Gynaecological cancer surveillance for women with Lynch syndrome: systematic review and cost-effectiveness evaluation.

Background: Lynch syndrome is an inherited condition which leads to an increased risk of colorectal, endometrial and ovarian cancer. Risk-reducing surgery is generally recommended to manage the risk of gynaecological cancer once childbearing is completed. The value of gynaecological colonoscopic surveillance as an interim measure or instead of risk-reducing surgery is uncertain.

Do we know enough about the effect of low-dose computed tomography screening for lung cancer on mortality to act? An updated systematic review, meta-analysis and network meta-analysis of randomised controlled trials 2017 to 2021.

Background: For people at high risk of lung cancer, low-dose computed tomography (LDCT) is proposed as a method to reduce mortality.

Methods: Our objective was to estimate the effect of LDCT lung cancer screening on mortality in high-risk populations. A systematic review of randomised controlled trials (RCTs) comparing LDCT screening programmes with usual care (no screening) or other imaging screening programme (such as chest X-ray (CXR)) was conducted.

Logical Inconsistencies in the Health Years in Total and Equal Value of Life-Years Gained.

Objectives: This study aimed to assess whether recently proposed alternatives to the quality-adjusted life-year (QALY), intended to address concerns about discrimination, are suitable for informing resource allocation decisions.

Methods: We consider 2 alternatives to the QALY: the health years in total (HYT), recently proposed by Basu et al, and the equal value of life-years gained (evLYG), currently used by the Institute for Clinical and Economic Review. For completeness we also consider unweighted life-years (LYs).

Motivational support intervention to reduce smoking and increase physical activity in smokers not ready to quit: the TARS RCT.

Background: Physical activity can support smoking cessation for smokers wanting to quit, but there have been no studies on supporting smokers wanting only to reduce. More broadly, the effect of motivational support for such smokers is unclear.

Objectives: The objectives were to determine if motivational support to increase physical activity and reduce smoking for smokers not wanting to immediately quit helps reduce smoking and increase abstinence and physical activity, and to determine if this intervention is cost-effective.

Effectiveness and cost-effectiveness of behavioural support for prolonged abstinence for smokers wishing to reduce but not quit: Randomised controlled trial of physical activity assisted reduction of smoking (TARS).

Aims: For smokers unmotivated to quit, we assessed the effectiveness and cost-effectiveness of behavioural support to reduce smoking and increase physical activity on prolonged abstinence and related outcomes.

Design: A multi-centred pragmatic two-arm parallel randomised controlled trial.

Setting: Primary care and the community across four United Kingdom sites.

Non-invasive fetal genotyping for maternal alleles with droplet digital PCR: A comparative study of analytical approaches.

Objectives: To develop a flexible droplet digital PCR (ddPCR) workflow to perform non-invasive prenatal diagnosis via relative mutation dosage (RMD) for maternal pathogenic variants with a range of inheritance patterns, and to compare the accuracy of multiple analytical approaches.

Methods: Cell free DNA (cfDNA) was tested from 124 archived maternal plasma samples: 88 cases for sickle cell disease and 36 for rare Mendelian conditions. Three analytical methods were compared: sequential probability ratio testing (SPRT), Bayesian and z-score analyses.

Modelling the Cost-Effectiveness of Diagnostic Tests.

Diagnostic tests are used to determine whether a disease or condition is present or absent in a patient, who will typically be suspected of having the disease or condition due to symptoms or clinical signs. Economic evaluations of diagnostic tests (e.g.

Variation in Model-Based Economic Evaluations of Low-Dose Computed Tomography Screening for Lung Cancer: A Methodological Review.

Objectives: There is significant heterogeneity in the results of published model-based economic evaluations of low-dose computed tomography (LDCT) screening for lung cancer. We sought to understand and demonstrate how these models differ.

Methods: An expansion and update of a previous systematic review (N = 19).

Cost-effectiveness of a physical activity and behaviour maintenance programme on functional mobility decline in older adults: an economic evaluation of the REACT (Retirement in Action) trial.

Background: Mobility limitations in older populations have a substantial impact on health outcomes, quality of life, and social care costs. The Retirement in Action (REACT) randomised controlled trial assessed a 12-month community-based group physical activity and behaviour maintenance intervention to help prevent decline in physical functioning in older adults at increased risk of mobility limitation. We aimed to do an economic evaluation of the REACT trial to investigate whether the intervention is cost-effective.

Effect of a physical activity and behaviour maintenance programme on functional mobility decline in older adults: the REACT (Retirement in Action) randomised controlled trial.

Background: Mobility limitations in old age can greatly reduce quality of life, generate substantial health and social care costs, and increase mortality. Through the Retirement in Action (REACT) trial, we aimed to establish whether a community-based active ageing intervention could prevent decline in lower limb physical functioning in older adults already at increased risk of mobility limitation.

Methods: In this pragmatic, multicentre, two-arm, single-blind, parallel-group, randomised, controlled trial, we recruited older adults (aged 65 years or older and who are not in full-time employment) with reduced lower limb physical functioning (Short Physical Performance Battery [SPPB] score 4-9) from 35 primary care practices across three sites (Bristol and Bath; Birmingham; and Devon) in England.

Lung cancer screening by low-dose computed tomography: a cost-effectiveness analysis of alternative programmes in the UK using a newly developed natural history-based economic model.

Background: A systematic review of economic evaluations for lung cancer identified no economic models of the UK setting based on disease natural history. We first sought to develop a new model of natural history for population screening, then sought to explore the cost-effectiveness of multiple alternative potential programmes.

Methods: An individual patient model (ENaBL) was constructed in MS Excel® and calibrated against data from the US National Lung Screening Trial.

Randomised controlled trial of tailored support to increase physical activity and reduce smoking in smokers not immediately ready to quit: protocol for the Trial of physical Activity-assisted Reduction of Smoking (TARS) Study.

Introduction: Smoking reduction can lead to increased success in quitting. This study aims to determine if a client-focused motivational support package for smoking reduction (and quitting) and increasing (or otherwise using) physical activity (PA) can help smokers who do not wish to quit immediately to reduce the amount they smoke, and ultimately quit. This paper reports the study design and methods.

The proportion of endometrial tumours associated with Lynch syndrome (PETALS): A prospective cross-sectional study.

Background: Lynch syndrome (LS) predisposes to endometrial cancer (EC), colorectal cancer, and other cancers through inherited pathogenic variants affecting mismatch-repair (MMR) genes. Diagnosing LS in women with EC can reduce subsequent cancer mortality through colonoscopic surveillance and aspirin chemoprevention; it also enables cascade testing of relatives. A growing consensus supports LS screening in EC; however, the expected proportion of test positives, and optimal testing strategy is uncertain.

Noninvasive Fetal Genotyping by Droplet Digital PCR to Identify Maternally Inherited Monogenic Diabetes Variants.

Background: Babies of women with heterozygous pathogenic glucokinase (GCK) variants causing mild fasting hyperglycemia are at risk of macrosomia if they do not inherit the variant. Conversely, babies who inherit a pathogenic hepatocyte nuclear factor 4α (HNF4A) diabetes variant are at increased risk of high birth weight. Noninvasive fetal genotyping for maternal pathogenic variants would inform pregnancy management.

Cost-Effectiveness of the Manchester Approach to Identifying Lynch Syndrome in Women with Endometrial Cancer.

Lynch syndrome (LS) is a hereditary cancer syndrome responsible for 3% of all endometrial cancer and 5% in those aged under 70 years. It is unclear whether universal testing for LS in endometrial cancer patients would be cost-effective. The Manchester approach to identifying LS in endometrial cancer patients uses immunohistochemistry (IHC) to detect mismatch repair (MMR) deficiency, incorporates testing for promoter hypermethylation, and incorporates genetic testing for pathogenic MMR variants.

Handsearching had best recall but poor efficiency when exporting to a bibliographic tool: case study.

Objectives: The objective of this study was to compare the effectiveness and efficiency of methods used to identify and export conference abstracts into a bibliographic management tool.

Study Design And Setting: This is a case study. The effectiveness and efficiency of methods to identify and export conference abstracts presented at the American Society of Hematology (ASH) conference 2016-2018 for a systematic review were evaluated.

The Tribulations of Trials: Lessons Learnt Recruiting 777 Older Adults Into REtirement in ACTion (REACT), a Trial of a Community, Group-Based Active Aging Intervention Targeting Mobility Disability.

Background: Challenges of recruitment to randomized controlled trials (RCTs) and successful strategies to overcome them should be clearly reported to improve recruitment into future trials. REtirement in ACTion (REACT) is a United Kingdom-based multicenter RCT recruiting older adults at high risk of mobility disability to a 12-month group-based exercise and behavior maintenance program or to a minimal Healthy Aging control intervention.

Methods: The recruitment target was 768 adults, aged 65 years and older scoring 4-9 on the Short Physical Performance Battery (SPPB).

Do we know enough about the effect of low-dose computed tomography screening for lung cancer on survival to act? A systematic review, meta-analysis and network meta-analysis of randomised controlled trials.

Background: Diagnosis of lung cancer frequently occurs in its later stages. Low-dose computed tomography (LDCT) could detect lung cancer early.

Methods: Our objective was to estimate the effect of LDCT lung cancer screening on mortality in high-risk populations.

The predicted impact and cost-effectiveness of systematic testing of people with incident colorectal cancer for Lynch syndrome.

Objectives: To evaluate the health impact and cost-effectiveness of systematic testing for Lynch syndrome (LS) in people with incident colorectal cancer (CRC) in Australia.

Design, Setting, Participants: We investigated the impact of LS testing strategies in a micro-simulation model (Policy1-Lynch), explicitly modelling the cost of testing all patients diagnosed with incident CRC during 2017, with detailed modelling of outcomes for patients identified as LS carriers (probands) and their at-risk relatives throughout their lifetimes. For people with confirmed LS, we modelled ongoing colonoscopic surveillance.

Cost-effectiveness analysis of reflex testing for Lynch syndrome in women with endometrial cancer in the UK setting.

Background: Lynch syndrome is a hereditary cancer syndrome caused by constitutional pathogenic variants in the DNA mismatch repair (MMR) system, leading to increased risk of colorectal, endometrial and other cancers. The study aimed to identify the incremental costs and consequences of strategies to identify Lynch syndrome in women with endometrial cancer.

Methods: A decision-analytic model was developed to evaluate the relative cost-effectiveness of reflex testing strategies for identifying Lynch syndrome in women with endometrial cancer taking the NHS perspective and a lifetime horizon.

A New Method for Model-Based Health Economic Evaluation Utilizing and Extending Moment-Generating Functions.

Health economic evaluations frequently include projections for lifetime costs and health effects using modeling frameworks such as Markov modeling or discrete event simulation (DES). Markov models typically cannot represent events whose risk is determined by the length of time spent in state (sojourn time) without the use of tunnel states. DES is very flexible but introduces Monte Carlo variation, which can significantly limit the complexity of model analyses.

The Manchester International Consensus Group recommendations for the management of gynecological cancers in Lynch syndrome.

Purpose: There are no internationally agreed upon clinical guidelines as to which women with gynecological cancer would benefit from Lynch syndrome screening or how best to manage the risk of gynecological cancer in women with Lynch syndrome. The Manchester International Consensus Group was convened in April 2017 to address this unmet need. The aim of the Group was to develop clear and comprehensive clinical guidance regarding the management of the gynecological sequelae of Lynch syndrome based on existing evidence and expert opinion from medical professionals and patients.