Comparison of two twice-daily doses of budesonide/formoterol maintenance and reliever therapy.

The aim of this study was to compare two budesonide/formoterol maintenance doses within the budesonide/formoterol maintenance and reliever therapy concept and to identify possible patient characteristics at baseline which would predict a better response to a higher than standard maintenance dose. A total of 8,424 patients with symptomatic asthma when using an inhaled corticosteroid (ICS) with or without a long-acting ß(2)-agonist were randomised to budesonide/formoterol 160/4.5 µg, one (1 × 2) or two (2 × 2) inhalations b.i.d. Patients used the same inhaler as needed for symptom relief. The primary outcome variable was time to first severe asthma exacerbation. In the total study population, the time to first severe asthma exacerbation was prolonged by 18% with 2 × 2 versus 1 × 2 (hazard ratio 0.82; p = 0.03). Lung function (peak expiratory flow) was the only statistically significant predictor of a better response to 2 × 2. The mean daily ICS doses were 737 and 463 µg in the 2 × 2 and 1 × 2 groups, respectively. In a real-life setting, budesonide/formoterol maintenance and reliever therapy at the 2 × 2 maintenance dose did prolong time to first severe exacerbation but at a higher medication load. Patients with low lung function benefited most from the higher maintenance dose.

Development and implementation of guidelines in allergic rhinitis ­ an ARIA-GA2LEN paper.

The links between asthma and rhinitis are well characterized. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines stress the importance of these links and provide guidance for their prevention and treatment. Despite effective treatments being available, too few patients receive appropriate medical care for both diseases. Most patients with rhinitis and asthma consult primary care physicians and therefore these physicians are encouraged to understand and use ARIA guidelines. Patients should also be informed about these guidelines to raise their awareness of optimal care and increase control of the two related diseases. To apply these guidelines, clinicians and patients need to understand how and why the recommendations were made. The goal of the ARIA guidelines is to provide recommendations about the best management options for most patients in most situations. These recommendations should be based on the best available evidence. Making recommendations requires the assessment of the quality of available evidence, deciding on the balance between benefits and downsides, consideration of patients' values and preferences, and, if applicable, resource implications. Guidelines must be updated as new management options become available or important new evidence emerges. Transparent reporting of guidelines facilitates understanding and acceptance, but implementation strategies need to be improved.

The Brussels Declaration: the need for change in asthma management.

Asthma is a highly prevalent condition across Europe and numerous guidelines have been developed to optimise management. However, asthma can be neither cured nor prevented, treatment choices are limited and many patients have poorly controlled or uncontrolled asthma. The Brussels Declaration on Asthma, sponsored by The Asthma, Allergy and Inflammation Research Charity, was developed to call attention to the shortfalls in asthma management and to urge European policy makers to recognise that asthma is a public health problem that should be a political priority. The Declaration urges recognition and action on the following points: the systemic inflammatory component of asthma should be better understood and considered in assessments of treatment efficacy; current research must be communicated and responded to quickly; the European Medicines Agency guidance note on asthma should be updated; "real world" studies should be funded and results used to inform guidelines; variations in care across Europe should be addressed; people with asthma should participate in their own care; the impact of environmental factors should be understood; and targets should be set for improvement. The present paper reviews the evidence supporting the need for change in asthma management and summarises the ten key points contained in the Brussels Declaration.

Linking NHS data for pediatric pharmacovigilance: Results of a Delphi survey.

BACKGROUND: Adverse drug events are a major cause of patient safety incidents. Current systems of pharmacovigilance under-report adverse drug reactions (ADRs), especially in children, leading to delays in their identification. This is of particular concern, as children especially have an increased vulnerability to ADRs. OBJECTIVES: The objective was to seek consensus among healthcare professionals (HCPs) about barriers and facilitators to the linkage of routinely collected health data for pediatric pharmacovigilance in Scotland. METHODS: A Delphi survey was conducted with a random sample of HCPs including nurses, pharmacists and doctors, working in primary or secondary care, in Scotland. Participants were identified from sampling frames of the target professionals such as an NHS workforce list for general practitioners and recruited by postal invitation. A total of 819 HCPs were invited to take part. Those agreeing to participate were given the option of completing the questionnaires online or as hard copy. Reminders were sent twice at a fortnightly interval. Questions content included description of professional role as well as testing for the willingness to support the proposed project and was informed by the Theoretical Domains Framework of Behavior Change (TDF) and earlier qualitative work. Three Delphi rounds were administered, including a first round for item generation. RESULTS: 121 of those invited agreed to take part (15%). The first round of the Delphi study included 21 open questions and generated over a 1000 individual statements from 61 participants that returned the questionnaires (50.4%). These were rationalized to 149 items for the second round in which participants rated their views on the importance (or not) of each item on a 9-point Likert scale (strongly disagree - strongly agree). After the third round, there was consensus on items that focused on professional standards, and practical requirements, overall there was support for data linkage and a multi-professional approach. CONCLUSIONS: It would be acceptable to stakeholders to introduce a data linkage system for pharmacovigilance as long as identified concerns are addressed. Concerns included adherence to current professional, legal and ethical standards, as well resolving practical issues.

Core requirements for successful data linkage: an example of a triangulation method.

OBJECTIVES: The aim was to explore the views of professional stakeholders and healthcare professionals (HCPs) on the linkage of UK National Health Service (NHS) data for paediatric pharmacovigilance purposes and to make recommendations for such a system. METHODS: A mixed methods approach including a literature review, interviews, focus groups and a three-round Delphi survey with HCPs in Scotland was followed by a triangulation process using a systematic protocol. The survey was structured using the Theoretical Domains Framework of behaviour change. Items retained after applying the matrix-based triangulation process were thematically coded. Ethical approval was granted by the North of Scotland Research Ethics Service. RESULTS: Results from 18 papers, 23 interviewees, 23 participants of focus groups and 61 completed questionnaires in the Delphi survey contributed to the triangulation process. A total of 25 key findings from all four studies were identified during triangulation. There was good convergence; 21 key findings were agreed and remained to inform recommendations. The items were coded as practical/technical (eg, decision about the unique patient identifier to use), mandatory (eg, governed by statute), essential (consistently mentioned in all studies and therefore needed to ensure professional support) or preferable. CONCLUSIONS: The development of a paediatric linked database has support from professional stakeholders and HCPs in Scotland. The triangulation identified three sets of core requirements for a new system of data linkage. An additional fourth set of 'preferable' requirements might increase engagement of HCPs and their support for the new system.

Adjustable and fixed dosing with budesonide/ formoterol via a single inhaler in asthma patients: the ASSURE study.

Patient-guided management of asthma using adjustable dosing of budesonide/formoterol in a single inhaler (Symbicort) was compared with fixed dosing in an open-label, multicentre, randomised study. Patients, uncontrolled on an inhaled corticosteroid (ICS) or controlled on an ICS and a long-acting beta2-agonist, entered a 4-week run-in period and received budesonide/formoterol (80/4.5 or 160/4.5 microg), 2 inhalations b.i.d. Following randomisation, the fixed-dosing group (n = 764) continued this regimen for a further 12 weeks. The adjustable-dosing group (n = 775) could step down to 1 inhalation b.i.d. if symptoms were controlled, and, at early signs of worsening symptoms, promptly step up to 4 inhalations b.i.d. for < or = 2 weeks. During run-in, National Heart, Lung and Blood Institute symptom-severity grading was maintained in 60% and improved in 31% of patients, clinic peak flow increased from 400 to 4191/min (P<0.001), and health-related quality of life (overall MiniAQLQ) improved from 4.6 to 5.4 (P<0.001). Patients effectively used the adjustable-dosing regimen; 79% reduced budesonide/formoterol dosage and, compared with fixed dosing, the number of inhalations were significantly lowered (3.2 vs. 3.8 inhalations/day, P<0.05). Both regimens were well tolerated. In both groups, symptom control was maintained or improved in 85-86% of patients, and 94% experienced no treatment failures. Consistent with current guidelines, adjustable maintenance dosing with budesonide/formoterol in a single inhaler provides effective asthma control at reduced medication doses.

Acute renal failure: the tip of the iceberg?

This study reports the experience, during a six-year period, of the Aberdeen Renal Unit in the treatment of patients with acute renal failure. The combination of a relatively stable population base and a single regional dialysis centre has allowed the incidence of acute renal failure to be assessed. Approximately 30 patients per million population were dialysed annually for acute renal failure; 69 per cent of these patients (20.5 per million population per year) were dialysed for acute reversible intrinsic renal failure (ARIRF) and mortality in this group was 44 per cent. Patients with more severe disease at the time of presentation to the renal unit, as defined by a clinical severity score, had significantly reduced survival rates. However, it was not possible to predict the outcome in individual cases; ten of 24 patients with clinical severity scores which indicated a poor prognosis survived the period of oliguria and were discharged from hospital. The fact that other renal units dialyse fewer patients per million population per year for ARIRF probably reflects a reluctance to refer patients whose general condition appears poor. As the overall mortality rate reported in this study does not differ significantly from rates reported previously from centres treating a smaller proportion of patients, such decisions may not be correct. It is well known that facilities in Britain for treating patients with end-stage renal disease are inadequate; it now appears likely that some patients who might benefit from acute dialysis are being denied treatment for a potentially reversible disease process.

Views of healthcare professionals to linkage of routinely collected healthcare data: a systematic literature review.

OBJECTIVE: To review the literature on the views of healthcare professionals to the linkage of healthcare data and to identify any potential barriers and/or facilitators to participation in a data linkage system. METHODS: Published papers describing the views of healthcare professionals (HCPs) to data sharing and linkage were identified by searches of Medline, EMBASE, SCOPUS, CINAHL, and PsychINFO. The searches were limited to papers published in the English language from 2001 to 2011. RESULTS: A total of 2917 titles were screened. From these, 18 papers describing the views of HCPs about data linkage or data sharing of routinely collected healthcare data at an individual patient level were included. Views were generally positive, and potential benefits were reported. Facilitators included having trust in the system including data governance, reliability, and feedback. Some negative views, identified as barriers were also expressed including costs, data governance, technical issues, and privacy concerns. Effects on the physician-patient relationship, and workload were also identified as deterrent. DISCUSSION: From the published literature included in this review, the views of HCPs were in general positive towards data sharing for public health purposes. The identification of barriers to contributing to a data linkage system allows these to be addressed in a planned data linkage project for pharmacovigilance. The main barriers identified were concerns about costs, governance and interference with the prescriber-patient relationship. These would have to be addressed if healthcare professionals are to support a data linkage system to improve patient safety.

Comparing asthma treatment in elderly versus younger patients.

A randomised 6-month study compared two maintenance doses of budesonide/formoterol (Symbicort® Turbuhaler® (h) maintenance and reliever therapy (Symbicort SMART®), 160/4.5 µg 1 × 2 and 2 × 2, in 8053 asthmatics with symptoms despite treatment with inhaled corticosteroids ± inhaled long-acting ß2-agonists. This analysis compared response to the two treatments in elderly patients, ≥ 65 years, with that in younger patients. Elderly patients with early- or late-onset asthma were also compared. Elderly patients had lower post-bronchodilator FEV1 percentage predicted normal at baseline than younger patients (85.6% vs. 91.0%, respectively). The elderly had more exacerbations and risk of first severe exacerbation was increased by 55.3% (hazard ratio 1.553; 95% confidence interval: 1.249-1.931, p < 0.0001). However, no differences in exacerbations were seen between 1 × 2 or 2 × 2 budesonide/formoterol maintenance and reliever therapy treatment in the elderly. Five-item Asthma Control Questionnaire (ACQ-5) scores improved equally in the two age groups. Changes in mean ACQ-5 scores between 1 × 2 and 2 × 2 were significant in both age groups but not clinically relevant (≥ 65 years, 0.12; p = 0.018; <65 years, 0.09; p < 0.0001). Elderly patients with early- and late-onset asthma responded equally well to treatment. Budesonide/formoterol maintenance and reliever therapy (1 × 2 or 2 × 2) is an effective, well-tolerated and practical treatment concept in elderly and younger asthmatic patients.

Exacerbations of COPD: quantifying the patient's perspective using discrete choice modelling.

Patient-centred care is the current vogue in chronic obstructive pulmonary disease (COPD), but it is only recently that robust techniques have become available to determine patients' values and preferences. In this international cross-sectional study, patients' concerns and expectations regarding COPD exacerbations were explored using discrete choice modelling. A fractional factorial design was used to develop scenarios comprising a combination of levels for nine different attributes. In face-to-face interviews, patients were presented with paired scenarios and asked to choose the least preferable. Multinomial logit (with hierarchical Bayes) methods were used to estimate utilities. A total of 125 patients (82 males; mean age 66 yrs; 4.6 mean exacerbations.yr-1) were recruited. The attributes of exacerbations considered most important were impact on everyday life (20%), need for medical care (16%), number of future attacks (12%) and breathlessness (11%). The next most important attributes were speed of recovery, productive cough and social impact (all 9%), followed by sleep disturbance and impact on mood (both 7%). Importantly, analysis of utility shifts showed that patients most feared being hospitalised, housebound or bedridden. These issues were more important than symptom improvement. Strategies for the clinical management of chronic obstructive pulmonary disease should clearly address patients' concerns and focus on preventing and treating exacerbations to avoid these feared outcomes.