Genetic‐guided pharmacotherapy for coronary artery disease: a systematic and critical review of economic evaluations

Background: Genetic‐guided pharmacotherapy (PGx) is not recommended in clinical guidelines for coronary artery disease (CAD). We aimed to examine the extent and quality of evidence from economic evaluations of PGx in CAD and to identify variables influential in changing conclusions on cost‐effectiveness. Methods and Results: From systematic searches across 6 databases, 2 independent reviewers screened, included, and rated the methodological quality of economic evaluations of PGx testing to guide pharmacotherapy for patients with CAD. Of 35 economic evaluations included, most were model‐based cost‐utility analyses alone, or alongside cost‐effectiveness analyses of PGx testing to stratify patients into antiplatelets (25/35), statins (2/35), pain killers (1/35), or angiotensin‐converting enzyme inhibitors (1/35) to predict CAD risk (8/35) or to determine the coumadin doses (1/35). To stratify patients into antiplatelets (96/151 comparisons with complete findings of PGx versus non‐PGx), PGx was more effective and more costly than non‐PGx clopidogrel (28/43) but less costly than non‐PGx prasugrel (10/15) and less costly and less effective than non‐PGx ticagrelor (22/25). To predict CAD risk (51/151 comparisons), PGx using genetic risk scores was more effective and less costly than clinical risk score (13/17) but more costly than no risk score (16/19) or no treatment (9/9). The remaining comparisons were too few to observe any trend. Mortality risk was the most common variable (47/294) changing conclusions. Conclusions: Economic evaluations to date found PGx to stratify patients with CAD into antiplatelets or to predict CAD risk to be cost‐effective, but findings varied based on the non‐PGx comparators, underscoring the importance of considering local practice in deciding whether to adopt PGx

The demand for sports and exercise: Results from an illustrative survey

Funding from the Department of Health policy research programme was used in this study.There is a paucity of empirical evidence on the extent to which price and perceived benefits affect the level of participation in sports and exercise. Using an illustrative sample of 60 adults at Brunel University, West London, we investigate the determinants of demand for sports and exercise. The data were collected through face-to-face interviews that covered indicators of sports and exercise behaviour; money/time price and perceived benefits of participation; and socio- economic/demographic details. Count, linear and probit regression models were fitted as appropriate. Seventy eight per cent of the sample participated in sports and exercise and spent an average of £27 per month and an average of 20 min travelling per occasion of sports and exercise. The demand for sport and exercise was negatively associated with time (travel or access time) and ‘variable’ price and positively correlated with ‘fixed’ price. Demand was price inelastic, except in the case of meeting the UK government’s recommended level of participation, which is time price elastic (elasticity = −2.2). The implications of data from a larger nationally representative sample as well as the role of economic incentives in influencing uptake of sports and exercise are discussed.This article is available through the Brunel Open Access Publishing Fund

A crossover randomised controlled trial of oral mandibular advancement devices for obstructive sleep apnoea-hypopnoea (TOMADO)

Rationale Mandibular advancement devices (MADs) are used to treat obstructive sleep apnoea-hypopnoea syndrome (OSAHS) but evidence is lacking regarding their clinical and cost-effectiveness in less severe disease. Objectives To compare clinical- and cost-effectiveness of a range of MADs against no treatment in mild to moderate OSAHS. Measurements and methods This open-label, randomised, controlled, crossover trial was undertaken at a UK sleep centre. Adults with Apnoea-Hypopnoea Index (AHI) 5–<30/h and Epworth Sleepiness Scale (ESS) score ≥9 underwent 6 weeks of treatment with three nonadjustable MADs: self-moulded (SleepPro 1; SP1); semi-bespoke (SleepPro 2; SP2); fully-bespoke MAD (bMAD); and 4 weeks no treatment. Primary outcome was AHI scored by a polysomnographer blinded to treatment. Secondary outcomes included ESS, quality of life, resource use and cost. Main results 90 patients were randomised and 83 were analysed. All devices reduced AHI compared with no treatment by 26% (95% CI 11% to 38%, p=0.001) for SP1, 33% (95% CI 24% to 41%) for SP2 and 36% (95% CI 24% to 45%, p<0.001) for bMAD. ESS was 1.51 (95% CI 0.73 to 2.29, p<0.001, SP1) to 2.37 (95% CI 1.53 to 3.22, p<0.001, bMAD) lower than no treatment (p<0.001 for all). Compliance was lower for SP1, which was the least preferred treatment at trial exit. All devices were cost-effective compared with no treatment at a £20 000/quality-adjusted life year (QALY) threshold. SP2 was the most cost-effective up to £39 800/QALY. Conclusions Non-adjustable MADs achieve clinically important improvements in mild to moderate OSAHS and are cost-effective

The costs of preventing and treating chagas disease in Colombia

Background: The objective of this study is to report the costs of Chagas disease in Colombia, in terms of vector disease control programmes and the costs of providing care to chronic Chagas disease patients with cardiomyopathy. Methods: Data were collected from Colombia in 2004. A retrospective review of costs for vector control programmes carried out in rural areas included 3,084 houses surveyed for infestation with triatomine bugs and 3,305 houses sprayed with insecticide. A total of 63 patient records from 3 different hospitals were selected for a retrospective review of resource use. Consensus methodology with local experts was used to estimate care seeking behaviour and to complement observed data on utilisation. Findings: The mean cost per house per entomological survey was $4.4 (in US$ of 2004), whereas the mean cost of spraying a house with insecticide was $27. The main cost driver of spraying was the price of the insecticide, which varied greatly. Treatment of a chronic Chagas disease patient costs between$46.4 and $7,981 per year in Colombia, depending on severity and the level of care used. Combining cost and utilisation estimates the expected cost of treatment per patient-year is$1,028, whereas lifetime costs averaged $11,619 per patient. Chronic Chagas disease patients have limited access to healthcare, with an estimated 22% of patients never seeking care. Conclusion: Chagas disease is a preventable condition that affects mostly poor populations living in rural areas. The mean costs of surveying houses for infestation and spraying infested houses were low in comparison to other studies and in line with treatment costs. Care seeking behaviour and the type of insurance affiliation seem to play a role in the facilities and type of care that patients use, thus raising concerns about equitable access to care. Preventing Chagas disease in Colombia would be cost-effective and could contribute to prevent inequalities in health and healthcare.Wellcome Trus

MesoTRAP: a feasibility study that includes a pilot clinical trial comparing video-assisted thoracoscopic partial pleurectomy decortication with indwelling pleural catheter in patients with trapped lung due to malignant pleural mesothelioma designed to address recruitment and randomisation uncertainties and sample size requirements for a phase III trial.

Introduction: One of the most debilitating symptoms of malignant pleural mesothelioma (MPM) is dyspnoea caused by pleural effusion. MPM can be complicated by the presence of tumour on the visceral pleura preventing the lung from re-expanding, known as trapped lung (TL). There is currently no consensus on the best way to manage TL. One approach is insertion of an indwelling pleural catheter (IPC) under local anaesthesia. Another is video-assisted thoracoscopic partial pleurectomy/decortication (VAT-PD). Performed under general anaesthesia, VAT-PD permits surgical removal of the rind of tumour from the visceral pleura thereby allowing the lung to fully re-expand. Methods and analysis: MesoTRAP is a feasibility study that includes a pilot multicentre, randomised controlled clinical trial comparing VAT-PD with IPC in patients with TL and pleural effusion due to MPM. The primary objective is to measure the SD of visual analogue scale scores for dyspnoea following randomisation and examine the patterns of change over time in each treatment group. Secondary objectives include documenting survival and adverse events, estimating the incidence and prevalence of TL in patients with MPM, examining completion of alternative forms of data capture for economic evaluation and determining the ability to randomise 38 patients in 18 months. Ethics and dissemination: This study was approved by the East of England-Cambridge Central Research Ethics Committee and the Health Research Authority (reference number 16/EE/0370). We aim to publish the outputs of this work in international peer-reviewed journals compliant with an Open Access policy. Trial registration: NCT03412357

The cost of changing physical activity behaviour: Evidence from a "physical activity pathway" in the primary care setting

Copyright @ 2011 Boehler et al.BACKGROUND: The ‘Physical Activity Care Pathway’ (a Pilot for the ‘Let’s Get Moving’ policy) is a systematic approach to integrating physical activity promotion into the primary care setting. It combines several methods reported to support behavioural change, including brief interventions, motivational interviewing, goal setting, providing written resources, and follow-up support. This paper compares costs falling on the UK National Health Service (NHS) of implementing the care pathway using two different recruitment strategies and provides initial insights into the cost of changing physical activity behaviour. METHODS: A combination of a time driven variant of activity based costing, audit data through EMIS and a survey of practice managers provided patient-level cost data for 411 screened individuals. Self reported physical activity data of 70 people completing the care pathway at three month was compared with baseline using a regression based ‘difference in differences’ approach. Deterministic and probabilistic sensitivity analyses in combination with hypothesis testing were used to judge how robust findings are to key assumptions and to assess the uncertainty around estimates of the cost of changing physical activity behaviour. RESULTS: It cost £53 (SD 7.8) per patient completing the PACP in opportunistic centres and £191 (SD 39) at disease register sites. The completer rate was higher in disease register centres (27.3% vs. 16.2%) and the difference in differences in time spent on physical activity was 81.32 (SE 17.16) minutes/week in patients completing the PACP; so that the incremental cost of converting one sedentary adult to an ‘active state’ of 150 minutes of moderate intensity physical activity per week amounts to £ 886.50 in disease register practices, compared to opportunistic screening. CONCLUSIONS: Disease register screening is more costly than opportunistic patient recruitment. However, additional costs come with a higher completion rate and better outcomes in terms of behavioural change in patients completing the care pathway. Further research is needed to rigorously evaluate intervention efficiency and to assess the link between behavioural change and changes in quality adjusted life years (QALYs).This article is available through the Brunel Open Access Publishing Fund

National surveillance data analysis of COVID-19 vaccine uptake in England by women of reproductive age

Women of reproductive age are a group of particular concern with regards to vaccine uptake, related to their unique considerations of menstruation, fertility, and pregnancy. To obtain vaccine uptake data specific to this group, we obtained vaccine surveillance data from the Office for National Statistics, linked with COVID-19 vaccination status from the National Immunisation Management Service, England, from 8 Dec 2020 to 15 Feb 2021; data from 13,128,525 such women at population-level, were clustered by age (18–29, 30–39, and 40–49 years), self-defined ethnicity (19 UK government categories), and index of multiple deprivation (IMD, geographically-defined IMD quintiles). Here we show that among women of reproductive age, older age, White ethnicity and being in the least-deprived index of multiple deprivation are each independently associated with higher vaccine uptake, for first and second doses; however, ethnicity exerts the strongest influence (and IMD the weakest). These findings should inform future vaccination public messaging and policy

Numbers are not the whole story: a qualitative exploration of barriers and facilitators to increased physical activity in a primary care based walking intervention.

BACKGROUND: The majority of mid-life and older adults in the UK are not achieving recommended physical activity levels and inactivity is associated with many health problems. Walking is a safe, appropriate exercise. The PACE-UP trial sought to increase walking through the structured use of a pedometer and handbook, with and without support from a practice nurse trained in behaviour change techniques (BCTs). Understanding barriers and facilitators to engagement with a primary care based physical activity intervention is essential for future trials and programmes. METHODS: We conducted semi-structured telephone interviews using a topic guide with purposive samples of participants who did and did not increase their walking from both intervention groups. Interviews were audio-recorded, transcribed and coded independently by researchers prior to performing a thematic analysis. Responsiveness to the specific BCTs used was also analysed. RESULTS: Forty-three trial participants were interviewed in early 2014. Almost all felt they had benefitted, irrespective of their change in step-count, and that primary care was an appropriate setting.Important facilitators included a desire for a healthy lifestyle, improved physical health, enjoyment of walking in the local environment, having a flexible routine allowing for an increase in walking, appropriate self and external monitoring and support from others.Important barriers included physical health problems, an inflexible routine, work and other commitments, the weather and a mistrust of the monitoring equipment.BCTs that were reported to have the most impact included: providing information about behaviour-health link; prompting self-monitoring and review of goals and outcomes; providing feedback; providing specific information about how to increase walking; planning social support/change; and relapse prevention. Rewards were unhelpful. CONCLUSIONS: Despite our expectation that there would be a difference between the experiences of those who did and did not objectively increase their walking, we found that most participants considered themselves to have succeeded in the trial and benefitted from taking part. Barriers and facilitators were similar across demographic groups and trial outcomes. Findings indicated several BCTs on which PA trial and programme planners could focus efforts with the expectation of greatest impact as well as strong support for primary care as an appropriate venue

Amaze: a randomized controlled trial of adjunct surgery for atrial fibrillation

OBJECTIVES: Atrial fibrillation (AF) reduces survival and quality of life (QoL). It can be treated at the time of major cardiac surgery using ablation procedures ranging from simple pulmonary vein isolation to a full maze procedure. The aim of this study is to evaluate the impact of adjunct AF surgery as currently performed on sinus rhythm (SR) restoration, survival, QoL and costeffectiveness. METHODS: In a multicentre, Phase III, pragmatic, double-blinded, parallel-armed randomized controlled trial, 352 cardiac surgery patients with >3 months of documented AF were randomized to surgery with or without adjunct maze or similar AF ablation between 2009 and 2014. Primary outcomes were SR restoration at 1 year and quality-adjusted life years at 2 years. Secondary outcomes included SR at 2 years, overall and stroke-free survival, medication, QoL, cost-effectiveness and safety. RESULTS: More ablation patients were in SR at 1 year [odds ratio (OR) 2.06, 95% confidence interval (CI) 1.20–3.54; P = 0.009]. At 2 years, the OR increased to 3.24 (95% CI 1.76–5.96). Quality-adjusted life years were similar at 2 years (ablation - control -0.025, P = 0.6319). Significantly fewer ablation patients were anticoagulated from 6 months postoperatively. Stroke rates were 5.7% (ablation) and 9.1% (control) (P = 0.3083). There was no significant difference in stroke-free survival [hazard ratio (HR) = 0.99, 95% CI 0.64–1.53; P = 0.949] nor in serious adverse events, operative or overall survival, cardioversion, pacemaker implantation, New York Heart Association, EQ-5D-3L and SF-36. The mean additional ablation cost per patient was £3533 (95% CI £1321–£5746). Cost-effectiveness was not demonstrated at 2 years. CONCLUSIONS: Adjunct AF surgery is safe and increases SR restoration and costs but not survival or QoL up to 2 years. A continued follow-up will provide information on these outcomes in the longer term

"It's not just about walking.....it's the practice nurse that makes it work": a qualitative exploration of the views of practice nurses delivering complex physical activity interventions in primary care

Background: Physical activity (PA) is important for physical and mental health in adults and older adults. Interventions incorporating theory-based behaviour change techniques (BCTs) can be useful in helping people to increase their PA levels and can be delivered by practice nurses in primary care. We undertook two primary care based complex walking interventions among adults and older adults. Both interventions were underpinned by BCTs and delivered by practice nurses and we sought their views and experiences of delivering over 1400 complex PA consultations. Methods: Semi structured interviews with two practice nurse groups (n = 4 and n = 5) and two individual interviews (total n = 11) were conducted by independent facilitators; audio-recorded, transcribed verbatim and analysed using thematic analysis. Results: Five key themes emerged as enablers and/or barriers to delivering the intervention: preparation and training; initial and ongoing support; adherence to the protocol; the use of materials and equipment; and engagement of participants. The themes were organised into a framework of ‘pre-trial’ and ‘delivery of the intervention’. Two additional ‘post-trial’ themes were identified; changed practice and the future feasibility of the intervention. Nurses believed that taking part in the trial, especially the BCT training, enhanced the quality and delivery of advice and support they provided within routine consultations, although the lack of time available routinely makes this challenging. Conclusion: Delivering an effective behaviour change intervention in primary care requires adequate training and support for practice nurses both initially and throughout the trial as well as adequate consultation time. Enhanced skills from participating in such trials can lead to long-term changes, including more patient-centred consulting. Trial registration: PACE-Lift ISRCTN 42122561, PACE-UP ISRCTN 98538934.The National Institute for Health Research (NIHR) through the Research for Patient Benefit Programme (RFPB) (PB-PG-0909- 20055) (PACE-Lift trial) and the Health Technology Assessment (HTA) Programme (10-32-02) (PACE-UP trial)