Does the Elicitation Mode Matter? Comparing Different Methods for Eliciting Expert Judgement

An expert elicitation is a method of eliciting subjective probability distributions over key parameters from experts. Traditionally an expert elicitation has taken the form of a face-to-face interview; however, interest in using online methods has been growing. This thesis compares two elicitation modes and examines the effectiveness of an interactive online survey compared to a face-to-face interview. Differences in central values, overconfidence, accuracy and satisficing were considered. The results of our analysis indicated that, in instances where the online and face-to-face elicitations were directly comparable, the differences between the modes was not significant. Consequently, a carefully designed online elicitation may be used successfully to obtain accurate forecasts

Comparing in-person and online modes of expert elicitation

Expert elicitation, a method of developing probability distributions over unknown parameters, traditionally involves in-person interviews by a trained analyst. There is growing interest in using the internet to enable participation of larger, more distributed groups of experts. However, analysts have questioned the quality of judgements elicited online rather than in person. We systematically compare online and in-person elicitation modes, finding no significant difference between the two modes across multiple measures: the two modes are similar in accuracy, uncertainty ranges, number of surprises, fatigue, and the substance of qualitative comments. These findings have an important caveat: many elicitation questions were subject to problems in online administration that made it impossible to compare to in-person results. We conclude that, although online elicitations represent a less resource-intensive option for large expert elicitations, they may require a higher level of testing and quality control since there is no analyst to catch errors or clarify small misunderstandings

A population based case control study of aetiological factors associated with vulval lichen sclerosus

Peer reviewedPublisher PD

Biopsy and selective recall compared with immediate large loop excision in management of women with low grade abnormal cervical cytology referred for colposcopy : multicentre randomised controlled trial

Peer reviewedPublisher PD

Dose-dependent relationship between acidosis at birth and likelihood of death or cerebral palsy

BackgroundThe acid-base status of infants around birth can provide information about their past, current and future condition. Although umbilical cord blood pH &lt;7.0 or base deficit ≥12 mmol/L is associated with increased risk of adverse outcome, there is uncertainty about the prognostic value of degree of acidosis as previous studies have used different variables, thresholds, outcomes and populations.MethodsRetrospective review of routinely collected clinical data in all live-born inborn infants of 35 weeks gestation or more delivered between January 2005 and December 2013 at the Simpson Centre for Reproductive Health, Edinburgh, UK. Infants were included if their lowest recorded pH was &lt;7 and/or highest base deficit ≥12 mmol/L on either umbilical cord blood and/or neonatal blood gas within 1 hour of birth. Neurodevelopmental outcome of the infants with encephalopathy was collected from the targeted follow-up database.Results56 574 infants were eligible. 506 infants (0.9%) met inclusion criteria. Poor condition at birth and all adverse outcomes increased with worsening acidosis. Combined outcome of death or cerebral palsy was 3%, 10% and 40% at lowest pH of 6.9–6.99, 6.8–6.89 and &lt;6.8, respectively, and 8%, 14% and 59% at a base deficit of 12–15.9, 16–19.9 and 20 mmol/L or more, respectively.ConclusionsThere is a dose-dependent relationship between the degree of acidosis within an hour of delivery, and the likelihood of adverse neonatal and later neurodevelopmental outcome in infants born at 35 weeks gestation or more.</jats:sec

Mini-AFTERc: a controlled pilot trial of a nurse-led psychological intervention for fear of breast cancer recurrence

Funding: The study was funded by the Chief Scientist Ofce (CSO), which is part of the Scottish Government Health Directorates (reference: HIPS/17/57).Objectives   To determine the feasibility and acceptability of implementing the Mini-AFTERc intervention. Design   Non-randomised cluster-controlled pilot trial. Setting  Four NHS out-patient breast cancer centres in Scotland. Participants  Ninety-two women who had successfully completed primary treatment for breast cancer were screened for moderate levels of fear of cancer recurrence (FCR). Forty-five were eligible (17 intervention and 28 control) and 34 completed 3-month follow-up (15 intervention and 21 control). Intervention   Mini-AFTERc, a single brief (30 min) structured telephone discussion with a specialist breast cancer nurse (SBCN) trained to target the antecedents of FCR. Outcomes   Feasibility and acceptability of Mini-AFTERc and the study design were assessed via recruitment, consent, retention rates, patient outcomes (measured at baseline, 2, 4, and 12 weeks), and post-study interviews with participants and SBCNs, which were guided by Normalisation Process Theory. Results   Mini-AFTERc was acceptable to patients and SBCNs. SBCNs believe the implementation of Mini-AFTERc to be feasible and an extension of discussions that already happen routinely. SBCNs believe delivery, however, at the scale required would be challenging given current competing demands for their time. Recruitment was impacted by variability in the follow-up practices of cancer centres and COVID-19 lockdown. Consent and follow-up procedures worked well, and retention rates were high. Conclusions   The study provided invaluable information about the potential challenges and solutions for testing the Mini-AFTERc intervention more widely where limiting high FCR levels is an important goal following recovery from primary breast cancer treatment.Publisher PDFPeer reviewe

FIGHT-PD: A feasibility study of periodized boxing training for Parkinson disease

Background: Boxing training has become a popular form of exercise for people with Parkinson disease (PD). There is a dearth of high-quality feasibility, safety, and efficacy data on boxing training for PD. Feasibility of Instituting Graduated High-intensity Training (FIGHT-PD) aimed to examine these features in a periodized boxing training program featuring high-intensity physical and cognitive demands. Objective: To conduct a feasibility study, aiming to address deficiencies in the current knowledge base and to provide data for future studies. Design: Single-arm, open-label feasibility. Setting: University department and medical research institute. Participants: Ten people with early stage PD without contraindications to intense exercise, identified from a database of participants interested in boxing training. Interventions: A 15-week exercise program with three 1-hour sessions per week, with each session including warmup and then rounds of noncontact boxing using a training device. Three distinct blocks of 5 weeks including active rest. Boxers Development: focus on training technique Boxers Cardio: increasing intensity, including high-intensity interval training Boxers Brain: focus on cognitively challenging dual task training. Main Outcome Measures: Process, resource, and management measures including recruitment and retention rates, timelines and costs, and compliance with prescribed exercise targets. Clinical outcomes were safety (adverse events), training intensity (using heart rate and perceived exertion monitoring), tolerability (pain, fatigue, and sleep scores), and pre- and postprogram Unified Parkinson Disease Rating Scale (UPDRS-III). Results: Among 10 participants from a pool of 82 (recruitment rate = 12%), there were no withdrawals; 348/360 workouts were completed (adherence = 97.7%); 4/348 (1.1%) workouts were missed due to minor injury. Nine of 10 participants showed improvement in UPDRS motor score. Conclusions: FIGHT-PD provides a depth of feasibility and safety data, methodological detail, and preliminary results that is not described elsewhere and could provide a useful basis for future studies of boxing training for PD

The use of composite pulses for improving DEER signal at 94 GHz

C.L.M. acknowledges funding from EPSRC as part of the iMRCDT. The W-band instrument was developed under the U.K. Research Councils Basic Technology Program (grant EP/F039034/1). S.V.D. acknowledges the Research Foundation Flanders (FWO) for financial support (grant G.0687.13). J.E.L. thanks the Royal Society for a University Research Fellowship. Sylvia Dewilde (Biomedical Sciences, University of Antwerp) is thanked for the purification of the Cys46Ser/ Cys55Ser mutant of human neuroglobin (NGB) used in this work. Adelheid Godt’s group is thanked for the synthesis of MSA236. We also thank the Wellcome Trust (grant 099149/Z/12/Z). The research data (and/or materials) supporting this publication can be accessed at http://dx.doi.org/10.17630/b65d05e6-6efa-48b9-a741-5a6322159a4a.The sensitivity of pulsed electron paramagnetic resonance (EPR) measurements on broad-line paramagnetic centers is often limited by the available excitation bandwidth. One way to increase excitation bandwidth is through the use of chirp or composite pulses. However, performance can be limited by cavity or detection bandwidth, which in commercial systems is typically 100-200 MHz. Here we demonstrate in a 94 GHz spectrometer, with > 800 MHz system bandwidth, an increase in signal and modulation depth in a 4-pulse DEER experiment through use of composite rather than rectangular π pulses. We show that this leads to an increase in sensitivity by a factor of 3, in line with theoretical predictions, although gains are more limited in nitroxide-nitroxide DEER measurements.PostprintPeer reviewe

Sequencing of Androgen-Deprivation Therapy of Short Duration With Radiotherapy for Nonmetastatic Prostate Cancer (SANDSTORM): A Pooled Analysis of 12 Randomized Trials

PURPOSE: The sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT). MATERIALS AND METHODS: Individual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer-specific mortality. RESULTS: Overall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points (P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer-specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT. CONCLUSION: ADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT

High-sensitivity troponin in the evaluation of patients with suspected acute coronary syndrome: a stepped-wedge, cluster-randomised controlled trial.

BACKGROUND: High-sensitivity cardiac troponin assays permit use of lower thresholds for the diagnosis of myocardial infarction, but whether this improves clinical outcomes is unknown. We aimed to determine whether the introduction of a high-sensitivity cardiac troponin I (hs-cTnI) assay with a sex-specific 99th centile diagnostic threshold would reduce subsequent myocardial infarction or cardiovascular death in patients with suspected acute coronary syndrome. METHODS: In this stepped-wedge, cluster-randomised controlled trial across ten secondary or tertiary care hospitals in Scotland, we evaluated the implementation of an hs-cTnI assay in consecutive patients who had been admitted to the hospitals' emergency departments with suspected acute coronary syndrome. Patients were eligible for inclusion if they presented with suspected acute coronary syndrome and had paired cardiac troponin measurements from the standard care and trial assays. During a validation phase of 6-12 months, results from the hs-cTnI assay were concealed from the attending clinician, and a contemporary cardiac troponin I (cTnI) assay was used to guide care. Hospitals were randomly allocated to early (n=5 hospitals) or late (n=5 hospitals) implementation, in which the high-sensitivity assay and sex-specific 99th centile diagnostic threshold was introduced immediately after the 6-month validation phase or was deferred for a further 6 months. Patients reclassified by the high-sensitivity assay were defined as those with an increased hs-cTnI concentration in whom cTnI concentrations were below the diagnostic threshold on the contemporary assay. The primary outcome was subsequent myocardial infarction or death from cardiovascular causes at 1 year after initial presentation. Outcomes were compared in patients reclassified by the high-sensitivity assay before and after its implementation by use of an adjusted generalised linear mixed model. This trial is registered with ClinicalTrials.gov, number NCT01852123. FINDINGS: Between June 10, 2013, and March 3, 2016, we enrolled 48 282 consecutive patients (61 [SD 17] years, 47% women) of whom 10 360 (21%) patients had cTnI concentrations greater than those of the 99th centile of the normal range of values, who were identified by the contemporary assay or the high-sensitivity assay. The high-sensitivity assay reclassified 1771 (17%) of 10 360 patients with myocardial injury or infarction who were not identified by the contemporary assay. In those reclassified, subsequent myocardial infarction or cardiovascular death within 1 year occurred in 105 (15%) of 720 patients in the validation phase and 131 (12%) of 1051 patients in the implementation phase (adjusted odds ratio for implementation vs validation phase 1·10, 95% CI 0·75 to 1·61; p=0·620). INTERPRETATION: Use of a high-sensitivity assay prompted reclassification of 1771 (17%) of 10 360 patients with myocardial injury or infarction, but was not associated with a lower subsequent incidence of myocardial infarction or cardiovascular death at 1 year. Our findings question whether the diagnostic threshold for myocardial infarction should be based on the 99th centile derived from a normal reference population. FUNDING: The British Heart Foundation