Examining the effects of early patient care and biomedical science integration on predoctoral dental student competence and confidence.

INTRODUCTION: Our study investigates early experiential learning as a method of curricular integration by allowing students to begin their clinical experience in the first year of the programme, as well as distributing biomedical classes throughout the predoctoral dental school curriculum. MATERIALS AND METHODS: This study utilises a quasi-experimental design with two different groups, Standard Curriculum Group and Integrated Curriculum Group, n = 87. Data were collected from 2017 to 2021. RESULTS: We found that, on average, it took 608 h less for the participants in an integrated curriculum group to reach clinical competence in comparison to peers who did not experience the same methods of integration in their programme. These data were collected through daily faculty evaluations of students' progression as well as participants' own self-assessment. Our results indicate that participants in the Integrated Curriculum Group also experienced a positive effect on their confidence in their ability to apply the biomedical sciences to patient care. DISCUSSION/CONCLUSION: Our findings demonstrate that predoctoral dental programmes may be able to bring about positive outcomes for students' clinical confidence and competence by providing patient care opportunities early in the programme and sequencing the biomedical sciences throughout the curriculum. As such, it appears that early experiential learning may be a viable option for curricular integration that can have a positive effect on both students' confidence in their clinical abilities and their progression to clinical competence.

Verbalized Studying and Elaborative Interrogation in the Virtual Classroom: Students with Social Anxiety Prefer Working Alone, but Working with a Peer Does Not Hurt Their Learning.

Due to public health measures enacted in response to the Covid-19 pandemic, educators and students alike have been suddenly thrust into the realm of online learning. To better understand how active and collaborative learning methods can apply to students studying in isolation, we compared the effects of two teach-and-question assignments: one that utilizes the active learning method of reciprocal peer tutoring and a solo version that requires individual verbalized studying and elaborative interrogation. We used a quasi-experimental design, with student participants enrolled in an online introductory human anatomy course. The first treatment group completed regular teach-and-question study assignments virtually with a peer, and the second treatment group completed the same assignment independently. We found no differences in exam scores between treatments, even for students with high social anxiety; however, student attitudes about the social versus individual assignment did differ for specific types of students. Students who reported experiencing high social anxiety preferred completing the active learning exercise by themselves, and students with low scientific reasoning ability preferred the partnered assignment. This research has potential implications for online classrooms. For instance, our results indicate that students who study independently, or in isolation, may have learning outcomes similar to those of students who study with a peer as long as they study actively. Because we found no negative impact on examination results, it also could be that virtually partnered or independent teach-and-question assignments could be helpful for instructors teaching large online classes to ensure all students are getting individualized feedback and attention.

Antibiotic Policies and Utilization in Oregon Hospice Programs.

Antibiotics are frequently used in hospice care, despite limited data on safety and effectiveness in this patient population. We surveyed Oregon hospice programs on antibiotic policies and prescribing practices. Among 39 responding hospice programs, the median reported proportion of current census using antibiotics was 10% (interquartile range = 3.5%-20.0%). Approximately 31% of responding hospice programs had policies for antibiotic initiation, 17% of hospice programs had policies for antibiotic discontinuation, and 95% of hospice programs had policies for managing drug interactions. Diarrhea, nausea/vomiting, and yeast infections were the most frequently reported antibiotic-associated adverse events, occurring "sometimes" or "often" among 62%, 47%, and 62% of respondents, respectively. In conclusion, less than a third of participating hospice programs reported having a policy for antibiotic initiation and even less frequently a policy for discontinuation. More data are needed on the risks and benefits of antibiotic use in hospice care to inform these policies and optimize outcomes in this vulnerable patient population.

FDA Approval Summary: Ramucirumab for Gastric Cancer.

The FDA approved ramucirumab (CYRAMZA; Eli Lilly and Company) for previously treated patients with advanced or metastatic gastric or gastroesophageal junction adenocarcinoma initially as monotherapy (April 21, 2014) and subsequently as combination therapy with paclitaxel (November 5, 2014). In the monotherapy trial, 355 patients in the indicated population were randomly allocated (2:1) to receive ramucirumab or placebo, 8 mg/kg intravenously every 2 weeks. In the combination trial, 665 patients were randomly allocated (1:1) to receive ramucirumab or placebo, 8 mg/kg intravenously every 2 weeks, in combination with paclitaxel, 80 mg/m(2) on days 1, 8, and 15 of 28-day cycles. Overall survival (OS) was increased in patients who received ramucirumab in both the monotherapy [HR, 0.78; 95% confidence interval (CI), 0.60-0.998; log rank P = 0.047] and combination trials (HR, 0.81; 95% CI, 0.68-0.96; P = 0.017). The most common adverse reactions were hypertension and diarrhea in the monotherapy trial and fatigue, neutropenia, diarrhea, and epistaxis in the combination trial. Because of concerns about the robustness of the monotherapy trial results, FDA approved the original application after receiving the results of the combination trial confirming the OS effect. Based on exploratory exposure-response analyses, there is residual uncertainty regarding the optimal dose of ramucirumab.

Requirements for medication monitoring in assisted living facilities.

OBJECTIVE: To determine requirements for medication monitoring in assisted living in the United States. DATA SOURCES: Comprehensive list maintained by the National Center for Assisted Living reporting individual state entities that are responsible for oversight of assisted living facilities. Reviews of respective entity Web sites were performed July to September 2011. STUDY SELECTION: Web sites of all 50 states reporting statutes and regulations pertaining to assisted living and medication review. DATA EXTRACTION: Appropriate state Web sites were reviewed to determine state-specific definitions, statutes, and regulations pertaining to requirements for medication review in assisted living and persons or entities responsible for this review. Telephone interviews were conducted with appropriate individuals when questions existed or clarifications were needed. DATA SYNTHESIS: Forty states recognize or define the living environment of assisted living, and 10 describe it using other terms. Thirty states have specific requirements for medication review in assisted living facilities, which vary greatly by required frequency, health care discipline responsible for conducting medication monitoring, and non-time-dependent criteria that trigger the review. CONCLUSION: Considerable diversity exists among states in requirements for medication review in the assisted living environment. The requirements in some states resemble national nursing facility standards of practice for pharmacy services, while others have few or no requirements for medication review. Regulations do not always require a pharmacist to perform this review.

Gene expression profiling and candidate gene resequencing identifies pathways and mutations important for malignant transformation caused by leukemogenic fusion genes.

NUP98-HOXD13 (NHD13) and CALM-AF10 (CA10) are oncogenic fusion proteins produced by recurrent chromosomal translocations in patients with acute myeloid leukemia (AML). Transgenic mice that express these fusions develop AML with a long latency and incomplete penetrance, suggesting that collaborating genetic events are required for leukemic transformation. We employed genetic techniques to identify both preleukemic abnormalities in healthy transgenic mice as well as collaborating events leading to leukemic transformation. Candidate gene resequencing revealed that 6 of 27 (22%) CA10 AMLs spontaneously acquired a Ras pathway mutation and 8 of 27 (30%) acquired an Flt3 mutation. Two CA10 AMLs acquired an Flt3 internal-tandem duplication, demonstrating that these mutations can be acquired in murine as well as human AML. Gene expression profiles revealed a marked upregulation of Hox genes, particularly Hoxa5, Hoxa9, and Hoxa10 in both NHD13 and CA10 mice. Furthermore, mir196b, which is embedded within the Hoxa locus, was overexpressed in both CA10 and NHD13 samples. In contrast, the Hox cofactors Meis1 and Pbx3 were differentially expressed; Meis1 was increased in CA10 AMLs but not NHD13 AMLs, whereas Pbx3 was consistently increased in NHD13 but not CA10 AMLs. Silencing of Pbx3 in NHD13 cells led to decreased proliferation, increased apoptosis, and decreased colony formation in vitro, suggesting a previously unexpected role for Pbx3 in leukemic transformation.

Knock-in of a FLT3/ITD mutation cooperates with a NUP98-HOXD13 fusion to generate acute myeloid leukemia in a mouse model.

Constitutive activation of FLT3 by internal tandem duplication (ITD) is one of the most common molecular alterations in acute myeloid leukemia (AML). FLT3/ITD mutations have also been observed in myelodysplastic syndrome patients both before and during progression to AML. Previous work has shown that insertion of an FLT3/ITD mutation into the murine Flt3 gene induces a myeloproliferative neoplasm, but not progression to acute leukemia, suggesting that additional cooperating events are required. We therefore combined the FLT3/ITD mutation with a model of myelodysplastic syndrome involving transgenic expression of the Nup98-HoxD13 (NHD13) fusion gene. Mice expressing both the FLT3/ITD and NHD13 transgene developed AML with 100% penetrance and short latency. These leukemias were driven by mutant FLT3 expression and were susceptible to treatment with FLT3 tyrosine kinase inhibitors. We also observed a spontaneous loss of the wild-type Flt3 allele in these AMLs, further modeling the loss of the heterozygosity phenomenon that is seen in human AML with FLT3-activating mutations. Because resistance to FLT3 inhibitors remains an important clinical issue, this model may help identify new molecular targets in collaborative signaling pathways.

Retroviral insertional mutagenesis identifies Zeb2 activation as a novel leukemogenic collaborating event in CALM-AF10 transgenic mice.

The t(10;11) translocation results in a CALM-AF10 fusion gene in a subset of leukemia patients. Expression of a CALM-AF10 transgene results in leukemia, with prolonged latency and incomplete penetrance, suggesting that additional events are necessary for leukemic transformation. CALM-AF10 mice infected with the MOL4070LTR retrovirus developed acute leukemia, and ligation-mediated polymerase chain reaction was used to identify retroviral insertions at 19 common insertion sites, including Zeb2, Nf1, Mn1, Evi1, Ift57, Mpl, Plag1, Kras, Erg, Vav1, and Gata1. A total of 26% (11 of 42) of the mice had retroviral integrations near Zeb2, a transcriptional corepressor leading to overexpression of the Zeb2-transcript. A total of 91% (10 of 11) of mice with Zeb2 insertions developed B-lineage acute lymphoblastic leukemia, suggesting that Zeb2 activation promotes the transformation of CALM-AF10 hematopoietic precursors toward B-lineage leukemias. More than half of the mice with Zeb2 integrations also had Nf1 integrations, suggesting cooperativity among CALM-AF10, Zeb2, and Ras pathway mutations. We searched for Nras, Kras, and Ptpn11 point mutations in the CALM-AF10 leukemic mice. Three mutations were identified, all of which occurred in mice with Zeb2 integrations, consistent with the hypothesis that Zeb2 and Ras pathway activation promotes B-lineage leukemic transformation in concert with CALM-AF10.

Xaf1 can cooperate with TNFalpha in the induction of apoptosis, independently of interaction with XIAP.

XIAP-associated factor 1 (Xaf1) binds XIAP and re-localizes it to the nucleus, thus inhibiting XIAP activity and enhancing apoptosis [1]. Xaf1 expression is reduced or absent in tumor samples and cell lines suggesting it may function as a tumor suppressor [2-5]. To further study Xaf1 function we generated Xaf1 inducible cells in the osteosarcoma cell line Saos-2. Despite Xaf1 inducing apoptosis that is dramatically enhanced by TNFalpha we find no evidence for an interaction between Xaf1 and XIAP. Furthermore, Xaf1 expression sensitized XIAP-/- fibroblasts to TNFalpha, demonstrating the existence of a novel mechanism of Xaf1 induced apoptosis distinct from antagonizing XIAP. Xaf1 expression promotes cytochrome c release that cannot be blocked by inhibition of caspase activity. This implicates a role for the mitochondrial apoptotic pathway, consistent with the ability of Bcl2 to block Xaf1 induced apoptosis. The data indicate that in Saos2 cells Xaf1 activates the mitochondrial apoptotic pathway to facilitate cytochrome c release, thus amplifying apoptotic signals from death receptors.