Engaging stakeholders to level up COPD care in LMICs: lessons learned from the "Breathe Well" programme in Brazil, China, Georgia, and North Macedonia.

BACKGROUND: Effective stakeholder engagement in health research is increasingly being recognised and promoted as an important pathway to closing the gap between knowledge production and its use in health systems. However, little is known about its process and impacts, particularly in low-and middle-income countries. This opinion piece draws on the stakeholder engagement experiences from a global health research programme on Chronic Obstructive Pulmonary Disease (COPD) led by clinician researchers in Brazil, China, Georgia and North Macedonia, and presents the process, outcomes and lessons learned. MAIN BODY: Each country team was supported with an overarching engagement protocol and mentored to develop a tailored plan. Patient involvement in research was previously limited in all countries, requiring intensive efforts through personal communication, meetings, advisory groups and social media. Accredited training programmes were effective incentives for participation from healthcare providers; and aligning research findings with competing policy priorities enabled interest and dialogue with decision-makers. The COVID-19 pandemic severely limited possibilities for planned engagement, although remote methods were used where possible. Planned and persistent engagement contributed to shared knowledge and commitment to change, including raised patient and public awareness about COPD, improved skills and practice of healthcare providers, increased interest and support from clinical leaders, and dialogue for integrating COPD services into national policy and practice. CONCLUSION: Stakeholder engagement enabled relevant local actors to produce and utilise knowledge for small wins such as improving day-to-day practice and for long-term goals of equitable access to COPD care. For it to be successful and sustained, stakeholder engagement needs to be valued and integrated throughout the research and knowledge generation process, complete with dedicated resources, contextualised and flexible planning, and commitment.

Comparison of health-care utilization, costs and health-related quality of life across the subgroups defined by the Keele STarT MSK Tool.

OBJECTIVES: The aim of this study was to describe and compare health economic outcomes [health-care utilization and costs, work outcomes, and health-related quality of life (EQ-5D-5L)] in patients classified into different levels-of-risk subgroups by the Keele STarT MSK Tool. METHODS: Data on health-care utilization, costs and EQ-5D-5L were collected from a health-care perspective within a primary care prospective observational cohort study. Patients presenting with one (or more) of the five most common musculoskeletal pain presentations were included: back, neck, shoulder, knee or multi-site pain. Participants at low, medium and high risk of persistent disabling pain were compared in relation to mean health-care utilization and costs, health-related quality of life, and employment status. Regression analysis was used to estimate costs. RESULTS: Over 6 months, the mean (s.d.) total health-care (National Health Service and private) costs associated with the low, medium, and high-risk subgroups were £132.92 (167.88), £279.32 (462.98) and £476.07 (716.44), respectively. Mean health-related quality of life over the 6-month period was lower and more people changed their employment status in the high-risk subgroup compared with the medium- and low-risk subgroups. CONCLUSIONS: This study demonstrates that subgroups of people with different levels of risk for poor musculoskeletal pain outcomes also have different levels of health-care utilization, health-care costs, health-related quality of life, and work outcomes. The findings show that the STarT MSK Tool not only identifies those at risk of a poorer outcome, but also those who will have more health-care visits and incur higher costs.

The effectiveness of corticosteroid injection versus night splints for carpal tunnel syndrome: 24-month follow-up of a randomized trial.

OBJECTIVES: This follow-up study of the INSTinCTS (INjection vs SplinTing in Carpal Tunnel Syndrome) trial compared the effects of corticosteroid injection (CSI) and night splinting (NS) for the initial management of mild-to-moderate CTS on symptoms, resource use and carpal tunnel surgery, over 24 months. METHODS: Adults with mild-to-moderate CTS were randomized 1:1 to a local corticosteroid injection or a night splint worn for 6 weeks. Outcomes at 12 and 24 months included the Boston Carpal Tunnel Questionnaire (BCTQ), hand/wrist pain intensity numeric rating scale (NRS), the number of patients referred for and undergoing CTS surgery, and healthcare utilization. A cost-utility analysis was conducted. RESULTS: One hundred and sixteen participants received a CSI and 118 a NS. The response rate at 24 months was 73% in the CSI arm and 71% in the NS arm. By 24 months, a greater proportion of the CSI group had been referred for (28% vs 20%) and undergone (22% vs 16%) CTS surgery compared with the NS group. There were no statistically significant between-group differences in BCTQ score or pain NRS at 12 or 24 months. CSI was more costly [mean difference £68.59 (95% CI: -120.84, 291.24)] with fewer quality-adjusted life-years than NS over 24 months [mean difference -0.022 (95% CI: -0.093, 0.045)]. CONCLUSION: Over 24 months, surgical intervention rates were low in both groups, but less frequent in the NS group. While there were no differences in the clinical effectiveness of CSI and NS, initial treatment with CSI may not be cost-effective in the long-term compared with NS.

Randomised controlled trial testing effectiveness of feedback about lung age or exhaled CO combined with very brief advice for smoking cessation compared to very brief advice alone in North Macedonia: findings from the Breathe Well group.

INTRODUCTION: In 2019, smoking prevalence in North Macedonia was one of the world's highest at around 46% in adults. However, access to smoking cessation treatment is limited and no co-ordinated smoking cessation programmes are provided in primary care. METHODS: We conducted a three parallel-armed randomised controlled trial (n = 1368) to investigate effectiveness and cost-effectiveness of lung age (LA) or exhaled carbon monoxide (CO) feedback combined with very brief advice (VBA) to prompt smoking cessation compared with VBA alone, delivered by GPs in primary care in North Macedonia. All participants who decided to attempt to quit smoking were advised about accessing smoking cessation medications and were also offered behavioural support as part of the "ACT" component of VBA. Participants were aged ≥ 35 years, smoked ≥ 10 cigarettes per day, were recruited from 31 GP practices regardless of motivation to quit and were randomised (1:1:1) using a sequence generated before the start of recruitment. The primary outcome was biochemically validated 7-day point prevalence abstinence at 4 weeks (wks). Participants and GPs were not blinded to allocation after randomisation, however outcome assessors were blind to treatment allocation. RESULTS: There was no evidence of a difference in biochemically confirmed quitting between intervention and control at 4wks (VBA + LA RR 0.90 (97.5%CI: 0.35, 2.27); VBA + CO RR 1.04 (97.5%CI: 0.44, 2.44)), however the absolute number of quitters was small (VBA + LA 1.6%, VBA + CO 1.8%, VBA 1.8%). A similar lack of effect was observed at 12 and 26wks, apart from in the VBA + LA arm where the point estimate was significant but the confidence intervals were very wide. In both treatment arms, a larger proportion reported a reduction in cigarettes smoked per day at 4wks (VBA + LA 1.30 (1.10, 1.54); VBA + CO 1.23 (1.03, 1.49)) compared with VBA. The point estimates indicated a similar direction of effect at 12wks and 26wks, but differences were not statistically significant. Quantitative process measures indicated high fidelity to the intervention delivery protocols, but low uptake of behavioural and pharmacological support. VBA was the dominant intervention in the health economic analyses. CONCLUSION: Overall, there was no evidence that adding LA or CO to VBA increased quit rates. However, a small effect cannot be ruled out as the proportion quitting was low and therefore estimates were imprecise. There was some evidence that participants in the intervention arms were more likely to reduce the amount smoked, at least in the short term. More research is needed to find effective ways to support quitting in settings like North Macedonia where a strong smoking culture persists. TRIAL REGISTRATION: The trial was registered at http://www.isrctn.com (ISRCTN54228638) on the 07/09/2018.

Cost-effectiveness of domiciliary non-invasive ventilation in patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic disease associated with recurring exacerbations, which influence morbidity and mortality for the patient, while placing significant resource burdens on healthcare systems. Non-invasive ventilation (NIV) in a domiciliary setting can help prevent admissions, but the economic evidence to support NIV use is limited. METHODS: A Markov model-based cost-utility analysis from the UK National Health Service perspective compared the cost-effectiveness of domiciliary NIV with usual care for two end-stage COPD populations; a stable COPD population commencing treatment with no recent hospital admission; and a posthospital population starting treatment following admission to hospital for an exacerbation. Hospitalisation rates in patients receiving domiciliary NIV compared with usual care were derived from randomised controlled studies in a recent systematic review. Other model parameters were updated with recent evidence. RESULTS: At the threshold of £20 000 per quality-adjusted life-year (QALY) domiciliary NIV is 99.9% likely cost-effective in a posthospital population, but unlikely (4%) to be cost-effective in stable populations. The incremental cost-effective ratio (ICER) was £11 318/QALY gained in the posthospital population and £27 380/QALY gained in the stable population. Cost-effectiveness estimates were sensitive to longer-term readmission and mortality risks, and duration of benefit from NIV. Indeed, for stable Global Initiative for Chronic Obstructive Lung Disease (GOLD) for stage 4 patients, or with higher mortality and exacerbation risks, ICERs were close to the £20 000/QALY threshold. CONCLUSION: Domiciliary NIV is likely cost-effective for posthospitalised patients, with uncertainty around the cost-effectiveness of domiciliary NIV in stable patients with COPD on which further research should focus.

The cost-effectiveness of different approaches to exercise and corticosteroid injection for subacromial pain (impingement) syndrome.

OBJECTIVES: To determine whether physiotherapist-led exercise intervention and US-guided subacromial CS injection is cost-effective when compared with standard advice and exercise leaflet and unguided injection in patients with subacromial pain (impingement) syndrome. METHODS: An incremental cost-utility analysis using patient responses to the five-level EuroQoL-5D (EQ-5D-5L) questionnaire was undertaken from a healthcare perspective alongside a 2 × 2 factorial randomized trial with 256 participants over a 12-month follow-up period. Uncertainty was explored through the use of cost-effectiveness acceptability curves. RESULTS: The cost-utility analysis indicated that physiotherapist-led exercise was associated with an incremental cost of £155.99 (95% CI 69.02, 241.93) and 0.031 (95% CI -0.01, 0.07) additional quality-adjusted life-years (QALYs), an incremental cost-effectiveness ratio (ICER) of £5031 per QALY gained and an 85% chance of being cost-effective at a threshold of £20 000 per QALY gained compared with the advice and exercise leaflet. US-guided injection was associated with an incremental cost of £15.89 (95% CI -59.36, 109.86) and 0.024 (95% CI -0.02, 0.07) additional QALYs, an ICER of £662 per QALY gained and a 83% chance of being cost-effective at a threshold of £20 000 per QALY gained compared with unguided injection. CONCLUSION: Physiotherapist-led exercise was cost-effective compared with the advice and exercise leaflet, and US-guided injection was cost-effective when compared with unguided injection. CLINICAL TRIAL REGISTRATION: ISRCTN, http://www.isrctn.com, ISRCTN42399123.

Management of fatigue with physical activity and behavioural change support in vasculitis: a feasibility study.

OBJECTIVE: Patients with ANCA-associated vasculitis (AAV) experience high levels of fatigue, despite disease remission. This study assessed the feasibility and acceptability of a definitive randomized controlled trial of a behavioural-based physical activity intervention to support fatigue self-management in AAV patients. METHODS: AAV patients in disease remission with fatigue (Multidimensional Fatigue Inventory-20 general fatigue domain ≥14) were randomly allocated to intervention or standard care in this single-centre open-label randomized controlled feasibility study. The intervention lasted 12 weeks and comprised eight face-to-face physical activity sessions with a facilitator and 12 weekly telephone calls. Participants were encouraged to monitor their physical activity using a tracker device (Fitbit). Standard care involved sign-posting to fatigue websites. The primary outcome was feasibility of a phase III trial assessed against three stop/go traffic light criteria, (recruitment, intervention adherence and study withdrawal). A qualitative study assessed participant views about the intervention. RESULTS: A total of 248 patients were screened and 134 were eligible to participate (54%). Stop/go criteria were amber for recruitment; 43/134 (32%, 95% CI: 24, 40) eligible participants randomized, amber for adherence; 73% of participants attended all eight physical activity sessions, but only 11/22 (50%, 95% CI: 29, 71%) completed the intervention as per the intended schedule, and green for study withdrawal; 2/43 participants withdrew before 24 weeks (5%, 95% CI: 0, 11). Qualitative results suggested the intervention was acceptable. CONCLUSION: This study suggests a behavioural-based physical activity intervention targeting fatigue self-management was acceptable to patients with AAV, although recruitment and protocol adherence will need modification prior to a definitive trial. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN11929227.

Optimising outcomes of exercise and corticosteroid injection in patients with subacromial pain (impingement) syndrome: a factorial randomised trial.

OBJECTIVES: To compare the clinical effectiveness of (1) physiotherapist-led exercise versus an exercise leaflet, and (2) ultrasound-guided subacromial corticosteroid injection versus unguided injection for pain and function in subacromial pain (formerly impingement) syndrome (SAPS). METHODS: This was a single-blind 2×2 factorial randomised trial. Adults with SAPS were randomised equally to one of four treatment groups: (1) ultrasound-guided corticosteroid injection and physiotherapist-led exercise, (2) ultrasound-guided corticosteroid injection and an exercise leaflet, (3) unguided corticosteroid injection and physiotherapist-led exercise and (4) unguided corticosteroid injection and an exercise leaflet. The primary outcome was the Shoulder Pain and Disability Index (SPADI), collected at 6 weeks, 6 and 12 months and compared at 6 weeks for the injection interventions and 6 months for the exercise interventions by intention to treat. RESULTS: We recruited 256 participants (64 treatment per group). Response rates for the primary outcome were 94% at 6 weeks, 88% at 6 months and 80% at 12 months. Greater improvement in total SPADI score was seen with physiotherapist-led exercise than with the exercise leaflet at 6 months (adjusted mean difference -8.23; 95% CI -14.14 to -2.32). There were no significant differences between the injection groups at 6 weeks (-2.04; -7.29 to 3.22), 6 months (-2.36; -8.16 to 3.44) or 12 months (1.59; -5.54 to 8.72). CONCLUSIONS: In patients with SAPS, physiotherapist-led exercise leads to greater improvements in pain and function than an exercise leaflet. Ultrasound guidance confers no additional benefit over unguided corticosteroid injection. TRIAL REGISTRATION NUMBER: ISRCTN42399123.

Open-label randomised pragmatic trial (CONTACT) comparing naproxen and low-dose colchicine for the treatment of gout flares in primary care.

OBJECTIVES: To compare the effectiveness and safety of naproxen and low-dose colchicine for treating gout flares in primary care. METHODS: This was a multicentre open-label randomised trial. Adults with a gout flare recruited from 100 general practices were randomised equally to naproxen 750 mg immediately then 250 mg every 8 hours for 7 days or low-dose colchicine 500 mcg three times per day for 4 days. The primary outcome was change in worst pain intensity in the last 24 hours (0-10 Numeric Rating Scale) from baseline measured daily over the first 7 days: mean change from baseline was compared between groups over days 1-7 by intention to treat. RESULTS: Between 29 January 2014 and 31 December 2015, we recruited 399 participants (naproxen n=200, colchicine n=199), of whom 349 (87.5%) completed primary outcome data at day 7. There was no significant between-group difference in average pain-change scores over days 1-7 (colchicine vs naproxen: mean difference -0.18; 95% CI -0.53 to 0.17; p=0.32). During days 1-7, diarrhoea (45.9% vs 20.0%; OR 3.31; 2.01 to 5.44) and headache (20.5% vs 10.7%; 1.92; 1.03 to 3.55) were more common in the colchicine group than the naproxen group but constipation was less common (4.8% vs 19.3%; 0.24; 0.11 to 0.54). CONCLUSION: We found no difference in pain intensity over 7 days between people with a gout flare randomised to either naproxen or low-dose colchicine. Naproxen caused fewer side effects supporting naproxen as first-line treatment for gout flares in primary care in the absence of contraindications. TRIAL REGISTRATION NUMBER: ISRCTN (69836939), clinicaltrials.gov (NCT01994226), EudraCT (2013-001354-95).

Effect of Antihypertensive Medication Reduction vs Usual Care on Short-term Blood Pressure Control in Patients With Hypertension Aged 80 Years and Older: The OPTIMISE Randomized Clinical Trial.

Importance: Deprescribing of antihypertensive medications is recommended for some older patients with polypharmacy and multimorbidity when the benefits of continued treatment may not outweigh the harms. Objective: This study aimed to establish whether antihypertensive medication reduction is possible without significant changes in systolic blood pressure control or adverse events during 12-week follow-up. Design, Setting, and Participants: The Optimising Treatment for Mild Systolic Hypertension in the Elderly (OPTIMISE) study was a randomized, unblinded, noninferiority trial conducted in 69 primary care sites in England. Participants, whose primary care physician considered them appropriate for medication reduction, were aged 80 years and older, had systolic blood pressure lower than 150 mm Hg, and were receiving at least 2 antihypertensive medications were included. Participants enrolled between April 2017 and September 2018 and underwent follow-up until January 2019. Interventions: Participants were randomized (1:1 ratio) to a strategy of antihypertensive medication reduction (removal of 1 drug [intervention], n = 282) or usual care (control, n = 287), in which no medication changes were mandated. Main Outcomes and Measures: The primary outcome was systolic blood pressure lower than 150 mm Hg at 12-week follow-up. The prespecified noninferiority margin was a relative risk (RR) of 0.90. Secondary outcomes included the proportion of participants maintaining medication reduction and differences in blood pressure, frailty, quality of life, adverse effects, and serious adverse events. Results: Among 569 patients randomized (mean age, 84.8 years; 276 [48.5%] women; median of 2 antihypertensive medications prescribed at baseline), 534 (93.8%) completed the trial. Overall, 229 (86.4%) patients in the intervention group and 236 (87.7%) patients in the control group had a systolic blood pressure lower than 150 mm Hg at 12 weeks (adjusted RR, 0.98 [97.5% 1-sided CI, 0.92 to ∞]). Of 7 prespecified secondary end points, 5 showed no significant difference. Medication reduction was sustained in 187 (66.3%) participants at 12 weeks. Mean change in systolic blood pressure was 3.4 mm Hg (95% CI, 1.1 to 5.8 mm Hg) higher in the intervention group compared with the control group. Twelve (4.3%) participants in the intervention group and 7 (2.4%) in the control group reported at least 1 serious adverse event (adjusted RR, 1.72 [95% CI, 0.7 to 4.3]). Conclusions and Relevance: Among older patients treated with multiple antihypertensive medications, a strategy of medication reduction, compared with usual care, was noninferior with regard to systolic blood pressure control at 12 weeks. The findings suggest antihypertensive medication reduction in some older patients with hypertension is not associated with substantial change in blood pressure control, although further research is needed to understand long-term clinical outcomes. Trial Registration: EudraCT Identifier: 2016-004236-38; ISRCTN identifier: 97503221.

The clinical and cost-effectiveness of corticosteroid injection versus night splints for carpal tunnel syndrome (INSTINCTS trial): an open-label, parallel group, randomised controlled trial.

BACKGROUND: To our knowledge, the comparative effectiveness of commonly used conservative treatments for carpal tunnel syndrome has not been evaluated previously in primary care. We aimed to compare the clinical and cost-effectiveness of night splints with a corticosteroid injection with regards to reducing symptoms and improving hand function in patients with mild or moderate carpal tunnel syndrome. METHODS: We did this randomised, open-label, pragmatic trial in adults (≥18 years) with mild or moderate carpal tunnel syndrome recruited from 25 primary and community musculoskeletal clinics and services. Patients with a new episode of idiopathic mild or moderate carpal tunnel syndrome of at least 6 weeks' duration were eligible. We randomly assigned (1:1) patients (permutated blocks of two and four by site) with an online web or third party telephone service to receive either a single injection of 20 mg methylprednisolone acetate (from 40 mg/mL) or a night-resting splint to be worn for 6 weeks. Patients and clinicians could not be masked to the intervention. The primary outcome was the overall score of the Boston Carpal Tunnel Questionnaire (BCTQ) at 6 weeks. We used intention-to-treat analysis, with multiple imputation for missing data, which was concealed to treatment group allocation. The trial is registered with the European Clinical Trials Database, number 2013-001435-48, and ClinicalTrial.gov, number NCT02038452. FINDINGS: Between April 17, 2014, and Dec 31, 2016, 234 participants were randomly assigned (118 to the night splint group and 116 to the corticosteroid injection group), of whom 212 (91%) completed the BCTQ at 6 weeks. The BCTQ score was significantly better at 6 weeks in the corticosteroid injection group (mean 2·02 [SD 0·81]) than the night splint group (2·29 [0·75]; adjusted mean difference -0·32; 95% CI -0·48 to -0·16; p=0·0001). No adverse events were reported. INTERPRETATION: A single corticosteroid injection shows superior clinical effectiveness at 6 weeks compared with night-resting splints, making it the treatment of choice for rapid symptom response in mild or moderate carpal tunnel syndrome presenting in primary care. FUNDING: Arthritis Research UK.

Model-based evaluation of the long-term cost-effectiveness of systematic case-finding for COPD in primary care.

INTRODUCTION: 'One-off' systematic case-finding for COPD using a respiratory screening questionnaire is more effective and cost-effective than routine care at identifying new cases. However, it is not known whether early diagnosis and treatment is beneficial in the longer term. We estimated the long-term cost-effectiveness of a regular case-finding programme in primary care. METHODS: A Markov decision analytic model was developed to compare the cost-effectiveness of a 3-yearly systematic case-finding programme targeted to ever smokers aged ≥50 years with the current routine diagnostic process in UK primary care. Patient-level data on case-finding pathways was obtained from a large randomised controlled trial. Information on the natural history of COPD and treatment effects was obtained from a linked COPD cohort, UK primary care database and published literature. The discounted lifetime cost per quality-adjusted life-year (QALY) gained was calculated from a health service perspective. RESULTS: The incremental cost-effectiveness ratio of systematic case-finding versus current care was £16 596 per additional QALY gained, with a 78% probability of cost-effectiveness at a £20 000 per QALY willingness-to-pay threshold. The base case result was robust to multiple one-way sensitivity analyses. The main drivers were response rate to the initial screening questionnaire and attendance rate for the confirmatory spirometry test. DISCUSSION: Regular systematic case-finding for COPD using a screening questionnaire in primary care is likely to be cost-effective in the long-term despite uncertainties in treatment effectiveness. Further knowledge of the natural history of case-found patients and the effectiveness of their management will improve confidence to implement such an approach.

Incorporating Household Spillovers in Cost Utility Analysis: A Case Study Using Behavior Change in COPD.

OBJECTIVES: It is important to capture all health effects of interventions in cost-utility analyses conducted under a societal or healthcare perspective. However, this is rarely done. Household spillovers (health effects on patients' other household members) may be particularly likely in the context of technologies and interventions to change behaviors that are interdependent in the household. Our objective was to prospectively collect outcome data from household members and illustrate how these can be included in a cost-utility analysis of a behavior change intervention in chronic obstructive pulmonary disease (COPD). METHODS: Data were collected from patients' household members (n = 153) alongside a randomized controlled trial of a COPD self-management intervention. The impact of the intervention on household members' EQ-5D-5L scores (primary outcome), was evaluated. Analyses were then carried out to estimate household members' quality-adjusted life-years (QALYs) and assess the impact of including these QALYs on cost-effectiveness. RESULTS: The intervention had a negligible spillover on household members' EQ-5D-5L scores (-0.007; p = .75). There were also no statistically significant spillovers at the 5 percent level in household member secondary outcomes. In the base-case model, the inclusion of household member QALYs in the incremental cost-effectiveness ratio (ICER) denominator marginally increased the ICER from GBP 10,271 (EUR 13,146) to GBP 10,991 (EUR 14,068) per QALY gained. CONCLUSIONS: This study demonstrates it is feasible to prospectively collect and include household members' outcome data in cost utility analysis, although the study highlighted several methodological issues. In this case, the intervention did not impact significantly on household members' health or health behaviors, but inclusion of household spillovers may make a difference in other contexts.

Cost-effectiveness of internet-based training for primary care clinicians on antibiotic prescribing for acute respiratory tract infections in Europe.

Objectives: Overprescribing of antibiotics by general practitioners (GPs) is seen as a major driver of antibiotic resistance. Training in communication skills and C-reactive protein (CRP) testing both appear effective in reducing such prescribing. This study assesses the cost-effectiveness (compared with usual care) of: (i) training GPs in the use of CRP testing; (ii) training GPs in communication skills; and (iii) training GPs in both CRP testing and communication skills. Methods: Economic analyses [cost-utility analysis (CUA) accounting for the cost of antibiotic resistance and cost-effectiveness analysis (CEA)] were both conducted from a healthcare perspective with a time horizon of 28 days alongside a multinational, cluster, randomized, factorial controlled trial in patients with respiratory tract infections in five European countries. The primary outcome measures were QALYs and percentage reduction in antibiotic prescribing. Hierarchical modelling was used to estimate an incremental cost per QALY gained and an incremental cost per percentage reduction in antibiotic prescribing. Results: Overall, the results of both the CUA and CEA showed that training in communication skills is the most cost-effective option. However, excluding the cost of antibiotic resistance in the CUA resulted in usual care being the most cost-effective option. Country-specific results from the CUA showed that training in communication skills was cost-effective in Belgium, UK and Netherlands whilst training in CRP was cost-effective in Poland. Conclusions: Internet-based training in communication skills is a cost-effective intervention to reduce antibiotic prescribing for respiratory tract infections in primary care if the cost of antibiotic resistance is accounted for.

Cost-effectiveness of a model consultation to support self-management in patients with osteoarthritis.

Objectives: The aim of this study was to estimate the cost-effectiveness of a model OA consultation for OA to support self-management compared with usual care. Methods: An incremental cost-utility analysis using patient responses to the three-level EuroQoL-5D (EQ-5D) questionnaire was undertaken from a UK National Health Service perspective alongside a two-arm cluster-randomized controlled trial. Uncertainty was explored through the use of cost-effectiveness acceptability curves. Results: Differences in health outcomes between the model OA consultation and usual care arms were not statistically significant. On average, visits to the orthopaedic surgeon were lower in the model OA consultation arm by -0.28 (95% CI: -0.55, -0.06). The cost-utility analysis indicated that the model OA consultation was associated with a non-significant incremental cost of £-13.11 (95% CI: -81.09 to 54.85) and an incremental quality adjusted life year (QALY) of -0.003 (95% CI: -0.03 to 0.02), with a 44% chance of being cost-effective at a threshold of £20 000 per QALY gained. The percentage of participants who took time off and the associated productivity cost were lower in the model OA consultation arm. Conclusion: Implementing National Institute for Health and Care Excellence guidelines using a model OA consultation in primary care does not appear to lead to increased costs, but health outcomes remain very similar to usual care. Even though the intervention seems to reduce the demand for orthopaedic surgery, overall it is unlikely to be cost-effective.

The Importance of Model Structure in the Cost-Effectiveness Analysis of Primary Care Interventions for the Management of Hypertension.

BACKGROUND: Management of hypertension can lead to significant reductions in blood pressure, thereby reducing the risk of cardiovascular disease. Modeling the course of cardiovascular disease is not without complications, and uncertainty surrounding the structure of a model will almost always arise once a choice of a model structure is defined. OBJECTIVES: To provide a practical illustration of the impact on the results of cost-effectiveness of changing or adapting model structures in a previously published cost-utility analysis of a primary care intervention for the management of hypertension Targets and Self-Management for the Control of Blood Pressure in Stroke and at Risk Groups (TASMIN-SR). METHODS: The case study assessed the structural uncertainty arising from model structure and from the exclusion of secondary events. Four alternative model structures were implemented. Long-term cost-effectiveness was estimated and the results compared with those from the TASMIN-SR model. RESULTS: The main cost-effectiveness results obtained in the TASMIN-SR study did not change with the implementation of alternative model structures. Choice of model type was limited to a cohort Markov model, and because of the lack of epidemiological data, only model 4 captured structural uncertainty arising from the exclusion of secondary events in the case study model. CONCLUSIONS: The results of this study indicate that the main conclusions drawn from the TASMIN-SR model of cost-effectiveness were robust to changes in model structure and the inclusion of secondary events. Even though one of the models produced results that were different to those of TASMIN-SR, the fact that the main conclusions were identical suggests that a more parsimonious model may have sufficed.

The effects of implementing a point-of-care electronic template to prompt routine anxiety and depression screening in patients consulting for osteoarthritis (the Primary Care Osteoarthritis Trial): A cluster randomised trial in primary care.

BACKGROUND: This study aimed to evaluate whether prompting general practitioners (GPs) to routinely assess and manage anxiety and depression in patients consulting with osteoarthritis (OA) improves pain outcomes. METHODS AND FINDINGS: We conducted a cluster randomised controlled trial involving 45 English general practices. In intervention practices, patients aged ≥45 y consulting with OA received point-of-care anxiety and depression screening by the GP, prompted by an automated electronic template comprising five questions (a two-item Patient Health Questionnaire-2 for depression, a two-item Generalized Anxiety Disorder-2 questionnaire for anxiety, and a question about current pain intensity [0-10 numerical rating scale]). The template signposted GPs to follow National Institute for Health and Care Excellence clinical guidelines for anxiety, depression, and OA and was supported by a brief training package. The template in control practices prompted GPs to ask the pain intensity question only. The primary outcome was patient-reported current pain intensity post-consultation and at 3-, 6-, and 12-mo follow-up. Secondary outcomes included pain-related disability, anxiety, depression, and general health. During the trial period, 7,279 patients aged ≥45 y consulted with a relevant OA-related code, and 4,240 patients were deemed potentially eligible by participating GPs. Templates were completed for 2,042 patients (1,339 [31.6%] in the control arm and 703 [23.1%] in the intervention arm). Of these 2,042 patients, 1,412 returned questionnaires (501 [71.3%] from 20 intervention practices, 911 [68.0%] from 24 control practices). Follow-up rates were similar in both arms, totalling 1,093 (77.4%) at 3 mo, 1,064 (75.4%) at 6 mo, and 1,017 (72.0%) at 12 mo. For the primary endpoint, multilevel modelling yielded significantly higher average pain intensity across follow-up to 12 mo in the intervention group than the control group (adjusted mean difference 0.31; 95% CI 0.04, 0.59). Secondary outcomes were consistent with the primary outcome measure in reflecting better outcomes as a whole for the control group than the intervention group. Anxiety and depression scores did not reduce following the intervention. The main limitations of this study are two potential sources of bias: an imbalance in cluster size (mean practice size 7,397 [intervention] versus 5,850 [control]) and a difference in the proportion of patients for whom the GP deactivated the template (33.6% [intervention] versus 27.8% [control]). CONCLUSIONS: In this study, we observed no beneficial effect on pain outcomes of prompting GPs to routinely screen for and manage comorbid anxiety and depression in patients presenting with symptoms due to OA, with those in the intervention group reporting statistically significantly higher average pain scores over the four follow-up time points than those in the control group. TRIAL REGISTRATION: ISRCTN registry ISRCTN40721988.

The Estimation and Inclusion of Presenteeism Costs in Applied Economic Evaluation: A Systematic Review.

OBJECTIVE: Given the significant costs of reduced productivity (presenteeism) in comparison to absenteeism, and overall societal costs, presenteeism has a potentially important role to play in economic evaluations. However, these costs are often excluded. The objective of this study is to review applied cost of illness studies and economic evaluations to identify valuation methods used for, and impact of including presenteeism costs in practice. METHODS: A structured systematic review was carried out to explore (i) the extent to which presenteeism has been applied in cost of illness studies and economic evaluations and (ii) the overall impact of including presenteeism on overall costs and outcomes. Potential articles were identified by searching Medline, PsycINFO and NHS EED databases. A standard template was developed and used to extract information from economic evaluations and cost of illness studies incorporating presenteeism costs. RESULTS: A total of 28 studies were included in the systematic review which also demonstrated that presenteeism costs are rarely included in full economic evaluations. Estimation and monetisation methods differed between the instruments. The impact of disease on presenteeism whilst in paid work is high. CONCLUSIONS: The potential impact of presenteeism costs needs to be highlighted and greater consideration should be given to including these in economic evaluations and cost of illness studies. The importance of including presenteeism costs when conducting economic evaluation from a societal perspective should be emphasised in national economic guidelines and more methodological work is required to improve the practical application of presenteeism instruments to generate productivity cost estimates.

Valuing productivity costs using the friction-cost approach: Estimating friction-period estimates by occupational classifications for the UK.

The friction cost approach has been proposed as an alternative to the human capital approach in estimating productivity costs. However, it is difficult, in practice, to apply this approach due to limited availability of context-specific data. Using national and firm-level data on vacancy durations sourced from 4 organisations, we estimated vacancy durations, and consequently, length of friction period for the United Kingdom disaggregated by occupational classification. We found comparable estimates to previously reported friction periods elsewhere. The disaggregated friction period analysis confirmed occupational class has an effect on the estimated length of the friction period. The research presents estimates on vacancy durations and friction periods necessary to use the friction cost approach in a practical way in economic evaluations.

The clinical and cost-effectiveness of stratified care for patients with sciatica: the SCOPiC randomised controlled trial protocol (ISRCTN75449581).

BACKGROUND: Sciatica has a substantial impact on patients, and is associated with high healthcare and societal costs. Although there is variation in the clinical management of sciatica, the current model of care usually involves an initial period of 'wait and see' for most patients, with simple measures of advice and analgesia, followed by conservative and/or more invasive interventions if symptoms fail to resolve. A model of care is needed that does not over-treat those with a good prognosis yet identifies patients who do need more intensive treatment to help with symptoms, and return to everyday function including work. The aim of the SCOPiC trial (SCiatica Outcomes in Primary Care) is to establish whether stratified care based on subgrouping using a combination of prognostic and clinical information, with matched care pathways, is more effective than non-stratified care, for improving time to symptom resolution in patients consulting with sciatica in primary care. We will also assess the impact of stratified care on service delivery and evaluate its cost-effectiveness compared to non-stratified care. METHODS/DESIGN: Multicentre, pragmatic, parallel arm randomised trial, with internal pilot, cost-effectiveness analysis and embedded qualitative study. We will recruit 470 adult patients with sciatica from general practices in England and Wales, over 24 months. Patients will be randomised to stratified care or non-stratified care, and treated in physiotherapy and spinal specialist services, in participating NHS services. The primary outcome is time to first resolution of sciatica symptoms, measured on a 6-point ordered categorical scale, collected using text messaging. Secondary outcomes include physical function, pain intensity, quality of life, work loss, healthcare use and satisfaction with treatment, and will be collected using postal questionnaires at 4 and 12-month follow-up. Semi-structured qualitative interviews with a subsample of participants and clinicians will explore the acceptability of stratified care. DISCUSSION: This paper presents the details of the rationale, design and processes of the SCOPiC trial. Results from this trial will contribute to the evidence base for management of patients with sciatica consulting in primary care. TRIAL REGISTRATION: ISRCTN75449581 , date: 20.11.2014.