Impact of Neoadjuvant Chemoimmunotherapy on Surgical Outcomes and Time to Radiation in Triple-Negative Breast Cancer.

BACKGROUND: We examined the association between immunotherapy-containing and standard chemotherapy regimens with treatment delays and postoperative complications in stage II-III triple-negative breast cancer. The effect of immune-related adverse events (irAEs) was compared. PATIENTS AND METHODS: We compared 139 women treated with neoadjuvant pembrolizumab plus chemotherapy (KEYNOTE-522 regimen) from August 2021 to September 2022 with 287 consecutive patients who received neoadjuvant chemotherapy alone prior to July 2021 and underwent surgery. Baseline characteristics, time to treatments, and surgical complications were compared using two-sample non-parametric tests. Linear regression evaluated association of irAEs with time to surgery and radiation. Logistic regression identified factors associated with surgical complications. RESULTS: Age, body mass index, race, American Society of Anesthesiologists (ASA) class, and mastectomy rates were similar among cohorts. No clinically relevant difference in time from end of neoadjuvant treatment to surgery was observed [KEYNOTE-522: median 32 (IQR 27, 43) days; non-KEYNOTE-522: median 31 (IQR 26, 37) days; P = 0.048]. Time to radiation did not differ (P = 0.7). A total of 26 patients (9%; non-KEYNOTE-522) versus 11 (8%; KEYNOTE-522) experienced postoperative complications (P = 0.6). In the KEYNOTE-522 cohort, 59 (43%) of 137 patients experienced 82 irAEs; 40 (68%) required treatment. Older age (P = 0.018) and ASA class 4 (P = 0.007) were associated with delays to surgery after adjusting for clinical factors. Experiencing ≥ 1 irAE was associated with delay to radiation (P = 0.029). IrAEs were not associated with surgical complications (P = 0.4). CONCLUSIONS: We observed no clinically meaningful difference between times to surgery/adjuvant radiation or postoperative complications and type of preoperative chemotherapy. IrAEs were associated with delay to adjuvant radiation but not with postoperative complications or delay to surgery.

Impact of Mastectomy Flap Necrosis on Patient-Reported Quality-of-Life Measures After Nipple-Sparing Mastectomy: A Preliminary Analysis.

BACKGROUND: Mastectomy skin flap necrosis (SFN) is common following nipple-sparing mastectomy (NSM), but studies on its quality-of-life (QOL) impact are limited. We examined patient-reported QOL and satisfaction after NSM with/without SFN utilizing the BREAST-Q patient-reported outcome measure (PROM) survey. PATIENTS AND METHODS: Patients undergoing NSM between April 2018 and July 2021 at our institution were examined; the BREAST-Q PROM was administered preoperatively, and at 6 months and 1 year postoperatively. SFN extent/severity was documented at 2-3 weeks postoperatively; QOL and satisfaction domains were compared between patients with/without SFN. RESULTS: A total of 573 NSMs in 333 patients were included, and 135 breasts in 82 patients developed SFN (24% superficial, 56% partial thickness, 16% full thickness). Patients with SFN reported significantly lower scores in the satisfaction with breasts (p = 0.032) and psychosocial QOL domains (p = 0.009) at 6 months versus those without SFN, with scores returning to baseline at 1 year in both domains. In the "physical well-being-of-the-chest" domain, there was an overall decline in scores among all patients; however, there were no significant differences at any time point between patients with or without SFN. Sexual well-being scores declined for patients with SFN compared with those without at 6 months and also at 1 year, but this did not reach significance (p = 0.13, p = 0.2, respectively). CONCLUSIONS: Patients undergoing NSM who developed SFN reported significantly lower satisfaction and psychosocial well-being scores at 6 months, which returned to baseline by 1 year. Physical well-being of the chest significantly declines after NSM regardless of SFN. Future studies with larger sample sizes and longer follow-up are needed to determine SFN's impact on long-term QOL.

Use of the Child Opportunity Index to Examine Racial Variations in Outpatient Antibiotic Prescribing to Children.

To examine further racial and ethnic variations in antibiotic prescribing to children, we used the Child Opportunity Index. Black children were less likely to be prescribed an antibiotic. Low- and moderate-opportunity areas were associated with greater rates of antibiotic prescribing, after adjusting for race and other factors.

Impact of menopausal symptoms on work and careers: a cross-sectional study.

BACKGROUND: Women over 50 years are one of the fastest-growing employment groups. Menopausal symptoms can adversely impact quality of life, work performance and attendance; however, few studies look at the impact of individual menopausal symptoms on work and career development. AIMS: To measure the prevalence of menopausal symptoms in employees in a healthcare setting, to assess the impact of individual symptoms on work, attendance and career development and to explore perceptions about workplace supports. METHODS: In this cross-sectional study of Irish hospital workers, menopausal employees were asked about the frequency of 10 menopausal symptoms and the extent to which each symptom impacted them at work. Impacts on performance, attendance and career development were assessed, along with the benefits of workplace support. RESULTS: Responses from 407 women showed that the most common menopausal symptoms affecting employees greater than 50% of the time while at work were fatigue (54%), difficulty sleeping (47%), poor concentration (44%) and poor memory (40%). Work performance was impacted for 65% of respondents and 18% had taken sick leave. There was a significant association between symptom severity at work and reduced work performance, career development decisions and attendance. Manager awareness about menopause (29%) and flexible working times (29%) were selected as the most important workplace supports. CONCLUSIONS: Female employees are negatively impacted by menopausal symptoms while at work, particularly by psychological and neurocognitive symptoms which were associated with reduced work performance, attendance and career decisions. Manager awareness and flexible schedules were considered the most beneficial workplace supports.

Investigating Effects of Mentoring for Youth with Assault Injuries: Results of a Randomized-Controlled Trial.

Mentoring is considered an evidence-based practice for violence prevention. This study presents a partial replication of the Take Charge! program implemented in partnership with Big Brothers Big Sisters of America (BBBS). One hundred and eighty-eight early adolescents (M age = 12.87; 61.17% male) who were treated for peer-related assault injury in two urban mid-Atlantic emergency departments were randomly assigned to receive a mentor from two BBBS affiliates. Mentors and organization staff were trained in the Take Charge! violence prevention curriculum, which had previously shown evidence of efficacy. Intent-to-treat analyses showed statistically significant improvements in conflict avoidance self-efficacy for the intervention group at 9 months and reductions in fighting at 21 months, but an increase in parental report of aggression at 9 months. Complier average causal effect models revealed evidence of an additional effect for reduced problem behavior at 21 months for intervention adolescents who received a mentor. No effects were found for youth-reported aggression, retaliatory attitudes, deviance acceptance, or commitment to learning. Sensitivity analyses suggested increased aggressive behavior for adolescents in the intervention group who did not receive a mentor (i.e., non-compliers). These findings extend the evidence-base for Take Charge! as a violence prevention curriculum for youth already engaged in violence to "real-world" implementation settings. However, they also suggest that challenges associated with providing youth with mentors can be consequential and that additional supports may be needed for these youth/parents. Clinical trials number: clinicaltrials.gov NCT01770873.

A clinical perspective on adipose-derived cell therapy for enhancing microvascular health and function: Implications and applications for reconstructive surgery.

Restoration of form and function requires apposition of tissues in the form of flaps to reconstitute local perfusion. Successful reconstruction relies on flap survival and its integration with the recipient bed. The flap's precariously perfused hypoxic areas undergo adaptive microvascular changes both internally and in connection with the recipient bed. A cell-mediated, coordinated response to hypoxia drives these adaptive processes, restoring a tissue's normoxic homeostasis via de novo vasculogenesis, sprouting angiogenesis, and stabilizing arterialization. As cells exert prolonged and coordinated effects on site, their use as biological agents merit translational consideration of sourcing angio-competent cells and delivering them to territories enduring microcirculatory acclimatization. Angio-competent cells abound in adipose tissue: a reliable, accessible, and expendable source of adipose-derived cells (ADC). When subject to enzymatic digestion and centrifugation, adipose tissue separates its various ADC: A subset of buoyant oil-dense adipocytes (the tissue's parenchymal component) accumulates on a supra-natant layer, whereas the mesenchymal component remains in the infra-natant sediment, containing the tissue's stromal vascular fraction (SVF), where angio-component cells abound. The SVF can be further manipulated, selected, or culture expanded into more specific stromal subsets (herein defined as adipose stromal cells, ASC). While promising clinical applications for ADC await clinical proof and regulatory authorization, basic science investigation is needed to elucidate the specific ADC mechanisms that influence microvascular growth, remodeling, and function following flap surgery. The objective of this article is to share the clinical perspectives of reconstructive plastic surgeons regarding the use of ADC-based therapies to help with flap tissue integration, revascularization, and wound healing. Specifically, the focus will be on considering the potential for ADC as therapeutic agents and how their clinical application motivates basic science opportunities.

High-level psychotropic polypharmacy: a retrospective comparison of children in foster care to their peers on Medicaid.

BACKGROUND: The use of antipsychotic medication and psychotropic polypharmacy has increased in the United States over the last two decades especially for children from low-income families and those in foster care. Although attention has been paid to providing greater insight, prescribing patterns remain concerning since there is a lack of evidence related to safety and efficacy. High-level psychotropic polypharmacy has not been described. We aim to compare the use of HLPP for children receiving Medicaid services and those in foster care and identify factors associated with the duration of use of high-level psychotropic polypharmacy. Additionally, we will examine the frequency of laboratory metabolic screening and emergency department, inpatient, and outpatient visits. METHODS: A cross-sectional, secondary analysis of statewide data describes trends in high-level psychotropic polypharmacy from 2012 to 2017 and the prevalence and predictors of high-level psychotropic polypharmacy duration and resource use in 2017 for all children on Medicaid and those in foster care. High-level psychotropic polypharmacy included concurrent use, at least four classes of medications including an antipsychotic, and at least 30 days duration. RESULTS: High-level psychotropic polypharmacy increased from 2012 to 2014 for both groups but stabilized in 2015-2016. Children in foster care showed a slight increase compared to their peers in 2017. There was no association between duration and demographic characteristics or foster care status. Diagnoses predicted duration. Neither group received metabolic monitoring at an acceptable rate. CONCLUSIONS: Concerning patterns of high-level psychotropic polypharmacy and metabolic monitoring were identified. Cautious use of high-level psychotropic polypharmacy and greater oversight to ensure that these children are receiving comprehensive services like behavioral health, primary care, and primary prevention.

Breast Reconstruction and Nipple-Sparing Mastectomy: Technical Modifications and Their Outcomes Over Time at an Academic Breast Center.

BACKGROUND: Superior aesthetic outcomes can be achieved with mastectomy techniques that maximize breast envelope preservation and maintain the nipple-areolar complex. This is the impetus for the popularization of the nipple-sparing mastectomy (NSM). Nipple-sparing mastectomy is a challenging procedure due to potential ischemia of the mastectomy flap (which includes the nipple-areolar complex) and the risk of incomplete oncologic resection. We review our experience with NSM, identify technique modifications used over time, and evaluate reconstructive outcomes of NSM and its modifications. METHODS: A retrospective review of consecutive patients with NSM and breast reconstruction over an 8-year period was completed. RESULTS: Fifty-five patients underwent 95 NSMs. Indications included invasive and in situ cancer, atypical ductal hyperplasia, and risk reduction. In the first 4 years of experience, the most frequently used NSM incision was radial (lateral) whereas use of a variety of incision patterns was noted in the second 4 years. Overall NSM and breast reconstruction complication rate for the entire study period was 50.9% and included a full-thickness mastectomy skin flap necrosis/nipple necrosis rate of 8.4%. In situ cancer of the nipple was identified in 3.2% of the patients, and 1 patient had locoregional recurrence. Overall complication rate was lower in the second 4 years of experience with NSM and reconstruction. One third of the patients underwent intraoperative fluorescent angiography (FA) to assess mastectomy skin perfusion before reconstruction start. Of the patients who had FA due to perfusion concerns, more than 70% of studies demonstrated poor perfusion and 83.3% of these patients had reconstruction delayed based on these results. Immediate, implant-based reconstruction was performed most commonly. An average of 2.66 procedures were required to achieve reconstruction completion, and 92.4% of the patients who sought reconstruction achieved completion. CONCLUSIONS: At our institution, NSM use is increasing, NSM incision pattern types used are expanding, and complication rates are decreasing. Immediate, implant-based reconstruction is most commonly used in combination with NSM at our institution. Fluorescent angiography is used to assess mastectomy skin perfusion and likely limits mastectomy complication effects on reconstruction. Despite the occurrence of complications, most patients will complete the breast reconstruction process.

Longitudinal Trends in the Diagnosis of Attention-Deficit/Hyperactivity Disorder and Stimulant Use in Preschool Children on Medicaid.

OBJECTIVES: To describe trends in the diagnosis of attention-deficit/hyperactivity disorder (ADHD) and prescribing of stimulants in preschool-age children receiving Medicaid and to identify factors associated with the receipt of psychosocial care. STUDY DESIGN: Data were extracted from 2012-2016 Kentucky Medicaid claims for children aged <6 years. ADHD was identified using International Classification of Diseases, Tenth Revision codes F90.0, F90.1, F90.2, F90.8, and F90.9. Psychosocial therapy was defined as having at least 1 relevant Current Procedural Terminology code in a claim within the year. A generalized linear model with a logit link and binomial distribution was used to assess factors associated with receipt of psychosocial treatment in 2016. RESULTS: More than 2500 (1.24%) preschool-aged children receiving Medicaid had a diagnosis of ADHD in 2016, with 988 (38.2%) of those receiving a stimulant medication. Children in foster care were diagnosed with and/or treated for ADHD 4 times more often than other Medicaid recipients. Of the 1091 preschoolers receiving stimulants, 99 (9%) did not have a diagnosis of ADHD. There were no significant differences in diagnoses by race/ethnicity, but children reported to be black, Hispanic, or other race/ethnicity received stimulants at a lower rate than white children. Positive predictors for receiving psychosocial therapy in 2016 included having the diagnosis but not receiving a stimulant, having at least 1 prescription written by a psychiatrist, having comorbidities, and age. The use of stimulants in children aged <6 years declined from 0.9% in 2012 to 0.5% in 2016. CONCLUSIONS: Promising trends demonstrate a decreasing use of stimulants in preschoolers; however, continued vigilance is needed to promote the optimal use of psychosocial interventions.

Keys to academic success for under-represented minority young investigators: recommendations from the Research in Academic Pediatrics Initiative on Diversity (RAPID) National Advisory Committee.

BACKGROUND: Although Latinos, African-Americans, and American Indians/Alaska Natives comprise 34% of Americans, these under-represented minorities (URMs) account for only 7% of US medical-school faculty. Even when URMs become faculty, they face many substantial challenges to success. Little has been published, however, on keys to academic success for URM young faculty investigators. METHODS: The Research in Academic Pediatrics Initiative on Diversity (RAPID) goal is to enhance the professional advancement of URM junior faculty pursuing research careers in general academic pediatrics. One important RAPID component is the annual mentoring/career-development conference, which targets URM residents, fellows, and junior faculty, and has included 62 URM participants since its 2013 inception. A conference highlight is the panel discussion on keys to academic success for URM young investigators, conducted by the RAPID National Advisory Committee, a diverse group of leading senior researchers. The article aim was to provide a guide to academic success for URM young investigators using the 2018 RAPID Conference panel discussion. A modified Delphi technique was used to provide a systematic approach to obtaining answers to six key questions using an expert panel: the single most important key to success for URM young investigators; ensuring optimal mentorship; how to respond when patients/families say, "I don't want you to see my child because you are ____"; best strategies for maximizing funding success; how to balance serving on time-consuming committees with enough time to advance research/career objectives; and the single thing you wish someone had told you which would have substantially enhanced your success early on. RESULTS/CONCLUSIONS: This is the first published practical guide on keys to academic success for URM young investigators. Identified keys to success included having multiple mentors, writing prolifically, being tenaciously persistent, having mentors who are invested in you, dealing with families who do not want you to care for their child because of your race/ethnicity by seeking to understand the reasons and debriefing with colleagues, seeking non-traditional funding streams, balancing committee work with having enough time to advance one's research and career by using these opportunities to generate scholarly products, and asking for all needed resources when negotiating for new jobs.

Engaging the Transgender Community to Improve Medical Education and Prioritize Healthcare Initiatives.

Phenomenon: Transgender patients experience discrimination, limited access to care, and inadequate provider knowledge in healthcare settings. Medical education to address transgender-specific disparities is lacking. Research that engages transgender community members may help address health disparities by empowering patients, increasing trust, and informing medical curricula to increase competence. APPROACH: A 2015 Community Forum on Transgender Health Care was hosted at the University of Louisville School of Medicine, which included healthcare professionals and transgender community members to facilitate dialogue among mixed-participant groups using a World Café model. Fifty-nine participants discussed the status of transgender healthcare and made recommendations for local improvements. A follow-up survey was administered to 100 individuals, including forum participants and their referrals. The forum discussion and survey responses were analyzed to determine common perceptions of transgender healthcare, priorities for improvement interventions, and themes to inform curriculum. FINDINGS: The community forum discussion showed that local transgender care is overwhelmingly underdeveloped and unresponsive to the needs of the transgender community. The follow-up survey revealed that priorities to improve transgender care included a multidisciplinary clinic for lesbian, gay, bisexual, and transgender (LGBT) patients, an LGBT-friendly network of physicians, and more training for providers and support staff. This mutually constructive engagement experience influenced reform in undergraduate curricula and continuing education opportunities. Insights: Community engagement in healthcare disparities research can cultivate improbable discussions, yield innovative insight from marginalized populations, and build relationships with community members for future collaborations and interventions. Societal acceptance of transgender identities, which could be promoted through healthcare providers, could stimulate significant progress in transgender healthcare. Supplemental educational interventions for practicing physicians will improve the current conditions of transgender healthcare, but a comprehensive medical school curriculum specifically for transgender health that includes interactions between the transgender community and medical students could be particularly impactful.

Changes in medical student implicit attitudes following a health equity curricular intervention.

PURPOSE: This study assessed the: (1) effect of an LGBTQI + health equity curriculum (eQuality) on implicit attitudes among first (M1) and second year (M2) medical students and (2) utility of dedicated time to explore implicit bias. METHOD: Implicit biases were assessed at baseline using implicit association tests (IAT) for all M2s and a random sample of first years (M1A). These students were then debriefed on strategies to mitigate bias. Following eQuality, all M1 and M2s completed post-intervention IATs. The remaining first years (M1B) were then debriefed. Paired sample t-tests assessed differences between pre/post. Independent sample t-tests assessed differences in post-IATs between M1 groups. RESULTS: IATs indicated preferences for "Straight," "White," and "Thin" at both pre and post. M2s demonstrated statistically significant improvements pre to post for sexuality (p = 0.01) and race (p = 0.03). There were significant differences in post-intervention IAT scores between M1As who received the IAT and debriefing prior to eQuality and M1Bs for sexuality (p = 0.002) and race (p = 0.046). There were no significant changes for weight. CONCLUSION: eQuality reduced implicit preference for "Straight" and "White." Differences in M1 post-intervention IAT scores between groups suggest dedicating time to debrief implicit attitudes enhances bias mitigation.

The transfer of diatoms from freshwater to footwear materials: An experimental study assessing transfer, persistence, and extraction methods for forensic reconstruction.

In recent years there has been growing interest in environmental forms of trace evidence, and ecological trace evidence collected from footwear has proved valuable within casework. Simultaneously, there has been growing awareness of the need for empirical experimentation to underpin forensic inferences. Diatoms are unicellular algae, and each cell (or 'frustule') consists of two valves which are made of silica, a robust material that favours their preservation both in sediments and within forensic scenarios. A series of experiments were carried out to investigate the transfer and persistence of diatoms upon common footwear materials, a recipient surface that has historically been overlooked by studies of persistence. The effectiveness of two novel extraction techniques (jet rinsing, and heating and agitation with distilled water) was compared to the established extraction technique of hydrogen peroxide digestion, for a suite of five common footwear materials: canvas, leather, and 'suede' (representing upper materials), and rubber and polyurethane (representing sole materials). It was observed that the novel extraction technique of heating and agitation with distilled water did not extract fewer diatom valves, or cause increased fragmentation of valves, when compared to peroxide digestion, suggesting that the method may be viable where potentially hazardous chemical reactions may be encountered with the peroxide digestion method. Valves could be extracted from all five footwear materials after 3min of immersion, and more valves were extracted from the rougher, woven upper materials than the smoother sole materials. Canvas yielded the most valves (a mean of 2511/cm2) and polyurethane the fewest (a mean of 15/cm2). The persistence of diatoms on the three upper materials was addressed with a preliminary pilot investigation, with ten intervals sampled between 0 and 168h. Valves were seen to persist in detectable quantities after 168h on all three upper materials. However, some samples produced slides with no valves, and the earliest time after which no diatom valves were found was 4h after the transfer. Analysis of the particle size distributions over time, by image analysis, suggests that the retention of diatoms may be size-selective; after 168h, no particles larger than 200µm2 could be found on the samples of canvas, and >95% of the particles on the samples of suede were less than or equal to 200µm2. A pilot investigation into the effects of immersion interval was carried out upon samples of canvas. Greater numbers of valves were extracted from the samples with longer immersion intervals, but even after 30s, >500 valves could be recovered per cm2, suggesting that footwear may be sampled for diatoms even if the contact with a water body may have been brief. These findings indicate that, if the variability within and between experimental runs can be addressed, there is significant potential for diatoms to be incorporated into the trace analysis of footwear and assist forensic reconstructions.

Indigenous cancer patient and staff attitudes towards unmet needs screening using the SCNAT-IP.

INTRODUCTION: Indigenous Australians have a higher cancer incidence, worse mortality and are less likely to receive optimal cancer treatment compared with non-Indigenous Australians. Culturally appropriate supportive care helps ensure that Indigenous patients engage in and receive optimal care. However, many existing supportive care needs tools lack cultural relevance for Indigenous people, and their feasibility with Indigenous people has not been demonstrated. The Supportive Care Needs Assessment Tool for Indigenous People (SCNAT-IP) assesses the unmet supportive care needs of Indigenous cancer patients. PURPOSE: This descriptive study evaluates the clinical implementation of the SCNAT-IP in routine care. METHODS: Two large tertiary cancer treatment centres and two regional oncology clinics participated. Participants included 10 clinical staff and 36 adult Indigenous cancer patients (mean age 54 years). Patients and clinicians completed brief, purpose-designed questionnaires and interviews. RESULTS: Patients reported high ratings (means >8/10) for acceptability, helpfulness and timing items. The majority (≥80%) of staff agreed that the SCNAT-IP was useful to clinical practice, should be used in routine care and was acceptable to their patients. CONCLUSIONS: The study provides empirical support for the feasibility and acceptability of the SCNAT-IP in routine cancer care with Indigenous Australians. Routine screening with the SCNAT-IP has the potential to improve cancer care for Indigenous people with cancer.

The Role of Stigma in Parental Help-Seeking for Perceived Child Behavior Problems in Urban, Low-Income African American Parents.

Significant numbers of children have diagnosable mental health problems, but only a small proportion of them receive appropriate services. Stigma has been associated with help-seeking for adult mental health problems and for Caucasian parents. The current study aims to understand factors, including stigma, associated with African American parents' help-seeking behavior related to perceived child behavior problems. Participants were a community sample of African American parents and/or legal guardians of children ages 3-8 years recruited from an urban primary care setting (N = 101). Variables included child behavior, stigma (self, friends/family, and public), object of stigma (parent or child), obstacles for engagement, intention to attend parenting classes, and demographics. Self-stigma was the strongest predictor of help-seeking among African American parents. The impact of self-stigma on parents' ratings of the likelihood of attending parenting classes increased when parents considered a situation in which their child's behavior was concerning to them. Findings support the need to consider parent stigma in the design of care models to ensure that children receive needed preventative and treatment services for behavioral/mental health problems in African American families.