Take a break: should breaks be enforced during digital breast tomosynthesis reading sessions?

OBJECTIVES: Digital breast tomosynthesis (DBT) can improve diagnostic accuracy compared to 2D mammography, but DBT reporting is time-consuming and potentially more fatiguing. Changes in diagnostic accuracy and subjective and objective fatigue were evaluated over a DBT reporting session, and the impact of taking a reporting break was assessed. MATERIALS AND METHODS: Forty-five National Health Service (NHS) mammography readers from 6 hospitals read a cancer-enriched set of 40 DBT cases whilst eye tracked in this prospective cohort study, from December 2020 to April 2022. Eye-blink metrics were assessed as objective fatigue measures. Twenty-one readers had a reporting break, 24 did not. Subjective fatigue questionnaires were completed before and after the session. Diagnostic accuracy and subjective and objective fatigue measures were compared between the cohorts using parametric and non-parametric significance testing. RESULTS: Readers had on average 10 years post-training breast screening experience and took just under 2 h (105.8 min) to report all cases. Readers without a break reported greater levels of subjective fatigue (44% vs. 33%, p = 0.04), which related to greater objective fatigue: an increased average blink duration (296 ms vs. 286 ms, p < 0.001) and a reduced eye-opening velocity (76 mm/s vs. 82 mm/s, p < 0.001). Objective fatigue increased as the trial progressed for the no break cohort only (ps < 0.001). No difference was identified in diagnostic accuracy between the groups (accuracy: 87% vs. 87%, p = 0.92). CONCLUSIONS: Implementing a break during a 2-h DBT reporting session resulted in lower levels of subjective and objective fatigue. Breaks did not impact diagnostic accuracy, which may be related to the extensive experience of the readers. CLINICAL RELEVANCE STATEMENT: DBT is being incorporated into many mammography screening programmes. Recognising that reporting breaks are required when reading large volumes of DBT studies ensures this can be factored in when setting up reading sessions. TRIAL REGISTRATION: Clinical trials registration number: NCT03733106 KEY POINTS: • Use of digital breast tomosynthesis (DBT) in breast screening programmes can cause significant reader fatigue. • The effectiveness of incorporating reading breaks into DBT reporting sessions, to reduce mammography reader fatigue, was investigated using eye tracking. • Integrating breaks into DBT reporting sessions reduced reader fatigue; however, diagnostic accuracy was unaffected.

Performance of Radiologists and Radiographers in Double Reading Mammograms: The UK National Health Service Breast Screening Program.

Background Double reading can be used in screening mammography, but it is labor intensive. There is limited evidence on whether trained radiographers (ie, technologists) may be used to provide double reading. Purpose To compare the performance of radiologists and radiographers double reading screening mammograms, considering reader experience level. Materials and Methods In this retrospective study, performance and experience data were obtained for radiologists and radiographer readers of all screening mammograms in England from April 2015 to March 2016. Cancer detection rate (CDR), recall rate (RR), and positive predictive value (PPV) of recall based on biopsy-proven findings were calculated for first readers. Performance metrics were analyzed according to reader professional group and years of reading experience using the analysis of variance test. P values less than .05 were considered to indicate statistically significant difference. Results During the study period, 401 readers (224 radiologists and 177 radiographers) double read 1 404 395 screening digital mammograms. There was no difference in CDR between radiologist and radiographer readers (mean, 7.84 vs 7.53 per 1000 examinations, respectively; P = .08) and no difference for readers with more than 10 years of experience compared with 5 years or fewer years of experience, regardless of professional group (mean, 7.75 vs 7.71 per 1000 examinations respectively, P = .87). No difference in the mean RR was observed between radiologists and radiographer readers (5.0% vs 5.2%, respectively, P = .63). A lower RR was seen for readers with more than 10 years of experience compared with 5 years or fewer, regardless of professional group (mean, 4.8% vs 5.8%, respectively; P = .001). No variation in PPV was observed between them (P = .42), with PPV values of 17.1% for radiologists versus 16.1% for radiographers. A higher PPV was seen for readers with more than 10 years of experience compared with 5 years or less, regardless of professional group (mean, 17.5% and 14.9%, respectively; P = .02). Conclusion No difference in performance was observed between radiographers and radiologists reading screening mammograms in a program that used double reading. Published under a CC BY 4.0 license Online supplemental material is available for this article. See also the editorial by Hooley and Durand in this issue.

Performance of a Breast Cancer Detection AI Algorithm Using the Personal Performance in Mammographic Screening Scheme.

Background The Personal Performance in Mammographic Screening (PERFORMS) scheme is used to assess reader performance. Whether this scheme can assess the performance of artificial intelligence (AI) algorithms is unknown. Purpose To compare the performance of human readers and a commercially available AI algorithm interpreting PERFORMS test sets. Materials and Methods In this retrospective study, two PERFORMS test sets, each consisting of 60 challenging cases, were evaluated by human readers between May 2018 and March 2021 and were evaluated by an AI algorithm in 2022. AI considered each breast separately, assigning a suspicion of malignancy score to features detected. Performance was assessed using the highest score per breast. Performance metrics, including sensitivity, specificity, and area under the receiver operating characteristic curve (AUC), were calculated for AI and humans. The study was powered to detect a medium-sized effect (odds ratio, 3.5 or 0.29) for sensitivity. Results A total of 552 human readers interpreted both PERFORMS test sets, consisting of 161 normal breasts, 70 malignant breasts, and nine benign breasts. No difference was observed at the breast level between the AUC for AI and the AUC for human readers (0.93% and 0.88%, respectively; P = .15). When using the developer's suggested recall score threshold, no difference was observed for AI versus human reader sensitivity (84% and 90%, respectively; P = .34), but the specificity of AI was higher (89%) than that of the human readers (76%, P = .003). However, it was not possible to demonstrate equivalence due to the size of the test sets. When using recall thresholds to match mean human reader performance (90% sensitivity, 76% specificity), AI showed no differences inperformance, with a sensitivity of 91% (P =. 73) and a specificity of 77% (P = .85). Conclusion Diagnostic performance of AI was comparable with that of the average human reader when evaluating cases from two enriched test sets from the PERFORMS scheme. © RSNA, 2023 See also the editorial by Philpotts in this issue.

Preoperative diagnosis of ductal carcinoma in situ of the breast over a 24-year period.

AIMS: The method of diagnosis of ductal carcinoma in situ (DCIS) has changed since the 1980s. The aim of this audit was to assess changes in the preoperative diagnosis of DCIS since the introduction of needle core biopsy, particularly the proportion with a preoperative biopsy diagnosis of DCIS. METHODS AND RESULTS: The preoperative diagnoses of patients with a final diagnosis of DCIS in the surgical specimen were reviewed (i) in 809 patients who presented through breast screening from 1997 to 2021, and (ii) in all patients in 5 individual years at 5-year intervals from 2000 to 2020 (254 in total). For screening-detected DCIS the proportion with a preoperative diagnosis of DCIS increased from 75% to 98% over the study period. In a detailed analysis of all cases of DCIS in 5 separate years the proportion with a preoperative diagnosis of DCIS increased from 68% in 2000 to 96% in 2020. For high-grade DCIS the proportion increased from 87% to 97%, and for low- or intermediate-grade DCIS from 48% to 93%. The proportion of women who had vacuum-assisted biopsy increased from 7% in 2000 to 58% in 2015. There was a small increase in the number of biopsies that had basal cytokeratin and oestrogen receptor immunohistochemistry to aid diagnosis. CONCLUSION: There has been an increase in the preoperative diagnosis of DCIS, particularly of low- or intermediate-grade, over the last two decades. The increasing use of vacuum-assisted biopsy is likely to be a major contributory factor to this increase.

Multi-vendor evaluation of artificial intelligence as an independent reader for double reading in breast cancer screening on 275,900 mammograms.

BACKGROUND: Double reading (DR) in screening mammography increases cancer detection and lowers recall rates, but has sustainability challenges due to workforce shortages. Artificial intelligence (AI) as an independent reader (IR) in DR may provide a cost-effective solution with the potential to improve screening performance. Evidence for AI to generalise across different patient populations, screening programmes and equipment vendors, however, is still lacking. METHODS: This retrospective study simulated DR with AI as an IR, using data representative of real-world deployments (275,900 cases, 177,882 participants) from four mammography equipment vendors, seven screening sites, and two countries. Non-inferiority and superiority were assessed for relevant screening metrics. RESULTS: DR with AI, compared with human DR, showed at least non-inferior recall rate, cancer detection rate, sensitivity, specificity and positive predictive value (PPV) for each mammography vendor and site, and superior recall rate, specificity, and PPV for some. The simulation indicates that using AI would have increased arbitration rate (3.3% to 12.3%), but could have reduced human workload by 30.0% to 44.8%. CONCLUSIONS: AI has potential as an IR in the DR workflow across different screening programmes, mammography equipment and geographies, substantially reducing human reader workload while maintaining or improving standard of care. TRIAL REGISTRATION: ISRCTN18056078 (20/03/2019; retrospectively registered).

Why do we evaluate 30-day readmissions in general medicine? A historical perspective and contemporary data.

Reducing preventable readmissions is important to help manage current strains on healthcare systems. The metric of 30-day readmissions is commonly cited in discussions regarding this topic. While such thresholds have contemporary funding implications, the rationale for individual cut-off points is partially historical in nature. Through the examination of the basis for the analysis of 30-day readmissions, greater insight into the possible benefits and limitations of such a metric may be obtained.

Differential Potency of Venlafaxine, Paroxetine, and Atomoxetine to Inhibit Serotonin and Norepinephrine Reuptake in Patients With Major Depressive Disorder.

BACKGROUND: Venlafaxine is a dual serotonin (5-HT) and norepinephrine reuptake inhibitor. The specific dose at which it begins to efficiently engage the norepinephrine transporter (NET) remained to be determined. Paroxetine is generally considered as a selective 5-HT reuptake inhibitor but exhibits some affinity for NET. Atomoxetine is a NET inhibitor but also has some affinity for the 5-HT reuptake transporter (SERT). METHODS: This study examined the effects of forced titration of venlafaxine from 75 to 300 mg/d, paroxetine from 20 to 50 mg/d, or atomoxetine from 25 to 80 mg/d in 32 patients with major depressive disorder. Inhibition of SERT was estimated using the depletion of whole-blood 5-HT. Inhibition of NET was assessed using the attenuation of the systolic blood pressure produced by i.v. injections of tyramine. RESULTS: All 3 medications significantly reduced 5-HT levels at the initiating regimens: venlafaxine and paroxetine by approximately 60% and atomoxetine by 16%. The 3 subsequent regimens of venlafaxine and paroxetine reduced 5-HT levels by over 90%, but the highest dose of atomoxetine only reached a 40% inhibition. Atomoxetine dose dependently inhibited the tyramine pressor response from the lowest dose, venlafaxine from 225 mg/d, and paroxetine left it unaltered throughout. CONCLUSION: These results confirm that venlafaxine and paroxetine are potent SERT inhibitors over their usual therapeutic range but that venlafaxine starts inhibiting NET only at 225 mg/d, whereas paroxetine remains selective for SERT up to 50 mg/d. Atomoxetine dose dependently inhibits NET from a low dose but does not inhibit SERT to a clinically relevant degree.

The molecular landscape of well differentiated retroperitoneal liposarcoma.

Well differentiated liposarcoma (WD-LPS) is a relatively rare tumour, with fewer than 50 cases occurring per year in the UK. These tumours are both chemotherapy- and radiotherapy-resistant and present a significant treatment challenge requiring radical surgery. Little is known of the molecular landscape of these tumours and no current targets for molecular therapy exist. We aimed to carry out a comprehensive molecular characterisation of WD-LPS via whole genome sequencing, RNA sequencing, and methylation array analysis. A recurrent mutation within exon 1 of FOXD4L3 was observed (chr9:70,918,189A>T; c.322A>T; p.Lys108Ter). Recurrent mutations were also observed in Wnt signalling, immunity, DNA repair, and hypoxia-associated genes. Recurrent amplification of HGMA2 was observed, although this was in fact part of a general amplification of the region around this gene. Recurrent gene fusions in HGMA2, SDHA, TSPAN31, and MDM2 were also observed as well as consistent rearrangements between chromosome 6 and chromosome 12. Our study has demonstrated a recurrent mutation within FOXD4L3, which shows evidence of interaction with the PAX pathway to promote tumourigenesis. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Effectiveness of percutaneous vacuum-assisted excision (VAE) of breast lesions of uncertain malignant potential (B3 lesions) as an alternative to open surgical biopsy.

OBJECTIVES: Traditionally B3 breast lesions are treated surgically, but overtreatment is a concern, as the majority have a final benign diagnosis. A national screening program introduced vacuum-assisted excision (VAE) for managing B3 lesions in late 2016. This retrospective study aimed to assess the outcomes associated with this approach. METHODS: All B3 lesions diagnosed between 01/2017 and 12/2019 were identified at two centres. Information was obtained on the initial biopsy and final histology, and method of VAE image guidance, needle size and number of cores. Lesions were excluded if there was cancer elsewhere in the breast at the time of diagnosis; the lesion was not suitable for VAE due to position in the breast or had B3 pathology for which open biopsy was still required. The final decision to offer VAE was always made at a multidisciplinary meeting (MDM). Risk difference was used to test the significance at p ≤ .05. RESULTS: In total, 258 B3 lesions were diagnosed, 105 (40.7%) met the inclusion criteria and underwent VAE. VAE was performed under X-ray (89/105) or ultrasound guidance (16/105), taking an average of 18.5 cores with the 10-G needle or 10.8 cores with the 7-G needle. Nine cases (8.6%) were upgraded to a malignant diagnosis following VAE. Malignancy was found in 15.5% (9/58) of B3 lesions with epithelial atypia, but in none without atypia (0/47) (p = .004). No new lesions or malignancy has occurred at the site of the VAE with an average mammographic follow-up of 2.2 years. CONCLUSION: Upgrade to malignancy following VAE was uncommon (8.6%) and associated with atypia in the initial biopsy. VAE is an alternative approach to the management of B3 lesions, reducing open surgical procedures. KEY POINTS: • Upgrade to malignancy after a vacuum-assisted excision of a B3 breast lesion is uncommon with an 8.6% upgrade rate. • The risk of a malignant diagnosis after a vacuum-assisted excision was significantly higher for B3 lesions with atypia compared to those without (+15.5% difference, p = .004).

Acceptability and Effectiveness of Artificial Intelligence Therapy for Anxiety and Depression (Youper): Longitudinal Observational Study.

BACKGROUND: Youper is a widely used, commercially available mobile app that uses artificial intelligence therapy for the treatment of anxiety and depression. OBJECTIVE: Our study examined the acceptability and effectiveness of Youper. Further, we tested the cumulative regulation hypothesis, which posits that cumulative emotion regulation successes with repeated intervention engagement will predict longer-term anxiety and depression symptom reduction. METHODS: We examined data from paying Youper users (N=4517) who allowed their data to be used for research. To characterize the acceptability of Youper, we asked users to rate the app on a 5-star scale and measured retention statistics for users' first 4 weeks of subscription. To examine effectiveness, we examined longitudinal measures of anxiety and depression symptoms. To test the cumulative regulation hypothesis, we used the proportion of successful emotion regulation attempts to predict symptom reduction. RESULTS: Youper users rated the app highly (mean 4.36 stars, SD 0.84), and 42.66% (1927/4517) of users were retained by week 4. Symptoms decreased in the first 2 weeks of app use (anxiety: d=0.57; depression: d=0.46). Anxiety improvements were maintained in the subsequent 2 weeks, but depression symptoms increased slightly with a very small effect size (d=0.05). A higher proportion of successful emotion regulation attempts significantly predicted greater anxiety and depression symptom reduction. CONCLUSIONS: Youper is a low-cost, completely self-guided treatment that is accessible to users who may not otherwise access mental health care. Our findings demonstrate the acceptability and effectiveness of Youper as a treatment for anxiety and depression symptoms and support continued study of Youper in a randomized clinical trial.

Loss of Adult 5-HT1A Autoreceptors Results in a Paradoxical Anxiogenic Response to Antidepressant Treatment.

Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are first-line antidepressants but require several weeks to elicit their actions. Chronic SSRI treatment induces desensitization of 5-HT1A autoreceptors to enhance 5-HT neurotransmission. Mice (both sexes) with gene deletion of 5-HT1A autoreceptors in adult 5-HT neurons (1AcKO) were tested for response to SSRIs. Tamoxifen-induced recombination in adult 1AcKO mice specifically reduced 5-HT1A autoreceptor levels. The 1AcKO mice showed a loss of 5-HT1A autoreceptor-mediated hypothermia and electrophysiological responses, but no changes in anxiety- or depression-like behavior. Subchronic fluoxetine (FLX) treatment induced an unexpected anxiogenic effect in 1AcKO mice in the novelty suppressed feeding and elevated plus maze tests, as did escitalopram in the novelty suppressed feeding test. No effect was seen in wild-type (WT) mice. Subchronic FLX increased 5-HT metabolism in prefrontal cortex, hippocampus, and raphe of 1AcKO but not WT mice, suggesting hyperactivation of 5-HT release. To detect chronic cellular activation, FosB+ cells were quantified. FosB+ cells were reduced in entorhinal cortex and hippocampus (CA2/3) and increased in dorsal raphe 5-HT cells of 1AcKO mice, suggesting increased raphe activation. In WT but not 1AcKO mice, FLX reduced FosB+ cells in the median raphe, hippocampus, entorhinal cortex, and median septum, which receive rich 5-HT projections. Thus, in the absence of 5-HT1A autoreceptors, SSRIs induce a paradoxical anxiogenic response. This may involve imbalance in activation of dorsal and median raphe to regulate septohippocampal or fimbria-fornix pathways. These results suggest that markedly reduced 5-HT1A autoreceptors may provide a marker for aberrant response to SSRI treatment.SIGNIFICANCE STATEMENT Serotonin-selective reuptake inhibitors (SSRIs) are effective in treating anxiety and depression in humans and mouse models. However, in some cases, SSRIs can increase anxiety, but the mechanisms involved are unclear. Here we show that, rather than enhancing SSRI benefits, adulthood knockout (KO) of the 5-HT1A autoreceptor, a critical negative regulator of 5-HT activity, results in an SSRI-induced anxiety effect that appears to involve a hyperactivation of the 5-HT system in certain brain areas. Thus, subjects with very low levels of 5-HT1A autoreceptors, such as during childhood or adolescence, may be at risk for an SSRI-induced anxiety response.

Whole Genome Methylation Analysis of Nondysplastic Barrett Esophagus that Progresses to Invasive Cancer.

OBJECTIVE: To investigate differences in methylation between patients with nondysplastic Barrett esophagus who progress to invasive adenocarcinoma and those who do not. BACKGROUND: Identifying patients with nondysplastic Barrett esophagus who progress to invasive adenocarcinoma remains a challenge. Previous studies have demonstrated the potential utility of epigenetic markers for identifying this group. METHODS: A whole genome methylation interrogation using the Illumina HumanMethylation 450 array of patients with nondysplastic Barrett esophagus who either develop adenocarcinoma or remain static, with validation of findings by bisulfite pyrosequencing. RESULTS: In all, 12 patients with "progressive" versus 12 with "nonprogressive" nondysplastic Barrett esophagus were analyzed via methylation array. Forty-four methylation markers were identified that may be able to discriminate between nondysplastic Barrett esophagus that either progress to adenocarcinoma or remain static. Hypomethylation of the recently identified tumor suppressor OR3A4 (probe cg09890332) validated in a separate cohort of samples (median methylation in progressors 67.8% vs 96.7% in nonprogressors; P = 0.0001, z = 3.85, Wilcoxon rank-sum test) and was associated with the progression to adenocarcinoma. There were no differences in copy number between the 2 groups, but a global trend towards hypomethylation in the progressor group was observed. CONCLUSION: Hypomethylation of OR3A4 has the ability to risk stratify the patient with nondysplastic Barrett esophagus and may form the basis of a future surveillance program.

Abrogated Freud-1/Cc2d1a Repression of 5-HT1A Autoreceptors Induces Fluoxetine-Resistant Anxiety/Depression-Like Behavior.

Freud-1/Cc2d1a represses the gene transcription of serotonin-1A (5-HT1A) autoreceptors, which negatively regulate 5-HT tone. To test the role of Freud-1 in vivo, we generated mice with adulthood conditional knock-out of Freud-1 in 5-HT neurons (cF1ko). In cF1ko mice, 5-HT1A autoreceptor protein, binding and hypothermia response were increased, with reduced 5-HT content and neuronal activity in the dorsal raphe. The cF1ko mice displayed increased anxiety- and depression-like behavior that was resistant to chronic antidepressant (fluoxetine) treatment. Using conditional Freud-1/5-HT1A double knock-out (cF1/1A dko) to disrupt both Freud-1 and 5-HT1A genes in 5-HT neurons, no increase in anxiety- or depression-like behavior was seen upon knock-out of Freud-1 on the 5-HT1A autoreceptor-negative background; rather, a reduction in depression-like behavior emerged. These studies implicate transcriptional dysregulation of 5-HT1A autoreceptors by the repressor Freud-1 in anxiety and depression and provide a clinically relevant genetic model of antidepressant resistance. Targeting specific transcription factors, such as Freud-1, to restore transcriptional balance may augment response to antidepressant treatment.SIGNIFICANCE STATEMENT Altered regulation of the 5-HT1A autoreceptor has been implicated in human anxiety, major depression, suicide, and resistance to antidepressants. This study uniquely identifies a single transcription factor, Freud-1, as crucial for 5-HT1A autoreceptor expression in vivo Disruption of Freud-1 in serotonin neurons in mice links upregulation of 5-HT1A autoreceptors to anxiety/depression-like behavior and provides a new model of antidepressant resistance. Treatment strategies to reestablish transcriptional regulation of 5-HT1A autoreceptors could provide a more robust and sustained antidepressant response.

A questionnaire to identify patellofemoral pain in the community: an exploration of measurement properties.

BACKGROUND: Community-based studies of patellofemoral pain (PFP) need a questionnaire tool that discriminates between those with and those without the condition. To overcome these issues, we have designed a self-report questionnaire which aims to identify people with PFP in the community. STUDY DESIGNS: comparative study and cross-sectional study. STUDY POPULATION: comparative study: PFP patients, soft-tissue injury patients and adults without knee problems. Cross-sectional study: adults attending a science festival. INTERVENTION: comparative study participants completed the questionnaire at baseline and two weeks later. Cross-sectional study participants completed the questionnaire once. The optimal scoring system and threshold was explored using receiver operating characteristic curves, test-retest reliability using Cohen's kappa and measurement error using Bland-Altman plots and standard error of measurement. Known-group validity was explored by comparing PFP prevalence between genders and age groups. RESULTS: Eighty-four participants were recruited to the comparative study. The receiver operating characteristic curves suggested limiting the questionnaire to the clinical features and knee pain map sections (AUC 0.97 95 % CI 0.94 to 1.00). This combination had high sensitivity and specificity (over 90 %). Measurement error was less than the mean difference between the groups. Test-retest reliability estimates suggest good agreement (N = 51, k = 0.74, 95 % CI 0.52-0.91). The cross-sectional study (N = 110) showed expected differences between genders and age groups but these were not statistically significant. CONCLUSION: A shortened version of the questionnaire, based on clinical features and a knee pain map, has good measurement properties. Further work is needed to validate the questionnaire in community samples.

The use of lower resolution viewing devices for mammographic interpretation: implications for education and training.

AIMS: To establish whether lower resolution, lower cost viewing devices have the potential to deliver mammographic interpretation training. METHODS: On three occasions over eight months, fourteen consultant radiologists and reporting radiographers read forty challenging digital mammography screening cases on three different displays: a digital mammography workstation, a standard LCD monitor, and a smartphone. Standard image manipulation software was available for use on all three devices. Receiver operating characteristic (ROC) analysis and ANOVA (Analysis of Variance) were used to determine the significance of differences in performance between the viewing devices with/without the application of image manipulation software. The effect of reader's experience was also assessed. RESULTS: Performance was significantly higher (p < .05) on the mammography workstation compared to the other two viewing devices. When image manipulation software was applied to images viewed on the standard LCD monitor, performance improved to mirror levels seen on the mammography workstation with no significant difference between the two. Image interpretation on the smartphone was uniformly poor. Film reader experience had no significant effect on performance across all three viewing devices. CONCLUSION: Lower resolution standard LCD monitors combined with appropriate image manipulation software are capable of displaying mammographic pathology, and are potentially suitable for delivering mammographic interpretation training. KEY POINTS: • This study investigates potential devices for training in mammography interpretation. • Lower resolution standard LCD monitors are potentially suitable for mammographic interpretation training. • The effect of image manipulation tools on mammography workstation viewing is insignificant. • Reader experience had no significant effect on performance in all viewing devices. • Smart phones are not suitable for displaying mammograms.

How long does it take to read a mammogram? Investigating the reading time of digital breast tomosynthesis and digital mammography.

PURPOSE: To analyse digital breast tomosynthesis (DBT) reading times in the screening setting, compared to 2D full-field digital mammography (FFDM), and investigate the impact of reader experience and professional group on interpretation times. METHOD: Reading time data were recorded in the PROSPECTS Trial, a prospective randomised trial comparing DBT plus FFDM or synthetic 2D mammography (S2D) to FFDM alone, in the National Health Service (NHS) breast screening programme, from January 2019-February 2023. Time to read DBT+FFDM or DBT+S2D and FFDM alone was calculated per case and reading times were compared between modalities using dependent T-tests. Reading times were compared between readers from different professional groups (radiologists and radiographer readers) and experience levels using independent T-tests. The learning curve effect of using DBT in screening on reading time was investigated using a Kruskal-Wallis test. RESULTS: Forty-eight readers interpreted 1,242 FFDM batches (34,210 FFDM cases) and 973 DBT batches (13,983 DBT cases). DBT reading time was doubled compared to FFDM (2.09 ± 0.64 min vs. 0.98 ± 0.30 min; p < 0.001), and DBT+S2D reading was longer than DBT + FFDM (2.24 ± 0.62 min vs. 2.04 ± 0.46 min; p = 0.006). No difference was identified in reading time between radiologists and radiographers (2.06 ± 0.71 min vs. 2.14 ± 0.46 min, respectively; p = 0.71). Readers with five or more years of experience reading DBT were quicker than those with less experience (1.86 ± 0.56 min vs. 2.37 ± 0.65 min; p = 0.008), and DBT reading time decreased after less than 9 months accrued screening experience (p = 0.01). CONCLUSIONS: DBT reading times were double those of FFDM in the screening setting, but there was a short learning curve effect with readers showing significant improvements in reading times within the first nine months of DBT experience. CLINICALTRIALS: gov Identifier: NCT03733106.

Phase 1, placebo-controlled, single ascending dose trial to evaluate the safety, pharmacokinetics and effect on altered states of consciousness of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine benzoate) in healthy participants.

AIMS: To investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of BPL-003, a novel intranasal benzoate salt formulation of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), in healthy participants. METHODS: In all, 44 psychedelic-naïve participants enrolled in the double-blind, placebo-controlled single ascending dose study (1-12 mg BPL-003). Concentrations of 5-MeO-DMT and its pharmacologically active metabolite, bufotenine, were determined in plasma and urine. PD endpoints included subjective drug intensity (SDI) rating, the Mystical Experience Questionnaire (MEQ-30) and the Ego Dissolution Inventory (EDI). RESULTS: BPL-003 was well tolerated at doses up to 12 mg. There were no serious adverse events (AEs), and most AEs were mild; the most common being nasal discomfort, nausea, headache and vomiting. 5-MeO-DMT was rapidly absorbed and eliminated; the median time to peak plasma concentration was approximately 8-10 min and the mean terminal elimination half-life was <27 min. 5-MeO-DMT systemic exposure increased approximately dose-proportionally, while plasma bufotenine concentrations and urinary excretion of 5-MeO-DMT and bufotenine were negligible. The intensity of the SDI ratings was associated with plasma 5-MeO-DMT concentrations. MEQ-30 and EDI scores generally increased with the BPL-003 dose; 60% of participants had a 'complete mystical experience' at 10 and 12 mg doses. Profound and highly emotional consciousness-altering effects were observed with BPL-003, with a rapid onset and short-lasting duration. CONCLUSION: The novel intranasal formulation of BPL-003 was well tolerated with dose-proportional increases in PK and PD effects. The short duration of action and induction of mystical experiences suggest clinical potential, warranting further trials. CLINICAL TRIAL REGISTRATION: NCT05347849.

Outcome of pure mucocele-like lesions diagnosed on breast core biopsy.

AIM: Current guidelines recommend that mucocele-like lesions (MLL) of the breast diagnosed on needle core biopsy (NCB) should be categorized as a lesion of uncertain malignant potential (B3). However, data on the outcome of MLL diagnosed on NCB remains limited due to the rarity of this lesion. The aim of this study was to assess the outcome of pure MLL without atypia diagnosed on NCB using a large series of cases and a review of the literature to provide evidence that can guide management. METHODS AND RESULTS: Patients who underwent diagnostic excision biopsy after a core biopsy diagnosis of MLL without atypia were identified from several centres. Two of 54 patients (4%) with MLL without atypia on core biopsy had ductal carcinoma in situ in the subsequent excision specimen. This is similar to the rate in previous studies of 4% (four of 106). If there is atypia in the core biopsy, previous studies found that the frequency of malignancy is much higher at 21% (seven of 33). CONCLUSIONS: Our results provide evidence that pure MLL without atypia diagnosed on NCB is usually associated with a benign outcome.