Evaluating Primary Treatment for People with Advanced Glaucoma: Five-Year Results of the Treatment of Advanced Glaucoma Study.

PURPOSE: To determine whether primary trabeculectomy or medical treatment produces better outcomes in terms of quality of life (QoL), clinical effectiveness, and safety in patients with advanced glaucoma. DESIGN: Multicenter randomized controlled trial. PARTICIPANTS: Between June 3, 2014, and May 31, 2017, 453 adults with newly diagnosed advanced open-angle glaucoma in at least 1 eye (Hodapp classification) were recruited from 27 secondary care glaucoma departments in the United Kingdom. Two hundred twenty-seven were allocated to trabeculectomy, and 226 were allocated medical management. METHODS: Participants were randomized on a 1:1 basis to have either mitomycin C-augmented trabeculectomy or escalating medical management with intraocular pressure (IOP)-reducing drops as the primary intervention and were followed up for 5 years. MAIN OUTCOME MEASURES: The primary outcome was vision-specific QoL measured with the 25-item Visual Function Questionnaire (VFQ-25) at 5 years. Secondary outcomes were general health status, glaucoma-related QoL, clinical effectiveness (IOP, visual field, and visual acuity), and safety. RESULTS: At 5 years, the mean ± standard deviation VFQ-25 scores in the trabeculectomy and medication arms were 83.3 ± 15.5 and 81.3 ± 17.5, respectively, and the mean difference was 1.01 (95% confidence interval [CI], -1.99 to 4.00; P = 0.51). The mean IOPs were 12.07 ± 5.18 mmHg and 14.76 ± 4.14 mmHg, respectively, and the mean difference was -2.56 (95% CI, -3.80 to -1.32; P < 0.001). Glaucoma severity measured with visual field mean deviation were -14.30 ± 7.14 dB and -16.74 ± 6.78 dB, respectively, with a mean difference of 1.87 (95% CI, 0.87-2.87 dB; P < 0.001). Safety events occurred in 115 (52.2%) of patients in the trabeculectomy arm and 124 (57.9%) of patients in the medication arm (relative risk, 0.92; 95% CI, 0.72-1.19; P = 0.54). Serious adverse events were rare. CONCLUSIONS: At 5 years, the Treatment of Advanced Glaucoma Study demonstrated that primary trabeculectomy surgery is more effective in lowering IOP and preventing disease progression than primary medical treatment in patients with advanced disease and has a similar safety profile. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Oestrogen therapy for treating pelvic organ prolapse in postmenopausal women.

BACKGROUND: Pelvic organ prolapse (POP) is the descent of a woman's uterus, bladder, or rectum into the vagina. It affects 50% of women over 50 years old who have given birth to at least one child, and recognised risk factors are older age, higher number of births, and higher body mass index. This review assesses the effects of oestrogen therapy, alone or in combination with other treatments, on POP in postmenopausal women. OBJECTIVES: To assess the benefits and harms of local and systemic oestrogen therapy in the management of pelvic organ prolapse symptoms in postmenopausal women, and to summarise the principal findings of relevant economic evaluations. SEARCH METHODS: We searched the Cochrane Incontinence Specialised Register (up to 20 June 2022), which includes CENTRAL, MEDLINE, two trials registers, and handsearching of journals and conference proceedings. We also checked the reference lists of relevant articles for additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi-RCTs, multi-arm RCTs, and cross-over RCTs that evaluated the effects of oestrogen therapy (alone or in combination with other treatments) versus placebo, no treatment, or other interventions in postmenopausal women with any grade of POP. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from the included trials using prespecified outcome measures and a piloted extraction form. The same review authors independently assessed the risk of bias of eligible trials using Cochrane's risk of bias tool. Had data allowed, we would have created summary of findings tables for our main outcome measures and assessed the certainty of the evidence using GRADE. MAIN RESULTS: We identified 14 studies including a total of 1002 women. In general, studies were at high risk of bias in terms of blinding of participants and personnel, and there were also some concerns about selective reporting. Owing to insufficient data for the outcomes of interest, we were unable to perform our planned subgroup analyses (systemic versus topical oestrogen, parous versus nulliparous women, women with versus without a uterus). No studies assessed the effects of oestrogen therapy alone versus no treatment, placebo, pelvic floor muscle training, devices such as vaginal pessaries, or surgery. However, we did identify three studies that assessed oestrogen therapy in conjunction with vaginal pessaries versus vaginal pessaries alone and 11 studies that assessed oestrogen therapy in conjunction with surgery versus surgery alone. AUTHORS' CONCLUSIONS: There was insufficient evidence from RCTs to draw any solid conclusions on the benefits or harms of oestrogen therapy for managing POP symptoms in postmenopausal women. Topical oestrogen in conjunction with pessaries was associated with fewer adverse vaginal events compared with pessaries alone, and topical oestrogen in conjunction with surgery was associated with reduced postoperative urinary tract infections compared with surgery alone; however, these findings should be interpreted with caution, as the studies that contributed data varied substantially in their design. There is a need for larger studies on the effectiveness and cost-effectiveness of oestrogen therapy, used alone or in conjunction with pelvic floor muscle training, vaginal pessaries, or surgery, for the management of POP. These studies should measure outcomes in the medium and long term.

Anti-vascular endothelial growth factor for proliferative diabetic retinopathy.

BACKGROUND: Proliferative diabetic retinopathy (PDR) is an advanced complication of diabetic retinopathy that can cause blindness. It consists of the presence of new vessels in the retina and vitreous haemorrhage. Although panretinal photocoagulation (PRP) is the treatment of choice for PDR, it has secondary effects that can affect vision. Anti-vascular endothelial growth factor (anti-VEGF), which produces an inhibition of vascular proliferation, could improve the vision of people with PDR. OBJECTIVES: To assess the effectiveness and safety of anti-VEGFs for PDR and summarise any relevant economic evaluations of their use. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 6); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov, and the WHO ICTRP. We did not use any date or language restrictions. We last searched the electronic databases on 1 June 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing anti-VEGFs to another active treatment, sham treatment, or no treatment for people with PDR. We also included studies that assessed the combination of anti-VEGFs with other treatments. We excluded studies that used anti-VEGFs in people undergoing vitrectomy. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias (RoB) for all included trials. We calculated the risk ratio (RR) or the mean difference (MD), and 95% confidence intervals (CI). We used GRADE to assess the certainty of evidence. MAIN RESULTS: We included 15 new studies in this update, bringing the total to 23 RCTs with 1755 participants (2334 eyes). Forty-five per cent of participants were women and 55% were men, with a mean age of 56 years (range 48 to 77 years). The mean glycosylated haemoglobin (Hb1Ac) was 8.45% for the PRP group and 8.25% for people receiving anti-VEGFs alone or in combination. Twelve studies included people with PDR, and participants in 11 studies had high-risk PDR (HRPDR). Twelve studies were of bevacizumab, seven of ranibizumab, one of conbercept, two of pegaptanib, and one of aflibercept. The mean number of participants per RCT was 76 (ranging from 15 to 305). Most studies had an unclear or high RoB, mainly in the blinding of interventions and outcome assessors. A few studies had selective reporting and attrition bias. No study reported loss or gain of 3 or more lines of visual acuity (VA) at 12 months. Anti-VEGFs ± PRP probably increase VA compared with PRP alone (mean difference (MD) -0.08 logMAR, 95% CI -0.12 to -0.04; I2 = 28%; 10 RCTS, 1172 eyes; moderate-certainty evidence). Anti-VEGFs ± PRP may increase regression of new vessels (MD -4.14 mm2, 95% CI -6.84 to -1.43; I2 = 75%; 4 RCTS, 189 eyes; low-certainty evidence) and probably increase a complete regression of new vessels (RR 1.63, 95% CI 1.19 to 2.24; I2 = 46%; 5 RCTS, 405 eyes; moderate-certainty evidence). Anti-VEGFs ± PRP probably reduce vitreous haemorrhage (RR 0.72, 95% CI 0.57 to 0.90; I2 = 0%; 6 RCTS, 1008 eyes; moderate-certainty evidence). Anti-VEGFs ± PRP may reduce the need for vitrectomy compared with eyes that received PRP alone (RR 0.67, 95% CI 0.49 to 0.93; I2 = 43%; 8 RCTs, 1248 eyes; low-certainty evidence). Anti-VEGFs ± PRP may result in little to no difference in the quality of life compared with PRP alone (MD 0.62, 95% CI -3.99 to 5.23; I2 = 0%; 2 RCTs, 382 participants; low-certainty evidence). We do not know if anti-VEGFs ± PRP compared with PRP alone had an impact on adverse events (very low-certainty evidence). We did not find differences in visual acuity in subgroup analyses comparing the type of anti-VEGFs, the severity of the disease (PDR versus HRPDR), time to follow-up (< 12 months versus 12 or more months), and treatment with anti-VEGFs + PRP versus anti-VEGFs alone. The main reasons for downgrading the certainty of evidence included a high RoB, imprecision, and inconsistency of effect estimates. AUTHORS' CONCLUSIONS: Anti-VEGFs ± PRP compared with PRP alone probably increase visual acuity, but the degree of improvement is not clinically meaningful. Regarding secondary outcomes, anti-VEGFs ± PRP produce a regression of new vessels, reduce vitreous haemorrhage, and may reduce the need for vitrectomy compared with eyes that received PRP alone. We do not know if anti-VEGFs ± PRP have an impact on the incidence of adverse events and they may have little or no effect on patients' quality of life. Carefully designed and conducted clinical trials are required, assessing the optimal schedule of anti-VEGFs alone compared with PRP, and with a longer follow-up.

Interventions for myopia control in children: a living systematic review and network meta-analysis.

BACKGROUND: Myopia is a common refractive error, where elongation of the eyeball causes distant objects to appear blurred. The increasing prevalence of myopia is a growing global public health problem, in terms of rates of uncorrected refractive error and significantly, an increased risk of visual impairment due to myopia-related ocular morbidity. Since myopia is usually detected in children before 10 years of age and can progress rapidly, interventions to slow its progression need to be delivered in childhood. OBJECTIVES: To assess the comparative efficacy of optical, pharmacological and environmental interventions for slowing myopia progression in children using network meta-analysis (NMA). To generate a relative ranking of myopia control interventions according to their efficacy. To produce a brief economic commentary, summarising the economic evaluations assessing myopia control interventions in children. To maintain the currency of the evidence using a living systematic review approach.  SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE; Embase; and three trials registers. The search date was 26 February 2022.  SELECTION CRITERIA: We included randomised controlled trials (RCTs) of optical, pharmacological and environmental interventions for slowing myopia progression in children aged 18 years or younger. Critical outcomes were progression of myopia (defined as the difference in the change in spherical equivalent refraction (SER, dioptres (D)) and axial length (mm) in the intervention and control groups at one year or longer) and difference in the change in SER and axial length following cessation of treatment ('rebound').  DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. We assessed bias using RoB 2 for parallel RCTs. We rated the certainty of evidence using the GRADE approach for the outcomes: change in SER and axial length at one and two years. Most comparisons were with inactive controls. MAIN RESULTS: We included 64 studies that randomised 11,617 children, aged 4 to 18 years. Studies were mostly conducted in China or other Asian countries (39 studies, 60.9%) and North America (13 studies, 20.3%). Fifty-seven studies (89%) compared myopia control interventions (multifocal spectacles, peripheral plus spectacles (PPSL), undercorrected single vision spectacles (SVLs), multifocal soft contact lenses (MFSCL), orthokeratology, rigid gas-permeable contact lenses (RGP); or pharmacological interventions (including high- (HDA), moderate- (MDA) and low-dose (LDA) atropine, pirenzipine or 7-methylxanthine) against an inactive control. Study duration was 12 to 36 months. The overall certainty of the evidence ranged from very low to moderate. Since the networks in the NMA were poorly connected, most estimates versus control were as, or more, imprecise than the corresponding direct estimates. Consequently, we mostly report estimates based on direct (pairwise) comparisons below. At one year, in 38 studies (6525 participants analysed), the median change in SER for controls was -0.65 D. The following interventions may reduce SER progression compared to controls: HDA (mean difference (MD) 0.90 D, 95% confidence interval (CI) 0.62 to 1.18), MDA (MD 0.65 D, 95% CI 0.27 to 1.03), LDA (MD 0.38 D, 95% CI 0.10 to 0.66), pirenzipine (MD 0.32 D, 95% CI 0.15 to 0.49), MFSCL (MD 0.26 D, 95% CI 0.17 to 0.35), PPSLs (MD 0.51 D, 95% CI 0.19 to 0.82), and multifocal spectacles (MD 0.14 D, 95% CI 0.08 to 0.21). By contrast, there was little or no evidence that RGP (MD 0.02 D, 95% CI -0.05 to 0.10), 7-methylxanthine (MD 0.07 D, 95% CI -0.09 to 0.24) or undercorrected SVLs (MD -0.15 D, 95% CI -0.29 to 0.00) reduce progression.  At two years, in 26 studies (4949 participants), the median change in SER for controls was -1.02 D. The following interventions may reduce SER progression compared to controls: HDA (MD 1.26 D, 95% CI 1.17 to 1.36), MDA (MD 0.45 D, 95% CI 0.08 to 0.83), LDA (MD 0.24 D, 95% CI 0.17 to 0.31), pirenzipine (MD 0.41 D, 95% CI 0.13 to 0.69), MFSCL (MD 0.30 D, 95% CI 0.19 to 0.41), and multifocal spectacles  (MD 0.19 D, 95% CI 0.08 to 0.30). PPSLs (MD 0.34 D, 95% CI -0.08 to 0.76) may also reduce progression, but the results were inconsistent. For RGP, one study found a benefit and another found no difference with control. We found no difference in SER change for undercorrected SVLs (MD 0.02 D, 95% CI -0.05 to 0.09). At one year, in 36 studies (6263 participants), the median change in axial length for controls was 0.31 mm. The following interventions may reduce axial elongation compared to controls: HDA (MD -0.33 mm, 95% CI -0.35 to 0.30), MDA (MD -0.28 mm, 95% CI -0.38 to -0.17), LDA (MD -0.13 mm, 95% CI -0.21 to -0.05), orthokeratology (MD -0.19 mm, 95% CI -0.23 to -0.15), MFSCL (MD -0.11 mm, 95% CI -0.13 to -0.09), pirenzipine (MD -0.10 mm, 95% CI -0.18 to -0.02), PPSLs (MD -0.13 mm, 95% CI -0.24 to -0.03), and multifocal spectacles (MD -0.06 mm, 95% CI -0.09 to -0.04). We found little or no evidence that RGP (MD 0.02 mm, 95% CI -0.05 to 0.10), 7-methylxanthine (MD 0.03 mm, 95% CI -0.10 to 0.03) or undercorrected SVLs (MD 0.05 mm, 95% CI -0.01 to 0.11) reduce axial length. At two years, in 21 studies (4169 participants), the median change in axial length for controls was 0.56 mm. The following interventions may reduce axial elongation compared to controls: HDA (MD -0.47mm, 95% CI -0.61 to -0.34), MDA (MD -0.33 mm, 95% CI -0.46 to -0.20), orthokeratology (MD -0.28 mm, (95% CI -0.38 to -0.19), LDA (MD -0.16 mm, 95% CI -0.20 to  -0.12), MFSCL (MD -0.15 mm, 95% CI -0.19 to -0.12), and multifocal spectacles (MD -0.07 mm, 95% CI -0.12 to -0.03). PPSL may reduce progression (MD -0.20 mm, 95% CI -0.45 to 0.05) but results were inconsistent. We found little or no evidence that undercorrected SVLs (MD -0.01 mm, 95% CI -0.06 to 0.03) or RGP (MD 0.03 mm, 95% CI -0.05 to 0.12) reduce axial length. There was inconclusive evidence on whether treatment cessation increases myopia progression. Adverse events and treatment adherence were not consistently reported, and only one study reported quality of life. No studies reported environmental interventions reporting progression in children with myopia, and no economic evaluations assessed interventions for myopia control in children. AUTHORS' CONCLUSIONS: Studies mostly compared pharmacological and optical treatments to slow the progression of myopia with an inactive comparator. Effects at one year provided evidence that these interventions may slow refractive change and reduce axial elongation, although results were often heterogeneous. A smaller body of evidence is available at two or three years, and uncertainty remains about the sustained effect of these interventions. Longer-term and better-quality studies comparing myopia control interventions used alone or in combination are needed, and improved methods for monitoring and reporting adverse effects.

ANTECEDENTES: La miopía es un defecto de refracción frecuente, en el que el alargamiento del globo ocular hace que los objetos lejanos aparezcan borrosos. La creciente prevalencia de la miopía es un problema de salud pública mundial cada vez mayor, en cuanto a tasas de defectos de refracción no corregidos y un significativamente mayor riesgo de discapacidad visual debido a la morbilidad ocular relacionada con la miopía. Dado que la miopía se suele detectar en niños antes de los 10 años y puede evolucionar rápidamente, las intervenciones para frenar su avance se deben realizar en la infancia. OBJETIVOS: Evaluar la eficacia comparativa de las intervenciones ópticas, farmacológicas y ambientales para frenar la progresión de la miopía en niños mediante un metanálisis en red (MAR). Generar una clasificación relativa de las intervenciones de control de la miopía en función de su eficacia. Elaborar un breve comentario económico que resuma las evaluaciones económicas de las intervenciones de control de la miopía en niños. Mantener la vigencia de la evidencia mediante un enfoque de revisión sistemática continua. MÉTODOS DE BÚSQUEDA: Se realizaron búsquedas en CENTRAL (que contiene el Registro de ensayos del Grupo Cochrane de Salud ocular y de la visión [Cochrane Eyes and Vision]), MEDLINE; Embase; y en tres registros de ensayos. La fecha de búsqueda fue el 26 de febrero de 2022. CRITERIOS DE SELECCIÓN: Se incluyeron ensayos controlados aleatorizados (ECA) de intervenciones ópticas, farmacológicas y ambientales para retrasar la progresión de la miopía en niños de hasta 18 años. Los desenlaces fundamentales fueron la progresión de la miopía (definida como la diferencia en el cambio del equivalente esférico de la refracción [EER, dioptrías (D)] y la longitud axial [mm] en los grupos de intervención y control al año o más) y la diferencia en el cambio del EER y la longitud axial tras el cese del tratamiento ("rebote"). OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Se utilizaron los métodos Cochrane estándar. El sesgo se evaluó mediante la herramienta RoB 2 en el caso de los ECA paralelos. La certeza de la evidencia se calificó mediante el método GRADE para los desenlaces: cambio del EER y la longitud axial al año y a los dos años. La mayoría de las comparaciones se realizaron con controles inactivos. RESULTADOS PRINCIPALES: Se incluyeron 64 estudios que asignaron al azar a 11 617 niños de cuatro a 18 años de edad. Los estudios se realizaron principalmente en China u otros países asiáticos (39 estudios; 60,9%) y Norteamérica (13 estudios; 20,3%). Cincuenta y siete estudios (89%) compararon intervenciones de control de la miopía (gafas multifocales, gafas periféricas plus [PPSL por sus siglas en inglés], gafas monofocales [SVL por sus siglas en inglés] subcorregidas, lentes de contacto multifocales blandas [MFSCL por sus siglas en inglés], ortoqueratología, lentes de contacto rígidas permeables al gas [RGP por sus siglas en inglés]); o intervenciones farmacológicas (incluidas atropina a dosis alta, media y baja, pirenzipina o 7­metilxantina) contra un control inactivo. La duración de los estudios fue de 12 a 36 meses. La certeza global de la evidencia varió entre muy baja y moderada. Debido a que las redes del MAR estaban mal conectadas, la mayoría de las estimaciones versus control fueron tan imprecisas o más que las correspondientes estimaciones directas. En consecuencia, a continuación se presentan principalmente estimaciones basadas en comparaciones directas (por pares). Al año, en 38 estudios (6525 participantes analizados), la mediana del cambio del EER para los controles fue de ­0,65 D. Las siguientes intervenciones podrían reducir la progresión del EER en comparación con los controles: atropina a dosis alta (diferencia de medias [DM] 0,90 D; intervalo de confianza [IC] del 95%: 0,62 a 1,18), atropina a dosis media (DM 0,65 D; IC del 95%: 0,27 a 1,03), atropina a dosis baja (DM 0,38 D; IC del 95%: 0,10 a 0,66), pirenzipina (DM 0,32 D; IC del 95%: 0,15 a 0,49), MFSCL (DM 0,26 D; IC del 95%: 0,17 a 0,35), PPSL (DM 0,51 D; IC del 95%: 0,19 a 0,82) y gafas multifocales (DM 0,14 D; IC del 95%: 0,08 a 0,21). Por el contrario, hubo poca o ninguna evidencia de que las RGP (DM 0,02 D; IC del 95%: ­0,05 a 0,10), la 7­metilxantina (DM 0,07 D; IC del 95%: ­0,09 a 0,24) o las SVL subcorregidas (DM ­0,15 D; IC del 95%: ­0,29 a 0,00) redujeran la progresión. A los dos años, en 26 estudios (4949 participantes), el cambio medio del EER para los controles fue de ­1,02 D. Las siguientes intervenciones podrían reducir la progresión del EER en comparación con los controles: atropina a dosis alta (DM 1,26 D; IC del 95%: 1,17 a 1,36), atropina a dosis media (DM 0,45 D; IC del 95%: 0,08 a 0,83), atropina a dosis baja (DM 0,24 D; IC del 95%: 0,17 a 0,31), pirenzipina (DM 0,41 D; IC del 95%: 0,13 a 0,69), MFSCL (DM 0,30 D; IC del 95%: 0,19 a 0,41) y gafas multifocales (DM 0,19 D; IC del 95%: 0,08 a 0,30). Las PPSL (DM 0,34 D; IC del 95%: ­0,08 a 0,76) también podrían reducir la progresión, pero los resultados no fueron consistentes. Para las RGP, un estudio encontró un efecto beneficioso y otro no encontró diferencias con el control. No se observaron diferencias en el cambio del EER para las SVL subcorregidas (DM 0,02 D; IC del 95%: ­0,05 a 0,09). Al año, en 36 estudios (6.263 participantes), el cambio medio en la longitud axial de los controles fue de 0,31 mm. Las siguientes intervenciones podrían reducir la elongación axial en comparación con los controles: atropina a dosis alta (DM ­0,33 mm; IC 95%: ­0,35 a 0,30), atropina a dosis media (DM ­0,28 mm; IC 95%: ­0,38 a ­0,17), atropina a dosis baja (DM ­0,13 mm; IC 95%: ­0,21 a ­0,05), ortoqueratología (DM ­0,19 mm; IC 95%: ­0,23 a ­0,15), MFSCL (DM ­0,11 mm; IC del 95%: ­0,13 a ­0,09), pirenzipina (DM ­0,10 mm; IC del 95%: ­0,18 a ­0,02), PPSL (DM ­0,13 mm; IC del 95%: ­0,24 a ­0,03) y gafas multifocales (DM ­0,06 mm; IC del 95%: ­0,09 a ­0,04). Se encontró poca o ninguna evidencia de que las RGP (DM 0,02 mm; IC del 95%: ­0,05 a 0,10), la 7­metilxantina (DM 0,03 mm; IC del 95%: ­0,10 a 0,03) o las SVL subcorregidas (DM 0,05 mm; IC del 95%: ­0,01 a 0,11) reduzcan la longitud axial. A los dos años, en 21 estudios (4169 participantes), la mediana del cambio en la longitud axial de los controles fue de 0,56 mm. Las siguientes intervenciones podrían reducir la elongación axial en comparación con los controles: atropina a dosis alta (DM ­0,47 mm; IC del 95%: ­0,61 a ­0,34), atropina a dosis media (DM ­0,33 mm; IC del 95%: ­0,46 a ­0,20), ortoqueratología (DM ­0,28 mm; IC del 95%: ­0,38 a ­0,19), atropina a dosis baja (DM ­0,16 mm; IC del 95%: ­0,20 a ­0,12), MFSCL (DM ­0,15 mm; IC del 95%: ­0,19 a ­0,12) y gafas multifocales (DM ­0,07 mm; IC del 95%: ­0,12 a ­0,03). Las PPSL podrían reducir la progresión (DM ­0,20 mm; IC del 95%: ­0,45 a 0,05), pero los resultados no fueron consistentes. Se encontró poca o ninguna evidencia de que las SVL subcorregidas (DM ­0,01 mm; IC del 95%: ­0,06 a 0,03) o las RGP (DM 0,03 mm; IC del 95%: ­0,05 a 0,12) reduzcan la longitud axial. No hubo evidencia concluyente sobre si el abandono del tratamiento aumenta la progresión de la miopía. Los eventos adversos y la adherencia al tratamiento no se comunicaron de forma consistente, y solo un estudio informó sobre la calidad de vida. Ningún estudio proporcionó información sobre intervenciones ambientales que informaran sobre la progresión en niños con miopía y ninguna evaluación económica analizó intervenciones para el control de la miopía en niños. CONCLUSIONES DE LOS AUTORES: La mayoría de los estudios compararon tratamientos farmacológicos y ópticos para enlentecer la progresión de la miopía con un comparador inactivo. Los efectos al año demostraron que estas intervenciones podrían ralentizar el cambio refractivo y reducir el alargamiento axial, aunque a menudo los resultados fueron heterogéneos. El conjunto de evidencia disponible a los dos o tres años fue más escaso, y persiste la incertidumbre sobre el efecto sostenido de estas intervenciones. Se necesitan estudios a más largo plazo y de mejor calidad que comparen las intervenciones para el control de la miopía utilizadas solas o en combinación, así como métodos mejorados de seguimiento y notificación de los efectos adversos.

Diagnostic accuracy of 1p/19q codeletion tests in oligodendroglioma: A comprehensive meta-analysis based on a Cochrane systematic review.

Codeletion of chromosomal arms 1p and 19q, in conjunction with a mutation in the isocitrate dehydrogenase 1 or 2 gene, is the molecular diagnostic criterion for oligodendroglioma, IDH mutant and 1p/19q codeleted. 1p/19q codeletion is a diagnostic marker and allows prognostication and prediction of the best drug response within IDH-mutant tumours. We performed a Cochrane review and simple economic analysis to establish the most sensitive, specific and cost-effective techniques for determining 1p/19q codeletion status. Fluorescent in situ hybridisation (FISH) and polymerase chain reaction (PCR)-based loss of heterozygosity (LOH) test methods were considered as reference standard. Most techniques (FISH, chromogenic in situ hybridisation [CISH], PCR, real-time PCR, multiplex ligation-dependent probe amplification [MLPA], single nucleotide polymorphism [SNP] array, comparative genomic hybridisation [CGH], array CGH, next-generation sequencing [NGS], mass spectrometry and NanoString) showed good sensitivity (few false negatives) for detection of 1p/19q codeletions in glioma, irrespective of whether FISH or PCR-based LOH was used as the reference standard. Both NGS and SNP array had a high specificity (fewer false positives) for 1p/19q codeletion when considered against FISH as the reference standard. Our findings suggest that G banding is not a suitable test for 1p/19q analysis. Within these limits, considering cost per diagnosis and using FISH as a reference, MLPA was marginally more cost-effective than other tests, although these economic analyses were limited by the range of available parameters, time horizon and data from multiple healthcare organisations.

Acupuncture for treating overactive bladder in adults.

BACKGROUND: Overactive bladder is a common, long-term symptom complex, which includes frequency of micturition, urgency with or without associated incontinence and nocturia. Around 11% of the population have symptoms, with this figure increasing with age. Symptoms can be linked to social anxiety and adaptive behavioural change. The cost of treating overactive bladder is considerable, with current treatments varying in effectiveness and being associated with side effects. Acupuncture has been suggested as an alternative treatment. OBJECTIVES: To assess the effects of acupuncture for treating overactive bladder in adults, and to summarise the principal findings of relevant economic evaluations. SEARCH METHODS: We searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (including In-Process, Epub Ahead of Print, Daily), ClinicalTrials.gov and WHO ICTRP (searched 14 May 2022). We also searched the Allied and Complementary Medicine database (AMED) and bibliographic databases where knowledge of the Chinese language was necessary: China National Knowledge Infrastructure (CNKI); Chinese Science and Technology Periodical Database (VIP) and WANFANG (China Online Journals), as well as the reference lists of relevant articles.  SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi-RCTs and cross-over RCTs assessing the effects of acupuncture for treating overactive bladder in adults. DATA COLLECTION AND ANALYSIS: Four review authors formed pairs to assess study eligibility and extract data. Both pairs used Covidence software to perform screening and data extraction. We assessed risk of bias using Cochrane's risk of bias tool and assessed heterogeneity using the Chi2 testand I2 statistic generated within the meta-analyses. We used a fixed-effect model within the meta-analyses unless there was a moderate or high level of heterogeneity, where we employed a random-effects model. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included 15 studies involving 1395 participants in this review (14 RCTs and one quasi-RCT). All included studies raised some concerns regarding risk of bias. Blinding of participants to treatment group was only achieved in 20% of studies, we considered blinding of outcome assessors and allocation concealment to be low risk in only 25% of the studies, and random sequence generation to be either unclear or high risk in more than 50% of the studies. Acupuncture versus no treatment One study compared acupuncture to no treatment. The evidence is very uncertain regarding the effect of acupuncture compared to no treatment in curing or improving overactive bladder symptoms and on the number of minor adverse events (both very low-certainty evidence). The study report explicitly stated that no major adverse events occurred. The study did not report on the presence or absence of urinary urgency, episodes of urinary incontinence, daytime urinary frequency or episodes of nocturia. Acupuncture versus sham acupuncture Five studies compared acupuncture with sham acupuncture. The evidence is very uncertain about the effect of acupuncture on curing or improving overactive bladder symptoms compared to sham acupuncture (standardised mean difference (SMD) -0.36, 95% confidence interval (CI) -1.03 to 0.31; 3 studies; 151 participants; I2 = 65%; very low-certainty evidence). All five studies explicitly stated that there were no major adverse events observed during the study. Moderate-certainty evidence suggests that acupuncture probably makes no difference to the incidence of minor adverse events compared to sham acupuncture (risk ratio (RR) 1.28, 95% CI 0.30 to 5.36; 4 studies; 222 participants; I² = 0%). Only one small study reported data for the presence or absence of urgency and for episodes of nocturia. The evidence is of very low certainty for both of these outcomes and in both cases the lower confidence interval is implausible. Moderate-certainty evidence suggests there is probably little or no difference in episodes of urinary incontinence between acupuncture and sham acupuncture (mean difference (MD) 0.55, 95% CI -1.51 to 2.60; 2 studies; 121 participants; I2 = 57%). Two studies recorded data regarding daytime urinary frequency but we could not combine them in a meta-analysis due to differences in methodologies (very low-certainty evidence). Acupuncture versus medication Eleven studies compared acupuncture with medication. Low-certainty evidence suggests that acupuncture may slightly increase how many people's overactive bladder symptoms are cured or improved compared to medication (RR 1.25, 95% CI 1.10 to 1.43; 5 studies; 258 participants; I2 = 19%). Low-certainty evidence suggests that acupuncture may reduce the incidence of minor adverse events when compared to medication (RR 0.34, 95% CI 0.26 to 0.45; 8 studies; 1004 participants; I² = 51%). The evidence is uncertain regarding the effect of acupuncture on the presence or absence of urinary urgency (MD -0.40, 95% CI -0.56 to -0.24; 2 studies; 80 participants; I2 = 0%; very low-certainty evidence) and episodes of urinary incontinence (MD -0.33, 95% CI -2.75 to 2.09; 1 study; 20 participants; very low-certainty evidence) compared to medication. Low-certainty evidence suggests there may be little to no effect of acupuncture compared to medication in terms of daytime urinary frequency (MD 0.73, 95% CI -0.39 to 1.85; 4 studies; 360 participants; I2 = 28%). Acupuncture may slightly reduce the number of nocturia episodes compared to medication (MD -0.50, 95% CI -0.65 to -0.36; 2 studies; 80 participants; I2 = 0%, low-certainty evidence). There were no incidences of major adverse events in any of the included studies. However, major adverse events are rare in acupuncture trials and the numbers included in this review may be insufficient to detect these events. AUTHORS' CONCLUSIONS: The evidence is very uncertain about the effect acupuncture has on cure or improvement of overactive bladder symptoms compared to no treatment. It is uncertain if there is any difference between acupuncture and sham acupuncture in cure or improvement of overactive bladder symptoms. This review provides low-certainty evidence that acupuncture may result in a slight increase in cure or improvement of overactive bladder symptoms when compared with medication and may reduce the incidence of minor adverse events. These conclusions must remain tentative until the completion of larger, higher-quality studies that use relevant, comparable outcomes. Timing and frequency of treatment, point selection, application and long-term follow-up are other areas relevant for research.

Diagnostic test accuracy and cost-effectiveness of tests for codeletion of chromosomal arms 1p and 19q in people with glioma.

BACKGROUND: Complete deletion of both the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q), known as 1p/19q codeletion, is a mutation that can occur in gliomas. It occurs in a type of glioma known as oligodendroglioma and its higher grade counterpart known as anaplastic oligodendroglioma. Detection of 1p/19q codeletion in gliomas is important because, together with another mutation in an enzyme known as isocitrate dehydrogenase, it is needed to make the diagnosis of an oligodendroglioma. Presence of 1p/19q codeletion also informs patient prognosis and prediction of the best drug treatment. The main two tests in use are fluorescent in situ hybridisation (FISH) and polymerase chain reaction (PCR)-based loss of heterozygosity (LOH) assays (also known as PCR-based short tandem repeat or microsatellite analysis). Many other tests are available. None of the tests is perfect, although PCR-based LOH is expected to have very high sensitivity. OBJECTIVES: To estimate the sensitivity and specificity and cost-effectiveness of different deoxyribonucleic acid (DNA)-based techniques for determining 1p/19q codeletion status in glioma. SEARCH METHODS: We searched MEDLINE, Embase and BIOSIS up to July 2019. There were no restrictions based on language or date of publication. We sought economic evaluation studies from the results of this search and using the National Health Service Economic Evaluation Database. SELECTION CRITERIA: We included cross-sectional studies in adults with glioma or any subtype of glioma, presenting raw data or cross-tabulations of two or more DNA-based tests for 1p/19q codeletion. We also sought economic evaluations of these tests. DATA COLLECTION AND ANALYSIS: We followed procedures outlined in the Cochrane Handbook for Diagnostic Test Accuracy Reviews. Two review authors independently screened titles/abstracts/full texts, performed data extraction, and undertook applicability and risk of bias assessments using QUADAS-2. Meta-analyses used the hierarchical summary ROC model to estimate and compare test accuracy. We used FISH and PCR-based LOH as alternate reference standards to examine how tests compared with those in common use, and conducted a latent class analysis comparing FISH and PCR-based LOH. We constructed an economic model to evaluate cost-effectiveness. MAIN RESULTS: We included 53 studies examining: PCR-based LOH, FISH, single nucleotide polymorphism (SNP) array, next-generation sequencing (NGS), comparative genomic hybridisation (CGH), array comparative genomic hybridisation (aCGH), multiplex-ligation-dependent probe amplification (MLPA), real-time PCR, chromogenic in situ hybridisation (CISH), mass spectrometry (MS), restriction fragment length polymorphism (RFLP) analysis, G-banding, methylation array and NanoString. Risk of bias was low for only one study; most gave us concerns about how patients were selected or about missing data. We had applicability concerns about many of the studies because only patients with specific subtypes of glioma were included. 1520 participants contributed to analyses using FISH as the reference, 1304 participants to analyses involving PCR-based LOH as the reference and 262 participants to analyses of comparisons between methods from studies not including FISH or PCR-based LOH. Most evidence was available for comparison of FISH with PCR-based LOH (15 studies, 915 participants): PCR-based LOH detected 94% of FISH-determined codeletions (95% credible interval (CrI) 83% to 98%) and FISH detected 91% of codeletions determined by PCR-based LOH (CrI 78% to 97%). Of tumours determined not to have a deletion by FISH, 94% (CrI 87% to 98%) had a deletion detected by PCR-based LOH, and of those determined not to have a deletion by PCR-based LOH, 96% (CrI 90% to 99%) had a deletion detected by FISH. The latent class analysis suggested that PCR-based LOH may be slightly more accurate than FISH. Most other techniques appeared to have high sensitivity (i.e. produced few false-negative results) for detection of 1p/19q codeletion when either FISH or PCR-based LOH was considered as the reference standard, although there was limited evidence. There was some indication of differences in specificity (false-positive rate) with some techniques. Both NGS and SNP array had high specificity when considered against FISH as the reference standard (NGS: 6 studies, 243 participants; SNP: 6 studies, 111 participants), although we rated certainty in the evidence as low or very low. NGS and SNP array also had high specificity when PCR-based LOH was considered the reference standard, although with much more uncertainty as these results were based on fewer studies (just one study with 49 participants for NGS and two studies with 33 participants for SNP array). G-banding had low sensitivity and specificity when PCR-based LOH was the reference standard. Although MS had very high sensitivity and specificity when both FISH and PCR-based LOH were considered the reference standard, these results were based on only one study with a small number of participants. Real-time PCR also showed high specificity with FISH as a reference standard, although there were only two studies including 40 participants. We found no relevant economic evaluations. Our economic model using FISH as the reference standard suggested that the resource-optimising test depends on which measure of diagnostic accuracy is most important. With FISH as the reference standard, MLPA is likely to be cost-effective if society was willing to pay GBP 1000 or less for a true positive detected. However, as the value placed on a true positive increased, CISH was most cost-effective. Findings differed when the outcome measure changed to either true negative detected or correct diagnosis. When PCR-based LOH was used as the reference standard, MLPA was likely to be cost-effective for all measures of diagnostic accuracy at lower threshold values for willingness to pay. However, as the threshold values increased, none of the tests were clearly more likely to be considered cost-effective. AUTHORS' CONCLUSIONS: In our review, most techniques (except G-banding) appeared to have good sensitivity (few false negatives) for detection of 1p/19q codeletions in glioma against both FISH and PCR-based LOH as a reference standard. However, we judged the certainty of the evidence low or very low for all the tests. There are possible differences in specificity, with both NGS and SNP array having high specificity (fewer false positives) for 1p/19q codeletion when considered against FISH as the reference standard. The economic analysis should be interpreted with caution due to the small number of studies.

Treatment options for progression or recurrence of glioblastoma: a network meta-analysis.

BACKGROUND: Glioblastoma (GBM) is a highly malignant brain tumour that almost inevitably progresses or recurs after first line standard of care. There is no consensus regarding the best treatment/s to offer people upon disease progression or recurrence. For the purposes of this review, progression and recurrence are considered as one entity. OBJECTIVES: To evaluate the effectiveness of further treatment/s for first and subsequent progression or recurrence of glioblastoma (GBM) among people who have received the standard of care (Stupp protocol) for primary treatment of the disease; and to prepare a brief economic commentary on the available evidence. SEARCH METHODS: We searched MEDLINE and Embase electronic databases from 2005 to December 2019 and the Cochrane Central Register of Controlled Trials (CENTRAL, in the Cochrane Library; Issue 12, 2019). Economic searches included the National Health Service Economic Evaluation Database (NHS EED) up to 2015 (database closure) and MEDLINE and Embase from 2015 to December 2019. SELECTION CRITERIA: Randomised controlled trials (RCTs) and comparative non-randomised studies (NRSs) evaluating effectiveness of treatments for progressive/recurrent GBM. Eligible studies included people with progressive or recurrent GBM who had received first line radiotherapy with concomitant and adjuvant temozolomide (TMZ). DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted data to a pre-designed data extraction form. We conducted network meta-analyses (NMA) and ranked treatments according to effectiveness for each outcome using the random-effects model and Stata software (version 15). We rated the certainty of evidence using the GRADE approach. MAIN RESULTS: We included 42 studies: these comprised 34 randomised controlled trials (RCTs) and 8 non-randomised studies (NRSs) involving 5236 participants. We judged most RCTs to be at a low risk of bias and NRSs at high risk of bias. Interventions included chemotherapy, re-operation, re-irradiation and novel therapies either used alone or in combination. For first recurrence, we included 11 interventions in the network meta-analysis (NMA) for overall survival (OS), and eight in the NMA for progression-free survival (PFS). Lomustine (LOM; also known as CCNU) was the most common comparator and was used as the reference treatment. No studies in the NMA evaluated surgery, re-irradiation, PCV (procarbazine, lomustine, vincristine), TMZ re-challenge or best supportive care. We could not perform NMA for second or later recurrence due to insufficient data. Quality-of-life data were sparse. First recurrence (NMA findings) Median OS across included studies in the NMA ranged from 5.5 to 12.6 months and median progression-free survival (PFS) ranged from 1.5 months to 4.2 months. We found no high-certainty evidence that any treatments tested were better than lomustine. These treatments included the following. Bevacizumab plus lomustine: Evidence suggested probably little or no difference in OS between bevacizumab (BEV) combined with lomustine (LOM) and LOM monotherapy (hazard ratio (HR) 0.91, 0.75 to 1.10; moderate-certainty evidence), although BEV + LOM may improve PFS (HR 0.57, 95% confidence interval (CI) 0.44 to 0.74; low-certainty evidence). Bevacizumab monotherapy: Low-certainty evidence suggested there may be little or no difference in OS (HR 1.22, 95% CI 0.84 to 1.76) and PFS (HR 0.90, 95% CI 0.58 to 1.38; low-certainty evidence) between BEV and LOM monotherapies; more evidence on BEV is needed. Regorafenib (REG): REG may improve OS compared with LOM (HR 0.50, 95% CI 0.33 to 0.76; low-certainty evidence). Evidence on PFS was very low certainty and more evidence on REG is needed. Temozolomide (TMZ) plus Depatux-M (ABT414): For OS, low-certainty evidence suggested that TMZ plus ABT414 may be more effective than LOM (HR 0.66, 95% CI 0.47 to 0.92) and may be more effective than BEV (HR 0.54, 95% CI 0.33 to 0.89; low-certainty evidence). This may be due to the TMZ component only and more evidence is needed. Fotemustine (FOM): FOM and LOM may have similar effects on OS (HR 0.89, 95% CI 0.51 to 1.57, low-certainty evidence). Bevacizumab and irinotecan (IRI): Evidence on BEV + irinotecan (IRI) versus LOM for both OS and PFS is very uncertain and there is probably little or no difference between BEV + IRI versus BEV monotherapy (OS: HR 0.95, 95% CI 0.70 to 1.30; moderate-certainty evidence). When treatments were ranked for OS, FOM ranked first, BEV + LOM second, LOM third, BEV + IRI fourth, and BEV fifth. Ranking does not take into account the certainty of the evidence, which also suggests there may be little or no difference between FOM and LOM. Other treatments Three studies evaluated re-operation versus no re-operation, with or without re-irradiation and chemotherapy, and these suggested possible survival advantages with re-operation within the context of being able to select suitable candidates for re-operation. A cannabinoid treatment in the early stages of evaluation, in combination with TMZ, merits further evaluation. Second or later recurrence Limited evidence from three heterogeneous studies suggested that radiotherapy with or without BEV may have a beneficial effect on survival but more evidence is needed. Evidence was insufficient to draw conclusions about the best radiotherapy dosage. Other evidence suggested that there may be little difference in survival with tumour-treating fields compared with physician's best choice of treatment. We found no reliable evidence on best supportive care. Severe adverse events (SAEs) The BEV+LOM combination was associated with significantly greater risk of SAEs than LOM monotherapy (RR 2.51, 95% CI 1.72 to 3.66, high-certainty evidence), and ranked joint worst with cediranib + LOM (RR 2.51, 95% CI 1.29 to 4.90; high-certainty evidence). LOM ranked best and REG ranked second best. Adding novel treatments to BEV was generally associated with a higher risk of severe adverse events compared with BEV alone. AUTHORS' CONCLUSIONS: For treatment of first recurrence of GBM, among people previously treated with surgery and standard chemoradiotherapy, the combination treatments evaluated did not improve overall survival compared with LOM monotherapy and were often associated with a higher risk of severe adverse events. Limited evidence suggested that re-operation with or without re-irradiation and chemotherapy may be suitable for selected candidates. Evidence on second recurrence is sparse. Re-irradiation with or without bevacizumab may be of value in selected individuals, but more evidence is needed.

ANTECEDENTES: El glioblastoma (GBM) es un tumor cerebral altamente maligno que casi inevitablemente progresa o recidiva después de un tratamiento de primera línea. No hay consenso sobre el mejor o los mejores tratamientos que se pueden ofrecer a las personas que presentan progresión o recidiva de la enfermedad. A los efectos de la presente revisión, la progresión y la recidiva se consideran como una sola entidad. OBJETIVOS: Evaluar la efectividad de los tratamientos adicionales para la primera y subsiguiente progresión o recidiva del glioblastoma (GBM) entre las personas que han recibido atención estándar (protocolo Stupp) para el tratamiento primario de la enfermedad, así como preparar un breve comentario económico sobre la evidencia disponible. MÉTODOS DE BÚSQUEDA: Se realizaron búsquedas en las bases de datos electrónicas de MEDLINE y Embase desde 2005 hasta diciembre de 2019 y en el Registro Cochrane central de ensayos controlados (Cochrane Central Register of Controlled Trials) (CENTRAL, en la Cochrane Library; Número 12, 2019). Las búsquedas económicas incluyeron la National Health Service Economic Evaluation Database (NHS EED) hasta 2015 (cierre de la base de datos) y MEDLINE y Embase desde 2015 hasta diciembre de 2019. CRITERIOS DE SELECCIÓN: Ensayos controlados aleatorizados (ECA) y estudios comparativos no aleatorizados (no ECA) que evaluaron la efectividad de los tratamientos para el GBM progresivo/recidivante. Los estudios elegibles incluyeron personas con GBM progresivo o recidivante que habían recibido radioterapia de primera línea con temozolomida (TMZ) concomitante y adyuvante. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión de forma independiente seleccionaron los estudios y extrajeron los datos en un formulario de extracción de datos prediseñado. Se realizaron metanálisis en red (MAR) y los tratamientos se clasificaron según la efectividad de cada desenlace, mediante el modelo de efectos aleatorios y el software Stata (versión 15). La certeza de la evidencia se evaluó mediante los criterios GRADE. RESULTADOS PRINCIPALES: Se incluyeron 42 estudios, que comprendieron 34 ensayos controlados aleatorizados (ECA) y ocho estudios no aleatorizados (no ECA), con 5236 participantes. Se consideró que la mayoría de los ECA tuvieron bajo riesgo de sesgo y que los no ECA tuvieron alto riesgo de sesgo. Las intervenciones incluyeron quimioterapia, reoperación, reirradiación y tratamientos nuevos, ya sea utilizadas solos o en combinación. Para la primera recidiva se incluyeron 11 intervenciones en el metanálisis en red (MAR) para la supervivencia general (SG), y ocho para la supervivencia sin progresión (SSP). La lomustina (LOM; también conocida como CCNU) fue el comparador más frecuente y se utilizó como tratamiento de referencia. Ningún estudio en el MAR evaluó la cirugía, la reirradiación, la PCV (procarbazina, lomustina, vincristina), la reexposición a TMZ o el mejor tratamiento de apoyo. No fue posible realizar un MAR para una segunda o posterior recidiva debido a que los datos no fueron suficientes. Los datos de calidad de vida fueron escasos. Primera recidiva (hallazgos del MAR) La mediana de la SG en los estudios incluidos en el MAR varió entre 5,5 y 12,6 meses y la mediana de la supervivencia sin progresión (SSP) varió entre 1,5 y 4,2 meses. No se encontró evidencia de certeza alta de que los tratamientos probados fueran mejores que la lomustina. Estos tratamientos incluyeron los siguientes. Bevacizumab más lomustina: La evidencia indicó probablemente poca o ninguna diferencia en la SG entre el bevacizumab (BEV) combinado con lomustina (LOM) y la monoterapia con LOM (cociente de riesgos instantáneo [CRI] 0,91; 0,75 a 1,10; evidencia de certeza moderada), aunque BEV + LOM puede mejorar la SSP (CRI 0,57; intervalo de confianza [IC] del 95%: 0,44 a 0,74; evidencia de certeza baja). Monoterapia con bevacizumab: La evidencia de certeza baja indicó que puede haber poca o ninguna diferencia en la SG (CRI 1,22; IC del 95%: 0,84 a 1,76) y la SSP (CRI 0,90; IC del 95%: 0,58 a 1,38; evidencia de certeza baja) entre las monoterapias con BEV y LOM; se necesita más evidencia sobre el BEV. Regorafenib (REG): El REG puede mejorar la SG en comparación con la LOM (CRI 0,50; IC del 95%: 0,33 a 0,76; evidencia de certeza baja). La evidencia sobre la SSP fue de certeza muy baja y se necesita más evidencia sobre el REG. Temozolomida (TMZ) más Depatux­M (ABT414): En cuanto a la SG, evidencia de certeza baja indicó que TMZ más ABT414 puede ser más efectiva que LOM (CRI 0,66; IC del 95%: 0,47 a 0,92) y puede ser más efectiva que BEV (CRI 0,54; IC del 95%: 0,33 a 0,89; evidencia de certeza baja). Lo anterior se puede deber solamente al componente de TMZ, y se necesita más evidencia. Fotemustina (FOM): FOM y LOM pueden tener efectos similares sobre la SG (CRI 0,89; IC del 95%: 0,51 a 1,57, evidencia de certeza baja). Bevacizumab e irinotecan (IRI): La evidencia sobre BEV + irinotecan (IRI) versus LOM para la SG y la SSP no está clara y probablemente hay poca o ninguna diferencia entre BEV + IRI versus la monoterapia con BEV (SG: CRI 0,95; IC del 95%: 0,70 a 1,30; evidencia de certeza moderada). Cuando los tratamientos se clasificaron según la SG, FOM se clasificó primero, BEV + LOM segundo, LOM tercero, BEV + IRI cuarto, y BEV quinto. La clasificación no tiene en cuenta la certeza de la evidencia, lo que también indica que puede haber poca o ninguna diferencia entre FOM y LOM. Otros tratamientos Tres estudios evaluaron la reoperación versus ninguna reoperación, con o sin reirradiación y quimioterapia, e indicaron posibles ventajas en la supervivencia con la reoperación, en el contexto de poder seleccionar candidatos adecuados para esta intervención. Un tratamiento con cannabinoides en las primeras etapas de evaluación, en combinación con TMZ, merece evaluación adicional. Segunda o posterior recidiva La evidencia limitada de tres estudios heterogéneos indicó que la radioterapia con o sin BEV puede tener un efecto beneficioso sobre la supervivencia, pero se necesita más evidencia. La evidencia no fue suficiente para establecer conclusiones sobre la mejor dosis de radioterapia. Otra evidencia indicó que puede haber poca diferencia en la supervivencia con los campos de tratamiento del tumor en comparación con la mejor opción de tratamiento del médico. No se encontró evidencia fiable sobre el mejor tratamiento de apoyo. Eventos adversos graves (EAG) La combinación BEV + LOM se asoció con un riesgo significativamente mayor de EAG que la monoterapia con LOM (RR 2,51; IC del 95%: 1,72 a 3,66; evidencia de certeza alta), y se clasificó peor junto con cediranib + LOM (RR 2,51; IC del 95%: 1,29 a 4,90; evidencia de certeza alta). LOM se clasificó como el mejor y REG como el segundo mejor. Agregar nuevos tratamientos al BEV se asoció generalmente con un mayor riesgo de eventos adversos graves, en comparación con BEV solo. CONCLUSIONES DE LOS AUTORES: Para el tratamiento de la primera recidiva del GBM en personas tratadas previamente con cirugía y quimiorradioterapia estándar, los tratamientos combinados evaluados no mejoraron la supervivencia general en comparación con la monoterapia con LOM, y a menudo se asociaron con un mayor riesgo de eventos adversos graves. Hay evidencia limitada que indica que la reoperación con o sin reirradiación y quimioterapia puede ser adecuada para candidatos seleccionados. La evidencia sobre la segunda recidiva es escasa. La reirradiación con o sin bevacizumab puede ser de valor en determinados individuos, pero se necesita más evidencia.

Intraoperative imaging technology to maximise extent of resection for glioma: a network meta-analysis.

BACKGROUND: Multiple studies have identified the prognostic relevance of extent of resection in the management of glioma. Different intraoperative technologies have emerged in recent years with unknown comparative efficacy in optimising extent of resection. One previous Cochrane Review provided low- to very low-certainty evidence in single trial analyses and synthesis of results was not possible. The role of intraoperative technology in maximising extent of resection remains uncertain. Due to the multiple complementary technologies available, this research question is amenable to a network meta-analysis methodological approach. OBJECTIVES: To establish the comparative effectiveness and risk profile of specific intraoperative imaging technologies using a network meta-analysis and to identify cost analyses and economic evaluations as part of a brief economic commentary. SEARCH METHODS: We searched CENTRAL (2020, Issue 5), MEDLINE via Ovid to May week 2 2020, and Embase via Ovid to 2020 week 20. We performed backward searching of all identified studies. We handsearched two journals, Neuro-oncology and the Journal of Neuro-oncology from 1990 to 2019 including all conference abstracts. Finally, we contacted recognised experts in neuro-oncology to identify any additional eligible studies and acquire information on ongoing randomised controlled trials (RCTs). SELECTION CRITERIA: RCTs evaluating people of all ages with presumed new or recurrent glial tumours (of any location or histology) from clinical examination and imaging (computed tomography (CT) or magnetic resonance imaging (MRI), or both). Additional imaging modalities (e.g. positron emission tomography, magnetic resonance spectroscopy) were not mandatory. Interventions included fluorescence-guided surgery, intraoperative ultrasound, neuronavigation (with or without additional image processing, e.g. tractography), and intraoperative MRI. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the search results for relevance, undertook critical appraisal according to known guidelines, and extracted data using a prespecified pro forma. MAIN RESULTS: We identified four RCTs, using different intraoperative imaging technologies: intraoperative magnetic resonance imaging (iMRI) (2 trials, with 58 and 14 participants); fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) (1 trial, 322 participants); and neuronavigation (1 trial, 45 participants). We identified one ongoing trial assessing iMRI with a planned sample size of 304 participants for which results are expected to be published around winter 2020. We identified no published trials for intraoperative ultrasound. Network meta-analyses or traditional meta-analyses were not appropriate due to absence of homogeneous trials across imaging technologies. Of the included trials, there was notable heterogeneity in tumour location and imaging technologies utilised in control arms. There were significant concerns regarding risk of bias in all the included studies. One trial of iMRI found increased extent of resection (risk ratio (RR) for incomplete resection was 0.13, 95% confidence interval (CI) 0.02 to 0.96; 49 participants; very low-certainty evidence) and one trial of 5-ALA (RR for incomplete resection was 0.55, 95% CI 0.42 to 0.71; 270 participants; low-certainty evidence). The other trial assessing iMRI was stopped early after an unplanned interim analysis including 14 participants; therefore, the trial provided very low-quality evidence. The trial of neuronavigation provided insufficient data to evaluate the effects on extent of resection. Reporting of adverse events was incomplete and suggestive of significant reporting bias (very low-certainty evidence). Overall, the proportion of reported events was low in most trials and, therefore, issues with power to detect differences in outcomes that may or may not have been present. Survival outcomes were not adequately reported, although one trial reported no evidence of improvement in overall survival with 5-ALA (hazard ratio (HR) 0.82, 95% CI 0.62 to 1.07; 270 participants; low-certainty evidence). Data for quality of life were only available for one study and there was significant attrition bias (very low-certainty evidence). AUTHORS' CONCLUSIONS: Intraoperative imaging technologies, specifically 5-ALA and iMRI, may be of benefit in maximising extent of resection in participants with high-grade glioma. However, this is based on low- to very low-certainty evidence. Therefore, the short- and long-term neurological effects are uncertain. Effects of image-guided surgery on overall survival, progression-free survival, and quality of life are unclear. Network and traditional meta-analyses were not possible due to the identified high risk of bias, heterogeneity, and small trials included in this review. A brief economic commentary found limited economic evidence for the equivocal use of iMRI compared with conventional surgery. In terms of costs, one non-systematic review of economic studies suggested that, compared with standard surgery, use of image-guided surgery has an uncertain effect on costs and that 5-ALA was more costly. Further research, including completion of ongoing trials of ultrasound-guided surgery, is needed.

ANTECEDENTES: En múltiples estudios se ha identificado la importancia pronóstica del alcance de la resección en el tratamiento del glioma. En los últimos años han surgido diferentes tecnologías intraoperatorias con una eficacia comparativa desconocida para optimizar el alcance de la resección. Una revisión Cochrane anterior proporcionó evidencia de certeza baja a muy baja en los análisis de un solo ensayo y no fue posible la síntesis de los resultados. La función de la tecnología intraoperatoria para maximizar el alcance de la resección aún no está clara. Debido a las múltiples tecnologías complementarias disponibles, esta pregunta de investigación se presta a un enfoque metodológico de metanálisis en red. OBJETIVOS: Establecer el perfil comparativo de efectividad y riesgo de determinadas tecnologías de imagenología intraoperatorias mediante un metanálisis en red e identificar análisis de costos y evaluaciones económicas como parte de un breve comentario económico. MÉTODOS DE BÚSQUEDA: Se hicieron búsquedas en CENTRAL (2020, número 5), MEDLINE vía Ovid hasta la semana 2 de mayo de 2020, y Embase vía Ovid hasta la semana 20 de 2020. Se realizó una búsqueda retrospectiva de todos los estudios identificados. Se hicieron búsquedas manuales en dos revistas, Neuro­oncology y Journal of Neuro­oncology, desde 1990 hasta 2019, y se incluyeron todos los resúmenes de congresos. Finalmente, se estableció contacto con expertos reconocidos en neurooncología para identificar cualquier estudio elegible adicional y obtener información sobre los ensayos controlados aleatorizados (ECA) en curso. CRITERIOS DE SELECCIÓN: ECA que evaluaron a personas de todas las edades con presuntos tumores gliales nuevos o recidivantes (de cualquier ubicación o histología) a partir del examen clínico y la imagenología (tomografía computarizada [TC] o imagenología de resonancia magnética [IRM], o ambas). Las modalidades adicionales de imagenología (p.ej., tomografía de emisión de positrones, espectroscopia de resonancia magnética) no fueron obligatorias. Las intervenciones incluyeron cirugía guiada por fluorescencia, ecografía intraoperatoria, neuronavegación (con o sin procesamiento adicional de las imágenes, p.ej., tractografía) e IRM intraoperatoria. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión, de forma independiente, evaluaron los resultados de la búsqueda en cuanto a su relevancia, realizaron la evaluación crítica según las guías conocidas y extrajeron los datos mediante un formulario predeterminado. RESULTADOS PRINCIPALES: Se identificaron cuatro ECA, que utilizaron diferentes tecnologías de imagenología intraoperatorias: la resonancia magnética (IRM) intraoperatoria (dos ensayos, con 58 y 14 participantes); la cirugía guiada por fluorescencia con ácido 5­aminolevulínico (5­ALA) (un ensayo, 322 participantes); y la neuronavegación (un ensayo, 45 participantes). Se identificó un ensayo en curso que evaluó la IRM con un tamaño de la muestra planificado de 304 participantes, del que se espera la publicación de los resultados alrededor del invierno de 2020. No se han identificado ensayos publicados sobre la ecografía intraoperatoria. Los metanálisis en red o los metanálisis tradicionales no fueron apropiados debido a la falta de ensayos homogéneos en tecnologías de imagenología. De los ensayos incluidos, hubo una notable heterogeneidad en la localización de los tumores y en las tecnologías de imagenología utilizadas en los brazos control. Hubo inquietudes significativas con respecto al riesgo de sesgo en todos los estudios incluidos. Un ensayo de IRM encontró un aumento en la extensión de la resección (razón de riesgos [RR] para la resección incompleta 0,13; intervalo de confianza [IC] del 95%: 0,02 a 0,96; 49 participantes; evidencia de certeza muy baja) y un ensayo de 5­ALA (RR para la resección incompleta 0,55; IC del 95%: 0,42 a 0,71; 270 participantes; evidencia de certeza baja). El otro ensayo que evaluó la IRM se interrumpió de forma temprana después de un análisis intermedio no planificado que incluyó 14 participantes; por lo tanto, el ensayo proporciona evidencia de calidad muy baja. El ensayo de neuronavegación no proporcionó datos suficientes para evaluar los efectos sobre el grado de resección. El informe de los eventos adversos fue incompleto e indicó la presencia de sesgo de informe significativo (evidencia de certeza muy baja). En general, la proporción de eventos informados fue baja en la mayoría de los ensayos y, por lo tanto, pueden haber estado presentes o no problemas relacionados con el poder estadístico suficiente para detectar diferencias en los desenlaces. No se informó adecuadamente sobre los desenlaces de supervivencia, aunque un ensayo no informó evidencia de mejora en la supervivencia general con 5­ALA (cociente de riesgos instantáneos [CRI] 0,82; IC del 95%: 0,62 a 1,07; 270 participantes; evidencia de certeza baja). Solo hubo datos disponibles sobre la calidad de vida de un estudio, con un sesgo de desgaste significativo (evidencia de certeza muy baja). CONCLUSIONES DE LOS AUTORES: Las tecnologías de imagenología intraoperatoria, específicamente la IRM y el 5­ALA, pueden ser beneficiosas para maximizar el grado de resección en los participantes con glioma de grado alto. Sin embargo, lo anterior se basa en evidencia de certeza baja a muy baja. Por lo tanto, los efectos neurológicos a corto y a largo plazo no están claros. No están claros los efectos de la cirugía guiada por imágenes sobre la supervivencia general, la supervivencia sin progresión ni la calidad de vida. No fue posible realizar metanálisis en red ni tradicionales debido al alto riesgo de sesgo identificado, a la heterogeneidad y a los ensayos pequeños incluidos en esta revisión. Un comentario económico breve encontró evidencia económica limitada sobre el uso equívoco de la IRM en comparación con la cirugía convencional. En cuanto a los costos, una revisión no sistemática de estudios económicos indicó que, en comparación con la cirugía estándar, el uso de la cirugía guiada por imágenes no tiene un efecto claro sobre los costos y que el ácido 5­aminolevulínico fue más costoso. Se necesitan estudios de investigación adicionales, incluida la finalización de los ensayos en curso sobre la cirugía guiada por ecografía.

Prognostic value of test(s) for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation for predicting overall survival in people with glioblastoma treated with temozolomide.

BACKGROUND: Glioblastoma is an aggressive form of brain cancer. Approximately five in 100 people with glioblastoma survive for five years past diagnosis. Glioblastomas that have a particular modification to their DNA (called methylation) in a particular region (the O6-methylguanine-DNA methyltransferase (MGMT) promoter) respond better to treatment with chemotherapy using a drug called temozolomide. OBJECTIVES: To determine which method for assessing MGMT methylation status best predicts overall survival in people diagnosed with glioblastoma who are treated with temozolomide. SEARCH METHODS: We searched MEDLINE, Embase, BIOSIS, Web of Science Conference Proceedings Citation Index to December 2018, and examined reference lists. For economic evaluation studies, we additionally searched NHS Economic Evaluation Database (EED) up to December 2014. SELECTION CRITERIA: Eligible studies were longitudinal (cohort) studies of adults with diagnosed glioblastoma treated with temozolomide with/without radiotherapy/surgery. Studies had to have related MGMT status in tumour tissue (assessed by one or more method) with overall survival and presented results as hazard ratios or with sufficient information (e.g. Kaplan-Meier curves) for us to estimate hazard ratios. We focused mainly on studies comparing two or more methods, and listed brief details of articles that examined a single method of measuring MGMT promoter methylation. We also sought economic evaluations conducted alongside trials, modelling studies and cost analysis. DATA COLLECTION AND ANALYSIS: Two review authors independently undertook all steps of the identification and data extraction process for multiple-method studies. We assessed risk of bias and applicability using our own modified and extended version of the QUality In Prognosis Studies (QUIPS) tool. We compared different techniques, exact promoter regions (5'-cytosine-phosphate-guanine-3' (CpG) sites) and thresholds for interpretation within studies by examining hazard ratios. We performed meta-analyses for comparisons of the three most commonly examined methods (immunohistochemistry (IHC), methylation-specific polymerase chain reaction (MSP) and pyrosequencing (PSQ)), with ratios of hazard ratios (RHR), using an imputed value of the correlation between results based on the same individuals. MAIN RESULTS: We included 32 independent cohorts involving 3474 people that compared two or more methods. We found evidence that MSP (CpG sites 76 to 80 and 84 to 87) is more prognostic than IHC for MGMT protein at varying thresholds (RHR 1.31, 95% confidence interval (CI) 1.01 to 1.71). We also found evidence that PSQ is more prognostic than IHC for MGMT protein at various thresholds (RHR 1.36, 95% CI 1.01 to 1.84). The data suggest that PSQ (mainly at CpG sites 74 to 78, using various thresholds) is slightly more prognostic than MSP at sites 76 to 80 and 84 to 87 (RHR 1.14, 95% CI 0.87 to 1.48). Many variants of PSQ have been compared, although we did not see any strong and consistent messages from the results. Targeting multiple CpG sites is likely to be more prognostic than targeting just one. In addition, we identified and summarised 190 articles describing a single method for measuring MGMT promoter methylation status. AUTHORS' CONCLUSIONS: PSQ and MSP appear more prognostic for overall survival than IHC. Strong evidence is not available to draw conclusions with confidence about the best CpG sites or thresholds for quantitative methods. MSP has been studied mainly for CpG sites 76 to 80 and 84 to 87 and PSQ at CpG sites ranging from 72 to 95. A threshold of 9% for CpG sites 74 to 78 performed better than higher thresholds of 28% or 29% in two of three good-quality studies making such comparisons.

The value of dementia care towards the end of life-A contingent valuation study.

OBJECTIVES: A dementia nurse specialist (DNS) is expected to improve the quality of care and support to people with dementia nearing, and at, the end of life (EoL) by facilitating some key features of care. The aim of this study was to estimate willingness-to-pay (WTP) values from the general public perspective, for the different levels of support that the DNS can provide. METHODS: Contingent valuation methods were used to elicit the maximum WTP for scenarios describing different types of support provided by the DNS for EoL care in dementia. In a general population online survey, 1002 participants aged 18 years or more sampled from the United Kingdom provided valuations. Five scenarios were valued with mean WTP value calculated for each scenario along with the relationship between mean WTP and participant characteristics. RESULTS: The mean WTP varied across scenarios with higher values for the scenarios offering more features. Participants with some experience of dementia were willing to pay more compared with those with no experience. WTP values were higher for high-income groups compared with the lowest income level (P < .05). There was no evidence to suggest that respondent characteristics such as age, gender, family size, health utility or education status influenced the WTP values. CONCLUSION: The general population values the anticipated improvement in dementia care provided by a DNS. This study will help inform judgements on interventions to improve the quality of EoL care.

Pelvic floor muscle training for preventing and treating urinary and faecal incontinence in antenatal and postnatal women.

BACKGROUND: About one-third of women have urinary incontinence (UI) and up to one-tenth have faecal incontinence (FI) after childbirth. Pelvic floor muscle training (PFMT) is commonly recommended during pregnancy and after birth for both preventing and treating incontinence. This is an update of a Cochrane Review previously published in 2017. OBJECTIVES: To assess the effects of PFMT for preventing or treating urinary and faecal incontinence in pregnant or postnatal women, and summarise the principal findings of relevant economic evaluations. 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, CINAHL, ClinicalTrials.gov, WHO ICTRP, and handsearched journals and conference proceedings (searched 7 August 2019), and the reference lists of retrieved studies. SELECTION CRITERIA: We included randomised or quasi-randomised trials in which one arm included PFMT. Another arm was no PFMT, usual antenatal or postnatal care, another control condition, or an alternative PFMT intervention. Populations included women who, at randomisation, were continent (PFMT for prevention) or incontinent (PFMT for treatment), and a mixed population of women who were one or the other (PFMT for prevention or treatment). DATA COLLECTION AND ANALYSIS: We independently assessed trials for inclusion and risk of bias. We extracted data and assessed the quality of evidence using GRADE. MAIN RESULTS: We included 46 trials involving 10,832 women from 21 countries. Overall, trials were small to moderately-sized. The PFMT programmes and control conditions varied considerably and were often poorly described. Many trials were at moderate to high risk of bias. Two participants in a study of 43 pregnant women performing PFMT for prevention of incontinence withdrew due to pelvic floor pain. No other trials reported any adverse effects of PFMT. Prevention of UI: compared with usual care, continent pregnant women performing antenatal PFMT probably have a lower risk of reporting UI in late pregnancy (62% less; risk ratio (RR) 0.38, 95% confidence interval (CI) 0.20 to 0.72; 6 trials, 624 women; moderate-quality evidence). Antenatal PFMT slightly decreased the risk of UI in the mid-postnatal period (more than three to six months' postpartum) (29% less; RR 0.71, 95% CI 0.54 to 0.95; 5 trials, 673 women; high-quality evidence). There was insufficient information available for the late postnatal period (more than six to 12 months) to determine effects at this time point (RR 1.20, 95% CI 0.65 to 2.21; 1 trial, 44 women; low-quality evidence). Treatment of UI: compared with usual care, there is no evidence that antenatal PFMT in incontinent women decreases incontinence in late pregnancy (very low-quality evidence), or in the mid-(RR 0.94, 95% CI 0.70 to 1.24; 1 trial, 187 women; low-quality evidence), or late postnatal periods (very low-quality evidence). Similarly, in postnatal women with persistent UI, there is no evidence that PFMT results in a difference in UI at more than six to 12 months postpartum (RR 0.55, 95% CI 0.29 to 1.07; 3 trials; 696 women; low-quality evidence). Mixed prevention and treatment approach to UI: antenatal PFMT in women with or without UI probably decreases UI risk in late pregnancy (22% less; RR 0.78, 95% CI 0.64 to 0.94; 11 trials, 3307 women; moderate-quality evidence), and may reduce the risk slightly in the mid-postnatal period (RR 0.73, 95% CI 0.55 to 0.97; 5 trials, 1921 women; low-quality evidence). There was no evidence that antenatal PFMT reduces the risk of UI at late postpartum (RR 0.85, 95% CI 0.63 to 1.14; 2 trials, 244 women; moderate-quality evidence). For PFMT started after delivery, there was uncertainty about the effect on UI risk in the late postnatal period (RR 0.88, 95% CI 0.71 to 1.09; 3 trials, 826 women; moderate-quality evidence). Faecal incontinence: eight trials reported FI outcomes. In postnatal women with persistent FI, it was uncertain whether PFMT reduced incontinence in the late postnatal period compared to usual care (very low-quality evidence). In women with or without FI, there was no evidence that antenatal PFMT led to a difference in the prevalence of FI in late pregnancy (RR 0.64, 95% CI 0.36 to 1.14; 3 trials, 910 women; moderate-quality evidence). Similarly, for postnatal PFMT in a mixed population, there was no evidence that PFMT reduces the risk of FI in the late postnatal period (RR 0.73, 95% CI 0.13 to 4.21; 1 trial, 107 women, low-quality evidence). There was little evidence about effects on UI or FI beyond 12 months' postpartum. There were few incontinence-specific quality of life data and little consensus on how to measure it. AUTHORS' CONCLUSIONS: This review provides evidence that early, structured PFMT in early pregnancy for continent women may prevent the onset of UI in late pregnancy and postpartum. Population approaches (recruiting antenatal women regardless of continence status) may have a smaller effect on UI, although the reasons for this are unclear. A population-based approach for delivering postnatal PFMT is not likely to reduce UI. Uncertainty surrounds the effects of PFMT as a treatment for UI in antenatal and postnatal women, which contrasts with the more established effectiveness in mid-life women. It is possible that the effects of PFMT might be greater with targeted rather than mixed prevention and treatment approaches, and in certain groups of women. Hypothetically, for instance, women with a high body mass index (BMI) are at risk of UI. Such uncertainties require further testing and data on duration of effect are also needed. The physiological and behavioural aspects of exercise programmes must be described for both PFMT and control groups, and how much PFMT women in both groups do, to increase understanding of what works and for whom. Few data exist on FI and it is important that this is included in any future trials. It is essential that future trials use valid measures of incontinence-specific quality of life for both urinary and faecal incontinence. In addition to further clinical studies, economic evaluations assessing the cost-effectiveness of different management strategies for FI and UI are needed.

Treatment of newly diagnosed glioblastoma in the elderly: a network meta-analysis.

BACKGROUND: A glioblastoma is a fatal type of brain tumour for which the standard of care is maximum surgical resection followed by chemoradiotherapy, when possible. Age is an important consideration in this disease, as older age is associated with shorter survival and a higher risk of treatment-related toxicity. OBJECTIVES: To determine the most effective and best-tolerated approaches for the treatment of elderly people with newly diagnosed glioblastoma. To summarise current evidence for the incremental resource use, utilities, costs and cost-effectiveness associated with these approaches. SEARCH METHODS: We searched electronic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase to 3 April 2019, and the NHS Economic Evaluation Database (EED) up to database closure. We handsearched clinical trial registries and selected neuro-oncology society conference proceedings from the past five years. SELECTION CRITERIA: Randomised trials (RCTs) of treatments for glioblastoma in elderly people. We defined 'elderly' as 70+ years but included studies defining 'elderly' as over 65+ years if so reported. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods for study selection and data extraction. Where sufficient data were available, treatment options were compared in a network meta-analysis (NMA) using Stata software (version 15.1). For outcomes with insufficient data for NMA, pairwise meta-analysis were conducted in RevMan. The GRADE approach was used to grade the evidence. MAIN RESULTS: We included 12 RCTs involving approximately 1818 participants. Six were conducted exclusively among elderly people (either defined as 65 years or older or 70 years or older) with newly diagnosed glioblastoma, the other six reported data for an elderly subgroup among a broader age range of participants. Most participants were capable of self-care. Study quality was commonly undermined by lack of outcome assessor blinding and attrition. NMA was only possible for overall survival; other analyses were pair-wise meta-analyses or narrative syntheses. Seven trials contributed to the NMA for overall survival, with interventions including supportive care only (one trial arm); hypofractionated radiotherapy (RT40; four trial arms); standard radiotherapy (RT60; five trial arms); temozolomide (TMZ; three trial arms); chemoradiotherapy (CRT; three trial arms); bevacizumab with chemoradiotherapy (BEV_CRT; one trial arm); and bevacizumab with radiotherapy (BEV_RT). Compared with supportive care only, NMA evidence suggested that all treatments apart from BEV_RT prolonged survival to some extent. Overall survival High-certainty evidence shows that CRT prolongs overall survival (OS) compared with RT40 (hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.56 to 0.80) and low-certainty evidence suggests that CRT may prolong overall survival compared with TMZ (TMZ versus CRT: HR 1.42, 95% CI 1.01 to 1.98). Low-certainty evidence also suggests that adding BEV to CRT may make little or no difference (BEV_CRT versus CRT: HR 0.83, 95% CrI 0.48 to 1.44). We could not compare the survival effects of CRT with different radiotherapy fractionation schedules (60 Gy/30 fractions and 40 Gy/15 fractions) due to a lack of data. When treatments were ranked according to their effects on OS, CRT ranked higher than TMZ, RT and supportive care only, with the latter ranked last. BEV plus RT was the only treatment for which there was no clear benefit in OS over supportive care only.   One trial comparing tumour treating fields (TTF) plus adjuvant chemotherapy (TTF_AC) with adjuvant chemotherapy alone could not be included in the NMA as participants were randomised after receiving concomitant chemoradiotherapy, not before. Findings from the trial suggest that the intervention probably improves overall survival in this selected patient population. We were unable to perform NMA for other outcomes due to insufficient data. Pairwise analyses were conducted for the following. Quality of life Moderate-certainty narrative evidence suggests that overall, there may be little difference in QoL between TMZ and RT, except for discomfort from communication deficits, which are probably more common with RT (1 study, 306 participants, P = 0.002). Data on QoL for other comparisons were sparse, partly due to high dropout rates, and the certainty of the evidence tended to be low or very low. Progression-free survival High-certainty evidence shows that CRT increases time to disease progression compared with RT40 (HR 0.50, 95% CI 0.41 to 0.61); moderate-certainty evidence suggests that RT60 probably increases time to disease progression compared with supportive care only (HR 0.28, 95% CI 0.17 to 0.46), and that BEV_RT probably increases time to disease progression compared with RT40 alone (HR 0.46, 95% CI 0.27 to 0.78). Evidence for other treatment comparisons was of low- or very low-certainty. Severe adverse events Moderate-certainty evidence suggests that TMZ probably increases the risk of grade 3+ thromboembolic events compared with RT60 (risk ratio (RR) 2.74, 95% CI 1.26 to 5.94; participants = 373; studies = 1) and also the risk of grade 3+ neutropenia, lymphopenia, and thrombocytopenia. Moderate-certainty evidence also suggests that CRT probably increases the risk of grade 3+ neutropenia, leucopenia and thrombocytopenia compared with hypofractionated RT alone. Adding BEV to CRT probably increases the risk of thromboembolism (RR 16.63, 95% CI 1.00 to 275.42; moderate-certainty evidence). Economic evidence There is a paucity of economic evidence regarding the management of newly diagnosed glioblastoma in the elderly. Only one economic evaluation on two short course radiotherapy regimen (25 Gy versus 40 Gy) was identified and its findings were considered unreliable. AUTHORS' CONCLUSIONS: For elderly people with glioblastoma who are self-caring, evidence suggests that CRT prolongs survival compared with RT and may prolong overall survival compared with TMZ alone. For those undergoing RT or TMZ therapy, there is probably little difference in QoL overall. Systemic anti-cancer treatments TMZ and BEV carry a higher risk of severe haematological and thromboembolic events and CRT is probably associated with a higher risk of these events. Current evidence provides little justification for using BEV in elderly patients outside a clinical trial setting. Whilst the novel TTF device appears promising, evidence on QoL and tolerability is needed in an elderly population. QoL and economic assessments of CRT versus TMZ and RT are needed. More high-quality economic evaluations are needed, in which a broader scope of costs (both direct and indirect) and outcomes should be included.

Interventions to reduce the time to diagnosis of brain tumours.

BACKGROUND: Brain tumours are recognised as one of the most difficult cancers to diagnose because presenting symptoms, such as headache, cognitive symptoms, and seizures, may be more commonly attributable to other, more benign conditions. Interventions to reduce the time to diagnosis of brain tumours include national awareness initiatives, expedited pathways, and protocols to diagnose brain tumours, based on a person's presenting symptoms and signs; and interventions to reduce waiting times for brain imaging pathways. If such interventions reduce the time to diagnosis, it may make it less likely that people experience clinical deterioration, and different treatment options may be available. OBJECTIVES: To systematically evaluate evidence on the effectiveness of interventions that may influence: symptomatic participants to present early (shortening the patient interval), thresholds for primary care referral (shortening the primary care interval), and time to imaging diagnosis (shortening the secondary care interval and diagnostic interval). To produce a brief economic commentary, summarising the economic evaluations relevant to these interventions. SEARCH METHODS: For evidence on effectiveness, we searched CENTRAL, MEDLINE, and Embase from January 2000 to January 2020; Clinicaltrials.gov to May 2020, and conference proceedings from 2014 to 2018. For economic evidence, we searched the UK National Health Services Economic Evaluation Database from 2000 to December 2014. SELECTION CRITERIA: We planned to include studies evaluating any active intervention that may influence the diagnostic pathway, e.g. clinical guidelines, direct access imaging, public health campaigns, educational initiatives, and other interventions that might lead to early identification of primary brain tumours. We planned to include randomised and non-randomised comparative studies. Included studies would include people of any age, with a presentation that might suggest a brain tumour. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed titles identified by the search strategy, and the full texts of potentially eligible studies. We resolved discrepancies through discussion or, if required, by consulting another review author. MAIN RESULTS: We did not identify any studies for inclusion in this review. We excluded 115 studies. The main reason for exclusion of potentially eligible intervention studies was their study design, due to a lack of control groups. We found no economic evidence to inform a brief economic commentary on this topic. AUTHORS' CONCLUSIONS: In this version of the review, we did not identify any studies that met the review inclusion criteria for either effectiveness or cost-effectiveness. Therefore, there is no evidence from good quality studies on the best strategies to reduce the time to diagnosis of brain tumours, despite the prioritisation of research on early diagnosis by the James Lind Alliance in 2015. This review highlights the need for research in this area.

Interval brain imaging for adults with cerebral glioma.

BACKGROUND: Clinical practice guidelines suggest that magnetic resonance imaging (MRI) of the brain should be performed at certain time points or intervals distant from diagnosis (interval or surveillance imaging) of cerebral glioma, to monitor or follow up the disease; it is not known, however, whether these imaging strategies lead to better outcomes among patients than triggered imaging in response to new or worsening symptoms. OBJECTIVES: To determine the effect of different imaging strategies (in particular, pre-specified interval or surveillance imaging, and symptomatic or triggered imaging) on health and economic outcomes for adults with glioma (grades 2 to 4) in the brain. SEARCH METHODS: The Cochrane Gynaecological, Neuro-oncology and Orphan Cancers (CGNOC) Group Information Specialist searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase up to 18 June 2019 and the NHS Economic Evaluation Database (EED) up to December 2014 (database closure). SELECTION CRITERIA: We included randomised controlled trials, non-randomised controlled trials, and controlled before-after studies with concurrent comparison groups comparing the effect of different imaging strategies on survival and other health outcomes in adults with cerebral glioma; and full economic evaluations (cost-effectiveness analyses, cost-utility analyses and cost-benefit analyses) conducted alongside any study design, and any model-based economic evaluations on pre- and post-treatment imaging in adults with cerebral glioma. DATA COLLECTION AND ANALYSIS: We used standard Cochrane review methodology with two authors independently performing study selection and data collection, and resolving disagreements through discussion. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included one retrospective, single-institution study that compared post-operative imaging within 48 hours (early post-operative imaging) with no early post-operative imaging among 125 people who had surgery for glioblastoma (GBM: World Health Organization (WHO) grade 4 glioma). Most patients in the study underwent maximal surgical resection followed by combined radiotherapy and temozolomide treatment. Although patient characteristics in the study arms were comparable, the study was at high risk of bias overall. Evidence from this study suggested little or no difference between early and no early post-operative imaging with respect to overall survival (deaths) at one year after diagnosis of GBM (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.61 to 1.21; 48% vs 55% died, respectively; very low certainty evidence) and little or no difference in overall survival (deaths) at two years after diagnosis of GBM (RR 1.06, 95% CI 0.91 to 1.25; 86% vs 81% died, respectively; very low certainty evidence). No other review outcomes were reported. We found no evidence on the effectiveness of other imaging schedules. In addition, we identified no relevant economic evaluations assessing the efficiency of the different imaging strategies. AUTHORS' CONCLUSIONS: The effect of different imaging strategies on survival and other health outcomes remains largely unknown. Existing imaging schedules in glioma seem to be pragmatic rather than evidence-based. The limited evidence suggesting that early post-operative brain imaging among GBM patients who will receive combined chemoradiation treatment may make little or no difference to survival needs to be further researched, particularly as early post-operative imaging also serves as a quality control measure that may lead to early re-operation if residual tumour is identified. Mathematical modelling of a large glioma patient database could help to distinguish the optimal timing of surveillance imaging for different types of glioma, with stratification of patients facilitated by assessment of individual tumour growth rates, molecular biomarkers and other prognostic factors. In addition, paediatric glioma study designs could be used to inform future research of imaging strategies among adults with glioma.

Toric intraocular lens versus limbal relaxing incisions for corneal astigmatism after phacoemulsification.

BACKGROUND: Cataract is the leading cause of blindness in the world, and clinically significant astigmatism may affect up to approximately 20% of people undergoing cataract surgery. Pre-existing astigmatism in people undergoing cataract surgery may be treated, among other techniques, by placing corneal incisions near the limbus (limbal relaxing incisions or LRIs) or by toric intraocular lens (IOLs) specially designed to reduce or treat the effect of corneal astigmatism on unaided visual acuity. OBJECTIVES: To assess the effects of toric IOLs compared with LRIs in the management of astigmatism during phacoemulsification cataract surgery. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register; 2019, Issue 9); Ovid MEDLINE; Ovid Embase and four other databases. The date of the search was 27 September 2019. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing toric IOLs with LRIs during phacoemulsification cataract surgery.  DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. We graded the certainty of the evidence using GRADE. Our primary outcome was the proportion of participants with postoperative residual refractive astigmatism of less than 0.50 dioptres (D) six months or more after surgery. We also collected data on mean residual refractive astigmatism. Secondary outcomes included: uncorrected distance visual acuity, vision-related quality of life, spectacle independence and adverse effects including postoperative lens rotation requiring re-alignment. To supplement the main systematic review assessing the effects of toric IOLs compared with LRIs in the management of astigmatism during phacoemulsification cataract surgery, we sought to identify economic evaluations on the subject. MAIN RESULTS: We identified 10 relevant studies including 517 people (626 eyes). These studies took place in China (three studies), UK (three), Brazil (one), India (one), Italy (one) and Spain (one). The median age of participants was 71 years. The level of corneal astigmatism specified in the inclusion criteria of these studies ranged from 0.75 D to 3 D. A variety of toric IOLs were used in these studies, in all but one study, these were monofocal. Studies used three different nomograms to determine the size and placement of the LRI. Two studies did not specify this. None of the studies were at low risk of bias in all domains, but two studies were at low risk of bias in all domains except selective outcome reporting, which was unclear. The remaining studies were at a mixture of low, unclear or high risk of bias. People receiving toric IOLs were probably more likely to achieve a postoperative residual refractive astigmatism of less than 0.5 D six months or more after surgery (risk ratio (RR) 1.40, 95% confidence interval (CI) 1.10 to 1.78; 5 RCTs, 262 eyes). We judged this to be moderate-certainty evidence, downgrading for risk of bias. In the included studies, approximately 500 eyes per 1000 achieved postoperative astigmatism less than 0.5 D in the LRI group compared with 700 per 1000 in the toric IOLs group. There was a small difference in residual astigmatism between the two groups, favouring toric IOLs (mean difference (MD) -0.32 D, 95% CI -0.48 to -0.15 D; 10 RCTs, 620 eyes). Although all studies favoured toric IOLs, the results of individual studies were inconsistent (range of effects -0.02 D to -0.71 D; I² = 89%). We considered this to be low-certainty evidence, downgrading for risk of bias and inconsistency. People receiving a toric IOL probably have a small improvement in visual acuity at six months or more after surgery compared to people receiving LRI, but the difference is small and probably clinically insignificant (MD -0.04 logMAR, 95% CI -0.07 to -0.02; 8 RCTs, 474 eyes; moderate-certainty evidence). Low-certainty evidence from one study of 40 people suggested little difference in vision-related quality of life measured using the Visual Function Index (VF-14) (MD -3.01, 95% CI -8.56 to 2.54). Two studies reported spectacle independence and suggested that people receiving toric IOLs may be more likely to be spectacle independent (RR 1.56, 95% CI 1.14 to 2.15; 100 people; low-certainty evidence). There were no cases of lens rotation requiring surgery (very low-certainty evidence). Five studies (320 eyes) commented on a range of other adverse effects including corneal oedema, endophthalmitis and corneal ectasia. All these studies reported that there were no adverse events with the exception of one study (40 eyes) where one participant in the LRI group had a central de-epithelisation which recovered over 10 days. We found no economic studies that compared toric IOLs with LRIs. AUTHORS' CONCLUSIONS: Toric IOLs probably provide a higher chance of achieving astigmatism within 0.5 D after cataract surgery compared with LRIs. There may be a small mean difference in postoperative astigmatism, favouring toric IOLs, but this difference is likely to be clinically unimportant. There was no evidence of an important difference in postoperative visual acuity or quality of life between the techniques. Evidence on adverse effects was uncertain. The apparent shortage of relevant economic evaluations indicates that economic evidence regarding the costs and consequence of these two procedures is currently lacking.

Long-term neurocognitive and other side effects of radiotherapy, with or without chemotherapy, for glioma.

BACKGROUND: Gliomas are brain tumours arising from glial cells with an annual incidence of 4 to 11 people per 100,000. In this review we focus on gliomas with low aggressive potential in the short term, i.e. low-grade gliomas. Most people with low-grade gliomas are treated with surgery and may receive radiotherapy thereafter. However, there is concern about the possible long-term effects of radiotherapy, especially on neurocognitive functioning. OBJECTIVES: To evaluate the long-term neurocognitive and other side effects of radiotherapy (with or without chemotherapy) compared with no radiotherapy, or different types of radiotherapy, among people with glioma (where 'long-term' is defined as at least two years after diagnosis); and to write a brief economic commentary. SEARCH METHODS: We searched the following databases on 16 February 2018 and updated the search on 14 November 2018: Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 11) in the Cochrane Library; MEDLINE via Ovid; and Embase via Ovid. We also searched clinical trial registries and relevant conference proceedings from 2014 to 2018 to identify ongoing and unpublished studies. SELECTION CRITERIA: Randomised and non-randomised trials, and controlled before-and-after studies (CBAS). Participants were aged 16 years and older with cerebral glioma other than glioblastoma. We included studies where patients in at least one treatment arm received radiotherapy, with or without chemotherapy, and where neurocognitive outcomes were assessed two or more years after treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias. We assessed the certainty of findings using the GRADE approach. MAIN RESULTS: The review includes nine studies: seven studies were of low-grade glioma and two were of grade 3 glioma. Altogether 2406 participants were involved but there was high sample attrition and outcome data were available for a minority of people at final study assessments. In seven of the nine studies, participants were recruited to randomised controlled trials (RCTs) in which longer-term follow-up was undertaken in a subset of people that had survived without disease progression. There was moderate to high risk of bias in studies due to lack of blinding and high attrition, and in two observational studies there was high risk of selection bias. Paucity of data and risk of bias meant that evidence was of low to very low certainty. We were unable to combine results in meta-analysis due to diversity in interventions and outcomes.The studies examined the following five comparisons.Radiotherapy versus no adjuvant treatmentTwo observational studies contributed data. At the 12-year follow-up in one study, the risk of cognitive impairment (defined as cognitive disability deficits in at least five of 18 neuropsychological tests) was greater in the radiotherapy group (risk ratio (RR) 1.95, 95% confidence interval (CI) 1.02 to 3.71; n = 65); at five to six years the difference between groups did not reach statistical significance (RR 1.38, 95% CI 0.92 to 2.06; n = 195). In the other study, one subject in the radiotherapy group had cognitive impairment (defined as significant deterioration in eight of 12 neuropsychological tests) at two years compared with none in the control group (very low certainty evidence).With regard to neurocognitive scores, in one study the radiotherapy group was reported to have had significantly worse mean scores on some tests compared with no radiotherapy; however, the raw data were only given for significant findings. In the second study, there were no clear differences in any of the various cognitive outcomes at two years (n = 31) and four years (n = 15) (very low certainty evidence).Radiotherapy versus chemotherapyOne RCT contributed data on cognitive impairment at up to three years with no clear difference between arms (RR 1.43, 95% CI 0.36 to 5.70, n = 117) (low-certainty evidence).High-dose radiotherapy versus low-dose radiotherapyOnly one of two studies reporting this comparison contributed data, and at two and five years there were no clear differences between high- and low-dose radiotherapy arms (very low certainty evidence).Conventional radiotherapy versus stereotactic conformal radiotherapyOne study involving younger people contributed limited data from the subgroup aged 16 to 25 years. The numbers of participants with neurocognitive impairment at five years after treatment were two out of 12 in the conventional arm versus none out of 11 in the stereotactic conformal radiotherapy arm (RR 4.62, 95% CI 0.25 to 86.72; n = 23; low-certainty evidence).Chemoradiotherapy versus radiotherapyTwo RCTs tested for cognitive impairment. One defined cognitive impairment as a decline of more than 3 points in MMSE score compared with baseline and reported data from 2-year (110 participants), 3-year (91 participants), and 5-year (57 participants) follow-up with no clear difference between the two arms at any time point. A second study did not report raw data but measured MMSE scores over five years in 126 participants at two years, 110 at three years, 69 at four years and 53 at five years. Authors concluded that there was no difference in MMSE scores between the two study arms (P = 0.4752) (low-certainty evidence).Two RCTs reported quality of life (QoL) outcomes for this comparison. One reported no differences in Brain-QoL scores between study arms over a 5-year follow-up period (P = 0.2767; no raw data were given and denominators were not stated). The other trial reported that the long-term results of health-related QoL showed no difference between the arms but did not give the raw data for overall HRQoL scores (low-certainty evidence).We found no comparative data on endocrine dysfunction; we planned to develop a brief economic commentary but found no relevant economic studies for inclusion. AUTHORS' CONCLUSIONS: Radiotherapy for gliomas with a good prognosis may increase the risk of neurocognitive side effects in the long term; however the magnitude of the risk is uncertain. Evidence on long-term neurocognitive side effects associated with chemoradiotherapy is also uncertain. Neurocognitive assessment should be an integral part of long-term follow-up in trials involving radiotherapy for lower-grade gliomas to improve the certainty of evidence regarding long-term neurocognitive effects. Such trials should also assess other potential long-term effects, including endocrine dysfunction, and evaluate costs and cost effectiveness.

Interventions for visual field defects in people with stroke.

BACKGROUND: Visual field defects are estimated to affect 20% to 57% of people who have had a stroke. Visual field defects can affect functional ability in activities of daily living (commonly affecting mobility, reading and driving), quality of life, ability to participate in rehabilitation, and depression and anxiety following stroke. There are many interventions for visual field defects, which are proposed to work by restoring the visual field (restitution); compensating for the visual field defect by changing behaviour or activity (compensation); substituting for the visual field defect by using a device or extraneous modification (substitution); or ensuring appropriate diagnosis, referral and treatment prescription through standardised assessment or screening, or both. OBJECTIVES: To determine the effects of interventions for people with visual field defects after stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register, the Cochrane Eyes and Vision Group Trials Register, CENTRAL, MEDLINE, Embase, CINAHL, AMED, PsycINFO, and PDQT Databse, and clinical trials databases, including ClinicalTrials.gov and WHO Clinical Trials Registry, to May 2018. We also searched reference lists and trials registers, handsearched journals and conference proceedings, and contacted experts. SELECTION CRITERIA: Randomised trials in adults after stroke, where the intervention was specifically targeted at improving the visual field defect or improving the ability of the participant to cope with the visual field loss. The primary outcome was functional ability in activities of daily living and secondary outcomes included functional ability in extended activities of daily living, reading ability, visual field measures, balance, falls, depression and anxiety, discharge destination or residence after stroke, quality of life and social isolation, visual scanning, adverse events, and death. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts, extracted data and appraised trials. We undertook an assessment of methodological quality for allocation concealment, blinding of outcome assessors, method of dealing with missing data, and other potential sources of bias. We assessed the quality of evidence for each outcome using the GRADE approach. MAIN RESULTS: Twenty studies (732 randomised participants, with data for 547 participants with stroke) met the inclusion criteria for this review. However, only 10 of these studies compared the effect of an intervention with a placebo, control, or no treatment group, and eight had data which could be included in meta-analyses. Only two of these eight studies presented data relating to our primary outcome of functional abilities in activities of daily living. One study reported evidence relating to adverse events.Three studies (88 participants) compared a restitutive intervention with a control, but data were only available for one study (19 participants). There was very low-quality evidence that visual restitution therapy had no effect on visual field outcomes, and a statistically significant effect on quality of life, but limitations with these data mean that there is insufficient evidence to draw any conclusions about the effectiveness of restitutive interventions as compared to control.Four studies (193 participants) compared the effect of scanning (compensatory) training with a control or placebo intervention. There was low-quality evidence that scanning training was more beneficial than control or placebo on quality of life, measured using the Visual Function Questionnaire (VFQ-25) (two studies, 96 participants, mean difference (MD) 9.36, 95% confidence interval (CI) 3.10 to 15.62). However, there was low or very-low quality evidence of no effect on measures of visual field, extended activities of daily living, reading, and scanning ability. There was low-quality evidence of no significant increase in adverse events in people doing scanning training, as compared to no treatment.Three studies (166 participants) compared a substitutive intervention (a type of prism) with a control. There was low or very-low quality evidence that prisms did not have an effect on measures of activities of daily living, extended activities of daily living, reading, falls, or quality of life, and very low-quality evidence that they may have an effect on scanning ability (one study, 39 participants, MD 9.80, 95% CI 1.91 to 17.69). There was low-quality evidence of an increased odds of an adverse event (primarily headache) in people wearing prisms, as compared to no treatment.One study (39 participants) compared the effect of assessment by an orthoptist to standard care (no assessment) and found very low-quality evidence that there was no effect on measures of activities of daily living.Due to the quality and quantity of evidence, we remain uncertain about the benefits of assessment interventions. AUTHORS' CONCLUSIONS: There is a lack of evidence relating to the effect of interventions on our primary outcome of functional ability in activities of daily living. There is limited low-quality evidence that compensatory scanning training may be more beneficial than placebo or control at improving quality of life, but not other outcomes. There is insufficient evidence to reach any generalised conclusions about the effect of restitutive interventions or substitutive interventions (prisms) as compared to placebo, control, or no treatment. There is low-quality evidence that prisms may cause minor adverse events.

Valuing selected WAItE health states using the Time Trade-Off methodology: findings from an online interviewer-assisted remote survey.

PURPOSE: The Weight-Specific Adolescent Instrument for Economic Evaluation (WAItE) is a physical weight-specific patient reported outcome measure for use in adolescence. The purpose of this study was to use the Time Trade-Off (TTO) methodology, administered using an online interviewer-assisted remote survey, to obtain utility values for several health states from the WAItE descriptive system from a sample of the UK adult general population. METHODS: The adult sample was gathered using a market research company and a sample of local residents. All participants completed the same interviewer-assisted remote survey, which included rating WAItE states of varying impairment using the TTO. RESULTS: 42 adults completed the survey. Utility values were gathered for four health states, ranging from low impairment to the most severe health from the WAItE descriptive system (the Pits state). Consistent orderings of the WAItE health states were observed; the health state with the lowest level of impairment was valued highest and the Pits state was valued lowest. Several respondents (n = 7, 17%) considered the Pits state to be worse than death; however, the mean value of this health state was 0.23. CONCLUSIONS: The utility value of the Pits state relative to death generated from this study will be used to anchor latent values for WAItE health states generated from a Discrete Choice Experiment onto the 0 = death, 1 = full health Quality Adjusted Life Year (QALY) scale as part of a valuation study for the WAItE in the UK population. This study also provides further evidence that interviewer-assisted digital studies are feasible for collecting TTO data.

Is primary trabeculectomy cost-effective for patients with advanced primary open angle glaucoma? Results from the Treatment of Advanced Glaucoma Study economic model.

BACKGROUND/AIMS: Advanced primary open angle glaucoma (POAG) is a lifelong condition. The aim of this study is to compare medical treatment against trabeculectomy for patients presenting with advanced POAG using an economic evaluation decision model. METHODS: A Markov model was used to compare the two treatments, medical treatment versus trabeculectomy for the management of advanced POAG, in terms of costs and quality-adjusted life-years (QALYs). The uncertainty surrounding the model findings was assessed using probabilistic sensitivity analysis and deterministic analysis. Data for the model came from Treatment of Advanced Glaucoma Study supplemented with data from the literature. The main outcomes of the model presented in terms of Incremental costs and QALYs based on responses to the EQ-5D-5L, Health Utilities Index-3 and a Glaucoma Utility Index. RESULTS: In the base-case analysis (lifetime horizon and EQ-5D-5L measure), participants receiving trabeculectomy had on average, an additional cost of £2687, an additional 0.28 QALYs and an incremental cost per QALY of £9679 compared with medical treatment. There was a 73% likelihood of trabeculectomy being considered cost-effective when society was willing to pay £20 000 for a QALY. Over shorter time horizons, the incremental cost per QALY gained from trabeculectomy compared with medical treatment was higher (47 663) for a 2-year time horizon. Our results are robust to changes in the key assumptions and input parameters values. CONCLUSION: In patients presenting with advanced POAG, trabeculectomy has a higher probability of being cost-effective over a patient's lifetime compared with medical treatment.