months</span><p id="par0140" class="elsevierStylePara elsevierViewall">The presence of acute cystitis at 6 months was identified by the typical symptoms of infection plus urinalysis, according to the number of bacteria per mL in urine samples. Studies included in this analysis: Frey, Tammen, Magasi and Bauer.</p><p id="par0145" class="elsevierStylePara elsevierViewall">Comparing OM-89 and control groups, acute cystitis at 6 months occurred in 45% (145/322) and 65.4% (212/324), respectively; odds ratio of 0.43, in favor of OM-89, with high heterogeneity, <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span>: 77% (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>).</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Discussion</span><p id="par0150" class="elsevierStylePara elsevierViewall">Although this meta-analysis shows the efficacy of OM-89 in the improvement of UTI, there are no data beyond 6 months, essential to validate the results. Additionally, unfortunately, there are no studies comparing directly antimicrobial prophylaxis with immunoactive prophylaxis, room for future studies.</p><p id="par0155" class="elsevierStylePara elsevierViewall">Among many limitations (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>), there was no adequate information on the methodologies regarding the method of randomization, the masking type, the description of outputs, the source of potential conflict of interest related to sponsorship provided by the pharmaceutical industry since they have interest to prove the benefit of the drug. Only Bauer et al. presented analysis by intention to treat.</p><p id="par0160" class="elsevierStylePara elsevierViewall">Because of these limitations and considering the poor quality of the studies analyzed, we put in doubt the validation of the meta-analysis on this issue, including the previously published,<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">9,10,15,16</span></a> resulting in a high heterogeneity in the data analyzed, especially in relation to bacteriuria and urinary tract infection.</p><p id="par0165" class="elsevierStylePara elsevierViewall">Furthermore, the definition of bacteriuria and UTI varied among studies. UTI: >10<span class="elsevierStyleSup">4</span> CFUs (Frey et al.); >10<span class="elsevierStyleSup">3</span> CFUs or two of the following symptoms for two days, dysuria, pollakiuria, burning (Bauer et al.); >10<span class="elsevierStyleSup">5</span> CFUs (Schulman et al., Tammen, Magasi et al.). Bacteriuria was better described only in the study of Schulman et al. (>10<span class="elsevierStyleSup">4</span> CFUs), while all the others considered bacteriuria as UTI synonyms, except for the symptoms.</p><p id="par0170" class="elsevierStylePara elsevierViewall">We realize that all works on the subject (<span class="elsevierStyleItalic">E. coli</span> extract) conclude in favor of the product. There is no work with negative results regarding the use of the OM-89, which could be considered a very important bias for this type of study, since it is a relatively unexplored subject. Some data may have been discarded or remained unpublished when negative or inexpressive results were found regarding the use of the product (publication bias). Also, no abstracts presented at meetings were included.</p><p id="par0175" class="elsevierStylePara elsevierViewall">Another interesting finding is the fact that the previous meta-analysis on the subject, virtually all funded by the pharmaceutical industry, included data that did not even come to be published in peer reviewed journal (Pisani G., 1992)<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">10,15,16</span></a> or was limited to UTI analysis, involving miscellaneous prophylactic agents (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>7), including acupuncture.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">9</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">Future trials are necessary, using uniform outcomes and definitions and including antimicrobial prophylaxis, which is the standard of care, once the effectiveness of non-antibiotic agents is substantially less than that of antibiotic prophylaxis.</p><p id="par0185" class="elsevierStylePara elsevierViewall">Additionally, data on quality of life, patient preference, and cost-effectiveness are lacking and should be considered to guide clinical practice and meta-analyses should obtain original research data on individual participants enrolled in trials as the gold standard methodology, not possible in the current work given that available studies are over 10 years old.</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conclusions</span><p id="par0190" class="elsevierStylePara elsevierViewall">Current literature on prospective randomized controlled trials evaluating the use of oral OM-89 vaccine in the recurrent urinary tract infection prophylaxis is of low quality, limited to the first six months only and with variable definition of bacteriuria and UTI. Although all studies show benefit in favor of vaccine, no robust trial was identified, resulting in a high heterogeneity in the data analyzed. Also, publication bias could not be excluded and future higher quality studies are warranted adding intermediate (>12 months) and long-term follow-up.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflict of interest</span><p id="par0195" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres631154" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec644007" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres631155" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec644008" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Research strategy" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Selection criteria for studies" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Data extraction" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0035" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Bacteriuria at 3 months" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Bacteriuria at 6 months" ] 2 => array:2 [ "identificador" => "sec0050" "titulo" => "Dysuria at 6 months" ] 3 => array:2 [ "identificador" => "sec0055" "titulo" => "Acute cystitis at 6 months" ] ] ] 7 => array:2 [ "identificador" => "sec0060" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0065" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0070" "titulo" => "Conflict of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-12-23" "fechaAceptado" => "2015-04-17" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec644007" "palabras" => array:6 [ 0 => "Bacterial vaccines" 1 => "Active immunization" 2 => "<span class="elsevierStyleItalic">Escherichia coli</span>" 3 => "Urinary tract infection" 4 => "Cystitis" 5 => "Dysuria" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec644008" "palabras" => array:6 [ 0 => "Vacunas bacterianas" 1 => "Inmunización activa" 2 => "Escherichia coli" 3 => "Infección del tracto urinario" 4 => "Cistitis" 5 => "Disuria" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To evaluate the efficacy of <span class="elsevierStyleItalic">Escherichia coli</span> extract (OM-89) in the prophylaxis of recurrent uncomplicated urinary tract infection (UTI) through a contemporary systematic review and meta-analysis.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Inclusion criteria were double-blind randomized trials using orally administrated OM-89, 6<span class="elsevierStyleHsp" style=""></span>mg daily, during three months with a minimum of three months of monitoring. Outcomes were the frequency of bacteriuria in 3 and 6 months, dysuria in 6 months and UTI in 6 months. Databases: PubMed, MEDLINE, Cochrane Collaboration and their key references. After analysis by three independent reviewers, 15 double-blind randomized trials were identified, 10 papers excluded due to methods flaws and 5 used for data analysis due to double blinding and reporting drop-outs.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Among 5 selected studies the date of publication ranged from 1985 to 2005, totalizing 396 patients in the OM-89 group and 392 in the control group. Overall, there were 61 dropouts in the control group and 76 in the OM-89 group. As a major limitation there was no appropriate description of their methodologies and none of the studies described conflict of interest or commitment to the pharmaceutical industry. All studies were multi-centric, except for two, which showed no clarity on allocation concealment. All studies show benefit in favor of vaccine.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Current literature on prospective randomized controlled trials evaluating the use of oral OM-89 vaccine in the recurrent UTI prophylaxis is of low quality, limited to the first six months only and with variable definition of bacteriuria and UTI. Although all studies show benefit in favor of vaccine, no robust trial was identified, resulting in a high heterogeneity in the data analyzed. Also, publication bias could not be excluded and future higher quality studies are warranted adding intermediate (>12 months) and long-term follow-up.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Evaluar la eficacia del extracto de Escherichia coli (OM-89) en la profilaxis de la infección del tracto urinario (ITU) no complicada recurrente a través de una revisión sistemática contemporánea y metaanálisis.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Los criterios de inclusión fueron ensayos aleatorios doble ciego usando 6<span class="elsevierStyleHsp" style=""></span>mg al día de OM-89 administrado por vía oral durante 3 meses, con un mínimo de 3 meses de seguimiento. Los resultados fueron la frecuencia de bacteriuria en 3 y 6 meses, disuria en 6 meses e ITU en 6 meses. Bases de datos: PubMed, MEDLINE, Cochrane Collaboration y sus referencias clave. Tras el análisis por 3 revisores independientes se identificaron 15 ensayos aleatorizados doble ciego, 10 documentos fueron excluidos debido a defectos de los métodos y 5 utilizados para el análisis de datos debido al doble cegamiento y la presentación de informes de abandonos.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Entre 5 estudios seleccionados la fecha de publicación varió desde 1985 hasta 2005, totalizando 396 pacientes en el grupo OM-89 y 392 en el grupo control. En total, hubo 61 abandonos en el grupo control y 76 en el grupo OM-89. Como una importante limitación no hubo descripción apropiada de sus metodologías, y ninguno de los estudios describió conflicto de intereses o compromiso con la industria farmacéutica. Todos los estudios fueron multicéntricos, a excepción de 2, que no mostraron claridad sobre ocultamiento de la asignación. Todos los estudios muestran beneficios a favor de la vacuna.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La literatura actual sobre ensayos controlados aleatorizados prospectivos que evalúan el uso de la vacuna oral de OM-89 en la profilaxis recurrente de ITU es de baja calidad, limitada únicamente a los primeros 6 meses y con definición variable de bacteriuria e ITU. Aunque todos los estudios muestran beneficio a favor de la vacuna, no se identificó ningún ensayo robusto, resultando en una alta heterogeneidad en los datos analizados. Además, el sesgo de publicación no pudo excluirse, y futuros estudios de mayor calidad están garantizados añadiendo seguimiento a medio (>12 meses) y largo plazo.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Taha Neto KA, Nogueira Castilho L, Reis LO. Vacuna oral (OM-89) en la profilaxis de infección urinaria recurrente: una revisión sistemática realista con metaanálisis. Actas Urol Esp. 2016;40:203–208.</p>" ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2463 "Ancho" => 2484 "Tamanyo" => 272985 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">PRISMA flow chart diagram.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 735 "Ancho" => 3221 "Tamanyo" => 209670 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Bacteriuria at 3 months.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 764 "Ancho" => 3259 "Tamanyo" => 204592 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Bacteriuria at 6 months.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 895 "Ancho" => 3219 "Tamanyo" => 256731 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Dysuria at 6 months.</p>" ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 844 "Ancho" => 3240 "Tamanyo" => 218921 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Urinary tract infection at 6 months.</p>" ] ] 5 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "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="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="5" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Author</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">Tammen \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">Schulman \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">Bauer \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">Frey \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">Magasi \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Randomization method \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Appropriate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unclear \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unclear \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unclear \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Appropriate \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Allocation concealment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unclear \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unclear \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Inappropriate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unclear \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unclear \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Masking of evaluators \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Masking of patients \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Masking of researchers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Description of “drop-outs” \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sample size predetermined \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Analysis by intention to treat \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Multicenter study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sponsorship \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unclear \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unclear \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unclear \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unclear \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unclear \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1035441.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Methodology of the clinical trials.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:16 [ 0 => array:3 [ "identificador" => "bib0085" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A long-term, multicenter, double-blind study of an <span class="elsevierStyleItalic">Escherichia coli</span> extract (OM-89) in female patients with recurrent urinary tract infections" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "H.W. 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