Fatigue and vigilance in medical experts detecting breast cancer.

An abundance of laboratory-based experiments has described a vigilance decrement of reducing accuracy to detect targets with time on task, but there are few real-world studies, none of which have previously controlled the environment to control for bias. We describe accuracy in clinical practice for 360 experts who examined >1 million women's mammograms for signs of cancer, whilst controlling for potential biases. The vigilance decrement pattern was not observed. Instead, test accuracy improved over time, through a reduction in false alarms and an increase in speed, with no significant change in sensitivity. The multiple-decision model explains why experts miss targets in low prevalence settings through a change in decision threshold and search quit threshold and propose it should be adapted to explain these observed patterns of accuracy with time on task. What is typically thought of as standard and robust research findings in controlled laboratory settings may not directly apply to real-world environments and instead large, controlled studies in relevant environments are needed.

Optimizing the Pairs of Radiologists That Double Read Screening Mammograms.

Background Despite variation in performance characteristics among radiologists, the pairing of radiologists for the double reading of screening mammograms is performed randomly. It is unknown how to optimize pairing to improve screening performance. Purpose To investigate whether radiologist performance characteristics can be used to determine the optimal set of pairs of radiologists to double read screening mammograms for improved accuracy. Materials and Methods This retrospective study was performed with reading outcomes from breast cancer screening programs in Sweden (2008-2015), England (2012-2014), and Norway (2004-2018). Cancer detection rates (CDRs) and abnormal interpretation rates (AIRs) were calculated, with AIR defined as either reader flagging an examination as abnormal. Individual readers were divided into performance categories based on their high and low CDR and AIR. The performance of individuals determined the classification of pairs. Random pair performance, for which any type of pair was equally represented, was compared with the performance of specific pairing strategies, which consisted of pairs of readers who were either opposite or similar in AIR and/or CDR. Results Based on a minimum number of examinations per reader and per pair, the final study sample consisted of 3 592 414 examinations (Sweden, n = 965 263; England, n = 837 048; Norway, n = 1 790 103). The overall AIRs and CDRs for all specific pairing strategies (Sweden AIR range, 45.5-56.9 per 1000 examinations and CDR range, 3.1-3.6 per 1000; England AIR range, 68.2-70.5 per 1000 and CDR range, 8.9-9.4 per 1000; Norway AIR range, 81.6-88.1 per 1000 and CDR range, 6.1-6.8 per 1000) were not significantly different from the random pairing strategy (Sweden AIR, 54.1 per 1000 examinations and CDR, 3.3 per 1000; England AIR, 69.3 per 1000 and CDR, 9.1 per 1000; Norway AIR, 84.1 per 1000 and CDR, 6.3 per 1000). Conclusion Pairing a set of readers based on different pairing strategies did not show a significant difference in screening performance when compared with random pairing. © RSNA, 2023.

Optimising breast cancer screening reading: blinding the second reader to the first reader's decisions.

OBJECTIVES: In breast cancer screening, two readers separately examine each woman's mammograms for signs of cancer. We examined whether preventing the two readers from seeing each other's decisions (blinding) affects behaviour and outcomes. METHODS: This cohort study used data from the CO-OPS breast-screening trial (1,119,191 women from 43 screening centres in England) where all discrepant readings were arbitrated. Multilevel models were fitted using Markov chain Monte Carlo to measure whether reader 2 conformed to the decisions of reader 1 when they were not blinded, and the effect of blinding on overall rates of recall for further tests and cancer detection. Differences in positive predictive value (PPV) were assessed using Pearson's chi-squared test. RESULTS: When reader 1 recalls, the probability of reader 2 also recalling was higher when not blinded than when blinded, suggesting readers may be influenced by the other's decision. Overall, women were less likely to be recalled when reader 2 was blinded (OR 0.923; 95% credible interval 0.864, 0.986), with no clear pattern in cancer detection rate (OR 1.029; 95% credible interval 0.970, 1.089; Bayesian p value 0.832). PPV was 22.1% for blinded versus 20.6% for not blinded (p < 0.001). CONCLUSIONS: Our results suggest that when not blinded, reader 2 is influenced by reader 1's decisions to recall (alliterative bias) which would result in bypassing arbitration and negate some of the benefits of double-reading. We found a relationship between blinding the second reader and slightly higher PPV of breast cancer screening, although this analysis may be confounded by other centre characteristics. KEY POINTS: • In Europe, it is recommended that breast screening mammograms are analysed by two readers but there is little evidence on the effect of 'blinding' the readers so they cannot see each other's decisions. • We found evidence that when the second reader is not blinded, they are more likely to agree with a recall decision from the first reader and less likely to make an independent judgement (alliterative error). This may reduce overall accuracy through bypassing arbitration. • This observational study suggests an association between blinding the second reader and higher positive predictive value of screening, but this may be confounded by centre characteristics.

Glioma patient-reported outcome assessment in clinical care and research: a Response Assessment in Neuro-Oncology collaborative report.

Clinical trials of treatments for high-grade gliomas have traditionally relied on measures of response or time-dependent metrics; however, these endpoints have limitations because they do not characterise the functional or symptomatic effect of the condition on the person. Including clinical outcome assessments, such as patient- reported outcomes (PROs), to determine net clinical benefit of a treatment strategy is needed because of the substantial burden of symptoms and impaired functioning in this patient population. The US National Cancer Institute convened a meeting to review previous recommendations and existing PRO measures of symptoms and function that can be applied to current trials and clinical practice for high-grade gliomas. Measures were assessed for relevance, relationship to disease and therapy, sensitivity to change, psychometric properties, response format, patient acceptability, and use of self-report. The group also relied on patient input including the results of an online survey, a literature review on available clinical outcomes, expert opinion, and alignment with work done by other organisations. A core set of priority constructs was proposed that allows more comprehensive evaluation of therapies and comparison of outcomes among studies, and enhances efforts to improve the measurement of these core clinical outcomes. The proposed set of constructs was then presented to the Society for Neuro-Oncology Response Assessment in Neuro-Oncology Working Group and feedback was solicited.

Double Reading in Breast Cancer Screening: Cohort Evaluation in the CO-OPS Trial.

Purpose To investigate the effect of double readings by a second radiologist on recall rates, cancer detection, and characteristics of cancers detected in the National Health Service Breast Screening Program in England. Materials and Methods In this retrospective analysis, 805 206 women were evaluated through screening and diagnostic test results by extracting 1 year of routine data from 33 English breast screening centers. Centers used double reading of digital mammograms, with arbitration if there were discrepant interpretations. Information on reader decisions, with results of follow-up tests, were used to explore the effect of the second reader. The statistical tests used were the test for equality of proportions, the χ2 test for independence, and the t test. Results The first reader recalled 4.76% of women (38 295 of 805 206 women; 95% confidence interval [CI]: 4.71%, 4.80%). Two readers recalled 6.19% of women in total (49 857 of 805 206 women; 95% CI: 6.14%, 6.24%), but arbitration of discordant readings reduced the recall rate to 4.08% (32 863 of 805 206 women; 95% CI: 4.04%, 4.12%; P < .001). A total of 7055 cancers were detected, of which 627 (8.89%; 95% CI: 8.22%, 9.55%; P < .001) were detected by the second reader only. These additional cancers were more likely to be ductal carcinoma in situ (30.5% [183 of 600] vs 22.0% [1344 of 6114]; P < .001), and additional invasive cancers were smaller (mean size, 14.2 vs 16.7 mm; P < .001), had fewer involved nodes, and were likely to be lower grade. Conclusion Double reading with arbitration reduces recall and increases cancer detection compared with single reading. Cancers detected only by the second reader were smaller, of lower grade, and had less nodal involvement. © RSNA, 2018.

Choice architecture modifies fruit and vegetable purchasing in a university campus grocery store: time series modelling of a natural experiment.

BACKGROUND: In developed countries, adolescent and young adult diets have been found to be nutritionally poor. The aim of this study was to examine whether a choice architecture intervention, re-arrangement of produce within a grocery store to increase the accessibility of fruit and vegetables, affected purchasing behaviour on a university campus. METHODS: A database of daily sales data from January 2012 to July 2017 was obtained from a campus grocery store. Two changes to the layout were made during this time period. In January 2015, fruit and vegetables were moved from the back of the store, furthest from the entrance, to the aisle closest to the entrance and an entrance-facing display increasing their accessibility. In April 2016, the entrance-facing display of fruit and vegetables was replaced with a chiller cabinet so that fruit and vegetables remained more accessible than during the baseline period, but less accessible than in the period immediately previously. A retrospective interrupted time series analysis using dynamic regression was used to model the data and to examine the effect of the store re-arrangements on purchasing. All analyses were carried out both for sales-by-quantity and for sales-by-money. RESULTS: The first shop re-arrangement which made fruit and vegetables more prominent, increased the percentage of total sales that were fruit and vegetables, when analysed by either items purchased or money spent. The second rearrangement also had a positive effect on the percentage of total sales that were fruit and vegetables compared to baseline, however this was not significant at the 5% level. Over the five year period, the percentage of sales that were fruit and vegetables declined both in terms of items purchased, and money spent. CONCLUSIONS: Increasing accessibility of fruit and vegetables in a grocery store is a feasible way to improve the diet of students in tertiary education. There is evidence of declining fruit and vegetable consumption among the studied population, which should be further investigated.

Where's WALY? : A proof of concept study of the 'wellbeing adjusted life year' using secondary analysis of cross-sectional survey data.

BACKGROUND: The Quality-Adjusted Life Year (QALY) is a measure that combines life extension and health improvement in a single score, reflecting preferences around different types of health gain. It can therefore be used to inform decision-making around allocation of health care resources to mutually exclusive options that would produce qualitatively different health benefits. A number of quality-of-life instruments can be used to calculate QALYs. The EQ-5D is one of the most commonly used, and is the preferred option for submissions to NICE ( https://www.nice.org.uk/process/pmg9/ ). However, it has limitations that might make it unsuitable for use in areas such as public and mental health where interventions may aim to improve well-being. One alternative to the QALY is a Wellbeing-Adjusted Life Year. In this study we explore the need for a Wellbeing-Adjusted Life Year measure by examining the extent to which a measure of wellbeing (the Warwick-Edinburgh Mental Well-being Scale) maps onto the EQ-5D-3L. METHODS: Secondary analyses were conducted on data from the Coventry Household Survey in which 7469 participants completed the EQ-5D-3L, Warwick-Edinburgh Mental Well-being Scale, and a measure of self-rated health. Data were analysed using descriptive statistics, Pearson's and Spearman's correlations, linear regression, and receiver operating characteristic curves. RESULTS: Approximately 75 % of participants scored the maximum on the EQ-5D-3L. Those with maximum EQ-5D-3L scores reported a wide range of levels of mental wellbeing. Both the Warwick-Edinburgh Mental Well-being Scale and the EQ-5D-3L were able to detect differences between those with higher and lower levels of self-reported health. Linear regression indicated that scores on the Warwick-Edinburgh Mental Well-being Scale and the EQ-5D-3L were weakly, positively correlated (with R(2) being 0.104 for the index and 0.141 for the visual analogue scale). CONCLUSION: The Warwick-Edinburgh Mental Well-being Scale maps onto the EQ-5D-3L to only a limited extent. Levels of mental wellbeing varied greatly amongst participants who had the maximum score on the EQ-5D-3L. To evaluate the relative effectiveness of interventions that impact on mental wellbeing, a new measure - a Wellbeing Adjusted Life Year - is needed.

Effect of Using the Same vs Different Order for Second Readings of Screening Mammograms on Rates of Breast Cancer Detection: A Randomized Clinical Trial.

IMPORTANCE: Interpreting screening mammograms is a difficult repetitive task that can result in missed cancers and false-positive recalls. In the United Kingdom, 2 film readers independently evaluate each mammogram to search for signs of cancer and examine digital mammograms in batches. However, a vigilance decrement (reduced detection rate with time on task) has been observed in similar settings. OBJECTIVE: To determine the effect of changing the order for the second film reader of batches of screening mammograms on rates of breast cancer detection. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, double-blind, cluster randomized clinical trial conducted at 46 specialized breast screening centers from the National Health Service Breast Screening Program in England for 1 year (all between December 20, 2012, and November 3, 2014). Three hundred sixty readers participated (mean, 7.8 readers per center)-186 radiologists, 143 radiography advanced practitioners, and 31 breast clinicians, all fully qualified to report mammograms in the NHS breast screening program. INTERVENTIONS: The 2 readers examined each batch of digital mammograms in the same order in the control group and in the opposite order to one another in the intervention group. MAIN OUTCOMES AND MEASURES: The primary outcome was cancer detection rate; secondary outcomes were rates of recall and disagreements between readers. RESULTS: Among 1,194,147 women (mean age, 59.3; SD, 7.49) who had screening mammograms (596,642 in the intervention group; 597,505 in the control group), the images were interpreted in 37,688 batches (median batch size, 35; interquartile range [IQR]; 16-46), with each reader interpreting a median of 176 batches (IQR, 96-278). After completion of all subsequent diagnostic tests, a total of 10,484 cases (0.88%) of breast cancer were detected. There was no significant difference in cancer detection rate with 5272 cancers (0.88%) detected in the intervention group vs 5212 cancers (0.87%) detected in the control group (difference, 0.01% points; 95% CI, -0.02% to 0.04% points; recall rate, 24,681 [4.14%] vs 24,894 [4.17%]; difference, -0.03% points; 95% CI, -0.10% to 0.04% points; or rate of reader disagreements, 20,471 [3.43%] vs 20,793 [3.48%]; difference, -0.05% points; 95% CI, -0.11% to 0.02% points). CONCLUSIONS AND RELEVANCE: Interpretation of batches of mammograms by qualified screening mammography readers using a different order vs the same order for the second reading resulted in no significant difference in rates of detection of breast cancer. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN46603370.

Protocol for evaluation of the cost-effectiveness of ePrescribing systems and candidate prototype for other related health information technologies.

BACKGROUND: This protocol concerns the assessment of cost-effectiveness of hospital health information technology (HIT) in four hospitals. Two of these hospitals are acquiring ePrescribing systems incorporating extensive decision support, while the other two will implement systems incorporating more basic clinical algorithms. Implementation of an ePrescribing system will have diffuse effects over myriad clinical processes, so the protocol has to deal with a large amount of information collected at various 'levels' across the system. METHODS/DESIGN: The method we propose is use of Bayesian ideas as a philosophical guide.Assessment of cost-effectiveness requires a number of parameters in order to measure incremental cost utility or benefit - the effectiveness of the intervention in reducing frequency of preventable adverse events; utilities for these adverse events; costs of HIT systems; and cost consequences of adverse events averted. There is no single end-point that adequately and unproblematically captures the effectiveness of the intervention; we therefore plan to observe changes in error rates and adverse events in four error categories (death, permanent disability, moderate disability, minimal effect). For each category we will elicit and pool subjective probability densities from experts for reductions in adverse events, resulting from deployment of the intervention in a hospital with extensive decision support. The experts will have been briefed with quantitative and qualitative data from the study and external data sources prior to elicitation. Following this, there will be a process of deliberative dialogues so that experts can "re-calibrate" their subjective probability estimates. The consolidated densities assembled from the repeat elicitation exercise will then be used to populate a health economic model, along with salient utilities. The credible limits from these densities can define thresholds for sensitivity analyses. DISCUSSION: The protocol we present here was designed for evaluation of ePrescribing systems. However, the methodology we propose could be used whenever research cannot provide a direct and unbiased measure of comparative effectiveness.

Modeling Radiologists' Assessments to Explore Pairing Strategies for Optimized Double Reading of Screening Mammograms.

PURPOSE: To develop a model that simulates radiologist assessments and use it to explore whether pairing readers based on their individual performance characteristics could optimize screening performance. METHODS: Logistic regression models were designed and used to model individual radiologist assessments. For model evaluation, model-predicted individual performance metrics and paired disagreement rates were compared against the observed data using Pearson correlation coefficients. The logistic regression models were subsequently used to simulate different screening programs with reader pairing based on individual true-positive rates (TPR) and/or false-positive rates (FPR). For this, retrospective results from breast cancer screening programs employing double reading in Sweden, England, and Norway were used. Outcomes of random pairing were compared against those composed of readers with similar and opposite TPRs/FPRs, with positive assessments defined by either reader flagging an examination as abnormal. RESULTS: The analysis data sets consisted of 936,621 (Sweden), 435,281 (England), and 1,820,053 (Norway) examinations. There was good agreement between the model-predicted and observed radiologists' TPR and FPR (r ≥ 0.969). Model-predicted negative-case disagreement rates showed high correlations (r ≥ 0.709), whereas positive-case disagreement rates had lower correlation levels due to sparse data (r ≥ 0.532). Pairing radiologists with similar FPR characteristics (Sweden: 4.50% [95% confidence interval: 4.46%-4.54%], England: 5.51% [5.47%-5.56%], Norway: 8.03% [7.99%-8.07%]) resulted in significantly lower FPR than with random pairing (Sweden: 4.74% [4.70%-4.78%], England: 5.76% [5.71%-5.80%], Norway: 8.30% [8.26%-8.34%]), reducing examinations sent to consensus/arbitration while the TPR did not change significantly. Other pairing strategies resulted in equal or worse performance than random pairing. CONCLUSIONS: Logistic regression models accurately predicted screening mammography assessments and helped explore different radiologist pairing strategies. Pairing readers with similar modeled FPR characteristics reduced the number of examinations unnecessarily sent to consensus/arbitration without significantly compromising the TPR. HIGHLIGHTS: A logistic-regression model can be derived that accurately predicts individual and paired reader performance during mammography screening reading.Pairing screening mammography radiologists with similar false-positive characteristics reduced false-positive rates with no significant loss in true positives and may reduce the number of examinations unnecessarily sent to consensus/arbitration.

Atypia detected during breast screening and subsequent development of cancer: observational analysis of the Sloane atypia prospective cohort in England.

OBJECTIVE: To explore how the number and type of breast cancers developed after screen detected atypia compare with the anticipated 11.3 cancers detected per 1000 women screened within one three year screening round in the United Kingdom. DESIGN: Observational analysis of the Sloane atypia prospective cohort in England. SETTING: Atypia diagnoses through the English NHS breast screening programme reported to the Sloane cohort study. This cohort is linked to the English Cancer Registry and the Mortality and Birth Information System for information on subsequent breast cancer and mortality. PARTICIPANTS: 3238 women diagnosed as having epithelial atypia between 1 April 2003 and 30 June 2018. MAIN OUTCOME MEASURES: Number and type of invasive breast cancers detected at one, three, and six years after atypia diagnosis by atypia type, age, and year of diagnosis. RESULTS: There was a fourfold increase in detection of atypia after the introduction of digital mammography between 2010 (n=119) and 2015 (n=502). During 19 088 person years of follow-up after atypia diagnosis (until December 2018), 141 women developed breast cancer. Cumulative incidence of cancer per 1000 women with atypia was 0.95 (95% confidence interval 0.28 to 2.69), 14.2 (10.3 to 19.1), and 45.0 (36.3 to 55.1) at one, three, and six years after atypia diagnosis, respectively. Women with atypia detected more recently have lower rates of subsequent cancers detected within three years (6.0 invasive cancers per 1000 women (95% confidence interval 3.1 to 10.9) in 2013-18 v 24.3 (13.7 to 40.1) in 2003-07, and 24.6 (14.9 to 38.3) in 2008-12). Grade, size, and nodal involvement of subsequent invasive cancers were similar to those of cancers detected in the general screening population, with equal numbers of ipsilateral and contralateral cancers. CONCLUSIONS: Many atypia could represent risk factors rather than precursors of invasive cancer requiring surgery in the short term. Women with atypia detected more recently have lower rates of subsequent cancers detected, which might be associated with changes to mammography and biopsy techniques identifying forms of atypia that are more likely to represent overdiagnosis. Annual mammography in the short term after atypia diagnosis might not be beneficial. More evidence is needed about longer term risks.

Development and quality appraisal of a new English breast screening linked data set as part of the age, test threshold, and frequency of mammography screening (ATHENA-M) study.

OBJECTIVES: To build a data set capturing the whole breast cancer screening journey from individual breast cancer screening records to outcomes and assess data quality. METHODS: Routine screening records (invitation, attendance, test results) from all 79 English NHS breast screening centres between January 1, 1988 and March 31, 2018 were linked to cancer registry (cancer characteristics and treatment) and national mortality data. Data quality was assessed using comparability, validity, timeliness, and completeness. RESULTS: Screening records were extracted from 76/79 English breast screening centres, 3/79 were not possible due to software issues. Data linkage was successful from 1997 after introduction of a universal identifier for women (NHS number). Prior to 1997 outcome data are incomplete due to linkage issues, reducing validity. Between January 1, 1997 and March 31, 2018, a total of 11 262 730 women were offered screening of whom 9 371 973 attended at least one appointment, with 139 million person-years of follow-up (a median of 12.4 person years for each woman included) with 73 810 breast cancer deaths and 1 111 139 any-cause deaths. Comparability to reference data sets and internal validity were demonstrated. Data completeness was high for core screening variables (>99%) and main cancer outcomes (>95%). CONCLUSIONS: The ATHENA-M project has created a large high-quality and representative data set of individual women's screening trajectories and outcomes in England from 1997 to 2018, data before 1997 are lower quality. ADVANCES IN KNOWLEDGE: This is the most complete data set of English breast screening records and outcomes constructed to date, which can be used to evaluate and optimize screening.

Evidence-informed recommendations on managing breast screening atypia: perspectives from an expert panel consensus meeting reviewing results from the Sloane atypia project.

Evidence-based clinical guidelines are essential to maximize patient benefit and to reduce clinical uncertainty and inconsistency in clinical practice. Gaps in the evidence base can be addressed by data acquired in routine practice. At present, there is no international consensus on management of women diagnosed with atypical lesions in breast screening programmes. Here, we describe how routine NHS breast screening data collected by the Sloane atypia project was used to inform a management pathway that maximizes early detection of cancer and minimizes over-investigation of lesions with uncertain malignant potential. A half-day consensus meeting with 11 clinical experts, 1 representative from Independent Cancer Patients' Voice, 6 representatives from NHS England (NHSE) including from Commissioning, and 2 researchers was held to facilitate discussions of findings from an analysis of the Sloane atypia project. Key considerations of the expert group in terms of the management of women with screen detected atypia were: (1) frequency and purpose of follow-up; (2) communication to patients; (3) generalizability of study results; and (4) workforce challenges. The group concurred that the new evidence does not support annual surveillance mammography for women with atypia, irrespective of type of lesion, or woman's age. Continued data collection is paramount to monitor and audit the change in recommendations.

Theoretical and empirical dimensions of the Aberdeen Glaucoma Questionnaire: a cross sectional survey and principal component analysis.

BACKGROUND: To develop patient-reported outcome instruments, statistical techniques (e.g., principal components analysis; PCA) are used to examine correlations among items and identify interrelated item subsets (empirical factors). However, interpretation and labelling of empirical factors is a subjective process, lacking precision or conceptual basis. We report a novel and reproducible method for mapping between theoretical and empirical factor structures. We illustrate the method using the pilot Aberdeen Glaucoma Questionnaire (AGQ), a new measure of glaucoma-related disability developed using the International Classification of Functioning and Disability (ICF) as a theoretical framework and tested in a sample representing the spectrum of glaucoma severity. METHODS: We used the ICF to code AGQ item content before mailing the AGQ to a UK sample (N = 1349) selected to represent people with a risk factor for glaucoma and people with glaucoma across a range of severity. Reflecting uncertainty in the theoretical framework (items with multiple ICF codes), an exploratory PCA was conducted. The theoretical structure informed our interpretation of the empirical structure and guided the selection of theoretically-derived factor labels. We also explored the discrimination of the AGQ across glaucoma severity groups. RESULTS: 656 (49%) completed questionnaires were returned. The data yielded a 7-factor solution with a simple structure (using cut-off point of a loading of 0.5) that together accounted for 63% of variance in the scores. The mapping process resulted in allocation of the following theoretically-derived factor labels: 1) Seeing Functions: Participation; 2) Moving Around & Communication; 3) Emotional Functions; 4) Walking Around Obstacles; 5) Light; 6) Seeing Functions: Domestic & Social Life; 7) Mobility. Using the seven factor scores as independent variables in a discriminant function analysis, the AGQ scores resulted in correct glaucoma severity grading of 32.5% of participants (p < 0.001). CONCLUSIONS: This paper addresses a methodological gap in the application of classical test theory (CTT) techniques, such as PCA, in instrument development. Labels for empirically-derived factors are often selected intuitively whereas they can inform existing bodies of knowledge if selected on the basis of theoretical construct labels, which are more explicitly defined and which relate to each other in ways that are evidence based.

Breast screening atypia and subsequent development of cancer: protocol for an observational analysis of the Sloane database in England (Sloane atypia cohort study).

INTRODUCTION: The National Health Service (NHS) Breast Screening Programme aims to detect cancer earlier when treatment is more effective but can harm women by over diagnosing and overtreating cancers which would never have become symptomatic. As well as breast cancer, a spectrum of atypical epithelial proliferations (atypia) can also be detected as part of screening. This spectrum of changes, while not cancer, may mean that a woman is more likely to develop breast cancer in the future. Follow-up of atypia is not evidence based. We currently do not know which atypia should be detected to avoid future cancer. This study will explore how atypia develops into breast cancer in terms of number of women, time of cancer development, cancer type and severity, and whether this varies for different types of atypia. METHODS AND ANALYSIS: The Sloane cohort study began in April 2003 with ongoing data collection including atypia diagnosed through screening at screening units in the UK. The database for England has 3645 cases (24 September 2020) of epithelial atypia, with follow-up from 1 to 15 years. The outcomes include subsequent invasive breast cancer and the nature of subsequent cancer. Descriptive statistics will be produced. The observed rates of breast cancer at 1, 3 and 6 years for types of atypia will be reported with CIs, to enable comparison to women in the general population. Time to event methods will be used to describe the time to breast cancer diagnosis for the types of atypia, including flexible parametric modelling if appropriate. Patient representatives from Independent Cancer Patients' Voice are included at every stage of the research. ETHICS AND DISSEMINATION: The study has received research ethics approval from the University of Warwick Biomedical and Scientific Research Ethics Committee (BSREC 10/20-21, 8 October 2020), Public Health England office for data release approvals (ODR1718_313) and approval from the English Breast Research Advisory Committee (BSPRAC_031). The findings will be disseminated to breast screening clinicians (via journal publication and conference presentation), to the NHS Breast Screening Programme to update their guidelines on how women with atypia should be followed up, and to the general public.

A conservative pattern of water use, rather than deep or profuse rooting, is critical for the terminal drought tolerance of chickpea.

Chickpea is mostly grown on stored soil moisture, and deep/profuse rooting has been hypothesized for almost three decades to be critical for improving chickpea tolerance to terminal drought. However, temporal patterns of water use that leave water available for reproduction and grain filling could be equally critical. Therefore, variation in water use pattern and root depth/density were measured, and their relationships to yield tested under fully irrigated and terminal drought stress, using lysimeters that provided soil volumes equivalent to field conditions. Twenty chickpea genotypes having similar plant phenology but contrasting for a field-derived terminal drought-tolerance index based on yield were used. The pattern of water extraction clearly discriminated tolerant and sensitive genotypes. Tolerant genotypes had a lower water uptake and a lower index of stomatal conductance at the vegetative stage than sensitive ones, while tolerant genotypes extracted more water than sensitive genotypes after flowering. The magnitude of the variation in root growth components (depth, length density, RLD, dry weight, RDW) did not distinguish tolerant from sensitive genotypes. The seed yield was not significantly correlated with the root length density (RLD) in any soil layers, whereas seed yield was both negatively related to water uptake between 23-38 DAS, and positively related to water uptake between 48-61 DAS. Under these conditions of terminal drought, the most critical component of tolerance in chickpea was the conservative use of water early in the cropping cycle, explained partly by a lower canopy conductance, which resulted in more water available in the soil profile during reproduction leading to higher reproductive success.

Determining the optimal pelvic floor muscle training regimen for women with stress urinary incontinence.

Pelvic floor muscle (PFM) training has received Level-A evidence rating in the treatment of stress urinary incontinence (SUI) in women, based on meta-analysis of numerous randomized control trials (RCTs) and is recommended in many published guidelines. However, the actual regimen of PFM training used varies widely in these RCTs. Hence, to date, the optimal PFM training regimen for achieving continence remains unknown and the following questions persist: how often should women attend PFM training sessions and how many contractions should they perform for maximal effect? Is a regimen of strengthening exercises better than a motor control strategy or functional retraining? Is it better to administer a PFM training regimen to an individual or are group sessions equally effective, or better? Which is better, PFM training by itself or in combination with biofeedback, neuromuscular electrical stimulation, and/or vaginal cones? Should we use improvement or cure as the ultimate outcome to determine which regimen is the best? The questions are endless. As a starting point in our endeavour to identify optimal PFM training regimens, the aim of this study is (a) to review the present evidence in terms of the effectiveness of different PFM training regimens in women with SUI and (b) to discuss the current literature on PFM dysfunction in SUI women, including the up-to-date evidence on skeletal muscle training theory and other factors known to impact on women's participation in and adherence to PFM training.

A Position Statement on the Utility of Interval Imaging in Standard of Care Brain Tumour Management: Defining the Evidence Gap and Opportunities for Future Research.

OBJECTIV E: To summarise current evidence for the utility of interval imaging in monitoring disease in adult brain tumours, and to develop a position for future evidence gathering while incorporating the application of data science and health economics. METHODS: Experts in 'interval imaging' (imaging at pre-planned time-points to assess tumour status); data science; health economics, trial management of adult brain tumours, and patient representatives convened in London, UK. The current evidence on the use of interval imaging for monitoring brain tumours was reviewed. To improve the evidence that interval imaging has a role in disease management, we discussed specific themes of data science, health economics, statistical considerations, patient and carer perspectives, and multi-centre study design. Suggestions for future studies aimed at filling knowledge gaps were discussed. RESULTS: Meningioma and glioma were identified as priorities for interval imaging utility analysis. The "monitoring biomarkers" most commonly used in adult brain tumour patients were standard structural MRI features. Interval imaging was commonly scheduled to provide reported imaging prior to planned, regular clinic visits. There is limited evidence relating interval imaging in the absence of clinical deterioration to management change that alters morbidity, mortality, quality of life, or resource use. Progression-free survival is confounded as an outcome measure when using structural MRI in glioma. Uncertainty from imaging causes distress for some patients and their caregivers, while for others it provides an important indicator of disease activity. Any study design that changes imaging regimens should consider the potential for influencing current or planned therapeutic trials, ensure that opportunity costs are measured, and capture indirect benefits and added value. CONCLUSION: Evidence for the value, and therefore utility, of regular interval imaging is currently lacking. Ongoing collaborative efforts will improve trial design and generate the evidence to optimise monitoring imaging biomarkers in standard of care brain tumour management.

Quality of life in the five years after intensive care: a cohort study.

INTRODUCTION: Data on quality of life beyond 2 years after intensive care discharge are limited and we aimed to explore this area further. Our objective was to quantify quality of life and health utilities in the 5 years after intensive care discharge. METHODS: A prospective longitudinal cohort study in a University Hospital in the UK. Quality of life was assessed from the period before ICU admission until 5 years and quality adjusted life years calculated. RESULTS: 300 level 3 intensive care patients of median age 60.5 years and median length of stay 6.7 days, were recruited. Physical quality of life fell to 3 months (P = 0.003), rose back to pre-morbid levels at 12 months then fell again from 2.5 to 5 years after intensive care (P = 0.002). Mean physical scores were below the population norm at all time points but the mean mental scores after 6 months were similar to those population norms. The utility value measured using the EuroQOL-5D quality of life assessment tool (EQ-5D) at 5 years was 0.677. During the five years after intensive care unit, the cumulative quality adjusted life years were significantly lower than that expected for the general population (P < 0.001). CONCLUSIONS: Intensive care unit admission is associated with a high mortality, a poor physical quality of life and a low quality adjusted life years gained compared to the general population for 5 years after discharge. In this group, critical illness associated with ICU admission should be treated as a life time diagnosis with associated excess mortality, morbidity and the requirement for ongoing health care support.