Early warnings and repayment plans: novel trial management methods for monitoring and managing data return rates in a multi-centre phase III randomised controlled trial with paper Case Report Forms.

BACKGROUND: Monitoring and managing data returns in multi-centre randomised controlled trials is an important aspect of trial management. Maintaining consistently high data return rates has various benefits for trials, including enhancing oversight, improving reliability of central monitoring techniques and helping prepare for database lock and trial analyses. Despite this, there is little evidence to support best practice, and current standard methods may not be optimal. METHODS: We report novel methods from the Trial of Imaging and Schedule in Seminoma Testis (TRISST), a UK-based, multi-centre, phase III trial using paper Case Report Forms to collect data over a 6-year follow-up period for 669 patients. Using an automated database report which summarises the data return rate overall and per centre, we developed a Microsoft Excel-based tool to allow observation of per-centre trends in data return rate over time. The tool allowed us to distinguish between forms that can and cannot be completed retrospectively, to inform understanding of issues at individual centres. We reviewed these statistics at regular trials unit team meetings. We notified centres whose data return rate appeared to be falling, even if they had not yet crossed the pre-defined acceptability threshold of an 80% data return rate. We developed a set method for agreeing targets for gradual improvement with centres having persistent data return problems. We formalised a detailed escalation policy to manage centres who failed to meet agreed targets. We conducted a post-hoc, descriptive analysis of the effectiveness of the new processes. RESULTS: The new processes were used from April 2015 to September 2016. By May 2016, data return rates were higher than they had been at any time previously, and there were no centres with return rates below 80%, which had never been the case before. In total, 10 centres out of 35 were contacted regarding falling data return rates. Six out of these 10 showed improved rates within 6-8 weeks, and the remainder within 4 months. CONCLUSIONS: Our results constitute preliminary effectiveness evidence for novel methods in monitoring and managing data return rates in randomised controlled trials. We encourage other researchers to work on generating better evidence-based methods in this area, whether through more robust evaluation of our methods or of others.

Methods for delivering the UK's multi-centre prison-based naloxone-on-release pilot randomised trial (N-ALIVE): Europe's largest prison-based randomised controlled trial.

INTRODUCTION AND AIMS: Naloxone is an opioid antagonist used for emergency resuscitation following opioid overdose. Prisoners with a history of heroin use by injection have a high risk of drug-related death in the first weeks after prison-release. The N-ALIVE trial was planned as a large prison-based randomised controlled trial (RCT) to test the effectiveness of naloxone-on-release in the prevention of fatal opiate overdoses soon after release. The N-ALIVE pilot trial was conducted to test the main trial's assumptions on recruitment of prisons and prisoners, and the logistics for ensuring that participants received their N-ALIVE pack on release. DESIGN AND METHODS: Adult prisoners who had ever injected heroin, were incarcerated for ≥7 days and were expected to be released within 3 months were eligible. Participants were randomised to receive, on liberation, a pack containing a single 'rescue' injection of naloxone or a control pack with no naloxone syringe. The trial was double-blind prior to prison-release. RESULTS: We randomised 1685 prisoners (842 naloxone; 843 control) across 16 prisons in England. We stopped randomisation on 8 December 2014 because only one-third of administrations of naloxone-on-release were to the randomised ex-prisoner; two-thirds were to others whom we were not tracing. DISCUSSION AND CONCLUSIONS: Prevention RCTs are seldom conducted within prisons; we demonstrated the feasibility of conducting a multi-prison RCT to prevent fatality from opioid overdose in the outside community. We terminated the N-ALIVE trial due to the infeasibility of individualised randomisation to naloxone-on-release. Large RCTs are feasible within prisons.

Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial.

BACKGROUND: The international standard of care for women with suspected advanced ovarian cancer is surgical debulking followed by platinum-based chemotherapy. We aimed to establish whether use of platinum-based primary chemotherapy followed by delayed surgery was an effective and safe alternative treatment regimen. METHODS: In this phase 3, non-inferiority, randomised, controlled trial (CHORUS) undertaken in 87 hospitals in the UK and New Zealand, we enrolled women with suspected stage III or IV ovarian cancer. We randomly assigned women (1:1) either to undergo primary surgery followed by six cycles of chemotherapy, or to three cycles of primary chemotherapy, then surgery, followed by three more cycles of completion chemotherapy. Each 3-week cycle consisted of carboplatin AUC5 or AUC6 plus paclitaxel 175 mg/m(2), or an alternative carboplatin combination regimen, or carboplatin monotherapy. We did the random assignment by use of a minimisation method with a random element, and stratified participants according to the randomising centre, largest radiological tumour size, clinical stage, and prespecified chemotherapy regimen. Patients and investigators were not masked to group assignment. The primary outcome measure was overall survival. Primary analyses were done in the intention-to-treat population. To establish non-inferiority, the upper bound of a one-sided 90% CI for the hazard ratio (HR) had to be less than 1.18. This trial is registered, number ISRCTN74802813, and is closed to new participants. FINDINGS: Between March 1, 2004, and Aug 30, 2010, we randomly assigned 552 women to treatment. Of the 550 women who were eligible, 276 were assigned to primary surgery and 274 to primary chemotherapy. All were included in the intention-to-treat analysis; 251 assigned to primary surgery and 253 to primary chemotherapy were included in the per-protocol analysis. As of May 31, 2014, 451 deaths had occurred: 231 in the primary-surgery group versus 220 in the primary-chemotherapy group. Median overall survival was 22.6 months in the primary-surgery group versus 24.1 months in primary chemotherapy. The HR for death was 0.87 in favour of primary chemotherapy, with the upper bound of the one-sided 90% CI 0.98 (95% CI 0.72-1.05). Grade 3 or 4 postoperative adverse events and deaths within 28 days after surgery were more common in the primary-surgery group than in the primary-chemotherapy group (60 [24%] of 252 women vs 30 [14%] of 209, p=0.0007, and 14 women [6%] vs 1 woman [<1%], p=0.001). The most common grade 3 or 4 postoperative adverse event was haemorrhage in both groups (8 women [3%] in the primary-surgery group vs 14 [6%] in the primary-chemotherapy group). 110 (49%) of 225 women receiving primary surgery and 102 (40%) of 253 receiving primary chemotherapy had a grade 3 or 4 chemotherapy related toxic effect (p=0.0654), mostly uncomplicated neutropenia (20% and 16%, respectively). One fatal toxic effect, neutropenic sepsis, occurred in the primary-chemotherapy group. INTERPRETATION: In women with stage III or IV ovarian cancer, survival with primary chemotherapy is non-inferior to primary surgery. In this study population, giving primary chemotherapy before surgery is an acceptable standard of care for women with advanced ovarian cancer. FUNDING: Cancer Research UK and the Royal College of Obstetricians and Gynaecologists.

Desastres naturais: sistemas de informação e vigilância: uma revisão da literatura / Natural disasters: information systems and surveillance system: a review of literature

Objetivo: realizar revisão bibliográfica sobre a construção e implementação de sistemas de informação e vigilância sobre desastres naturais. Metodologia: o presente artigo apresenta uma revisão de literatura de artigos científicos realizada nas bases de dados Pubmed e Scielo. Resultados: demonstraram que os sistemas de informação e/ou vigilância utilizados tinham como objetivos principais a análise da extensão dos danos, identificação das áreas e populações vulneráveis e avaliação das necessidades em saúde de grupos populacionais mais expostos à ocorrência dos desastres. Conclusões: há a necessidade de sistemas de informação e vigilância integrados entre áreas como Saúde Pública, Defesa Civil e Ambiental para a análise dos efeitos dos desastres sobre a saúde das populações.

Objective: literature review on the construction and implementation of information systems and surveillance of natural disasters. Methodology: this article presents a literature review of papers held in the databases Pubmed and Scielo. Results: showed that information systems and/or surveillance were used as main objectives the analysis of the extent of the damage, identifying areas and vulnerable populations and assessment of health needs of population groups most exposed to the occurrence of disasters. Conclusions: there is need for information systems and integrated monitoring within areas such as Public Health, Civil and Environmental Defense to analyze the effects of disasters on the health of populations.

Experiências de avaliação do setor suplementar de saúde: contribuições da integralidade / Evaluation experiences of the supplementary care sector: contributions of integrality

Este trabalho identifica aspectos de integralidade nas propostas de avaliação de assistência à saúde da Agência Nacional de Saúde Suplementar (ANS), no Brasil, e do National Commitee for Quality Assurance (NCQA), nos Estados Unidos. A metodologia adotada foi a da análise documental das propostas encontradas nos sítios eletrônicos das instituições no segundo semestre de 2006. Os dados foram sistematizados numa matriz analítica com atributos das práticas de gestão e organização de serviços; dos conhecimentos e práticas dos trabalhadores de saúde; e das práticas de controle pela sociedade. Os resultados apresentados destacam, no caso brasileiro, uma ênfase no primeiro e terceiro atributos, com a avaliação centrada nas operadoras os planos de saúde não foram avaliados. No caso americano, houve um equilíbrio nos três conjuntos de atributos, sendo a avaliação direcionada aos planos de saúde. Ambas as propostas mensuraram a satisfação dos beneficiários e divulgam os resultados das avaliações em sítios eletrônicos. Em conclusão, destaca-se a importância de conceitos e abordagens avaliativas da integralidade nas operadoras de planos privados de saúde no setor suplementar brasileiro.

This work identifies aspects of comprehensiveness in the proposals for healthcare evaluation of the Agência Nacional de Saúde Suplementar (ANS) in Brazil, and of the National Commitee Quality Assurance (NCQA) in the U.S.A. The investigation was based on a documental analysis of the proposals found in the websites of both institutions in the second semester of 2006. The data were systemized according to pre-established attributes, building an analytical matrix for evaluating the following three dimensions: management practices and service organization; quality of knowledge and of practices of the health workers; and quality of the control practices of the society. In the Brazilian case there was an emphasis on the first and the third dimensions. The evaluation focalized the operators; the health plans were not evaluated. In the American case there was a balance between the three sets of attributes and the evaluation was focused on the health plans. Both proposals measured the satisfaction of the beneficiaries and made the results of the evaluations available in their websites. In conclusion we emphasize the importance of evaluative concepts and approaches for measuring the integrality of private health plan operators in the Brazilian supplementary health sector.

[Evaluation experiences of the supplementary care sector: contributions of integrality]. / Experiências de avaliação do setor suplementar de saúde: contribuições da integralidade.

This work identifies aspects of comprehensiveness in the proposals for healthcare evaluation of the Agência Nacional de Saúde Suplementar (ANS) in Brazil, and of the National Commitee Quality Assurance (NCQA) in the U.S.A. The investigation was based on a documental analysis of the proposals found in the websites of both institutions in the second semester of 2006. The data were systemized according to pre-established attributes, building an analytical matrix for evaluating the following three dimensions: management practices and service organization; quality of knowledge and of practices of the health workers; and quality of the control practices of the society. In the Brazilian case there was an emphasis on the first and the third dimensions. The evaluation focalized the operators; the health plans were not evaluated. In the American case there was a balance between the three sets of attributes and the evaluation was focused on the health plans. Both proposals measured the satisfaction of the beneficiaries and made the results of the evaluations available in their websites. In conclusion we emphasize the importance of evaluative concepts and approaches for measuring the integrality of private health plan operators in the Brazilian supplementary health sector.

[Political, institutional, and organizational evaluation of primary health care with an emphasis on comprehensiveness]. / Avaliação da atenção básica pela ótica político-institucional e da organização da atenção com ênfase na integralidade.

This article presents part of the data from an evaluation of primary care, implemented as part of research funded by the Brazilian Ministry of Health in 2005. Thirty-one municipalities from the States of Minas Gerais and Espírito Santo comprised the study sample. Data collected with qualitative methods (interviews and documents) were summarized, with the production of a set of categorical variables. The article presents the distribution of values for the variables by municipality. The variables were submitted to correspondence analysis, which showed their internal validity. The article also provides observations on relevant aspects of the field. In conclusion, the evaluation demonstrates advances in the Family Health Strategy in Brazil, with important contributions to the Project for Expansion and Consolidation of the Family Health Strategy, despite persistent obstacles, particularly related to human resources in the family health strategies and local use of the data produced.

Avaliação da atenção básica pela ótica político-institucional e da organização da atenção com ênfase na integralidade / Political, institutional, and organizational evaluation of primary health care with an emphasis on comprehensiveness

Este artigo apresenta parte dos dados de uma avaliação da Atenção Básica, implementada como parte de uma pesquisa com financiamento do Ministério da Saúde durante o ano de 2005. Trinta e um municípios, dos estados de Minas Gerais e Espírito Santo, Brasil, formaram a amostra do estudo. Dados coletados com base em métodos qualitativos (entrevistas e análise de documentos) foram sintetizados com a produção de um conjunto de variáveis categoriais. A distribuição dos diversos valores assumidos pelas variáveis nos diferentes municípios são apresentadas. Essas variáveis foram submetidas à análise de correspondência, que mostrou sua validade interna. Adicionalmente, observações sobre aspectos relevantes do campo são apresentados. Em conclusão, a avaliação mostra avanços da estratégia de saúde na família, com importantes contribuições do Projeto de Expansão e Consolidação do Saúde da Família, embora obstáculos consideráveis ainda permaneçam, em particular no que diz respeito à força de trabalho das estratégias de saúde na família e na utilização local das informações produzidas.

This article presents part of the data from an evaluation of primary care, implemented as part of research funded by the Brazilian Ministry of Health in 2005. Thirty-one municipalities from the States of Minas Gerais and Espírito Santo comprised the study sample. Data collected with qualitative methods (interviews and documents) were summarized, with the production of a set of categorical variables. The article presents the distribution of values for the variables by municipality. The variables were submitted to correspondence analysis, which showed their internal validity. The article also provides observations on relevant aspects of the field. In conclusion, the evaluation demonstrates advances in the Family Health Strategy in Brazil, with important contributions to the Project for Expansion and Consolidation of the Family Health Strategy, despite persistent obstacles, particularly related to human resources in the family health strategies and local use of the data produced.

Avaliação da cobertura do sistema de informação da atenção básica em sáude (SIAB): uma aplicação da metodologia de amostragem para garantia da qualidade de lotes / Assessment of coverage of the information system of the basic health care system (SIAB): an application of sampling methodology to ensure quality of allotments

Para o desenvolvimento de estudos consistentes de morbidade e de mortalidade e sua utlização na formulação de políticas públicas na área de saúde é necessário que os sistemas de informação seja de boa qualidade . São utilizadas técnicas de amostragem para avaliações rápidas para verificar a qualidade de dados do Sistema de Informação da Atenção Básica, o SIAB. Foram utilizados dados do acompanhamento dos programas de controle de hipertensão arterial, gestantes e crianças menores de um ano dos relatórios do SIAB referentes a Unidades de Saúde da Família de Juiz de Fora, Patos de Minas e Belo Horizonte. Testou-se a hipótese de que as coberturas informadas pelo SIAV seriam iguais às observadas com base nos registros das unidades de saúde. Os resultados indicam que as coberturas informadas pelos agentes comunitários não correspondiam a aquelas obtidas com os registros das unidades. Estes resultados sugerem que os agentes comunitários informam ao SIAB uma cobertura maior do que o real, os agentes informam corretamente, mas as unidades de saúde não atualizam seus registros e conseqüentemente não se beneficiam daquelas informações, há uma combinação das duas situações anteriores. Em síntese, conclui-se que há falta de sintonia entre o trabalho externo dos agentes comunitários e dos profissionais de saúde das unidades (AU)

Adolescentes e suas relações com serviços de saúde: estudo transversal em escolares de Niterói, Rio de Janeiro, Brasil / Adolescents and their relationship to health services: a school-based cross-sectional study in Niterói, Rio de Janeiro, Brazil

Este estudo transversal, realizado nas escolas de um bairro do Município de Niterói, Rio de Janeiro, Brasil, descreve a relação de adolescentes, entre 12 e 17 anos, com os serviços de saúde, através dos indicadores ­ morbidade referida, auto-avaliação do estado de saúde, necessidade de saúde sentida, demanda, utilização, fidelidade aos serviços de saúde e adesão aos cuidados de saúde ­ e sua associação com variáveis sócio-demográficas. O nível sócio-econômico, representado pelo tipo de escola, mostrou-se associado a todos os indicadores. Os alunos das escolas públicas tinham uma chance maior do que os alunos das escolas privadas de avaliarem seu estado de saúde como regular ou ruim e uma chance menor de expressarem necessidade sentida positivamente, demandarem serviços de saúde, obterem acesso aos serviços procurados e manterem-se fiéis aos serviços utilizados. As meninas apresentaram maior chance de auto-avaliarem seu estado de saúde como ruim ou muito ruim e de demandarem serviços de saúde. A adesão, tanto à realização de exames quanto ao tratamento prescrito por médicos, mostrou-se elevada na amostra investigada.

[Adolescents and their relationship to health services: a school-based cross-sectional study in Niterói, Rio de Janeiro, Brazil]. / Adolescentes e suas relações com serviços de saúde: estudo transversal em escolares de Niterói, Rio de Janeiro, Brasil.

This cross-sectional study describes the relationship between adolescents and health services using several indicators (self-reported diseases, self-rated health status, the need and search for health care, health care utilization and fidelity, adherence to medical prescription) and their association with socio-demographic variables. The adolescents (aged 12 to 17 years) were enrolled in schools from a district in Niteroi, Rio de Janeiro State, Brazil. Type of school, representing the participants' socioeconomic status, was associated with all the indicators. Adolescents in public schools tended to rate their health status as fair or poor. They also showed lower odds of reporting health needs, the search for health care, obtaining access, and remaining faithful to health services. Girls rated their health status as fair or poor and sought health care more frequently boys. High adherence to medical prescription of medicines and tests was observed in the sample.

Implementação da atenção básica em saúde no Município de Niterói, RJ: estudo de caso em unidade básica de saúde tradicional e módulo do programa médico de família / Implementation of the basic attention in health in the Municipal district of Niterói, RJ: I study of case in basic unit of traditional health and module of the medical program of family

A implementação da atenção básica em saúde no município de Niterói/RJ foi avaliada através de estudos de caso de uma Unidade Básica de Saúde, no bairro de Santa Bárbara, e de um módulo do Programa Médico de Família, no bairro de Jurujuba. Para a medida do grau de implementação utilizaram-se, como condições traçadoras da atenção, os programas de pré-natal e o de controle da hipertensão arterial. Adotaram-se os seguintes pressupostos teóricos: a) o grau de implementação dessas ações (cobertura, integralidade e qualidade), nas unidades de saúde selecionadas, está associado aos processos de trabalho; b) os dois modelos assistenciais de atenção básica em saúde apresentam diferenças nos processos de trabalho relacionadas às dimensões de acolhimento e vínculo / responsabilização entre profissionais de saúde e população. A metodologia de pesquisa avaliativa baseou-se em revisão de literatura e pesquisa documental, checagem dos protocolos em coleta de dados de prontuários, roteiro para entrevista semi-estruturada, observação participante, gravações, depoimentos de amostra dos usuários e dos membros das equipes de saúde, incluindo avaliação da estrutura e funcionamento das unidades através de instrumento validado pelo Ministério da Saúde. Entre os resultados observados, destacou-se o grau de implementação mais adequado do programa de pré-natal e de algumas dimensões do controle da hipertensão arterial, no módulo do PMFN, em relação à situação da UBS; e, no processo de trabalho das duas unidades, verificou-se que o módulo do PMFN tem melhor desempenho, em termos de acolhimento e vínculo/responsabilização, do que na UBS. Embora os estudos de caso não permitam estabelecer relações de causa-efeito entre os dois modelos assistenciais, os diferenciais observados fortalecem o pressuposto das relações entre processo de trabalho e qualidade da Atenção Básica em Saúde, coerentes com a percepção referida pelos profissionais e usuários dos programas analisados

O Programa Médico de Família de Niterói (PMFN): uma agenda para reflexão / The Family Doctor Program in Niterói: an agenda for reflection

O artigo aborda aspectos sobre a mudança do modelo assistencial, a partir da implementação do Programa Médico de Família (PMFN) e propõe elementos que ajudam essa reflexão. É apresentado um histórico dos antecedentes do PMFN; ajudam essa reflexão. É apresentado um hsitórico dos antecedentes do PMFN; descrevem-se as principais diretrizes; resumem-se dados disponíveis sobre sua implantação e a relação com os serviços locais de saúde; discutem-se alguns dos problemas que emergem com sua implantação e conclui apontando questões que merecem pesquisa e investimento. Espera-se contribuir para a reorganização de serviços de saúde e estimular o desenvolvimento de estudos que subsidiem a implantação do Sistem Único de Saúde (SUS).

O programa médico de família de Niterói (PMFN): uma agenda para reflexäo / The family doctor program in Niterói: an agenda for reflection

Aborda aspectos sobre a mudança do modelo assistencial, a partir da implementaçäo do programa saúde da família. Resgata a história do programa médico de família de Niterói (PMFN) e propöe elementos que ajudam essa reflexäo. É apresentado um histórico dos antecedentes do PMFN; descrevem-se as principais diretrizes; resumem-se dados disponíveis sobre sua implantaçäo e a relaçäo com os serviços locais de saúde; discutem-se alguns dos problemas que emergem com sua implantaçäo e conclui apontando questöes que merecem pesquisa e investimento. Espera-se contribuir para a reorganizaçäo de serviços de saúde e estimular o desenvolvimento de estudos que subsidiem a implantaçäo do Sistema Unico de Saúde (SUS). (AU)

Co-selection of the H63D mutation and the HLA-A29 allele: a new paradigm of linkage disequilibrium?

The major histocompatibility complex (MHC) shows a remarkable conservation of particular HLA antigens and haplotypes in linkage disequilibrium in most human populations, suggesting the existence of a convergent evolution. A recent example of such conservation is the association of particular HLA haplotypes with the HFE mutations. With the objective of exploring the significance of that association, the present paper offers an analysis of the linkage disequilibrium between HLA alleles or haplotypes and the HFE mutations in a Portuguese population. Allele and haplotype associations between HLA and HFE mutations were first reviewed in a population of 43 hemochromatosis families. The results confirmed the linkage disequilibrium of the HLA haplotype HLA-A3-B7 and the HLA-A29 allele, respectively, with the HFE mutations C282Y and H63D. In order to extend the study of the linkage disequilibrium between H63D and the HLA-A29-containing haplotypes in a normal, random population, an additional sample of 398 haplotypes was analyzed. The results reveal significant linkage disequilibrium between the H63D mutation and all HLA-A29-containing haplotypes, favoring the hypothesis of a co-selection of H63D and the HLA-A29 allele itself. An insight into the biological significance of this association is given by the finding of significantly higher CD8(+) T-lymphocyte counts in subjects simultaneously carrying the H63D mutation and the HLA-A29 allele.