Increased Risk for Ipsilateral Breast Tumor Recurrence in Invasive Lobular Carcinoma after Accelerated Partial Breast Irradiation Brachytherapy.

BACKGROUND: The suitability criteria for accelerated partial breast irradiation (APBI) from the American Brachytherapy Society (ABS), American Society for Radiation Oncology (ASTRO), and The Groupe Européende Curiethérapie European SocieTy for Radiotherapy & Oncology (GEC-ESTRO) have significant differences. MATERIALS AND METHODS: This is a single institution retrospective review of 946 consecutive patients with invasive breast cancer who underwent lumpectomy and APBI intracavitary brachytherapy from 2003 to 2018. Overall survival (OS), breast cancer-specific survival (BCSS), relapse-free survival (RFS), and ipsilateral breast tumor recurrence (IBTR) were estimated with Kaplan-Meier method. RESULTS: Median follow-up time was 60.2 months. Median age was 68 years (46-94 years). The majority of patients had estrogen receptor (ER)-positive disease (94%). There were 821 (87%) cases of invasive ductal carcinoma and 68 cases (7%) of invasive lobular carcinoma (ILC). The 5-year OS, BCSS, RFS, and IBTR were 93%, 99%, 90%, and 1.5%, respectively. Upon univariate analysis, ILC (hazard ratio [HR], 4.6; p = .008) and lack of nodal evaluation (HR, 6.9; p = .01) were risk factors for IBTR. The 10-year IBTR was 2.5% for IDC and 14% for ILC. While the ABS and ASTRO criteria could not predict IBTR, the GEC-ESTRO intermediate risk group was associated with inferior IBTR (p = .04) when compared to both low risk and high risk groups. None of the suitability criteria was able to predict RFS. CONCLUSION: These results show that APBI is an effective treatment for patients with invasive breast cancer. Expansion of the current eligibility criteria should be considered, although prospective validation is needed. Caution is required when considering APBI for patients with ILC. IMPLICATIONS FOR PRACTICE: In a large retrospective review of 946 patients with early breast cancer treated with partial mastectomy and accelerated partial breast irradiation (APBI) intracavitary brachytherapy, this study demonstrates durable local control. Patients deemed unsuitable or high risk by the American Brachytherapy Society, American Society for Radiation Oncology, and European Society for Radiotherapy and Oncology guidelines were not at increased risk for ipsilateral breast tumor recurrence (IBTR), suggesting that expansion of the current criteria should be considered. Importantly, however, these results demonstrate that caution should be taken when considering APBI for patients with invasive lobular carcinoma, as these patients had relatively high risk for IBTR (10-year IBTR, 14%).

Teacher Outcomes from the Second Step Child Protection Unit: Moderating Roles of Prior Preparedness, and Treatment Acceptability.

Teachers play a critical role in child sexual abuse (CSA) prevention and intervention efforts. We examined the impact of the Second Step Child Protection Unit (CPU) on improving teacher awareness, attitudes, and teacher-student relations for 161 teachers. Teacher baseline scores and treatment acceptability were examined as moderators. Structural equation modeling (SEM) revealed a significant effect of the CPU on teachers' awareness, attitudes, and teacher-student relations, particularly for teachers with lower prior knowledge, attitudes, and student relationships. Teachers' acceptability of the CPU also moderated outcomes, where a higher level of acceptability of CSA interventions was associated with an increase in outcomes.

Recent declines in cancer incidence: related to the Great Recession?

PURPOSE: In recent years, cancer case counts in the U.S. underwent a large, rapid decline-an unexpected change given population growth for older persons at highest cancer risk. As these declines coincided with the Great Recession, we examined whether they were related to economic conditions. METHODS: Using California Cancer Registry data from California's 30 most populous counties, we analyzed trends in cancer incidence during pre-recession (1996-2007) and recession/recovery (2008-2012) periods for all cancers combined and the ten most common sites. We evaluated the recession's association with rates using a multifactorial index that measured recession impact, and modeled associations between case counts and county-level unemployment rates using Poisson regression. RESULTS: Yearly cancer incidence rate declines were greater during the recession/recovery (3.3% among males, 1.4% among females) than before (0.7 and 0.5%, respectively), particularly for prostate, lung, and colorectal cancers. Lower case counts, especially for prostate and liver cancer among males and breast cancer, melanoma, and ovarian cancer among females, were associated with higher unemployment rates, irrespective of time period, but independent of secular effects. The associations for melanoma translated up to a 3.6% decrease in cases with each 1% increase in unemployment. Incidence declines were not greater in counties with higher recession impact index. CONCLUSIONS: Although recent declines in incidence of certain cancers are not differentially impacted by economic conditions related to the Great Recession relative to pre-recession conditions, the large recent absolute declines in the case counts of some cancer may be attributable to the large declines in unemployment in the recessionary period. This may occur through decreased engagement in preventive health behaviors, particularly for clinically less urgent cancers. Continued monitoring of trends is important to detect any rises in incidence rates as deferred diagnoses come to clinical attention.

Service providers' perceptions of and responses to bullying of individuals with disabilities.

A sample of 124 service providers (e.g. mental health professionals, educators, administrators) completed a survey about bullying of individuals with disabilities and the use and perceived effectiveness of resources and strategies to address bullying. Providing support and performing an action in response to bullying were reported to be used more often and were perceived as more effective than education and minimizing/ignoring. Service providers who reported that the individuals they worked with experienced cyberbullying more frequently were more likely to take action and use education. Those who attributed victimization to social differences were more likely to provide support.

A Prospective, Single Arm, Multi-site, Clinical Evaluation of a Nonradioactive Surgical Guidance Technology for the Location of Nonpalpable Breast Lesions during Excision.

OBJECTIVES: This study was a multicenter evaluation of the SAVI SCOUT(®) breast localization and surgical guidance system using micro-impulse radar technology for the removal of nonpalpable breast lesions. The study was designed to validate the results of a recent 50-patient pilot study in a larger multi-institution trial. The primary endpoints were the rates of successful reflector placement, localization, and removal. METHODS: This multicenter, prospective trial enrolled patients scheduled to have excisional biopsy or breast-conserving surgery of a nonpalpable breast lesion. From March to November 2015, 154 patients were consented and evaluated by 20 radiologists and 16 surgeons at 11 participating centers. Patients had SCOUT(®) reflectors placed up to 7 days before surgery, and placement was confirmed by mammography or ultrasonography. Implanted reflectors were detected by the SCOUT(®) handpiece and console. Presence of the reflector in the excised surgical specimen was confirmed radiographically, and specimens were sent for routine pathology. RESULTS: SCOUT(®) reflectors were successfully placed in 153 of 154 patients. In one case, the reflector was placed at a distance from the target that required a wire to be placed. All 154 lesions and reflectors were successfully removed during surgery. For 101 patients with a preoperative diagnosis of cancer, 86 (85.1 %) had clear margins, and 17 (16.8 %) patients required margin reexcision. CONCLUSIONS: SCOUT(®) provides a reliable and effective alternative method for the localization and surgical excision of nonpalpable breast lesions using no wires or radioactive materials, with excellent patient, radiologist, and surgeon acceptance.

Gene expression patterns in CD4+ peripheral blood cells in healthy subjects and stage IV melanoma patients.

Melanoma patients exhibit changes in immune responsiveness in the local tumor environment, draining lymph nodes, and peripheral blood. Immune-targeting therapies are revolutionizing melanoma patient care increasingly, and studies show that patients derive clinical benefit from these newer agents. Nonetheless, predicting which patients will benefit from these costly therapies remains a challenge. In an effort to capture individual differences in immune responsiveness, we are analyzing patterns of gene expression in human peripheral blood cells using RNAseq. Focusing on CD4+ peripheral blood cells, we describe multiple categories of immune regulating genes, which are expressed in highly ordered patterns shared by cohorts of healthy subjects and stage IV melanoma patients. Despite displaying conservation in overall transcriptome structure, CD4+ peripheral blood cells from melanoma patients differ quantitatively from healthy subjects in the expression of more than 2000 genes. Moreover, 1300 differentially expressed genes are found in transcript response patterns following activation of CD4+ cells ex vivo, suggesting that widespread functional discrepancies differentiate the immune systems of healthy subjects and melanoma patients. While our analysis reveals that the transcriptome architecture characteristic of healthy subjects is maintained in cancer patients, the genes expressed differentially among individuals and across cohorts provide opportunities for understanding variable immune states as well as response potentials, thus establishing a foundation for predicting individual responses to stimuli such as immunotherapeutic agents.

NIH Toolbox Cognition Battery (CB): validation of executive function measures in adults.

This study describes psychometric properties of the NIH Toolbox Cognition Battery (NIHTB-CB) executive function measures in an adult sample. The NIHTB-CB was designed for use in epidemiologic studies and clinical trials for ages 3 to 85. A total of 268 self-described healthy adults were recruited at four university-based sites, using stratified sampling guidelines to target demographic variability for age (20-85 years), gender, education and ethnicity. The NIHTB-CB contains two computer-based instruments assessing executive function: the Dimensional Change Card Sort (a measure of cognitive flexibility) and a flanker task (a measure of inhibitory control and selective attention). Participants completed the NIHTB-CB, corresponding gold standard convergent and discriminant measures, and sociodemographic questionnaires. A subset of participants (N=89) was retested 7 to 21 days later. Results reveal excellent sensitivity to age-related changes during adulthood, excellent test-retest reliability, and adequate to good convergent and discriminant validity. The NIH Toolbox EF measures can be used effectively in epidemiologic and clinical studies.

The cognition battery of the NIH toolbox for assessment of neurological and behavioral function: validation in an adult sample.

This study introduces a special series on validity studies of the Cognition Battery (CB) from the U.S. National Institutes of Health Toolbox for the Assessment of Neurological and Behavioral Function (NIHTB) (Gershon, Wagster et al., 2013) in an adult sample. This first study in the series describes the sample, each of the seven instruments in the NIHTB-CB briefly, and the general approach to data analysis. Data are provided on test-retest reliability and practice effects, and raw scores (mean, standard deviation, range) are presented for each instrument and the gold standard instruments used to measure construct validity. Accompanying papers provide details on each instrument, including information about instrument development, psychometric properties, age and education effects on performance, and convergent and discriminant construct validity. One study in the series is devoted to a factor analysis of the NIHTB-CB in adults and another describes the psychometric properties of three composite scores derived from the individual measures representing fluid and crystallized abilities and their combination. The NIHTB-CB is designed to provide a brief, comprehensive, common set of measures to allow comparisons among disparate studies and to improve scientific communication.

The epitope integration site for vaccine antigens determines virus control while maintaining efficacy in an engineered cancer vaccine.

Picornaviruses have been developed as potential therapies for gene delivery and vaccination. One drawback to their use is the potential for recombination and viral persistence. Therefore, the engineering strategies used must take into account the possibility for virus escape. We have developed Theiler's murine encephalomyelitis virus (TMEV) as a potential vaccine vector for use in immunotherapy. This study shows that insertion of a vaccine epitope at a unique site within the TMEV leader protein can dramatically increase the type I interferon (IFN) response to infection and promote rapid viral clearance. This live virus vaccine maintains its ability to drive antigen-specific CD8(+) T-cell responses to a model antigen as well as to the weakly immunogenic tumor antigen Her2/neu. Furthermore, the epitope integration site does not affect the efficacy of this vaccine as cancer immunotherapy for treating models of melanoma and breast cancer as demonstrated by delayed tumor outgrowth and increased survival in animals implanted with these tumors. These findings show that an attenuated virus retaining limited ability to replicate nonetheless can effectively mobilize CD8(+) cellular immunity and will be important for the design of picornavirus vectors used as immunotherapy in clinical settings.

Infective Endocarditis Complicated With a Large Left Coronary Cusp Aneurysm: A Condition With Undefined Natural History and Treatment.

The natural history and treatment of an aortic cusp aneurysm with or without rupture because of native aortic valve infective endocarditis (NAV-IE) have not been well defined. This may explain why current guidelines for the management of valvular heart disease do not include this complication as an indication for surgical aortic valve replacement or repair or transcatheter aortic valve replacement (TAVR). We describe herein the first case of a man aged 76 years with multiple co-morbidities with a NAV-IE associated large left coronary cusp aneurysm with subsequent rupture and consequent severe aortic regurgitation and heart failure for which he underwent an off-label successful TAVR. This patient's scenario suggests that a cusp aneurysm because of NAV-IE poses a high risk for subsequent rupture, severe aortic regurgitation, and heart failure. In conclusion, TAVR may be a reasonable alternative to high-risk surgical aortic valve replacement in patients with NAV-IE associated cusp aneurysms with or without but impending rupture.

Prescriber Acceptability of a Direct-to-Patient Intervention for Benzodiazepine Receptor Agonist Deprescribing and Behavioural Management of Insomnia in Older Adults.

Behavioural treatments are recommended first-line for insomnia, but long-term benzodiazepine receptor agonist (BZRA) use remains common and engaging patients in a deprescribing consultation is challenging. Few deprescribing interventions directly target patients. Prescribers' support of patient-targeted interventions may facilitate their uptake. Recently assessed in the Your Answers When Needing Sleep in New Brunswick (YAWNS NB) study, Sleepwell (mysleepwell.ca) was developed as a direct-to-patient behaviour change intervention promoting BZRA deprescribing and non-pharmacological insomnia management. BZRA prescribers of YAWNS NB participants were invited to complete an online survey assessing the acceptability of Sleepwell as a direct-to-patient intervention. The survey was developed using the seven construct components of the theoretical framework of acceptability (TFA) framework. Respondents (40/250, 17.2%) indicated high acceptability, with positive responses per TFA construct averaging 32.3/40 (80.7%). Perceived as an ethical, credible, and useful tool, Sleepwell also promoted prescriber-patient BZRA deprescribing engagements (11/19, 58%). Prescribers were accepting of Sleepwell and supported its application as a direct-to-patient intervention.

II. NIH Toolbox Cognition Battery (CB): measuring executive function and attention.

In this chapter, we discuss two measures designed to assess executive function (EF) as part of the NIH Toolbox Cognition Battery (CB) and report pediatric data from the validation study. EF refers to the goal-directed cognitive control of thought, action, and emotion. Two measures were adapted for standardized computer administration: the Dimensional Change Card Sort (a measure of cognitive flexibility) and a flanker task (a measure of inhibitory control in the context of selective visual attention). Results reveal excellent developmental sensitivity across childhood, excellent reliability, and (in most cases) excellent convergent validity. Correlations between the new NIH Toolbox measures and age were higher for younger children (3-6 years) than for older children (8-15 years), and evidence of increasing differentiation of EF from other aspects of cognition (indexed by receptive vocabulary) was obtained.

IV. NIH Toolbox Cognition Battery (CB): measuring language (vocabulary comprehension and reading decoding).

Mastery of language skills is an important predictor of daily functioning and health. Vocabulary comprehension and reading decoding are relatively quick and easy to measure and correlate highly with overall cognitive functioning, as well as with success in school and work. New measures of vocabulary comprehension and reading decoding (in both English and Spanish) were developed for the NIH Toolbox Cognition Battery (CB). In the Toolbox Picture Vocabulary Test (TPVT), participants hear a spoken word while viewing four pictures, and then must choose the picture that best represents the word. This approach tests receptive vocabulary knowledge without the need to read or write, removing the literacy load for children who are developing literacy and for adults who struggle with reading and writing. In the Toolbox Oral Reading Recognition Test (TORRT), participants see a letter or word onscreen and must pronounce or identify it. The examiner determines whether it was pronounced correctly by comparing the response to the pronunciation guide on a separate computer screen. In this chapter, we discuss the importance of language during childhood and the relation of language and brain function. We also review the development of the TPVT and TORRT, including information about the item calibration process and results from a validation study. Finally, the strengths and weaknesses of the measures are discussed.

I. NIH Toolbox Cognition Battery (CB): introduction and pediatric data.

This monograph presents the pediatric portion of the National Institutes of Health (NIH) Toolbox Cognition Battery (CB) of the NIH Toolbox for the Assessment of Neurological and Behavioral Function. The NIH Toolbox is an initiative of the Neuroscience Blueprint, a collaborative framework through which 16 NIH Institutes, Centers, and Offices jointly support neuroscience-related research, to accelerate discoveries and reduce the burden of nervous system disorders. The CB is one of four modules that measure cognitive, emotional, sensory, and motor health across the lifespan. The CB is unique in its continuity across childhood, adolescence, early adulthood, and old age, and in order to help create a common currency among disparate studies, it is also available at low cost to researchers for use in large-scale longitudinal and epidemiologic studies. This chapter describes the evolution of the CB; methods for selecting cognitive subdomains and instruments; the rationale for test design; and a validation study in children and adolescents, ages 3-15 years. Subsequent chapters feature detailed discussions of each test measure and its psychometric properties (Chapters 2-6), the factor structure of the test battery (Chapter 7), the effects of age and education on composite test scores (Chapter 8), and a final summary and discussion (Chapter 9). As the chapters in this monograph demonstrate, the CB has excellent psychometric properties, and the validation study provided evidence for the increasing differentiation of cognitive abilities with age.

A qualitative analysis of participant experiences with universal school-based depression screening.

Screening in High Schools to Identify, Evaluate and Lower Depression (SHIELD) was a randomized clinical trial of school-based universal depression screening conducted with public high schools in Pennsylvania, United States. Screened adolescents were twice as likely to initiate depression treatment compared to peers who were not screened. The purpose of this qualitative study was to understand the experience of communities participating in universal screening via SHIELD. Semi-structured interviews were conducted with school staff (n = 11), parents (n = 4) and adolescents (n = 7) from April-October 2021. A codebook was developed with 20 % of audio transcripts coded for inter-rater reliability (staff k = 0.88, parents k = 0.90, adolescent k = 0.74). The two coders divided and individually coded remaining transcripts for thematic content analysis. Three themes were identified: 1) Depression screening was well-received; 2) The main challenge with screening was inadequate staffing to manage referrals; and 3) School staff suggested alternate formats and methods for future screening. In summary, school-based depression screening was well-received, but schools experienced challenges with staffing and resources to support identified adolescents and offered alternative suggestions for future screening. Schools interested in depression screening need education and capacity building focused on barriers and challenges with the process. Learning from staff who have realized this evidence-based practice in their respective districts will support next steps towards implementation.

Examining Implicit Biases of Pre-Service Educators Within a Professional Development Context.

The opportunity gap, or conditions and barriers that impede the academic performance and school experience of minoritized students, may be exacerbated by educators' implicit biases. The aim of this qualitative study was to understand preservice educators' awareness of individual, structural, and systemic racism with regard to implicit bias. Our sample included 154 preservice educators, enrolled in an anti-bullying/harassment/discrimination training, which is required for any New York State (NYS) educator certification. Educators responded to questions about group generalizations, factors contributing to these biases, and how biases may affect their behavior toward students. Our content analysis revealed several themes, most notably that frequent biases existed toward Asian/Asian Americans, Black/African Americans, males, and people from socioeconomically disadvantaged backgrounds. Although participant responses reflect an open-minded approach to discussing bias, many responses reflected no observable desire to change potentially biased interactions with students. Responses with racially held biases aligned with the tenets of critical race theory (CRT), particularly racism as permanent and racism as normalized. Implications for practice, with an emphasis on anti-bias training and professional development, are discussed.

Effectiveness and cost analysis of methods used to recruit older adult sedative users to a deprescribing randomized controlled trial during the COVID-19 pandemic.

Background: Recruitment to clinical trials is a challenge for researchers that became more pronounced because of COVID-19 public health protective measures, especially with respect to studies enrolling older adults. We completed an effectiveness and cost analysis of the recruitment methods used in The Your Answers When Needing Sleep in New Brunswick (YAWNS NB) study, a randomized controlled trial of a deprescribing intervention that recruited older adults with chronic use of sedatives during the pandemic. Methods: Study recruitment began during the COVID-19 pandemic. Strategies included random digit dialing (RDD), a targeted mail campaign and advertising through newspapers, online platforms (Google and Facebook), and television. Other awareness raising and recruitment strategies involved seniors' organizations, pharmacies, television news stories, and referrals. Recruitment effectiveness and cost analysis involved enrollment rate (ER), cost per randomized participant (CPRP), fractional cost (FC), fractional enrollment (FE), fractional enrollment-cost ratio (FEC), and efficacy index (EI) calculations. Results: There were 1295 interested older adults with 594 randomized into the study for an enrollment rate of 46%. The efficacy index (EI) was highest for Facebook ads (EI = 0.683) followed by television (EI = 0.426), and newsprint ads (EI = 0.298). The cost of RDD was highest per randomized participant at $1117.90 and produced the lowest EI (0.013). Conclusion: Facebook ads had the best efficacy index for recruiting older adults to the YAWNS NB study during the COVID-19 pandemic and television ads produced the most enrollments. RDD was expensive and yielded few recruits. Recruitment costs can be significant for recruiting community-dwelling older adults. This experience can inform recruitment strategy and budget development for future community studies enrolling older adults, especially in the context of the COVID-19 pandemic.