Efficacy of prescribed injectable diacetylmorphine in the Andalusian trial: Bayesian analysis of responders and non-responders according to a multi domain outcome index.

BACKGROUND The objective of this research was to evaluate data from a randomized clinical trial that tested injectable diacetylmorphine (DAM) and oral methadone (MMT) for substitution treatment, using a multi-domain dichotomous index, with a Bayesian approach. METHODS Sixty two long-term, socially-excluded heroin injectors, not benefiting from available treatments were randomized to receive either DAM or MMT for 9 months in Granada, Spain. Completers were 44 and data at the end of the study period was obtained for 50. Participants were determined to be responders or non responders using a multi-domain outcome index accounting for their physical and mental health and psychosocial integration, used in a previous trial. Data was analyzed with Bayesian methods, using information from a similar study conducted in The Netherlands to select a priori distributions. On adding the data from the present study to update the a priori information, the distribution of the difference in response rates were obtained and used to build credibility intervals and relevant probability computations. RESULTS In the experimental group (n = 27), the rate of responders to treatment was 70.4% (95% CI 53.287.6), and in the control group (n = 23), it was 34.8% (95% CI 15.354.3). The probability of success in the experimental group using the a posteriori distributions was higher after a proper sensitivity analysis. Almost the whole distribution of the rates difference (the one for diacetylmorphine minus methadone) was located to the right of the zero, indicating the superiority of the experimental treatment. CONCLUSION The present analysis suggests a clinical superiority of injectable diacetylmorphine compared to oral methadone in the treatment of severely affected heroin injectors not benefiting sufficiently from the available treatments. TRIAL REGISTRATION Current Controlled Trials ISRCTN52023186.

Risk assessment of recurrence in sporadic retinoblastoma using a molecular-based algorithm.

PURPOSE: Most RB1 mutations are unique and distributed throughout the RB1 gene. Their detection can be time-consuming and the yield especially low in cases of conservatively-treated sporadic unilateral retinoblastoma (Rb) patients. In order to identify patients with true risk of developing Rb, and to reduce the number of unnecessary examinations under anesthesia in all other cases, we developed a universal sensitive, efficient and cost-effective strategy based on intragenic haplotype analysis. METHODS: This algorithm allows the calculation of the a posteriori risk of developing Rb and takes into account (a) RB1 loss of heterozygosity in tumors, (b) preferential paternal origin of new germline mutations, (c) a priori risk derived from empirical data by Vogel, and (d) disease penetrance of 90% in most cases. We report the occurrence of Rb in first degree relatives of patients with sporadic Rb who visited the Jules Gonin Eye Hospital, Lausanne, Switzerland, from January 1994 to December 2006 compared to expected new cases of Rb using our algorithm. RESULTS: A total of 134 families with sporadic Rb were enrolled; testing was performed in 570 individuals and 99 patients younger than 4 years old were identified. We observed one new case of Rb. Using our algorithm, the cumulated total a posteriori risk of recurrence was 1.77. CONCLUSIONS: This is the first time that linkage analysis has been validated to monitor the risk of recurrence in sporadic Rb. This should be a useful tool in genetic counseling, especially when direct RB1 screening for mutations leaves a negative result or is unavailable.

A PARIDADE CAMBIAL E AS SUAS VANTAGENS PARA A ECONOMIA CABOVERDIANA

A gestão da economia é uma actividade inerente a todos os países, uma vez que a escassez de recursos é uma realidade inquestionável. Cabo Verde elegeu a estabilidade de preços como um dos principais pilares da sua política económica e, neste contexto identificou a Paridade Cambial ao Euro como um meio privilegiado para a sua consecução. Neste âmbito, assinou o Acordo de Cooperação Cambial (ACC) em 1998 com Portugal como forma de credibilizar a Paridade Cambial com o Euro. Este trabalho, embora de cariz académico, tem por objectivo estudar as vantagens da Paridade Cambial para a Economia Cabo-verdiana. É composto por quatro capítulos e um glossário. Para sua realização foram consultados livros, Decretos-Lei, sítios, relatórios e boletins do Banco de Cabo Verde (BCV). O Capítulo I descreve os principais regimes cambiais existentes, apresentando as suas características, suas vantagens e desvantagens. O Capítulo II apresenta os critérios e indicadores, normalmente utilizados pelos países na escolha do regime cambial. O Capítulo III fala dos regimes cambiais em Cabo Verde, mostra que até se chegar ao regime cambial actual o país já passou por várias experiências cambiais. O Capítulo IV descreve o ACC, começando por apresentar as suas características e os seus objectivos, analisa as vantagens e os eventuais custos da Paridade Cambial CVE/Euro e por fim fala da credibilidade do regime cambial de Cabo Verde.

Aplicação de um modelo de Balanced Scorecard na Clínica Medicentro: Vantagens e desvantagens

Este trabalho procura descrever uma aplicação de uma ferramenta de gestão, designada de Balanced Scorecard, numa Clínica privada. Para fundamentação de todo o trabalho, iniciamos com uma revisão bibliográfica dos diversos conceitos relacionados com o Balanced Scorecard, nomeadamente os seus componentes, os seus princípios, as suas vantagens e desvantagens, bem como também as suas diversas fases de implementação. Posteriormente, foi desenvolvido um estudo de caso numa Clínica privada, onde fizemos uma proposta de aplicação de um instrumento de gestão, neste caso o Balanced Scorecard. Para a recolha de dados, aplicámos um guião de entrevista aos responsáveis da Medicentro, um questionário aos pacientes, utilizámos documentos fornecidos pela Instituição, e ainda utilizámos a técnica da observação directa. Neste estudo, optámos por seguir uma metodologia de implementação proposta por RUSSO (2006), adaptadas às PME, onde, em primeiro lugar, fizemos uma análise da estratégia, através de um diagnóstico da situação da Clínica, e,posteriormente, uma formulação da mesma onde foram abordados a visão da Clínica, os factores críticos de sucesso e os diversos componentes do Balanced Scorecard. Nesta metodologia proposta por RUSSO, não é evidenciado o Mapa Estratégico, logo elaborámos o mesmo, e colocamo-lo nos apêndices. Os resultados obtidos com o estudo revelaram que a Clínica possui algumas insuficiências no que concerne a sua gestão, derivadas principalmente da sua situação financeira. This work seeks to describe an application of a management tool called the balanced scorecard, in a private Clinic. Strategically we began with a literature review of the various concepts related to the balanced scorecard, including its components, their principles, their advantages and disadvantages and also their several stages of implementation. On the second step, we developed a case study in a private clinic where we made a proposal for implementation of a management tool, that is, the balanced scorecard. For data collection, we have applied an interview guide to the responsible for Medicentro, a questionnaire to patients, using documents supplied by the Institution and, in addition, of a direct observation. In this study, we have followed a methodology of implementation proposed by Russo (2006), adapted SMEs, where in first place we made an analysis of the strategy through a diagnosis of the situation of the Clinic, and later a formulation of the same were addressed to Clinical view, the critical factors of success, and the various components of the balanced scorecard. This methodology proposed by Russo is not evidenced the strategic map. Therefore we elaborated the same and we have placed it in the appendices. The results obtained from the study revealed that the Clinic has some inadequacies in what concern its management because of its financial situation.

Vantagens de uma empresa estar cotada na Bolsa de Valores de Cabo Verde

É de conhecimento de todos, ou pelo menos daqueles que estão mais atentos às questões de natureza económica, que um dos grandes desafios das empresas nos dias que correm, é garantirem a sua sustentabilidade financeira no longo prazo. Nesse sentido, são várias as estratégias elaboradas pelos responsáveis das diversas empresas, e decisores políticos, no sentido colmatar esta dificuldade. Cabo Verde, como país de Desenvolvimento Médio, muito dependente do exterior, apresenta muitas dificuldades em gerar recursos que garantam a sustentabilidade da sua economia. Como forma de reestruturar e dinamizar a economia e o tecido empresarial nacional, foi reaberta em 2005 a Bolsa de Valores de Cabo Verde. E para retratar o impato positivo da sua reabertura, referir que nesse mesmo ano, a Sociedade Caboverdiana de Tabacos, S.A., realizou na Bolsa de Valores de Cabo Verde, uma Oferta Pública de Venda, que segundo os analístas, foi muito superior a oferta, deixando assim, uma ideia clara de que este, com mais incentivo, tem margem de crescimento. Este trabalho visa numa primeira parte caraterizar o mercado de capitais em Cabo Verde, onde está inserida a Bolsa de Valores Local. Num segundo momento, pretendese fazer uma resenha bibliográfica dos principais métodos de avaliação das empresas e de seguida procurar-se, através de um estudo de caso, a Sociedade Cabo-verdiana de Tabacos, identificar algumas possíveis vantagens provenientes da sua entrada na Bolsa de Valores, mediante a avaliação de alguns indicadores de desempenho da empresa. It is known to all, or at least to those who are more attentive to the matters of economic issues, that one of the biggest problems facing companies today is to ensure their financial sustainability. Accordingly, there are several strategies drawn up by leaders of various companies in order to face this difficulty. Cape Verde, as a medium-developed country, is very dependent on other countries‟ help and has great difficulty in generating resources that guarantee a good and healthy economy. As a way to restructure the economy and minimize some financial problems, in 2005 the Stock Exchange of Cape Verde was reopened, to remedy this deficiency. For one to have a clear idea of the importance of this reopening, we can look at the example of Sociedade Caboverdiana de Tabacos – tobacco national company – that, still in this year, has made a bid on Stock Exchange, which, according to specialists, demonstrated an offer a lot greater than the demand, clearly a sign that this company, has a great margin for growth, if it has more financial incentives. This paper seeks to demonstrate and characterize the capital market of Cape Verde, where we will find the National Stock Exchange. Secondly, we intend to make a bibliographical research of the main assessment methods companies use here, to finally, through a case study, at SCT, identify possible advantages that might come from being listed in the Stock Exchange, through the analysis of some performance indicators from this company.

Sistema de apoio à decisão na gestão de Estabelecimento de ensino O caso da Unipiaget

A memória apresentada à Universidade Jean Piaget de cabo Verde, apresenta um estudo sobre Sistemas de Apoio à Decisão (SAD) na gestão de um estabelecimento de ensino, mais especificamente a análise da sua arquitectura bem como os aspectos que estão minimamente ligados ao tema em estudo, onde para além disso demostramos casos de organizações educativas que estão utilizando um SAD para a gestão dos mesmos. Ainda apresentamos um estudo de caso sobre a Unipiaget, a partir do qual concluímos que a Universidade ainda não dispõe de um sistema de apoio à decisão, o que remete-nos para uma questão muito importante, relativamente à partilha de informação e uso da mesma no processo de tomada de decisões, sendo que esta ainda precisa melhorar muito estes aspectos. Apesar disso, constatámos que a Unipiaget tem feito e está fazer o possível para melhorar o seu sistema, e a prova disso é a implementação de um sistema de informação académico, que está a ser desenvolvido na universidade, o SIAC. Portanto é de realçar que felizmente conseguimos alcançar os objectivos traçados a priori, embora tenham surgido alguns obstáculos, nomeadamente a escassez bibliográfica, mas isso não é nada que dedicação/ boa vontade não consigam superar.

A fast Bayesian reconstruction algorithm for emission tomography with entropy prior converging to feasible images

The development and tests of an iterative reconstruction algorithm for emission tomography based on Bayesian statistical concepts are described. The algorithm uses the entropy of the generated image as a prior distribution, can be accelerated by the choice of an exponent, and converges uniformly to feasible images by the choice of one adjustable parameter. A feasible image has been defined as one that is consistent with the initial data (i.e. it is an image that, if truly a source of radiation in a patient, could have generated the initial data by the Poisson process that governs radioactive disintegration). The fundamental ideas of Bayesian reconstruction are discussed, along with the use of an entropy prior with an adjustable contrast parameter, the use of likelihood with data increment parameters as conditional probability, and the development of the new fast maximum a posteriori with entropy (FMAPE) Algorithm by the successive substitution method. It is shown that in the maximum likelihood estimator (MLE) and FMAPE algorithms, the only correct choice of initial image for the iterative procedure in the absence of a priori knowledge about the image configuration is a uniform field.

Time-lapse and probabilistic inversion strategies for plane-wave electromagnetic data.

L'utilisation efficace des systèmes géothermaux, la séquestration du CO2 pour limiter le changement climatique et la prévention de l'intrusion d'eau salée dans les aquifères costaux ne sont que quelques exemples qui démontrent notre besoin en technologies nouvelles pour suivre l'évolution des processus souterrains à partir de la surface. Un défi majeur est d'assurer la caractérisation et l'optimisation des performances de ces technologies à différentes échelles spatiales et temporelles. Les méthodes électromagnétiques (EM) d'ondes planes sont sensibles à la conductivité électrique du sous-sol et, par conséquent, à la conductivité électrique des fluides saturant la roche, à la présence de fractures connectées, à la température et aux matériaux géologiques. Ces méthodes sont régies par des équations valides sur de larges gammes de fréquences, permettant détudier de manières analogues des processus allant de quelques mètres sous la surface jusqu'à plusieurs kilomètres de profondeur. Néanmoins, ces méthodes sont soumises à une perte de résolution avec la profondeur à cause des propriétés diffusives du champ électromagnétique. Pour cette raison, l'estimation des modèles du sous-sol par ces méthodes doit prendre en compte des informations a priori afin de contraindre les modèles autant que possible et de permettre la quantification des incertitudes de ces modèles de façon appropriée. Dans la présente thèse, je développe des approches permettant la caractérisation statique et dynamique du sous-sol à l'aide d'ondes EM planes. Dans une première partie, je présente une approche déterministe permettant de réaliser des inversions répétées dans le temps (time-lapse) de données d'ondes EM planes en deux dimensions. Cette stratégie est basée sur l'incorporation dans l'algorithme d'informations a priori en fonction des changements du modèle de conductivité électrique attendus. Ceci est réalisé en intégrant une régularisation stochastique et des contraintes flexibles par rapport à la gamme des changements attendus en utilisant les multiplicateurs de Lagrange. J'utilise des normes différentes de la norme l2 pour contraindre la structure du modèle et obtenir des transitions abruptes entre les régions du model qui subissent des changements dans le temps et celles qui n'en subissent pas. Aussi, j'incorpore une stratégie afin d'éliminer les erreurs systématiques de données time-lapse. Ce travail a mis en évidence l'amélioration de la caractérisation des changements temporels par rapport aux approches classiques qui réalisent des inversions indépendantes à chaque pas de temps et comparent les modèles. Dans la seconde partie de cette thèse, j'adopte un formalisme bayésien et je teste la possibilité de quantifier les incertitudes sur les paramètres du modèle dans l'inversion d'ondes EM planes. Pour ce faire, je présente une stratégie d'inversion probabiliste basée sur des pixels à deux dimensions pour des inversions de données d'ondes EM planes et de tomographies de résistivité électrique (ERT) séparées et jointes. Je compare les incertitudes des paramètres du modèle en considérant différents types d'information a priori sur la structure du modèle et différentes fonctions de vraisemblance pour décrire les erreurs sur les données. Les résultats indiquent que la régularisation du modèle est nécessaire lorsqu'on a à faire à un large nombre de paramètres car cela permet d'accélérer la convergence des chaînes et d'obtenir des modèles plus réalistes. Cependent, ces contraintes mènent à des incertitudes d'estimations plus faibles, ce qui implique des distributions a posteriori qui ne contiennent pas le vrai modèledans les régions ou` la méthode présente une sensibilité limitée. Cette situation peut être améliorée en combinant des méthodes d'ondes EM planes avec d'autres méthodes complémentaires telles que l'ERT. De plus, je montre que le poids de régularisation des paramètres et l'écart-type des erreurs sur les données peuvent être retrouvés par une inversion probabiliste. Finalement, j'évalue la possibilité de caractériser une distribution tridimensionnelle d'un panache de traceur salin injecté dans le sous-sol en réalisant une inversion probabiliste time-lapse tridimensionnelle d'ondes EM planes. Etant donné que les inversions probabilistes sont très coûteuses en temps de calcul lorsque l'espace des paramètres présente une grande dimension, je propose une stratégie de réduction du modèle ou` les coefficients de décomposition des moments de Legendre du panache de traceur injecté ainsi que sa position sont estimés. Pour ce faire, un modèle de résistivité de base est nécessaire. Il peut être obtenu avant l'expérience time-lapse. Un test synthétique montre que la méthodologie marche bien quand le modèle de résistivité de base est caractérisé correctement. Cette méthodologie est aussi appliquée à un test de trac¸age par injection d'une solution saline et d'acides réalisé dans un système géothermal en Australie, puis comparée à une inversion time-lapse tridimensionnelle réalisée selon une approche déterministe. L'inversion probabiliste permet de mieux contraindre le panache du traceur salin gr^ace à la grande quantité d'informations a priori incluse dans l'algorithme. Néanmoins, les changements de conductivités nécessaires pour expliquer les changements observés dans les données sont plus grands que ce qu'expliquent notre connaissance actuelle des phénomenès physiques. Ce problème peut être lié à la qualité limitée du modèle de résistivité de base utilisé, indiquant ainsi que des efforts plus grands devront être fournis dans le futur pour obtenir des modèles de base de bonne qualité avant de réaliser des expériences dynamiques. Les études décrites dans cette thèse montrent que les méthodes d'ondes EM planes sont très utiles pour caractériser et suivre les variations temporelles du sous-sol sur de larges échelles. Les présentes approches améliorent l'évaluation des modèles obtenus, autant en termes d'incorporation d'informations a priori, qu'en termes de quantification d'incertitudes a posteriori. De plus, les stratégies développées peuvent être appliquées à d'autres méthodes géophysiques, et offrent une grande flexibilité pour l'incorporation d'informations additionnelles lorsqu'elles sont disponibles. -- The efficient use of geothermal systems, the sequestration of CO2 to mitigate climate change, and the prevention of seawater intrusion in coastal aquifers are only some examples that demonstrate the need for novel technologies to monitor subsurface processes from the surface. A main challenge is to assure optimal performance of such technologies at different temporal and spatial scales. Plane-wave electromagnetic (EM) methods are sensitive to subsurface electrical conductivity and consequently to fluid conductivity, fracture connectivity, temperature, and rock mineralogy. These methods have governing equations that are the same over a large range of frequencies, thus allowing to study in an analogous manner processes on scales ranging from few meters close to the surface down to several hundreds of kilometers depth. Unfortunately, they suffer from a significant resolution loss with depth due to the diffusive nature of the electromagnetic fields. Therefore, estimations of subsurface models that use these methods should incorporate a priori information to better constrain the models, and provide appropriate measures of model uncertainty. During my thesis, I have developed approaches to improve the static and dynamic characterization of the subsurface with plane-wave EM methods. In the first part of this thesis, I present a two-dimensional deterministic approach to perform time-lapse inversion of plane-wave EM data. The strategy is based on the incorporation of prior information into the inversion algorithm regarding the expected temporal changes in electrical conductivity. This is done by incorporating a flexible stochastic regularization and constraints regarding the expected ranges of the changes by using Lagrange multipliers. I use non-l2 norms to penalize the model update in order to obtain sharp transitions between regions that experience temporal changes and regions that do not. I also incorporate a time-lapse differencing strategy to remove systematic errors in the time-lapse inversion. This work presents improvements in the characterization of temporal changes with respect to the classical approach of performing separate inversions and computing differences between the models. In the second part of this thesis, I adopt a Bayesian framework and use Markov chain Monte Carlo (MCMC) simulations to quantify model parameter uncertainty in plane-wave EM inversion. For this purpose, I present a two-dimensional pixel-based probabilistic inversion strategy for separate and joint inversions of plane-wave EM and electrical resistivity tomography (ERT) data. I compare the uncertainties of the model parameters when considering different types of prior information on the model structure and different likelihood functions to describe the data errors. The results indicate that model regularization is necessary when dealing with a large number of model parameters because it helps to accelerate the convergence of the chains and leads to more realistic models. These constraints also lead to smaller uncertainty estimates, which imply posterior distributions that do not include the true underlying model in regions where the method has limited sensitivity. This situation can be improved by combining planewave EM methods with complimentary geophysical methods such as ERT. In addition, I show that an appropriate regularization weight and the standard deviation of the data errors can be retrieved by the MCMC inversion. Finally, I evaluate the possibility of characterizing the three-dimensional distribution of an injected water plume by performing three-dimensional time-lapse MCMC inversion of planewave EM data. Since MCMC inversion involves a significant computational burden in high parameter dimensions, I propose a model reduction strategy where the coefficients of a Legendre moment decomposition of the injected water plume and its location are estimated. For this purpose, a base resistivity model is needed which is obtained prior to the time-lapse experiment. A synthetic test shows that the methodology works well when the base resistivity model is correctly characterized. The methodology is also applied to an injection experiment performed in a geothermal system in Australia, and compared to a three-dimensional time-lapse inversion performed within a deterministic framework. The MCMC inversion better constrains the water plumes due to the larger amount of prior information that is included in the algorithm. The conductivity changes needed to explain the time-lapse data are much larger than what is physically possible based on present day understandings. This issue may be related to the base resistivity model used, therefore indicating that more efforts should be given to obtain high-quality base models prior to dynamic experiments. The studies described herein give clear evidence that plane-wave EM methods are useful to characterize and monitor the subsurface at a wide range of scales. The presented approaches contribute to an improved appraisal of the obtained models, both in terms of the incorporation of prior information in the algorithms and the posterior uncertainty quantification. In addition, the developed strategies can be applied to other geophysical methods, and offer great flexibility to incorporate additional information when available.

Microbiologia do solo no ensino médio de Lavras, MG

Os microrganismos realizam processos imprescindíveis para a sustentabilidade dos ecossistemas e para a vida no planeta; apesar disso, a sociedade de modo geral ignora esse papel e os considera apenas do ponto de vista de patógenos. Este trabalho foi realizado com os objetivos de analisar o conteúdo sobre os microrganismos do solo nos livros didáticos de Biologia adotados nas escolas de ensino médio de Lavras, MG; caracterizar estudantes e professores de três escolas desta cidade; e avaliar a percepção sobre Microbiologia do Solo de 334 estudantes do ensino médio dessas escolas após a apresentação do assunto em diversos formatos atrativos (palestras, workshops e aulas práticas). A coleta de dados, a priori e posteriori, foi realizada por questionários; avaliou-se ainda a viabilidade de trabalhar esse conteúdo no ensino médio. Apesar da importância dos microrganismos do solo, os materiais didáticos para o ensino de Biologia no ensino médio os abordam superficialmente e não destacam sua relevância nos contextos agrícola e ambiental. Após apresentação do assunto, houve diferenças significativas na percepção por estudantes das escolas tanto públicas como privadas. Concluiu-se ser possível ensinar e melhorar esse conteúdo da disciplina de Biologia por meio de recursos acessíveis e constatou-se a necessidade de levar os avanços científicos conhecidos na universidade para atualizar o ensino médio.

Improving Satellite Image Based Forest Inventory by Using A Priori Site Quality Information

Summary

Benchmarking therapeutic drug monitoring software: A systematic evaluation of available computer tools

Introduction: Therapeutic drug monitoring (TDM) aims at optimizing treatment by individualizing dosage regimen based on measurement of blood concentrations. Maintaining concentrations within a target range requires pharmacokinetic and clinical capabilities. Bayesian calculation represents a gold standard in TDM approach but requires computing assistance. In the last decades computer programs have been developed to assist clinicians in this assignment. The aim of this benchmarking was to assess and compare computer tools designed to support TDM clinical activities.¦Method: Literature and Internet search was performed to identify software. All programs were tested on common personal computer. Each program was scored against a standardized grid covering pharmacokinetic relevance, user-friendliness, computing aspects, interfacing, and storage. A weighting factor was applied to each criterion of the grid to consider its relative importance. To assess the robustness of the software, six representative clinical vignettes were also processed through all of them.¦Results: 12 software tools were identified, tested and ranked. It represents a comprehensive review of the available software's characteristics. Numbers of drugs handled vary widely and 8 programs offer the ability to the user to add its own drug model. 10 computer programs are able to compute Bayesian dosage adaptation based on a blood concentration (a posteriori adjustment) while 9 are also able to suggest a priori dosage regimen (prior to any blood concentration measurement), based on individual patient covariates, such as age, gender, weight. Among those applying Bayesian analysis, one uses the non-parametric approach. The top 2 software emerging from this benchmark are MwPharm and TCIWorks. Other programs evaluated have also a good potential but are less sophisticated (e.g. in terms of storage or report generation) or less user-friendly.¦Conclusion: Whereas 2 integrated programs are at the top of the ranked listed, such complex tools would possibly not fit all institutions, and each software tool must be regarded with respect to individual needs of hospitals or clinicians. Interest in computing tool to support therapeutic monitoring is still growing. Although developers put efforts into it the last years, there is still room for improvement, especially in terms of institutional information system interfacing, user-friendliness, capacity of data storage and report generation.

Benchmarking therapeutic drug monitoring software: A systematic evaluation of available computer tools

Objectives: Therapeutic drug monitoring (TDM) aims at optimizing treatment by individualizing dosage regimen based on blood concentrations measurement. Maintaining concentrations within a target range requires pharmacokinetic (PK) and clinical capabilities. Bayesian calculation represents a gold standard in TDM approach but requires computing assistance. The aim of this benchmarking was to assess and compare computer tools designed to support TDM clinical activities.¦Methods: Literature and Internet were searched to identify software. Each program was scored against a standardized grid covering pharmacokinetic relevance, user-friendliness, computing aspects, interfacing, and storage. A weighting factor was applied to each criterion of the grid to consider its relative importance. To assess the robustness of the software, six representative clinical vignettes were also processed through all of them.¦Results: 12 software tools were identified, tested and ranked. It represents a comprehensive review of the available software characteristics. Numbers of drugs handled vary from 2 to more than 180, and integration of different population types is available for some programs. Nevertheless, 8 programs offer the ability to add new drug models based on population PK data. 10 computer tools incorporate Bayesian computation to predict dosage regimen (individual parameters are calculated based on population PK models). All of them are able to compute Bayesian a posteriori dosage adaptation based on a blood concentration while 9 are also able to suggest a priori dosage regimen, only based on individual patient covariates. Among those applying Bayesian analysis, MM-USC*PACK uses a non-parametric approach. The top 2 programs emerging from this benchmark are MwPharm and TCIWorks. Others programs evaluated have also a good potential but are less sophisticated or less user-friendly.¦Conclusions: Whereas 2 software packages are ranked at the top of the list, such complex tools would possibly not fit all institutions, and each program must be regarded with respect to individual needs of hospitals or clinicians. Programs should be easy and fast for routine activities, including for non-experienced users. Although interest in TDM tools is growing and efforts were put into it in the last years, there is still room for improvement, especially in terms of institutional information system interfacing, user-friendliness, capability of data storage and automated report generation.

[Pérouse. Fontana Maggiore, Palazzo dei Priori]

Référence bibliographique : Weigert, 336