Multivariate guard-bands and total risk assessment on multiparameter evaluations with correlated and uncorrelated measured values

Abstract The quality, efficacy, and safety of medicines are usually verified by analytical results. Measurement uncertainty is a critical aspect for the reliability of these analytical results. The pharmacopeial compendia usually adopt a simple acceptance rule that does not consider information from measurement uncertainty. In this work, we compared decision-making using simple acceptance and decision rules with the use of guard-band for multiparameter evaluation of ofloxacin ophthalmic solution and acyclovir topical cream. Ciprofloxacin ophthalmic solution and acyclovir topical cream samples were subject to pharmacopeial tests and assays. Multivariate guard-band widths were calculated by multiplying the standard uncertainty (u) by an appropriate multivariate coverage factor (k'). The multivariate coverage factor (k') was obtained by the Monte Carlo method. According to the simple acceptance rule, all the results obtained for ciprofloxacin ophthalmic solution and acyclovir topical cream are within the specification limits. However, the risk of false conformity decisions increases for ciprofloxacin tests. Decisions made using the simple acceptance rule and decision rules with the use of guard-band may differ. The simple acceptance rule may increase the risk of false conformity decisions when the measured value is close to the regulatory specification limits and/or when the measurement uncertainty value is inappropriately high. Nevertheless, the guard-band decision rule will always reduce the risk of false conformity decisions. Therefore, using information on measurement uncertainty in conformity assessment is highly recommended to ensure the proper efficacy, safety, and quality of medicines.

Diethylpropion and mazindol: An end to the discussion?

Antiobesity pharmacotherapy remains the main point of disagreement among both scientists and regulators. This is probably due to small sample sizes, high levels of heterogeneity, and low methodological quality. For many years, Brazil was one of the largest consumers of appetite suppressants worldwide, with evidence of irrational use of this drug class. Therefore, the country was the scene of a debate that divided the Brazilian Health Surveillance Agency (Anvisa - Agência Nacional de Vigilância Sanitária) and medical societies over the maintenance record of diethylpropion, mazindol and fenproporex. In this context, this commentary presents new arguments to contribute to the discussion, as well as recommendations for future studies.

Invasion risks posed by ornamental freshwater fish trade to southeastern Brazilian rivers

A model was developed to assess the risk of invasion of ornamental non-native fishes to six rivers in the state of Minas Gerais, southeastern Brazil, with focus on species popularity. Thirty-nine aquarium shops, in six cities, were visited monthly from January to December 2007. In each city, fish species were identified, and their biology and invasion history information was obtained from the literature. We calculated the annual frequency of occurrence and average number of specimens monthly available in stores. Quarterly water temperature and dissolved oxygen data from 1997 to 2007 were obtained for the Velhas, Muriaé, Uberabinha, Sapucaí-Mirim, Doce and Todos os Santos Rivers from public databases. The invasion risk of each species was assessed through a model comprising nine parameters grouped in four variables: (i) Invasiveness (thermal and dissolved oxygen ranges, diet, parental care or fecundity), (ii) History of invasions (establishment), (iii) Propagule pressure (commercial success, comprising annual frequency of occurrence and number of specimens available monthly at stores), and (iv) Invasibility (water temperature and dissolved oxygen in the target river compatible with the species ranges). Of the 345 ornamental fish species for sale, 332 are non-native to either Minas Gerais (n = 151) or Brazil (n = 194). Based on the proposed cutting values, in particular the compatibility between species and recipient thermal ranges, five ornamental non-native species (Cyprinus rubrofuscus, Carassius auratus, Xiphophorus hellerii, Poecilia reticulata, and P. latipinna) can potentially invade the Velhas and Muriaé Rivers, four species (Cyprinus rubrofuscus, Carassius auratus, X. helleri, and P. reticulata) the Uberabinha River, four species (Cyprinus rubrofuscus, Carassius auratus, X. maculatus, and P. reticulata) the Sapucaí-Mirim River, three species (Carassius auratus, X. hellerii, and P. reticulata) the Doce River, and three species (Cyprinus rubrofuscus, P. reticulata, and Amatitlania nigrofasciata) can potentially invade the Todos os Santos River. Six recommendations are suggested to reduce the invasion risk of non-native fish on the rivers surveyed posed by aquarium trade.(AU)

Um modelo foi desenvolvido para avaliar o risco de invasão de peixes ornamentais não-nativos em seis rios do estado de Minas Gerais, sudeste do Brasil, com foco na popularidade das espécies. Trinta e nove lojas de aquário em seis cidades foram visitadas mensalmente de janeiro a dezembro de 2007. Em cada cidade, as espécies foram identificadas e suas biologias e histórias de invasão foram obtidas da literatura. Calculou-se a frequência de ocorrência anual e quantidade média mensal de exemplares disponíveis nas lojas. Foram obtidas temperaturas trimestrais da água e dados de oxigênio dissolvido de 1997 a 2007 dos rios Velhas, Muriaé, Uberabinha, Sapucaí-Mirim, Doce e Todos os Santos a partir de bases de dados públicas. O risco de invasão de cada espécie foi avaliado através de um modelo composto por nove parâmetros agrupados em quatro variáveis: (i) Invasividade (limite de alcance térmico/oxigênio dissolvido, dieta, cuidado parental ou fecundidade), (ii) Histórico de invasões (estabelecimento), (iii) Pressão de propágulos (sucesso comercial, composto pela frequência de ocorrência anual e número de exemplares disponíveis mensalmente nas lojas), e (iv) Invasibilidade (temperatura da água/oxigênio dissolvido dos rios compatível com o limite de alcance térmico/ oxigênio dissolvido das espécies). Das 345 espécies de peixes ornamentais para venda, 332 são não-nativos para Minas Gerais (n = 151) ou Brasil (n = 194). Com base nos valores de corte propostos, cinco espécies de peixes ornamentais não-nativos (Cyprinus rubrofuscus, Carassius auratus, Xiphophorus hellerii, Poecilia reticulata e P. latipinna) podem potencialmente invadir os rios Velhas e Muriaé, quatro espécies (C. rubrofuscus, C. auratus, X. helleri, P. reticulata) podem ...(AU)

Invasion risks posed by ornamental freshwater fish trade to southeastern Brazilian rivers

A model was developed to assess the risk of invasion of ornamental non-native fishes to six rivers in the state of Minas Gerais, southeastern Brazil, with focus on species popularity. Thirty-nine aquarium shops, in six cities, were visited monthly from January to December 2007. In each city, fish species were identified, and their biology and invasion history information was obtained from the literature. We calculated the annual frequency of occurrence and average number of specimens monthly available in stores. Quarterly water temperature and dissolved oxygen data from 1997 to 2007 were obtained for the Velhas, Muriaé, Uberabinha, Sapucaí-Mirim, Doce and Todos os Santos Rivers from public databases. The invasion risk of each species was assessed through a model comprising nine parameters grouped in four variables: (i) Invasiveness (thermal and dissolved oxygen ranges, diet, parental care or fecundity), (ii) History of invasions (establishment), (iii) Propagule pressure (commercial success, comprising annual frequency of occurrence and number of specimens available monthly at stores), and (iv) Invasibility (water temperature and dissolved oxygen in the target river compatible with the species ranges). Of the 345 ornamental fish species for sale, 332 are non-native to either Minas Gerais (n = 151) or Brazil (n = 194). Based on the proposed cutting values, in particular the compatibility between species and recipient thermal ranges, five ornamental non-native species (Cyprinus rubrofuscus, Carassius auratus, Xiphophorus hellerii, Poecilia reticulata, and P. latipinna) can potentially invade the Velhas and Muriaé Rivers, four species (Cyprinus rubrofuscus, Carassius auratus, X. helleri, and P. reticulata) the Uberabinha River, four species (Cyprinus rubrofuscus, Carassius auratus, X. maculatus, and P. reticulata) the Sapucaí-Mirim River, three species (Carassius auratus, X. hellerii, and P. reticulata) the Doce River, and three species (Cyprinus rubrofuscus, P. reticulata, and Amatitlania nigrofasciata) can potentially invade the Todos os Santos River. Six recommendations are suggested to reduce the invasion risk of non-native fish on the rivers surveyed posed by aquarium trade.

Um modelo foi desenvolvido para avaliar o risco de invasão de peixes ornamentais não-nativos em seis rios do estado de Minas Gerais, sudeste do Brasil, com foco na popularidade das espécies. Trinta e nove lojas de aquário em seis cidades foram visitadas mensalmente de janeiro a dezembro de 2007. Em cada cidade, as espécies foram identificadas e suas biologias e histórias de invasão foram obtidas da literatura. Calculou-se a frequência de ocorrência anual e quantidade média mensal de exemplares disponíveis nas lojas. Foram obtidas temperaturas trimestrais da água e dados de oxigênio dissolvido de 1997 a 2007 dos rios Velhas, Muriaé, Uberabinha, Sapucaí-Mirim, Doce e Todos os Santos a partir de bases de dados públicas. O risco de invasão de cada espécie foi avaliado através de um modelo composto por nove parâmetros agrupados em quatro variáveis: (i) Invasividade (limite de alcance térmico/oxigênio dissolvido, dieta, cuidado parental ou fecundidade), (ii) Histórico de invasões (estabelecimento), (iii) Pressão de propágulos (sucesso comercial, composto pela frequência de ocorrência anual e número de exemplares disponíveis mensalmente nas lojas), e (iv) Invasibilidade (temperatura da água/oxigênio dissolvido dos rios compatível com o limite de alcance térmico/ oxigênio dissolvido das espécies). Das 345 espécies de peixes ornamentais para venda, 332 são não-nativos para Minas Gerais (n = 151) ou Brasil (n = 194). Com base nos valores de corte propostos, cinco espécies de peixes ornamentais não-nativos (Cyprinus rubrofuscus, Carassius auratus, Xiphophorus hellerii, Poecilia reticulata e P. latipinna) podem potencialmente invadir os rios Velhas e Muriaé, quatro espécies (C. rubrofuscus, C. auratus, X. helleri, P. reticulata) podem ...

Relationship between Helicobacter pylori detection and an increased risk of infection in childhood

The risk of developing gastric cancer is believed to be related to differences among Helicobacter pylori strains and the inflammatory responses mediated by host genetic factors. H. pylori infection is acquired at an early age and in the absence of appropriate antibiotic therapy, it generally persists for life. Tp53 gene regulates the transcription of several cytokines and chemokines involved in innate immunity and its action may be influenced by the presence of different H. pylori strains. The present study aimed to detect H. pylori in pediatric patients, to access Tp53 polymorphism at codon 72 and to correlate such findings with age and histopathological results. Three hundred and forty-two patients were analyzed. DNA from their gastric biopsies was extracted and the detection of H. pylori was performed through polymerase chain reaction assays, urease test and histopathologic examination. Allelic discrimination of SNP rs1042522 (Tp53) was performed by real-time polymerase chain reaction. Our results suggest a possible relationship between the presence of H. pylori and chronic gastritis in children and young patients, and showed a significant association between ageing and positivity for H. pylori. It was verified that patients aged < 10 years were 1.3 times more likely to have infection by H. pylori when compared with those aged > 10 years. Finally, no association was found between Tp53 polymorphisms and the presence of H. pylori.(AU)

International versus national regulations: concerns and trends.

The existence of a traceable relationship between national regulatory standards and international recommendations is important especially when the national regulations have to be justified and explained to the public and their representatives. Guidance on various types of radiological levels in environmental media related to public exposure has been provided by the relevant international organizations, constituting a basis for the development of national regulations. However, international standards need to be clear and based on solid technical criteria. In their preparation, consideration should be given to the implications for different countries, and the differences that exist between them, for example, in social, economic and climatic aspects.

Standardizing measurement, sampling and reporting for public exposure assessments.

UNSCEAR assesses worldwide public exposure from natural and man-made sources of ionizing radiation based on information submitted to UNSCEAR by United Nations Member States and from peer reviewed scientific literature. These assessments are used as a basis for radiation protection programs of international and national regulatory and research organizations. Although UNSCEAR describes its assessment methodologies, the data are based on various monitoring approaches. In order to reduce uncertainties and improve confidence in public exposure assessments, it would be necessary to harmonize the methodologies used for sampling, measuring and reporting of environmental results.

Estimating the relative recurrence risk ratio using a global cross-ratio model

The relative recurrence risk ratio lambdaR (and particularly the sibling recurrence risk ratio, lambdaS) is often of interest to those wanting to quantify the genetic contribution towards risk of disease or to discriminate between different genetic models. However, estimating lambdaR for complex diseases for which genetic and environmental risk factors are both involved is not straightforward. Ignoring environmental factors may lead to inflated estimates of lambdaR. We present a marginal model which uses a copula function to model the association in cumulative incidence rates between pairs of relatives. This model is applicable to present-state data and allows estimation of risk of disease in a pair of relatives (and hence lambdaR), given measured environmental covariates. We apply the model to leprosy among sibling pairs from the Karonga district, Malawi. If risk factors are ignored, the apparent lambdaS in this population is over 3. Accounting for known nongenetic risk factors reduces it to just under 2.

La medición de la conducta suicida en México: estimaciones y procedimientos / The measurement of suicide behavior in Mexico: estimates and procedures

Este es un análisis de los resultados de varios estudios en diferentes poblaciones de México sobre el intento y la ideación suicida, en el que se utilizaron diferentes metodologías e instrumentos para medirlos. En su mayoría, estos fueron encuestas representativas de muestras de hogares y escuelas, así como, estudios en escenarios clínicos.La prevalencia más alta de intento de suicidio fue de 10 por ciento. La prevalencia de ideación suicida más alta fue de 40.7 por ciento. Se encontraron diferencias importantes en los instrumentos utilizados para medir la conducta suicida y su temporalidad, y en los puntos de corte utilizados para definir los casos. Este análisis de la información nos permitirá obtener datos más precisos sobre el intento y la ideación suicida en la población mexicana, los cuales son muy importantes para diseñar las políticas de salud. Unificando los criterios de los investigadores, se contará con mejores registros sobre el intento y la ideación suicida.

Evaluación conjunta del programa nacional de control de tuberculosis (PNT): Bolivia, 11-21 de octubre de 1999b / Joint evaluation of the national program for tuberculosis control (PNT): Bolivia, 11-21 of October 1999

La tuberculosis es una enfermedad de extrema gravedad que afecta al país de forma endémica, es prevenible y de fácil control, sin embargo es la causa más importante de mortalidad producida por un solo agente en el ámbito nacional. La presente evaluación muestra que el Programa Nacional de Control de Tuberculosis(PNT) tiene una distribución a nivel nacional que es irregular y de mayor importancia en áreas densamente pobladas y con condiciones de hacinamiento y desnutrición, es así que el 76 por ciento del total de los casos diagnosticados se encuentran en los departamentos de La Paz, Santa Cruz y Cochabamba. Así que el PNT solo logra una cobertura en la localización de casos del 60 por ciento y solo alcanza a curar el 70 por ciento de los enfermos que inician tratamiento, con tasas de deserción por encima del 15 por ciento con actividades mínimas de control del entorno del paciente y menos aun la utilización de la quimioprofiláxis de casos de riesgo

Evaluación conjunta del programa nacional de control de tuberculosis: Bolivia, 11-21 de octubre de 1999 / Joint evaluation of the national program for tuberculosis control: Bolivia, 11-21 of October 1999

La tuberculosis es una enfermedad de extrema gravedad que afecta al país de forma endémica, es prevenible y de fácil control, sin embargo es la causa más importante de mortalidad producida por un solo agente en el ámbito nacional. La presente evaluación muestra que el Programa Nacional de Control de Tuberculosis(PNT) tiene una distribución a nivel nacional que es irregular y de mayor importancia en áreas densamente pobladas y con condiciones de hacinamiento y desnutrición, es así que el 76 por ciento del total de los casos diagnosticados se encuentran en los departamentos de La Paz, Santa Cruz y Cochabamba. Así que el PNT solo logra una cobertura en la localización de casos del 60 por ciento y solo alcanza a curar el 70 por ciento de los enfermos que inician tratamiento, con tasas de deserción por encima del 15 por ciento con actividades mínimas de control del entorno del paciente y menos aun la utilización de la quimioprofiláxis de casos de riesgo