Subcutaneous vs Intravenous Trastuzumab/Pertuzumab: A Time and Motion Substudy of a Phase II Trial of Adjuvant Trastuzumab/Pertuzumab for Stage I HER2+ Breast Cancer (ADEPT trial).

PURPOSE: The time required for in-clinic drug administration can substantially affect breast cancer patients' quality of life. Subcutaneous (SC) drug administration, as opposed to intravenous (IV), may reduce this time commitment. This study sought to estimate the difference in time burden between IV and SC administration of trastuzumab and pertuzumab (HP). METHODS: We prospectively enrolled a subcohort of patients participating in the ADEPT trial (ClinicalTrials.gov identifier: NCT04569747, investigating adjuvant HP plus endocrine therapy for stage I human epidermal growth factor receptor 2-positive breast cancer) to this single-arm crossover time and motion substudy. Patients received two cycles of IV HP followed by two cycles of SC HP. During each cycle, time points in drug preparation and administration were captured. The primary end point was total patient time in the treatment chair. Additional end points included total patient treatment experience time and total pharmacy workflow time. A sample size of 22 patients was estimated to provide 90.7% power with two-sided alpha .05 to detect a difference of 70 minutes in the primary end point by treatment arm (IV v SC). RESULTS: Twenty-two patients were enrolled. The mean total patient time in the treatment chair was 61.8 minutes shorter with SC versus IV HP (22.5 v 84.3 minutes; P < .0001). The mean total patient treatment experience time (incorporating time spent waiting for treatment initiation and time spent in the treatment chair) was 81.8 minutes shorter for SC administration (96 v 177.8 minutes; P < .0001). The pharmacy workflow time was 78.2 minutes shorter for SC versus IV formulation (41 v 119.2 minutes; P < .0001). CONCLUSION: SC administration of HP shortened patient time burden by approximately 1 hour. SC drug administration can facilitate faster workflows for health care professionals and improve patients' breast cancer treatment experience.

"I didn't come here for your judgement" alongside "they understand you and encourage you": Exploring the narratives of young black and mixed-race LGBTQ+ people who have a physical health condition and their experiences within physical health services.

Lesbian, gay, bisexual, transgender, and queer or questioning (LGBTQ+) individuals experience health inequalities. Young people living with a health condition are also more likely to experience adverse mental health outcomes. Developing positive identity can help to mitigate the impact of this. Young black LGBTQ+ people have additional barriers to developing positive identity. Current research rarely considers the intersection of these identities for young people despite the discrimination they may face, and the impact this may have on their health. A narrative approach allows these voices to be heard in research. Eight participants were interviewed using a narrative approach. Interviews were analysed using content and thematic narrative analysis. Global summaries of each interview were developed and 'plot lines' emerged from these. A central plot related to identity development, with two plots embedded in these exploring experiences of illness and of healthcare. Participants had positive experiences of healthcare despite encountering stigma. Access to positive role models and being able link in with various communities allowed participants to integrate and accept their identities. A key discussion point in this study is the ways in which healthcare staff could become role models for young LGBTQ+ people and help them to integrate and accept their identities.

Young LGBTQ+ people can experience discrimination which can impact on their health, including preexisting health conditions. Having a positive identity can help young people to be more resilient in the face of these difficulties. Current research has rarely given young black and mixed-race LGBTQ+ people with a physical health condition an opportunity to share their stories and explore their identity. Eight young people were interviewed using a narrative approach, which allowed them an opportunity to tell their whole life story. Shared plot lines emerged from the young people's life stories about identity development, experience of illness, and experiences of healthcare. The young people had all had positive experiences of healthcare staff as well as some negative experiences of discrimination. It was important to the young people to have positive role models who supported their identity and access to supportive communities. This study suggests that healthcare staff could be suited to become positive role models for the young people they care for.

"I make myself get busy": Resilience and social connection among low-income older adults living in subsidized housing.

BACKGROUND: Social isolation and loneliness are pervasive issues among older adults in the United States, carrying significant health risks. Low-income older adults are particularly vulnerable to these challenges compared with their higher-income counterparts due to their limited access to resources and social networks. Many low-income older adults live in subsidized housing, which has the potential to offer unique support tailored to their needs. The intersection of aging and the unique social circumstances faced by low-income older adults significantly influences how they navigate crises. METHODS: We conducted semi-structured interviews with 24 older adults aged 63-86 residing in subsidized housing communities in the United States. The data were collected from August 2021 to November 2022 and subsequently analyzed using a thematic constant comparison analysis approach. RESULTS: Many participants felt connected to their housing community. Participants reported that their lives changed substantially due to the pandemic: communal activities ceased leading to isolation and feelings of loneliness. Amid this challenge, participants were resourceful and found creative ways to manage. Many emphasized the crucial role of technology in maintaining emotional support despite physical separation. CONCLUSIONS: Participants in subsidized housing shared their experiences before and during this unique crisis highlighting the challenges they face, as well as their resilience and adaptability when facing challenges. Our findings underscore the significance of community activation, demonstrating that activities motivated older adults to improve their well-being. Additionally, the role of technology in maintaining connections proved to be crucial.

The survival benefit of adjuvant trastuzumab with or without chemotherapy in the management of small (T1mic, T1a, T1b, T1c), node negative HER2+ breast cancer.

There is limited data regarding the added benefit of adjuvant systemic therapy in the management of small, node-negative, HER2+ breast cancer. In a multi-institutional retrospective analysis using the American Society of Clinical Oncology CancerLinQ database, we compared survival outcomes among T1a-c N0 HER2+ patients diagnosed between 2010 to 2021 who received locoregional therapy alone or in combination with adjuvant trastuzumab (+/- chemotherapy). Primary outcomes were invasive disease-free survival (iDFS) and overall survival (OS). Of the 1,184 patients, 436 received locoregional therapy alone. We found a statistically significant improvement in iDFS (HR 0.73, P = 0.003) and OS (HR 0.63, P = 0.023) on univariate analysis with adjuvant trastuzumab with or without chemotherapy which remained statistically significant on multivariate analysis. Three-arm univariate analysis found that iDFS was significantly improved with trastuzumab monotherapy (P = 0.003) and combination therapy (P = 0.027) compared to observation. Subgroup data suggests that T1b/c tumors derive the greatest benefit.

Real-world treatment patterns of adjuvant endocrine therapy and ovarian suppression in premenopausal HR+/HER2+ breast cancer.

BACKGROUND: The optimal adjuvant endocrine therapy (ET) in hormone receptor positive (HR+) and human epidermal growth factor receptor 2 positive (HER2+) premenopausal breast cancer (BC) remains unclear. Moreover, the benefit and clinical indications of ovarian suppression (OS) is poorly elucidated. We described real-world patterns surrounding choice of ET and clinicopathologic features which predicted treatment with OS in a contemporary cohort of premenopausal women with HR+/HER2+ BC. METHODS: This retrospective analysis included premenopausal patients with nonmetastatic HR+/HER2+ BC from the CancerLinQ Discovery database from January 2010 to May 2020. Women were less than 50 years and received chemotherapy, anti-HER2 therapy, and ET. They were categorized into 1 of 4 groups based on type of ET prescribed at initiation: aromatase inhibitor (AI) + OS, OS, tamoxifen + OS, or tamoxifen. Multivariable logistic regression assessed associations between clinicopathologic features and OS use. RESULTS: Out of 360,540 patients with BC, 937 were included. The majority (n = 818, 87%) were prescribed tamoxifen, whereas 4 (0.4%), 50 (5.3%), and 65 (6.9%) received OS, tamoxifen + OS and AI + OS, respectively. No clinicopathologic features predicted OS use apart from age; patients <35 years were more likely to receive OS compared with those ≥35 years (odds ratio 2.33, p < 0.001). CONCLUSIONS: This is the first real-world study evaluating ET treatment patterns in HR+/HER2+ premenopausal BC. OS use was uncommon and the majority received tamoxifen as the preferred ET regardless of most clinicopathologic risk factors. Additional research is needed to optimize ET decisions in young women with this distinct BC subtype.

Auditory feedback decreases timing variability for discontinuous and continuous motor tasks in autistic adults.

Introduction: Autistic individuals demonstrate greater variability and timing error in their motor performance than neurotypical individuals, likely due at least in part to atypical cerebellar characteristics and connectivity. These motor difficulties may differentially affect discrete as opposed to continuous movements in autistic individuals. Augmented auditory feedback has the potential to aid motor timing and variability due to intact auditory-motor pathways in autism and high sensitivity in autistic individuals to auditory stimuli. Methods: This experiment investigated whether there were differences in timing accuracy and variability in autistic adults as a function of task (discontinuous vs. continuous movements) and condition (augmented auditory feedback vs. no auditory feedback) in a synchronization-continuation paradigm. Ten autistic young adults aged 17-27 years of age completed the within-subjects study that involved drawing circles at 800 milliseconds intervals on a touch screen. In the discontinuous task, participants traced a series of discrete circles and paused at the top of each circle for at least 60 milliseconds. In the continuous task, participants traced the circles without pausing. Participants traced circles in either a non-auditory condition, or an auditory condition in which they heard a tone each time that they completed a circle drawing. Results: Participants had significantly better timing accuracy on the continuous timing task as opposed to the discontinuous task. Timing consistency was significantly higher for tasks performed with auditory feedback. Discussion: This research reveals that motor difficulties in autistic individuals affect discrete timing tasks more than continuous tasks, and provides evidence that augmented auditory feedback may be able to mitigate some of the timing variability present in autistic persons' movements. These results provide support for future investigation on the use of music-based therapies involving auditory feedback to address motor dysfunction in autistic individuals.

Improved motor skills in autistic children after three weeks of neurologic music therapy via telehealth: a pilot study.

Background: Many autistic children experience motor skill deficits which can impact other areas of functioning, and research on therapeutic interventions for motor skills in autism is in a preliminary stage. Music-based therapies have been used extensively to address motor skills in non-autistic populations. Though a handful of studies exist on the effects of music-based therapies for movement in autistic children, none have investigated the possibility of administering sessions via telehealth. This mixed-methods pilot study investigated whether nine Neurologic Music Therapy (NMT)® sessions via telehealth would improve motor and attention skills in autistic children. Methods: Five autistic children between five and 10 years of age participated in the study, with support from their caregivers. Motor skills were assessed using the Bruininks-Oseretsky Test of Motor Proficiency second edition, short form (BOT-2 SF), and a selective attention and sustained attention task were taken from the Test of Everyday Attention for Children, Second Edition (TEA-Ch2). Caregivers and the two neurologic music therapists involved in the study provided qualitative input about the perceived effectiveness of telehealth NMT for the children involved. Their responses were analyzed using qualitative content analysis. Caregivers also filled out a Sensory Profile 2 assessment prior to the onset of sessions so that each child's sensory profile could be compared to their motor and attention results. Results: Statistically significant improvements in motor skills were observed between pre-test assessment and a two-week follow-up assessment. Results from attention test scores were not significant. Caregivers and neurologic music therapists generally perceived sessions positively and noted the importance of having caregivers actively involved. When compared with individual progress on the BOT-2 SF assessment, sensory profile results revealed that children with fewer sensory sensitivities tended to improve the most on motor skills. The improvements in motor skills and positive caregiver and therapist views of telehealth indicate that NMT motor interventions administered via telehealth are a promising avenue of therapeutic support for movement skill development in autistic children.

Occupational hazards and pregnancy in orthopaedics: female surgeons are at increased risk of infertility and pregnancy complications.

Female surgeons have increased rates of infertility and pregnancy complications compared to the general population. Reported infertility rates in surgeons are 32% compared to 10.9% in the general population. Reported pregnancy complication rates in surgeons range from 25% to 35%. In the orthopaedic operating theatre occupational hazards that have an effect on pregnancy outcomes include radiation, exposure to methyl methacrylate in bone cement, surgical smoke, sharps injuries, exposure to anaesthetic waste gases and the effects of the physical demands of surgery including prolonged work hours and night shift work. Outside the operating theatre exposure to nitrous oxide, formaldehyde, surgical scrub also have evidence of negative pregnancy outcomes. This review summarizes the available evidence as it relates to specific occupational hazards that face health workers in an orthopaedic operating theatre. This information, while targeted at orthopaedic health workers, is also relevant to anaesthetists, radiographers, nursing staff, medical device company representatives and female surgeons in other specialties.

Pregnancy Outcomes After Laparoscopic Radiofrequency Ablation of Uterine Leiomyomas Compared With Myomectomy.

OBJECTIVE: To compare pregnancy outcomes after laparoscopic radiofrequency ablation and myomectomy. METHODS: The ULTRA (Uterine Leiomyoma Treatment With Radiofrequency Ablation) study is an ongoing multicenter prospective cohort study with longitudinal follow-up up to 5 years comparing outcomes of radiofrequency ablation with myomectomy in premenopausal women older than age 21 years with symptomatic uterine leiomyomas. Participants were queried every 6 months after surgery to assess the incidence of pregnancy and pregnancy outcomes. RESULTS: Among 539 women enrolled in ULTRA, a total of 37 participants (mean age at first pregnancy 35.0±4.7 years) conceived 43 times as of March 2023 (22 radiofrequency ablation, 21 myomectomy). The average length of follow-up time after all procedures was 2.5±1.0 years. The baseline miscarriage rate in the study population was 33.3%. In participants who underwent radiofrequency ablation, 9 of 22 pregnancies (40.9%, 95% CI, 20.3-61.5%) ended in first-trimester miscarriage, 11 resulted in live births (50.0%, 95% CI, 29.1-70.9%), one resulted fetal death at 30 weeks of gestation, and one resulted in uterine rupture during miscarriage treatment with misoprostol 10 weeks after radiofrequency ablation. Among the live births in the radiofrequency ablation group, 45.5% were by vaginal delivery. In the myomectomy group, 9 of 21 pregnancies (42.9%, 95% CI, 21.7-64.0%) ended in first-trimester miscarriage and 12 resulted in live births (57.1%, 95% CI, 36.0-78.3%). There were no significant differences in the likelihood of live birth or miscarriage between the study groups. CONCLUSION: Full-term pregnancy and vaginal delivery are achievable after radiofrequency ablation of leiomyomas. However, in this interim analysis, the miscarriage rate in both radiofrequency ablation and myomectomy groups was higher than expected for women in this age group. Long-term data collection in the ongoing ULTRA study aims to further understand pregnancy outcomes after radiofrequency ablation compared with myomectomy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT0210094.

Factors Influencing Music Therapists' Retention of Clinical Hours with Autistic Clients over Telehealth During the COVID-19 Pandemic.

The 2019 coronavirus disease pandemic influenced music therapists to migrate services to online platforms, though some lost clinical hours during the pandemic when telehealth was not a viable option. This survey study aimed to ascertain factors that helped music-based therapists to continue serving autistic clients over telehealth during the pandemic. We surveyed 193 accredited music therapists located mainly in Canada and the US. In addition to gathering data on general perceptions of telehealth music therapy and Neurologic Music Therapy (NMT), one-way ANOVAs were applied to determine differences in percent-change loss of clinical hours for music therapists: (1) working in different employment settings; (2) serving children, youth, adults, or a mixture of ages; and (3) practicing NMT or not. The general perception of telehealth music therapy was positive, and NMTs believed that the clear protocols and transformation design model were helpful to them in adapting services to telehealth. There were no significant differences in percent-change of clinical hours among music therapists in different employment settings or serving different client age groups. Music therapists who said they practiced within the NMT treatment model lost a significantly lower percentage of clinical hours with autistic clients than those who did not practice NMT. Possible reasons for this result and the need for further research are discussed.

Outcomes of proximal humerus fractures in children: a retrospective cohort study.

OBJECTIVE: Paediatric proximal humerus fractures (PHFs) have historically been treated non-operatively. However, the management of severely displaced PHFs in older children has been debated over the years, with contemporary studies advocating for surgery. The purpose of this study was to review the outcomes of a cohort of paediatric patients treated for a PHF to guide management of future paediatric PHFs. METHODS: The records of the Women's and Children's Hospital in South Australia were reviewed to identify paediatric PHFs occurring between 1 January 2010 and 1 June 2020. Participants completed the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH), the Shoulder Pain and Disability Index, and the Paediatric Outcomes Data Collection Instrument via phone interview. Participants' shoulder range-of-motion was assessed via telehealth using Zoom. Multivariable logistic regression was used to identify patient and clinical variables that were associated with a poorer outcome. RESULTS: Of 307 patients contacted, 125 participated. Forty-six patients met the definition of a poorer clinical outcome, defined as a QuickDASH score of ≥2. Fractures of greater severity were predictive of a poorer outcome, and patients aged ≥12 years old at the time of injury had higher total QuickDASH scores. The findings did not suggest that these subgroups of patients have superior outcomes if treated surgically. CONCLUSION: The majority of paediatric PHFs have an acceptable clinical outcome, irrespective of treatment methodology. Multicentre prospective studies are required to establish the indications for surgery for adolescent patients with severely displaced PHFs.

Phase Ib study of HSP90 inhibitor, onalespib (AT13387), in combination with paclitaxel in patients with advanced triple-negative breast cancer.

Background: Heat shock protein 90 (HSP90) is a molecular chaperone required for stabilization of client proteins over-activated in triple-negative breast cancer (TNBC). Over-expression of HSP90 client proteins has been implicated in paclitaxel resistance. Onalespib (AT13387) is a potent inhibitor of HSP90 that could improve paclitaxel efficacy when administered in combination. Design: This phase Ib trial administered onalespib with paclitaxel in patients with advanced TNBC to assess safety and establish a recommended phase II dose (RP2D). Objectives: The primary objectives were determining the dose-limiting toxicities and maximum tolerated dose of combination therapy. Secondary objectives included pharmacokinetic (PK) analysis and determination of overall response rate (ORR), duration of response (DOR), and progression-free survival (PFS). Methods: Patients with advanced TNBC were treated with standard dose intravenous paclitaxel in combination with intravenous onalespib at doses ranging from 120 to 260 mg/m2 administered on days 1, 8, and 15 of a 28-day cycle using a standard 3 + 3 design. A total of 15 patients were enrolled to dose expansion cohort at RP2D to confirm safety profile. Results: Thirty-one patients were enrolled in the study, of which over 90% had received prior taxane therapy. Paclitaxel was given for metastatic disease in 23% of patients. Adverse events (AEs) included anemia (grade 3: 20%), lymphopenia (grade 3: 17%), and neutropenia (grade 3: 33%, grade 4: 4%). The most frequent grade ⩾3 non-hematologic AE was diarrhea (7%). The established RP2D was 260 mg/m2 onalespib when given with paclitaxel at 80 mg/m2. PK analysis revealed a modest drug interaction profile for onalespib in the combination regimen. ORR was 20%. Three patients achieved complete responses, all of whom had received prior taxane therapy. Median DOR was 5.6 months; median PFS was 2.9 months. Conclusion: Combination treatment with onalespib and paclitaxel had an acceptable toxicity profile and RP2D was determined to be 260 mg/m2 of onalespib. Combination therapy showed antitumor activity in patients with advanced TNBC. Trial registration: Onalespib and paclitaxel in treating patients with advanced TNBC https://clinicaltrials.gov/ct2/show/NCT02474173.

Phase 1b study of HSP90 inhibitor called onalespib in combination with paclitaxel in patients with advanced triple-negative breast cancer This Phase 1b study demonstrated that treatment with a combination of onalespib and paclitaxel was reasonably well tolerated by most patients. Onalespib at 260 mg/m² given intravenously on days 1, 8 and 15 on 28-day cycles in combination with standard dose and schedule of paclitaxel was established as the recommended phase 2 dose for further clinical development. Despite minor drug-drug interactions between these 2 agents, onalespib did not alter paclitaxel exposure and paclitaxel did not affect exposure to onalespib. While onalespib with paclitaxel combination therapy did not yield durable objective responses or prolonged progression-free survival, there were several patients with long-lasting benefit from this combination including patients who previously experienced progression on taxane therapy.

Stereotactic Radiosurgery for Women Older than 65 with Breast Cancer Brain Metastases.

BACKGROUND: Breast cancer is the second most common cause of brain metastases (BM). Despite increasing incidence of BM in older women, there are limited data on the optimal management of BM in this age group. In this study, we assessed the survival outcomes and treatment patterns of older breast cancer patients ≥65 years old with BM compared to younger patients at our institution. METHODS: An IRB-approved single-institutional retrospective review of biopsy-proven breast cancer patients with BM treated with 1- to 5-fraction stereotactic radiation therapy (SRS) from 2015 to 2020 was performed. Primary endpoint was intracranial progression-free survival (PFS) defined as the time interval between the end of SRS to the date of the first CNS progression. Secondary endpoints were overall survival (OS) from the end of SRS and radiation treatment patterns. Kaplan-Meier estimates and Cox proportional hazard regression method were used for survival analyses. RESULTS: A total of 112 metastatic breast cancer patients with BMs were included of which 24 were ≥65 years old and 88 were <65 years old. Median age at RT was 72 years (range 65-84) compared to 52 years (31-64) in younger patients. There were significantly higher number of older women with ER/PR positive disease (75% vs. 49%, p = 0.036), while younger patients were more frequently triple negative (32% vs. 12%, p = 0.074) and HER2 positive (42% vs. 29%, p = 0.3). Treatment-related adverse events were similar in both groups. Overall, 14.3% patients had any grade radiation necrosis (RN) (older vs. young: 8.3% vs. 16%, p = 0.5) while 5.4% had grade 3 or higher RN (0% vs. 6.8%, p = 0.7). Median OS after RT was poorer in older patients compared to younger patients (9.5 months vs. 14.5 months, p = 0.037), while intracranial PFS from RT was similar between the two groups (9.7 months vs. 7.1 months, p = 0.580). On univariate analysis, significant predictors of OS were age ≥65 years old (hazard risk, HR = 1.70, p = 0.048), KPS ≤ 80 (HR = 2.24, p < 0.001), HER2 positive disease (HR = 0.46, p < 0.001), isolated CNS metastatic disease (HR = 0.29, p < 0.001), number of brain metastases treated with RT (HR = 1.06, p = 0.028), and fractionated SRS (HR = 0.53, p = 0.013). On multivariable analysis, KPS ≤ 80, HER2 negativity and higher number of brain metastases predicted for poorer survival, while age was not a significant factor for OS after adjusting for other variables. Patients who received systemic therapy after SRS had a significantly improved OS on univariate and multivariable analysis (HR = 0.32, p < 0.001). Number of brain metastases treated was the only factor predictive of worse PFS (HR = 1.06, p = 0.041), which implies a 6% additive risk of progression for every additional metastasis treated. CONCLUSIONS: Although older women had poorer OS than younger women, OS was similar after adjusting for KPS, extracranial progression, and systemic therapy; and there was no difference in rates of intracranial PFS, neurological deaths, and LMD in the different age groups. This study suggests that age alone may not play an independent role in treatment-selection and that outcomes for breast cancer patients with BMs and personalized decision-making including other clinical factors should be considered. Future studies are warranted to assess neurocognitive outcomes and other radiation treatment toxicities in older patients.