Annie Blyth

Leukotriene Antagonists as First-Line or Add-on Asthma-Controller Therapy

BACKGROUND Most randomized trials of treatment for asthma study highly selected patients under idealized conditions. METHODS We conducted two parallel, multicenter, pragmatic trials to evaluate the real-world effectiveness of a leukotriene-receptor antagonist (LTRA) as compared with either an inhaled glucocorticoid for first-line asthma-controller therapy or a long-acting beta(2)-agonist (LABA) as add-on therapy in patients already receiving inhaled glucocorticoid therapy. Eligible primary care patients 12 to 80 years of age had impaired asthma-related quality of life (Mini Asthma Quality of Life Questionnaire [MiniAQLQ] score ≤6) or inadequate asthma control (Asthma Control Questionnaire [ACQ] score ≥1). We randomly assigned patients to 2 years of open-label therapy, under the care of their usual physician, with LTRA (148 patients) or an inhaled glucocorticoid (158 patients) in the first-line controller therapy trial and LTRA (170 patients) or LABA (182 patients) added to an inhaled glucocorticoid in the add-on therapy trial. RESULTS Mean MiniAQLQ scores increased by 0.8 to 1.0 point over a period of 2 years in both trials. At 2 months, differences in the MiniAQLQ scores between the two treatment groups met our definition of equivalence (95% confidence interval [CI] for an adjusted mean difference, -0.3 to 0.3). At 2 years, mean MiniAQLQ scores approached equivalence, with an adjusted mean difference between treatment groups of -0.11 (95% CI, -0.35 to 0.13) in the first-line controller therapy trial and of -0.11 (95% CI, -0.32 to 0.11) in the add-on therapy trial. Exacerbation rates and ACQ scores did not differ significantly between the two groups. CONCLUSIONS Study results at 2 months suggest that LTRA was equivalent to an inhaled glucocorticoid as first-line controller therapy and to LABA as add-on therapy for diverse primary care patients. Equivalence was not proved at 2 years. The interpretation of results of pragmatic research may be limited by the crossover between treatment groups and lack of a placebo group. (Funded by the National Coordinating Centre for Health Technology Assessment U.K. and others; Controlled Clinical Trials number, ISRCTN99132811.).

A cohort study of influences, health outcomes and costs of patients’ health-seeking behaviour for minor ailments from primary and emergency care settings

Objectives To compare health-related and cost-related outcomes of consultations for symptoms suggestive of minor ailments in emergency departments (EDs), general practices and community pharmacies. Design Observational study; prospective cohort design. Setting EDs (n=2), general practices (n=6) and community pharmacies (n=10) in a mix of rural/urban and deprived/affluent areas across North East Scotland and East Anglia. Participants Adults (≥18 years) presenting between 09:00 and 18:00 (Monday–Friday) in general practices and 09:00–18:00 (Monday–Saturday) in pharmacies and EDs with ≥1 of the following: musculoskeletal pain; eye discomfort; gastrointestinal disturbance; or upper respiratory tract-related symptoms. Interventions Participants completed three questionnaires: baseline (prior to index consultation); satisfaction with index consultation and follow-up (2 weeks after index consultation). Main outcome measures Symptom resolution, quality of life, costs, satisfaction and influences on care-seeking behaviour. Results 377 patients participated, recruited from EDs (81), general practices (162) and community pharmacies (134). The 2-week response rate was 70% (264/377). Symptom resolution was similar across all three settings: ED (37.3%), general practice (35.7%) and pharmacy (44.3%). Mean overall costs per consultation were significantly lower for pharmacy (£29.30 (95% CI £21.60 to £37.00)) compared with general practice (£82.34 (95% CI £63.10 to £101.58)) and ED (£147.09 (95% CI £125.32 to £168.85)). Satisfaction varied across settings and by measure used. Compared with pharmacy and general practice use, ED use was significantly (p<0.001) associated with first episode and short duration of symptom(s), as well as higher levels of perceived seriousness and urgency for seeking care. Convenience of location was the most common reason for choice of consultation setting. Conclusions These results suggest similar health-related outcomes and substantially lower costs with pharmacy consultations for minor ailments. Effective strategies are now needed to shift demand for minor ailment management away from EDs and general practices to the community pharmacy setting.

Postpartum smoking relapse--a thematic synthesis of qualitative studies.

BACKGROUND AND AIMS Many women quit smoking during pregnancy, but relapse after the baby is born. To understand why and identify ways of preventing this, this study reviewed the qualitative literature on womens experience of postpartum smoking relapse. METHODS A systematic review of qualitative studies and process evaluations of trials. We undertook a thematic synthesis of published qualitative data. RESULTS We screened 1336 papers. Twenty-two papers reporting on 16 studies were included, reporting on the views of 1031 postpartum women. Factors affecting relapse and barriers and facilitators to relapse prevention were identified around the key themes of beliefs, social influences, motivation, physiological factors and identity. Womens beliefs about smoking as a means of coping with stress and the need for social support, especially from a partner, emerged as important. Extrinsic motivation to quit during the pregnancy (for the health of the fetus) appeared to be a factor in prompting relapse after the baby was born. During the immediate postpartum period women believed that physiological changes influence cigarette cravings. The stress of caring for a newborn, sleeplessness and adjusting to a new mothering identity were also reported to be important. CONCLUSIONS Among women who quit smoking during pregnancy, those who relapse postpartum talk commonly about no longer needing to protect the baby and the effects of stress. Partner support and a sense of changed identity are cited as factors preventing relapse.

Estimating the burden of minor ailment consultations in general practices and emergency departments through retrospective review of routine data in North East Scotland

Background. Minor ailment attendances in general practices and emergency departments (EDs) place significant burden on health care resources. Objectives. To estimate the prevalence and type of minor ailment consultations for adults in general practice and ED that could be managed in a community pharmacy. Methods. Retrospective review of routine data from general practices (n = 2) and one ED in North East Scotland. Two independent consensus panels assessed each consultation summary to determine whether it represented a minor ailment. Outcomes included prevalence of consultations for minor ailments in general practice and ED and frequency of different minor ailment type that could be managed in community pharmacies. Results. In total, of the 494 general practice and 550 ED consultations assessed, 13.2% [95% confidence interval (CI): 18.6–25.9%] and 5.3% (95% CI: 4.0–8.0%), respectively, were categorized as minor ailments suitable for management in community pharmacies. Consensus among panel members was moderate for general practice consultations, but fair to poor for ED consultations. Agreement between uni- and multi-disciplinary panels was good. Applied to national data, these estimates would equate to ~18 million general practice and 6500000 ED consultations that could be redirected to community pharmacy, equating to ~£1.1 billion in resources. Conclusion. Minor ailment consultations still present a major burden on higher cost settings. Effective strategies are needed to raise awareness among patients and health professionals regarding conditions that can be managed effectively in pharmacies and to change patient health-seeking behaviour for such conditions.

A randomised controlled equivalence trial to determine the effectiveness and cost-utility of manual chest physiotherapy techniques in the management of exacerbations of chronic obstructive pulmonary disease (MATREX).

OBJECTIVES To estimate the effect, if any, of manual chest physiotherapy (MCP) administered to patients hospitalised with chronic obstructive pulmonary disease (COPD) exacerbation on both disease-specific and generic health-related quality of life. To compare the health service costs for those receiving and not receiving MCP. DESIGN A pragmatic, randomised controlled trial powered for equivalence. It was not possible to blind participants, clinicians or research staff to study arm allocation during the intervention. SETTING Four UK hospitals in Norwich, Great Yarmouth, Kings Lynn and Liverpool. PARTICIPANTS 526 participants aged 34-91 years were recruited between November 2005 and April 2008; of these, 372 provided evaluable data for the primary outcome. All persons hospitalised with COPD exacerbation and evidence of sputum production on examination were eligible for the trial providing there were no contraindications to performing MCP. INTERVENTIONS Participants were allocated to either MCP or no MCP on an intention-to-treat (ITT) basis. However, active cycle of breathing techniques (ACBT) was used in both arms. Participants allocated to the intervention were guided to perform ACBT while the physiotherapist delivered MCP. Participants allocated to the control arm received instruction on ACBT only. MAIN OUTCOME MEASURES The primary outcome was COPD-specific quality of life, measured using the St Georges Respiratory Questionnaire (SGRQ) at 6 months post randomisation. The European Quality of Life-5 Dimensions (EQ-5D) questionnaire was used to calculate the quality-adjusted life-year (QALY) gain associated with MCP compared with no MCP. Secondary physiological outcome measures were also used. RESULTS Of the 526 participants, 261 were allocated to MCP and 264 to control, with 186 participants evaluable in each arm. ITT analyses indicated no significant difference at 6 months post randomisation in total SGRQ score [adjusted effect size (no MCP - MCP) 0.03 (95% confidence interval, CI -0.14 to 0.19)], SGRQ symptom score [adjusted effect size 0.04 (95% CI -0.15 to 0.23)], SGRQ activity score [adjusted effect size -0.02 (95% CI -0.20 to 0.16)] or SGRQ impact score [adjusted effect size 0.02 (95% CI -0.15 to 0.18)]. The imputed ITT and per-protocol results were similar. No significant differences were observed in any of the outcome measures or subgroup analyses. Compared with no MCP, employing MCP was associated with a slight loss in quality of life (0.001 QALY loss) but lower health service costs (cost saving of 410.79 pounds). Based on these estimates, at a cost-effectiveness threshold of lambda = 20,000 pounds per QALY, MCP would constitute a cost-effective use of resources (net benefit = 376.14 pounds). There was, however, a high level of uncertainty associated with these results and it is possible that the lower health service costs could have been due to other factors. CONCLUSIONS In terms of longer-term quality of life the use of MCP did not appear to affect outcome. However, this does not mean that MCP is of no therapeutic value to patients with COPD in specific circumstances. Although the cost-effectiveness analysis suggested that its use was cost-effective, much uncertainty was associated with this finding and it would be difficult to justify providing MCP therapy on the basis of cost-effectiveness alone. Future research should include evaluation of MCP for patients with COPD producing high volumes of sputum, and an evaluation of the effectiveness of ACBT in COPD exacerbation. TRIAL REGISTRATION Current Controlled Trials ISRCTN13825248.

A pragmatic single-blind randomised controlled trial and economic evaluation of the use of leukotriene receptor antagonists in primary care at steps 2 and 3 of the national asthma guidelines (ELEVATE study).

This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 15, No. 21. See the HTA programme website for further project information.

Cost effectiveness of leukotriene receptor antagonists versus long-acting beta-2 agonists as add-on therapy to inhaled corticosteroids for asthma: a pragmatic trial

BACKGROUND Information is lacking on the relative effectiveness and cost effectiveness--in a primary-care setting--of leukotriene receptor antagonists (LTRAs) as an alternative to inhaled corticosteroids (ICS) for initial asthma controller therapy. OBJECTIVE To compare the cost effectiveness of LTRAs versus ICS for patients initiating asthma controller therapy. METHODS An economic evaluation was conducted alongside a 2-year, pragmatic, randomized controlled trial set in 53 primary-care practices in the UK. Patients aged 12-80 years with asthma and symptoms requiring regular anti-inflammatory therapy (n = 326) were randomly assigned to LTRAs (n = 162) or ICS (n = 164). The main outcome measures were the incremental costs per point improvement in the Mini Asthma Quality of Life Questionnaire, per point improvement in the Asthma Control Questionnaire and per QALY gained from the UK NHS and societal perspectives. RESULTS Over 2 years, resource use was similar between the two treatment groups, but the cost to society per patient was significantly higher for the LTRA group, at pounds sterling 711 versus pounds sterling 433 for the ICS group (adjusted difference pounds sterling 204; 95% CI 74, 308) [year 2005 values]. Cost differences were driven primarily by differences in prescription drug costs, particularly study drug costs. There was a nonsignificant (imputed, adjusted) difference between treatment groups, favouring ICS, in QALYs gained at 2 years of -0.073 (95% CI -0.143, 0.010). Therapy with LTRAs was, on average, a dominated strategy, and, at a threshold for willingness to pay of pounds sterling 30,000 per QALY gained, the probability of LTRAs being cost effective compared with ICS was approximately 3% from both societal and NHS perspectives. CONCLUSIONS There is a very low probability of LTRAs being cost effective in the UK, at 2005 values, compared with ICS for initial asthma controller therapy. TRIAL REGISTRATION UK National Research Register N0547145240; Controlled Clinical Trials ISRCTN99132811.Background: Information is lacking on the relative effectiveness and cost effectiveness — in a real-life primary-care setting — of leukotriene receptor antagonists (LTRAs) and long-acting β2 adrenergic receptor agonists (β2 agonists) as add-on therapy for patients whose asthma symptoms are not controlled on low-dose inhaled corticosteroids (ICS).Objective: To estimate the cost effectiveness of LTRAs compared with longacting β2 agonists as add-on therapy for patients whose asthma symptoms are not controlled on low-dose ICS.Methods: An economic evaluation was conducted alongside a 2-year, pragmatic, randomized controlled trial set in 53 primary-care practices in the UK. Patients aged 1280 years with asthma insufficiently controlled with ICS (n = 361) were randomly assigned to add-on LTRAs (n = 176) or long-acting β2 agonists (n = 185). The main outcome measures were the incremental cost per point improvement in the Mini Asthma Quality of Life Questionnaire (MiniAQLQ), per point improvement in the Asthma Control Questionnaire (ACQ) and per QALY gained from perspectives of the UK NHS and society.Results: Over 2 years, the societal cost per patient receiving LTRAs was £1157 versus £952 for long-acting b2 agonists, a (significant, adjusted) increase of d214 (95%CI 2, 411) [year 2005 values]. Patients receiving LTRAs experienced a non-significant incremental gain of 0.009 QALYs (95% CI −0.077, 0.103). The incremental cost per QALY gained from the societal (NHS) perspective was £22 589 (£11 919). Uncertainty around this point estimate suggested that, given a maximum willingness to pay of £30 000 per QALY gained, the probability that LTRAs are a cost-effective alternative to long-acting β2 agonists as add-on therapy was approximately 52% from both societal and NHS perspectives.Conclusions: On balance, these results marginally favour the repositioning of LTRAs as a cost-effective alternative to long-acting β2 agonists as add-on therapy to ICS for asthma. However, there is much uncertainty surrounding the incremental cost effectiveness because of similarity of clinical benefit and broad confidence intervals for differences in healthcare costs.Trial registration: UK National Research Register N0547145240; Controlled Clinical Trials ISRCTN99132811.

Cost Effectiveness of Leukotriene Receptor Antagonists versus Inhaled Corticosteroids for Initial Asthma Controller Therapy A Pragmatic Trial

BACKGROUND Information is lacking on the relative effectiveness and cost effectiveness--in a primary-care setting--of leukotriene receptor antagonists (LTRAs) as an alternative to inhaled corticosteroids (ICS) for initial asthma controller therapy. OBJECTIVE To compare the cost effectiveness of LTRAs versus ICS for patients initiating asthma controller therapy. METHODS An economic evaluation was conducted alongside a 2-year, pragmatic, randomized controlled trial set in 53 primary-care practices in the UK. Patients aged 12-80 years with asthma and symptoms requiring regular anti-inflammatory therapy (n = 326) were randomly assigned to LTRAs (n = 162) or ICS (n = 164). The main outcome measures were the incremental costs per point improvement in the Mini Asthma Quality of Life Questionnaire, per point improvement in the Asthma Control Questionnaire and per QALY gained from the UK NHS and societal perspectives. RESULTS Over 2 years, resource use was similar between the two treatment groups, but the cost to society per patient was significantly higher for the LTRA group, at pounds sterling 711 versus pounds sterling 433 for the ICS group (adjusted difference pounds sterling 204; 95% CI 74, 308) [year 2005 values]. Cost differences were driven primarily by differences in prescription drug costs, particularly study drug costs. There was a nonsignificant (imputed, adjusted) difference between treatment groups, favouring ICS, in QALYs gained at 2 years of -0.073 (95% CI -0.143, 0.010). Therapy with LTRAs was, on average, a dominated strategy, and, at a threshold for willingness to pay of pounds sterling 30,000 per QALY gained, the probability of LTRAs being cost effective compared with ICS was approximately 3% from both societal and NHS perspectives. CONCLUSIONS There is a very low probability of LTRAs being cost effective in the UK, at 2005 values, compared with ICS for initial asthma controller therapy. TRIAL REGISTRATION UK National Research Register N0547145240; Controlled Clinical Trials ISRCTN99132811.Background: Information is lacking on the relative effectiveness and cost effectiveness — in a real-life primary-care setting — of leukotriene receptor antagonists (LTRAs) and long-acting β2 adrenergic receptor agonists (β2 agonists) as add-on therapy for patients whose asthma symptoms are not controlled on low-dose inhaled corticosteroids (ICS).Objective: To estimate the cost effectiveness of LTRAs compared with longacting β2 agonists as add-on therapy for patients whose asthma symptoms are not controlled on low-dose ICS.Methods: An economic evaluation was conducted alongside a 2-year, pragmatic, randomized controlled trial set in 53 primary-care practices in the UK. Patients aged 1280 years with asthma insufficiently controlled with ICS (n = 361) were randomly assigned to add-on LTRAs (n = 176) or long-acting β2 agonists (n = 185). The main outcome measures were the incremental cost per point improvement in the Mini Asthma Quality of Life Questionnaire (MiniAQLQ), per point improvement in the Asthma Control Questionnaire (ACQ) and per QALY gained from perspectives of the UK NHS and society.Results: Over 2 years, the societal cost per patient receiving LTRAs was £1157 versus £952 for long-acting b2 agonists, a (significant, adjusted) increase of d214 (95%CI 2, 411) [year 2005 values]. Patients receiving LTRAs experienced a non-significant incremental gain of 0.009 QALYs (95% CI −0.077, 0.103). The incremental cost per QALY gained from the societal (NHS) perspective was £22 589 (£11 919). Uncertainty around this point estimate suggested that, given a maximum willingness to pay of £30 000 per QALY gained, the probability that LTRAs are a cost-effective alternative to long-acting β2 agonists as add-on therapy was approximately 52% from both societal and NHS perspectives.Conclusions: On balance, these results marginally favour the repositioning of LTRAs as a cost-effective alternative to long-acting β2 agonists as add-on therapy to ICS for asthma. However, there is much uncertainty surrounding the incremental cost effectiveness because of similarity of clinical benefit and broad confidence intervals for differences in healthcare costs.Trial registration: UK National Research Register N0547145240; Controlled Clinical Trials ISRCTN99132811.

Patients’ perceptions of physical activity before and after joint replacement: a systematic review with meta-ethnographic analysis

Background It has been perceived that people following total hip arthroplasty (THA) or total knee arthroplasty (TKA) have the capability, with reduced pain, to increase their levels of physical activity. Objectives To determine the attitudes and perceptions of people awaiting or having undergone THA or TKA to physical activity post-arthroplasty and to identify potential facilitators or barriers to engage in active living and physical activity pursuits. Methods Systematic review of published and unpublished databases was undertaken from their inception to November 2014. Studies exploring the attitudes and perceptions of people awaiting or having undergone THA or TKA to physical activity post-arthroplasty were included. Data were analysed through a meta-ethnography approach. Results From 528 citations, 13 papers were eligible, sampling 282 people post-THA or TKA. The literature was judged moderate to high quality. Following THA and TKA, people either wished to return to their pre-pathology level of physical activity or simply be able to engage in less physically demanding activities that are meaningful to them and their lifestyles. Barriers to engaging in higher levels of physical activity were largely related to limited information, which culminated in fear surrounding ‘doing the right thing’ both for individuals recovery and the longevity of the joint replacement. Conclusions While many people post-THA or TKA wish to return to pre-pathological physical activity status, there is limited interest in actually undertaking greater levels of physical activity post-arthroplasty either for pleasure or health gains. Improvement in education and awareness of this may be key drivers to improve habitualisation of physical activity post-arthroplasty. Trial registration number CRD42014014995.

Evaluation of the effectiveness of manual chest physiotherapy techniques on quality of life at six months post exacerbation of COPD (MATREX): a randomised controlled equivalence trial

BackgroundManual chest physiotherapy (MCP) techniques involving chest percussion, vibration, and shaking have long been used in the treatment of respiratory conditions. However, methodological limitations in existing research have led to a state of clinical equipoise with respect to this treatment. Thus, for patients hospitalised with an exacerbation of Chronic Obstructive Pulmonary Disease (COPD), clinical preference tends to dictate whether MCP is given to assist with sputum clearance. We standardised the delivery of MCP and assessed its effectiveness on disease-specific quality of life.MethodsIn this randomised, controlled trial powered for equivalence, 526 patients hospitalised with acute COPD exacerbation were enrolled from four centres in the UK. Patients were allocated to receive MCP plus advice on airway clearance or advice on chest clearance alone. The primary outcome was a COPD specific quality of life measure, the Saint Georges Respiratory Questionnaire (SGRQ) at six months post randomisation. Analyses were by intention to treat (ITT). This study was registered, ISRCTN13825248.ResultsAll patients were included in the analyses, of which 372 (71%) provided evaluable data for the primary outcome. An effect size of 0·3 standard deviations in SGRQ score was specified as the threshold for superiority. The ITT analyses showed no significant difference in SGRQ for patients who did, or did not receive MCP (95% CI −0·14 to 0·19).ConclusionsThese data do not lend support to the routine use of MCP in the management of acute exacerbation of COPD. However, this does not mean that MCP is of no therapeutic value to COPD patients in specific circumstances.