What do patients want to know about their medicines, and what do doctors want to tell them?: a comparative study

A two phase study is reported. In the first phase, we asked a number of doctors to rate a list of information categories (identified by Berry, Gillie and Banbury 1995) in terms of how important they felt it was for the items to be included in an explanation to a patient about a drug prescription. In the second phase, we presented a large sample of people with a scenario about visiting their doctor and being prescribed medication, together with an explanation about the prescription which was said to be provided by the doctor. Four different explanations were compared, which were either based on what people in our earlier study wanted to know about drug prescriptions or on what the doctors thought it was important lo tell them. We also manipulated whether or not the explanations conveyed negative information (e.g. about the possible side effects of the medication). The results showed that people 'preferred' the explanations based on what the participants in the earlier study wanted to know about their medicines, rather than those based on what the doctors thought they should be told. They also 'preferred' the explanations that did not convey negative information, rather than those that did convey some negative information. In addition, the inclusion of negative information affected ratings of likely compliance with the prescribed medication.

What do patients want to know? An empirical approach to explanation generation and validation

This article describes an empirical, user-centred approach to explanation design. It reports three studies that investigate what patients want to know when they have been prescribed medication. The question is asked in the context of the development of a drug prescription system called OPADE. The system is aimed primarily at improving the prescribing behaviour of physicians, but will also produce written explanations for indirect users such as patients. In the first study, a large number of people were presented with a scenario about a visit to the doctor, and were asked to list the questions that they would like to ask the doctor about the prescription. On the basis of the results of the study, a categorization of question types was developed in terms of how frequently particular questions were asked. In the second and third studies a number of different explanations were generated in accordance with this categorization, and a new sample of people were presented with another scenario and were asked to rate the explanations on a number of dimensions. The results showed significant differences between the different explanations. People preferred explanations that included items corresponding to frequently asked questions in study 1. For an explanation to be considered useful, it had to include information about side effects, what the medication does, and any lifestyle changes involved. The implications of the results of the three studies are discussed in terms of the development of OPADE's explanation facility.

Future innovations in anti-platelet therapies

Platelets have long been recognized to be of central importance in haemostasis, but their participation in pathological conditions such as thrombosis, atherosclerosis and inflammation is now also well established. The platelet has therefore become a key target in therapies to combat cardiovascular disease. Anti-platelet therapies are used widely, but current approaches lack efficacy in a proportion of patients, and are associated with side effects including problem bleeding. In the last decade, substantial progress has been made in understanding the regulation of platelet function, including the characterization of new ligands, platelet-specific receptors and cell signalling pathways. It is anticipated this progress will impact positively on the future innovations towards more effective and safer anti-platelet agents. In this review, the mechanisms of platelet regulation and current anti-platelet therapies are introduced, and strong, and some more speculative, potential candidate target molecules for future anti-platelet drug development are discussed.

Targeting the cell cycle machinery for the treatment of cardiovascular disease

Cardiovascular disease represents a major clinical problem affecting a significant proportion of the world's population and remains the main cause of death in the UK. The majority of therapies currently available for the treatment of cardiovascular disease do not cure the problem but merely treat the symptoms. Furthermore, many cardioactive drugs have serious side effects and have narrow therapeutic windows that can limit their usefulness in the clinic. Thus, the development of more selective and highly effective therapeutic strategies that could cure specific cardiovascular diseases would be of enormous benefit both to the patient and to those countries where healthcare systems are responsible for an increasing number of patients. In this review, we discuss the evidence that suggests that targeting the cell cycle machinery in cardiovascular cells provides a novel strategy for the treatment of certain cardiovascular diseases. Those cell cycle molecules that are important for regulating terminal differentiation of cardiac myocytes and whether they can be targeted to reinitiate cell division and myocardial repair will be discussed as will the molecules that control vascular smooth muscle cell (VSMC) and endothelial cell proliferation in disorders such as atherosclerosis and restenosis. The main approaches currently used to target the cell cycle machinery in cardiovascular disease have employed gene therapy techniques. We will overview the different methods and routes of gene delivery to the cardiovascular system and describe possible future drug therapies for these disorders. Although the majority of the published data comes from animal studies, there are several instances where potential therapies have moved into the clinical setting with promising results.

Cost-benefit evaluation of routine influenza immunisation in people 65-74 years of age

OBJECTIVES: To determine the cost-effectiveness of influenza vaccination in people aged 65-74 years in the absence of co-morbidity. DESIGN: Primary research: randomised controlled trial. SETTING: Primary care. PARTICIPANTS: People without risk factors for influenza or contraindications to vaccination were identified from 20 general practitioner (GP) practices in Liverpool in September 1999 and invited to participate in the study. There were 5875/9727 (60.4%) people aged 65-74 years identified as potentially eligible and, of these, 729 (12%) were randomised. INTERVENTION: Participants were randomised to receive either influenza vaccine or placebo (ratio 3:1), with all individuals receiving pneumococcal vaccine unless administered in the previous 10 years. Of the 729 people randomised, 552 received vaccine and 177 received placebo; 726 individuals were administered pneumococcal vaccine. MAIN OUTCOME MEASURES AND METHODOLOGY OF ECONOMIC EVALUATION: GP attendance with influenza-like illness (ILI) or pneumonia (primary outcome measure); or any respiratory symptoms; hospitalisation with a respiratory illness; death; participant self-reported ILI; quality of life (QoL) measures at 2, 4 and 6 months post-study vaccination; adverse reactions 3 days after vaccination. A cost-effectiveness analysis was undertaken to identify the incremental cost associated with the avoidance of episodes of influenza in the vaccination population and an impact model was used to extrapolate the cost-effectiveness results obtained from the trial to assess their generalisability throughout the NHS. RESULTS: In England and Wales, weekly consultations for influenza and ILI remained at baseline levels (less than 50 per 100,000 population) until week 50/1999 and then increased rapidly, peaking during week 2/2000 with a rate of 231/100,000. This rate fell within the range of 'higher than expected seasonal activity' of 200-400/100,000. Rates then quickly declined, returning to baseline levels by week 5/2000. The predominant circulating strain during this period was influenza A (H3N2). Five (0.9%) people in the vaccine group were diagnosed by their GP with an ILI compared to two (1.1%) in the placebo group [relative risk (RR), 0.8; 95% confidence interval (CI) = 0.16 to 4.1]. No participants were diagnosed with pneumonia by their GP and there were no hospitalisations for respiratory illness in either group. Significantly fewer vaccinated individuals self-reported a single ILI (4.6% vs 8.9%, RR, 0.51; 95% CI for RR, 0.28 to 0.96). There was no significant difference in any of the QoL measurements over time between the two groups. Reported systemic side-effects showed no significant differences between groups. Local side-effects occurred with a significantly increased incidence in the vaccine group (11.3% vs 5.1%, p = 0.02). Each GP consultation avoided by vaccination was estimated from trial data to generate a net NHS cost of 174 pounds. CONCLUSIONS: No difference was seen between groups for the primary outcome measure, although the trial was underpowered to demonstrate a true difference. Vaccination had no significant effect on any of the QoL measures used, although vaccinated individuals were less likely to self-report ILI. The analysis did not suggest that influenza vaccination in healthy people aged 65-74 years would lead to lower NHS costs. Future research should look at ways to maximise vaccine uptake in people at greatest risk from influenza and also the level of vaccine protection afforded to people from different age and socio-economic populations.

The benefits of providing benefit information: examining the effectiveness of provision of simple benefit statements on people's judgements about a medicine

Three experiments examined the effects of adding information about medication benefits to a short written explanation about a medicine. Participants were presented with a fictitious scenario about visiting the doctor, being prescribed an antibiotic and being given information about the medicine. They were asked to make various judgements relating to the information, the medicine and their intention to take it. Experiment 1 found that information about benefits enhanced the judgements, but did not influence the intention to comply. Experiment 2 compared the relative effectiveness of two different forms of the benefit statement, and found that both were effective in improving judgements, but had no effect on intention to comply. Experiment 3 compared the effectiveness of the two forms of benefit information but participants were told that the medicine was associated with four named side effects. Both types of statement improved ratings of the intention to comply, as well as ratings on the other measures. The experiments provide fairly consistent support for the inclusion of benefit information in medicine information leaflets, particularly to balance concerns about side effects.

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.

Interpretation of recommended risk terms: differences between doctors and lay people

Objectives: To examine doctors' (Experiment 1) and doctors' and lay people's (Experiment 2) interpretations of two sets of recommended verbal labels for conveying information about side effects incidence rates. Method: Both studies used a controlled empirical methodology in which participants were presented with a hypothetical, but realistic, scenario involving a prescribed medication that was said to be associated with either mild or severe side effects. The probability of each side effect was described using one of the five descriptors advocated by the European Union (Experiment 1) or one of the six descriptors advocated in Calman's risk scale (Experiment 2), and study participants were required to estimate (numerically) the probability of each side effect occurring. Key findings: Experiment 1 showed that the doctors significantly overestimated the risk of side effects occurring when interpreting the five EU descriptors, compared with the assigned probability ranges. Experiment 2 showed that both groups significantly overestimated risk when given the six Calman descriptors, although the degree of overestimation was not as great for the doctors as for the lay people. Conclusion: On the basis of our findings, we argue that we are still a long way from achieving a standardised language of risk for use by both professionals and the general public, although there might be more potential for use of standardised terms among professionals. In the meantime, the EU and other regulatory bodies and health professionals should be very cautious about advocating the use of particular verbal labels for describing medication side effects.

Over the counter medicines and the need for immediate action: a further evaluation of European Commission recommended wordings for communicating risk

A study examined people's interpretation of European Commission (EC) recommended verbal descriptors for risk of medicine side effects, and actions to take if they do occur. Members of the general public were presented with a fictitious (but realistic) scenario about suffering from a stiff neck, visiting the local pharmacy and purchasing an over the counter (OTC) medicine (Ibruprofen). The medicine came with an information leaflet which included information about the medicine's side effects, their risk of occurrence, and recommended actions to take if adverse effects are experienced. Probability of occurrence was presented numerically (6%) or verbally, using the recommended EC descriptor (common). Results showed that, in line with findings of our earlier work with prescribed medicines, participants significantly overestimated side effect risk. Furthermore, the differences in interpretation were reflected in their judgements of satisfaction, side effect severity, risk to health, and intention to take the medicine. Finally, we observed no significant difference between people's interpretation of the recommended action descriptors ('immediately' and 'as soon as possible'). (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

Perceptions of the risks and benefits of medicines in patients with rheumatoid arthritis and other painful musculoskeletal conditions

Objectives. To examine beliefs about medication risks and benefits in patients attending a specialist rheumatology clinic for pain-related conditions. Methods. Eighty-one patients (37 first attendees and 44 existing clinic patients) completed a written questionnaire which asked about current treatments, perceived effectiveness, main risks and benefits, and compliance. Results. Existing clinic patients perceived medications to be more effective and more risky than did the new patients, although both groups rated risks to be moderately low. The main perceived risks were adverse side-effects, although patients reported only moderately low levels of experiencing such effects. Conclusions. In contrast to some other studies, many of our patients were aware of medication risks and were prepared to accept them provided benefits were seen to be high. Existing clinic patients were more aware of risks and benefits, and reported higher compliance levels than new patients, possibly as a result of the hospital education programme. Future studies should evaluate the effects of the programme more systematically.

In vitro examination of the effect of Orlistat on the ability of the faecal microbiota to utilize dietary lipids

Orlistat is an anti-obesity treatment with which several gastrointestinal (GI) side-effects are commonly associated in the initial stages of therapy. There is no physiological explanation as to why two-thirds of those who take the drug experience one or more side-effects. It has been hypothesized that the GI microbiota may protect from or contribute to these GI disturbances. Using in vitro batch culture and human gut model systems, studies were conducted to determine whether increased availability of dietary lipids and/or orlistat affect the composition and/or activity of the faecal microbiota. Results from 24-h batch culture fermentation experiments demonstrated no effect of orlistat in the presence or absence of a dietary lipid (olive oil) on the composition of bacterial communities [as determined by fluorescence in situ hybridization (FISH) and denaturing gradient gel electrophoresis (DGGE) analyses], but did show there was great variability in the lipolytic activities of the microbiotas of individuals, as determined by gas chromatography analysis of long-chain fatty acids in samples. Subsequent studies focused on the effect of orlistat in the presence and absence of lipid in in vitro human gut model systems. Systems were run for 14 days with gut model medium (GMM) only (to steady state, SS), then fed at 12-h intervals with 50 mg orlistat, 2 g olive oil or a mixture of both for 14 days. FISH and DGGE were used to monitor changes in bacterial populations. Bacteria were cultivated from the GMM only (control) systems at SS. All strains isolated were screened for lipolytic activity using tributyrin agar. FISH and DGGE demonstrated that none of the compounds (singly or in combination) added to the systems had any notable effect on microbial population dynamics for any of the donors, although Subdoligranulum populations appeared to be inhibited by orlistat in the presence or absence of lipid. Orlistat had little or no effect on the metabolism of indigenous and added lipids in the fermentation systems, but there was great variability in the way the faecal microbiotas of the donors were able to degrade added lipids. Variability in lipid degradation could be correlated with the number and activity of isolated lipolytic bacteria. The mechanism by which orlistat and the GI microbiota cause side-effects in individuals is unknown, but several hypotheses have been proposed to account for their manifestation. The demonstration of great variability in the lipolytic activity of microbiotas to degrade lipids led to a large-scale cultivation-based study of lipolytic/lipase-positive bacteria present in the human faecal microbiota. Of 4,000 colonies isolated from 15 donors using five different agars, 378 strains were identified that had lipase activity. Molecular identification of strains isolated from five donors demonstrated that lipase activity is more prevalent in the human GI microbiota than previously thought, with members of the phyla Firmicutes, Bacteroidetes and Actinobacteria identified. Molecular identification and characterization of the substrate specificities of the strains will be carried out as part of ongoing work.

Cannabis sativa and the endogenous cannabinoid system: therapeutic potential for appetite regulation

The herb Cannabis sativa (C. sativa) has been used in China and on the Indian subcontinent for thousands of years as a medicine. However, since it was brought to the UK and then the rest of the western world in the late 19th century, its use has been a source of controversy. Indeed, its psychotropic side effects are well reported but only relatively recently has scientific endeavour begun to find valuable uses for either the whole plant or its individual components. Here, we discuss evidence describing the endocannabinoid system, its endogenous and exogenous ligands and their varied effects on feeding cycles and meal patterns. Furthermore we also critically consider the mounting evidence which suggests non‐tetrahydrocannabinol phytocannabinoids play a vital role in C. sativa‐induced feeding pattern changes. Indeed, given the wide range of phytocannabinoids present in C. sativa and their equally wide range of intra‐, inter‐ and extra‐cellular mechanisms of action, we demonstrate that non‐Δ9tetrahydrocannabinol phytocannabinoids retain an important and, as yet, untapped clinical potential.

Nitrogen processes in aquatic ecosystems

Executive summary Nature of the problem (science/management/policy) • Freshwater ecosystems play a key role in the European nitrogen (N) cycle, both as a reactive agent that transfers, stores and processes N loadings from the atmosphere and terrestrial ecosystems, and as a natural environment severely impacted by the increase of these loadings. Approaches • This chapter is a review of major processes and factors controlling N transport and transformations for running waters, standing waters, groundwaters and riparian wetlands. Key findings/state of knowledge • The major factor controlling N processes in freshwater ecosystems is the residence time of water, which varies widely both in space and in time, and which is sensitive to changes in climate, land use and management. • The effects of increased N loadings to European freshwaters include acidification in semi-natural environments, and eutrophication in more disturbed ecosystems, with associated loss of biodiversity in both cases. • An important part of the nitrogen transferred by surface waters is in the form of organic N, as dissolved organic N (DON) and particulate organic N (PON). This part is dominant in semi-natural catchments throughout Europe and remains a significant component of the total N load even in nitrate enriched rivers. • In eutrophicated standing freshwaters N can be a factor limiting or co-limiting biological production, and control of both N and phosphorus (P) loading is oft en needed in impacted areas, if ecological quality is to be restored. Major uncertainties/challenges • The importance of storage and denitrifi cation in aquifers is a major uncertainty in the global N cycle, and controls in part the response of catchments to land use or management changes. In some aquifers, the increase of N concentrations will continue for decades even if efficient mitigation measures are implemented now. • Nitrate retention by riparian wetlands has oft en been highlighted. However, their use for mitigation must be treated with caution, since their effectiveness is difficult to predict, and side effects include increased DON emissions to adjacent open waters, N2O emissions to the atmosphere, and loss of biodiversity. • In fact, the character and specific spatial origins of DON are not fully understood, and similarly the quantitative importance of indirect N2O emissions from freshwater ecosystems as a result of N leaching losses from agricultural soils is still poorly known at the regional scale. • These major uncertainties remain due to the lack of adequate monitoring (all forms of N at a relevant frequency), especially – but not only – in the southern and eastern EU countries. Recommendations (research/policy) • The great variability of transfer pathways, buffering capacity and sensitivity of the catchments and of the freshwater ecosystems calls for site specific mitigation measures rather than standard ones applied at regional to national scale. • The spatial and temporal variations of the N forms, the processes controlling the transport and transformation of N within freshwaters, require further investigation if the role of N in influencing freshwater ecosystem health is to be better understood, underpinning the implementation of the EU Water Framework Directive for European freshwaters.

Getting pupils to 'see the point' of school subjects: history, a case study

This paper examines the factors that influence pupil take up of a subject, in this case history, at GCSE. The research indicates that pupils enjoy history but significant factors prevent many from choosing it for further study; these include factors that are beyond the control of teachers, such as government policy and the way this is interpreted by senior managers in school, and factors that are within the control of teachers. The paper suggests that there are lessons that departments can learn from more successful departments but there are also important side effects of government policy that are having unintended consequences.

Reaping the benefits: science and the sustainable intensification of global agriculture

Food security is one of this century’s key global challenges. By 2050 the world will require increased crop production in order to feed its predicted 9 billion people. This must be done in the face of changing consumption patterns, the impacts of climate change and the growing scarcity of water and land. Crop production methods will also have to sustain the environment, preserve natural resources and support livelihoods of farmers and rural populations around the world. There is a pressing need for the ‘sustainable intensifi cation’ of global agriculture in which yields are increased without adverse environmental impact and without the cultivation of more land. Addressing the need to secure a food supply for the whole world requires an urgent international effort with a clear sense of long-term challenges and possibilities. Biological science, especially publicly funded science, must play a vital role in the sustainable intensifi cation of food crop production. The UK has a responsibility and the capacity to take a leading role in providing a range of scientifi c solutions to mitigate potential food shortages. This will require signifi cant funding of cross-disciplinary science for food security. The constraints on food crop production are well understood, but differ widely across regions. The availability of water and good soils are major limiting factors. Signifi cant losses in crop yields occur due to pests, diseases and weed competition. The effects of climate change will further exacerbate the stresses on crop plants, potentially leading to dramatic yield reductions. Maintaining and enhancing the diversity of crop genetic resources is vital to facilitate crop breeding and thereby enhance the resilience of food crop production. Addressing these constraints requires technologies and approaches that are underpinned by good science. Some of these technologies build on existing knowledge, while others are completely radical approaches, drawing on genomics and high-throughput analysis. Novel research methods have the potential to contribute to food crop production through both genetic improvement of crops and new crop and soil management practices. Genetic improvements to crops can occur through breeding or genetic modifi cation to introduce a range of desirable traits. The application of genetic methods has the potential to refi ne existing crops and provide incremental improvements. These methods also have the potential to introduce radical and highly signifi cant improvements to crops by increasing photosynthetic effi ciency, reducing the need for nitrogen or other fertilisers and unlocking some of the unrealised potential of crop genomes. The science of crop management and agricultural practice also needs to be given particular emphasis as part of a food security grand challenge. These approaches can address key constraints in existing crop varieties and can be applied widely. Current approaches to maximising production within agricultural systems are unsustainable; new methodologies that utilise all elements of the agricultural system are needed, including better soil management and enhancement and exploitation of populations of benefi cial soil microbes. Agronomy, soil science and agroecology—the relevant sciences—have been neglected in recent years. Past debates about the use of new technologies for agriculture have tended to adopt an either/or approach, emphasising the merits of particular agricultural systems or technological approaches and the downsides of others. This has been seen most obviously with respect to genetically modifi ed (GM) crops, the use of pesticides and the arguments for and against organic modes of production. These debates have failed to acknowledge that there is no technological panacea for the global challenge of sustainable and secure global food production. There will always be trade-offs and local complexities. This report considers both new crop varieties and appropriate agroecological crop and soil management practices and adopts an inclusive approach. No techniques or technologies should be ruled out. Global agriculture demands a diversity of approaches, specific to crops, localities, cultures and other circumstances. Such diversity demands that the breadth of relevant scientific enquiry is equally diverse, and that science needs to be combined with social, economic and political perspectives. In addition to supporting high-quality science, the UK needs to maintain and build its capacity to innovate, in collaboration with international and national research centres. UK scientists and agronomists have in the past played a leading role in disciplines relevant to agriculture, but training in agricultural sciences and related topics has recently suffered from a lack of policy attention and support. Agricultural extension services, connecting farmers with new innovations, have been similarly neglected in the UK and elsewhere. There is a major need to review the support for and provision of extension services, particularly in developing countries. The governance of innovation for agriculture needs to maximise opportunities for increasing production, while at the same time protecting societies, economies and the environment from negative side effects. Regulatory systems need to improve their assessment of benefits. Horizon scanning will ensure proactive consideration of technological options by governments. Assessment of benefi ts, risks and uncertainties should be seen broadly, and should include the wider impacts of new technologies and practices on economies and societies. Public and stakeholder dialogue—with NGOs, scientists and farmers in particular—needs to be a part of all governance frameworks.