The relationship between prescription rates of oral corticosteroids for respiratory diseases and deprivation in England.

Respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD), are common in England with the worst respiratory outcomes observed in the most deprived areas. There is limited published research to establish whether the rate of oral corticosteroid (OCS) prescribing for asthma and COPD is linked to levels of deprivation. This study carried out a multivariable regression analysis of publicly available data and found that deprivation is associated with a statistically significant increase in the proportion of patients receiving an OCS prescription for asthma or COPD at a GP practice level (p < 0.001). The model estimated that the proportion of prescriptions is 1.88% (95% CI 1.83% to 1.92%) and 2.84% (95% CI 2.70% to 2.98%) for the least deprived GP practice and the most deprived GP practice, respectively. This study lays the groundwork for future research using individual patient level data to consider the impact of variation in OCS prescribing rates.

Renal denervation for uncontrolled hypertension: a systematic review and meta-analysis examining multiple subgroups.

This systematic review and meta-analysis was conducted to assess the randomized controlled trial (RCT) evidence available for renal denervation (RDN) in uncontrolled arterial hypertension. Twenty-five RCTs met the eligibility criteria for the systematic review, and 16 RCTs were included in the meta-analysis. The results of the random effects meta-analysis estimated a mean difference of -8.5 mmHg [95% confidence interval (CI) -13.5 to -3.6] for office SBP, -3.6 mmHg (95% CI -5.2 to -2.0) for 24 h SBP and -3.9 mmHg (95% CI -5.6 to -2.2) for ambulatory daytime SBP in favour of RDN compared with control (medication and/or sham-only) at primary follow-up. Similarly favourable results were observed across a range of prespecified subgroup analyses, including treatment-resistant hypertension. This meta-analysis suggests that the use of RDN in uncontrolled hypertension leads to consistent reductions in blood pressure. Reductions appear to be statistically consistent in the presence or absence of medications and in populations resistant to the use of three medications.

Systematic Review and Metaanalysis of Pharmacological Interventions in Adult-Onset Still Disease and the Role of Biologic Disease-Modifying Antirheumatic Drugs.

OBJECTIVE: To conduct a systematic review of the effectiveness and safety of pharmacological treatments for adult-onset Still disease (AOSD). METHODS: Six databases, 2 trial registries, and conference abstracts were searched from January 2012 to February 2023 for studies of pharmacological interventions in people with AOSD. Outcomes were rates of remission and response, discontinuation of concurrent treatments, complications of AOSD, and treatment-related adverse events. Risk of bias was assessed with the Cochrane risk of bias tool and the Joanna Briggs Institute tool for case series. RESULTS: Forty-four studies evaluated treatments, including nonsteroidal antiinflammatory drugs (NSAIDs), corticosteroids (CS), conventional synthetic disease-modifying antirheumatic drugs (DMARDs), and biologic DMARDs (bDMARDs). For bDMARDs, tocilizumab (TCZ), anakinra (ANK), and canakinumab (CNK) had the most available data. Although 3 randomized controlled trials did not show statistically significant benefits of bDMARDs, metaanalyses showed high rates of complete remission and CS discontinuation. Complete remission was 80% (95% CI 59-92%, I 2 36%), 73% (95% CI 58-84%, I 2 66%), and 77% (95% CI 29-97%, I 2 82%) and CS discontinuation was 57% (95% CI 29-81%, I 2 66%), 47% (95% CI 18-78%, I 2 79%), and 34% (95% CI 6-81%, I 2 59%), respectively, for TCZ, ANK, and CNK. Studies with a higher proportion of patients previously treated with bDMARDs showed a trend toward lower rates of CS discontinuation (P = 0.05). The analyses had high clinical heterogeneity, largely because treatments were prescribed as different lines of therapy. CONCLUSION: Evidence supports TCZ, ANK, and CNK therapy for AOSD. However, the magnitude of effect and comparative effectiveness of treatments is uncertain.

An Economic Evaluation of a Streamlined Day-Case Atrial Fibrillation Ablation Protocol and Conventional Cryoballoon Ablation versus Antiarrhythmic Drugs in a UK Paroxysmal Atrial Fibrillation Population.

BACKGROUND AND AIMS: Symptom control for atrial fibrillation can be achieved by catheter ablation or drug therapy. We assessed the cost effectiveness of a novel streamlined atrial fibrillation cryoballoon ablation protocol (AVATAR) compared with optimised antiarrhythmic drug (AAD) therapy and a conventional catheter ablation protocol, from a UK National Health Service (NHS) perspective. METHODS: Data from the AVATAR study were assessed to determine the cost effectiveness of the three protocols in a two-step process. In the first stage, statistical analysis of clinical efficacy outcomes was conducted considering either a three-way comparison (AVATAR vs. conventional ablation vs. optimised AAD therapies) or a two-way comparison (pooled ablation protocol data vs. optimised AAD therapies). In the second stage, models assessed the cost effectiveness of the protocols. Costs and some of the clinical inputs in the models were derived from within-trial cost analysis and published literature. The remaining inputs were derived from clinical experts. RESULTS: No significant differences between the ablation protocols were found for any of the clinical outcomes used in the model. Results of a within-trial cost analysis show that AVATAR is cost-saving (£1279 per patient) compared with the conventional ablation protocol. When compared with optimised AAD therapies, AVATAR (pooled conventional and AVATAR ablation protocols efficacy) was found to be more costly while offering improved clinical benefits. Over a lifetime time horizon, the incremental cost-effectiveness ratio of AVATAR was estimated as £21,046 per quality-adjusted life-year gained (95% credible interval £7086-£71,718). CONCLUSIONS: The AVATAR streamlined protocol is likely to be a cost-effective option versus both conventional ablation and optimised AAD therapy in the UK NHS healthcare setting.

Economic evaluation of first-line cryoballoon ablation versus antiarrhythmic drug therapy for the treatment of paroxysmal atrial fibrillation from an English National Health Service perspective.

INTRODUCTION: Three recent randomised controlled trials have demonstrated that pulmonary vein isolation as an initial rhythm control strategy with cryoablation reduces atrial arrhythmia recurrence in patients with symptomatic paroxysmal atrial fibrillation (PAF) compared with antiarrhythmic drug (AAD) therapy. The aim of this study was to evaluate the cost-effectiveness of first-line cryoablation compared with first-line AADs for treating symptomatic PAF in an English National Health Service (NHS) setting. METHODS: Individual patient-level data from 703 participants with PAF enrolled into Cryo-FIRST (Catheter Cryoablation Versus Antiarrhythmic Drug as First-Line Therapy of Paroxysmal Atrial Fibrillation), STOP AF First (Cryoballoon Catheter Ablation in an Antiarrhythmic Drug Naive Paroxysmal Atrial Fibrillation) and EARLY-AF (Early Aggressive Invasive Intervention for Atrial Fibrillation) were used to derive the parameters applied in the cost-effectiveness model (CEM). The CEM comprised a hybrid decision tree and Markov structure. The decision tree had a 1-year time horizon and was used to inform the initial health state allocation in the first cycle of the Markov model (40-year time horizon; 3-month cycle length). Health benefits were expressed in quality-adjusted life years (QALYs). Costs and benefits were discounted at 3.5% per year. Model outcomes were generated using probabilistic sensitivity analysis. RESULTS: The results estimated that cryoablation would yield more QALYs (+0.17) and higher costs (+£641) per patient over a lifetime than AADs. This produced an incremental cost-effectiveness ratio of £3783 per QALY gained. Independent of initial treatment, individuals were expected to receive ~1.2 ablations over a lifetime. There was a 45% relative reduction in time spent in AF health states for those initially treated with cryoablation. DISCUSSION: AF rhythm control with first-line cryoablation is cost effective compared with first-line AADs in an English NHS setting.

The Cost-Effectiveness of First-Line Cryoablation vs First-Line Antiarrhythmic Drugs in Canadian Patients With Paroxysmal Atrial Fibrillation.

BACKGROUND: The EARLY-AF (NCT02825979), STOP AF First (NCT03118518), and Cryo-FIRST (NCT01803438) randomised controlled trials (RCTs) demonstrated that cryoballoon pulmonary vein isolation reduces atrial fibrillation (AF) recurrence compared with antiarrhythmic drugs (AADs) in patients with symptomatic paroxysmal atrial fibrillation (PAF). The present study developed a cost-effectiveness model (CEM) of first-line cryoablation compared with first-line AADs for PAF, from the Canadian health care payer's perspective. METHODS: Data from the 3 RCTs were analysed to estimate key CEM parameters. The model structure used a decision tree for the first 12 months and a Markov model with a 3-month cycle length for the remaining lifetime time horizon. Costs were set at 2023 Canadian dollars, health benefits were expressed as quality-adjusted life years (QALYs), and both were discounted 3% annually. Probabilistic sensitivity analysis (PSA) considered parameter uncertainty. RESULTS: The statistical analysis estimated that first-line cryoablation generates a 47% reduction (P < 0.001) in the rate of AF recurrence, a 73% reduction in the rate of subsequent ablation (P < 0.001), and a 4.3% (P = 0.025) increase in health-related quality of life, compared with first-line AADs. The PSA indicates that an individual treated with first-line cryoablation accrues less costs (-$3,862) and more QALYs (0.19) compared with first-line AADs. Cryoablation is cost-saving in 98.4% of PSA iterations and has a 99.9% probability of being cost-effective at a cost-effectiveness threshold of $50,000 per QALY gained. Cost-effectiveness results were robust to changes in key model parameters. CONCLUSIONS: First-line cryoballoon ablation is cost-effective when compared with AADs for patients with symptomatic PAF.

An economic evaluation of first-line cryoballoon ablation vs antiarrhythmic drug therapy for the treatment of paroxysmal atrial fibrillation from a U.S. Medicare perspective.

Background: Three recent randomized controlled trials have demonstrated that, as an initial rhythm control strategy, first-line cryoballoon ablation (cryoablation) reduces atrial arrhythmia recurrence compared with antiarrhythmic drugs (AADs) in patients with symptomatic paroxysmal atrial fibrillation (PAF). Objective: The study sought to evaluate the cost-effectiveness of first-line cryoablation compared with first-line AADs for treating symptomatic PAF from a U.S. Medicare payer perspective. Methods: Individual patient-level data from 703 participants with PAF enrolled into the Cryo-FIRST (NCT01803438), STOP AF First (NCT03118518), and EARLY-AF (NCT02825979) trials were used to derive parameters for the cost-effectiveness model. The cost-effectiveness model used a hybrid decision tree and Markov structure. The decision tree had a 1-year time horizon and was used to inform the initial health state allocation in the first cycle of the Markov model. The Markov model used a 40-year time horizon (3-month cycle length). Health benefits were expressed in quality-adjusted life years (QALYs). Costs and benefits were discounted at 3% per year. Results: Cryoablation was estimated to yield higher QALYs (+0.17) and higher costs (+$4274) per patient over a 40-year time horizon than AADs. Ultimately, this produced an average incremental cost-effectiveness ratio of $24,637 per QALY gained. Independent of initial treatment, individuals were expected to receive ∼1.2 ablations over a lifetime. There was a 45% relative reduction in time spent in atrial fibrillation health states for those initially treated with cryoablation compared with AADs. Conclusion: Initial rhythm control with first-line cryoballoon ablation is highly cost-effective compared with first-line AADs from a U.S. Medicare payer perspective.

Development of a health economic model to evaluate the cost-effectiveness of roxadustat in treating anemia associated with non-dialysis-dependent chronic kidney disease.

BACKGROUND: Treatment for anemia of chronic kidney disease (CKD) largely consists of erythropoiesis-stimulating agents (ESAs) with iron supplementation. Although ESAs are well-established and efficacious, their use has been associated with considerable economic and humanistic burdens. Roxadustat, an oral medication, is a hypoxia-inducible factor prolyl hydroxylase inhibitor that targets multiple causes of CKD and has a similar efficacy and safety profile to ESAs. The cost-effectiveness of this treatment, however, has yet to be investigated. OBJECTIVE: The study objective was to develop a health economic model to evaluate the cost-effectiveness of roxadustat compared with ESAs for treating anemia of non-dialysis-dependent (NDD) CKD. METHODS: A cohort-based model was developed for a hypothetical cohort of 1,000 patients with anemia of NDD CKD, incorporating eight health states, representing the hemoglobin level of each patient. The model was informed by individual patient-level data from the roxadustat global phase 3 clinical trial program. Total and incremental costs as well as quality-adjusted life-years (QALYs) associated with roxadustat versus ESAs were estimated from the perspective of the UK National Health Service. Sensitivity analyses were performed to assess the robustness of the model. Analyses exploring alternative scenarios were also conducted. RESULTS: On a per-person basis, over 1,000 simulations, roxadustat was found to be on average less costly (-£32) and more effective (+0.01 QALYs) than ESAs, with a dominant incremental cost-effectiveness ratio. The probability of cost-effectiveness at a £20,000 per QALY willingness-to-pay threshold from the UK perspective was 67%. CONCLUSION: The model developed may be a useful instrument that, alongside expert clinical opinion, can inform clinical and policy decision-making regarding treatment of anemia of NDD CKD. The model highlights the cost-effectiveness of roxadustat, as well as its potential to have a meaningful impact in reducing the burden of anemia of NDD CKD.

Economic assessment of the impact of telecare on the use of social care resources using a zero-inflated, hierarchical linear statistical model.

INTRODUCTION: There is an ever-increasing demand for social care in the UK, with expenditure predicted to double to £56 billion by 2038/39. Many councils are under budget restrictions putting pressure on the number of services provided and their quality. Telecare complements social care and involves the implementation of technology to keep individuals more independent. METHODS: This study utilised a retrospective time-series analysis of data provided by Lancashire County Council between the period January-2013 to March-2018. A generalised linear mixed model (GLMM) was used to control for potential confounders. Two groups were identified: those using telecare (telecare group, n = 699) and those who did not (control group, n = 839). RESULTS: The fixed effects data showed that telecare group start £75 per week lower in cost and as time progressed this reduced further by 9p per service user per week. In contrast, control group costs rose 5p per week per user. This effect was independent of age but was affected by measure of dependency. Analysis was then utilised to make predictions based on weighted averages. The scenario showed a total difference of £4,949 per service user over the whole year. A second scenario pro-rata'd costs for the full year showed a difference of £6,214, where telecare would avoid costs of £17 million per year. DISCUSSION: This analysis demonstrates that there is evident potential for the use of telecare to reduce social care resource use and costs. This study also highlights the use of a GLMM as a novel method of analysing observed data by controlling confounders.

Modelling the cost-effectiveness of subepidermal moisture measurement as part of a process of assessment and intervention to prevent hospital-acquired pressure ulcers.

Skin tissue assessment is traditionally used to identify early signs of pressure damage from changes observed at the skin surface. However, the early onset of tissue damage induced by pressure and shear forces is likely to be on soft tissues beneath the surface of the skin. Subepidermal moisture (SEM) is a biophysical marker for the detection of early and deep pressure-induced tissue damage. Measurement of SEM can detect early pressure ulcers up to 5 days before visible skin changes occur. The aim of this study was to evaluate the cost-effectiveness of SEM measurement compared with visual skin assessment (VSA). A decision-tree model was developed. Outcomes are the incidence of hospital-acquired pressure ulcers, quality-adjusted life-years (QALYs) and costs to the UK National Health Service. Costs are at 2020/21 prices. The effects of parameter uncertainty are tested in univariate and probabilistic sensitivity analysis. In a representative NHS acute hospital, the incremental cost of SEM assessment as an adjunct to VSA is -£8.99 per admission, and SEM assessment is expected to reduce the incidence of hospital-acquired pressure ulcers by 21.1%, reduce NHS costs and lead to a gain of 3.634 QALYs. The probability of cost-effectiveness at a threshold of £30 000 per quality-adjusted life year is 61.84%. Pathways that include SEM assessment make it possible to implement early and anatomy-specific interventions which have the potential to improve the effectiveness of pressure ulcer prevention and reduce healthcare costs.

(+)-Catechin Attenuates Multiple Atherosclerosis-Associated Processes In Vitro, Modulates Disease-Associated Risk Factors in C57BL/6J Mice and Reduces Atherogenesis in LDL Receptor Deficient Mice by Inhibiting Inflammation and Increasing Markers of Plaque Stability.

SCOPE: A prospective study of 34492 participants shows an inverse association between (+)-catechin intake and coronary heart disease. The effects of (+)-catechin on atherosclerosis and associated risk factors are poorly understood and are investigated. METHODS AND RESULTS: (+)-Catechin attenuates reactive oxygen species production in human macrophages, endothelial cells and vascular smooth muscle cells, chemokine-driven monocytic migration, and proliferation of human macrophages and their expression of several pro-atherogenic genes. (+)-Catechin also improves oxidized LDL-mediated mitochondrial membrane depolarization in endothelial cells and attenuates growth factor-induced smooth muscle cell migration. In C57BL/6J mice fed high fat diet (HFD) for 3 weeks, (+)-catechin attenuates plasma levels of triacylglycerol and interleukin (IL)-1ß and IL-2, produces anti-atherogenic changes in liver gene expression, and reduces levels of white blood cells, myeloid-derived suppressor cells, Lin- Sca+ c-Kit+ cells, and common lymphoid progenitor cells within the bone marrow. In LDL receptor deficient mice fed HFD for 12 weeks, (+)-catechin attenuates atherosclerotic plaque burden and inflammation with reduced macrophage content and increased markers of plaque stability; smooth muscle cell and collagen content. CONCLUSION: This study provides novel, detailed insights into the cardio-protective actions of (+)-catechin together with underlying molecular mechanisms and supports further assessments of its beneficial effects in human trials.

A cost-effectiveness evaluation of latent tuberculosis infection screening of a migrant population in Malaysia.

To estimate the costs and benefits of screening for latent tuberculosis infection (LTBI) in a migrant population in Malaysia. An economic model was developed from a Malaysian healthcare perspective to compare QuantiFERON-TB Gold Plus (QuantiFERON) with the tuberculin skin test (TST). A decision tree was used to capture outcomes relating to LTBI screening followed by a Markov model that simulated the lifetime costs and benefits of the patient cohort. The Markov model did not capture the impact of secondary infections. The model included an R shiny interactive interface to allow adaptation to other scenarios and settings. QuantiFERON is both more effective and less costly than TST (dominant). Compared with QuantiFERON, the lifetime risk of developing active TB increases by approximately 40% for TST due to missed LTBI cases during screening (i.e. a higher number of false negative cases for TST). For a migrant population in Malaysia, QuantiFERON is cost-effective when compared with TST. Further research should consider targeted LTBI screening for migrants in Malaysia based on common risk factors.

Cost-effectiveness of high dose versus adjuvanted trivalent influenza vaccines in England and Wales.

AIMS: High dose trivalent influenza vaccine (HD TIV) and adjuvant TIV (aTIV) have been developed specifically for adults aged 65 and older (65+) who are at high risk of life-threatening complications. However, there is a scarcity of evidence comparing the clinical and cost-effectiveness of HD TIV and aTIV. The aim of this study was to determine the cost-effectiveness of HD TIV versus aTIV in the England and Wales 65+ population. METHODS: A cost-utility analysis was conducted using a decision tree with two influenza related outcomes: Laboratory confirmed cases that could result in GP consultation, and hospitalizations that may result in premature mortality. Due to a lack of comparative evidence, the effectiveness of HD TIV versus aTIV was calculated indirectly, based on relative effectiveness estimates for each vaccine versus a common comparator, standard dose (SD) TIV. The primary analysis included hospitalizations explicitly due to influenza/pneumonia. Cost-effectiveness was established for three scenarios applying differing relative effectiveness estimates for aTIV versus SD TIV. Uncertainty was analysed in one-way deterministic sensitivity analyses. A secondary analysis included hospitalizations due to any respiratory illness. RESULTS: The minimum population impact of vaccination with HD TIV rather than aTIV was 13,092 fewer influenza cases, 1,109 fewer influenza related deaths, 4,673 fewer hospitalizations, and 3,245 fewer GP appointments. HD TIV was cost-effective versus aTIV for all three effectiveness scenarios, with incremental cost-effectiveness ratios (ICER) equal to £1,932, £4,181, and £8,767 per quality adjusted life year. Results were consistent across the secondary analysis and deterministic sensitivity analyses. LIMITATIONS: The analysis was limited by a lack of robust and consistent effectiveness data for aTIV. CONCLUSION: HD TIV is cost-effective versus aTIV in people aged 65+ in England and Wales. Use of HD TIV over aTIV could increase clinical benefits and reduce the public health and economic burden of influenza.

Protective effects of a unique combination of nutritionally active ingredients on risk factors and gene expression associated with atherosclerosis in C57BL/6J mice fed a high fat diet.

Atherosclerosis, an inflammatory disorder of the vasculature and the underlying cause of cardiovascular disease, is responsible for one in three global deaths. Consumption of active food ingredients such as omega-3 polyunsaturated fatty acids, flavanols and phytosterols has many beneficial effects on cardiovascular disease. However, their combined actions on the risk factors for atherosclerosis remains poorly understood. We have previously shown that a formulation containing each of these active components at physiologically relevant doses modulated several monocyte/macrophage processes associated with atherosclerosis in vitro, including inhibition of cytokine-induced pro-inflammatory gene expression, chemokine-driven monocyte migration, expression of M1 phenotype markers, and promotion of cholesterol efflux. The objectives of the present study were to investigate whether the protective actions of the formulation extended in vivo and to delineate the potential underlying mechanisms. The formulation produced several favourable changes, including higher plasma levels of HDL and reduced levels of macrophages and myeloid-derived suppressor cells in the bone marrow. The mRNA expression of liver-X-receptor-α, peroxisome proliferator-activated receptor-γ and superoxide dismutase-1 was induced in the liver and that of interferon-γ and the chemokine (C-X-C motif) ligand 1 decreased, thereby suggesting the potential mechanisms for many beneficial effects. Other changes were also observed such as increased plasma levels of triglycerides and lipid peroxidation that may reflect potential activation of brown fat. This study provides new insights into the protective actions and the potential underlying mechanisms of the formulation in vivo, particularly in relation to risk factors together with changes in systemic inflammation and hepatic lipid alterations associated with atherosclerosis and metabolic syndrome, and supports further assessments in human trials.

The impact of surgical site infection on hospitalisation, treatment costs, and health-related quality of life after vascular surgery.

Surgical site infections (SSI) substantially increase costs for healthcare providers because of additional treatments and extended patient recovery. The objective of this study was to assess the cost and health-related quality of life impact of SSI, from the perspective of a large teaching hospital in England. Data were available for 144 participants undergoing clean or clean-contaminated vascular surgery. SSI development, length of hospital stay, readmission, and antibiotic use were recorded over a 30-day period. Patient-reported EQ-5D scores were obtained at baseline, day 7 and day 30. Linear regressions were used to control for confounding variables. A mean SSI-associated length of stay of 9.72 days resulted in an additional cost of £3776 per patient (including a mean antibiotic cost of £532). Adjusting for age, smoking status, and procedure type, SSI was associated with a 92% increase in length of stay (P < 0.001). The adjusted episode cost was £3040. SSI reduced patient utility between baseline and day 30 by 0.156 (P = 0.236). Readmission rates were higher with SSI (P = 0.017), and the rate to return to work within 90 days was lower. Therefore, strategies to reduce the risk of surgical site infection for high-risk vascular patients should be investigated.

Quantifying the direct secondary health care cost of seasonal influenza in England.

BACKGROUND: The winter pressure often experienced by NHS hospitals in England is considerably contributed to by severe cases of seasonal influenza resulting in hospitalisation. The prevention planning and commissioning of the influenza vaccination programme in the UK does not always involve those who control the hospital budget. The objective of this study was to describe the direct medical costs of secondary care influenza-related hospital admissions across different age groups in England during two consecutive influenza seasons. METHODS: The number of hospital admissions, length of stay, and associated costs were quantified as well as determining the primary costs of influenza-related hospitalisations. Data were extracted from the Hospital Episode Statistics (HES) database between September 2017 to March 2018 and September 2018 to March 2019 in order to incorporate the annual influenza seasons. The use of international classification of disease (ICD)-10 codes were used to identify relevant influenza hospitalisations. Healthcare Resource Group (HRG) codes were used to determine the costs of influenza-related hospitalisations. RESULTS: During the 2017/18 and 2018/19 seasons there were 46,215 and 39,670 influenza-related hospital admissions respectively. This resulted in a hospital cost of £128,153,810 and £99,565,310 across both seasons. Results showed that those in the 65+ year group were associated with the highest hospitalisation costs and proportion of in-hospital deaths. In both influenza seasons, the HRG code WJ06 (Sepsis without Interventions) was found to be associated with the longest average length of stay and cost per admission, whereas PD14 (Paediatric Lower Respiratory Tract Disorders without Acute Bronchiolitis) had the shortest length of stay. CONCLUSION: This study has shown that influenza-related hospital admissions had a considerable impact on the secondary healthcare system during the 2017/18 and 2018/19 influenza seasons, before taking into account its impact on primary health care.

The interleukin-33-mediated inhibition of expression of two key genes implicated in atherosclerosis in human macrophages requires MAP kinase, phosphoinositide 3-kinase and nuclear factor-κB signaling pathways.

Atherosclerosis, a chronic inflammatory disorder of the walls of arteries, causes more deaths worldwide than any other disease. Cytokines, which are present at high levels in atherosclerotic plaques, play important roles in regulating the initiation and the progression of the disease. Previous studies using animal and cell culture model systems revealed protective, anti-atherogenic effects of the cytokine interleukin-33 (IL-33). The action of this cytokine involves both the induction and suppression of expression of many genes. Unfortunately, the signaling pathways that are responsible for the inhibition of gene expression by this cytokine are poorly understood. Further studies are required given the important roles of genes whose expression is inhibited by IL-33 in key cellular processes associated with atherosclerosis such as monocyte recruitment, foam cell formation and lipoprotein metabolism. We have investigated here the roles of various known IL-33 activated signaling pathways in such inhibitory actions using RNA interference-mediated knockdown assays and monocyte chemotactic protein-1 and intercellular adhesion molecule-1 as model genes. Key roles were identified for extracellular signal-regulated kinase-1/2, p38α kinase, c-Jun N-terminal kinase-1/2, phosphoinositide 3-kinase-γ, and p50 and p65 nuclear factor-κB in such inhibitory action of IL-33. These studies provide new insights on the signaling pathways through which IL-33 inhibits the macrophage expression of key atherosclerosis-associated genes.

Cost-effectiveness of a cardiac contractility modulation device in heart failure with normal QRS duration.

AIMS: The objective of this paper is to assess whether cardiac contractility modulation (via the Optimizer System) plus standard of care (SoC) is a cost-effective treatment for people with heart failure [New York Heart Association (NYHA) III, left ventricular ejection fraction of 25-45%, and narrow QRS] compared against SoC alone from the perspective of the English National Health Service. METHODS AND RESULTS: We developed a regression equation-based cost-effectiveness model, using individual patient data from three randomized control trials (FIX-HF-5 Phases 1 and 2, and FIX-HF-5C) to populate the majority of parameters. A series of regression equations predicted NYHA class over time, mortality, all-cause hospitalization rates, and health-related quality of life. We conducted the analysis in line with the National Institute for Health and Care Excellence reference case, modelling costs from an English National Health Service perspective, and considering outcomes in quality-adjusted life years (QALYs) over a patient lifetime perspective. Our base case analysis produced an incremental cost per additional QALY of GBP22 988 (€25 750) when comparing Optimizer + SoC to SoC alone. This result was not sensitive to parameter uncertainty but was sensitive to the time horizon over which costs and QALYs were captured and the duration over which a survival benefit with Optimizer + SoC can be assumed to apply. CONCLUSIONS: Cardiac contractility modulation is likely to be cost-effective in people with heart failure with reduced ejection fraction, NYHA III, and narrow QRS, provided that the treatment benefit can be maintained beyond the duration of the existing clinical trial follow-up. This analysis supports the current recommendations of the European Society of Cardiology that this therapy may be considered for such patients.

Nutraceuticals as therapeutic agents for atherosclerosis.

Atherosclerosis, a chronic inflammatory disorder of medium and large arteries and an underlying cause of cardiovascular disease (CVD), is responsible for a third of all global deaths. Current treatments for CVD, such as optimized statin therapy, are associated with considerable residual risk and several side effects in some patients. The outcome of research on the identification of alternative pharmaceutical agents for the treatment of CVD has been relatively disappointing with many promising leads failing at the clinical level. Nutraceuticals, products from food sources with health benefits beyond their nutritional value, represent promising agents in the prevention of CVD or as an add-on therapy with current treatments. This review will highlight the potential of several nutraceuticals, including polyunsaturated fatty acids, flavonoids and other polyphenols, as anti-CVD therapies based on clinical and pre-clinical mechanism-based studies.

Nutraceutical therapies for atherosclerosis.

Atherosclerosis is a chronic inflammatory disease affecting large and medium arteries and is considered to be a major underlying cause of cardiovascular disease (CVD). Although the development of pharmacotherapies to treat CVD has contributed to a decline in cardiac mortality in the past few decades, CVD is estimated to be the cause of one-third of deaths globally. Nutraceuticals are natural nutritional compounds that are beneficial for the prevention or treatment of disease and, therefore, are a possible therapeutic avenue for the treatment of atherosclerosis. The purpose of this Review is to highlight potential nutraceuticals for use as antiatherogenic therapies with evidence from in vitro and in vivo studies. Furthermore, the current evidence from observational and randomized clinical studies into the role of nutraceuticals in preventing atherosclerosis in humans will also be discussed.