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Background: Social skills interventions are commonly recommended to help children and young people with autism spectrum disorder develop social skills, but some struggle to engage in these interventions. LEGO® (LEGO System A/S, Billund, Denmark) based therapy, a group social skills intervention, aims to be more interesting and engaging. Objective: To evaluate the clinical effectiveness of LEGO® based therapy on the social and emotional skills of children and young people with autism spectrum disorder in school settings compared with usual support. Secondary objectives included evaluations of cost-effectiveness, acceptability and treatment fidelity. Design: A cluster randomised controlled trial randomly allocating participating schools to either LEGO® based therapy and usual support or usual support only. Setting: Mainstream schools in the north of England. Participants: Children and young people (aged 7-15 years) with autism spectrum disorder, their parent/guardian, an associated teacher/teaching assistant and a facilitator teacher/teaching assistant (intervention schools only). Intervention: Schools randomised to the intervention arm delivered 12 weekly sessions of LEGO® based therapy, which promotes collaborative play and encourages social problem-solving in groups of three children and young people with a facilitator (trained teacher or teaching assistant). Participants received usual support from school and community services. Participants in the control arm received usual support only. Research assistants and statisticians were blind to treatment allocation. Main outcome measure: The social skills subscale of the Social Skills Improvement System (SSIS), completed by the children and young people's unblinded teacher pre randomisation and 20 weeks post randomisation. The SSIS social skills subscale measures social skills including social communication, co-operation, empathy, assertion, responsibility and self-control. Participants completed a number of other pre- and post-randomisation measures of emotional health, quality of life, loneliness, problem behaviours, academic competence, service resource utilisation and adverse events. Results: A total of 250 children and young people from 98 schools were randomised: 127 to the intervention arm and 123 to the control arm. Intention-to-treat analysis of the main outcome measure showed a modest positive difference of 3.74 points (95% confidence interval -0.16 to 7.63 points, standardised effect size 0.18; p = 0.06) in favour of the intervention arm. Statistical significance increased in per-protocol analysis, with a modest positive difference (standardised effect size 0.21; p = 0.036). Cost-effectiveness of the intervention was found in reduced service use costs and a small increase in quality-adjusted life-years. Intervention fidelity and acceptability were positive. No intervention-related adverse events or effects were reported. Conclusions: The primary and pre-planned sensitivity analysis of the primary outcome consistently showed a positive clinical difference, with modest standardised effect sizes of between 0.15 and 0.21. There were positive health economics and qualitative findings, corroborated by the difference between arms for the majority of secondary outcomes, which were not statistically significant but favoured the intervention arm. Post hoc additional analysis was exploratory and was not used in drawing this conclusion. Given the small positive change, LEGO® based therapy for children and young people with autism spectrum disorder in schools should be considered. Limitations: The primary outcome measure was completed by an unblinded teacher (rather than by the facilitator). Future work: The study team recommends future research into LEGO® based therapy, particularly in school environments. Trial registration: This trial is registered as ISRCTN64852382. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: 15/49/32) and is published in full in Public Health Research; Vol. 11, No. 12. See the NIHR Funding and Awards website for further award information.
Autism spectrum disorder is characterised by difficulties with social relationships and communication, which can make it difficult to make friends. Social skills training is commonly used to help children and young people learn different social skills, but some children and young people do not enjoy these therapies. LEGO® (LEGO System A/S, Billund, Denmark) based therapy takes a new approach by focusing on making the process interesting and fun. This research investigated the effect of LEGO® based therapy groups in schools on the social and emotional abilities of children and young people with autism spectrum disorder. It was a randomised controlled trial, so each school that was taking part was randomly chosen to provide either usual support (from the school or NHS services) or 12 sessions of LEGO® based therapy with a trained school staff member as well as usual support. Children and young people played one of three roles the 'engineer' (gives instructions), the 'supplier' (finds the pieces) or the 'builder' (builds the model) and worked together. Questionnaires completed by children and young people, their parents/guardians and teachers were used to look at the intervention's effects. The main objective was to see if there was a change in social skills measured by a teacher-completed questionnaire. Results showed that the social skills of children and young people in the LEGO® based therapy groups did improve a little. We found that the intervention is not very costly for schools to run. Many parents/guardians and teachers thought that the intervention was beneficial and that the children and young people enjoyed it.
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Transtorno do Espectro Autista , Habilidades Sociais , Criança , Humanos , Adolescente , Transtorno do Espectro Autista/terapia , Qualidade de Vida , Inglaterra , Resultado do TratamentoRESUMO
LAY ABSTRACT: Autism is characterised by keen interests and differences in social interactions and communication. Activities that help autistic children and young people with social skills are commonly used in UK schools. LEGO® based therapy is a new activity that provides interesting and fun social opportunities for children and young people and involves building LEGO® models together. This study looked at LEGO® based therapy for the social skills of autistic children and young people in schools. It was a randomised controlled trial, meaning each school was randomly chosen (like flipping a coin) to either run LEGO® based therapy groups in school over 12 weeks and have usual support from school or other professionals, or only have usual support from school or other professionals. The effect of the LEGO® based therapy groups was measured by asking children and young people, their parents/guardians, and a teacher at school in both arms of the study to complete some questionnaires. The main objective was to see if the teacher's questionnaire answers about the children and young people's social skills changed between their first and second completions. The social skills of participants in the LEGO® based therapy groups were found to have improved in a small way when compared to usual support only. The study also found that LEGO® based therapy was not very costly for schools to run and parents/guardians and teachers said they thought it was good for their children and young people. We suggest further research into different potential benefits of LEGO® based therapy.
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OBJECTIVE: To date, there have been no reviews bringing together evidence on the clinical management of functional neurological disorder (FND) and patients', caregivers', and healthcare workers' experiences. This review provides an overview of the literature focused on the clinical management of FND. METHODS: Four databases were searched, and a consultation exercise was conducted to retrieve relevant records dated from September 2010 to September 2020. Articles documenting diagnostic methods, treatments or interventions, or the experiences and perspectives of patients and healthcare workers in the clinical management of FND were included. RESULTS: In total, 2756 records were retrieved, with 162 included in this review. The diagnostic methods reported predominantly included positive clinical signs, v-EEG and EEG. Psychological treatments and medication were the most reported treatments. Mixed findings of the effectiveness of CBT were found. Haloperidol, physiotherapy and scripted diagnosis were found to be effective in reducing FND symptoms. Several facilitators and barriers for patients accessing treatment for FND were reported. CONCLUSION: The literature describing the clinical management for FND has increased considerably in recent times. A wide variety of diagnostic tools and treatments and interventions were found, with more focus being placed on tests that confirm a diagnosis than 'rule-out' tests. The main treatment type found in this review was medication. This review revealed that there is a lack of high-quality evidence and reflects the need for official clinical guidelines for FND, providing healthcare workers and patients the support needed to navigate the process to diagnose and manage FND.
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Transtorno Conversivo , Doenças do Sistema Nervoso , Humanos , Doenças do Sistema Nervoso/psicologia , Transtorno Conversivo/diagnóstico , Pessoal de SaúdeRESUMO
OBJECTIVES: This study establishes research priorities for medically not yet explained symptoms (MNYES), also known as persistent physical symptoms or medically unexplained symptoms, from the perspective of patients, caregivers and clinicians, in a priority setting partnership (PSP) following the James Lind Alliance (JLA) approach. Research into such symptoms in general has been poorly funded over the years and so far has been primarily researcher-led with minimal input from patients, caregivers and clinicians; and sometimes has been controversial. DESIGN: JLA PSP method. The PSP termed these symptoms MNYES. METHODS: The study was conducted according to the JLA's detailed methodology for conducting priority setting exercises. It involved five key stages: defining the appropriate term for the conditions under study by the PSP Steering Group; gathering questions on MNYES from patients, caregivers and clinicians in a publicly accessible survey; checking these research questions against existing evidence; interim prioritisation in a second survey; and a final multi-stakeholder consensus meeting to determine the top 10 unanswered research questions using the modified nominal group methodology. RESULTS: Over 700 responses from UK patients, caregivers and clinicians were identified in the two surveys and charities contributed from a broad range of medical specialties and primary care. The final top 10 unanswered research questions cover, among others: treatment strategies, personalisation of treatment, collaborative care pathways, training for clinicians and outcomes that matter to patients. INTERPRETATION: The top 10 unanswered research questions are expected to generate much needed, relevant and impactful research into MNYES.
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Cuidadores , Projetos de Pesquisa , Consenso , Humanos , Pesquisadores , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: To assess the cost-effectiveness of LEGO-based therapy compared with usual support. DESIGN: Cost-utility analysis alongside randomised control trial. SETTING: Mainstream primary and secondary schools in the UK. PARTICIPANTS: 248 children and young people (CYP) with autism spectrum disorder (ASD) aged 7-15 years. INTERVENTION: LEGO-based therapy is a group social skills intervention designed specifically for CYP with ASD. Through play, CYP learn to use the skills such as joint attention, sharing, communication and group problem-solving. CYP randomised to the intervention arm received 12 weekly sessions of LEGO-based therapy and usual support, while CYP allocated to control arm received usual support only. MAIN OUTCOME MEASURES: Average costs based on National Health Service (NHS) and personal social services perspective and quality-adjusted life years (QALYs) measured by EQ-5D-Y over time horizon of 1 year were collected during the trial. Incremental cost-effectiveness ratio (ICER) was calculated, and non-parametric bootstrapping was conducted. The uncertainty around the ICER estimates was presented using cost-effectiveness acceptability curve (CEAC). A set of sensitivity analyses were conducted to assess the robustness of the primary findings. RESULTS: After adjustment and bootstrapping, on average, CYP in LEGO-based therapy group incurred less costs (incremental cost was -£251 (95% CI -£752 to £268)) and gained marginal improvement in QALYs (QALYs gained 0.009 (95% CI -0.008 to 0.028)). The CEAC shows that the probability of LEGO-based therapy being cost-effective was 94% at the willingness-to-pay threshold of £20 000 per QALY gained. Results of sensitivity analyses were consistent with the primary outcomes. CONCLUSION: Compared with usual support, LEGO-based therapy produced marginal reduction in costs and improvement in QALYs. Results from both primary and sensitivity analyses suggested that LEGO-based therapy was likely to be cost-effective. TRIAL REGISTRATION NUMBER: ISRCTN64852382.
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Transtorno do Espectro Autista , Adolescente , Transtorno do Espectro Autista/terapia , Criança , Análise Custo-Benefício , Humanos , Resolução de Problemas , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Medicina EstatalRESUMO
BACKGROUND: Conversion disorder/functional neurological disorder (CD/FND) occurs often in neurological settings and can lead to long-term distress, disability and demand on health care services. Systemic low-grade inflammation might play a role, however, the pathogenic mechanism is still unknown. AIM: 1) To explore the feasibility to establish and assess a cohort of CD/FND with motor symptoms, involving persons with lived experience (PPI). 2) To generate proof of concept regarding a possible role for cytokines, microRNA, cortisol levels and neurocognitive symptoms in patients with motor CD/FND. METHOD: Feasibility study. RESULTS: The study showed active involvement of patients despite high clinical illness burden and disability, neurocognitive symptoms, childhood adverse experiences (ACE) and current life events. The study provided valuable knowledge regarding the feasibility of conducting a study in these patients that will inform future study phases. In the sample there were elevated levels of IL6, IL12, IL17A, IFNg, TNFa and VEGF-a, suggesting systemic low-grade inflammation. Also, microRNAs involved in inflammation and vascular inflammation were correlated with TNFa and VEGFa respectively, suggesting proof of concept for an epigenetic mechanism. Owing to the COVID-19 outbreak, the patient sample was limited to 15 patients. CONCLUSION: It is a novelty that this study is conducted in the clinical setting. This innovative, translational study explores stress-related SLI in CD/FND patients and the feasibility of a larger project aiming to develop new treatments for this vulnerable population. Given the positive findings, there is scope to conduct further research into the mechanism of disease in CD/FND.
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BACKGROUND: Non-attendance at initial appointments is a widespread problem which affects mental health services and patients. METHODS: This mixed methods systematic review identified and synthesised the available literature on factors, which could be modified either by patients or by services, that can influence early attrition to services offering psychological support for common mental health problems. Searches were conducted January 2017, updated Oct 2019, in MEDLINE, CINAHL Plus, EMBASE, Cochrane Library and PsycINFO. Screening, data extraction and quality appraisal were completed independently by two reviewers. Quality appraisals used Joanna Briggs Institute tools. RESULTS: Of the 31,758 references identified (21,123 unique), 34 studies were selected for inclusion. Studies used cohort (14), cross-sectional (10) and qualitative (9) designs. An additional study reported both quantitative and qualitative components. Findings from observational studies related to the presenting problem, beliefs about symptoms and treatment, contact with services, practical challenges and social support. Themes from qualitative studies centred around individual perceptions of symptoms and support, social and cultural influences, experiences with services and practical issues. Similarities and differences between quantitative and qualitative syntheses are discussed in a combined synthesis. LIMITATIONS: This review did not attempt to measure the effect of factors affecting attendance, or the effectiveness of interventions to reduce non-attendance to initial treatment appointments. CONCLUSIONS: Ensuring treatments offered matched patient perceptions of problems, reducing patient concerns around engagement, and offering prompt responses with flexibility to accommodate patient circumstances consistently influenced initial attendance. More work is needed to improve perceptions of mental health services in the community.
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Saúde Mental , Apoio Social , Estudos Transversais , Humanos , Pesquisa QualitativaRESUMO
INTRODUCTION: Social skills training interventions for children with autism spectrum disorder (ASD) typically focus on a skills deficit model rather than building on existing skills or encouraging the child to seek their own solutions. LEGO-based therapy is a child-oriented intervention to help improve social interactional skills and reduce isolation. The therapy is designed for school-age children with ASD and uses group-based play in a school setting to encourage peer relationships and social learning. Despite the reported potential benefits of LEGO-based therapy in a prior randomised controlled trial (RCT) and its adoption by many schools, the evidence to support its effectiveness on the social and emotional well-being of children with ASD is limited and includes no assessment of cost-effectiveness. METHODS AND ANALYSIS: This multicentre, pragmatic, cluster RCT will randomise 240 participants (aged 7-15 years) with a clinical diagnosis of ASD to receive usual care or LEGO-based therapy with usual care. Cluster randomisation will be conducted on a school level, randomising each school as opposed to each individual child within a school. All prospective participants will be screened for eligibility before assenting to the study (with parents giving informed consent on behalf of their child). All participants will be followed up at 20 and 52 weeks after randomisation to assess for social, emotional and behavioural changes. The primary outcome measure is the social skills subscale of the Social Skills Improvement System completed by a teacher or teaching assistant associated with participating children at the 20-week follow-up time point. ETHICS AND DISSEMINATION: Ethics approval has been obtained via the University of York Research Ethics Committee. The results of the trial will be submitted for publication in a peer-reviewed journal and will be disseminated to participating families, education practitioners and the third sector including voluntary and community organisations. TRIAL REGISTRATION NUMBER: ISRCTN64852382; Pre-results.
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Transtorno do Espectro Autista/terapia , Jogos e Brinquedos/psicologia , Psicoterapia de Grupo/métodos , Habilidades Sociais , Transtorno do Espectro Autista/psicologia , Criança , Feminino , Humanos , Masculino , Ensaios Clínicos Pragmáticos como Assunto , Instituições Acadêmicas , Método Simples-Cego , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: To assess the feasibility of recruitment, retention, outcome measures and intervention training/delivery among teachers, parents and children. To calculate a sample size estimation for full trial. DESIGN: A single-centre, unblinded, cluster feasibility randomised controlled trial examining Social Stories delivered within a school environment compared with an attentional control. SETTING: 37 primary schools in York, UK. PARTICIPANTS: 50 participants were recruited and a cluster randomisation approach by school was examined. Participants were randomised into the treatment group (n=23) or a waiting list control group (n=27). OUTCOME MEASURES: Acceptability and feasibility of the trial, intervention and of measurements required to assess outcomes in a definitive trial. RESULTS: An assessment of the questionnaire completion rates indicated teachers would be most appropriate to complete the primary outcome measure. 2 outcome measures: the Social Responsiveness Scale (SRS)-2 and a goal-based measure showed both the highest levels of completion rates (above 80%) at the primary follow-up point (6â weeks postintervention) and captured relevant social and behaviour outcomes. Power calculations were based on these 2 outcome measures leading to a total proposed sample size of 180 participant groups. CONCLUSIONS: Results suggest that a future trial would be feasible to conduct and could inform the policy and practice of using Social Stories in mainstream schools. TRIAL REGISTRATION NUMBER: ISRCTN96286707; Results.
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Transtorno do Espectro Autista , Terapia Comportamental/métodos , Instituições Acadêmicas , Comportamento Social , Atenção , Criança , Comunicação , Estudos de Viabilidade , Feminino , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Pais , Seleção de Pacientes , Projetos de Pesquisa , Professores Escolares , Inquéritos e Questionários , Reino UnidoRESUMO
BACKGROUND AND AIMS: Key information summary is one of the first national shared electronic patient records enabling GPs to share clinical information with unscheduled care providers, including out-of-hours. Implemented during 2013, over 90,000 patient records have been created. This evaluation identified the impact of key information summary on healthcare services. METHODS: Evidence was collected using online questionnaires and structured telephone interviews. Opinions providing a numerical estimate of value were analysed using statistical methods, while qualitative responses were synthesised using thematic analysis. RESULTS: The vast majority of respondents from 441 GP practices and 33 out-of-hours clinicians show that key information summary enhances patient safety, improves clinical management, reduces hospital admissions, empowers clinicians, aids communication across services and enables decisions to be responsive to patients' wishes. CONCLUSIONS: Patients willingly consent to share data with unscheduled care clinicians. Patients benefitting include those with palliative, complex or multiple conditions, at high risk of using emergency services. Out-of-hours clinicians would welcome more key information summaries, all well-completed and including social care information. Improvements include software enhancements and wider sharing of information with all unscheduled care services.
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Plantão Médico/organização & administração , Registros Eletrônicos de Saúde , Serviços Médicos de Emergência/organização & administração , Medicina Geral/organização & administração , Disseminação de Informação , Confidencialidade , Continuidade da Assistência ao Paciente , Necessidades e Demandas de Serviços de Saúde/organização & administração , Humanos , Escócia/epidemiologia , Medicina Estatal , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Since 2005, International Committee of Medical Journal Editors (ICMJE) member journals have required that clinical trials be registered in publicly available trials registers before they are considered for publication. OBJECTIVES: The research explores whether it is adequate, when searching to inform systematic reviews, to search for relevant clinical trials using only public trials registers and to identify the optimal search approaches in trials registers. METHODS: A search was conducted in ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP) for research studies that had been included in eight systematic reviews. Four search approaches (highly sensitive, sensitive, precise, and highly precise) were performed using the basic and advanced interfaces in both resources. RESULTS: On average, 84% of studies were not listed in either resource. The largest number of included studies was retrieved in ClinicalTrials.gov and ICTRP when a sensitive search approach was used in the basic interface. The use of the advanced interface maintained or improved sensitivity in 16 of 19 strategies for Clinicaltrials.gov and 8 of 18 for ICTRP. No single search approach was sensitive enough to identify all studies included in the 6 reviews. CONCLUSIONS: Trials registers cannot yet be relied upon as the sole means to locate trials for systematic reviews. Trials registers lag behind the major bibliographic databases in terms of their search interfaces. IMPLICATIONS: For systematic reviews, trials registers and major bibliographic databases should be searched. Trials registers should be searched using sensitive approaches, and both the registers consulted in this study should be searched.
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Ensaios Clínicos como Assunto/estatística & dados numéricos , Armazenamento e Recuperação da Informação/métodos , Literatura de Revisão como Assunto , Indexação e Redação de Resumos/estatística & dados numéricos , Medicina Baseada em Evidências , Humanos , Disseminação de Informação , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema de Registros , DescritoresRESUMO
Recent systematic reviews have reported a positive, although modest, effect of probiotics in terms of preventing common cold symptoms. In this systematic review, the effect of probiotics, specifically Lactobacillus and Bifidobacterium strains, on the duration of acute respiratory infections in otherwise healthy children and adults was evaluated. To identify relevant trials, eight databases, including MEDLINE, Embase, the Cochrane Database of Systematic Reviews (CDSR), the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA), Science Citation Index (SCI) and OAISTER, were searched from inception to 20 July 2012. Details regarding unpublished studies/databases were also obtained from probiotic manufacturers. Study selection, data extraction and quality assessment were carried out by two reviewers. Risk of bias was assessed using criteria adapted from those published by the Centre for Reviews and Dissemination. In this review, twenty randomised controlled trials (RCT) were included, of which twelve were considered to have a low risk of bias. Meta-analysis revealed significantly fewer numbers of days of illness per person (standardised mean difference (SMD) - 0·31 (95% CI - 0·41, - 0·11), I²= 3%), shorter illness episodes by almost a day (weighted mean difference - 0·77 (95% CI - 1·50, - 0·04), I²= 80%) (without an increase in the number of illness episodes), and fewer numbers of days absent from day care/school/work (SMD - 0·17 (95% CI - 0·31, - 0·03), I²= 67%) in participants who received a probiotic intervention than in those who had taken a placebo. Reasons for heterogeneity between the studies were explored in subgroup analysis, but could not be explained, suggesting that the effect sizes found may differ between the population groups. This systematic review provides evidence from a number of good-quality RCT that probiotics reduce the duration of illness in otherwise healthy children and adults.
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Anti-Infecciosos/uso terapêutico , Medicina Baseada em Evidências , Imunidade nas Mucosas , Probióticos/uso terapêutico , Mucosa Respiratória/imunologia , Infecções Respiratórias/imunologia , Doença Aguda , Adulto , Bifidobacterium/imunologia , Criança , Resistência à Doença , Humanos , Lactobacillus/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções Respiratórias/dietoterapia , Infecções Respiratórias/prevenção & controle , Fatores de TempoRESUMO
BACKGROUND: Search filters or hedges are search strategies developed to assist information specialists and librarians to retrieve different types of evidence from bibliographic databases. The objectives of this project were to learn about searchers' filter use, how searchers choose search filters and what information they would like to receive to inform their choices. METHODS: Interviews with information specialists working in, or for, the National Institute for Health and Care Excellence (NICE) were conducted. An online questionnaire survey was also conducted and advertised via a range of email lists. RESULTS: Sixteen interviews were undertaken and 90 completed questionnaires were received. The use of search filters tends to be linked to reducing a large amount of literature, introducing focus and assisting with searches that are based on a single study type. Respondents use numerous ways to identify search filters and can find choosing between different filters problematic because of knowledge gaps and lack of time. CONCLUSIONS: Search filters are used mainly for reducing large result sets (introducing focus) and assisting with searches focused on a single study type. Features that would help with choosing filters include making information about filters less technical, offering ratings and providing more detail about filter validation strategies and filter provenance.
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Serviços de Informação , Armazenamento e Recuperação da Informação/métodos , Ferramenta de Busca/métodos , Bases de Dados Bibliográficas , Humanos , Inquéritos e QuestionáriosRESUMO
Postmenopausal women with advanced breast cancer recurring/progressing on or after initial (adjuvant or first-line) endocrine therapy may be treated multiple times with one of several endocrine or combinatorial targeted treatment options before initiating chemotherapy. In the absence of direct head-to-head comparisons of these treatment options, an indirect comparison can inform treatment choice. This network meta-analysis compared the efficacy of everolimus plus exemestane with that of fulvestrant 250 and 500 mg in the advanced breast cancer setting following adjuvant or first-line endocrine therapy. The reported hazard ratios (HRs) for progression-free survival (PFS) or time to progression from six studies that formed a network to compare everolimus plus exemestane (BOLERO-2 trial) with fulvestrant were analyzed by means of a Bayesian network meta-analysis. In the primary comparison (PFS analysis based on the local review of disease progression from BOLERO-2 with the data from the other studies), everolimus plus exemestane appeared to be more efficacious than both fulvestrant 250 mg (HR = 0.47; 95 % credible interval [CrI] 0.38-0.58) and 500 mg (HR = 0.59; 95 % CrI 0.45-0.77). Similar results were obtained in an alternate comparison based on central review of disease progression from BOLERO-2 with the data from the other studies (HR = 0.40; 95 % CrI 0.31-0.51 and HR = 0.50; 95 % CrI 0.37-0.67, respectively), and in a subgroup analysis of patients who had received prior aromatase inhibitor therapy (HR = 0.47; 95 % CrI 0.38-0.58 and HR = 0.55; 95 % CrI 0.40-0.76, respectively). These results suggest that everolimus plus exemestane may be more efficacious than fulvestrant in patients with advanced breast cancer who progress on or after adjuvant or first-line therapy with a nonsteroidal aromatase inhibitor.