Treatment of HER2-positive (HER2+) hormonereceptor positive (HR+) metastatic breast cancer (mBC) with the novel combination of zanidatamab, palbociclib, and fulvestrant

Background: HER2+ mBC remains incurable, with a need for new HER2-directed therapies and regimens, including chemotherapy-free options. Zanidatamab (zani) is a novel HER2-targeted bispecific antibody that binds HER2 in a unique trans configuration, driving multiple mechanisms of antitumor activity, including complement-dependent cytotoxicity. A CDK4/6 inhibitor combined with endocrine therapy is an approved treatment for HER2-negative/HR+ mBC and this combination has also demonstrated encouraging antitumor activity when paired with HER2-targeted therapy(ies) in HER2+/HR+ mBC. Here, we report results from ZWI-ZW25-202 (NCT04224272), an ongoing singlearm phase 2 study of zani combined with palbociclib (palbo) and fulvestrant (fulv) in pts with HER2+/HR+ mBC. Method(s): Eligibility requirements include: HER2+/HR+ unresectable, locally advanced BC or mBC;ECOG PS of 0 or 1;prior treatment with trastuzumab, pertuzumab and T DM1 (additional prior HER2-targeting agents are permitted);and no prior treatment with CDK4/6 inhibitors. Part 1 of the study evaluated the safety and tolerability of the zani/palbo/fulv combination and determined the recommended doses for use in Part 2, where the antitumor activity of the combination is being evaluated. Endpoints include safety outcomes, progression-free survival at 6 months (PFS6), confirmed objective response rate (cORR) per RECIST v1.1;disease control rate (DCR=complete response [CR] plus partial response [PR] plus stable disease [SD]);duration of response (DOR);PFS;and overall survival. Result(s): As of 24 Feb 2022, 34 pts (33 HER2+/HR+ per central analysis) with a median age of 52 (range 36-77) have been treated. In the metastatic setting, pts had received a median (range) of 4 (1-10) prior systemic regimens, including 3 (1-8) different prior HER2 targeted therapies, and 1 (0-4) endocrine therapy. Seven pts (20%) had prior T DXd treatment and 7 pts had prior fulv treatment. All pts received zani (20 mg/kg Q2W) and standard doses of palbo and fulv. Eighteen pts (53%) remained on treatment;median duration of zani treatment was 6.9 mo (range 0.5- 16.3). A dose-limiting toxicity (DLT) of neutropenia occurred in 1 of 7 DLT-evaluable pts in Part 1. Among all pts (n=34), the most common (>20%) treatment (zani, palbo and/or fulv)-related adverse events (TRAEs) were diarrhea (74%), neutrophil count decreased/neutropenia (62%), stomatitis (41%), asthenia (26%), nausea (24%), and anemia (21%). Grade (Gr) >=3 TRAEs in 2 or more pts included neutrophil count decreased/neutropenia (50%), anemia (6%), diarrhea (6%), and thrombocytopenia (6%). AEs of special interest were all Gr <=2 and included 4 pts with cardiac events (LVEF decrease of >=10% from baseline) and 1 pt with infusion-related reaction. There were no treatment-related serious AEs. Palbo was discontinued for 1 pt due to an AE (AST increase);no pt discontinued zani treatment as a result of AEs. Two deaths occurred: 1 due to disease progression and 1 due to an unrelated AE of pneumonia caused by COVID-19. In 29 pts with measurable disease, the cORR was 34.5% (95% CI: 17.9, 54.3), all responses were cPRs, of which 1 is pending CR confirmation. DOR ranged from 2.3 to 14.9+ mo, with 8 confirmed responses ongoing, and the DCR was 93.1% (95% CI: 77.2, 99.2). Interim median PFS was 11.3 mo (range 0.03-16.7;95% CI: 5.6, not estimable). PFS6 analysis is planned following the completion of enrollment. Conclusion(s): Zani in combination with palbo and fulv shows encouraging antitumor activity with durable responses in heavily pretreated pts and a manageable safety profile. This regimen has the potential to be a chemotherapy-free treatment option in pts with HER2+/HR+ mBC. Enrollment in the study is continuing.

Remote Access Active Experiential Learning with Industrial Instruments

One of the grand challenges recently thrust on engineering education is providing active, experiential learning that can flex with significant global events such as pandemics and meet the needs of individual students. The COVID pandemic is a prominent driving force for change, but beyond that, meeting the needs of students with physical, economic, or temporal barriers, such as with professional learning, is critical for our education system. This is especially true for university laboratories, where hands-on nature is often more challenging to provide remote learning services to engineering students. In electrical engineering education, the immediate response to the pandemic-induced closure of university laboratories was to cancel laboratory learning, assemble hobbyist-type experimental kits, and ship the kits to students to learn fundamentals. This approach provided a flexible experimental arrangement for students but was limited due to a lack of student exposure to tools and processes used in the industry. These learnings are critical to students who want to excel in internships or their first regular employment. Here, we describe the development of a remote active, experiential training program based on industrial tools for students to learn at a distance with industrial-type laboratory equipment. A pedagogical electronic amplifier was set up in the laboratory. Instead of students attaching probe clips to various parts of the amplifier to test, electronic laboratory switches, controlled remotely by students, allowed them to probe salient parts of the amplifier and even substitute different electronic components. Based on newly available commercial software and hardware, the system will enable students access to a laboratory session, interact with other students via online chat, and conduct experiments. In this innovative practice full paper, we will review the method approach, experimental laboratory configurations, and the learning outcomes of this remote learning technique. This method is an innovative approach to remote learning. It is potentially extensible beyond electrical and electronic engineering to other engineering domains, such as photonics, mechatronics, civil, and perhaps chemical, where electronically controlled laboratory equipment is included in the student's experiential learning. © 2022 IEEE.

Clinical Management of Patients with Schizophrenia Treated with Long-Acting Injectable Antipsychotics and Telepsychiatry Use During COVID-19 Pandemic

BACKGROUND: The COVID-19 pandemic substantially impacted care of patients with schizophrenia treated with long-acting injectable antipsychotics (LAIs). This study examined how clinics adapted operations to maintain a standard of care for these patients after pandemic onset. METHODS: Online surveys were completed in October-November 2020 by one principal investigator (PI) or PI-appointed designee at 35 clinics participating in OASIS (NCT03919994). Items concerned pandemic impacts on clinic operations, particularly telepsychiatry, and on the care of patients with schizophrenia treated with LAIs. RESULTS: All 35 clinics reported using telepsychiatry;20 (57%) implemented telepsychiatry after pandemic onset. Telepsychiatry visits increased from 12%-15% to 45%-69% across outpatient visit types after pandemic onset;frequency of no-show and/or canceled telepsychiatry visits decreased by approximately one-third. Nearly half of clinics increased the frequency of telepsychiatry visits for patients with schizophrenia treated with LAIs. Approximately one-third of participants each reported switching patients treated with LAIs to longer injection interval LAIs or to oral antipsychotics. The most common system/clinic- and patient-related barrier for telepsychiatry visits was lower reimbursement rate and access to technology/reliable internet, respectively. Almost all participants (94%) were satisfied with telepsychiatry for maintaining care of patients with schizophrenia treated with LAIs;most predicted a hybrid of telepsychiatry and office visits post-pandemic. CONCLUSIONS: Changes made by clinics after pandemic onset were viewed by almost all participants as satisfactory for maintaining a standard of care for patients with schizophrenia treated with LAIs. Most participants predicted continuing telepsychiatry to support patient care post-pandemic;equitable access to telepsychiatry will be important in this regard. FUNDING: Alkermes, Inc.

Case series of maternal mortality and maternal near miss due to severe acute respiratory syndrome coronavirus 2

The severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) that causes the COVID-19 pandemic has affected every household of the remotest part of North East India, Mizoram. The pregnant women do not have a higher chance of getting infected, yet the infection seems to be more severe. We are reporting five cases of maternal death and two cases of maternal near miss in ZMC of Mizoram. Case 1 to 5 were maternal death due to COVID-19. All of them were multigravida within the age group of 27–41 years with a period of gestation 24–37 weeks. The presenting complaints were fever and cough more than 3 days with an investigation report revealing raised C-reactive protein (CRP) and severe pneumonia. Case 6 (Near miss) was 20 years, primigravida at term pregnancy in labor with a history of fever for 2 days with an investigation report revealing raised CRP and severe pneumonia, the baby was delivered asphyxiated and died. Case 7 (Near miss) was 17 years old primigravida at term pregnancy admitted as asymptomatic COVID-19 positive, elective caesarean section was done for Obstetrics indication, the patient later developed fever and moderate pneumonia on 5 days of hospitalization, she also developed eclampsia on 7th hospital day, she survived after intensive care in the intensive care unit. [ FROM AUTHOR] Copyright of Asian Journal of Medical Sciences is the property of Manipal Colleges of Medical Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Large differences in IBD care and education across Europe, first results of the pan-european viper survey

Introduction: More than 2.5 million people in Europe are diagnosed with inflammatory bowel diseases (IBD). IBD affects the quality of life, but also has important consequences for health systems. It remains unknown if variations in IBD care and education differs across Europe and to help address this question, we conducted this European Variation In IBD PracticE suRvey (VIPER) to study potential differences. Aims & Methods: This trainee-initiated survey, run through SurveyMonkey ®, consisted of 47 questions inquiring basic demographics, IBD training and clinical care. The survey was distributed through social media and national GI societies from December 2020 - January 2021. Results were compared according to GDP per capita, for which countries were divided into 2 groups (low/high income, according to the World Bank). Differences between groups were calculated using the chi2 statistic. Results: The online survey was completed by 1268 participants from 39 European countries. Most of the participants are specialists (65.3 %), followed by fellows in training (>/< 3 years, 19.1%, 15.6 %). Majority of the responders are working in academic institutions (50.4 %), others in public/ district hospitals (33.3 %) or private practices (16.3 %). Despite significant differences in access to IBD-specific training between high (56.4%) and low (38.5%) GDP countries (p<0.001), majority of clinicians feels comfortable in treating IBD (77.2% vs 72.0%, p=0.04). GDP was not a factor that dictated confidence in treating patients. IBD patients seen per week, IBD boards and especially IBD specific training were factors increasing confidence in managing IBD patients. Interestingly, a difference in availability of dedicated IBD units could be observed (58.5% vs 39.7%, p<0.001), as well as an inequality in multidisciplinary meetings (72.6% vs 40.2%, p<0.001), which often take place on a weekly basis (53.0%). In high GDP countries, IBD nurses are more common (86.2%) than in low GDP countries (36.0%, p<0.001), which is mirrored by differences in nurse-led IBD clinics (40.6% vs 13.8%, p<0.001). IBD dieticians (32.4% vs 16.6%) and psychologists (16.7% vs 7.5%) are mainly present in high GDP countries (p<0.001). In the current COVID era, telemedicine is available in 58.4% vs 21.4% of the high/low GDP countries respectively (p<0.001), as well as urgent flare clinics (58.6% vs 38.7%, p<0.001) and endoscopy within 24 hours if needed (83.0% vs 86.7% p=0.1). Treat-to-target approaches are implemented everywhere (85.0%), though access to biologicals and small molecules differs significantly. Almost all (94.7%) use faecal calprotectin for routine monitoring, whereas half also use intestinal ultrasound (47.9%). Conclusion: A lot of variability in IBD practice exists across Europe, with marked differences between high vs low GDP countries. Further work is required to help address some of these inequalities, aiming to improve and standardise IBD care across Europe.