Protocol for the economic evaluation of metacognitive therapy for cardiac rehabilitation participants with symptoms of anxiety and/or depression

INTRODUCTION: Cardiac rehabilitation (CR) is offered to reduce the risk of further cardiac events and to improve patients' health and quality of life following a cardiac event. Psychological care is a common component of CR as symptoms of depression and/or anxiety are more prevalent in this population, however evidence for the cost-effectiveness of current interventions is limited. Metacognitive therapy (MCT), is a recent treatment development that is effective in treating anxiety and depression in mental health settings and is being evaluated in CR patients. This protocol describes the planned approach to the economic evaluation of MCT for CR patients. METHODS AND ANALYSIS: The economic evaluation work will consist of a within-trial analysis and an economic model. The PATHWAY Group MCT study has been prospectively designed to collect comprehensive self-reported resource use and health outcome data, including the EQ-5D, within a randomised controlled trial study design (UK Clinical Trials Gateway). A within-trial economic evaluation and economic model will compare the cost-effectiveness of MCT plus usual care (UC) to UC, from a health and social care perspective in the UK. The within-trial analysis will use intention-to-treat and estimate total costs and quality-adjusted life-years (QALYs) for the trial follow-up. Single imputation will be used to impute missing baseline variables. Multiple imputation will be used to impute values missing at follow-up. Items of resource use will be multiplied by published national healthcare costs. Regression analysis will be used to estimate net costs and net QALYs and these estimates will be bootstrapped to generate 10 000 net pairs of costs and QALYs to inform the probability of cost-effectiveness. A decision analytical economic model will be developed to synthesise trial data with the published literature over a longer time frame. Sensitivity analysis will explore uncertainty. Guidance of the methods for economic models will be followed and dissemination will adhere to reporting guidelines. ETHICS AND DISSEMINATION: The economic evaluation includes a within-trial analysis. The trial which included the collection of this data was reviewed and approved by Ethics. Ethics approval was obtained by the Preston Research Ethics Committee (project ID 156862). The modelling analysis is not applicable for Ethics as it will use data from the trial (secondary analysis) and the published literature. Results of the main trial and economic evaluation will be published in the peer-reviewed National Institute for Health Research (NIHR) journals library (Programme Grants for Applied Research), submitted to a peer-reviewed journal and presented at appropriate conferences. TRIAL REGISTRATION NUMBER: ISRCTN74643496; Pre-results

Obesity-related perivascular adipose tissue damage is reversed by sustained weight loss in the rat

Objective – Perivascular adipose tissue (PVAT) exerts an anticontractile effect in response to various vasoconstrictor agonists and this is lost in obesity. A recent study reported that bariatric surgery reverses the damaging effects of obesity on PVAT function. However, PVAT function has not been characterised following weight loss induced by caloric restriction, which is often the first line treatment for obesity. Approach and Results – Contractility studies were performed using wire myography on small mesenteric arteries with and without PVAT from control, diet-induced obese, calorie restricted and sustained weight loss rats. Changes in the PVAT environment were assessed using immunohistochemistry. PVAT from healthy animals elicited an anticontractile effect in response to norepinephrine. This was abolished in diet-induced obesity through a mechanism involving increased local TNFα and reduced nitric oxide bioavailability within PVAT. Sustained weight loss led to improvement in PVAT function associated with restoration of adipocyte size, reduced TNFα and increased nitric oxide synthase function. This was associated with reversal of obesity-induced hypertension and normalisation of plasma adipokine levels, including leptin and insulin. Conclusions – We have shown that diet-induced weight loss reverses obesity-induced PVAT damage through a mechanism involving reduced inflammation and increased nitric oxide synthase activity within PVAT. These data reveal inflammation and nitric oxide synthase, particularly eNOS, as potential targets for the treatment of PVAT dysfunction associated with obesity and the metabolic syndrome

Advanced cardiovascular risk prediction in the emergency department: updating a clinical prediction model - a large database study protocol.

From Europe PMC via Jisc Publications RouterHistory: ppub 2021-10-01, epub 2021-10-07Publication status: PublishedFunder: Department of Health; Grant(s): NIHR300246Funder: national institute for health research; Grant(s): NIHR300246BackgroundPatients presenting with chest pain represent a large proportion of attendances to emergency departments. In these patients clinicians often consider the diagnosis of acute myocardial infarction (AMI), the timely recognition and treatment of which is clinically important. Clinical prediction models (CPMs) have been used to enhance early diagnosis of AMI. The Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision aid is currently in clinical use across Greater Manchester. CPMs have been shown to deteriorate over time through calibration drift. We aim to assess potential calibration drift with T-MACS and compare methods for updating the model.MethodsWe will use routinely collected electronic data from patients who were treated using TMACS at two large NHS hospitals. This is estimated to include approximately 14,000 patient episodes spanning June 2016 to October 2020. The primary outcome of acute myocardial infarction will be sourced from NHS Digital's admitted patient care dataset. We will assess the calibration drift of the existing model and the benefit of updating the CPM by model recalibration, model extension and dynamic updating. These models will be validated by bootstrapping and one step ahead prequential testing. We will evaluate predictive performance using calibrations plots and c-statistics. We will also examine the reclassification of predicted probability with the updated TMACS model.DiscussionCPMs are widely used in modern medicine, but are vulnerable to deteriorating calibration over time. Ongoing refinement using routinely collected electronic data will inevitably be more efficient than deriving and validating new models. In this analysis we will seek to exemplify methods for updating CPMs to protect the initial investment of time and effort. If successful, the updating methods could be used to continually refine the algorithm used within TMACS, maintaining or even improving predictive performance over time.Trial registrationISRCTN number: ISRCTN41008456

Effects of Bariatric Surgery on Human Small Artery Function Evidence for Reduction in Perivascular Adipocyte Inflammation, and the Restoration of Normal Anticontractile Activity Despite Persistent Obesity

ObjectivesThe aim of this study was to investigate the effects of bariatric surgery on small artery function and the mechanisms underlying this.BackgroundIn lean healthy humans, perivascular adipose tissue (PVAT) exerts an anticontractile effect on adjacent small arteries, but this is lost in obesity-associated conditions such as the metabolic syndrome and type II diabetes where there is evidence of adipocyte inflammation and increased oxidative stress.MethodsSegments of small subcutaneous artery and perivascular fat were harvested from severely obese individuals before (n = 20) and 6 months after bariatric surgery (n = 15). Small artery contractile function was examined in vitro with wire myography, and perivascular adipose tissue (PVAT) morphology was assessed with immunohistochemistry.ResultsThe anticontractile activity of PVAT was lost in obese patients before surgery when compared with healthy volunteers and was restored 6 months after bariatric surgery. In vitro protocols with superoxide dismutase and catalase rescued PVAT anticontractile function in tissue from obese individuals before surgery. The improvement in anticontractile function after surgery was accompanied by improvements in insulin sensitivity, serum glycemic indexes, inflammatory cytokines, adipokine profile, and systolic blood pressure together with increased PVAT adiponectin and nitric oxide bioavailability and reduced macrophage infiltration and inflammation. These changes were observed despite the patients remaining severely obese.ConclusionsBariatric surgery and its attendant improvements in weight, blood pressure, inflammation, and metabolism collectively reverse the obesity-induced alteration to PVAT anticontractile function. This reversal is attributable to reductions in local adipose inflammation and oxidative stress with improved adiponectin and nitric oxide bioavailability

Metacognitive Therapy Self-Help for Anxiety-Depression: Single-Blind Randomized Feasibility Trial in Cardiovascular Disease

BACKGROUND: One in three cardiovascular disease (CVD) patients experience significant anxiety and depression. Current psychological interventions have limited efficacy in reducing such symptoms and are offered as a face-to-face intervention that may be a barrier to accessing treatment. We evaluated the feasibility and acceptability of delivering assisted home-based self-help metacognitive therapy (home-MCT) to cardiac rehabilitation (CR) patients experiencing anxiety and depression. METHOD: One hundred eight CR patients with elevated anxiety and/or depression were recruited to a single-blind randomized feasibility trial across two United Kingdom National Health Service Trusts and were randomized to usual CR or usual CR plus home-MCT. The feasibility and acceptability of adding home-MCT to CR was based on credibility or expectancy ratings, recruitment rate, drop-outs, number of CR and home-MCT modules completed, and ability of outcome measures to discriminate between patients. The study was used to refine the sample size estimate for a full-scale trial. The quality of telephone support calls delivered by CR staff trained in MCT was assessed. RESULTS: Home-MCT was found to be feasible and acceptable for the current CR patients with anxiety and depression. Recruitment and retention of participants was high, and attendance at CR was similar for both groups. Completion of home-MCT was high, but the quality of telephone support calls delivered was lower than expected. CONCLUSIONS: Home-MCT was acceptable and feasible to deliver to CR patients experiencing anxiety and depression, and the feasibility of conducting a full-scale trial of the intervention was established. Home-MCT may provide additional treatment options for cardiac patients experiencing psychological distress. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

Metacognitive therapy home-based self-help for anxiety and depression in cardiovascular disease patients in the UK: A single-blind randomised controlled trial.

BackgroundAnxiety and depression in cardiac rehabilitation (CR) are associated with greater morbidity, mortality, and increased healthcare costs. Current psychological interventions within CR have small effects based on low-quality studies of clinic-based interventions with limited access to home-based psychological support. We tested the effectiveness of adding self-help metacognitive therapy (Home-MCT) to CR in reducing anxiety and depression in a randomised controlled trial (RCT).Methods and findingsWe ran a single-blind, multi-centre, two-arm RCT. A total of 240 CR patients were recruited from 5 NHS-Trusts across North West England between April 20, 2017 and April 6, 2020. Patients were randomly allocated to Home-MCT+CR (n = 118, 49.2%) or usual CR alone (n = 122, 50.8%). Randomisation was 1:1 via randomised blocks within hospital site, balancing arms on sex and baseline Hospital Anxiety and Depression Scale (HADS) scores. The primary outcome was the HADS total score at posttreatment (4-month follow-up). Follow-up data collection occurred between August 7, 2017 and July 20, 2020. Analysis was by intention to treat. The 4-month outcome favoured the MCT intervention group demonstrating significantly lower end of treatment scores (HADS total: adjusted mean difference = -2.64 [-4.49 to -0.78], p = 0.005, standardised mean difference (SMD) = 0.38). Sensitivity analysis using multiple imputation (MI) of missing values supported these findings. Most secondary outcomes also favoured Home-MCT+CR, especially in reduction of post-traumatic stress symptoms (SMD = 0.51). There were 23 participants (19%) lost to follow-up in Home-MCT+CR and 4 participants (3%) lost to follow-up in CR alone. No serious adverse events were reported. The main limitation is the absence of longer term (e.g., 12-month) follow-up data.ConclusionSelf-help home-based MCT was effective in reducing total anxiety/depression in patients undergoing CR. Improvement occurred across most psychological measures. Home-MCT was a promising addition to cardiac rehabilitation and may offer improved access to effective psychological treatment in cardiovascular disease (CVD) patients.Trial registrationNCT03999359

Restoring Perivascular Adipose Tissue Function in Obesity Using Exercise

From Springer Nature via Jisc Publications RouterHistory: accepted 2020-12-21, registration 2020-12-21, pub-electronic 2021-03-09, online 2021-03-09, pub-print 2021-12Publication status: PublishedFunder: British Heart Foundation; doi: http://dx.doi.org/10.13039/501100000274; Grant(s): FS/13/56/30645, FS/16/58/32734, PG/16/52/32229Abstract: Purpose: Perivascular adipose tissue (PVAT) exerts an anti-contractile effect which is vital in regulating vascular tone. This effect is mediated via sympathetic nervous stimulation of PVAT by a mechanism which involves noradrenaline uptake through organic cation transporter 3 (OCT3) and β3-adrenoceptor-mediated adiponectin release. In obesity, autonomic dysfunction occurs, which may result in a loss of PVAT function and subsequent vascular disease. Accordingly, we have investigated abnormalities in obese PVAT, and the potential for exercise in restoring function. Methods: Vascular contractility to electrical field stimulation (EFS) was assessed ex vivo in the presence of pharmacological tools in ±PVAT vessels from obese and exercised obese mice. Immunohistochemistry was used to detect changes in expression of β3-adrenoceptors, OCT3 and tumour necrosis factor-α (TNFα) in PVAT. Results: High fat feeding induced hypertension, hyperglycaemia, and hyperinsulinaemia, which was reversed using exercise, independent of weight loss. Obesity induced a loss of the PVAT anti-contractile effect, which could not be restored via β3-adrenoceptor activation. Moreover, adiponectin no longer exerts vasodilation. Additionally, exercise reversed PVAT dysfunction in obesity by reducing inflammation of PVAT and increasing β3-adrenoceptor and OCT3 expression, which were downregulated in obesity. Furthermore, the vasodilator effects of adiponectin were restored. Conclusion: Loss of neutrally mediated PVAT anti-contractile function in obesity will contribute to the development of hypertension and type II diabetes. Exercise training will restore function and treat the vascular complications of obesity

The prognostic value of emergency department measured hypertension: A systematic review and meta‐analysis

From Wiley via Jisc Publications RouterHistory: received 2021-03-25, rev-recd 2021-06-07, accepted 2021-06-15, pub-electronic 2021-09-22Article version: VoRPublication status: PublishedFunder: Royal College of Emergency Medicine; Id: http://dx.doi.org/10.13039/501100007566Funder: National Institute of Health Research (UK)Abstract: Objectives: The objective was to assess the prognostic value of hypertension detected in the emergency department (ED). Methods: The ED presents a unique opportunity to predict long‐term cardiovascular disease (CVD) outcomes with its potential for high‐footfall, and large‐scale routine data collection applied to underserved patient populations. A systematic review and meta‐analyses were conducted to assess the prognostic performance and feasibility of ED‐measured hypertension as a risk factor for long‐term CVD outcomes. We searched MEDLINE and Embase databases and gray literature sources. The target populations were undifferentiated ED patients. The prognostic factor of interest was hypertension. Feasibility outcomes included prevalence, reliability, and follow‐up attendance. Meta‐analyses were performed for feasibility using a random effect and exact likelihood. Results: The searches identified 1072 studies after title and abstract review, 53 studies had their full text assessed for eligibility, and 26 studies were included. Significant heterogeneity was identified, likely due to the international populations and differing study design. The meta‐analyses estimate of prevalence for ED‐measured hypertension was 0.31 (95% confidence interval 0.25–0.37). ED hypertension was persistent outside the ED (FE estimate of 0.50). The proportion of patients attending follow‐up was low with an exact likelihood estimate of 0.41. Three studies examined the prognostic performance of hypertension and demonstrated an increased risk of long‐term CVD outcomes. Conclusion: Hypertension can be measured feasibly in the ED and consequently used in a long‐term cardiovascular risk prediction model. There is an opportunity to intervene in targeted individuals, using routinely collected data