Development and trialling of a behavioural intervention for patients with atrial fibrillation initiating oral anticoagulation:the 'treat' study

Purpose: Atrial fibrillation (AF) is the most common heart arrhythmia and is associated with an increased risk of stroke. Stroke risk is commonly treated with oral anticoagulation (OAC) with a narrow therapeutic range (INR 2.0 to 3.0); which is poorly controlled in practice. Barriers to adherence include poor knowledge, and inaccurate perceptions surrounding illness and medications. Trial registration: ISRCTN93952605. Systematic review: Seven trials of educational, self-monitoring and decision aid interventions were included in a systematic review. Pooled analysis suggested education OR, 95% CI 7.89 (5.54-10.24) and self monitoring OR (95% CI) 5.47(2.55-8.39) significantly improve TTR; whereas decision aids are no more effective in reducing decision conflict than usual care, OR (95% CI) -0.10 (-0.17 to -0.02). Intervention development: The intervention was theoretically-driven (utilising the common sense and beliefs about medication models) and developed with expert patient feedback. Described using behavioural change techniques, the one-off group session included an educational booklet, ‘expert-patient’ focussed DVD, and worksheet. Methods: Ninety seven warfarin-naïve AF patients were randomised to receive the intervention (n=43), or usual care (n=54). The primary endpoint was time within therapeutic range (TTR), secondary endpoints included knowledge, quality of life (AF-QoL-18), beliefs about medication (BMQ), illness perceptions (IPQ-B), and anxiety and depression (HADS). Results: Intervention group had significantly higher TTR than usual care (78.5% vs. 66.7%; p=0.01). Knowledge changed significantly across time (F (3, 47) = 6.4; p<0.01), but not between groups (F (1, 47) = 3.3; p = 0.07). At six months knowledge predicted TTR (r=0.245; p=0.04). Illness concern negatively correlated with TTR (r= - 0.199; p=0.05). General Harm scores at one month predicted TTR (F (1, 72) = 4.08; p=0.048). There were significant differences in emotional representations (F (3, 49) = 3.3 (3, 49); p= 0.03), anxiety (F (3, 46) = 25.2; p<0.01) and depression (F (3, 46) = 37.7; p<0.01) across time. Conclusion: A theory-driven educational intervention can improve TTR in AF patients and potentially reduce the risk of adverse clinical outcomes. Improving education provision for AF patients is essential to ensure efficacious treatment.

Developing a complex educational–behavioural intervention:the TREAT intervention for patients with atrial fibrillation

This article describes the theoretical and pragmatic development of a patient-centred intervention for patients with atrial fibrillation (AF). Theoretical models (Common Sense Model, Necessity-Concerns Framework), clinical frameworks, and AF patient feedback contributed to the design of a one-off hour-long behaviour-change intervention package. Intervention materials consisted of a DVD, educational booklet, diary and worksheet, which were patient-centred and easy to administer. The intervention was evaluated within a randomised controlled trial. Several “active theoretical ingredients” were identified (for e.g., where patients believed their medication was less harmful they spent more time within the therapeutic range (TTR), with general harm scores predicting TTR at 6 months). Allowing for social comparison and adopting behaviour change techniques enabled accurate patient understanding of their condition and medication. The process of developing the intervention using theory-derived content and evaluation tools allowed a greater understanding of the mechanisms by which this intervention was successful. Alleviating concerns about treatment medication by educating patients can help to improve adherence. This process of intervention development could be adopted for a range of chronic illnesses and treatments. Critical elements should include the use of: (1) clinical guidelines; (2) appropriate theoretical models; (3) patient input; and (4) appropriate evaluation tools.

TRial of an Educational intervention on patients' knowledge of Atrial fibrillation and anticoagulant therapy, INR control, and outcome of Treatment with warfarin (TREAT)

Background Atrial fibrillation (AF) patients with a high risk of stroke are recommended anticoagulation with warfarin. However, the benefit of warfarin is dependent upon time spent within the target therapeutic range (TTR) of their international normalised ratio (INR) (2.0 to 3.0). AF patients possess limited knowledge of their disease and warfarin treatment and this can impact on INR control. Education can improve patients' understanding of warfarin therapy and factors which affect INR control. Methods/Design Randomised controlled trial of an intensive educational intervention will consist of group sessions (between 2-8 patients) containing standardised information about the risks and benefits associated with OAC therapy, lifestyle interactions and the importance of monitoring and control of their International Normalised Ratio (INR). Information will be presented within an 'expert-patient' focussed DVD, revised educational booklet and patient worksheets. 200 warfarin-naïve patients who are eligible for warfarin will be randomised to either the intervention or usual care groups. All patients must have ECG-documented AF and be eligible for warfarin (according to the NICE AF guidelines). Exclusion criteria include: aged < 18 years old, contraindication(s) to warfarin, history of warfarin USE, valvular heart disease, cognitive impairment, are unable to speak/read English and disease likely to cause death within 12 months. Primary endpoint is time spent in TTR. Secondary endpoints include measures of quality of life (AF-QoL-18), anxiety and depression (HADS), knowledge of AF and anticoagulation, beliefs about medication (BMQ) and illness representations (IPQ-R). Clinical outcomes, including bleeding, stroke and interruption to anticoagulation will be recorded. All outcome measures will be assessed at baseline and 1, 2, 6 and 12 months post-intervention. Discussion More data is needed on the clinical benefit of educational intervention with AF patients receiving warfarin. Trial registration ISRCTN93952605

Advancing age and bleeding risk are the strongest barriers to anticoagulant prescription in atrial fibrillation

In clinical practice many patients with atrial fibrillation (AF) at high thromboembolic risk fail to receive adequate oral anticoagulation (OAC) [1]. The complex management of anticoagulant therapy [frequent international normalised ratio (INR) monitoring because of narrow therapeutic window, interaction with food and alcohol, concomitant medications and comorbities], the overestimation of bleeding risk and the underestimation of stroke risk, may partially explain physicians' reluctance to prescribe anticoagulation. In the current issue of Age and Ageing, Pugh and Mead [2] report a systematic review on physicians' attitudes concerning anticoagulant treatment among AF patients. Through surveys (questionnaire, clinical vignette and interview) on hypothetical case scenarios, they have identified the barriers to effective anticoagulant prescription, as follows: increasing age, bleeding risk or previous bleeding, fall risk, co-morbidities (e.g. chronic alcoholism or cognitive impairment) and lack of compliance. In particular, advanced age has been reported as the most striking reason for with-holding anticoagulation, while risk of falls and previous bleeding are also disproportionate barriers to warfarin prescription.

Educational and behavioural interventions for anticoagulant therapy in patients with atrial fibrillation

Background Current guidelines recommend oral anticoagulation therapy for patients with atrial fibrillation who are at moderate-to-high risk of stroke, however anticoagulation control (time in therapeutic range (TTR)) is dependent on many factors. Educational and behavioural interventions may impact on patients’ ability to maintain their International Normalised Ratio (INR) control. Objectives To evaluate the effects on TTR of educational and behavioural interventions for oral anticoagulation therapy (OAT) in patients with atrial fibrillation (AF). Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews of Effects (DARE) in The Cochrane Library (2012, Issue 7 of 12), MEDLINE Ovid (1950 to week 4 July 2012), EMBASE Classic + EMBASE Ovid (1947 to Week 31 2012), PsycINFO Ovid (1806 to 2012 week 5 July) on 8 August 2012 and CINAHL Plus with Full Text EBSCO (to August 2012) on 9 August 2012. We applied no language restrictions. Selection criteria The primary outcome analysed was TTR. Secondary outcomes included decision conflict (patient's uncertainty in making health-related decisions), percentage of INRs in the therapeutic range, major bleeding, stroke and thromboembolic events, patient knowledge, patient satisfaction, quality of life (QoL), and anxiety. Data collection and analysis The two review authors independently extracted data. Where insufficient data were present to conduct a meta-analysis, effect sizes and confidence intervals (CIs) of the included studies were reported. Data were pooled for two outcomes, TTR and decision conflict. Main results Eight trials with a total of 1215 AF patients (number of AF participants included in the individual trials ranging from 14 to 434) were included within the review. Studies included education, decision aids, and self-monitoring plus education. For the primary outcome of TTR, data for the AF participants in two self-monitoring plus education trials were pooled and did not favour self-monitoring plus education or usual care in improving TTR, with a mean difference of 6.31 (95% CI -5.63 to 18.25). For the secondary outcome of decision conflict, data from two decision aid trials favoured usual care over the decision aid in terms of reducing decision conflict, with a mean difference of -0.1 (95% CI -0.2 to -0.02). Authors' conclusions This review demonstrated that there is insufficient evidence to draw definitive conclusions regarding the impact of educational or behavioural interventions on TTR in AF patients receiving OAT. Thus, more trials are needed to examine the impact of interventions on anticoagulation control in AF patients and the mechanisms by which they are successful. It is also important to explore the psychological implications for patients suffering from this long-term chronic condition.

Educational intervention improves anticoagulation control in atrial fibrillation patients:the TREAT randomised trial

Background: Stroke prevention in atrial fibrillation (AF), most commonly with warfarin, requires maintenance of a narrow therapeutic target (INR 2.0 to 3.0) and is often poorly controlled in practice. Poor patient-understanding surrounding AF and its’ treatment may contribute to patient’s willingness to adhere to recommendations. Method: A theory-driven intervention, developed using patient interviews and focus groups, consisting of a one-off group session (1-6 patients) utilising an ‘expert-patient’ focussed DVD, educational booklet, self-monitoring diary and worksheet, was compared in a randomised controlled trial (ISRCTN93952605) against usual care, with patient postal follow-ups at 1, 2, 6, and 12-months. Ninety-seven warfarin-naïve AF patients were randomised to intervention (n=46, mean age (SD) 72.0 (8.2), 67.4% men), or usual care (n=51, mean age (SD) 73.7 (8.1), 62.7% men), stratified by age, sex, and recruitment centre. Primary endpoint was time within therapeutic range (TTR); secondary endpoints included knowledge, quality of life, anxiety/depression, beliefs about medication, and illness perceptions. Main findings: Intervention patients had significantly higher TTR than usual care at 6-months (76.2% vs. 71.3%; p=0.035); at 12-months these differences were not significant (76.0% vs. 70.0%; p=0.44). Knowledge increased significantly across time (F (3, 47) = 6.4; p<0.01), but there were no differences between groups (F (1, 47) = 3.3; p = 0.07). At 6-months, knowledge scores predicted TTR (r=0.245; p=0.04). Patients’ scores on subscales representing their perception of the general harm and overuse of medication, as well as the perceived necessity of their AF specific medications predicted TTR at 6- and 12-months. Conclusions: A theory-driven educational intervention significantly improves TTR in AF patients initiating warfarin during the first 6-months. Adverse clinical outcomes may potentially be reduced by improving patients’ understanding of the necessity of warfarin and reducing their perception of treatment harm. Improving education provision for AF patients is essential to ensure efficacious and safe treatment.

Educational and behavioural interventions for anticoagulant therapy in patients with atrial fibrillation

background Current guidelines recommend oral anticoagulation therapy for patients with atrial fibrillation who are at moderate-to-high risk of stroke, however anticoagulation control (time in therapeutic range (TTR)) is dependent on many factors. Educational and behavioural interventions may impact on patients’ ability to maintain their International Normalised Ratio (INR) control. Objectives To evaluate the effects on TTR of educational and behavioural interventions for oral anticoagulation therapy (OAT) in patients with atrial fibrillation (AF). Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews of Effects (DARE) in The Cochrane Library (2012, Issue 7 of 12), MEDLINE Ovid (1950 to week 4 July 2012), EMBASE Classic + EMBASE Ovid (1947 to Week 31 2012), PsycINFO Ovid (1806 to 2012 week 5 July) on 8 August 2012 and CINAHL Plus with Full Text EBSCO (to August 2012) on 9 August 2012. We applied no language restrictions. Selection criteria The primary outcome analysed was TTR. Secondary outcomes included decision conflict (patient's uncertainty in making health-related decisions), percentage of INRs in the therapeutic range, major bleeding, stroke and thromboembolic events, patient knowledge, patient satisfaction, quality of life (QoL), and anxiety. Data collection and analysis The two review authors independently extracted data. Where insufficient data were present to conduct a meta-analysis, effect sizes and confidence intervals (CIs) of the included studies were reported. Data were pooled for two outcomes, TTR and decision conflict. Main results Eight trials with a total of 1215 AF patients (number of AF participants included in the individual trials ranging from 14 to 434) were included within the review. Studies included education, decision aids, and self-monitoring plus education. For the primary outcome of TTR, data for the AF participants in two self-monitoring plus education trials were pooled and did not favour self-monitoring plus education or usual care in improving TTR, with a mean difference of 6.31 (95% CI -5.63 to 18.25). For the secondary outcome of decision conflict, data from two decision aid trials favoured usual care over the decision aid in terms of reducing decision conflict, with a mean difference of -0.1 (95% CI -0.2 to -0.02). Authors' conclusions This review demonstrated that there is insufficient evidence to draw definitive conclusions regarding the impact of educational or behavioural interventions on TTR in AF patients receiving OAT. Thus, more trials are needed to examine the impact of interventions on anticoagulation control in AF patients and the mechanisms by which they are successful. It is also important to explore the psychological implications for patients suffering from this long-term chronic condition.

Form follows function:model-driven engineering for clinical trials

We argue that, for certain constrained domains, elaborate model transformation technologies-implemented from scratch in general-purpose programming languages-are unnecessary for model-driven engineering; instead, lightweight configuration of commercial off-the-shelf productivity tools suffices. In particular, in the CancerGrid project, we have been developing model-driven techniques for the generation of software tools to support clinical trials. A domain metamodel captures the community's best practice in trial design. A scientist authors a trial protocol, modelling their trial by instantiating the metamodel; customized software artifacts to support trial execution are generated automatically from the scientist's model. The metamodel is expressed as an XML Schema, in such a way that it can be instantiated by completing a form to generate a conformant XML document. The same process works at a second level for trial execution: among the artifacts generated from the protocol are models of the data to be collected, and the clinician conducting the trial instantiates such models in reporting observations-again by completing a form to create a conformant XML document, representing the data gathered during that observation. Simple standard form management tools are all that is needed. Our approach is applicable to a wide variety of information-modelling domains: not just clinical trials, but also electronic public sector computing, customer relationship management, document workflow, and so on. © 2012 Springer-Verlag.

New biomarkers and risk stratification in atrial fibrillation:simplicity and practicality matter

Advances in our understanding of pathological mechanisms can inform the identification of various biomarkers for risk stratification, monitoring drug efficacy and toxicity; and enabling careful monitoring of polypharmacy. Biomarkers in the broadest sense refer to 'biological markers' and this can be blood-based (eg. fibrin D-dimer, von Willebrand factor, etc) urine-based (eg. thromboxane), or even related to cardiac or cerebral imaging(1). Most biomarkers offer improvements over clinical risk scores in predicting high risk patients - at least statistically - but usually at the loss of simplicity and practicality for easy application in everyday clinical practice. Given the various biomarkers can be informed by different aspects of pathophysiology (e.g. inflammation, clotting, collagen turnover) they can nevertheless contribute to a better understanding of underlying disease processes(2). Indeed, many age-related diseases share common modifiable underpinning mechanisms e.g. inflammation, oxidative stress and visceral adiposity.

Prediction of paroxysmal atrial fibrillation

We present a novel method for prediction of the onset of a spontaneous (paroxysmal) atrial fibrilation episode by representing the electrocardiograph (ECG) output as two time series corresponding to the interbeat intervals and the lengths of the atrial component of the ECG. We will then show how different entropy measures can be calulated from both of these series and then combined in a neural network trained using the Bayesian evidence procedure to form and effective predictive classifier.

Patients’ and health professionals’ views and experiences of atrial fibrillation and oral-anticoagulant therapy:a qualitative meta-synthesis

Objective - Atrial fibrillation (AF) patients are prescribed oral-anticoagulant (OAC) therapy, often warfarin, to reduce stroke risk. We explored existing qualitative evidence about patients’ and health professionals’ experiences of OAC therapy. Methods - Systematic searches of eight bibliographic databases were conducted. Quality was appraised using the Critical Appraisal Skills Programme tool and data from ten studies were synthesised qualitatively. Results - Four third-order constructs, emerged from the final step in the analysis process: (1) diagnosing AF and the communication of information, (2) deciding on OAC therapy, (3) challenges revolving around patient issues, and (4) healthcare challenges. Synthesis uncovered perspectives that could not be achieved through individual studies. Conclusion - Physicians’ and patients’ experiences present a dichotomy of opinion on decision-making, which requires further exploration and changes in practice. Outcomes of workload pressure on both health professionals and patients should be investigated. The need for on-going support and education to patients and physicians is critical to achieve best practice and treatment adherence. Practice implications - Such research could encourage health professionals to understand and attend better to the needs and concerns of the patient. Additionally these findings can be used to inform researchers and healthcare providers in developing educational interventions with both patients and health professionals.

Reducing suffering in animal models and procedures involving seizures, convulsions and epilepsy

This report is based on discussions and submissions from an expert working group consisting of veterinarians, animal care staff and scientists with expert knowledge relevant to the field and aims to facilitate the implementation of the Three Rs (replacement, reduction and refinement) in the use of animal models or procedures involving seizures, convulsions and epilepsy. Each of these conditions will be considered, the specific welfare issues discussed, and practical measures to reduce animal use and suffering suggested. The emphasis is on refinement since this has the greatest potential for immediate implementation, and some general issues for refinement are summarised to help achieve this, with more detail provided on a range of specific refinements.

Patients’ and physicians’ experiences of atrial fibrillation and anticoagulation therapy:a qualitative journey

Background: Oral anticoagulation (OAC) reduces stroke risk in patients with atrial fibrillation (AF) however it is often underutilized and sometimes refused by patients. This programme of work included a meta-synthesis and two inter-linking studies aiming to explore patients’ and physicians’ experiences of AF and OAC. Methods: A meta-synthesis of qualitative evidence was conducted which informed the empirical work. Semi-structured individual interviews were utilised. Study 1: Three AF patient sub-groups were interviewed; accepted (n=4), refused (n=4), or discontinued (n=3) warfarin. Study 2: Four physician sub-groups (n=4 each group) prescribing OAC to AF patients were interviewed: consultant cardiologists, consultant general physicians, general practitioners and cardiology registrars. Data was analysed using interpretative phenomenological analysis. Results: Study 1: Three over-arching themes comprised patients’ experiences: (1) the initial consultation, (2) life after the consultation, and (3) patients’ reflections. Patients commented on the relief and reassurance experienced during the consultation but they perceived the decision making process mostly led by the physician. Lack of education and take-home materials distributed during the initial consultation was highlighted. Patients who had experienced stroke themselves or were caregivers, were more receptive to education aimed towards stroke risk reduction rather than bleeding risk. Warfarin monitoring was challenging for patients, however some patients perceived it as beneficial as it served to enhance patient-physician relationship. Study 2: Two over-arching themes emerged from physicians’ experiences: (1) communicating information and (2) challenges with OAC prescription for AF. Physicians’ approach to the consultation style shifted through a continuum of compliance-adherence-concordance during the consultation. They aimed for concordance, however challenges such as time and the perceived patient trust in them as the expert, led to physicians adopting a paternalistic approach. Physicians also pointed out challenges associated with guideline adherence and the need to adopt a multi-disciplinary approach, where other health professionals could provide on-going education. Conclusion: This programme of work has illustrated the benefit of taking an in depth phenomenological approach to understanding the lived experience of the physician-patient consultation. Together with the meta-synthesis, this work has strengthened the evidence base and demonstrated that there is a need to target patients' and physicians' ability to communicate with each other in a comprehensible way.

Children's views on unlicensed/off-label paediatric prescribing and paediatric clinical trials

Objectives - To explore the views and perspectives of children on the unlicensed/off-label use of medicines in children and on the participation of children in clinical trials. Methods - Focus-group discussions, involving school children, were carried out in a range of primary and secondary schools in Northern Ireland. A purposeful sample was chosen to facilitate representation of various socioeconomic groupings. Results - A total of 123 pupils, aged from 10 to 16 years, from six schools, participated in 16 focus groups. In general, pupils viewed the unlicensed/off-label use of medicines in children as unsafe and unethical and felt it is necessary to test medicines in children to improve the availability of licensed products. The majority felt that older children should be told, and that parents should be told, about the unlicensed/off-label use of medicines in children, yet they recognised some implications of this, such as potential medication non-adherence. Conclusions - This is the first study to explore the views of healthy children on unlicensed medicine use in children. Children were able to recognise potential risks associated with the unlicensed use of medicines and felt it is necessary to test and license more medicines in children. Practice implications - Health care professionals should consider the views of children in decisions that affect their health.