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Item A Case of Autoimmune Hemolytic Anemia after the First Dose of COVID-19 mRNA-1273 Vaccine with Undetected Pernicious Anemia(Hindawi, 2022-01-29) Jaydev, Fnu; Kumar, Vinod; Khatri, Jaikumar; Shahani, Shobha; Beganovic, Sead; Medicine, School of MedicineBy this time, multiple vaccines have been approved to limit the spread of SARS-CoV-2 worldwide. These include new-generation vaccines that contain mRNA of the target organism. Some common side effects were identified and reported during phase 3 clinical trials of vaccination, but more rare adverse events were reported in the literature. One such concern is autoimmune conditions that SARS-CoV-2 viral antigens could have possibly incited. We are presenting here a case of a young female with no known autoimmune diseases, diagnosed with autoimmune hemolytic anemia about a week after receiving her first dose of the COVID-19 mRNA vaccine. We discuss the possible culprit for precipitation of autoimmune hemolytic anemia after the SARS-CoV-2 mRNA vaccine, which encodes virus spike protein. This case highlights the importance of being vigilant for identifying rare adverse events that could appear during mass vaccination.Item The decision making process in women diagnosed with estrogen receptor-positive breast cancer experiencing side effects related to oral endocrine therapy(2017-02-06) Milata, Jennifer Lynn; Carpenter, Janet S.; Draucker, Claire Burke; Otte, Julie; Zimet, GregOral endocrine therapy (OET) is standard therapy for millions of estrogen receptor-positive breast cancer survivors (ER+BCS). OET reduces recurrence, mortality, and metastasis. ER+BCS often do not take their OET as recommended due to adverse side effects. The purpose of this dissertation was to develop an explanatory framework of decision making by women with ER+ breast cancer who report experiencing side effects from OET. This project was comprised of two components. The first component was a systematic review with three main findings: (1) side effects negatively impact OET non-adherence, (2) there is an absence of decisional supports provided to or available for ER+BCS who are experiencing OET side effects,, and (3) ER+BCS likely have unmet decisional needs related to OET. The second component was a grounded theory study that included 31 ER+BCS reporting OET side effects. During a single semi-structured interview, participants described the experience of OET over time. This study produced two qualitatively derived projects. First, a theoretical framework was developed that depicted four stages through which the experience of OET decision making unfolded. The stages were (1) being told what I need to do to live, (2) doing what I need to do to live, (3) enduring what I need to do to live, and (4) deciding how I want to live. Second, a typology was developed that depicted six sources of external decisional supports (healthcare providers, husbands, other breast cancer survivors, friends and family, the internet and other media sources, and God) that met four types of decisional needs (information about OET and its side effects, in-depth discussions about side effects, help in managing side effects, and emotional support). Findings can be used to develop interventions, such as decision aids, to promote quality decision making in women experiencing OET side effects.Item Hypogammaglobulinemia in Adolescents and Young Adults with Acute Lymphoblastic Leukemia(Mary Ann Liebert, Inc., 2020-12) Lange, Cassandra S.; Rahrig, April; Althouse, Sandra K.; Nelson, Robert P.; Batra, Sandeep; Medicine, School of MedicineHypogammaglobulinemia is a poorly described complication of chemotherapy in adolescents and young adults (AYAs, 15–39 years) with acute lymphoblastic leukemia (ALL). The majority of AYAs treated on a Berlin–Frankfurt–Munster-based ALL regimen experienced hypogammaglobulinemia (65.0% [13/20]). Febrile neutropenia episodes (throughout the treatment course) and infectious events during maintenance occurred more frequently in hypogammaglobulinemic patients compared with patients with normal immunoglobulin G levels (n = 7) (median 1.0 vs. 0.0, p = 0.02; 7.0 vs. 3.0, p = 0.02, respectively). Hypogammaglobulinemia did not impact overall or event-free survival. Further studies are needed to elucidate the etiology of hypogammaglobulinemia and to establish criteria for immunoglobulin replacement in these patients.Item Lessons from a BACE1 inhibitor trial: off-site but not off base(Elsevier, 2014-10) Lahiri, Debomoy K.; Maloney, Bryan; Long, Justin M.; Greig, Nigel H.; Department of Medical & Molecular Genetics, IU School of MedicineAlzheimer's disease (AD) is characterized by formation of neuritic plaque primarily composed of a small filamentous protein called amyloid-β peptide (Aβ). The rate-limiting step in the production of Aβ is the processing of Aβ precursor protein (APP) by β-site APP-cleaving enzyme (BACE1). Hence, BACE1 activity plausibly plays a rate-limiting role in the generation of potentially toxic Aβ within brain and the development of AD, thereby making it an interesting drug target. A phase II trial of the promising LY2886721 inhibitor of BACE1 was suspended in June 2013 by Eli Lilly and Co., due to possible liver toxicity. This outcome was apparently a surprise to the study's team, particularly since BACE1 knockout mice and mice treated with the drug did not show such liver toxicity. Lilly proposed that the problem was not due to LY2886721 anti-BACE1 activity. We offer an alternative hypothesis, whereby anti-BACE1 activity may induce apparent hepatotoxicity through inhibiting BACE1's processing of β-galactoside α-2,6-sialyltransferase I (STGal6 I). In knockout mice, paralogues, such as BACE2 or cathepsin D, could partially compensate. Furthermore, the short duration of animal studies and short lifespan of study animals could mask effects that would require several decades to accumulate in humans. Inhibition of hepatic BACE1 activity in middle-aged humans would produce effects not detectable in mice. We present a testable model to explain the off-target effects of LY2886721 and highlight more broadly that so-called off-target drug effects might actually represent off-site effects that are not necessarily off-target. Consideration of this concept in forthcoming drug design, screening, and testing programs may prevent such failures in the future.Item Oral Endocrine Therapy Nonadherence, Adverse Effects, Decisional Support, and Decisional Needs in Women With Breast Cancer(Wolters Kluwer, 2018-01) Milata, Jennifer L.; Otte, Julie L.; Carpenter, Janet S.; School of NursingBACKGROUND: Oral endocrine therapy (OET) such as tamoxifen or aromatase inhibitors reduces recurrence and mortality for the 75% of breast cancer survivors (BCSs) with a diagnosis of estrogen receptor-positive breast cancer. Because many BCSs decide not take OET as recommended because of adverse effects, understanding BCSs' decisional supports and needs is foundational to supporting quality OET decision making about whether to adhere to OET. OBJECTIVE: The aim of this study was to examine literature pertaining to OET nonadherence and adverse effects using the Ottawa Decision Support Framework categories of decisional supports and decisional needs because these factors potentially influence OET use. METHODS: A systematic literature search was performed in PubMed and CINAHL using combined search terms "aromatase inhibitors and adherence" and "tamoxifen and adherence." Studies that did not meet criteria were excluded. Relevant data from 25 publications were extracted into tables and reviewed by 2 authors. RESULTS: Findings identified the impact of adverse effects on OET nonadherence, an absence of decisional supports provided to or available for BCSs who are experiencing OET adverse effects, and the likelihood of unmet decisional needs related to OET. CONCLUSIONS: Adverse effects contribute to BCSs decisions to stop OET, yet there has been little investigation of the process through which that occurs. This review serves as a call to action for providers to provide support to BCSs experiencing OET adverse effects and facing decisions related to nonadherence. IMPLICATIONS FOR PRACTICE: Findings suggest BCSs prescribed OET have unmet decisional needs, and more decisional supports are needed for BCSs experiencing OET adverse effects.Item Response to “Radiation Therapeutic Gain and Asian Botanicals,” by Stephen Sagar(SAGE Publications, 2010-03-21) Lawenda, Brian D.; Radiation Oncology, School of MedicineNumerous botanical agents, many of which are used in whole medical system practices (i.e. traditional Chinese medicine, Ayurvedic medicine, etc.), have been shown to exhibit radiomodifying effects on tumors and normal tissues in-vitro and invivo studies. Some of these agents can enhance the therapeutic gain of radiation therapy by either acting as a radiosensitizer to tumor cells and/or as a radioprotector to normal cells. Botanical agents are comprised of multiple phytochemical compounds that may work individually or synergistically to not only improve radiation therapy outcomes, but may also exhibit a variety of anti-cancer effects as well. It will be important to evaluate these botanicals for efficacy, tumor specificity, and safety profiles before they can be recommended during radiation therapy.