La cara oculta del estudio 329 y la manipulación de la evidencia científica / Study's 329 hiddens face and scientifics evidence manipulation

El emblemático ensayo clínico 329, financiado por Smith Kline Beecham (actualmente GlaxoSmith-Kline) y publicado en2001, permitió posicionar a la paroxetina como un tratamiento efectivo y seguro para la depresión mayor en adolescentes. En la presente editorial el autor describe los sucesos ocurridos luego de su publicación, partiendo de los cuestionamientos iniciales respecto de su eficacia, hasta llegar a los resultados de su reciente reanálisis (llevando adelante por la iniciativa internacional RIAT), el cual concluyo que dicho fármaco no solo no provee un beneficio adicional al placebo para la condición y población utilizada, sino que además se asocia a efectos adversos sustanciales que no habían sido reportados en el informe original. Se exploran además las repercusiones de este suceso en la comunidad científica y se hace un señalamiento de la necesidad de permitir el acceso a las bases de datos originales que sustentan los resultados y conclusiones de las investigaciones publicadas, como mecanismo de transparencia superador a la revisión por pares. (AU)

The emblematic 329 study, funded by Smith Kline Beecham (now GlaxoSmith-Kline) and published in 2001, allowed to position paroxetine as an effective and safe treatment for major depression in adolescents. In this editorial, the author describes the events after its publication, from the initial concerns about its effectiveness, to the results of its recent reanalysis (accounted by the international RIAT initiative), which concluded that the drug not only does not provide an additional benefit than placebo, but is also associated with significant adverse effects that were not reported in the original report. It also explores the repercussions generated in the scientific community by this event, pointing out the need to allow access to original databases that support the findings and conclusions of published research, as an overcoming mechanism for transparency to the traditional peerreview. Agustín Ciapponi Study's 329 hiddens face and scientifics evidence manipulation. (AU)

The brain monitoring with Information Technology (BrainIT) collaborative network: EC feasibility study results and future direction.

BACKGROUND: The BrainIT group works collaboratively on developing standards for collection and analyses of data from brain-injured patients and to facilitate a more efficient infrastructure for assessing new health care technology with the primary objective of improving patient care. European Community (EC) funding supported meetings over a year to discuss and define a core dataset to be collected from patients with traumatic brain injury using IT-based methods. We now present the results of a subsequent EC-funded study with the aim of testing the feasibility of collecting this core dataset across a number of European sites and discuss the future direction of this research network. METHODS: Over a 3-year period, data collection client- and web-server-based tools were developed and core data (grouped into nine categories) were collected from 200 head-injured patients by local nursing staff in 22 European neuro-intensive care centres. Data were uploaded through the BrainIT website and random samples of received data were selected automatically by computer for validation by data validation staff against primary sources held in each local centre. Validated data were compared with originally transmitted data and percentage error rates calculated by data category. Feasibility was assessed in terms of the proportion of missing data, accuracy of data collected and limitations reported by users of the IT methods. FINDINGS: Thirteen percent of data files required cleaning. Thirty "one-off" demographic and clinical data elements had significant amounts of missing data (>15%). Validation staff conducted 19,461 comparisons between uploaded database data with local data sources and error rates were commonly less than or equal to 6%, the exception being the surgery data class where an unacceptably high error rate of 34% was found. Nearly 10,000 therapies were successfully recorded with start-times but approximately a third had inaccurate or missing "end-times" which limits the analysis of duration of therapy. Over 40,000 events and procedures were recorded but events with long durations (such as transfers) were more likely to have end-times missed. CONCLUSIONS: The BrainIT core dataset is a rich dataset for hypothesis generation and post hoc analyses, provided that studies avoid known limitations in the dataset. Limitations in the current IT-based data collection tools have been identified and have been addressed. In order for multi-centre data collection projects to be viable, the resource intensive validation procedures will require a more automated process and this may include direct electronic access to hospital-based clinical data sources for both validation purposes and for minimising the duplication of data entry. This type of infrastructure may foster and facilitate the remote monitoring of patient management and protocol adherence in future trials of patient management and monitoring.

Vigilância das intoxicações por agrotóxicos no estado do Mato Grosso do Sul: uma proposta de relacionamento entre banco de dados / Surveillance of pesticide poisoning in the state of Mato Grosso do Sul: a proposed relationship between database

Os agrotóxicos são utilizados em grande escala pelo setor agropecuário etrazem, em decorrência do seu uso indiscriminado, uma série de graves problemas, que incluem o risco da exposição da população, a intoxicação dos trabalhadores e a contaminação do meio ambiente. As intoxicações por agrotóxicos representam atualmente, um dos mais alarmantes problemas de saúde pública, principalmente nos países em desenvolvimento. O Brasil é umdos líderes mundiais em consumo de agrotóxicos e os trabalhadores expostos são numerosos e diversificados. No estado de Mato Grosso do Sul, cuja economia é predominantemente agrícola, persiste a carência de estudos epidemiológicos nessa área e apesar de existirem vários sistemas de informação que notificam os casos de intoxicações, na prática dos serviços de vigilância, não há um perfil epidemiológico traçado das intoxicações por agrotóxicos e tampouco uma proposta de monitoramento das mesmas. Objetivos: Traçar o perfil epidemiológico das intoxicações por agrotóxicos registrados no Estado de Mato Grosso do Sul, no período de 1998 a 2007, e propor um método de pareamento dos bancos de dados com o intuito de melhor estimar o número total de casos ocorridos. Métodos: Estudo descritivo transversal baseado na análise de 2.442 registros de casos notificados de intoxicações por agrotóxicos no Centro Integrado de Vigilância Toxicológica (CIVITOX) e no Sistema de Informação de Agravos de Notificação (SINAN). Foram estudadas variáveis sócio–demográficas, ocupacionais, relacionadas ao produto agrotóxico, e relacionadas à intoxicação. O pareamento dos dados foi realizado pelo método probabilístico do Link Plus. Também foi analisada a qualidade de preenchimento das variáveis nos dois sistemas...

Pesticides are widely used in the agricultural sector and as a result of their indiscriminate use, a number of serious problems occurs, which includes the risk of exposure in the population, the poisoning of workers and environmental contamination. The pesticide poisoning currently represent one of the most alarming public health problems, especially in developing countries. Currently Brazil is a world leader in pesticide consumption and exposed workers are numerous and diverse. In the state of Mato Grosso do Sul, whose economy is predominantly agricultural, there remains a lack of epidemiological studies inthis area and although there are several information systems that report casesof poisoning in the routine of the health services, there is no epidemiologicaltracing of pesticide poisoning and not even a proposal for monitoring them.Objectives: To describe the epidemiology of pesticide poisoning reported in the State of Mato Grosso do Sul in the period 1998-2007 and propose a method of matching of the databases in order to better estimate the total number of cases occurred. Methods: A cross-sectional analysis based on 2.442 records of reported cases of pesticide poisoning in the Centro Integrado de Vigilância Toxicológica (CIVITOX) and Sistema de Informação de Agravos de Notificação (SINAN). We studied socio-demographic, occupational, pesticide-related products, and related to intoxication. The pairing of the data was performed by the probabilistic method of Link Plus. We analyzed the quality of filling of the variables in both systems...

Nomenclature and databases for the surgical treatment of congenital cardiac disease--an updated primer and an analysis of opportunities for improvement.

This review discusses the historical aspects, current state of the art, and potential future advances in the areas of nomenclature and databases for the analysis of outcomes of treatments for patients with congenitally malformed hearts. We will consider the current state of analysis of outcomes, lay out some principles which might make it possible to achieve life-long monitoring and follow-up using our databases, and describe the next steps those involved in the care of these patients need to take in order to achieve these objectives. In order to perform meaningful multi-institutional analyses, we suggest that any database must incorporate the following six essential elements: use of a common language and nomenclature, use of an established uniform core dataset for collection of information, incorporation of a mechanism of evaluating case complexity, availability of a mechanism to assure and verify the completeness and accuracy of the data collected, collaboration between medical and surgical subspecialties, and standardised protocols for life-long follow-up. During the 1990s, both The European Association for Cardio-Thoracic Surgery and The Society of Thoracic Surgeons created databases to assess the outcomes of congenital cardiac surgery. Beginning in 1998, these two organizations collaborated to create the International Congenital Heart Surgery Nomenclature and Database Project. By 2000, a common nomenclature, along with a common core minimal dataset, were adopted by The European Association for Cardio-Thoracic Surgery and The Society of Thoracic Surgeons, and published in the Annals of Thoracic Surgery. In 2000, The International Nomenclature Committee for Pediatric and Congenital Heart Disease was established. This committee eventually evolved into the International Society for Nomenclature of Paediatric and Congenital Heart Disease. The working component of this international nomenclature society has been The International Working Group for Mapping and Coding of Nomenclatures for Paediatric and Congenital Heart Disease, also known as the Nomenclature Working Group. By 2005, the Nomenclature Working Group crossmapped the nomenclature of the International Congenital Heart Surgery Nomenclature and Database Project of The European Association for Cardio-Thoracic Surgery and The Society of Thoracic Surgeons with the European Paediatric Cardiac Code of the Association for European Paediatric Cardiology, and therefore created the International Paediatric and Congenital Cardiac Code, which is available for free download from the internet at [http://www.IPCCC.NET]. This common nomenclature, the International Paediatric and Congenital Cardiac Code, and the common minimum database data set created by the International Congenital Heart Surgery Nomenclature and Database Project, are now utilized by both The European Association for Cardio-Thoracic Surgery and The Society of Thoracic Surgeons. Between 1998 and 2007 inclusive, this nomenclature and database was used by both of these two organizations to analyze outcomes of over 150,000 operations involving patients undergoing surgical treatment for congenital cardiac disease. Two major multi-institutional efforts that have attempted to measure the complexity of congenital heart surgery are the Risk Adjustment in Congenital Heart Surgery-1 system, and the Aristotle Complexity Score. Current efforts to unify the Risk Adjustment in Congenital Heart Surgery-1 system and the Aristotle Complexity Score are in their early stages, but encouraging. Collaborative efforts involving The European Association for Cardio-Thoracic Surgery and The Society of Thoracic Surgeons are under way to develop mechanisms to verify the completeness and accuracy of the data in the databases. Under the leadership of The MultiSocietal Database Committee for Pediatric and Congenital Heart Disease, further collaborative efforts are ongoing between congenital and paediatric cardiac surgeons and other subspecialties, including paediatric cardiac anaesthesiologists, via The Congenital Cardiac Anesthesia Society, paediatric cardiac intensivists, via The Pediatric Cardiac Intensive Care Society, and paediatric cardiologists, via the Joint Council on Congenital Heart Disease and The Association for European Paediatric Cardiology. In finalizing our review, we emphasise that analysis of outcomes must move beyond mortality, and encompass longer term follow-up, including cardiac and non cardiac morbidities, and importantly, those morbidities impacting health related quality of life. Methodologies must be implemented in these databases to allow uniform, protocol driven, and meaningful, long term follow-up.

Tactical increases in operating room block time based on financial data and market growth estimates from data envelopment analysis.

BACKGROUND: Data envelopment analysis (DEA) is an established technique that hospitals and anesthesia groups can use to understand their potential to grow different specialties of inpatient surgery. Often related decisions such as recruitment of new physicians are made promptly. A practical challenge in using DEA in practice for this application has been the time to obtain access to and preprocess discharge data from states. METHODS: A case study is presented to show how results of DEA are linked to financial analysis for purposes of deciding which surgical specialties should be provided more resources and institutional support, including the allocation of additional operating room (OR) block time on a tactical (1 yr) time course. State discharge abstract databases were used to study how to perform and present the DEA using data from websites of the United States' (US) Healthcare Cost and Utilization Project (HCUPNet) and Census Bureau (American FactFinder). RESULTS: DEA was performed without state discharge data by using census data with federal surgical rates adjusted for age and gender. Validity was assessed based on multiple criteria, including: satisfaction of statistical assumptions, face validity of results for hospitals, differentiation between efficient and inefficient hospitals on other measures of how much surgery is done, and correlation of estimates of each hospital's potential to grow the workload of each of eight specialties with estimates obtained using unrelated statistical methods. CONCLUSIONS: A hospital can choose specialties to target for expanded OR capacity based on its financial data, its caseloads for specific specialties, the caseloads from hospitals previously examined, and surgical rates from federal census data.

Lifestyle-related cancer death rates in Ireland: decreasing or increasing?

We examined death patterns of tobacco-related cancers (lung, oesophagus, larynx, and pharynx) and of non-tobacco related cancers (breast and prostate) from 1972 to 2001 in Ireland, utilizing the WHO Cancer Mortality Database. Estimated-annual-percent-changes (EAPC) in age-adjusted cancer death rates (standardised to world standard population) were calculated by age (10-year groups), period (10-year intervals) and sex. Overall, EAPCs of all the cancer sites studied showed a declining trend in the most recent period (1992-2001), with male oesophageal cancer rates showing a deceleration between 1992 and 2001. In 1992-2001, the youngest age-group studied (45-54 year-olds) showed a statistically significant declining annual rate particularly for lung cancer (males), breast and laryngeal cancer (females); prostate cancer death rates have slowed down in the youngest adults (45-54 year-olds); and the oldest age-groups studied (75-84 year-olds) are also showing an annual deceleration in some cancer sites, with a significant declining annual rate for breast cancer. In conclusion, the current and the future cancer death rates of some common life-style related cancers in Ireland are encouraging.

Mining the NCI screening database: explorations of agents involved in cell cycle regulation.

We propose an integrated application of technologies, computation and statistical methods to design experiments for examination of cellular pathways that are necessary for cell survival and that are candidates for cancer therapy. Our design combines information derived from two very different data sets: tumor screening data from over 36,000 synthetic compounds screened against over 60 tumor cell lines, and replicate microarray gene expression measurements using one cell line and one compound. Data filtering, based on restricted cellular cytotoxicity profiles from chemically similar sets of compounds, has been used to select a class of benzothiazoles for subsequent microarray gene expression measurements in the most chemosensitive tumor cell line. The results confirmed observations that P450 metabolizing isoforms, CYP1A1 and CYP1B1, are overexpressed in MCF-7 tumor cells following treatment with benzothiazole. These results are consistent with the proposed inactivity of the CYP1A1-mediated metabolism of benzothiazole and the antitumor activity of the metabolically resistant halogenated forms.

Bioinformática: caracterizaçäo, principais aplicaçöes e pesquisa computacional subjacente / Bioinformatics: characterization, main applications and subjacent computational research

Este artigo evidencia a Bioinformática como uma área emergente de pesquisa, caracterizando-a como uma área multidisciplinar, que faz uso de técnicas computacionais já existentes e que investe no estabelecimento e desenvolvimento de outras novas. Mostra que um dos principais objetivos da área é o de adequar e desenvolver técnicas computacionais, que visam o armazenamento, a análise, a recuperaçäo e a interpretaçäo de informaçöes biológicas, que possibilitem, entre outros, a reduçäo na duplicidade de esforços para a obtençäo daquelas informaçöes, a sua rápida difusäo e a sua transformaçäo em conhecimento.