Provision of information about drug side-effects to patients

To make informed decisions about taking medicinal drugs, people need accurate information about side-effects. A European Union guideline now recommends use of qualitative descriptions for five bands of risk, ranging from very rare (affecting < 0·01% of the population), to very common (>10%). We did four studies of more than 750 people, whom we asked to estimate the probability of having a side-effect on the basis of qualitative and quantitative descriptions. Our results showed that qualitative descriptions led to gross overestimation of risk. Until further work is done on how patients taking the drugs interpret these terms, the terms should not be used in drug information leaflets.

Aging is associated with positive responding to neutral information but reduced recovery from negative information

Studies on aging and emotion suggest an increase in reported positive affect, a processing bias of positive over negative information, as well as increasingly adaptive regulation in response to negative events with advancing age. These findings imply that older individuals evaluate information differently, resulting in lowered reactivity to, and/or faster recovery from, negative information, while maintaining more positive responding to positive information. We examined this hypothesis in an ongoing study on Midlife in the US (MIDUS II) where emotional reactivity and recovery were assessed in a large number of respondents (N = 159) from a wide age range (36–84 years). We recorded eye-blink startle magnitudes and corrugator activity during and after the presentation of positive, neutral and negative pictures. The most robust age effect was found in response to neutral stimuli, where increasing age is associated with a decreased corrugator and eyeblink startle response to neutral stimuli. These data suggest that an age-related positivity effect does not essentially alter the response to emotion-laden information, but is reflected in a more positive interpretation of affectively ambiguous information. Furthermore, older women showed reduced corrugator recovery from negative pictures relative to the younger women and men, suggesting that an age-related prioritization of well-being is not necessarily reflected in adaptive regulation of negative affect.

Choosing the number of doses and the cohort size for phase I dose-escalation studies

This paper reviews Bayesian procedures for phase 1 dose-escalation studies and compares different dose schedules and cohort sizes. The methodology described is motivated by the situation of phase 1 dose-escalation studiesin oncology, that is, a single dose administered to each patient, with a single binary response ("toxicity"' or "no toxicity") observed. It is likely that a wider range of applications of the methodology is possible. In this paper, results from 10000-fold simulation runs conducted using the software package Bayesian ADEPT are presented. Four designs were compared under six scenarios. The simulation results indicate that there are slight advantages of having more dose levels and smaller cohort sizes.

Linking public issues with private troubles: panel studies in developing countries

Accompanying the call for increased evidence-based policy the developed world is implementing more longitudinal panel studies which periodically gather information about the same people over a number of years. Panel studies distinguish between transitory and persistent states (e.g. poverty, unemployment) and facilitate causal explanations of relationships between variables. However, they are complex and costly. A growing number of developing countries are now implementing or considering starting panel studies. The objectives of this paper are to identify challenges that arise in panel studies, and to give examples of how these have been addressed in resource-constrained environments. The main issues considered are: the development of a conceptual framework which links macro and micro contexts; sampling the cohort in a cost-effective way; tracking individuals; ethics and data management and analysis. Panel studies require long term funding, a stable institution and an acceptance that there will be limited value for money in terms of results from early stages, with greater benefits accumulating in the study's mature years. Copyright © 2003 John Wiley & Sons, Ltd.

A likelihood ratio appropach to family-based association studies with covariates

We introduce a procedure for association based analysis of nuclear families that allows for dichotomous and more general measurements of phenotype and inclusion of covariate information. Standard generalized linear models are used to relate phenotype and its predictors. Our test procedure, based on the likelihood ratio, unifies the estimation of all parameters through the likelihood itself and yields maximum likelihood estimates of the genetic relative risk and interaction parameters. Our method has advantages in modelling the covariate and gene-covariate interaction terms over recently proposed conditional score tests that include covariate information via a two-stage modelling approach. We apply our method in a study of human systemic lupus erythematosus and the C-reactive protein that includes sex as a covariate.

Efficient and accurate experimental design for enzyme kinetics: Bayesian studies reveal a systematic approach

In areas such as drug development, clinical diagnosis and biotechnology research, acquiring details about the kinetic parameters of enzymes is crucial. The correct design of an experiment is critical to collecting data suitable for analysis, modelling and deriving the correct information. As classical design methods are not targeted to the more complex kinetics being frequently studied, attention is needed to estimate parameters of such models with low variance. We demonstrate that a Bayesian approach (the use of prior knowledge) can produce major gains quantifiable in terms of information, productivity and accuracy of each experiment. Developing the use of Bayesian Utility functions, we have used a systematic method to identify the optimum experimental designs for a number of kinetic model data sets. This has enabled the identification of trends between kinetic model types, sets of design rules and the key conclusion that such designs should be based on some prior knowledge of K-M and/or the kinetic model. We suggest an optimal and iterative method for selecting features of the design such as the substrate range, number of measurements and choice of intermediate points. The final design collects data suitable for accurate modelling and analysis and minimises the error in the parameters estimated. (C) 2003 Elsevier Science B.V. All rights reserved.

What have we learnt about heavy carbenes through laser flash photolysis studies?

Time resolved gas-phase kinetic studies have contributed a great deal of fundamental information about the reactions and reactivity of heavy carbenes (silylenes, germylenes and stannylenes) during the past two decades. In this article we trace the development of our understanding through the mechanistic themes of intermediate complexes, third body assisted associations, catalysed reactions, non-observed reactions and substituent effects. Ab initio (quantum chemical) calculations have substantially assisted mechanistic interpretation and are discussed where appropriate. Trends in reactivity are identified and some signposts to future studies are indicated. This review, although detailed, is not comprehensive.

Vision 2020 - A whole life-cycle information management system for built environments

A whole life-cycle information management vision is proposed, the organizational requirements for the realization of the scenario is investigated. Preliminary interviews with construction professionals are reported. Discontinuities at information transfer throughout life-cycle of built environments are resulting from lack of coordination and multiple data collection/storage practices. A more coherent history of these activities can improve the work practices of various teams by augmenting decision making processes and creating organizational learning opportunities. Therefore, there is a need for unifying these fragmented bits of data to create a meaningful, semantically rich and standardized information repository for built environment. The proposed vision utilizes embedded technologies and distributed building information models. Two diverse construction project types (large one-off design, small repetitive design) are investigated for the applicability of the vision. A functional prototype software/hardware system for demonstrating the practical use of this vision is developed and discussed. Plans for case-studies for validating the proposed model at a large PFI hospital and housing association projects are discussed.

Effects of active information processing on the understanding of risk information

Two experiments investigated effects of active processing of risk information on participants' understanding and judgments. It was hypothesized that more active processing would lead to better understanding and differences in affective judgments (e.g. increased satisfaction and reduced perceived risk to health). In both experiments participants were given a written scenario about their being prescribed a fictitious medication. This medication was said to cause side effects in 2% of people who took it. Before answering a series of written questions, participants in the active conditions of both experiments were asked to carry out a reflective task (portraying the size of risk on a bar chart in Experiment 1 and answering a reflective question in Experiment 2). The results showed that active participants rated the likelihood of experiencing possible side effects significantly lower than passive participants (Experiment 1), and that active participants were significantly more satisfied with the information and judged perceived risk to health from taking the medication significantly lower than passive participants (Experiment 2). In both experiments, active participants were significantly more correct in their probability and frequency estimates. The studies demonstrate that active processing of risk information leads to improved understanding of the information given. This has important implications for risk communication. In the context of health, better understanding should lead to improved decision-making and health outcomes. Copyright (C) 2004 John Wiley Sons, Ltd.

Communicating information about medication: the benefits of making it personal

Two experiments, using a controlled empirical methodology, investigated the effects of presenting information about medicines using a more personalised style of expression. In both studies, members of the general public were given a hypothetical scenario about visiting the doctor, being diagnosed with a particular illness, and being prescribed a medication. They were also given a written explanation about the medicine and were asked to provide ratings on a number of measures, including satisfaction, perceived risk to health, and intention to comply. In Experiment 1 the explanation focused only on possible side effects of the medicine, whereas in Experiment 2 a fuller explanation was provided, which included information about the illness, prescribed drug, its dosage and contraindications as well as its side effects. In both studies, use of a more personalised style resulted in significantly higher ratings of satisfaction and significantly lower ratings of likelihood of side effects occurring and of perceived risk to health. In Experiment 2 it also led to significantly improved recall for the written information.