Self-reported transvaginal ultrasound visualization of normal ovaries in postmenopausal women is not reliable: results of expert review of archived images in UKCTOCS.

OBJECTIVE: In UKCTOCS self-reported visualization rates(srVR) at annual TVS scan was a key quality control(QC) metric. Our objective was to independently assess srVR using expert review and develop software capable of monitoring it. METHODS: Images from 1,000 examinations randomly selected from 68,951 archived annual TVS exams undertaken between 2008-2011 where the ovaries were reported as 'seen and normal' were reviewed by a single expert. Software was developed to identify exact images used to measure ovaries by measuring caliper dimensions and matching them to that recorded by the sonographer. A logistic regression classifier to determine visualization was trained and validated using ovarian dimension and visualization data reported by the expert . RESULTS: The expert confirmed both ovaries were visualized (cVR-Both) in 50.2%(502/1000) of the exams. The software identified the measurement image in 534 exams which were split 2:1:1 providing training, validating and testing data. Classifier accuracy on validation data was 70.9%(CI-95% 70.0,71.8). Analysis of test data (133 exams) resulted in sensitivity of 90.5%(CI-95% 80.9,95.8) and specificity of 47.5%(CI-95% 34.5,60.8) in detecting expert confirmed cVR-Both. CONCLUSIONS: Our results suggest that in a significant proportion of TVS annual screens the sonographers may have mistaken other structures for normal ovaries. It is uncertain whether or not this affected the sensitivity and stage at detection of ovarian cancer in the ultrasound arm of UKCTOCS, but we conclude QC metrics based on self-reported visualization of normal ovaries are unreliable. The classifier shows some potential for addressing this problem, though further research is needed

Sonographers' self-reported visualization of normal postmenopausal ovaries on transvaginal ultrasound is not reliable: results of expert review of archived images from UKCTOCS.

OBJECTIVE: In the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), self-reported visualization rate (VR) of the ovaries by the sonographer on annual transvaginal sonographic (TVS) examinations was a key quality control (QC) metric. The objective of this study was to assess self-reported VR using expert review of a random sample of archived images of TVS examinations from UKCTOCS, and then to develop software for measuring VR automatically. METHODS: A single expert reviewed images archived from 1000 TVS examinations selected randomly from 68 931 TVS scans performed in UKCTOCS between 2008 and 2011 with ovaries reported as 'seen and normal'. Software was developed to identify the exact images used by the sonographer to measure the ovaries. This was achieved by measuring caliper dimensions in the image and matching them to those recorded by the sonographer. A logistic regression classifier to determine visualization was trained and validated using ovarian dimensions and visualization data reported by the expert. RESULTS: The expert reviewer confirmed visualization of both ovaries (VR-Both) in 50.2% (502/1000) of the examinations. The software identified the measurement image in 534 exams, which were split 2:1:1 providing training, validation and test data. Classifier mean accuracy on validation data was 70.9% (95% CI, 70.0-71.8%). Analysis of test data (133 exams) provided a sensitivity of 90.5% (95% CI, 80.9-95.8%) and specificity of 47.5% (95% CI, 34.5-60.8%) in detecting expert confirmed visualization of both ovaries. CONCLUSIONS: Our results suggest that, in a significant proportion of TVS annual screens, the sonographers may have mistaken other structures for normal ovaries. It is uncertain whether or not this affected the sensitivity and stage at detection of ovarian cancer in the ultrasound arm of UKCTOCS, but we conclude that QC metrics based on self-reported visualization of normal ovaries are unreliable. The classifier shows some potential for addressing this problem, though further research is needed. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology

The opposites task: Using general rules to test cognitive flexibility in preschoolers

A brief narrative description of the journal article, document, or resource. Executive functions play an important role in cognitive development, and during the preschool years especially, children's performance is limited in tasks that demand flexibility in their behavior. We asked whether preschoolers would exhibit limitations when they are required to apply a general rule in the context of novel stimuli on every trial (the "opposites" task). Two types of inhibitory processing were measured: response interference (resistance to interference from a competing response) and proactive interference (resistance to interference from a previously relevant rule). Group data show 3-year-olds have difficulty inhibiting prepotent tendencies under these conditions, whereas 5-year-olds' accuracy is near ceiling in the task. (Contains 4 footnotes and 1 table.

Risk algorithm using serial biomarker measurements doubles the number of screen-detected cancers compared with a single-threshold rule in the United Kingdom collaborative trial of ovarian cancer screening

PURPOSE: Cancer screening strategies have commonly adopted single-biomarker thresholds to identify abnormality. We investigated the impact of serial biomarker change interpreted through a risk algorithm on cancer detection rates. PATIENTS AND METHODS: In the United Kingdom Collaborative Trial of Ovarian Cancer Screening, 46,237 women, age 50 years or older underwent incidence screening by using the multimodal strategy (MMS) in which annual serum cancer antigen 125 (CA-125) was interpreted with the risk of ovarian cancer algorithm (ROCA). Women were triaged by the ROCA: normal risk, returned to annual screening; intermediate risk, repeat CA-125; and elevated risk, repeat CA-125 and transvaginal ultrasound. Women with persistently increased risk were clinically evaluated. All participants were followed through national cancer and/or death registries. Performance characteristics of a single-threshold rule and the ROCA were compared by using receiver operating characteristic curves. RESULTS: After 296,911 women-years of annual incidence screening, 640 women underwent surgery. Of those, 133 had primary invasive epithelial ovarian or tubal cancers (iEOCs). In all, 22 interval iEOCs occurred within 1 year of screening, of which one was detected by ROCA but was managed conservatively after clinical assessment. The sensitivity and specificity of MMS for detection of iEOCs were 85.8% (95% CI, 79.3% to 90.9%) and 99.8% (95% CI, 99.8% to 99.8%), respectively, with 4.8 surgeries per iEOC. ROCA alone detected 87.1% (135 of 155) of the iEOCs. Using fixed CA-125 cutoffs at the last annual screen of more than 35, more than 30, and more than 22 U/mL would have identified 41.3% (64 of 155), 48.4% (75 of 155), and 66.5% (103 of 155), respectively. The area under the curve for ROCA (0.915) was significantly (P = .0027) higher than that for a single-threshold rule (0.869). CONCLUSION: Screening by using ROCA doubled the number of screen-detected iEOCs compared with a fixed cutoff. In the context of cancer screening, reliance on predefined single-threshold rules may result in biomarkers of value being discarded

Evidence-Based Guideline on Laparoscopy in Pregnancy: Commissioned by the British Society for Gynaecological Endoscopy (BSGE) Endorsed by the Royal College of Obstetricians & Gynaecologists (RCOG).

Laparoscopy is widely utilised to diagnose and treat acute and chronic, gynaecological and general surgical conditions. It has only been in recent years that laparoscopy has become an acceptable surgical alternative to open surgery in pregnancy. To date there is little clinical guidance pertaining to laparoscopic surgery in pregnancy. This is why the BSGE commissioned this guideline. MEDLINE, EMBASE, CINAHL and the Cochrane library were searched up to February 2017 and evidence was collated and graded following the NICE-approved process. The conditions included in this guideline are laparoscopic management of acute appendicitis, acute gall bladder disease and symptomatic benign adnexal tumours in pregnancy. The intended audience for this guideline is obstetricians and gynaecologists in secondary and tertiary care, general surgeons and anaesthetists. However, only laparoscopists who have adequate laparoscopic skills and who perform complex laparoscopic surgery regularly should undertake laparoscopy in pregnant women, since much of the evidence stems from specialised centres

Audit of transvaginal sonography of normal postmenopausal ovaries by sonographers from the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

BACKGROUND: We report on a unique audit of seven sonographers self-reporting high visualization rates of normal postmenopausal ovaries in the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). This audit was ordered by the trial’s Ultrasound Management Subcommittee after an initiative taken in 2008 to improve the quality of scanning and the subsequent increase in the number of sonographers claiming very high ovary visualisation rates. METHODS: Seven sonographers reporting high rates (>89%) of visualizing normal postmenopausal ovaries in examinations performed between 1st January and 31st December 2008 were identified. Eight experts in gynaecological scanning reviewed a random selection of exams performed by these sonographers and assessed whether visualization of both ovaries could be confirmed (cVR-Both) in the examinations. A random effects bivariate probit model was fitted to analyse the results. RESULTS: The eight experts reviewed images from 357 examinations performed on 349 postmenopausal women (mean age 60.0 years, range 50.2-73.3) by the seven sonographers. The mean cVR-Both obtained from the model for these sonographers was 67.2% with a range of 47.6-86.5% (95%CI 63.9-70.5%). The range of cVR-Both between the experts was 47.3-88.3% and the intra-class correlation coefficient (ICC) for left and right ovary confirmation was 0.39. CONCLUSIONS: The audit suggests that self-reported visualization of postmenopausal ovaries is unreliable, as visualisation of both ovaries could not be confirmed in almost a third of examinations. The agreement for visualization of both ovaries based on review of a static image between experts and sonographers and between expert reviewers alone was only moderate. Further research is needed to develop reliable Quality Control metrics for transvaginal ultrasound

The cost-effectiveness of screening for ovarian cancer: results from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

Background: To assess the within trial cost-effectiveness of an NHS ovarian cancer screening (OCS) programme using data from UKCTOCS and extrapolate results based on average life expectancy. Methods: Within trial economic evaluation of no screening (C) versus either (1) an annual OCS programme using transvaginal ultrasound (USS) or (2) an annual ovarian cancer multimodal screening programme with serum CA125 interpreted using a risk algorithm (ROCA) and transvaginal ultrasound as a second line test (MMS), plus comparison of lifetime extrapolation of the no screening arm and the MMS programme using both a predictive and a Markov model. Results: Using a CA125-ROCA cost of £20, the within trial results show USS to be strictly dominated by MMS, with the MMS versus C comparison returning an Incremental Cost-Effectiveness ratio (ICER) of £91,452 per life year gained (LYG). If the CA125-ROCA unit cost is reduced to £15 the ICER becomes £77,818 per LYG. Predictive extrapolation over the expected lifetime of the UKCTOCS women returns an ICER of £30,033 per LYG, while Markov modelling produces an ICER of £46,922 per QALY. Conclusions: Analysis suggests that, after accounting for the lead-time required to establish full mortality benefits, a national OCS programme based on the MMS strategy quickly approaches the current NICE thresholds for cost-effectiveness when extrapolated out to lifetime as compared to the within trial ICER estimates. Whether MMS could be recommended on economic grounds would depend on the confirmation and size of the mortality benefit at the end of an ongoing follow-up of the UKCTOCS cohort

Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial

Background Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the eff ect of early detection by screening on ovarian cancer mortality. Methods In this randomised controlled trial, we recruited postmenopausal women aged 50–74 years from 13 centres in National Health Service Trusts in England, Wales, and Northern Ireland. Exclusion criteria were previous bilateral oophorectomy or ovarian malignancy, increased risk of familial ovarian cancer, and active non-ovarian malignancy. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computergenerated random numbers to annual multimodal screening (MMS) with serum CA125 interpreted with use of the risk of ovarian cancer algorithm, annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. The primary outcome was death due to ovarian cancer by Dec 31, 2014, comparing MMS and USS separately with no screening, ascertained by an outcomes committee masked to randomisation group. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have ovarian cancer, or had exited the registry before recruitment. Investigators and participants were aware of screening type. This trial is registered with ClinicalTrials.gov, number NCT00058032. Findings Between June 1, 2001, and Oct 21, 2005, we randomly allocated 202 638 women: 50 640 (25·0%) to MMS, 50 639 (25·0%) to USS, and 101 359 (50·0%) to no screening. 202 546 (>99·9%) women were eligible for analysis: 50 624 (>99·9%) women in the MMS group, 50 623 (>99·9%) in the USS group, and 101 299 (>99·9%) in the no screening group. Screening ended on Dec 31, 2011, and included 345 570 MMS and 327 775 USS annual screening episodes. At a median follow-up of 11·1 years (IQR 10·0–12·0), we diagnosed ovarian cancer in 1282 (0·6%) women: 338 (0·7%) in the MMS group, 314 (0·6%) in the USS group, and 630 (0·6%) in the no screening group. Of these women, 148 (0·29%) women in the MMS group, 154 (0·30%) in the USS group, and 347 (0·34%) in the no screening group had died of ovarian cancer. The primary analysis using a Cox proportional hazards model gave a mortality reduction over years 0–14 of 15% (95% CI –3 to 30; p=0·10) with MMS and 11% (–7 to 27; p=0·21) with USS. The Royston-Parmar fl exible parametric model showed that in the MMS group, this mortality eff ect was made up of 8% (–20 to 31) in years 0–7 and 23% (1–46) in years 7–14, and in the USS group, of 2% (–27 to 26) in years 0–7 and 21% (–2 to 42) in years 7–14. A prespecified analysis of death from ovarian cancer of MMS versus no screening with exclusion of prevalent cases showed significantly diff erent death rates (p=0·021), with an overall average mortality reduction of 20% (–2 to 40) and a reduction of 8% (–27 to 43) in years 0–7 and 28% (–3 to 49) in years 7–14 in favour of MMS. Interpretation Although the mortality reduction was not signifi cant in the primary analysis, we noted a signifi cant mortality reduction with MMS when prevalent cases were excluded. We noted encouraging evidence of a mortality reduction in years 7–14, but further follow-up is needed before firm conclusions can be reached on the efficacy and cost-eff ectiveness of ovarian cancer screening

Beyond the Bayley: Neurocognitive Assessments of Development During Infancy and Toddlerhood

The use of global, standardized instruments is conventional among clinicians and researchers interested in assessing neurocognitive development. Exclusively relying on these tests for evaluating effects may underestimate or miss specific effects on early cognition. The goal of this review is to identify alternative measures for possible inclusion in future clinical trials and interventions evaluating early neurocognitive development. The domains included for consideration are attention, memory, executive function, language and socio-emotional development. Although domain-based tests are limited, as psychometric properties have not yet been well-established, this review includes tasks and paradigms that have been reliably used across various developmental psychology laboratories