The tribulations of trials: Lessons learnt recruiting 777 older adults into REtirement in ACTion (REACT), a trial of a community, group-based active ageing intervention targeting mobility disability

© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. 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). Recruitment methods include the following: (a) invitations mailed by general practitioners (GPs); (b) invitations distributed via third-sector organizations; and (c) public relations (PR) campaign. Yields, efficiency, and costs were calculated. RESULTS: The study recruited 777 (33.9% men) community-dwelling, older adults (mean age 77.55 years (SD 6.79), mean SPPB score 7.37 (SD 1.56)), 95.11% white (n = 739) and broadly representative of UK quintiles of deprivation. Over a 20-month recruitment period, 25,559 invitations were issued. Eighty-eight percent of the participants were recruited via GP invitations, 5.4% via the PR campaign, 3% via word-of-mouth, and 2.5% via third-sector organizations. Mean recruitment cost per participant was £78.47, with an extra £26.54 per recruit paid to GPs to cover research costs. CONCLUSIONS: REACT successfully recruited to target. Response rates were lower than initially predicted and recruitment timescales required adjustment. Written invitations from GPs were the most efficient method for recruiting older adults at risk of mobility disability. Targeted efforts could achieve more ethnically diverse cohorts. All trials should be required to provide recruitment data to enable evidence-based planning of future trials

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. Methods: Droplet digital PCR was used to quantify reference and variant alleles in cell-free DNA extracted from blood from 38 pregnant women heterozygous for a GCK or HNF4A variant and to determine fetal fraction by measurement of informative maternal and paternal variants. Droplet numbers positive for the reference/alternate allele together with the fetal fraction were used in a Bayesian analysis to derive probability for the fetal genotype. The babies' genotypes were ascertained postnatally by Sanger sequencing. Results: Droplet digital PCR assays for GCK or HNF4A variants were validated for testing in all 38 pregnancies. Fetal fraction of ≥2% was demonstrated in at least 1 cell-free DNA sample from 33 pregnancies. A threshold of ≥0.95 for calling homozygous reference genotypes and ≤0.05 for heterozygous fetal genotypes allowed correct genotype calls for all 33 pregnancies with no false-positive results. In 30 of 33 pregnancies, a result was obtained from a single blood sample. Conclusions: This assay can be used to identify pregnancies at risk of macrosomia due to maternal monogenic diabetes variants.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.A.T. Hattersley and M.H. Shepherd are supported by the NIHR Exeter Clinical Research Facility, which is a partnership between the University of Exeter Medical School College of Medicine and Health, and Royal Devon and Exeter NHS Foundation Trust

A new method for model-based health economic evaluation utilising and extending moment-generating functions: Example model

The VBA macros are only used in the workbook for the probabilistic sensitivity analysis and do not need to be enabled unless the user wishes to conduct a new probabilistic sensitivity analysis.The article associated with this dataset is located in ORE at: http://hdl.handle.net/10871/37395This Excel workbook provides a reference implementation of the moment-generating functions (MGF) method for health economic modelling, to accompany the article "A new method for model-based health economic evaluation utilising and extending moment-generating functions" by Tristan Snowsill (2019) published in Medical Decision Making

Data mining in text streams using suffix trees

Data mining in text streams, or text stream mining, is an increasingly im- portant topic for a number of reasons, including the recent explosion in the availability of textual data and an increasing need for people and organi- sations to process and understand as much of that information as possible, from single users to multinational corporations and governments. In this thesis we present a data structure based on a generalised suffix tree which is capable of solving a number of text stream mining tasks. It can be used to detect changes in the text stream, detect when chunks of text are reused and detect events through identifying when the frequencies of phrases change in a statistically significant way. Suffix trees have been used for many years in the areas of combinatorial pattern matching and computational genomics. In this thesis we demonstrate how the suffix tree can become more widely applicable by making it possible to use suffix trees to analyse streams of data rather than static data sets, opening up a number of future avenues for research. The algorithms which we present are designed to be efficient in an on-line setting by having time complexity independent of the total amount of text seen and polynomial in the rate at which text is seen. We demonstrate the effectiveness of our methods on a large text stream comprising thousands of documents every day. This text stream is the stream of text news coming from over 600 online news outlets and the results ob- tained are of interest to news consumers, journalists and social scientists.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

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 MLH1 promoter hypermethylation, and incorporates genetic testing for pathogenic MMR variants. We aimed to assess the cost-effectiveness of the Manchester approach on the basis of primary research data from clinical practice in Manchester. The Proportion of Endometrial Tumours Associated with Lynch Syndrome (PETALS) study informed estimates of diagnostic performances for a number of different strategies. A recent microcosting study was adapted and was used to estimate diagnostic costs. A Markov model was used to predict long-term costs and health outcomes (measured in quality-adjusted life years, QALYs) for individuals and their relatives. Bootstrapping and probabilistic sensitivity analysis were used to estimate the uncertainty in cost-effectiveness. The Manchester approach dominated other reflex testing strategies when considering diagnostic costs and Lynch syndrome cases identified. When considering long-term costs and QALYs the Manchester approach was the optimal strategy, costing £5459 per QALY gained (compared to thresholds of £20,000 to £30,000 per QALY commonly used in the National Health Service (NHS)). Cost-effectiveness is not an argument for restricting testing to younger patients or those with a strong family history. Universal testing for Lynch syndrome in endometrial cancer patients is expected to be cost-effective in the U.K. (NHS), and the Manchester approach is expected to be the optimal testing strategy

Detecting events in a million New York times articles

We present a demonstration of a newly developed text stream event detection method on over a million articles from the New York Times corpus. The event detection is designed to operate in a predominantly on-line fashion, reporting new events within a specified timeframe. The event detection is achieved by detecting significant changes in the statistical properties of the text where those properties are efficiently stored and updated in a suffix tree. This particular demonstration shows how our method is effective at discovering both short- and long-term events (which are often denoted topics), and how it automatically copes with topic drift on a corpus of 1 035 263 articles