Patient Experience of Women With Dense Breasts Undergoing Screening Contrast-Enhanced Mammography.

OBJECTIVE: We investigated patient experience with screening contrast-enhanced mammography (CEM) to determine whether a general population of women with dense breasts would accept CEM in a screening setting. METHODS: In this institutional review board-approved prospective study, patients with heterogeneous and extremely dense breasts on their mammogram were invited to undergo screening CEM and complete pre-CEM and post-CEM surveys. On the pre-CEM survey, patients were asked about their attitudes regarding supplemental screening in general. On the post-CEM survey, patients were asked about their experience undergoing screening CEM, including causes and severity of any discomfort and whether they would consider undergoing screening CEM again in the future or recommend it to a friend. RESULTS: One hundred sixty-three women were surveyed before and after screening CEM. Most patients, 97.5% (159/163), reported minimal or no unpleasantness associated with undergoing screening CEM. In addition, 91.4% (149/163) said they would probably or very likely undergo screening CEM in the future if it cost the same as a traditional screening mammogram, and 95.1% (155/163) said they would probably or very likely recommend screening CEM to a friend. Patients in this study, who were all willing to undergo CEM, more frequently reported a family history of breast cancer than a comparison cohort of women with dense breasts (58.2% vs 47.1%, P = .027). CONCLUSION: Patients from a general population of women with dense breasts reported a positive experience undergoing screening CEM, suggesting screening CEM might be well received by this patient population, particularly if the cost was comparable with traditional screening mammography.

Remote pulmonary rehabilitation for interstitial lung disease: developing the model using experience-based codesign.

BACKGROUND: Remote delivery may improve access to pulmonary rehabilitation (PR). Existing studies are largely limited to individuals with COPD, and the interventions have lacked codesign elements to reflect the needs and experiences of people with chronic respiratory disease, their carers/families and healthcare professionals. The aim of this study was, using experience-based codesign (EBCD), to collaborate with people with interstitial lung disease (ILD), their carers/families and healthcare professionals, to codesign a remote PR programme ready for testing in a future study. METHODS: EBCD comprises interviews, stakeholder workshops and codesign meetings. One-to-one videorecorded interviews with purposively selected people with ILD with experience of PR, their carers/families and healthcare professionals, were edited into a 20 min film. The film was shown at three audiorecorded stakeholder feedback events to identify key themes and touchpoints, and short-list key programme components. The programme was finalised at two further codesign workshops. RESULTS: Ten people with ILD, four carers/families and seven healthcare professionals were interviewed. Participants in the codesign workshops included service-user group: n=14 and healthcare professional group: n=11; joint event: n=21. Final refinements were made with small codesign teams, one comprising three people with ILD and one carer/family member, one with five healthcare professionals. The final codesigned model is a group based, supervised programme delivered by videoconference. Key elements of programme specific to ILD include recommendations to ensure participant safety in the context of desaturation risk, dedicated time for peer support and adaption of the education programme for ILD needs, including signposting to palliative care. CONCLUSION: In this EBCD project, a remote PR programme for people with ILD was codesigned by service-users, their carers/families and multidisciplinary healthcare professionals. Future research should explore the feasibility and acceptability of this intervention.

The Breast-Imaging Operations, Practices and Systems Inventory: A framework to examine mammography facility effects on screening in rural communities.

PURPOSE: Develop and test a measurement framework of mammogram facility resources, policies, and practices in Appalachia. METHODS: Survey items describing 7 domains of imaging facility qualities were developed and tested in the Appalachian regions of Kentucky, Ohio, Pennsylvania, Virginia, and West Virginia. Medicare claims data (2016-2018) were obtained on catchment area mammogram services. Construct validity was examined from associations with facility affiliation, community characteristics, mammogram screening uptake, and market reach. Analyses were performed with t-tests and ANOVA. RESULTS: A total of 192 (of 377) sites completed the survey. Five factors were initially selected in exploratory factor analysis (FA) and refined in confirmatory FA: capacity, outreach & marketing, operational support, radiology review (NNFI = .94, GFI = 0.93), and diagnostic services (NNFI = 1.00, GFI = 0.99). Imaging capacity and diagnostic services were associated with screening uptake, with capacity strongly associated with catchment area demographic and economic characteristics. Imaging facilities in economically affluent versus poorer areas belong to larger health systems and have significantly more resources (P < .001). Facilities in economically distressed locations in Appalachia rely more heavily on outreach activities (P < .001). Higher facility capacity was significantly associated (P < .05) with larger catchment area size (median split: 48.5 vs 51.6), mammogram market share (47.4 vs 52.7), and screening uptake (47.6 vs 52.4). CONCLUSIONS: A set of 18 items assessing breast imaging services and facility characteristics was obtained, representing policies and practices related to a facility's catchment area size, market share, and mammogram screening uptake.

Embracing Remote Academic Radiologists.

Over the past two years at our large academic center, we successfully developed a formal remote academic radiologist division - composed of permanent fully remote radiologists across multiple subspecialties, living geographically distant from our institution. In this article, we share our experience implementing a remote radiologist division, review the benefits and challenges of this approach, discuss expectations of academic remote radiologists as clinicians, educators, and scholars, and provide tips for success.

Spirometry services in England post-pandemic and the potential role of AI support software: a qualitative study of challenges and opportunities.

BACKGROUND: Spirometry services to diagnose and monitor lung disease in primary care were identified as a priority in the NHS Long Term Plan, and are restarting post-COVID-19 pandemic in England; however, evidence regarding best practice is limited. AIM: To explore perspectives on spirometry provision in primary care, and the potential for artificial intelligence (AI) decision support software to aid quality and interpretation. DESIGN AND SETTING: Semi-structured interviews with stakeholders in spirometry services across England. METHOD: Participants were recruited by snowball sampling. Interviews explored the pre- pandemic delivery of spirometry, restarting of services, and perceptions of the role of AI. Transcripts were analysed thematically. RESULTS: In total, 28 participants (mean years' clinical experience = 21.6 [standard deviation 9.4, range 3-40]) were interviewed between April and June 2022. Participants included clinicians (n = 25) and commissioners (n = 3); eight held regional and/or national respiratory network advisory roles. Four themes were identified: 1) historical challenges in provision of spirometry services; 2) inequity in post- pandemic spirometry provision and challenges to restarting spirometry in primary care; 3) future delivery closer to patients' homes by appropriately trained staff; and 4) the potential for AI to have supportive roles in spirometry. CONCLUSION: Stakeholders highlighted historic challenges and the damaging effects of the pandemic contributing to inequity in provision of spirometry, which must be addressed. Overall, stakeholders were positive about the potential of AI to support clinicians in quality assessment and interpretation of spirometry. However, it was evident that validation of the software must be sufficiently robust for clinicians and healthcare commissioners to have trust in the process.

Mood disorder in idiopathic pulmonary fibrosis: response to pulmonary rehabilitation.

Background: Pulmonary rehabilitation improves mood disorder in COPD, but there are limited data in idiopathic pulmonary fibrosis (IPF). The aims of this cohort study were to investigate whether pulmonary rehabilitation reduces mood disorder in IPF, and estimate the minimal important difference (MID) of the Hospital Anxiety and Depression Scale (HADS). Methods: HADS and core pulmonary rehabilitation outcomes were measured in 166 participants before and after an 8-week, in-person, outpatient pulmonary rehabilitation programme. Anchor- and distribution-based methods were used to calculate the MID of HADS-Anxiety (A) and HADS-Depression (D). Results: Suggestive or probable anxiety and depression (HADS ≥8) were present in 35% and 37% of participants, respectively, at baseline, and this reduced significantly following pulmonary rehabilitation (post-pulmonary rehabilitation: HADS-A 23%, HADS-D 26%). Overall, there was a significant reduction in HADS-D (mean change -1.1, 95% CI -1.6- -0.5), but not HADS-A (-0.6, -1.3-0.15) with pulmonary rehabilitation. Subgroup analysis of those with HADS ≥8 revealed significant improvements in HADS domains (mean change: HADS-A -4.5, 95% CI -5.7- -3.4; median change: HADS-D -4.0, interquartile range -6.0- -1.0). The mean (range) MID estimates for HADS-A and HADS-D were -2 (-2.3- -1.7) and -1.2 (-1.9- -0.5), respectively. Conclusion: In people with IPF and suggestive or probable mood disorder, pulmonary rehabilitation reduces anxiety and depression.

Factors associated with perceived personal risk for breast cancer among women with dense breasts.

PURPOSE: To determine what patient factors are associated with a high or an accurate perceived personal risk (PPR) for breast cancer. METHODS: An IRB-approved survey study of women with dense breasts presenting for annual screening mammography was previously conducted from March 2017 to February 2018. Patients were asked to estimate their personal risk for breast cancer and to answer questions about prior breast care-related medical interactions. Survey data were combined post hoc with demographic and clinical data, including breast cancer risk status, and socioeconomic data imputed for each patient from census data. Logistic regression was used to determine which patient factors were associated with a high or accurate PPR. RESULTS: Surveys were completed by 508 women with dense breasts (median age 59.0 years). A high PPR was independently associated with younger age (AOR, 1.71 [95% CI, 1.13, 2.60]), family history of breast cancer (AOR 4.27 [95% CI, 2.81-7.34]), having a clinical "high-risk" designation (AOR, 3.43 [95% CI, 1.13-10.39], and having been called back from screening (AOR, 1.94 [95% CI, 1.14-3.32]). A lower accuracy of PPR was independently associated with a family history of breast cancer (AOR, 0.25 [95% CI, 0.14-0.42]) and having been called back from screening (AOR, 0.58 [95% CI, 0.35-0.98]). CONCLUSION: Women with dense breasts who had a family history of breast cancer or who had been called back from screening had a higher but less accurate PPR. Women with a "high-risk" clinical designation had a higher PPR, even when controlling for family history.

Factors Associated With Breast Cancer Screening Behaviors Among Women With Dense Breasts.

OBJECTIVE: We sought to identify patient factors associated with patient-reported screening behaviors in women with dense breasts. METHODS: An IRB-approved survey study of women with dense breasts presenting for annual screening mammography at an outpatient imaging center was previously conducted from March 2017 to February 2018. The survey included questions regarding mammographic screening frequency and recent participation in supplemental screening. These survey data were combined post hoc with clinical and demographic data and socioeconomic data imputed from census data. Logistic regression was used to identify patient factors associated with reported screening behaviors. RESULTS: Surveys were completed by 508 women (median age, 59.0 years; range, 31.0-86.0 years) with dense breasts. Multivariable analysis demonstrated an independent association of undergoing mammographic screening annually with a history of discussing breast density with a doctor (adjusted odds ratio [AOR], 2.60; P = 0.019). Undergoing supplemental screening in the previous three years was independently associated with younger age (AOR, 1.59; P = 0.004), strong family history of breast cancer (AOR, 3.84; P = 0.027), higher perceived personal risk for breast cancer (AOR, 3.47; P = 0.004), and increased concern about radiation associated with screening examinations (AOR, 3.31; P = 0.006). CONCLUSION: Women with dense breasts who had discussed breast density with a doctor were more likely to report undergoing annual screening mammography, while younger women and women with a strong family history of breast cancer, higher perceived personal risk for breast cancer, or greater concern about radiation were more likely to report recently undergoing supplemental screening.

Radiation doses and fractionation schedules in non-low-risk ductal carcinoma in situ in the breast (BIG 3-07/TROG 07.01): a randomised, factorial, multicentre, open-label, phase 3 study.

BACKGROUND: Whole breast irradiation (WBI) after conservative surgery for ductal carcinoma in situ (DCIS) reduces local recurrence. We investigated whether a tumour bed boost after WBI improved outcomes, and examined radiation dose fractionation sensitivity for non-low-risk DCIS. METHODS: The study was an international, randomised, unmasked, phase 3 trial involving 136 participating centres of six clinical trials organisations in 11 countries (Australia, New Zealand, Singapore, Canada, the Netherlands, Belgium, France, Switzerland, Italy, Ireland, and the UK). Eligible patients were women aged 18 years or older with unilateral, histologically proven, non-low-risk DCIS treated by breast-conserving surgery with at least 1 mm of clear radial resection margins. They were assigned to one of four groups (1:1:1:1) of no tumour bed boost versus boost after conventional versus hypofractionated WBI, or randomly assigned to one of two groups (1:1) of no boost versus boost after each centre prespecified conventional or hypofractionated WBI. The conventional WBI used was 50 Gy in 25 fractions, and hypofractionated WBI was 42·5 Gy in 16 fractions. A boost dose of 16 Gy in eight fractions, if allocated, was delivered after WBI. Patients and clinicians were not masked to treatment allocation. The primary endpoint was time to local recurrence. This trial is registered with ClinicalTrials.gov (NCT00470236). FINDINGS: Between June 25, 2007, and June 30, 2014, 1608 patients were randomly assigned to have no boost (805 patients) or boost (803 patients). Conventional WBI was given to 831 patients, and hypofractionated WBI was given to 777 patients. Median follow-up was 6·6 years. The 5-year free-from-local-recurrence rates were 92·7% (95% CI 90·6-94·4%) in the no-boost group and 97·1% (95·6-98·1%) in the boost group (hazard ratio 0·47; 0·31-0·72; p<0·001). The boost group had higher rates of grade 2 or higher breast pain (10% [8-12%] vs 14% [12-17%], p=0·003) and induration (6% [5-8%] vs 14% [11-16%], p<0·001). INTERPRETATION: In patients with resected non-low-risk DCIS, a tumour bed boost after WBI reduced local recurrence with an increase in grade 2 or greater toxicity. The results provide the first randomised trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control. The international scale of the study supports the generalisability of the results. FUNDING: National Health and Medical Research Council of Australia, Susan G Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, Canadian Cancer Trials Group.

Combinations of scleroderma hallmark autoantibodies associate with distinct clinical phenotypes.

Systemic sclerosis (SSc) is characterized by the presence of SSc-specific or SSc-associated antibodies (SSc-Abs): anti-topoisomerase I (ATA), anti-centromere (ACA), anti-RNA polymerase III (ARA), anti-U3RNP (U3RNP), anti-U1RNP (U1RNP), anti-PmScl (PmScl), anti-Ku (Ku) and anti-Th/To (Th/To), each being associated with specific clinical features and prognosis. The detection of more than one SSc-Abs in SSc patients is rare and only few data about these patients' clinical phenotype is available. The aim of our study was to evaluate the frequency and the disease's features associated with the presence of > 1 SSc-Abs positivity in a large cohort of SSc patients. The autoantibody profiles of 2799 SSc patients from February 2001 to June 2017 were retrospectively reviewed. Patients with > 1 SSc-Abs were identified. Clinical features were collected and compared to a large historical cohort of SSc patients with single SSc-Ab positivity. SSc patients were excluded if previously treated with rituximab, intravenous immunoglobulins or stem cell transplantation. Non-parametric tests were used for statistical analysis. Nearly 5% of SSc patients from our cohort had ≥ 2 autoantibody positivity, and 2.3% (n = 72) had ≥ 2 SSc-Abs positivity. Th e most common combination was U1RNP and ATA (35%). These patients were younger than patients with single autoantibody positivity and showed more commonly a diffuse cutaneous SSc form. They also had higher rates of overlap features compared to ATA patients. Other combinations included U1RNP and ACA (13%), ATA and ACA (7%) and U1RNP and PmScl (5%). In our study we observed that, while infrequently, SSc patients can present with a combination of two SSc-Abs and that the double positivity can influence their clinical phenotype compared to patients with single SSc-Ab positivity. The importance of re-testing SSc-Abs in patients with changing clinical phenotypes was also highlighted, as this may confer a differing risk stratification.

Acute toxicity and patient-reported outcomes in anal canal cancer: results of a pilot study.

INTRODUCTION: Anal canal cancer (ACC) is uncommon. The gold standard of care is chemoradiotherapy treatment. However, this treatment is associated with considerable acute and late side effects. The aim of this pilot study was to evaluate acute toxicity and patient-reported outcomes (PRO) in these patients from planning to 3 months after treatment. METHODS: Sixteen patients were recruited to this prospective observational study from March 2015 to December 2017. All patients received volumetric modulated arc therapy (VMAT) in 30#. Toxicity data were graded by a Radiation Oncologist using the Common Terminology Criteria for Adverse Effects (CTCAE) version 4 at planning, weekly during treatment, 6-week and 3-month post-treatment. PRO data were collected using the EORTC QLQ C30 and CR29 questionnaires completed by patients at planning, mid and end treatment and 3-month post-treatment. RESULTS: The majority of toxicity and PRO items peaked in severity at the end of treatment (week 6). Skin was the only item where >50% of patients had ≥ grade 2 toxicity at any point with 75% having ≥ grade 2 at week 6. Patient-reported embarrassment significantly increased over time (P < 0.001). No meaningful relationships were found between PRO and CTCAE results. CONCLUSION: After reaching their maximum severity at the end of treatment, the majority of toxicity and PRO items approached baseline levels by 3-month post-treatment. The results of this study suggest that PROs are an important complementary tool to CTCAE and provide greater understanding of patients' perception of treatment side effects.

TNFR2 Depletion Reduces Psoriatic Inflammation in Mice by Downregulating Specific Dendritic Cell Populations in Lymph Nodes and Inhibiting IL-23/IL-17 Pathways.

TNF-α, a proinflammatory cytokine, is a crucial mediator of psoriasis pathogenesis. TNF-α functions by activating TNFR1 and TNFR2. Anti-TNF drugs that neutralize TNF-α, thus blocking the activation of TNFR1 and TNFR2, have been proven highly therapeutic in psoriatic diseases. TNF-α also plays an important role in host defense; thus, anti-TNF therapy can cause potentially serious adverse effects, including opportunistic infections and latent tuberculosis reactivation. These adverse effects are attributed to TNFR1 inactivation. Therefore, understanding the relative contributions of TNFR1 and TNFR2 has clinical implications in mitigating psoriasis versus global TNF-α blockade. We found a significant reduction in psoriasis lesions as measured by epidermal hyperplasia, characteristic gross skin lesion, and IL-23 or IL-17A levels in Tnfr2-knockout but not in Tnfr1-knockout mice in the imiquimod psoriasis model. Furthermore, imiquimod-mediated increase in the myeloid dendritic cells, TNF/inducible nitric oxide synthase‒producing dendritic cells, and IL-23 expression in the draining lymph nodes were dependent on TNFR2 but not on TNFR1. Together, our results support that psoriatic inflammation is not dependent on TNFR1 activity but is driven by a TNFR2-dependent IL-23/IL-17 pathway activation. Thus, targeting the TNFR2 pathway may emerge as a potential next-generation therapeutic approach for psoriatic diseases.

Comparison of whole breast dosimetry techniques - From 3DCRT to VMAT and the impact on heart and surrounding tissues.

INTRODUCTION: Various techniques for whole breast radiation therapy (WBRT) have been reported to increase dose to contralateral tissues. Heart dose is of critical importance as there is no apparent dose threshold below which there is no risk. The aim of this study was to compare planning techniques for WBRT that achieves the best target dosimetry and lowest organ at risk (OAR) dose. METHODS: Thirty early-stage whole breast patient datasets, 15 each left- and right-sided cases, were retrospectively selected. Five techniques were generated for each data set: three-dimensional conformal radiation therapy (3DCRT), hybrid intensity modulated radiation therapy (HYI), hybrid volumetric modulated arc therapy (VMAT) - (HYV), reduced arc VMAT - bowtie (BT), and BT flattening filter free (FFF) - (BTFFF). Plan goals and OARs were evaluated and compared between techniques. RESULTS: BT had the highest median conformity index (CI) values (0.82, IQR: 0.80-0.85 left and 0.83, IQR 0.80-0.86 right). BT recorded lower mean heart doses (median value 1.19Gy, IQR: 0.90-1.55), and BTFFF recorded lower heart V2.5 Gy , V5 Gy ; median 3.96% (IQR: 2.90-6.80) and 0.90% (IQR: 0.50-1.50) respectively for left-sided patients. There was a statistically significant difference in all ipsilateral lung measures, (p < 0.001) with BTFFF producing significantly lower doses across all measures: mean, V5 Gy , V10 Gy and V20 Gy . CONCLUSION: Overall BT and BTFFF techniques produced lower OAR doses and equivalent PTV coverage for WBRT. BT and BTFFF techniques increased contralateral lung and breast doses; however, these were within prescribed tolerances and comparable to results published in the literature.