Optimising clinical effectiveness and quality along the atrial fibrillation anticoagulation pathway: an economic analysis.

BACKGROUND: Atrial fibrillation (AF) represents the most common sustained cardiac arrhythmia. A service evaluation was carried out at an anticoagulation clinic in Newcastle upon-Tyne to explore the efficacy of introducing self-testing of anticoagulation status for AF patients on warfarin. The analysis presented aims to assess the potential cost savings and clinical outcomes associated with introducing self-testing at a clinic in the Northeast of England, and to determine the cost-effectiveness of a redesigned treatment pathway including genetic testing and self-testing components. METHODS: Questionnaires were administered to individuals participating in the service evaluation to understand the patient costs associated with clinical monitoring (139 patients), and quality-of-life before and after the introduction of self-testing (varying numbers). Additionally, data on time in therapeutic range (TTR) were captured at multiple time points to identify any change in outcome. Finally, an economic model was developed to assess the cost-effectiveness of introducing a redesigned treatment pathway, including genetic testing and self-testing, for AF patients. RESULTS: The average cost per patient of attending the anticoagulation clinic was £16.24 per visit (including carer costs). Costs were higher amongst patients tested at the hospital clinic than those tested at the community clinic. Improvements in quality-of-life across all psychological topics, and improved TTR, were seen following the introduction of self-testing. Results of the cost-effectiveness analysis showed that the redesigned treatment pathway was less costly and more effective than current practice. CONCLUSIONS: Allowing AF patients on warfarin to self-test, rather than attend clinic to have their anticoagulation status assessed, has the potential to reduce patient costs. Additionally, self-testing may result in improved quality-of-life and TTR. Introducing genetic testing to guide patient treatment based on sensitivity to warfarin, and applying this in combination with self-testing, may also result in improved patient outcomes and reduced costs to the health service in the long-term.

Evaluation of a complex healthcare intervention to increase smoking cessation in pregnant women: interrupted time series analysis with economic evaluation.

OBJECTIVES: To evaluate the effectiveness of a complex intervention to improve referral and treatment of pregnant smokers in routine practice, and to assess the incremental costs to the National Health Service (NHS) per additional woman quitting smoking. DESIGN: Interrupted time series analysis of routine data before and after introducing the intervention, within-study economic evaluation. SETTING: Eight acute NHS hospital trusts and 12 local authority areas in North East England. PARTICIPANTS: 37 726 records of singleton delivery including 10 594 to mothers classified as smoking during pregnancy. INTERVENTIONS: A package of measures implemented in trusts and smoking cessation services, aimed at increasing the proportion of pregnant smokers quitting during pregnancy, comprising skills training for healthcare and smoking cessation staff; universal carbon monoxide monitoring with routine opt-out referral for smoking cessation support; provision of carbon monoxide monitors and supporting materials; and an explicit referral pathway and follow-up protocol. MAIN OUTCOME MEASURES: Referrals to smoking cessation services; probability of quitting smoking during pregnancy; additional costs to health services; incremental cost per additional woman quitting. RESULTS: After introduction of the intervention, the referral rate increased more than twofold (incidence rate ratio=2.47, 95% CI 2.16 to 2.81) and the probability of quitting by delivery increased (adjusted OR=1.81, 95% CI 1.54 to 2.12). The additional cost per delivery was £31 and the incremental cost per additional quit was £952; 31 pregnant women needed to be treated for each additional quitter. CONCLUSIONS: The implementation of a system-wide complex healthcare intervention was associated with significant increase in rates of quitting by delivery.

Treatments for Hyperemesis Gravidarum and Nausea and Vomiting in Pregnancy: A Systematic Review.

Importance: Nausea and vomiting affects approximately 85% of pregnant women. The most severe form, hyperemesis gravidarum, affects up to 3% of women and can have significant adverse physical and psychological sequelae. Objective: To summarize current evidence on effective treatments for nausea and vomiting in pregnancy and hyperemesis gravidarum. Evidence Review: Databases were searched to June 8, 2016. Relevant websites and bibliographies were also searched. Titles and abstracts were assessed independently by 2 reviewers. Results were narratively synthesized; planned meta-analysis was not possible because of heterogeneity and incomplete reporting of findings. Findings: Seventy-eight studies (n = 8930 participants) were included: 67 randomized clinical trials (RCTs) and 11 nonrandomized studies. Evidence from 35 RCTs at low risk of bias indicated that ginger, vitamin B6, antihistamines, metoclopramide (for mild symptoms), pyridoxine-doxylamine, and ondansetron (for moderate symptoms) were associated with improved symptoms compared with placebo. One RCT (n = 86) reported greater improvements in moderate symptoms following psychotherapy (change in Rhodes score [range, 0 {no symptoms} to 40 {worst possible symptoms}], 18.76 [SD, 5.48] to 7.06 [SD, 5.79] for intervention vs 19.18 [SD, 5.63] to 12.81 [SD, 6.88] for comparator [P < .001]). For moderate-severe symptoms, 1 RCT (n = 60) suggested that pyridoxine-doxylamine combination taken preemptively reduced risk of recurrence of moderate-severe symptoms compared with treatment once symptoms begin (15.4% vs 39.1% [P < .04]). One RCT (n = 83) found that ondansetron was associated with lower nausea scores on day 4 than metoclopramide (mean visual analog scale [VAS] score, 4.1 [SD, 2.9] for ondansetron vs 5.7 [SD, 2.3] for metoclopramide [P = .023]) but not episodes of emesis (5.0 [SD, 3.1] vs 3.3 [SD, 3], respectively [P = .013]). Although there was no difference in trend in nausea scores over the 14-day study period, trend in vomiting scores was better in the ondansetron group (P = .042). One RCT (n = 159) found no difference between metoclopramide and promethazine after 24 hours (episodes of vomiting, 1 [IQR, 0-5] for metoclopramide vs 2 [IQR, 0-3] for promethazine [P = .81], VAS [0-10 scale] for nausea, 2 [IQR, 1-5] vs 2 [IQR, 1-4], respectively [P = .99]). Three RCTs compared corticosteroids with placebo or promethazine or metoclopramide in women with severe symptoms. Improvements were seen in all corticosteroid groups, but only a significant difference between corticosteroids vs metoclopramide was reported (emesis reduction, 40.9% vs 16.5% at day 2; 71.6% vs 51.2% at day 3; 95.8% vs 76.6% at day 7 [n = 40, P < .001]). For other interventions, evidence was limited. Conclusions and Relevance: For mild symptoms of nausea and emesis of pregnancy, ginger, pyridoxine, antihistamines, and metoclopramide were associated with greater benefit than placebo. For moderate symptoms, pyridoxine-doxylamine, promethazine, and metoclopramide were associated with greater benefit than placebo. Ondansetron was associated with improvement for a range of symptom severity. Corticosteroids may be associated with benefit in severe cases. Overall the quality of evidence was low.

Digital variance angiography in patients undergoing lower limb arterial recanalization: cost-effectiveness analysis within the English healthcare setting.

Aim: Digital variance angiography (DVA) is a recently developed image processing method capable of improving image quality compared with the traditionally used digital subtraction angiography (DSA), among patients undergoing lower limb x-ray angiography. This study aims to explore the potential cost-effectiveness of DVA from an English National Health Service perspective. Materials & methods: A two-part economic model, consisting of a decision tree and a Markov model, was developed to consider the costs and health outcomes associated with the use of DVA as part of current practice imaging, compared with x-ray angiography using standard DSA. The model explored the impact of DVA on the development of acute kidney injury (AKI), chronic kidney disease and radiation-induced cancer over a lifetime horizon. Both deterministic and probabilistic analyses were performed to assess the cost per quality-adjusted life-year (QALY). Results: Base-case results indicate that DVA results in cost savings of £309 per patient, with QALYs also improving (+0.025) over a lifetime. As shown in sensitivity analysis, a key driver of model results is the relative risk (RR) reduction of contrast-associated acute kidney injury associated with use of DVA. The intervention also decreases the risk of carcinoma over a lifetime. Scenario analyses show that cost savings range from £310 to £553, with QALY gains ranging from 0.048 to 0.109 per patient. Conclusion: The use of DVA could result in a decrease in costs and an increase in QALYs over a lifetime, compared with existing imaging practice. The potential for this technology to offer an economically viable alternative to existing image processing methods, through a reduction in contrast media volume and radiation exposure, has been demonstrated.

Cost-Utility Analysis of the Caresyntax Platform to Identify Patients at Risk of Surgical Site Infection Undergoing Colorectal Surgery.

BACKGROUND: Surgical site infections (SSIs) account for up to 18% of all healthcare-associated infections (HAIs). The Caresyntax data-driven surgery platform incorporates the most common risk factors for SSI, to identify high-risk surgical patients before they leave the operating theatre and treat them prophylactically with negative pressure wound therapy (NPWT). An economic analysis was performed to assess the costs and health outcomes associated with introduction of the technology in the English healthcare setting. METHODS: A hybrid decision tree/Markov model was developed to reflect the treatment pathways that patients undergoing colorectal surgery would typically follow, both over the short term (30-day hospital setting) and long term (lifetime). The analysis considered implementation of Caresyntax's platform-based SSI predictive algorithm in the hospital setting, compared with standard of care, from an English National Health Service (NHS) perspective. The base-case analysis presents results in terms of cost per quality-adjusted life-year (QALY) gained, as well as operational impact. RESULTS: The base-case analysis indicates that the intervention leads to a cost saving of £55.52m across the total NHS colorectal surgery patient population in 1 year. In addition, the intervention has a 98.36% probability of being cost effective over a lifetime horizon. The intervention results in the avoidance of 19,744 SSI events, as well 191,911 excess hospital bed days saved. CONCLUSION: Caresyntax's platform-based SSI predictive algorithm has the potential to result in cost savings and improved patient quality of life. Additionally, operational gains for the healthcare provider, including reduced infection rates and hospital bed days saved, have been shown through the economic modeling.

Early Cost-Effectiveness and Price Threshold Analyses of Resmetirom: An Investigational Treatment for Management of Nonalcoholic Steatohepatitis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is characterized by inflammation and hepatocellular damage caused by accumulation of fat in the liver. Resmetirom (MGL-3196) is an orally administered, small-molecule, liver-targeted, selective thyroid hormone receptor-ß agonist. This early analysis explored the potential cost effectiveness of resmetirom for the treatment of NASH from a US commercial payer perspective. METHODS: An early economic model was developed to reflect the clinical pathways typically followed by patients with NASH and liver fibrosis. Use of resmetirom, compared with placebo, was assessed. The Markov model structure was informed by a previous modeling study and a randomized, double-blind, placebo-controlled, phase II trial of resmetirom. Costs and outcomes were assessed over a lifetime time horizon with results presented in terms of cost per quality-adjusted life-year (QALY) gained. RESULTS: Resmetirom treatment resulted in increased costs of US$66,764 per patient, while increasing QALYs by 1.24. The incremental cost-effectiveness ratio was US$53,929 per QALY gained, indicating resmetirom treatment would potentially be cost effective at a willingness-to-pay (WTP) threshold of US$100,000. Results indicated that resmetirom would reduce the lifetime number of cases of decompensated cirrhosis (- 87), hepatocellular carcinoma (- 59), and liver transplants (- 30) per 1,000 patients compared with placebo. Resmetirom treatment remained cost effective at a US$100,000 WTP threshold up to a daily price point of US$72.00. CONCLUSION: Resmetirom is a potentially cost-effective treatment option for patients with NASH and liver fibrosis based on an analysis performed from a US commercial payer perspective. Future economic analyses of the technology should, however, focus on overcoming the limitations of existing modeling methodology.

Impact of a social prescribing intervention in North East England on adults with type 2 diabetes: the SPRING_NE multimethod study.

Background: Link worker social prescribing enables health-care professionals to address patients' non-medical needs by linking patients into various services. Evidence for its effectiveness and how it is experienced by link workers and clients is lacking. Objectives: To evaluate the impact and costs of a link worker social prescribing intervention on health and health-care costs and utilisation and to observe link worker delivery and patient engagement. Data sources: Quality Outcomes Framework and Secondary Services Use data. Design: Multimethods comprising (1) quasi-experimental evaluation of effects of social prescribing on health and health-care use, (2) cost-effectiveness analysis, (3) ethnographic methods to explore intervention delivery and receipt, and (4) a supplementary interview study examining intervention impact during the first UK COVID-19 lockdown (April-July 2020). Study population and setting: Community-dwelling adults aged 40-74 years with type 2 diabetes and link workers in a socioeconomically deprived locality of North East England, UK. Intervention: Link worker social prescribing to improve health and well-being-related outcomes among people with long-term conditions. Participants: (1) Health outcomes study, approximately n = 8400 patients; EuroQol-5 Dimensions, five-level version (EQ-5D-5L), study, n = 694 (baseline) and n = 474 (follow-up); (2) ethnography, n = 20 link workers and n = 19 clients; and COVID-19 interviews, n = 14 staff and n = 44 clients. Main outcome measures: The main outcome measures were glycated haemoglobin level (HbA1c; primary outcome), body mass index, blood pressure, cholesterol level, smoking status, health-care costs and utilisation, and EQ-5D-5L score. Results: Intention-to-treat analysis of approximately 8400 patients in 13 intervention and 11 control general practices demonstrated a statistically significant, although not clinically significant, difference in HbA1c level (-1.11 mmol/mol) and a non-statistically significant 1.5-percentage-point reduction in the probability of having high blood pressure, but no statistically significant effects on other outcomes. Health-care cost estimates ranged from £18.22 (individuals with one extra comorbidity) to -£50.35 (individuals with no extra comorbidity). A statistically non-significant shift from unplanned (non-elective and accident and emergency admissions) to planned care (elective and outpatient care) was observed. Subgroup analysis showed more benefit for individuals living in more deprived areas, for the ethnically white and those with fewer comorbidities. The mean cost of the intervention itself was £1345 per participant; the incremental mean health gain was 0.004 quality-adjusted life-years (95% confidence interval -0.022 to 0.029 quality-adjusted life-years); and the incremental cost-effectiveness ratio was £327,250 per quality-adjusted life-year gained. Ethnographic data showed that successfully embedded, holistic social prescribing providing supported linking to navigate social determinants of health was challenging to deliver, but could offer opportunities for improving health and well-being. However, the intervention was heterogeneous and was shaped in unanticipated ways by the delivery context. Pressures to generate referrals and meet targets detracted from face-to-face contact and capacity to address setbacks among those with complex health and social problems. Limitations: The limitations of the study include (1) a reduced sample size because of non-participation of seven general practices; (2) incompleteness and unreliability of some of the Quality and Outcomes Framework data; (3) unavailability of accurate data on intervention intensity and patient comorbidity; (4) reliance on an exploratory analysis with significant sensitivity analysis; and (5) limited perspectives from voluntary, community and social enterprise. Conclusions: This social prescribing model resulted in a small improvement in glycaemic control. Outcome effects varied across different groups and the experience of social prescribing differed depending on client circumstances. Future work: To examine how the NHS Primary Care Network social prescribing is being operationalised; its impact on health outcomes, service use and costs; and its tailoring to different contexts. Trial registration: This trial is registered as ISRCTN13880272. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme, Community Groups and Health Promotion (grant no. 16/122/33) and will be published in full in Public Health Research; Vol. 11, No. 2. See the NIHR Journals Library website for further project information.

Social prescribing happens when health-care staff refer patients to a link worker. Link workers support and help patients to access community services to improve their health and well-being. Social prescribing is popular within the NHS, but there is little evidence that it works. We looked at a social prescribing model being delivered in a disadvantaged area in north-east England.

Cost-Effectiveness Analysis of a Medial Meniscus Replacement Prosthesis for the Treatment of Patients with Medial Compartment Pain in the United Kingdom.

BACKGROUND: The most common intra-articular knee injury is a meniscal tear, which commonly occurs secondary to trauma following twisting or hyperflexion. Treatment options for meniscal tears can either be surgical or non-surgical, and range from rest, exercise, bracing and physical therapy to surgical intervention, including meniscal repair and partial meniscectomy. In patients with persistent pain following loss of meniscus tissue, treatment can include partial replacement or meniscal allograft transplantation. The NUsurface® prosthesis has been developed as a treatment option for patients experiencing persistent knee pain post medial meniscus (MM) surgery. OBJECTIVE: The aim of this study was to assess the cost effectiveness of MM replacement using NUsurface for the treatment of patients with medial compartment pain following previous partial medial meniscectomy, from a UK health service perspective. METHODS: An economic decision-analytic model was developed to assess the cost per quality-adjusted life-year (QALY) gained associated with the introduction of MM replacement using NUsurface compared with non-surgical standard of care, over a lifetime time horizon. The model structure was primarily informed by a previous clinical trial (VENUS) and was developed based on the clinical pathways typically followed by patients with this condition, with treatment pathways and probabilities of clinical progression adjusted depending on whether patients were receiving the intervention or undergoing current practice. A hypothetical cohort of adult patients (mean age of 50 years) was modelled, with clinical data sourced from the VENUS study as well as relevant UK literature. Both deterministic and probabilistic sensitivity analyses were carried out to explore uncertainty in the model results. RESULTS: The base-case probabilistic results indicate that MM replacement using NUsurface is likely to be cost effective across a range of willingness-to-pay (WTP) thresholds (95% probability of being cost effective at the National Institute for Health and Care Excellence (NICE)-recommended £20,000 WTP threshold). Although per-patient costs increase, QALYs are also gained, with the incremental cost per QALY (probabilistic value = £5011) being below £20,000. Deterministic sensitivity analyses indicate that the parameters that have the greatest impact on results are the failure rate in the control group (current practice), utility scores, and the cost of undergoing MM replacement using NUsurface. CONCLUSIONS: Based on the analysis presented, MM replacement with the NUsurface prosthetic implant is likely to be a cost-effective use of UK health care service resources compared with current standard care.

Systematic review of the cost-effectiveness of screening for lung cancer with low dose computed tomography.

OBJECTIVES: Lung cancer (LC) remains a burden for patients and healthcare systems, with most cases only diagnosed once disease is late stage. Screening for LC with low-dose computed tomography (LDCT) has shown a stage shift and led to a lung cancer-specific mortality reduction. Economic evaluations have been conducted which explore the benefits and costs of screening, however, previous systematic reviews concluded results were heterogeneous. LC screening has evolved and there have been further cost-effectiveness analyses conducted. The aim of this study was to provide an up-to-date systematic review of the cost-effectiveness of LC screening with LDCT. METHODS AND MATERIALS: Databases were searched for full papers published in English 01/1994-02/2022. Inclusion criteria was full economic evaluation of LC screening using LDCT compared to either no screening or chest X-ray. RESULTS: Forty-five evaluations were identified, three conducted alongside trials and 42 modelling studies. Thirty-nine evaluations (86.7%) found LC screening with LDCT to be cost-effective. Several findings were broadly consistent across studies: cost-effectiveness was optimal in those age 55-75 years and smoking history of at least 20 pack-years. Biennial screening was often more cost-effective than annual screening and would likely result in less additional findings and radiation exposure. A smoking cessation intervention alongside screening improved cost-effectiveness, but which intervention was optimal was unclear. Risk predictions models using more parameters to target participants for screening did not have more benefits than those using age and smoking alone, and cost-effectiveness was equivalent. Cost-effectiveness was sensitive to cost and specificity of LDCT, and disutility associated with screening. CONCLUSION: Overall, LC screening with LDCT is cost-effective in a high-risk population. Questions remain regarding risk prediction models, smoking cessation interventions and appropriateness of utility values in the screened population. Once these uncertainties are addressed, further economic evaluation may be required to inform policymakers prior to implementation.

Economic Analysis of the CADScor System for Ruling Out Coronary Artery Disease in England.

BACKGROUND: Coronary artery disease (CAD) is the most common type of heart and circulatory disease and is the leading cause of death worldwide. The current diagnostic pathway can lead to patient complications and is also extremely costly. A new medical device, the CADScor System (Acarix AB), was developed for the acoustic detection of CAD before patients undergo invasive diagnostic procedures. OBJECTIVES: Our objective was to assess the cost utility of the CADScor System for the diagnosis of CAD at an early stage in the diagnostic testing pathway in England. METHODS: A two-part economic model, consisting of a decision tree and Markov model, was developed to consider the cost utility (cost per quality-adjusted life-year [QALY] gained) of introducing the CADScor System for the diagnosis of CAD. The decision tree component explored the short-term costs and diagnostic outcomes associated with introduction of the test compared with the existing testing pathway. A Markov model was developed to explore the longer-term health and economic implications of the condition and original diagnosis, with costs and health effects estimated over different time horizons. Parameter uncertainty was explored in deterministic and probabilistic sensitivity analyses. RESULTS: Base-case results indicated that the CADScor System would result in cost savings (- £131 per patient) and a marginal increase in QALYs (0.00001) over a 1-year time horizon. Probabilistic results indicated that the intervention had a > 99% probability of being cost effective at a willingness-to-pay threshold of £20,000 per QALY gained and 100% probability of being cost saving. Results from the deterministic sensitivity analyses indicated that variations in parameters related to the accuracy and cost of the CADScor System, and the prevalence of CAD, had the greatest impact on the overall results. The overall cost saving was estimated to be over £12.3 million per 100,000 eligible patient population. CONCLUSIONS: The CADScor System is a potentially cost-saving test for the diagnosis of CAD. When initiated before the use of non-invasive cardiac imaging tests such as computed tomography coronary angiography, the test reduced costs to the healthcare service over various time horizons.

DyeVert Contrast Reduction System Use in Patients Undergoing Coronary and/or Peripheral Angiography: A Systematic Literature Review and Meta-Analysis.

Background: Contrast-associated acute kidney injury (CA-AKI) is an important adverse effect associated with injecting iodinated intra-arterial contrast media (CM) during coronary angiography. The DyeVert™ Contrast Reduction System is a medical device intended to reduce the intra-arterial CM volume (CMV) administered. The aim of this study was to assess DyeVert System clinical effectiveness and safety by implementing a systematic review and meta-analysis of existing evidence. Methods: Systematic electronic literature searches were conducted in MEDLINE, Embase, the Cochrane Database of Systematic Reviews, ClinicalTrials.gov, and the International Clinical Trials Registry Platform database. Relevant data were extracted from included studies and meta-analyses were performed to synthesize evidence across studies. Results: The review included 17 eligible studies involving 1,731 DyeVert System cases and 1,387 control cases (without the use of DyeVert). Meta-analyses demonstrated use of the DyeVert System reduced CMV delivered to the patient by 39.27% (95% CI, 36.10-42.48%, P < 0.001), reduced CMV/baseline renal function ratios (Hedges's g, -0.56; 95% CI, -0.70 to -0.42, P < 0.001) and percentage of cases exceeding the maximum CMV threshold (risk difference -0.31, 95% CI, -0.48 to -0.13, P < 0.001) while maintaining adequate image quality in 98% of cases. DyeVert System cases demonstrated lower CA-AKI incidence vs. controls (absolute risk reduction 5.00% (95% CI, 0.40-9.80%; P = 0.03), relative risk 0.60 (95% CI, 0.40-0.90; P = 0.01) with a pooled estimate of the number needed to treat with the DyeVert System to avoid 1 CA-AKI event of 20. Conclusion: DyeVert System use significantly reduces CMV delivered to the patient, CMV/baseline renal function ratios, and CA-AKI incidence while maintaining image quality. Accordingly, the device may serve as an adjunctive, procedure-based strategy to prevent CA-AKI. Future multi-center studies are needed to further assess effects of minimizing CMV on endpoints such as CA-AKI prevention, incidence of adverse cardiac and renal events, and health care costs.

Safety and impact of eculizumab withdrawal in patients with atypical haemolytic uraemic syndrome: protocol for a multicentre, open-label, prospective, single-arm study.

INTRODUCTION: Atypical haemolytic uraemic syndrome (aHUS) is a rare, life-threatening disease caused by excessive activation of part of the immune system called complement. Eculizumab is an effective treatment, controlling aHUS in 90% of patients. Due to the risk of relapse, lifelong treatment is currently recommended. Eculizumab treatment is not without problems, foremost being the risk of severe meningococcal infection, the burden of biweekly intravenous injections and the high cost.This paper describes the design of the Stopping Eculizumab Treatment Safely in aHUS trial that aims to establish whether a safety monitoring protocol, including the reintroduction of eculizumab for those who relapse, could be a safe, alternative treatment strategy for patients with aHUS. METHODS AND ANALYSIS: This is a multicentre, non-randomised, open-label study of eculizumab withdrawal with continuous monitoring of thrombotic microangiopathy-related serious adverse events using the Bayes factor single-arm design. 30 patients will be recruited to withdraw from eculizumab and have regular blood and urine tests for 24 months, to monitor for disease activity. If relapse occurs, treatment will be restarted within 24 hours of presentation. 20 patients will remain on treatment and complete health economic questionnaires only. An embedded qualitative study will explore the views of participants. ETHICS AND DISSEMINATION: A favourable ethical opinion and approval was obtained from the North East-Tyne & Wear South Research Ethics Committee. Outcomes will be disseminated via peer-reviewed articles and conference presentations. TRIAL REGISTRATION NUMBER: EudraCT number: 2017-003916-37 and ISRCTN number: ISRCTN17503205.

Utility of Routine Laboratory Biomarkers to Detect COVID-19: A Systematic Review and Meta-Analysis.

No routine laboratory biomarkers perform well enough in diagnosing COVID-19 in isolation for them to be used as a standalone diagnostic test or to help clinicians prioritize patients for treatment. Instead, other diagnostic tests are needed. The aim of this work was to statistically summarise routine laboratory biomarker measurements in COVID-19-positive and -negative patients to inform future work. A systematic literature review and meta-analysis were performed. The search included names of commonly used, routine laboratory tests in the UK NHS, and focused on research papers reporting laboratory results of patients diagnosed with COVID-19. A random effects meta-analysis of the standardized mean difference between COVID-19-positive and -negative groups was conducted for each biomarker. When comparing reported laboratory biomarker results, we identified decreased white blood cell, neutrophil, lymphocyte, eosinophil, and platelet counts; while lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase were elevated in COVID-19-positive compared to COVID-19-negative patients. Differences were identified across a number of routine laboratory biomarkers between COVID-19-positive and -negative patients. Further research is required to identify whether routine laboratory biomarkers can be used in the development of a clinical scoring system to aid with triage of patients.

COVID-19 pandemic in the United Kingdom.

OBJECTIVES: To describe epidemiological data on cases of COVID-19 and the spread of Severe Acute Respiratory Syndrome Coronavirus 2 in the United Kingdom (UK), and the subsequent policy and technological response to the pandemic, including impact on healthcare, business and the economy. METHODS: Epidemiological, business and economic data were extracted from official government sources covering the period 31st January to 13th August 2020; healthcare system data up to end of June 2019. RESULTS: UK-wide COVID-19 cases and deaths were 313,798 and 46,706 respectively (472 cases and 70 deaths per 100,000 population) by 12th August. There were regional variations in England, with London and North West (756 and 666 cases per 100,000 population respectively) disproportionately affected compared with other regions. As of 11th August, 13,618,470 tests had been conducted in the UK. Increased risk of mortality was associated with age (≥60 years), gender (male) and BAME groups. Since onset of the pandemic, emergency department attendance, primary care utilisation and cancer referrals and inpatient/outpatient referrals have declined; emergency ambulance and NHS111 calls increased. Business sectors most impacted are the arts, entertainment and recreation, followed by accommodation and food services. Government interventions aimed at curtailing the business and economic impact have been implemented, but applications for state benefits have increased. CONCLUSIONS: The impact of COVID-19 on the UK population, health system and economy has been profound. More data are needed to implement the optimal policy and technological responses to preventing further spikes in COVID-19 cases, and to inform strategic planning to manage future pandemics.

The COVID-19 pandemic in Ireland: An overview of the health service and economic policy response.

OBJECTIVES: To outline the situation in Ireland with regard to the COVID-19 pandemic. METHODS: Analyse the evolution of the COVID-19 pandemic in Ireland. Review the key public health and health system responses. RESULTS: Over 1700 people have died with COVID-19 by July 19th while almost 3000 people had been admitted to hospital with COVID-19. A high proportion of the deaths occurred in nursing homes and other residential centres who did not receive sufficient attention during the early phase of the pandemic. CONCLUSIONS: Ireland's response to the COVID-19 crisis has been comprehensive and timely. Transparency, a commitment to a relatively open data policy, the use of traditional and social media to inform the population, and the frequency of updates from the Department of Health and the Health Services Executive are all commendable and have led to a high level of compliance among the general public with the various non-medical measures introduced by the government.

Surgical treatments for women with stress urinary incontinence: a systematic review of economic evidence.

BACKGROUND: Surgical interventions for the treatment of stress urinary incontinence (SUI) in women are commonly employed following the failure of minimally invasive therapies. Due to the limited information available on the relative cost-effectiveness of available surgeries for treating SUI, a de novo economic analysis was conducted to assess costs and effects of all relevant surgeries. To inform the economic analysis, the objective of this review was to identify and assess the quality of existing economic evaluation studies on different surgical interventions for the treatment of SUI in women. METHODS: The following databases were searched during the review process: Medical Literature Analysis and Retrieval System Online (MEDLINE), MEDLINE In-Process, Excerpta Medica Database (Embase), National Health Service Economic Evaluation Database (NHS EED), and Health Management Information Consortium and Cost-Effectiveness Analysis Registry (CEA registry). The key criteria for inclusion were that the study population included women with SUI and that the surgical interventions considered were utilised as either a primary or a follow-up surgery. The review included only full economic evaluations. Studies were quality assessed using the Drummond checklist for economic evaluations. No quantitative synthesis of the results by meta-analysis was conducted due to the high methodological heterogeneity. RESULTS: Twenty-six economic evaluations were included, of which 13 were model-based analyses. Surgical treatments assessed most frequently were mid-urethral slings and open and laparoscopic colposuspension. There were some differences in the methodological approaches taken, including differences in type of economic analysis, perspective, time horizon, types of resource use, and costs and outcomes that were included in the analysis. The majority of studies conducted a cost-utility analysis from a health system perspective and applied a time horizon of between 1 and 5 years. The cost-effectiveness results suggest that single-incision mini-sling and mid-urethral slings are among the most cost-effective options. CONCLUSIONS: The review has shown that methods used for the economic evaluation of surgical treatments for SUI vary widely in terms of study design, analysis type, compared alternatives, time horizon, costing methodologies and effect outcomes. Future economic evaluation studies on surgical treatments for SUI may be improved by the application of available guidelines. SYSTEMATIC REVIEW REGISTRATION: Registered in PROSPERO in 2016, CRD42016049339.

Economic evaluation of surgical treatments for women with stress urinary incontinence: a cost-utility and value of information analysis.

OBJECTIVES: Stress urinary incontinence (SUI) and stress-predominant mixed urinary incontinence (MUI) are common conditions that can have a negative impact on the quality of life of patients and serious cost implications for healthcare providers. The objective of this study was to assess the cost-effectiveness of nine different surgical interventions for treatment of SUI and stress-predominant MUI from a National Health Service and personal social services perspective in the UK. METHODS: A Markov microsimulation model was developed to compare the costs and effectiveness of nine surgical interventions. The model was informed by undertaking a systematic review of clinical effectiveness and network meta-analysis. The main clinical parameters in the model were the cure and incidence rates of complications after different interventions. The outcomes from the model were expressed in terms of cost per quality-adjusted life-years (QALYs) gained. In addition, expected value of perfect information (EVPI) analyses were conducted to quantify the main uncertainties facing decision-makers. RESULTS: The base-case results suggest that retropubic mid-urethral sling (retro-MUS) is the most cost-effective surgical intervention over a 10-year and lifetime time horizon. The probabilistic results show that retro-MUS and traditional sling are the interventions with the highest probability of being cost-effective across all willingness-to-pay thresholds over a lifetime time horizon. The value of information analysis results suggest that the largest value appears to be in removing uncertainty around the incidence rates of complications, the relative treatment effectiveness and health utility values. CONCLUSIONS: Although retro-MUS appears, at this stage, to be a cost-effective intervention, research is needed on possible long-term complications of all surgical treatments to provide reassurance of safety, or earlier warning of unanticipated adverse effects. The value of information analysis supports the need, as a first step, for further research to improve our knowledge of the actual incidence of complications.

A PCR-based diagnostic testing strategy to identify carbapenemase-producing Enterobacteriaceae carriers upon admission to UK hospitals: early economic modelling to assess costs and consequences.

BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE), bacteria which are resistant to the carbapenem class of antibiotics, present an urgent public health risk. The objective of this study was to assess the potential costs and consequences of implementing a testing strategy involving a polymerase chain reaction (PCR)-based diagnostic test for CPE amongst high risk patients upon admission to UK hospitals, to replace the current culture-based testing strategy. METHODS: A decision-analytic model was developed to estimate the expected medical care costs associated with a PCR testing strategy for CPE compared with the current culture testing strategy, and to consider the consequences, in terms of the diagnostic accuracy and associated cost implications, of each approach. The modelled population were patients admitted to hospital at high risk of colonisation with CPE, with model pathways for current practice based on those described in the Public Health England (PHE) toolkit for CPE testing. Costs were estimated from a UK National Health Service (NHS) perspective, with outcomes presented in terms of percentage of samples identified as true positive, false positive, true negative and false negative following each method of testing. RESULTS: Results indicated that the PCR testing strategy led to an estimated cost saving of £462 per patient for a 5-day hospital stay. For all sensitivity analyses conducted, PCR testing resulted in an expected cost saving. Potential cost savings approached £850 per patient for the sensitivity analysis assuming a 15-day hospital stay, indicating that PCR testing results in greater cost savings as length of stay increases. Fewer false positive, and more true negative, cases were identified with the PCR testing strategy in all analyses conducted. CONCLUSIONS: This economic analysis gives an insight into the potential cost savings that could be made by the UK NHS through the introduction of a PCR-based diagnostic testing strategy to replace current recommended culture-based methods for the detection of CPE. Savings are due primarily to a faster time to result with PCR, meaning that CPE-free patients are not isolated unnecessarily. Therefore, a PCR-based diagnostic may aid appropriate use of isolation resource.

Early Economic Evaluation of Diagnostic Technologies: Experiences of the NIHR Diagnostic Evidence Co-operatives.

Diagnostic tests are expensive and time-consuming to develop. Early economic evaluation using decision modeling can reduce commercial risk by providing early evidence on cost-effectiveness. The National Institute for Health Research Diagnostic Evidence Co-operatives (DECs) was established to catalyze evidence generation for diagnostic tests by collaborating with commercial developers; DEC researchers have consequently made extensive use of early modeling. The aim of this article is to summarize the experiences of the DECs using early modeling for diagnostics. We draw on 8 case studies to illustrate the methods, highlight methodological strengths and weaknesses particular to diagnostics, and provide advice. The case studies covered diagnosis, screening, and treatment stratification. Treatment effectiveness was a crucial determinant of cost-effectiveness in all cases, but robust evidence to inform this parameter was sparse. This risked limiting the usability of the results, although characterization of this uncertainty in turn highlighted the value of further evidence generation. Researchers evaluating early models must be aware of the importance of treatment effect evidence when reviewing the cost-effectiveness of diagnostics. Researchers planning to develop an early model of a test should also 1) consult widely with clinicians to ensure the model reflects real-world patient care; 2) develop comprehensive models that can be updated as the technology develops, rather than taking a "quick and dirty" approach that may risk producing misleading results; and 3) use flexible methods of reviewing evidence and evaluating model results, to fit the needs of multiple decision makers. Decision models can provide vital information for developers at an early stage, although limited evidence mean researchers should proceed with caution.

Systematic Review of Economic Models Used to Compare Techniques for Detecting Peripheral Arterial Disease.

BACKGROUND AND OBJECTIVE: Peripheral arterial disease (PAD) is a common condition, in which atherosclerotic narrowing in the arteries restricts blood supply to the leg muscles. In order to support future model-based economic evaluations comparing methods of diagnosis in this area, a systematic review of economic modelling studies was conducted. METHODS: A systematic literature review was performed in June 2017 to identify model-based economic evaluations of diagnostic tests to detect PAD, with six individual databases searched. The review was conducted in accordance with the methods outlined in the Centre for Reviews and Dissemination's guidance for undertaking reviews in healthcare, and appropriate inclusion criteria were applied. Relevant data were extracted, and studies were quality assessed. RESULTS: Seven studies were included in the final review, all of which were published between 1995 and 2014. There was wide variation in the types of diagnostic test compared. The majority of the studies (six of seven) referenced the sources used to develop their model, and all studies stated and justified the structural assumptions. Reporting of the data within the included studies could have been improved. Only one identified study focused on the cost-effectiveness of a test typically used in primary care. CONCLUSIONS: This review brings together all applied modelling methods for tests used in the diagnosis of PAD, which could be used to support future model-based economic evaluations in this field. The limited modelling work available on tests typically used for the detection of PAD in primary care, in particular, highlights the importance of future work in this area.