Interleukin-6 blocking agents for treating COVID-19: a living systematic review.

BACKGROUND: It has been reported that people with COVID-19 and pre-existing autoantibodies against type I interferons are likely to develop an inflammatory cytokine storm responsible for severe respiratory symptoms. Since interleukin 6 (IL-6) is one of the cytokines released during this inflammatory process, IL-6 blocking agents have been used for treating people with severe COVID-19. OBJECTIVES: To update the evidence on the effectiveness and safety of IL-6 blocking agents compared to standard care alone or to a placebo for people with COVID-19. SEARCH METHODS: We searched the World Health Organization (WHO) International Clinical Trials Registry Platform, the Living OVerview of Evidence (L·OVE) platform, and the Cochrane COVID-19 Study Register to identify studies on 7 June 2022. SELECTION CRITERIA: We included randomized controlled trials (RCTs) evaluating IL-6 blocking agents compared to standard care alone or to placebo for people with COVID-19, regardless of disease severity. DATA COLLECTION AND ANALYSIS: Pairs of researchers independently conducted study selection, extracted data and assessed risk of bias. We assessed the certainty of evidence using the GRADE approach for all critical and important outcomes. In this update we amended our protocol to update the methods used for grading evidence by establishing minimal important differences for the critical outcomes. MAIN RESULTS: This update includes 22 additional trials, for a total of 32 trials including 12,160 randomized participants all hospitalized for COVID-19 disease. We identified a further 17 registered RCTs evaluating IL-6 blocking agents without results available as of 7 June 2022.  The mean age range varied from 56 to 75 years; 66.2% (8051/12,160) of enrolled participants were men. One-third (11/32) of included trials were placebo-controlled. Twenty-two were published in peer-reviewed journals, three were reported as preprints, two trials had results posted only on registries, and results from five trials were retrieved from another meta-analysis. Eight were funded by pharmaceutical companies.  Twenty-six included studies were multicenter trials; four were multinational and 22 took place in single countries. Recruitment of participants occurred between February 2020 and June 2021, with a mean enrollment duration of 21 weeks (range 1 to 54 weeks). Nineteen trials (60%) had a follow-up of 60 days or more. Disease severity ranged from mild to critical disease. The proportion of participants who were intubated at study inclusion also varied from 5% to 95%. Only six trials reported vaccination status; there were no vaccinated participants included in these trials, and 17 trials were conducted before vaccination was rolled out. We assessed a total of six treatments, each compared to placebo or standard care. Twenty trials assessed tocilizumab, nine assessed sarilumab, and two assessed clazakizumab. Only one trial was included for each of the other IL-6 blocking agents (siltuximab, olokizumab, and levilimab). Two trials assessed more than one treatment. Efficacy and safety of tocilizumab and sarilumab compared to standard care or placebo for treating COVID-19 At day (D) 28, tocilizumab and sarilumab probably result in little or no increase in clinical improvement (tocilizumab: risk ratio (RR) 1.05, 95% confidence interval (CI) 1.00 to 1.11; 15 RCTs, 6116 participants; moderate-certainty evidence; sarilumab: RR 0.99, 95% CI 0.94 to 1.05; 7 RCTs, 2425 participants; moderate-certainty evidence). For clinical improvement at ≥ D60, the certainty of evidence is very low for both tocilizumab (RR 1.10, 95% CI 0.81 to 1.48; 1 RCT, 97 participants; very low-certainty evidence) and sarilumab (RR 1.22, 95% CI 0.91 to 1.63; 2 RCTs, 239 participants; very low-certainty evidence). The effect of tocilizumab on the proportion of participants with a WHO Clinical Progression Score (WHO-CPS) of level 7 or above remains uncertain at D28 (RR 0.90, 95% CI 0.72 to 1.12; 13 RCTs, 2117 participants; low-certainty evidence) and that for sarilumab very uncertain (RR 1.10, 95% CI 0.90 to 1.33; 5 RCTs, 886 participants; very low-certainty evidence). Tocilizumab reduces all cause-mortality at D28 compared to standard care/placebo (RR 0.88, 95% CI 0.81 to 0.94; 18 RCTs, 7428 participants; high-certainty evidence). The evidence about the effect of sarilumab on this outcome is very uncertain (RR 1.06, 95% CI 0.86 to 1.30; 9 RCTs, 3305 participants; very low-certainty evidence). The evidence is uncertain for all cause-mortality at ≥ D60 for tocilizumab (RR 0.91, 95% CI 0.80 to 1.04; 9 RCTs, 2775 participants; low-certainty evidence) and very uncertain for sarilumab (RR 0.95, 95% CI 0.84 to 1.07; 6 RCTs, 3379 participants; very low-certainty evidence). Tocilizumab probably results in little to no difference in the risk of adverse events (RR 1.03, 95% CI 0.95 to 1.12; 9 RCTs, 1811 participants; moderate-certainty evidence). The evidence about adverse events for sarilumab is uncertain (RR 1.12, 95% CI 0.97 to 1.28; 4 RCT, 860 participants; low-certainty evidence).  The evidence about serious adverse events is very uncertain for tocilizumab (RR 0.93, 95% CI 0.81 to 1.07; 16 RCTs; 2974 participants; very low-certainty evidence) and uncertain for sarilumab (RR 1.09, 95% CI 0.97 to 1.21; 6 RCTs; 2936 participants; low-certainty evidence). Efficacy and safety of clazakizumab, olokizumab, siltuximab and levilimab compared to standard care or placebo for treating COVID-19 The evidence about the effects of clazakizumab, olokizumab, siltuximab, and levilimab comes from only one or two studies for each blocking agent, and is uncertain or very uncertain. AUTHORS' CONCLUSIONS: In hospitalized people with COVID-19, results show a beneficial effect of tocilizumab on all-cause mortality in the short term and probably little or no difference in the risk of adverse events compared to standard care alone or placebo. Nevertheless, both tocilizumab and sarilumab probably result in little or no increase in clinical improvement at D28. Evidence for an effect of sarilumab and the other IL-6 blocking agents on critical outcomes is uncertain or very uncertain. Most of the trials included in our review were done before the waves of different variants of concern and before vaccination was rolled out on a large scale. An additional 17 RCTs of IL-6 blocking agents are currently registered with no results yet reported. The number of pending studies and the number of participants planned is low. Consequently, we will not publish further updates of this review.

Comparison of different human papillomavirus (HPV) vaccine types and dose schedules for prevention of HPV-related disease in females and males.

BACKGROUND: Uptake of human papillomavirus (HPV) vaccine remains low in many countries, although the bivalent and quadrivalent HPV vaccines given as a three-dose schedule are effective in the prevention of precancerous lesions of the cervix in women. Simpler immunisation schedules, such as those with fewer doses, might reduce barriers to vaccination, as may programmes that include males. OBJECTIVES: To evaluate the efficacy, immunogenicity, and harms of different dose schedules and different types of HPV vaccines in females and males. SEARCH METHODS: We conducted electronic searches on 27 September 2018 in Ovid MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL) (in the Cochrane Library), and Ovid Embase. We also searched the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov (both 27 September 2018), vaccine manufacturer websites, and checked reference lists from an index of HPV studies and other relevant systematic reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with no language restriction. We considered studies if they enrolled HIV-negative males or females aged 9 to 26 years, or HIV-positive males or females of any age. DATA COLLECTION AND ANALYSIS: We used methods recommended by Cochrane. We use the term 'control' to refer to comparator products containing an adjuvant or active vaccine and 'placebo' to refer to products that contain no adjuvant or active vaccine. Most primary outcomes in this review were clinical outcomes. However, for comparisons comparing dose schedules, the included RCTs were designed to measure antibody responses (i.e. immunogenicity) as the primary outcome, rather than clinical outcomes, since it is unethical to collect cervical samples from girls under 16 years of age. We analysed immunogenicity outcomes (i.e. geometric mean titres) with ratios of means, clinical outcomes (e.g. cancer and intraepithelial neoplasia) with risk ratios or rate ratios and, for serious adverse events and deaths, we calculated odds ratios. We rated the certainty of evidence with GRADE. MAIN RESULTS: We included 20 RCTs with 31,940 participants. The length of follow-up in the included studies ranged from seven months to five years. Two doses versus three doses of HPV vaccine in 9- to 15-year-old females Antibody responses after two-dose and three-dose HPV vaccine schedules were similar after up to five years of follow-up (4 RCTs, moderate- to high-certainty evidence). No RCTs collected clinical outcome data. Evidence about serious adverse events in studies comparing dose schedules was of very low-certainty owing to imprecision and indirectness (three doses 35/1159; two doses 36/1158; 4 RCTs). One death was reported in the three-dose group (1/898) and none in the two-dose group (0/899) (low-certainty evidence). Interval between doses of HPV vaccine in 9- to 14-year-old females and males Antibody responses were stronger with a longer interval (6 or 12 months) between the first two doses of HPV vaccine than a shorter interval (2 or 6 months) at up to three years of follow-up (4 RCTs, moderate- to high-certainty evidence). No RCTs collected data about clinical outcomes. Evidence about serious adverse events in studies comparing intervals was of very low-certainty, owing to imprecision and indirectness. No deaths were reported in any of the studies (0/1898, 3 RCTs, low-certainty evidence). HPV vaccination of 10- to 26-year-old males In one RCT there was moderate-certainty evidence that quadrivalent HPV vaccine, compared with control, reduced the incidence of external genital lesions (control 36 per 3081 person-years; quadrivalent 6 per 3173 person-years; rate ratio 0.16, 95% CI 0.07 to 0.38; 6254 person-years) and anogenital warts (control 28 per 2814 person-years; quadrivalent 3 per 2831 person-years; rate ratio 0.11, 95% CI 0.03 to 0.38; 5645 person-years). The quadrivalent vaccine resulted in more injection-site adverse events, such as pain or redness, than control (537 versus 601 per 1000; risk ratio (RR) 1.12, 95% CI 1.06 to 1.18, 3895 participants, high-certainty evidence). There was very low-certainty evidence from two RCTs about serious adverse events with quadrivalent vaccine (control 12/2588; quadrivalent 8/2574), and about deaths (control 11/2591; quadrivalent 3/2582), owing to imprecision and indirectness. Nonavalent versus quadrivalent vaccine in 9- to 26-year-old females and males Three RCTs were included; one in females aged 9- to 15-years (n = 600), one in females aged 16- to 26-years (n = 14,215), and one in males aged 16- to 26-years (n = 500). The RCT in 16- to 26-year-old females reported clinical outcomes. There was little to no difference in the incidence of the combined outcome of high-grade cervical epithelial neoplasia, adenocarcinoma in situ, or cervical cancer between the HPV vaccines (quadrivalent 325/6882, nonavalent 326/6871; OR 1.00, 95% CI 0.85 to 1.16; 13,753 participants; high-certainty evidence). The other two RCTs did not collect data about clinical outcomes. There were slightly more local adverse events with the nonavalent vaccine (905 per 1000) than the quadrivalent vaccine (846 per 1000) (RR 1.07, 95% CI 1.05 to 1.08; 3 RCTs, 15,863 participants; high-certainty evidence). Comparative evidence about serious adverse events in the three RCTs (nonavalent 243/8234, quadrivalent 192/7629; OR 0.60, 95% CI 0.14 to 2.61) was of low certainty, owing to imprecision and indirectness. HPV vaccination for people living with HIV Seven RCTs reported on HPV vaccines in people with HIV, with two small trials that collected data about clinical outcomes. Antibody responses were higher following vaccination with either bivalent or quadrivalent HPV vaccine than with control, and these responses could be demonstrated to have been maintained for up to 24 months in children living with HIV (low-certainty evidence). The evidence about clinical outcomes and harms for HPV vaccines in people with HIV is very uncertain (low- to very low-certainty evidence), owing to imprecision and indirectness. AUTHORS' CONCLUSIONS: The immunogenicity of two-dose and three-dose HPV vaccine schedules, measured using antibody responses in young females, is comparable. The quadrivalent vaccine probably reduces external genital lesions and anogenital warts in males compared with control. The nonavalent and quadrivalent vaccines offer similar protection against a combined outcome of cervical, vaginal, and vulval precancer lesions or cancer. In people living with HIV, both the bivalent and quadrivalent HPV vaccines result in high antibody responses. For all comparisons of alternative HPV vaccine schedules, the certainty of the body of evidence about serious adverse events reported during the study periods was low or very low, either because the number of events was low, or the evidence was indirect, or both. Post-marketing surveillance is needed to continue monitoring harms that might be associated with HPV vaccines in the population, and this evidence will be incorporated in future updates of this review. Long-term observational studies are needed to determine the effectiveness of reduced-dose schedules against HPV-related cancer endpoints, and whether adopting these schedules improves vaccine coverage rates.

ANTECEDENTES: La aceptación de la vacuna contra el virus del papiloma humano (VPH) sigue siendo baja en muchos países, aunque las vacunas bivalentes y cuadrivalentes contra el VPH administradas en un calendario de tres dosis son efectivas para prevenir las lesiones precancerosas del cuello uterino en las mujeres. Los calendarios de vacunación más sencillos, como los que incluyen menos dosis, podrían reducir las barreras a la vacunación, al igual que los calendarios que incluyen a los hombres. OBJETIVOS: Evaluar la eficacia, la inmunogenicidad y los efectos perjudiciales de diferentes calendarios de dosis y diferentes tipos de vacunas contra el VPH en mujeres y hombres. MÉTODOS DE BÚSQUEDA: Se realizaron búsquedas electrónicas el 27 de septiembre 2018 en Ovid MEDLINE, el Registro Cochrane Central de Ensayos Controlados (CENTRAL) (en la Biblioteca Cochrane) y Ovid Embase. También se realizaron búsquedas en la International Clinical Trials Registry Platform de la OMS y en ClinicalTrials.gov (ambas el 27 de septiembre 2018), en sitios web de fabricantes de vacunas y se verificaron las listas de referencias de un índice de estudios sobre el VPH y otras revisiones sistemáticas pertinentes. CRITERIOS DE SELECCIÓN: Se incluyeron ensayos controlados aleatorizados (ECA) sin restricciones de idioma. Se consideraron los estudios cuando habían reclutado a hombres o mujeres con pruebas negativas para el VIH de 9 a 26 años de edad, o a hombres o mujeres con pruebas positivas para el VIH de cualquier edad. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Se siguieron los métodos recomendados por Cochrane. Se utilizó el término "control" para hacer referencia a los productos de comparación que contienen un adyuvante o vacuna activa y "placebo" para hacer referencia a los productos que no contienen un adyuvante ni vacuna activa. La mayoría de los resultados primarios de esta revisión fueron resultados clínicos. Sin embargo, para las comparaciones de los calendarios de dosis, los ECA incluidos se diseñaron para medir las respuestas de los anticuerpos (es decir, la inmunogenicidad) como resultado primario, en lugar de los resultados clínicos, debido a que no es ético recoger muestras del cuello uterino de niñas menores de 16 años de edad. Se analizaron los resultados de inmunogenicidad (es decir, títulos de la media geométrica) con los cocientes de medias, los resultados clínicos (p.ej. cáncer y neoplasia intraepitelial) con los cocientes de riesgos o los cocientes de tasas y, para los eventos adversos graves y las muertes, se calcularon los odds­ratios. La certeza de la evidencia se evaluó con los criterios GRADE. RESULTADOS PRINCIPALES: Se incluyeron 20 ECA con 31 940 participantes. La duración del seguimiento en los estudios incluidos varió de siete meses a cinco años. Dos dosis frente a tres dosis de la vacuna contra el VPH en mujeres de 9 a 15 años de edad Las respuestas de los anticuerpos después de los calendarios de dos y tres dosis de la vacuna contra el VPH fueron similares después de hasta cinco años de seguimiento (4 ECA, evidencia de certeza moderada a alta). Ningún ECA recopiló datos de los resultados clínicos. La evidencia acerca de los eventos adversos graves en los estudios que compararon los calendarios de dosis fue de certeza muy baja debido a la imprecisión y a la falta de direccionalidad (tres dosis 35/1159; dos dosis 36/1158; 4 ECA). Se informó una muerte en el grupo de tres dosis (1/898) y ninguna en el grupo de dos dosis (0/899) (evidencia de certeza baja). Intervalo entre las dosis de la vacuna contra el VPH en mujeres y hombres de 9 a 14 años de edad Las respuestas de los anticuerpos fueron más significativas con un intervalo más largo (6 o 12 meses) entre las dos primeras dosis de la vacuna contra el VPH que con un intervalo más corto (2 o 6 meses) al momento del seguimiento de hasta tres años (4 ECA, evidencia de certeza moderada a alta). Ningún ECA recopiló datos sobre los resultados clínicos. La evidencia acerca de los eventos adversos graves en los estudios que compararon los intervalos fue de certeza muy baja, debido a la imprecisión y a la falta de direccionalidad. No se informaron muertes en ninguno de los estudios (0/1898, 3 ECA, evidencia de certeza baja). Vacunación contra el VPH en hombres de 10 a 26 años de edad En un ECA hubo evidencia de certeza moderada de que la vacuna cuadrivalente contra el VPH, en comparación con el control, redujo la incidencia de lesiones genitales externas (control 36 por 3081 personas­año; cuadrivalente 6 por 3173 personas­año; cociente de tasas 0,16; IC del 95%: 0,07 a 0,38; 6254 personas­año) y verrugas anogenitales (control 28 por 2814 personas­año; cuadrivalente 3 por 2831 años­persona; cociente de tasas 0,11; IC del 95%: 0,03 a 0,38; 5645 años­persona). La vacuna cuadrivalente produjo más eventos adversos relacionados con el sitio de la inyección, como dolor o enrojecimiento, que el control (537 frente a 601 por 1000; cociente de riesgos [CR] 1,12; IC del 95%: 1,06 a 1,18; 3895 participantes, evidencia de certeza alta). Hubo evidencia de certeza muy baja de dos ECA acerca de eventos adversos graves con la vacuna cuadrivalente (control 12/2588; cuadrivalente 8/2574), y acerca de las muertes (control 11/2591; cuadrivalente 3/2582), debido a la imprecisión y la falta de direccionalidad. Vacuna nonavalente frente a cuadrivalente en mujeres y hombres de 9 a 26 años de edad Se incluyeron tres ECA; uno en mujeres de 9 a 15 años de edad (n = 600), uno en mujeres de 16 a 26 años de edad (n = 14 215) y uno en hombres de 16 a 26 años de edad (n = 500). El ECA en mujeres de 16 a 26 años informó de los resultados clínicos. Hubo poca o ninguna diferencia en la incidencia del resultado combinado de neoplasia epitelial de cuello de útero de grado alto, adenocarcinoma in situ o cáncer de cuello de útero entre las vacunas contra el VPH (cuadrivalente 325/6882, nonavalente 326/6871; OR 1,00; IC del 95%: 0,85 a 1,16; 13 753 participantes; evidencia de certeza alta). Los otros dos ECA no recopilaron datos sobre los resultados clínicos. Hubo un número ligeramente mayor de eventos adversos locales con la vacuna nonavalente (905 por 1000) que con la vacuna cuadrivalente (846 por 1000) (CR 1,07; IC del 95%: 1,05 a 1,08; 3 ECA, 15 863 participantes; evidencia de certeza alta). La evidencia comparativa acerca de los eventos adversos graves en los tres ECA (nonavalente 243/8234, cuadrivalente 192/7629; OR 0,60; IC del 95%: 0,14 a 2,61) fue de certeza baja, debido a la imprecisión y a la falta de direccionalidad. Vacunación contra el VPH para las personas que conviven con el VIH Siete ECA informaron sobre las vacunas contra el VPH en personas con VIH, y dos ensayos pequeños recopilaron datos sobre los resultados clínicos. Las respuestas de los anticuerpos fueron más altas después de la vacunación con la vacuna bivalente o cuadrivalente contra el VPH que con el control, y se pudo demostrar que estas respuestas se mantuvieron hasta 24 meses en niños que convivían con el VIH (evidencia de certeza baja). La evidencia acerca de los resultados clínicos y los efectos perjudiciales de las vacunas contra el VPH en las personas con VIH es muy incierta (evidencia de certeza baja a muy baja), debido a la imprecisión y a la falta de direccionalidad. CONCLUSIONES DE LOS AUTORES: Es similar la inmunogenicidad de los calendarios de dos y tres dosis de la vacuna contra el VPH, medida con las respuestas de los anticuerpos en mujeres jóvenes. La vacuna cuadrivalente probablemente reduce las lesiones genitales externas y las verrugas anogenitales en los hombres en comparación con el control. Las vacunas nonavalentes y cuadrivalentes ofrecen una protección similar en cuanto a un resultado combinado de lesiones precancerosas o cáncer de cuello de útero, vaginal y vulvar. En los individuos que conviven con el VIH, tanto las vacunas bivalentes como las cuadrivalentes contra el VPH producen respuestas altas de los anticuerpos. Para todas las comparaciones de los calendarios alternativos de la vacuna contra el VPH, la certeza del conjunto de evidencia sobre los eventos adversos graves notificados durante los períodos de estudio fue baja o muy baja, debido a que el número de eventos fue escaso, o a que la evidencia fue indirecta, o ambos. La vigilancia posterior a la comercialización es necesaria para continuar con el control de los efectos perjudiciales que podrían estar asociados con las vacunas contra el VPH en la población, y esta evidencia se incorporará en las actualizaciones futuras de esta revisión. Se necesitan estudios observacionales a largo plazo para determinar la efectividad de los calendarios de dosis reducidas con respecto a las variables de evaluación del cáncer relacionado con el VPH, y si la adopción de estos calendarios mejora las tasas de cobertura de la vacuna.

Interventions for treating recurrent stress urinary incontinence after failed minimally invasive synthetic midurethral tape surgery in women.

BACKGROUND: Surgery is a common treatment modality for stress urinary incontinence (SUI), usually offered to women for whom conservative treatments have failed. Midurethral tapes have superseded colposuspension because cure rates are comparable and recovery time is reduced. However, some women will not be cured after midurethral tape surgery. Currently, there is no consensus on how to manage the condition in these women.This is an update of a Cochrane Review first published in 2013. OBJECTIVES: To assess the effects of interventions for treating recurrent stress urinary incontinence after failed minimally invasive synthetic midurethral tape surgery in women; and to summarise the principal findings of economic evaluations of these interventions. SEARCH METHODS: We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 9 November 2018). We also searched the reference lists of relevant articles. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials in women who had recurrent stress urinary incontinence after previous minimally invasive midurethral tape surgery. We included conservative, pharmacological and surgical treatments. DATA COLLECTION AND ANALYSIS: Two review authors checked the abstracts of identified studies to confirm their eligibility. We obtained full-text reports of relevant studies and contacted study authors directly for additional information where necessary. We extracted outcome data onto a standard proforma and processed them according to the guidance in the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: We included one study in this review. This study was later reported in an originally unplanned secondary analysis of 46 women who underwent transobturator tape for recurrent SUI after one or more previous failed operations. We were unable to use the data, as they were not presented according to the nature of the first operation.We excluded 12 studies, five because they were not randomised controlled trials (RCTs) and four because previous incontinence surgery was not performed using midurethral tape. We considered a further three to be ineligible because neither the trial report nor personal communication with the trialists could confirm whether any of the participants had previously undergone surgery with tape.We had also planned to develop a brief economic commentary summarising the principal findings of relevant economic evaluations but supplementary systematic searches did not identify any such studies. AUTHORS' CONCLUSIONS: There were insufficient data to assess the effects of any of the different management strategies for recurrent or persistent stress incontinence after failed midurethral tape surgery. No published papers have reported exclusively on women whose first operation was a midurethral tape. Evidence from further RCTs and economic evaluations is required to address uncertainties about the effects and costs of these treatments.

Understanding variations in patient screening and recruitment in a multicentre pilot randomised controlled trial: a vignette-based study.

BACKGROUND: The INVESTIGATE-I study was designed to inform a future definitive randomised trial of invasive urodynamic testing, compared to basic clinical assessment with noninvasive tests prior to surgical treatment, in women with stress urinary incontinence or stress-predominant mixed urinary incontinence. In a pilot randomised controlled trial, women from seven participating sites were screened, consented and randomised. Overall, 771 patients were identified from clinic notes and correspondence as being potential recruits and were sent the Patient Information Leaflet. Of those screened, 284 were deemed eligible, giving an overall 'screen positive' rate of 37 %. The numbers screened at individual centres varied between 14 and 399; the 'screen positive' rate varied between 22 and 79 % and the percentage of eligible women recruited varied between 55 and 100 %. The aim of this additional substudy was to explore why 'screen positive' rates may have varied so widely between apparently similar sites. RESULTS: All 11 trial staff involved in screening in the seven recruiting sites were asked to evaluate a series of 20 identical vignettes, mainly based on actual general practitioner referral letters. Of the vignettes, 16 mentioned one or more definite inclusion criteria; the remainder had possible inclusions. Four had definite exclusions; 12 had possible exclusions. Free-text comments were sought to clarify the screeners' decisions. For six vignettes everyone agreed that the patient was eligible; for one all agreed she was not eligible; the breakdown for the remainder was mixed. Free-text comments illuminated uncertainties that may have led to variability in judging potential eligibility. CONCLUSIONS: Variability in judgements about potential trial eligibility highlights the importance of explicit and objective inclusion and exclusion criteria, and of agreed strategies for making judgements when information is missing. During the development and planning of trials, vignettes might be a valuable tool for training those involved in screening and recruiting patients, for identifying potential problems and ensuring greater consistency in the application of eligibility criteria. TRIAL REGISTRATION: ISTCTN registry: ISRCTN71327395 , registered on 7 June 2010.

A mixed methods study to assess the feasibility of a randomised controlled trial of invasive urodynamic testing versus clinical assessment and non-invasive tests prior to surgery for stress urinary incontinence in women: the INVESTIGATE-I study.

BACKGROUND: The position of invasive urodynamic testing (IUT) in diagnostic pathways for urinary incontinence is unclear, and systematic reviews have called for further trials evaluating clinical utility. The objective of this study was to inform the decision whether to proceed to a definitive randomised trial of IUT compared to clinical assessment with non-invasive tests, prior to surgery in women with stress urinary incontinence (SUI) or stress-predominant mixed urinary incontinence (MUI). METHODS: A mixed methods study comprising a pragmatic multicentre randomised pilot trial, a qualitative face-to face interview study with patients eligible for the trial, an exploratory economic evaluation including value of information study, a survey of clinicians' views about IUT, and qualitative telephone interviews with purposively sampled survey respondents. Only the first and second of these elements are reported here. Trial participants were randomised to either clinical assessment with non-invasive tests (control arm) or clinical assessment with non-invasive tests plus IUT (intervention arm). The main outcome measures of these feasibility studies were confirmation that units can identify and recruit eligible women, acceptability of investigation strategies and data collection tools, and acquisition of outcome data to determine the sample size for a definitive trial. The primary outcome proposed for a definitive trial was ICIQ-FLUTS (total score) 6 months after surgery or the start of nonsurgical treatment. RESULTS: Of 284 eligible women, 222 (78%) were recruited, 165/219 (75%) returned questionnaires at baseline, and 125/200 returned them (63%) at follow-up. Most women underwent surgery; management plans were changed in 19 (19%) participants following IUT. Participants interviewed were positive about the trial and the associated documentation. CONCLUSIONS: All elements of a definitive trial were rehearsed. Such a trial would require between 232 and 922 participants, depending on the target difference in the primary outcome. We identified possible modifications to our protocol for application in a definitive trial including clarity over inclusion/exclusions, screening processes, reduction in secondary outcomes, and modification to patient questionnaire booklets and bladder diaries. A definitive trial of IUT versus clinical assessment prior to surgery for SUI or stress predominant MUI is feasible and remains relevant. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN 71327395, registered 7 June 2010.

INVESTIGATE-I (INVasive Evaluation before Surgical Treatment of Incontinence Gives Added Therapeutic Effect?): a mixed-methods study to assess the feasibility of a future randomised controlled trial of invasive urodynamic testing prior to surgery for stress urinary incontinence in women.

BACKGROUND: The position of invasive urodynamic testing in the diagnostic pathway for urinary incontinence (UI) is unclear. Systematic reviews have called for further trials evaluating clinical utility, although a preliminary feasibility study was considered appropriate. OBJECTIVES: To inform the decision whether or not to proceed to a definitive randomised trial of invasive urodynamic testing compared with clinical assessment with non-invasive tests, prior to surgery in women with stress UI (SUI) or stress predominant mixed UI (MUI). DESIGN: A mixed-methods study comprising a pragmatic multicentre randomised pilot trial; economic evaluation; survey of clinicians' views about invasive urodynamic testing; qualitative interviews with clinicians and trial participants. SETTING: Urogynaecology, female urology and general gynaecology units in Newcastle, Leicester, Swansea, Sheffield, Northumberland, Gateshead and South Tees. PARTICIPANTS: Trial recruits were women with SUI or stress predominant MUI who were considering surgery after unsuccessful conservative treatment. Relevant clinicians completed two online surveys. Subsets of survey respondents and trial participants took part in separate qualitative interview studies. INTERVENTIONS: Pilot trial participants were randomised to undergo clinical assessment with non-invasive tests (control arm); or assessment as controls, plus invasive urodynamic testing (intervention arm). MAIN OUTCOME MEASURES: Confirmation that units can identify and recruit eligible women; acceptability of investigation strategies and data collection tools; acquisition of outcome data to determine the sample size for a definitive trial. The proposed primary outcome for the definitive trial was International Consultation on Incontinence Modular Questionnaire (ICIQ) Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) (total score) 6 months after surgery or the start of non-surgical treatment; secondary outcomes included: ICIQ-FLUTS (subscales); ICIQ Urinary Incontinence Short Form; ICIQ Lower Urinary Tract Symptoms Quality of Life; Urogenital Distress Inventory; EuroQol-5D; costs, quality-adjusted life-years (QALYs) and incremental cost per QALY, Short Form 12; 3-day bladder diary. RESULTS: Of 284 eligible women, 222 (78%) were recruited; 165/219 (75%) returned questionnaires at baseline and 125/200 (63%) who were sent questionnaires at follow-up. There were few missing data items in returned questionnaires, with individual outcome scales calculable for 81%-94%. Most women underwent surgery; management plans were changed in 19 (19%) participants following invasive urodynamic testing. Participant Costs Questionnaires were returned by 53% 6 months after treatment; complete data to undertake cost-utility analysis were available in 27% (intervention) and 47% (control). While insufficient to recommend changes in practice, the results suggest further research would be valuable. All clinicians responding to the survey had access to invasive urodynamic testing, and most saw it as essential prior to surgery in women with SUI with or without other symptoms; nevertheless, 70% considered the research question underlying INVESTIGATE important and most were willing to randomise patients in a definitive trial. Participants interviewed were positive about the trial and associated documentation; the desire of some women to avoid invasive urodynamic testing contrasted with opinions expressed by clinicians through both survey and interview responses. CONCLUSIONS: All elements of a definitive trial and economic evaluation were rehearsed; several areas for protocol modification were identified. Such a trial would require to 400-900 participants, depending on the difference in primary outcome sought. FUTURE WORK: A definitive trial of invasive urodynamic testing versus clinical assessment prior to surgery for SUI or stress predominant MUI should be undertaken. TRIAL REGISTRATION: Current Controlled Trials ISRCTN71327395. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Treatment of recurrent stress urinary incontinence after failed minimally invasive synthetic suburethral tape surgery in women.

BACKGROUND: Surgery is a common treatment modality for stress urinary incontinence (SUI), usually offered for women who fail conservative treatments. Suburethral tapes have superseded colposuspension because cure rates are comparable and recovery time reduced. However, some women will not be cured after suburethral tape surgery, and currently there is no consensus on how to manage these women. OBJECTIVES: To obtain and examine evidence supporting different management strategies for recurrent/persistent stress urinary incontinence (SUI) in women after failed suburethral tape surgery. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Register of controlled trials (searched 18 December 2012), which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and PreMEDLINE; and handsearched journals and conference proceedings, and the reference lists of included studies and previous Cochrane reviews for randomised or quasi-randomised studies treating patients with recurrent incontinence, either as the sole population or a subset. Conservative, medical and surgical treatments were included. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials in women who had recurrent urinary incontinence after previous minimally invasive suburethral tape surgery. DATA COLLECTION AND ANALYSIS: Abstracts of identified studies were checked by two authors to confirm eligibility. Full text reports of relevant studies were obtained, and authors were contacted directly where necessary. Outcome data were extracted onto a standard proforma and processed according to the methods in the Cochrane Handbook for Systematic Reviews of Interventions. MAIN RESULTS: Twelve studies were identified, but all were excluded because they did not meet the eligibility criteria. Six were randomised controlled trials (RCTs) but were not eligible because the previous incontinence surgery was not a suburethral tape. A subset of one RCT may have been eligible for inclusion because some of the women were having repeat surgery, but we were unable to obtain from the authors the data according to primary surgery for this cohort. AUTHORS' CONCLUSIONS: There were no data to recommend or refute any of the different management strategies for recurrent or persistent stress incontinence after failed suburethral tape surgery. Evidence is urgently required to address this deficiency, ideally from RCTs.

A randomized, double-blinded placebo-controlled clinical trial of the routine use of preoperative antibiotic prophylaxis in modified radical mastectomy.

BACKGROUND: The effectiveness of antibiotic prophylaxis for prevention of surgical site infection (SSI) following specific types of breast cancer surgery remains uncertain. This study assessed the effectiveness of prophylaxis in modified radical mastectomy (MRM). METHODS: Women undergoing MRM for breast cancer were recruited. Women were excluded who had diabetes mellitus, severe malnutrition or known allergy to cephalosporins; were receiving corticosteroid therapy or were treated with antibiotics within one week prior to surgery; were scheduled for simultaneous breast reconstruction or bilateral oophorectomy; had existing local infection. Participants were randomized to receive either intravenous cefazolin 1 g or placebo within 30 min prior to skin incision. Standard skin preparation and operative technique for MRM were carried out. Wounds were assessed for SSI and other complications weekly for 30 days. RESULTS: A total of 254 women were recruited. Age, clinical stage, prior chemotherapy, and operative time were similar for antibiotic and placebo groups. The overall incidence of SSI was 14.2 %. There were no significant differences in the infection rate over the 30-day follow-up period between the placebo and antibiotic groups (15 % vs 13.4 %; p = 0.719) or at each week. The majority of SSI were either cellulitis or superficial infection for both groups. There were no significant differences between groups in treatments required for SSI, incidence of hematoma or seroma. CONCLUSIONS: The findings of this study, alone and when meta-analyzed with data from studies in similar surgical populations, do not support the use of antibiotic prophylaxis in MRM.

Assessing professional equipoise and views about a future clinical trial of invasive urodynamics prior to surgery for stress urinary incontinence in women: a survey within a mixed methods feasibility study.

AIMS: To determine surgeons' views on invasive urodynamic testing (IUT) prior to surgery for stress (SUI) or stress predominant mixed urinary incontinence (MUI). METHODS: Members of British Society of Urogynaecology (BSUG) and British Association of Urological Surgeons Section of Female, Neurological and Urodynamic Urology (BAUS-SFNUU) were sent an email invitation to complete an online "SurveyMonkey®" questionnaire regarding their current use of IUT prior to surgical treatment of SUI, their view about the necessity for IUT in various clinical scenarios, and their willingness to randomize patients into a future trial of IUT. A purposive sample of respondents was invited for telephone interview to explore further how they use IUT to inform clinical decisions, and to contextualize questionnaire responses. RESULTS: There were 176/517 (34%) responses, 106/332 (32%) from gynecologists/urogynecologists and 67/185 (36%) from urologists; all respondents had access to IUT, and 89% currently arrange IUT for most women with SUI or stress predominant MUI. For a variety of scenarios with increasingly complex symptoms the level of individual equipoise ("undecided" about IUT) was very low (1-6%) and community equipoise was, at best, 66:34 (IUT "essential" vs. "unnecessary") even for the simplest scenario. Nevertheless, 70% rated the research question underlying the proposed studies "very important" or "extremely important;" 60% recorded a "willingness to randomize" score ≥8/10. CONCLUSIONS: Most urogynecologists and urologists consider IUT essential before surgery in SUI with or without other symptoms. Most however recognize the need for further research, and indicated a willingness to recruit into multicenter trials addressing this question.

Repeated in vivo inguinal measurements to estimate a single optimal mesh size for inguinal herniorrhaphy.

BACKGROUND: Inguinal hernia is a common condition and its repair (herniorrhaphy) is one of the most commonly performed procedures in general surgery. The Lichtenstein herniorrhaphy technique is a widely used and effective surgery that uses mesh to reinforce the area of weakness. Although a wide range of mesh sizes are available for use in hernia repair, in low-resource health care settings the provision of multiple products may not be supportable and it may be necessary for the provision and use of a single mesh size. This study aimed to determine whether the recommended 7.0 cm x 15.0 cm size is an appropriate single mesh size. METHODS: In order to determine the optimal mesh size according to recommended surgical practices, in vivo measurements of key dimensions of the inguinal floor were taken in patients undergoing herniorrhaphy. RESULTS: Measurements were taken in 43 patients: 40 men and 3 women, mean age 43 years (SD 13.6); 39 with indirect hernias, 4 with direct. Allowing for recommended mesh overlaps, the optimal mesh size for provision to be appropriate for the majority of patients was determined to be 8.5 cm x 14.0 cm, 21% wider than the mesh size currently recommended for use in Lichtenstein herniorrhaphy. CONCLUSIONS: An appropriate size for routine provision in low-resource settings, or other settings where the provision of several mesh sizes is not supportable, may be 8.5 cm x 14.0 cm.

Individual-based primary prevention of cardiovascular disease in Cambodia and Mongolia: early identification and management of hypertension and diabetes mellitus.

BACKGROUND: To assess the coverage of individual-based primary prevention strategies for cardiovascular disease (CVD) in Cambodia and Mongolia: specifically the early identification of hypertension and diabetes mellitus, major proximate physiological CVD risk factors, and management with pharmaceutical and lifestyle advice interventions. METHODS: Analysis of data collected in national cross-sectional STEPS surveys in 2009 (Mongolia) and 2010 (Cambodia) involving participants aged 25-64 years: 5433 in Cambodia and 4539 in Mongolia. RESULTS: Mongolia has higher prevalence of CVD risk factors than Cambodia--hypertension (36.5% versus 12.3%), diabetes (6.3% versus 3.1%), hypercholesterolemia (8.5% versus 3.2%), and overweight (52.5% versus 15.5%). The difference in tobacco smoking was less notable (32.1% versus 29.4%).Coverage with prior testing for blood glucose in the priority age group 35-64 years remains limited (16.5% in Cambodia and 21.7% in Mongolia). Coverage is higher for hypertension. A large burden of both hypertension and diabetes remains unidentified at current strategies for early identification: only 45.4% (Cambodia) to 65.8% (Mongolia) of all hypertensives and 22.8% (Mongolia) to 50.3% (Cambodia) of all diabetics in the age group 35-64 years had been previously diagnosed. Approximately half of all hypertensives and of all diabetics in both countries were untreated. 7.2% and 12.2% of total hypertensive population and 5.9% and 16.1% of total diabetic population in Cambodia and Mongolia, respectively, were untreated despite being previously diagnosed.Only 24.1% and 28.6% of all hypertensives and 15.9% and 23.9% of all diabetics in Mongolia and Cambodia, respectively were adequately controlled. Estimates suggest deficits in delivery of important advice for lifestyle interventions. CONCLUSIONS: Multifaceted strategies are required to improve early identification, initiation of treatment and improving quality of treatment for common CVD risk factors. Periodic population-based surveys including questions on medical and treatment history and the context of testing and treatment can facilitate monitoring of individual-based prevention strategies.

The effect of urinary incontinence on health utility and health-related quality of life in men following prostate surgery.

AIMS: The impact of urinary incontinence (UI) on health-related quality of life (HRQoL) has been less well researched in men than women and the general population. This study aims to assess the association between UI and HRQoL in men 1 year after prostate surgery. METHODS: Planned secondary analysis of data from two parallel randomized controlled trials of active conservative treatment for UI in 853 men following radical prostatectomy (RP) and transurethral resection of the prostate (TURP). Men of any age were eligible for trial inclusion if they were experiencing UI 6 weeks after undergoing RP or TURP at 34 centers in the United Kingdom. Univariate and multivariate analysis considered associations between health status (SF-12 and EQ-5D) and self-reported UI. Multivariate analysis controlled for age, obesity, UI prior to surgery, and concomitant fecal incontinence. RESULTS: Mean age of 411 men in the RP trial was 62.3 years (SD 5.7) and 442 men in the TURP trial was 68.0 (SD 7.9). Of men with UI at 6 weeks after surgery, 76.7% in the RP group and 63.2% in the TURP group still had UI at 12 months. Any UI at 12 months was significantly associated with reduced HRQoL in the RP group and lower EQ-5D and SF-12 Mental Component Scores in the TURP group. CONCLUSION: Any UI is a significant factor in reduced HRQoL in men following prostate surgery, particularly younger men who undergo RP. Its importance to patients as an adverse outcome should not be underestimated.

Risk of prostate cancer associated with benign prostate disease: a primary care case-control study.

BACKGROUND: Benign diseases of the prostate are common in the general male population, and prostate cancer is the most common cancer in men. Uncertainty as to the nature of the association between benign and malignant disease is a source of concern for patients and clinicians. AIM: To determine the likelihood of men with benign prostate disease developing prostate cancer compared with men without disease. DESIGN: Incident matched case-control study. METHOD: All incident cases of prostate cancer (n = 984) were identified in a nationally representative community-based population, and each was matched by age with two controls with no prostate cancer (n = 1968). Participants' records of the previous 5 years were searched for diagnoses of benign prostate disease. Analyses investigated an a priori hypothesis that clinicians may record disease as benign until proven to be malignant, causing misleading significant associations between benign and malignant diagnoses. RESULTS: There was a significant association between a diagnosis of prostate cancer and a benign diagnosis at any time in the previous 5 years: odds ratio (OR) 1.57 (95% confidence interval [CI] = 1.32 to 1.88). However, there was no significant association when benign diagnoses within 6 months and within 12 months of cancer diagnoses were excluded: OR 1.19 (95% CI = 0.97 to 1.46) and OR 1.00 (95% CI = 0.79 to 1.27) respectively. CONCLUSION: Findings from this study suggest that unless prostate cancer is detected within 6 months, men diagnosed for the first time with benign disease are at no greater risk of prostate cancer than those with no recorded prostate disease.

Five-year prognosis in an incident cohort of people presenting with acute myocardial infarction.

BACKGROUND: Following an AMI, it is important for patients and their physicians to appreciate the subsequent risk of death, and the potential benefits of invasive cardiac procedures and secondary preventive therapy. Studies, to-date, have focused largely on high-risk populations. We wished to determine the risk of death in a population-derived cohort of 2,887 patients after a first acute myocardial infarction (AMI). METHODS: Logistic regression and survival analysis were conducted to investigate the effect of different baseline characteristics, pharmacological therapies and revascularization procedures on coronary heart disease (CHD) and all-cause mortality outcomes. RESULTS: Within five years 44.4% of patients died (27.1% short-term [<30 days] and 23.7% longer-term [≥30 days]). Percutaneous transluminal coronary angioplasty (Adjusted Hazards Ratio (AHR) = 0.49, 95% Confidence Interval (CI) 0.26-0.93), ß-blockers (AHR = 0.58, 95%CI 0.46-0.74) and statins (AHR = 0.60, 95%CI 0.47-0.77) were all associated with significant reductions in longer-term CHD-related mortality. However, not all patients received secondary preventive therapy (8.7%). Diabetes (AHR = 1.83, 95%CI 1.43-2.34), stroke (AHR = 1.73, 95%CI 1.35-2.22), heart failure (AHR = 1.69, 95%CI 1.28-2.22), smoking (AHR = 1.72, 95%CI 1.18-2.51) and obesity (>30 kg/m2; AHR = 1.39, 95%CI 1.01-1.90) increased the risk of longer-term mortality independent of other risk factors. CONCLUSIONS: It is encouraging that the coronary procedure PTCA and pharmacological secondary prevention therapies were found to be strongly associated with an important reduced risk of subsequent death, although not all patients received these interventions. Smoking, being obese and having cardiovascular related disease at baseline were also associated with an increased likelihood of longer-term mortality, independent of other baseline characteristics. Thus, the provision of smoking cessation, advice on diet (for obese patients) and optimal treatment is likely to be crucial for reducing mortality in all patients after AMI.

INVESTIGATE-I (INVasive Evaluation before Surgical Treatment of Incontinence Gives Added Therapeutic Effect?): study protocol for a mixed methods study to assess the feasibility of a future randomised controlled trial of the clinical utility of invasive urodynamic testing.

BACKGROUND: Urinary incontinence is an important health problem to the individual sufferer and to health services. Stress and stress predominant mixed urinary incontinence are increasingly managed by surgery due to advances in surgical techniques. Despite the lack of evidence for its clinical utility, most clinicians undertake invasive urodynamic testing (IUT) to confirm a functional diagnosis of urodynamic stress incontinence before offering surgery for this condition. IUT is expensive, embarrassing and uncomfortable for women and carries a small risk. Recent systematic reviews have confirmed the lack of high quality evidence of effectiveness.The aim of this pilot study is to test the feasibility of a future definitive randomised control trial that would address whether IUT alters treatment decisions and treatment outcome in these women and would test its clinical and cost effectiveness. METHODS/DESIGN: This is a mixed methods pragmatic multicentre feasibility pilot study with four components:-(a) A multicentre, external pilot randomised trial comparing basic clinical assessment with non-invasive tests and IUT. The outcome measures are rates of recruitment, randomisation and data completion. Data will be used to estimate sample size necessary for the definitive trial.(b) Qualitative interviews of a purposively sampled sub-set of women eligible for the pilot trial will explore willingness to participate, be randomised and their overall trial experience.(c) A national survey of clinicians to determine their views of IUT in this context, the main outcome being their willingness to randomise patients into the definitive trial.(d) Qualitative interviews of a purposively sampled group of these clinicians will explore whether and how they use IUT to inform their decisions. DISCUSSION: The pilot trial will provide evidence of feasibility and acceptability and therefore inform the decision whether to proceed to the definitive trial. Results will inform the design and conduct of the definitive trial and ensure its effectiveness in achieving its research aim. TRIAL REGISTRATION NUMBER: Current Controlled Trials ISRCTN71327395 assigned 7th June 2010.

Impact of palliative urinary diversion by percutaneous nephrostomy drainage and ureteral stenting among patients with advanced cervical cancer and obstructive uropathy: a prospective cohort.

AIM: Obstructive uropathy is a recognized complication in advanced cervical cancer. Urinary diversion is commonly used to bypass the obstruction and improve renal function. The degree of survival benefit that diversion offers is not well established and its impact on quality of life (QoL) is uncertain. This study considered these factors in order to inform treatment decisions. METHODS: This study examined a prospective cohort of patients with advanced cervical cancer and obstructive uropathy in Manila, Philippines. Age, cancer treatment status, comorbidities, serum creatinine level, degree of obstructive uropathy and QoL were recorded at baseline. Patients with creatinine values >150 µmol/L, or who were being considered for radiotherapy or nephrotoxic chemotherapy or manifesting uncontrolled or recurrent uropathy-related urinary tract infection, were offered diversion. Follow-up data collection was at 3, 6, 9 and 12 months from cohort entry. RESULTS: Of the 230 patients invited, 205 patients joined the cohort. Complete data were available for 198, of whom 93 underwent diversion, 56 required diversion but elected not to receive it, and 49 did not require it. Although survival at 12 months among those who underwent diversion was no greater than among those who required but elected not to receive the procedure, diversion was associated with significantly improved chance of survival in the shorter term. There was no significant difference in the QoL between the groups throughout the study. CONCLUSION: With no evidence of an impact on QoL, the decision to offer diversionary surgery might be based solely on a survival benefit, which is modest but potentially important to patients.

Drugs for treatment of urinary retention after surgery in adults.

BACKGROUND: Post-operative urinary retention, the inability to void following surgery despite a full bladder, is usually transitory but can be prolonged in some cases. It can lead to several complications including urinary tract infection, long term bladder dysfunction and kidney damage leading to chronic kidney disease. Catheterisation, generally regarded as the optimal management method, is associated with risks and so pharmacological treatment of post-operative urinary retention that could remove or reduce the need for catheterisation is desirable. OBJECTIVES: To assess the effectiveness of drugs for treatment of post-operative urinary retention either alone or as an adjunct to catheterisation. SEARCH STRATEGY: We searched the Cochrane Incontinence Group Specialised Register (searched 10 February 2010), CENTRAL (2010, Issue 1), MEDLINE (January 1950 to Week 1 January 2010), EMBASE (January 1980 to 2010 Week 5) and the reference lists of relevant articles.  SELECTION CRITERIA: Randomised and quasi randomised controlled trials in which at least one arm of the study included a drug treatment for post-operative urinary retention. DATA COLLECTION AND ANALYSIS: Published reports of all potentially eligible studies were evaluated by two reviewers independently. No language or other limitations were applied. Standardised data extraction forms were used by two reviewers independently and cross-checked. Where insufficient data were reported authors were contacted where possible for further information. The risk of bias in eligible trials was assessed independently by two reviewers using the Cochrane risk of bias tool. MAIN RESULTS: Seven studies including 494 participants formed the evidence base for this review. Drug treatments assessed in studies in the review included cholinergic agents, alpha-blockers, sedatives and prostaglandin on their own or in combinations. No statistically significant associations were reported between successful treatment or any other outcome and cholinergic agents, alpha-blockers and sedatives as monotherapies. A statistically significant association between intravesically administered prostaglandin and successful voiding was detected, Risk Ratio 3.07 (95% CI 1.22 to 7.72). A statistically significant association was detected between cholinergic agents combined with sedative and an improved likelihood of spontaneous voiding compared with placebo, Risk Ratio 1.39 (95% CI 1.07 to 1.82). Significant heterogeneity was identified between the two studies in this analysis, however. AUTHORS' CONCLUSIONS: Whilst it may appear that cholinergic agents and intravesically administered prostaglandin offer most promise in the treatment of post-operative urinary retention, the evidence is weak. There is a need for further research into pharmacological alternatives to catheterisation in the treatment of this common surgical complication.

Prevalence of urinary incontinence in men, women, and children--current evidence: findings of the Fourth International Consultation on Incontinence.

OBJECTIVES: To summarize existing evidence relating to the prevalence and risk factors of urinary incontinence in order to provide a concise reference source for clinicians, health researchers, and service planners. METHODS: For the Fourth International Consultation on Incontinence (4th ICI) world experts identified, collated, and reviewed the best available evidence. Estimates of prevalence from different studies are presented as ranges. RESULTS: Most studies report some degree of urinary incontinence (UI) in 25-45% of women; 7-37% of women aged 20-39 report some UI; "daily UI" is reported by 9% to 39% of women over 60. Pregnancy, childbirth, diabetes and increased body mass index are associated with an increased risk of UI. Prevalence of UI in men approximately half that in women: UI is seen in 11-34% of older men, with 2-11% reporting daily UI. Surgery for prostate disease is associated with an increased risk. Some 10% of children aged seven, 3% of 11-12 years olds and 1% of 16-17 year olds are not dry at night. CONCLUSIONS: UI is clearly common, but accurate prevalence data have proven difficult to establish because of heterogeneity between studies in terms of methodologies, definitions of UI and populations considered. Future research should use standardized, validated and more readily comparable methods.

Service organisation for the secondary prevention of ischaemic heart disease in primary care.

BACKGROUND: Ischaemic heart disease (IHD) is a major cause of mortality and morbidity and its prevalence is set to increase. Secondary prevention aims to prevent subsequent acute events in people with established IHD. While the benefits of individual medical and lifestyle interventions is established, the effectiveness of interventions which seek to improve the way secondary preventive care is delivered in primary care or community settings is less so. OBJECTIVES: To assess the effectiveness of service organisation interventions, identifying which types and elements of service change are associated with most improvement in clinician and patient adherence to secondary prevention recommendations relating to risk factor levels and monitoring (blood pressure, cholesterol and lifestyle factors such as diet, exercise, smoking and obesity) and appropriate prophylactic medication. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2007, Issue 4), MEDLINE (1966 to Feb 2008), EMBASE (1980 to Feb 2008), and CINAHL (1981 to Feb 2008). Bibliographies were checked. No language restrictions were applied. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials of service organisation interventions in primary care or community settings in populations with established IHD. DATA COLLECTION AND ANALYSIS: Analyses were conducted according to Cochrane recommendations and Odds Ratios (with 95% confidence intervals) reported for dichotomous outcomes, mean differences (with 95% CIs) for continuous outcomes. MAIN RESULTS: Eleven studies involving 12,074 people with IHD were included. Increased proportions of patients with total cholesterol levels within recommended levels at 12 months, OR 1.90 (1.04 to 3.48), were associated with interventions that included regular planned appointments, patient education and structured monitoring of medication and risk factors, but significant heterogeneity was apparent. Results relating to blood pressure within target levels bordered on statistical significance. There were no significant effects of interventions on mean blood pressure or cholesterol levels, prescribing, smoking status or body mass index. Few data were available on the effect on diet. There was some suggestion of a "ceiling effect" whereby interventions have a diminishing beneficial effect once certain levels of risk factor management are reached. AUTHORS' CONCLUSIONS: There is weak evidence that regular planned recall of patients for appointments, structured monitoring of risk factors and prescribing, and education for patients can be effective in increasing the proportions of patients within target levels for cholesterol control and blood pressure. Further research in this area would benefit from greater standardisation of the outcomes measured.