How is the language of medicines use review leaflets symbolising the service?

Introduction The medicines use review (MUR), a new community pharmacy ‘service’, was launched in England and Wales to improve patients’ knowledge and use of medicines through a private, patient–pharmacist appointment. After 18 months, only 30% of pharmacies are providing MURs; at an average of 120 per annum (maximum 400 allowed).1 One reason linked to low delivery is patient recruitment.2 Our aim was to examine how the MUR is symbolised and given meaning via printed patient information, and potential implications. Method The language of 10 MUR patient leaflets, including the NHS booklet,3 and leaflets from multiples and wholesalers was evaluated by discourse analysis. Results and Discussion Before experiencing MURs, patients conceivably ‘categorise’ relationships with pharmacists based on traditional interactions.4 Yet none of the leaflets explicitly describe the MUR as ‘new’ and presuppose patients would become involved in activities outside of their pre-existing relationship with pharmacists such as appointments, self-completion of charts, and pharmacy action plans. The MUR process is described inconsistently, with interchangeable use of formal (‘review meeting‘) and informal (‘friendly’) terminology, the latter presumably to portray an intended ‘negotiation model’ of interaction.5 Assumptions exist about attitudes (‘not understanding’; ‘problems’) that might lead patients to an appointment. However, research has identified a multitude of reasons why patients choose (or not) to consult practitioners,6 and marketing of MURs should also consider other barriers. For example, it may be prudent to remove time limits to avoid implying patients might not be listened to fully, during what is for them an additional practitioner consultation.

A conceptual framework of patient satisfaction with a pharmacy adherence service

Background Patients do not adhere to their medicines for a host of reasons which can include their underlying beliefs as well as the quality of their interactions with healthcare professionals. One way of measuring the outcome of pharmacy adherence services is to assess patient satisfaction but no questionnaire exists that truly captures patients' experiences with these relatively new services. Objective Our objective was to develop a conceptual framework specific to patient satisfaction with a community pharmacy adherence service based on criteria used by patients themselves. Setting The study was based in community pharmacies in one large geographical area of the UK (Surrey). All the work was conducted between October 2008 and September 2010. Methods This study involved qualitative non-participant observation and semi-structured interviewing. We observed the recruitment of patients to the Medicines Use Review (MUR) service and also actual MUR consultations (7). We also interviewed patients (15). Data collection continued until no new themes were identified during analysis. We analysed interviews to firstly create a comprehensive account of themes which had significance within the transcripts, then created sub-themes within super-ordinate categories. We used a structure-process-outcome approach to develop a conceptual framework relating to patient satisfaction with the MUR. Favourable ethical opinion for this study was received from the NHS Surrey Research Ethics Committee on 2nd June 2008. Results Five super-ordinate themes linked to patient satisfaction with the MUR service were identified, including relationships with healthcare providers; attitudes towards healthcare providers; patients' experience of health, healthcare and medicines; patients' views of the MUR service; the logistics of the MUR service. In the conceptual framework, structure was conceptualised as existing relationships, environment, and time; process was conceptualised as related to recruitment and consultation stages; and outcome as two concepts of immediate patient outcomes and satisfaction on reflection. Conclusion We identified and highlighted factors that can influence patient satisfaction with the MUR service and this led to the development of a conceptual framework of patient satisfaction with the MUR service. This can form the basis for developing a questionnaire for measuring patient satisfaction with this and similar pharmacy adherence services. Impact of findings on practice * Pharmacists and researchers can access the relevant ideas presented here in relation to patient satisfaction with pharmacy adherence services. * Researcher can use the conceptual framework as a basis for measuring the quality of pharmacy adherence services. * Community pharmacists can improve the quality of healthcare they provide by realizing concepts relevant to patient satisfaction with adherence services.

Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Background Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers (“biomarkers”) of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10–20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2–10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research.

Failure to regulate: counterproductive recruitment of top-down prefrontal-subcortical circuitry in major depression

Although depressed mood is a normal occurrence in response to adversity in all individuals, what distinguishes those who are vulnerable to major depressive disorder (MDD) is their inability to effectively regulate negative mood when it arises. Investigating the neural underpinnings of adaptive emotion regulation and the extent to which such processes are compromised in MDD may be helpful in understanding the pathophysiology of depression. We report results from a functional magnetic resonance imaging study demonstrating left-lateralized activation in the prefrontal cortex (PFC) when downregulating negative affect in nondepressed individuals, whereas depressed individuals showed bilateral PFC activation. Furthermore, during an effortful affective reappraisal task, nondepressed individuals showed an inverse relationship between activation in left ventrolateral PFC and the amygdala that is mediated by the ventromedial PFC (VMPFC). No such relationship was found for depressed individuals, who instead show a positive association between VMPFC and amygdala. Pupil dilation data suggest that those depressed patients who expend more effort to reappraise negative stimuli are characterized by accentuated activation in the amygdala, insula, and thalamus, whereas nondepressed individuals exhibit the opposite pattern. These findings indicate that a key feature underlying the pathophysiology of major depression is the counterproductive engagement of right prefrontal cortex and the lack of engagement of left lateral-ventromedial prefrontal circuitry important for the downregulation of amygdala responses to negative stimuli.

How was patient empowerment portrayed in information leaflets describing the community pharmacy Medicines Use Review service in the UK?

Objective The Medicines Use Review (MUR) community pharmacy service was introduced in 2005 to enhance patient empowerment but the service has not been taken up as widely as expected. We investigated the depiction of the patient–pharmacist power relationship within MUR patient information leaflets. Methods We identified 11 MUR leaflets including the official Department of Health MUR booklet and through discourse analysis examined the way language and imagery had been used to symbolise and give meaning to the MUR service, especially the portrayal of the patient–pharmacist interactions and the implied power relations. Results A variety of terminology was used to describe the MUR, a service that aimed ultimately to produce more informed patients through the information imparted by knowledgeable, skilled pharmacists. Conclusion The educational role of the MUR overshadowed the intended patient empowerment that would take place with a true concordance-centred approach. Although patient empowerment was implied, this was within the boundaries of the biomedical model with the pharmacist as the expert provider of medicines information. Practice implications If patient empowerment is to be conveyed this needs to be communicated to patients through consistent use of language and imagery that portrays the inclusivity intended.

What is the new medicines use review ‘patient survey’ attempting to capture in the context of existing patient satisfaction with pharmacy questionnaires and a new conceptual framework?

The community pharmacy service medicines use review (MUR) was introduced in 2005 ‘to improve patient knowledge, concordance and use of medicines’ through a private patient–pharmacist consultation. The MUR presents a fundamental change in community pharmacy service provision. While traditionally pharmacists are dispensers of medicines and providers of medicines advice, and patients as recipients, the MUR considers pharmacists providing consultation-type activities and patients as active participants. The MUR facilitates a two-way discussion about medicines use. Traditional patient–pharmacist behaviours transform into a new set of behaviours involving the booking of appointments, consultation processes and form completion, and the physical environment of the patient–pharmacist interaction moves from the traditional setting of the dispensary and medicines counter to a private consultation room. Thus, the new service challenges traditional identities and behaviours of the patient and the pharmacist as well as the environment in which the interaction takes place. In 2008, the UK government concluded there is at present too much emphasis on the quantity of MURs rather than on their quality.[1] A number of plans to remedy the perceived imbalance included a suggestion to reward ‘health outcomes’ achieved, with calls for a more focussed and scientific approach to the evaluation of pharmacy services using outcomes research. Specifically, the UK government set out the main principal research areas for the evaluation of pharmacy services to include ‘patient and public perceptions and satisfaction’as well as ‘impact on care and outcomes’. A limited number of ‘patient satisfaction with pharmacy services’ type questionnaires are available, of varying quality, measuring dimensions relating to pharmacists’ technical competence, behavioural impressions and general satisfaction. For example, an often cited paper by Larson[2] uses two factors to measure satisfaction, namely ‘friendly explanation’ and ‘managing therapy’; the factors are highly interrelated and the questions somewhat awkwardly phrased, but more importantly, we believe the questionnaire excludes some specific domains unique to the MUR. By conducting patient interviews with recent MUR recipients, we have been working to identify relevant concepts and develop a conceptual framework to inform item development for a Patient Reported Outcome Measure questionnaire bespoke to the MUR. We note with interest the recent launch of a multidisciplinary audit template by the Royal Pharmaceutical Society of Great Britain (RPSGB) in an attempt to review the effectiveness of MURs and improve their quality.[3] This template includes an MUR ‘patient survey’. We will discuss this ‘patient survey’ in light of our work and existing patient satisfaction with pharmacy questionnaires, outlining a new conceptual framework as a basis for measuring patient satisfaction with the MUR. Ethical approval for the study was obtained from the NHS Surrey Research Ethics Committee on 2 June 2008. References 1. Department of Health (2008). Pharmacy in England: Building on Strengths – Delivering the Future. London: HMSO. www. official-documents.gov.uk/document/cm73/7341/7341.pdf (accessed 29 September 2009). 2. Larson LN et al. Patient satisfaction with pharmaceutical care: update of a validated instrument. JAmPharmAssoc 2002; 42: 44–50. 3. Royal Pharmaceutical Society of Great Britain (2009). Pharmacy Medicines Use Review – Patient Audit. London: RPSGB. http:// qi4pd.org.uk/index.php/Medicines-Use-Review-Patient-Audit. html (accessed 29 September 2009).

Direct versus indirect sexual selection: genetic basis of colour, size and recruitment in a wild bird

Indirect and direct models of sexual selection make different predictions regarding the quantitative genetic relationships between sexual ornaments and fitness. Indirect models predict that ornaments should have a high heritability and that strong positive genetic covariance should exist between fitness and the ornament. Direct models, on the other hand, make no such assumptions about the level of genetic variance in fitness and the ornament, and are therefore likely to be more important when environmental sources of variation are large. Here we test these predictions in a wild population of the blue tit (Parus caeruleus), a species in which plumage coloration has been shown to be under sexual selection. Using 3 years of cross-fostering data from over 250 breeding attempts, we partition the covariance between parental coloration and aspects of nestling fitness into a genetic and environmental component. Contrary to indirect models of sexual selection, but in agreement with direct models, we show that variation in coloration is only weakly heritable (h(2) < 0.11), and that two components of offspring fitness-nestling size and fledgling recruitment-are strongly dependent on parental effects, rather than genetic effects. Furthermore, there was no evidence of significant positive genetic covariation between parental colour and offspring traits. Contrary to direct benefit models, however, we find little evidence that variation in colour reliably indicates the level of parental care provided by either males or females. Taken together, these results indicate that the assumptions of indirect models of sexual selection are not supported by the genetic basis of the traits reported on here.

Donepezil for the symptomatic treatment of patients with mild to moderate Alzheimer's disease: a meta-analysis of individual patient data from randomised controlled trials

Background: The objective was to evaluate the efficacy and tolerability of donepezil (5 and 10 mg/day) compared with placebo in alleviating manifestations of mild to moderate Alzheimer's disease (AD). Method: A systematic review of individual patient data from Phase II and III double-blind, randomised, placebo-controlled studies of up to 24 weeks and completed by 20 December 1999. The main outcome measures were the ADAS-cog, the CIBIC-plus, and reports of adverse events. Results: A total of 2376 patients from ten trials were randomised to either donepezil 5 mg/day (n = 821), 10 mg/day (n = 662) or placebo (n = 893). Cognitive performance was better in patients receiving donepezil than in patients receiving placebo. At 12 weeks the differences in ADAS-cog scores were 5 mg/day-placebo: - 2.1 [95% confidence interval (CI), - 2.6 to - 1.6; p < 0.001], 10 mg/day-placebo: - 2.5 ( - 3.1 to - 2.0; p < 0.001). The corresponding results at 24 weeks were - 2.0 ( - 2.7 to - 1.3; p < 0.001) and - 3.1 ( - 3.9 to - 2.4; p < 0.001). The difference between the 5 and 10 mg/day doses was significant at 24 weeks (p = 0.005). The odds ratios (OR) of improvement on the CIBIC-plus at 12 weeks were: 5 mg/day-placebo 1.8 (1.5 to 2.1; p < 0.001), 10 mg/day-placebo 1.9 (1.5 to 2.4; p < 0.001). The corresponding values at 24 weeks were 1.9 (1.5 to 2.4; p = 0.001) and 2.1 (1.6 to 2.8; p < 0.001). Donepezil was well tolerated; adverse events were cholinergic in nature and generally of mild severity and brief in duration. Conclusion: Donepezil (5 and 10 mg/day) provides meaningful benefits in alleviating deficits in cognitive and clinician-rated global function in AD patients relative to placebo. Increased improvements in cognition were indicated for the higher dose. Copyright © 2004 John Wiley & Sons, Ltd.

Meta-analysis of individual patient data from randomised trials: a review of methods used in practice

Background: Meta-analyses based on individual patient data (IPD) are regarded as the gold standard for systematic reviews. However, the methods used for analysing and presenting results from IPD meta-analyses have received little discussion. Methods We review 44 IPD meta-analyses published during the years 1999–2001. We summarize whether they obtained all the data they sought, what types of approaches were used in the analysis, including assumptions of common or random effects, and how they examined the effects of covariates. Results: Twenty-four out of 44 analyses focused on time-to-event outcomes, and most analyses (28) estimated treatment effects within each trial and then combined the results assuming a common treatment effect across trials. Three analyses failed to stratify by trial, analysing the data is if they came from a single mega-trial. Only nine analyses used random effects methods. Covariate-treatment interactions were generally investigated by subgrouping patients. Seven of the meta-analyses included data from less than 80% of the randomized patients sought, but did not address the resulting potential biases. Conclusions: Although IPD meta-analyses have many advantages in assessing the effects of health care, there are several aspects that could be further developed to make fuller use of the potential of these time-consuming projects. In particular, IPD could be used to more fully investigate the influence of covariates on heterogeneity of treatment effects, both within and between trials. The impact of heterogeneity, or use of random effects, are seldom discussed. There is thus considerable scope for enhancing the methods of analysis and presentation of IPD meta-analysis.

A score test for binary data with patient non-compliance

A score test is developed for binary clinical trial data, which incorporates patient non-compliance while respecting randomization. It is assumed in this paper that compliance is all-or-nothing, in the sense that a patient either accepts all of the treatment assigned as specified in the protocol, or none of it. Direct analytic comparisons of the adjusted test statistic for both the score test and the likelihood ratio test are made with the corresponding test statistics that adhere to the intention-to-treat principle. It is shown that no gain in power is possible over the intention-to-treat analysis, by adjusting for patient non-compliance. Sample size formulae are derived and simulation studies are used to demonstrate that the sample size approximation holds. Copyright © 2003 John Wiley & Sons, Ltd.

Action following the discovery of a global association between the whole genome and adverse event risk in a clinical drug-development programme

Observation of adverse drug reactions during drug development can cause closure of the whole programme. However, if association between the genotype and the risk of an adverse event is discovered, then it might suffice to exclude patients of certain genotypes from future recruitment. Various sequential and non-sequential procedures are available to identify an association between the whole genome, or at least a portion of it, and the incidence of adverse events. In this paper we start with a suspected association between the genotype and the risk of an adverse event and suppose that the genetic subgroups with elevated risk can be identified. Our focus is determination of whether the patients identified as being at risk should be excluded from further studies of the drug. We propose using a utility function to? determine the appropriate action, taking into account the relative costs of suffering an adverse reaction and of failing to alleviate the patient's disease. Two illustrative examples are presented, one comparing patients who suffer from an adverse event with contemporary patients who do not, and the other making use of a reference control group. We also illustrate two classification methods, LASSO and CART, for identifying patients at risk, but we stress that any appropriate classification method could be used in conjunction with the proposed utility function. Our emphasis is on determining the action to take rather than on providing definitive evidence of an association. Copyright (C) 2008 John Wiley & Sons, Ltd.

Genetic evidence of frequent long-distance recruitment in a vertebrate-dispersed tree

The importance of dispersal for the maintenance of biodiversity, while long-recognized, has remained unresolved. We used molecular markers to measure effective dispersal in a natural population of the vertebrate-dispersed Neotropical tree, Simarouba amara (Simaroubaceae) by comparing the distances between maternal parents and their offspring and comparing gene movement via seed and pollen in the 50 ha plot of the Barro Colorado Island forest, Central Panama. In all cases (parent-pair, mother-offspring, father-offspring, sib-sib) distances between related pairs were significantly greater than distances to nearest possible neighbours within each category. Long-distance seedling establishment was frequent: 74% of assigned seedlings established > 100 m from the maternal parent [mean = 392 +/- 234.6 m (SD), range = 9.3-1000.5 m] and pollen-mediated gene flow was comparable to that of seed [mean = 345.0 +/- 157.7 m (SD), range 57.6-739.7 m]. For S. amara we found approximately a 10-fold difference between distances estimated by inverse modelling and mean seedling recruitment distances (39 m vs. 392 m). Our findings have important implications for future studies in forest demography and regeneration, with most seedlings establishing at distances far exceeding those demonstrated by negative density-dependent effects.