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.

Breast density effect on the sensitivity of digital screening mammography in a UK cohort.

OBJECTIVES: To assess the performance of breast cancer screening by category of breast density and age in a UK screening cohort. METHODS: Raw full-field digital mammography data from a single site in the UK, forming a consecutive 3-year cohort of women aged 50 to 70 years from 2016 to 2018, were obtained retrospectively. Breast density was assessed using Volpara software. Examinations were grouped by density category and age group (50-60 and 61-70 years) to analyse screening performance. Statistical analysis was performed to determine the association between density categories and age groups. Volumetric breast density was assessed as a binary classifier of interval cancers (ICs) to find an optimal density threshold. RESULTS: Forty-nine thousand nine-hundred forty-eight screening examinations (409 screen-detected cancers (SDCs) and 205 ICs) were included in the analysis. Mammographic sensitivity, SDC/(SDC + IC), decreased with increasing breast density from 75.0% for density a (p = 0.839, comparisons made to category b), to 73.5%, 59.8% (p = 0.001), and 51.3% (p < 0.001) in categories b, c, and d, respectively. IC rates were highest in the densest categories with rates of 1.8 (p = 0.039), 3.2, 5.7 (p < 0.001), and 7.9 (p < 0.001) per thousand for categories a, b, c, and d, respectively. The recall rate increased with breast density, leading to more false positive recalls, especially in the younger age group. There was no significant difference between the optimal density threshold found, 6.85, and that Volpara defined as the b/c boundary, 7.5. CONCLUSIONS: The performance of screening is significantly reduced with increasing density with IC rates in the densest category four times higher than in women with fatty breasts. False positives are a particular issue for the younger subgroup without prior examinations. CLINICAL RELEVANCE STATEMENT: In women attending screening there is significant underdiagnosis of breast cancer in those with dense breasts, most marked in the highest density category but still three times higher than in women with fatty breasts in the second highest category. KEY POINTS: Breast density can mask cancers leading to underdiagnosis on mammography. Interval cancer rate increased with breast density categories 'a' to 'd'; 1.8 to 7.9 per thousand. Recall rates increased with increasing breast density, leading to more false positive recalls.

Mammography Breast Cancer Screening Triage Using Deep Learning: A UK Retrospective Study.

Background Breast screening enables early detection of cancers; however, most women have normal mammograms, resulting in repetitive and resource-intensive reading tasks. Purpose To investigate if deep learning (DL) algorithms can be used to triage mammograms by identifying normal results to reduce workload or flag cancers that may be overlooked. Materials and Methods In this retrospective study, three commercial DL algorithms were investigated using consecutive mammograms from two UK Breast Screening Program sites from January 2015 to December 2017 and January 2017 to December 2018 on devices from two mammography vendors. Normal mammograms with a 3-year follow-up and histopathologically proven cancer detected at screening, the subsequent round, or in the 3-year interval were included. Two algorithm thresholds were set: in scenario A, 99.0% sensitivity for rule-out triage to a lone reader, and in scenario B, approximately 1.0% additional recall providing a rule-in triage for further assessment. Both thresholds were then applied to the screening workflow in scenario C. The sensitivity and specificity were used to assess the overall predictive performance of each DL algorithm. Results The data set comprised 78 849 patients (median age, 59 years [IQR, 53-63 years]) and 887 screening-detected, 439 interval, and 688 subsequent screening round-detected cancers. In scenario A (rule-out triage), models DL-1, DL-2, and DL-3 triaged 35.0% (27 565 of 78 849), 53.2% (41 937 of 78 849), and 55.6% (43 869 of 78 849) of mammograms, respectively, with 0.0% (0 of 887) to 0.1% (one of 887) of screening-detected cancers undetected. In scenario B, DL algorithms triaged in 4.6% (20 of 439) to 8.2% (36 of 439) of interval and 5.2% (36 of 688) to 6.1% (42 of 688) of subsequent-round cancers when applied after the routine double-reading workflow. Combining both approaches in scenario C resulted in an overall noninferior specificity (difference, -0.9%; P < .001) and superior sensitivity (difference, 2.7%; P < .001) for the adaptive workflow compared with routine double reading for all three algorithms. Conclusion Rule-out and rule-in DL-adapted triage workflows can improve the efficiency and efficacy of mammography breast cancer screening. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Nishikawa and Lu in this issue.

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.

High-Fidelity Simulation Versus Case Study: Which Is Best for Practical Nursing Students?

ABSTRACT: There is a gap in the literature regarding how simulation affects critical thinking skills for practical nursing students. A quasi-experimental two-group pretest-posttest study was conducted to determine the effects of high-fidelity simulation and interactive case studies on critical thinking scores of 29 practical nursing students. Both interventions had significant results (p = .001) between pretest and posttest; however, significance was not found regarding posttest scores between the high-fidelity simulation and interactive case study groups. Identifying pedagogical strategies that increase critical thinking skills for certificate-seeking practical nursing students is necessary to provide excellent nursing care and promote better patient outcomes.

Lessons From the Heart: A Kinesthetic Activity for Practical Nursing Students.

Current trends in health care delivery require nursing programs to change how education is presented to nursing students. Active learning strategies, such as discovery learning through kinesthetic activities, have been associated with increases in student engagement and satisfaction. A kinesthetic learning strategy was developed and implemented at a licensed practical nursing program to increase student engagement and provide knowledge of cardiovascular function and various etiologies associated with the heart. The goals of the activity were to provide deeper understanding and improve critical thinking and clinical application for the student.

Adjusting for BMI in analyses of volumetric mammographic density and breast cancer risk.

BACKGROUND: Fully automated assessment of mammographic density (MD), a biomarker of breast cancer risk, is being increasingly performed in screening settings. However, data on body mass index (BMI), a confounder of the MD-risk association, are not routinely collected at screening. We investigated whether the amount of fat in the breast, as captured by the amount of mammographic non-dense tissue seen on the mammographic image, can be used as a proxy for BMI when data on the latter are unavailable. METHODS: Data from a UK case control study (numbers of cases/controls: 414/685) and a Norwegian cohort study (numbers of cases/non-cases: 657/61059), both with volumetric MD measurements (dense volume (DV), non-dense volume (NDV) and percent density (%MD)) from screening-age women, were analysed. BMI (self-reported) and NDV were taken as measures of adiposity. Correlations between BMI and NDV, %MD and DV were examined after log-transformation and adjustment for age, menopausal status and parity. Logistic regression models were fitted to the UK study, and Cox regression models to the Norwegian study, to assess associations between MD and breast cancer risk, expressed as odds/hazard ratios per adjusted standard deviation (OPERA). Adjustments were first made for standard risk factors except BMI (minimally adjusted models) and then also for BMI or NDV. OPERA pooled relative risks (RRs) were estimated by fixed-effect models, and between-study heterogeneity was assessed by the I2 statistics. RESULTS: BMI was positively correlated with NDV (adjusted r = 0.74 in the UK study and r = 0.72 in the Norwegian study) and with DV (r = 0.33 and r = 0.25, respectively). Both %MD and DV were positively associated with breast cancer risk in minimally adjusted models (pooled OPERA RR (95% confidence interval): 1.34 (1.25, 1.43) and 1.46 (1.36, 1.56), respectively; I2 = 0%, P >0.48 for both). Further adjustment for BMI or NDV strengthened the %MD-risk association (1.51 (1.41, 1.61); I2 = 0%, P = 0.33 and 1.51 (1.41, 1.61); I2 = 0%, P = 0.32, respectively). Adjusting for BMI or NDV marginally affected the magnitude of the DV-risk association (1.44 (1.34, 1.54); I2 = 0%, P = 0.87 and 1.49 (1.40, 1.60); I2 = 0%, P = 0.36, respectively). CONCLUSIONS: When volumetric MD-breast cancer risk associations are investigated, NDV can be used as a measure of adiposity when BMI data are unavailable.

Effect of second timed appointments for non-attenders of breast cancer screening in England: a randomised controlled trial.

BACKGROUND: In England, participation in breast cancer screening has been decreasing in the past 10 years, approaching the national minimum standard of 70%. Interventions aimed at improving participation need to be investigated and put into practice to stop this downward trend. We assessed the effect on participation of sending invitations for breast screening with a timed appointment to women who did not attend their first offered appointment within the NHS Breast Screening Programme (NHSBSP). METHODS: In this open, randomised controlled trial, women in six centres in the NHSBSP in England who were invited for routine breast cancer screening were randomly assigned (1:1) to receive an invitation to a second appointment with fixed date and time (intervention) or an invitation letter with a telephone number to call to book their new screening appointment (control) in the event of non-attendance at the first offered appointment. Randomisation was by SX number, a sequential unique identifier of each woman within the NHSBSP, and at the beginning of the study a coin toss decided whether women with odd or even SX numbers would be allocated to the intervention group. Women aged 50-70 years who did not attend their first offered appointment were eligible for the analysis. The primary endpoint was participation (ie, attendance at breast cancer screening) within 90 days of the date of the first offered appointment; we used Poisson regression to compare the proportion of women who participated in screening in the study groups. All analyses were by intention to treat. This trial is registered with Barts Health, number 009304QM. FINDINGS: We obtained 33 146 records of women invited for breast cancer screening at the six centres between June 2, 2014, and Sept 30, 2015, who did not attend their first offered appointment. 26 054 women were eligible for this analysis (12 807 in the intervention group and 13 247 in the control group). Participation within 90 days of the first offered appointment was significantly higher in the intervention group (2861 [22%] of 12 807) than in the control group (1632 [12%] of 13 247); relative risk of participation 1·81 (95% CI 1·70-1·93; p<0·0001). INTERPRETATION: These findings show that a policy of second appointments with fixed date and time for non-attenders of breast screening is effective in improving participation. This strategy can be easily implemented by the screening sites and, if combined with simple interventions, could further increase participation and ensure an upward shift in the participation trend nationally. Whether the policy should vary by time since last attended screen will have to be considered. FUNDING: National Health Service Cancer Screening Programmes and Department of Health Policy Research Programme.

A randomised trial of the effect of postal reminders on attendance for breast screening.

BACKGROUND: Some women make an informed choice not to attend breast screening, whereas others may have forgotten about the appointment. We report on a randomised trial that investigates whether a reminder letter affects attendance. METHODS: Women scheduled for a breast screening appointment were randomised to either receive a reminder letter a few days before their breast screening appointment in addition to the standard invitation letter (intervention) or not (control). The primary outcome was attendance within 30 days of the first offered appointment. Secondary outcomes were attendance within 90 and 180 days. RESULTS: In all, 11,383 (49.9%) women were randomised to the intervention and 11,445 (50.1%) to the control. In the intervention arm, 7759 (68.2%) attended within 30 days of the first offered appointment compared with 7349 (64.2%) in the control arm. This difference was significant (P<0.001). The odds ratio (OR) (95% confidence interval) for the primary end point was 1.19 (1.13-1.26). This was not significantly affected by age, socioeconomic status or type of screen (prevalent or incident). Secondary endpoint analyses supported these results. Results did differ, however, between the different centres studied. CONCLUSIONS: This study found that postal reminders increase breast screening uptake, and could be practicable to implement in the NHS Breast Screening Programme.

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.

Percentage mammographic density or absolute breast density for risk stratification in breast screening: Possible implications for socioeconomic health disparity.

OBJECTIVES: Obesity levels and mortality from breast cancer are higher in more deprived areas of the UK, despite lower breast cancer incidence. Supplemental imaging for women with dense breasts has been proposed as a potential improvement to screening, but it is not clear how stratification by percentage mammographic density (%MD) would be reflected across socioeconomic groups. This study aims to clarify the associations between breast composition (dense and fatty tissue) and socioeconomic status in a multi-ethnic screening population. METHODS: Demographic characteristics were collected for 62,913 participants in a UK breast screening programme (age, ethnicity, Index of Multiple Deprivation (IMD)). Automated mammographic measurements were derived: dense volume (DV), non-dense volume (NDV) and percent density (%MD). Correlations between deprivation and mammographic composition were examined before and after adjustment for age, ethnicity and NDV, using non-dense breast volume as a proxy for body mass index (BMI). RESULTS: There was negligible correlation between deprivation and DV (r = 0.017; P < 0.001 in all cases), but NDV increased with increasing deprivation (Pearson r = 0.101). Correlations were weaker in the Asian and Chinese ethnic groups. %MD decreased with deprivation (r = -0.094) and adjustment for ethnicity did not alter the association between %MD and IMD (relative change, most to least deprived quintile IMD: 1.18; 95% confidence interval: 1.16, 1.21). CONCLUSIONS: Deprivation-related differences in %MD in the screening population are largely explained by differences in breast fat volume (NDV) which reflects BMI. Women in more deprived areas, where obesity and breast cancer mortality rates are higher, have increased breast adiposity and may miss out on risk-adapted screening if stratification is based solely on %MD or BIRADS classification.

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.

Did the use of open invitations in place of timed appointment invitations reduce the uptake of breast screening in the London region during the COVID-19 recovery?

OBJECTIVE: The Covid-19 pandemic created a backlog of women awaiting an invitation for breast screening in the UK. To recover in a timely fashion, the National Health Service programme opted to issue open invitations (OI) to women rather than the standard pre-booked timed appointments (TA). Historically, OIs have been shown to result in lower uptake. The aim of this study was to make use of a natural experiment to compare uptake in groups sent an OI with those sent a TA during a period when both invitation methods were in use. METHODS: Women invited for routine screening at one of the six London breast screening services from September 2020 to March 2021 were included and grouped according to the type of invitation they had received (TA or OI). The outcome was attendance within 6 months of opening the screening episode. Data were analysed by logistic regression. RESULTS: During the period of the study, 78,192 (32.5%) women received a TA and 162,680 (67.5%) received an OI. In the TA group, 47,391 (60.6%) attended within six months of offered appointment and in the OI group 86,430 (53.1%) attended. This difference was significant (p < 0.001). The odds ratio (95% CI) for the attended outcome was 1.44 (1.33-1.55) adjusted for differences in deprivation and for invitation category (first invitation or subsequent invitation). CONCLUSIONS: This study supports the view that TA delivers a higher uptake than OI. It suggests that during this period over 12,000 women in London, who would have been expected to attend if given the standard TA, did not attend their appointment having received an OI.

To what extent are objectively measured mammographic imaging techniques associated with compression outcomes.

OBJECTIVE: To describe the association between objectively measurable imaging techniques and the resulting compression thickness and dose. METHODS: The study included 80,495 routine screens from the South-West London Breast Screening Service between March 2013 and July 2017. Average compression force, paddle tilt and dose were calculated. The Volpara® DensityTM algorithm was used to estimate pressure, breast volume and density.Linear regression models, using generalized estimating equations (GEEs) to account for clustering by practitioner, assessed the strength of the associations between the imaging compression outcomes, (thickness, dose) and imaging techniques (force, pressure and paddle tilt), adjusting for the subject's characteristics (age, ethnicity, breast volume and percent mammographic density). RESULTS: Fully adjusted linear regression models showed that compression thickness decreased by ~1 mm (~2% of mean thickness) for every 1daN increase in force and decreased by ~0.8 mm with an increase of 1 kPa of pressure (at median pressure). Increasing pressure above 15 kPa resulted in minimal reduction in thickness. Dose increased with increased force but decreased by ~1% of mean dose with every increase in 1 kPa of pressure. For 1o increase in paddle tilt, the compression thickness increased by ~1.5 mm (~2.5%) and dose increased by ~2.5%, (Pt <0.001 in all cases). CONCLUSION: Differences in imaging technique are associated with imaging outcome measures (thickness and dose). A better understanding of the association between objective image acquisition parameters and tumour conspicuity could lead to clearer guidelines for practitioners. ADVANCES IN KNOWLEDGE: Increased paddle tilt is associated with increased compression thickness and increased dose after adjustment for breast volume and force applied.

Are mammography image acquisition factors, compression pressure and paddle tilt, associated with breast cancer detection in screening?

OBJECTIVES: To assess the associations between objectively measured mammographic compression pressure and paddle tilt and breast cancer (BC) detected at the same ("contemporaneous") screen, subsequent screens, or in-between screens (interval cancers). METHODS: Automated pressure and paddle tilt estimates were derived for 80,495 mammographic examinations in a UK population-based screening programme. Adjusted logistic regression models were fitted to estimate the associations of compression parameters with BC detected at contemporaneous screen (777 cases).Nested case-control designs were used to estimate associations of pressure and tilt with: (a) interval cancer (148 cases/625 age-matched controls) and (b) subsequent screen-detected cancer (344/1436), via conditional logistic regression. RESULTS: Compression pressure was negatively associated with odds of BC at contemporaneous screen (odds ratio (OR) for top versus bottom third of the pressure distribution: 0.74; 95% CI 0.60, 0.92; P-for-linear-trend (Pt) = 0.007). There was weak evidence that moderate pressure at screening was associated with lower odds of interval cancer (OR for middle versus bottom third: 0.63; 95% CI 0.38, 1.05; p = 0.079), but no association was found between pressure and the odds of BC at subsequent screen. There was no evidence that paddle tilt was associated with the odds of contemporaneous, subsequent screen or interval cancer detection. CONCLUSIONS: Findings are consistent with compression pressure, but not paddle tilt, affecting the performance of mammographic screening by interfering with its ability to detect cancers. ADVANCES IN KNOWLEDGE: Inadequate or excessive compression pressure at screening may contribute to a reduced ability to detect cancers, resulting in a greater number of interval cancer cases.

Recovery of the breast screening programme following pandemic-related delays: Should we focus on round length or uptake?

OBJECTIVES: The NHS Breast Screening programme is recovering from the hiatus in screening in 2020 due to the COVID-19 pandemic. Currently, open rather than timed invitations are issued, which leads to lower uptake but more rapid coverage of the eligible population by invitation and therefore closer adherence to a round length of 3 years. We aimed to estimate the likely effect on numbers of cancers detected at incident screens of a range of round lengths and uptake rates. METHODS: We assumed exponential distributions of time to incidence of preclinical screen-detectable cancer and of time to progression thereafter to symptomatic clinical disease. We derived numerical values of these, along with screening sensitivity, from published research results and statistics from the NHS Breast Screening programme. These were used to calculate numbers of cancers detected at incident screens at ages 51-70 by round length and uptake rates. RESULTS: We found that in a homogeneous population of cancers, a 4-year round length with uptake of 62%, as observed with timed appointments in London before the pandemic, would result in 295 cancers screen detected per 10,000 invited, compared to 222 cancers with a 3-year round and uptake of 46%, as observed in London during the recovery period. Similar results were found when we posited two populations, one of rapidly progressing and one of slowly progressing cancers. CONCLUSIONS: It may be more productive in terms of early detection to focus on uptake rather than round length in the programme's recovery from the pandemic.

The National Patient Notification Exercise: How well did local breast screening services cope with the additional workload?

OBJECTIVE: To describe how three English breast screening services responded to the 2018 Patient Notification Exercise, a national intervention whereby women who had potentially missed their final screening invitation were offered new appointments. To compare key performance indicators for women thus invited with key performance indicators for women invited routinely in the same period. METHODS: Uptake, assessment and cancer detection for 9439 women aged over 70 in the Patient Notification Exercise were compared with key performance indicators for 14,824 women, of similar age, who were routinely invited in the same period, using chi squared (χ2) tests. Invitation cancellation and attendance levels were also compared. RESULTS: Uptake was significantly lower among Patient Notification Exercise women sent a new, timed appointment than for women who were routinely invited (67.3% and 70.8%, respectively, p = 0.001). Assessment rates were higher for Patient Notification Exercise women (5.2% vs. 4.4%, p = 0.192) as were cancer detection rates (1.87% vs. 1.28%, p = 0.080). Services achieved national round-length standards for routine invitations during and after the Patient Notification Exercise but screen-to-assessment standards were breached (80%) in the smallest service. More Patient Notification Exercise women than routinely invited women rebooked appointments (43.6% and 33.2%, respectively); they were also slightly more likely to miss their appointments (24.5% vs. 21.2%). CONCLUSIONS: Screening invitation performance can be maintained whilst responding to an additional demand of ∼5%. Larger services that cover a compact geographical area may find it easier to respond. Women affected by the incident are not more likely to attend but may require relatively more assessment capacity in incidents where invitations have been delayed.

Tigecycline resistance in Serratia marcescens associated with up-regulation of the SdeXY-HasF efflux system also active against ciprofloxacin and cefpirome.

OBJECTIVES: Efflux by RND-type transporters is known to confer resistance to tigecycline in several Enterobacteriaceae species and we examined the potential of this mechanism in Serratia marcescens using a clinical isolate and laboratory-selected mutants. METHODS: Expression of RND-type efflux pump genes was analysed by real-time RT-PCR. Laboratory mutants were selected by exposure to either tigecycline or tetracycline in vitro. Efflux pump genes were inactivated by suicide plasmids containing the R6K gamma origin of replication. RESULTS: Higher tigecycline MICs correlated with elevated expression of the RND-type efflux pump genes sdeXY. Inactivation of sdeY or the outer membrane component gene hasF reduced MICs of tigecycline, tetracycline, ciprofloxacin and cefpirome to below those for strain NCTC 10211. A tetracycline-selected laboratory mutant also showed increases in sdeXY expression and tigecycline MIC. CONCLUSIONS: Up-regulation of endogenous SdeXY-HasF-mediated efflux is associated with tigecycline resistance in S. marcescens along with MIC rises for tetracycline, ciprofloxacin and cefpirome. Inactivation of this efflux system reduced MICs of those compounds to below those for strain NCTC 10211.

Left-right breast asymmetry and risk of screen-detected and interval cancers in a large population-based screening population.

OBJECTIVES: To assess the associations between automated volumetric estimates of mammographic asymmetry and breast cancers detected at the same ("contemporaneous") screen, at subsequent screens, or in between (interval cancers). METHODS: Automated measurements from mammographic images (N = 79,731) were used to estimate absolute asymmetry in breast volume (BV) and dense volume (DV) in a large ethnically diverse population of attendees of a UK breast screening programme. Logistic regression models were fitted to assess asymmetry associations with the odds of a breast cancer detected at contemporaneous screen (767 cases), adjusted for relevant confounders.Nested case-control investigations were designed to examine associations between asymmetry and the odds of: (a) interval cancer (numbers of cases/age-matched controls: 153/646) and (b) subsequent screen-detected cancer (345/1438), via conditional logistic regression. RESULTS: DV, but not BV, asymmetry was positively associated with the odds of contemporaneous breast cancer (P-for-linear-trend (Pt) = 0.018). This association was stronger for first (prevalent) screens (Pt = 0.012). Both DV and BV asymmetry were positively associated with the odds of an interval cancer diagnosis (Pt = 0.060 and 0.030, respectively). Neither BV nor DV asymmetry were associated with the odds of having a subsequent screen-detected cancer. CONCLUSIONS: Increased DV asymmetry was associated with the risk of a breast cancer diagnosis at a contemporaneous screen or as an interval cancer. BV asymmetry was positively associated with the risk of an interval cancer diagnosis. ADVANCES IN KNOWLEDGE: The findings suggest that DV and BV asymmetry may provide additional signals for detecting contemporaneous cancers and assessing the likelihood of interval cancers in population-based screening programmes.

Ethnic and age differences in right-left breast asymmetry in a large population-based screening population.

OBJECTIVE: Exposure to sex hormones is important in the pathogenesis of breast cancer and inability to tolerate such exposure may be reflected in increased asymmetrical growth of the breasts. This study aims to characterize, for the first time, asymmetry in breast volume (BV) and radiodense volume (DV) in a large ethnically diverse population. METHODS: Automated measurements from digital raw mammographic images of 54,591 cancer-free participants (aged 47-73) in a UK breast screening programme were used to calculate absolute (cm3) and relative asymmetry in BV and DV. Logistic regression models were fitted to assess asymmetry associations with age and ethnicity. RESULTS: BV and DV absolute asymmetry were positively correlated with the corresponding volumetric dimension (BV or DV). BV absolute asymmetry increased, whilst DV absolute asymmetry decreased, with increasing age (P-for-linear-trend <0.001 for both). Relative to Whites, Blacks had statistically significantly higher, and Chinese lower, BV and DV absolute asymmetries. However, after adjustment for the corresponding underlying volumetric dimension the age and ethnic differences were greatly attenuated. Median relative (fluctuating) BV and DV asymmetry were 2.34 and 3.28% respectively. CONCLUSION: After adjusting for the relevant volumetric dimension (BV or DV), age and ethnic differences in absolute breast asymmetry were largely resolved. ADVANCES IN KNOWLEDGE: Previous small studies have reported breast asymmetry-breast cancer associations. Automated measurements of asymmetry allow the conduct of large-scale studies to further investigate these associations.