Cost-effectiveness of natriuretic peptide-based screening and collaborative care: a report from the STOP-HF (St Vincent's Screening TO Prevent Heart Failure) study

AIMS: Prevention of cardiovascular disease and heart failure (HF) in a cost-effective manner is a public health goal. This work aims to assess the cost-effectiveness of the St Vincent's Screening TO Prevent Heart Failure (STOP-HF) intervention.

METHODS AND RESULTS: This is a substudy of 1054 participants with cardiovascular risk factors [median age 65.8 years, interquartile range (IQR) 57.8:72.4, with 4.3 years, IQR 3.4:5.2, follow-up]. Annual natriuretic peptide-based screening was performed, with collaborative cardiovascular care between specialist physicians and general practitioners provided to patients with BNP levels >50 pg/mL. Analysis of cost per case prevented and cost-effectiveness per quality-adjusted life year (QALY) gained was performed. The primary clinical endpoint of LV dysfunction (LVD) with or without HF was reduced in intervention patients [odds ratio (OR) 0.60; 95% confidence interval (CI) 0.38-0.94; P = 0.026]. There were 157 deaths and/or emergency hospitalizations for major adverse cardiac events (MACE) in the control group vs. 102 in the intervention group (OR 0.68; 95% CI 0.49-0.93; P = 0.01). The cost per case of LVD/HF prevented was €9683 (sensitivity range -€843 to €20 210), whereas the cost per MACE prevented was €3471 (sensitivity range -€302 to €7245). Cardiovascular hospitalization savings offset increased outpatient and primary care costs. The cost per QALY gain was €1104 and the intervention has an 88% probability of being cost-effective at a willingness to pay threshold of €30 000.

CONCLUSION: Among patients with cardiovascular risk factors, natriuretic peptide-based screening and collaborative care reduced LVD, HF, and MACE, and has a high probability of being cost-effective.

TRIAL REGISTRATION: NCT00921960.

Effectiveness and cost-effectiveness of a physical activity loyalty scheme for behaviour change maintenance: a cluster randomised controlled trial

Background
Increasing physical activity in the workplace can provide employee physical and mental health benefits, and employer economic benefits through reduced absenteeism and increased productivity. The workplace is an opportune setting to encourage habitual activity. However, there is limited evidence on effective behaviour change interventions that lead to maintained physical activity. This study aims to address this gap and help build the necessary evidence base for effective, and cost-effective, workplace interventions

Methods/design
This cluster randomised control trial will recruit 776 office-based employees from public sector organisations in Belfast and Lisburn city centres, Northern Ireland. Participants will be randomly allocated by cluster to either the Intervention Group or Control Group (waiting list control). The 6-month intervention consists of rewards (retail vouchers, based on similar principles to high street loyalty cards), feedback and other evidence-based behaviour change techniques. Sensors situated in the vicinity of participating workplaces will promote and monitor minutes of physical activity undertaken by participants. Both groups will complete all outcome measures. The primary outcome is steps per day recorded using a pedometer (Yamax Digiwalker CW-701) for 7 consecutive days at baseline, 6, 12 and 18 months. Secondary outcomes include health, mental wellbeing, quality of life, work absenteeism and presenteeism, and use of healthcare resources. Process measures will assess intervention “dose”, website usage, and intervention fidelity. An economic evaluation will be conducted from the National Health Service, employer and retailer perspective using both a cost-utility and cost-effectiveness framework. The inclusion of a discrete choice experiment will further generate values for a cost-benefit analysis. Participant focus groups will explore who the intervention worked for and why, and interviews with retailers will elucidate their views on the sustainability of a public health focused loyalty card scheme.

Discussion
The study is designed to maximise the potential for roll-out in similar settings, by engaging the public sector and business community in designing and delivering the intervention. We have developed a sustainable business model using a ‘points’ based loyalty platform, whereby local businesses ‘sponsor’ the incentive (retail vouchers) in return for increased footfall to their business.

Using virtual topology operations to generate analysis topology

Virtual topology operations have been utilized to generate an analysis topology definition suitable for downstream mesh generation. Detailed descriptions are provided for virtual topology merge and split operations for all topological entities. Current virtual topology technology is extended to allow the virtual partitioning of volume cells and the topological queries required to carry out each operation are provided. Virtual representations are robustly linked to the underlying geometric definition through an analysis topology. The analysis topology and all associated virtual and topological dependencies are automatically updated after each virtual operation, providing the link to the underlying CAD geometry. Therefore, a valid description of the analysis topology, including relative orientations, is maintained. This enables downstream operations, such as the merging or partitioning of virtual entities, and interrogations, such as determining if a specific meshing strategy can be applied to the virtual volume cells, to be performed on the analysis topology description. As the virtual representation is a non-manifold description of the sub-divided domain the interfaces between cells are recorded automatically. This enables the advantages of non-manifold modelling to be exploited within the manifold modelling environment of a major commercial CAD system, without any adaptation of the underlying CAD model. A hierarchical virtual structure is maintained where virtual entities are merged or partitioned. This has a major benefit over existing solutions as the virtual dependencies are stored in an open and accessible manner, providing the analyst with the freedom to create, modify and edit the analysis topology in any preferred sequence, whilst the original CAD geometry is not disturbed. Robust definitions of the topological and virtual dependencies enable the same virtual topology definitions to be accessed, interrogated and manipulated within multiple different CAD packages and linked to the underlying geometry.

FcγRIIa and FcγRIIIa polymorphisms and cetuximab benefit in the microscopic disease

Purpose: FcγR polymorphisms have been reported to enhance the immune-mediated effects of cetuximab in metastatic colorectal cancer. There are no data on the relationship between these polymorphisms and cetuximab in the early-stage setting. We performed a pharmacogenomic analysis of EXPERT-C, a randomized phase II trial of neoadjuvant CAPOX followed by chemoradiotherapy, surgery, and adjuvant CAPOX ± cetuximab in high-risk, locally advanced rectal cancer.

Experimental Design: FcγRIIa-H131R and FcγRIIIa-V158F polymorphisms were analyzed on DNA from peripheral blood samples. Kaplan–Meier method and Cox regression analysis were used to calculate survival estimates and compare treatment arms.

Results: Genotyping was successfully performed in 105 of 164 (64%) patients (CAPOX = 54, CAPOX-C = 51). No deviation from the Hardy–Weinberg equilibrium or association of these polymorphisms with tumor RAS status was observed. FcγRIIa-131R (HR, 0.38; P = 0.058) and FcγRIIIa-158F alleles (HR, 0.21; P = 0.007) predicted improved progression-free survival (PFS) in patients treated with cetuximab. In the CAPOX-C arm, carriers of both 131R and 158F alleles had a statistically significant improvement in PFS (5 years: 78.4%; HR, 0.22; P = 0.002) and overall survival (OS; 5 years: 86.4%; HR, 0.24; P = 0.018) when compared with patients homozygous for 131H and/or 158V (5-year PFS: 35.7%; 5-year OS: 57.1%). An interaction between cetuximab benefit and 131R and 158F alleles was found for PFS (P = 0.017) and remained significant after adjusting for prognostic variables (P = 0.003).

Conclusion: This is the first study investigating FcγRIIa and FcγRIIIa polymorphisms in patients with early-stage colorectal cancer treated with cetuximab. We showed an increased clinical benefit from cetuximab in the presence of 131R and 158F alleles.

TP53 mutational status and cetuximab benefit in rectal cancer: 5-year results of the EXPERT-C trial.

In this updated analysis of the EXPERT-C trial we show that, in magnetic resonance imaging-defined, high-risk, locally advanced rectal cancer, adding cetuximab to a treatment strategy with neoadjuvant CAPOX followed by chemoradiotherapy, surgery, and adjuvant CAPOX is not associated with a statistically significant improvement in progression-free survival (PFS) and overall survival (OS) in both KRAS/BRAF wild-type and unselected patients. In a retrospective biomarker analysis, TP53 was not prognostic but emerged as an independent predictive biomarker for cetuximab benefit. After a median follow-up of 65.0 months, TP53 wild-type patients (n = 69) who received cetuximab had a statistically significant better PFS (89.3% vs 65.0% at 5 years; hazard ratio [HR] = 0.23; 95% confidence interval [CI] = 0.07 to 0.78; two-sided P = .02 by Cox regression) and OS (92.7% vs 67.5% at 5 years; HR = 0.16; 95% CI = 0.04 to 0.70; two-sided P = .02 by Cox regression) than TP53 wild-type patients who were treated in the control arm. An interaction between TP53 status and cetuximab effect was found (P <.05) and remained statistically significant after adjusting for statistically significant prognostic factors and KRAS.

Review and analysis of solar thermal facades

Harnessing solar energy to provide for the thermal needs of buildings is one of the most promising solutions to the global energy issue. Exploiting the additional surface area provided by the building’s façade can significantly increase the solar energy output. Developing a range of integrated and adaptable products that do not significantly affect the building’s aesthetics is vital to enabling the building integrated solar thermal market to expand and prosper. This work reviews and evaluates solar thermal facades in terms of the standard collector type, which they are based on, and their component make-up. Daily efficiency models are presented, based on a combination of the Hottel Whillier Bliss model and finite element simulation. Novel and market available solar thermal systems are also reviewed and evaluated using standard evaluation methods, based on experimentally determined parameters ISO 9806. Solar thermal collectors integrated directly into the facade benefit from the additional wall insulation at the back; displaying higher efficiencies then an identical collector offset from the facade. Unglazed solar thermal facades with high capacitance absorbers (e.g. concrete) experience a shift in peak maximum energy yield and display a lower sensitivity to ambient conditions than the traditional metallic based unglazed collectors. Glazed solar thermal facades, used for high temperature applications (domestic hot water), result in overheating of the building’s interior which can be reduced significantly through the inclusion of high quality wall insulation. For low temperature applications (preheating systems), the cheaper unglazed systems offer the most economic solution. The inclusion of brighter colour for the glazing and darker colour for the absorber shows the lowest efficiency reductions (<4%). Novel solar thermal façade solutions include solar collectors integrated into balcony rails, shading devices, louvers, windows or gutters.

Patient-reported quality-of-life analysis of radium-223 dichloride from the phase III ALSYMPCA study

BACKGROUND: Radium-223 dichloride (radium-223), a first-in-class α-emitting radiopharmaceutical, is recommended in both pre- and post-docetaxel settings in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases based on overall survival benefit demonstrated in the phase III ALSYMPCA study. ALSYMPCA included prospective measurements of health-related quality of life (QOL) using two validated instruments: the general EuroQoL 5D (EQ-5D) and the disease-specific Functional Assessment of Cancer Therapy-Prostate (FACT-P).

PATIENTS AND METHODS: Analyses were conducted to determine treatment effects of radium-223 plus standard of care (SOC) versus placebo plus SOC on QOL using FACT-P and EQ-5D. Outcomes assessed were percentage of patients experiencing improvement, percentage of patients experiencing worsening, and mean QOL scores during the study.

RESULTS: Analyses were carried out on the intent-to-treat population of patients randomized to receive radium-223 (n = 614) or placebo (n = 307). The mean baseline EQ-5D utility and FACT-P total scores were similar between treatment groups. A significantly higher percentage of patients receiving radium-223 experienced meaningful improvement in EQ-5D utility score on treatment versus placebo {29.2% versus 18.5%, respectively; P = 0.004; odds ratio (OR) = 1.82 [95% confidence interval (CI) 1.21-2.74]}. Findings were similar for FACT-P total score [24.6% versus 16.1%, respectively; P = 0.020; OR = 1.70 (95% CI 1.08-2.65)]. A lower percentage of patients receiving radium-223 experienced meaningful worsening versus placebo measured by EQ-5D utility score and FACT-P total score. Prior docetaxel use and current bisphosphonate use did not affect these findings. Treatment was a significant predictor of EQ-5D utility score, with radium-223 associated with higher scores versus placebo (0.56 versus 0.50, respectively; P = 0.002). Findings were similar for FACT-P total score (99.08 versus 95.22, respectively; P = 0.004).

CONCLUSIONS: QOL data from ALSYMPCA demonstrated that improved survival with radium-223 is accompanied by significant QOL benefits, including a higher percentage of patients with meaningful QOL improvement and a slower decline in QOL over time in patients with CRPC.

Does video feedback analysis improve CPR performance in phase 5 medical students?

Background The use of simulation in medical education is increasing, with students taught and assessed using simulated patients and manikins. Medical students at Queen’s University of Belfast are taught advanced life support cardiopulmonary resuscitation as part of the undergraduate curriculum. Teaching and feedback in these skills have been developed in Queen’s University with high-fidelity manikins. This study aimed to evaluate the effectiveness of video compared to verbal feedback in assessment of student cardiopulmonary resuscitation performance Methods Final year students participated in this study using a high-fidelity manikin, in the Clinical Skills Centre, Queen’s University Belfast. Cohort A received verbal feedback only on their performance and cohort B received video feedback only. Video analysis using ‘StudioCode’ software was distributed to students. Each group returned for a second scenario and evaluation 4 weeks later. An assessment tool was created for performance assessment, which included individual skill and global score evaluation. Results One hundred thirty eight final year medical students completed the study. 62 % were female and the mean age was 23.9 years. Students having video feedback had significantly greater improvement in overall scores compared to those receiving verbal feedback (p = 0.006, 95 % CI: 2.8–15.8). Individual skills, including ventilation quality and global score were significantly better with video feedback (p = 0.002 and p < 0.001, respectively) when compared with cohort A. There was a positive change in overall score for cohort B from session one to session two (p < 0.001, 95 % CI: 6.3–15.8) indicating video feedback significantly benefited skill retention. In addition, using video feedback showed a significant improvement in the global score (p < 0.001, 95 % CI: 3.3–7.2) and drug administration timing (p = 0.004, 95 % CI: 0.7–3.8) of cohort B participants, from session one to session two. Conclusions There is increased use of simulation in medicine but a paucity of published data comparing feedback methods in cardiopulmonary resuscitation training. Our study shows the use of video feedback when teaching cardiopulmonary resuscitation is more effective than verbal feedback, and enhances skill retention. This is one of the first studies to demonstrate the benefit of video feedback in cardiopulmonary resuscitation teaching.