Using affective judgement to increase physical activity in British adults.

Mobile phone apps have been shown to increase physical activity (PA), but existing apps fail to target the emotional aspects of PA, which influence whether individuals are active. We developed an app that encourages individuals to focus on the emotional aspects of PA. We aimed to assess the acceptability of this app, and conduct a preliminary evaluation of efficacy. The app was developed in collaboration with users through focus groups. Seven users tested the app over 4 months and provided feedback on acceptability, aesthetics and functionality in a follow-up focus group. Results were summarized descriptively. Before testing the app, participants completed a questionnaire assessing their current PA and psychological antecedents of PA. A second questionnaire was completed at the follow-up focus group. Change scores are reported for each participant and overall.The social and reminder aspects facilitated motivation to be active and many found it easy to integrate into their lives. Most suggested modifications. Small improvements in number of minutes spent walking per week were observed (overall mean change +25 min) and some psychological antecedents of PA (overall mean change for social support for PA +0.14, self-efficacy for PA +0.17, outcome expectations about PA +0.20; all five-point scales), but reductions were seen in other domains. The app was acceptable to users, although developments are required. Testing with a small number of individuals, offering preliminary evidence of efficacy of this app, provides justification for further evaluation on a larger scale.

A model for measuring the health burden of classic congenital adrenal hyperplasia in adults.

AIM: Patients with classic congenital adrenal hyperplasia (CAH) have poor health outcomes. In the absence of a comprehensive observational study, this manuscript provides a model to estimate the lifetime disease burden of adults with classic CAH. METHODS: The model, built in Excel, comprises subdomains addressing the health consequences of CAH and synthesises evidence from clinical and epidemiological studies on health outcomes. RESULTS: The model estimates that adults with classic CAH will implement 'sick day rules' (doubling or tripling glucocorticoid and/or use of parenteral therapy) 171 times over their lifetime and attend hospital for adrenal crisis on 11 occasions. In a population of 1000, over 200 will die of a condition complicated by adrenal crisis resulting, on average, in a loss of 7 years of life. Patients with CAH may also suffer from excess CVD events. Treatment with glucocorticoids almost doubles the risk of bone fractures in patients with CAH compared to the general population, leading on average to an additional 0·8 fractures per patient with CAH over their lifetime. CONCLUSIONS: The disease burden model highlights gaps in evidence, particularly regarding intensity of care and adrenal crisis, and the relationship between control of CAH and risks of CVD, osteoporosis, diabetes and infertility. The model can be used for research on the impact of new clinical pathways and therapeutic interventions in terms of clinical events and cost.

Comparative efficacy of advanced treatments in biologic-naïve or biologic-experienced patients with ulcerative colitis: a systematic review and network meta-analysis.

BACKGROUND: Only one head-to-head comparison of advanced treatments in moderately to severely active ulcerative colitis (UC) has been published; therefore, there remains a need for further comparisons. AIM: The relative treatment effects of filgotinib and adalimumab, golimumab, infliximab, tofacitinib, ustekinumab and vedolizumab were estimated using a network meta-analysis (NMA). METHOD: Systematically identified studies (MEDLINE, Embase and Cochrane Library; searched: inception-May 2019, updated November 2020) investigating treatments for moderately to severely active UC were re-evaluated for inclusion in a Bayesian NMA (fixed-effects model). Relative treatment effects were estimated using different permutations of patient population (biologic-naïve or biologic-experienced), treatment phase (induction or maintenance) and outcomes (MCS response/remission or endoscopic mucosal healing). RESULTS: Seventeen trials (13 induction; 9 maintenance) were included in the NMA; 8 treatment networks were constructed. Most targeted therapies were superior to placebo in terms of MCS response/remission and endoscopic mucosal healing; filgotinib 200 mg was similar to most other treatments. Infliximab 5 mg/kg was superior to filgotinib 200 mg (biologic-naïve; induction) for MCS response/remission (mean relative effect, 0.34 [95% credible interval: 0.05, 0.62]). Filgotinib 200 mg was superior to adalimumab 160/80/40 mg for MCS response/remission (biologic-experienced; induction; - 0.75 [- 1.16, - 0.35]), and endoscopic mucosal healing (biologic-naïve; maintenance; - 0.90 [- 1.89, - 0.01]); and to golimumab 50 mg every 4 weeks (biologic-naïve; maintenance; - 0.46 [- 0.94, 0]) for MCS response/remission. CONCLUSION: The current treatment landscape benefits patients with moderately to severely active UC, improving key outcomes; filgotinib 200 mg was similar to current standard of care in most outcomes.

Cost-effectiveness analysis of bimekizumab for the treatment of active psoriatic arthritis in Sweden.

AIMS: To evaluate the cost-effectiveness of bimekizumab, an inhibitor of IL-17F and IL-17A, against biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARD) for psoriatic arthritis (PsA) from the Swedish healthcare system perspective. MATERIALS AND METHODS: A Markov model was developed to simulate the clinical pathway of biologic [b] DMARD-naïve or tumor necrosis factor inhibitor experienced [TNFi-exp] PsA patients over a lifetime horizon. Treatment response was incorporated as achievement of the American College of Rheumatology 50% (ACR50) and Psoriasis Area and Severity Index 75% (PASI75) response, and changes in the Health Assessment Questionnaire-Disability Index (HAQ-DI) score. The efficacy of bimekizumab was obtained from the BE OPTIMAL (bDMARD-naïve) and BE COMPLETE (TNFi-experienced) trials while a network meta-analysis (NMA) informed the efficacy of the comparators. Resource use and drug costs were obtained from published studies and databases of drug retail prices in Sweden. A willingness-to-pay threshold of €50,000 per quality-adjusted life year (QALY) was applied. RESULTS: In bDMARD-naïve patients, bimekizumab achieved greater QALYs (14.08) than with all comparators except infliximab (14.22), dominated guselkumab every 4 and 8 weeks, ixekizumab, secukinumab 300 mg, ustekinumab 45 mg and 90 mg, and was cost-effective against risankizumab, tofacitinib, upadacitinib and TNFis, except adalimumab biosimilar. In TNFi-experienced patients, bimekizumab led to greater QALYs (13.56) than all comparators except certolizumab pegol (13.84), and dominated ixekizumab and secukinumab 300 mg while being cost-effective against all other IL-17A-, IL-23- and JAK inhibitors. LIMITATIONS: An NMA informed the comparative effectiveness estimates. Given gaps in evidence of disease management and indirect costs specific to HAQ-DI scores, and sequential clinical trial evidence in PsA, non-PsA cost data from similar joint conditions were used, and one line of active treatment followed by best supportive care was assumed. CONCLUSIONS: Bimekizumab was cost-effective against most available treatments for PsA in Sweden, irrespective of prior TNFi exposure.

The cost effectiveness of REACH-HF and home-based cardiac rehabilitation compared with the usual medical care for heart failure with reduced ejection fraction: A decision model-based analysis.

BACKGROUND: The REACH-HF (Rehabilitation EnAblement in CHronic Heart Failure) trial found that the REACH-HF home-based cardiac rehabilitation intervention resulted in a clinically meaningful improvement in disease-specific health-related quality of life in patients with reduced ejection fraction heart failure (HFrEF). The aims of this study were to assess the long-term cost-effectiveness of the addition of REACH-HF intervention or home-based cardiac rehabilitation to usual care compared with usual care alone in patients with HFrEF. DESIGN AND METHODS: A Markov model was developed using a patient lifetime horizon and integrating evidence from the REACH-HF trial, a systematic review/meta-analysis of randomised trials, estimates of mortality and hospital admission and UK costs at 2015/2016 prices. Taking a UK National Health and Personal Social Services perspective we report the incremental cost per quality-adjusted life-year (QALY) gained, assessing uncertainty using probabilistic and deterministic sensitivity analyses. RESULTS: In base case analysis, the REACH-HF intervention was associated with per patient mean QALY gain of 0.23 and an increased mean cost of £400 compared with usual care, resulting in a cost per QALY gained of £1720. Probabilistic sensitivity analysis indicated a 78% probability that REACH-HF is cost effective versus usual care at a threshold of £20,000 per QALY gained. Results were similar for home-based cardiac rehabilitation versus usual care. Sensitivity analyses indicate the findings to be robust to changes in model assumptions and parameters. CONCLUSIONS: Our cost-utility analyses indicate that the addition of the REACH-HF intervention and home-based cardiac rehabilitation programmes are likely to be cost-effective treatment options versus usual care alone in patients with HFrEF.

The effects and costs of home-based rehabilitation for heart failure with reduced ejection fraction: The REACH-HF multicentre randomized controlled trial.

BACKGROUND: Cardiac rehabilitation improves health-related quality of life (HRQoL) and reduces hospitalizations in patients with heart failure, but international uptake of cardiac rehabilitation for heart failure remains low. DESIGN AND METHODS: The aim of this multicentre randomized trial was to compare the REACH-HF (Rehabilitation EnAblement in CHronicHeart Failure) intervention, a facilitated self-care and home-based cardiac rehabilitation programme to usual care for adults with heart failure with reduced ejection fraction (HFrEF). The study primary hypothesis was that the addition of the REACH-HF intervention to usual care would improve disease-specific HRQoL (Minnesota Living with Heart Failure questionnaire (MLHFQ)) at 12 months compared with usual care alone. RESULTS: The study recruited 216 participants, predominantly men (78%), with an average age of 70 years and mean left ventricular ejection fraction of 34%. Overall, 185 (86%) participants provided data for the primary outcome. At 12 months, there was a significant and clinically meaningful between-group difference in the MLHFQ score of -5.7 points (95% confidence interval -10.6 to -0.7) in favour of the REACH-HF intervention group ( p = 0.025). With the exception of patient self-care ( p < 0.001) there was no significant difference in other secondary outcomes, including clinical events ( p > 0.05) at follow-up compared with usual care. The mean cost of the REACH-HF intervention was £418 per participant. CONCLUSIONS: The novel REACH-HF home-based facilitated intervention for HFrEF was clinically superior in disease-specific HRQoL at 12 months and offers an affordable alternative to traditional centre-based programmes to address current low cardiac rehabilitation uptake rates for heart failure.

A randomised controlled trial of a facilitated home-based rehabilitation intervention in patients with heart failure with preserved ejection fraction and their caregivers: the REACH-HFpEF Pilot Study.

INTRODUCTION: Home-based cardiac rehabilitation may overcome suboptimal rates of participation. The overarching aim of this study was to assess the feasibility and acceptability of the novel Rehabilitation EnAblement in CHronic Hear Failure (REACH-HF) rehabilitation intervention for patients with heart failure with preserved ejection fraction (HFpEF) and their caregivers. METHODS AND RESULTS: Patients were randomised 1:1 to REACH-HF intervention plus usual care (intervention group) or usual care alone (control group). REACH-HF is a home-based comprehensive self-management rehabilitation programme that comprises patient and carer manuals with supplementary tools, delivered by trained healthcare facilitators over a 12 week period. Patient outcomes were collected by blinded assessors at baseline, 3 months and 6 months postrandomisation and included health-related quality of life (primary) and psychological well-being, exercise capacity, physical activity and HF-related hospitalisation (secondary). Outcomes were also collected in caregivers.We enrolled 50 symptomatic patients with HF from Tayside, Scotland with a left ventricular ejection fraction ≥45% (mean age 73.9 years, 54% female, 100% white British) and 21 caregivers. Study retention (90%) and intervention uptake (92%) were excellent. At 6 months, data from 45 patients showed a potential direction of effect in favour of the intervention group, including the primary outcome of Minnesota Living with Heart Failure Questionnaire total score (between-group mean difference -11.5, 95% CI -22.8 to 0.3). A total of 11 (4 intervention, 7 control) patients experienced a hospital admission over the 6 months of follow-up with 4 (control patients) of these admissions being HF-related. Improvements were seen in a number intervention caregivers' mental health and burden compared with control. CONCLUSIONS: Our findings support the feasibility and rationale for delivering the REACH-HF facilitated home-based rehabilitation intervention for patients with HFpEF and their caregivers and progression to a full multicentre randomised clinical trial to test its clinical effectiveness and cost-effectiveness. TRIAL REGISTRATION NUMBER: ISRCTN78539530.

An Early Health Economic Analysis of the Potential Cost Effectiveness of an Adherence Intervention to Improve Outcomes for Patients with Cystic Fibrosis.

BACKGROUND: Cystic fibrosis (CF) negatively impacts upon health-related quality of life and survival. Adherence to nebulised treatments is low; improving adherence is hypothesised to reduce rates of exacerbation requiring intravenous antibiotics and lung function decline. OBJECTIVE: A state transition model was developed to assess the cost effectiveness of an intervention aimed at increasing patient adherence to nebulised and inhaled antibiotics compared with current CF care, in advance of the forthcoming CFHealthHub randomised controlled trial (RCT). METHODS: The model estimated the costs and health outcomes for each option from the perspective of the UK National Health Service and Personal Social Services over a lifetime horizon. Health gains were valued in terms of quality-adjusted life-years (QALYs) gained. Forced expiratory volume in 1 second (FEV1) trajectories were predicted over three lung function strata: (1) FEV1 ≥70%, (2) FEV1 40-69% and (3) FEV1 <40%. Additional states were included to represent 'post-lung transplantation' and 'dead'. The model was populated using CF Registry data, literature and expert opinion. Costs were presented at 2016 values. Uncertainty was assessed using deterministic and probabilistic sensitivity analyses. RESULTS: If effective, the adherence intervention is expected to produce an additional 0.19 QALYs and cost savings of £64,078 per patient. Across all analyses, the intervention dominated current care. Over a 5-year period, the intervention is expected to generate cost savings of £49.5 million for the estimated 2979 patients with CF with Pseudomonas aeruginosa currently aged ≥16 years in the UK. If applied to a broader population of adult patients with CF receiving any nebulised therapy, the expected savings could be considerably greater. CONCLUSIONS: If effective, the adherence intervention is expected to produce additional health gains at a lower cost than current CF care. However, the economic analysis should be revisited upon completion of the full RCT. More generally, the analysis suggests that considerable gains could be accrued through the implementation of adherence interventions that shift care from expensive hospital-based rescue to community-based prevention.

Cost-effectiveness of antibiotic treatment of uncomplicated urinary tract infection in women: a comparison of four antibiotics.

BACKGROUND: Urinary tract infections (UTIs) are one of the most common reasons for women to attend primary care. There are four different antibiotics currently recommended in England for treatment of uncomplicated UTI but little evidence on their comparative cost-effectiveness. AIM: To assess the relative cost-effectiveness of the four antibiotics currently recommended in England for treatment of uncomplicated UTI in adult women. DESIGN & SETTING: A cost-effectiveness model in adult women with signs and symptoms of uncomplicated UTI in primary care in England treated with fosfomycin, nitrofurantoin, pivmecillinam, or trimethoprim. METHOD: A decision tree economic model of the treatment pathway encompassed up to two rounds of treatment, accounting for different resistance levels. End points included recovery, persistence, pyelonephritis, and/or hospitalisation. Prescription, primary and secondary care treatment, and diagnostic testing costs were aggregated. Cost-effectiveness was assessed as cost per UTI resolved. RESULTS: Trimethoprim 200 mg twice daily (for 3 or 7 days) was estimated to be the most cost-effective treatment (£70 per UTI resolved) when resistance was <30%. However, if resistance to trimethoprim was ≥30%, fosfomycin 3 g once became more cost-effective; at resistance levels of ≥35% for trimethoprim, both fosfomycin 3 g once and nitrofurantoin 100 mg twice daily for 7 days were shown to be more cost-effective. CONCLUSION: Knowing local resistance levels is key to effective and cost-effective empirical prescribing. Recent estimates of trimethoprim resistance rates are close to 50%, in which case a single 3 g dose of fosfomycin is likely to be the most cost-effective treatment option.

Understanding the alcohol harm paradox: an analysis of sex- and condition-specific hospital admissions by socio-economic group for alcohol-associated conditions in England.

BACKGROUND AND AIMS: In many countries, conflicting gradients in alcohol consumption and alcohol-associated mortality have been observed. To understand this 'alcohol harm paradox' we analysed the socio-economic gradient in alcohol-associated hospital admissions to test whether it was greater in conditions which were: (1) chronic (associated with long-term drinking) and partially alcohol-attributable, (2) chronic and wholly alcohol-attributable, (3) acute (associated with intoxication) and partially alcohol-attributable and (4) acute and wholly alcohol-attributable. Our aim was to clarify how (1) drinking patterns (e.g. intoxication linked to acute admissions or dependence linked to chronic conditions) and (2) non-alcohol causes (e.g. smoking and poor diet which are risks for partially alcohol-attributable conditions) contribute to the paradox. DESIGN: Regression analysis testing the modifying effects of condition-group (1-4 above) and sex on the relationship between area-based deprivation and admissions. SETTING: England, April 2010-March 2013. PARTICIPANTS: A total of 9 239 629 English hospital admissions where a primary or secondary cause was one of 36 alcohol-associated conditions. MEASUREMENTS: Admissions by condition and deciles of Index of Multiple Deprivation (IMD). Socio-economic gradient measured as the relative index of inequality (RII, the slope of a linear regression of IMD on admissions adjusted for overall admission rate). Conditions were categorized by ICD-10 code. FINDINGS: A socio-economic gradient in hospitalizations was seen for all conditions, except partially attributable chronic conditions. The gradient was significantly steeper for conditions which were wholly attributable to alcohol and for acute conditions than for conditions partially alcohol-attributable and for chronic conditions. Gradients were steeper for men than for women in cases of wholly alcohol attributable conditions. CONCLUSIONS: There is a socio-economic gradient in English hospital admission for most alcohol-associated conditions. The greatest inequalities are in conditions associated with alcohol dependence, such as liver disease and mental and behavioural conditions, and in acute conditions, such as alcohol poisoning and assault. Socio-economic differences in harmful drinking patterns (dependence and intoxication) may contribute to the 'alcohol harm paradox'.

A cost-effectiveness analysis of condom distribution programmes for the prevention of sexually transmitted infections in England.

BACKGROUND: Prevention of sexually transmitted infection (STI) incidence in England is a high priority, particularly among young people, men who have sex with men (MSM) and black ethnic minorities. An economic evaluation of condom distribution programmes (CDPs) to reduce STI transmission is presented. METHODS: An economic model using a Bernoulli process estimated the number of people acquiring an STI as a function of its prevalence, transmission rate, condom use, condom failure rate and number of sexual contacts. Models were developed for young people (13-24 years), black ethnic minorities, MSM and the general English population. Effectiveness evidence came from a recent systematic review. For young people, a CDP was modelled (relative risk for condom use=1.23), along with an exploratory analysis of the impact on unintended pregnancies. For other populations, threshold analyses were used to identify the combination of costs and effect size required to make a programme cost-effective. RESULTS: The base case predicted that CDP for all young people in England could avert 5123 STI cases per annum, with an incremental cost-effectiveness ratio of £17 411. In addition, it could avert 118 pregnancies and 82 abortions and save £333 000 in associated costs. Schemes for black ethnic minorities and MSM could also be cost-effective even with relatively high costs and small effect sizes. CONCLUSION: CDPs for young people are likely to be cost-effective or cost-saving. CDPs for other high-risk populations may also be cost-effective if they can increase condom use, since high HIV prevalence in these groups imposes a considerable health and cost burden.