GLP-1 Agonists in Type 1 Diabetes Mellitus: A Review of the Literature

Objective: To review the use of GLP-1 agonists in patients with type 1 diabetes mellitus (T1DM). Data Sources: A search using the MEDLINE database, EMBASE, and Cochrane Database was performed through March 2016 using the search terms glucagon-like peptide 1 (GLP-1) agonists, incretin, liraglutide, exenatide, albiglutide, dulaglutide, type 1 diabetes mellitus. Study Selection and Data Extraction: All English-language trials that examined glycemic end points using GLP- 1 agonists in humans with T1DM were included. Data Synthesis: A total of 9 clinical trials examining the use of GLP-1 agonists in T1DM were identified. On average, hemoglobin A1C (A1C) was lower than baseline, with a maximal lowering of 0.6%. This effect was not significant when tested against a control group, with a relative decrease in A1C of 0.1% to 0.2%. In all trials examined, reported hypoglycemia was low, demonstrating no difference when compared with insulin monotherapy. Weight loss was seen in all trials, with a maximum weight loss of 6.4 kg over 24 weeks. Gastrointestinal adverse effects are potentially limiting, with a significant number of patients in trials reporting nausea. Conclusion: The use of GLP-1 agonists should be considered in T1DM patients who are overweight or obese and not at glycemic goals despite aggressive insulin therapy; however, tolerability of these agents is a potential concern. Liraglutide has the strongest evidence for use and would be the agent of choice for use in overweight or obese adult patients with uncontrolled T1DM

Strategies for the Management of Postoperative Anemia in Elective Orthopedic Surgery

Objective: To assess the use of oral iron, intravenous (IV) iron, and erythropoiesis-stimulating agents (ESAs) for the prevention and management of perioperative anemia in elective orthopedic surgery patients, and to provide a clinical algorithm for use. Data Sources: A PubMed and MEDLINE search was conducted from 1964 through March 2016 using the following search terms alone or in combination: orthopedic, surgery, elective, anemia, blood transfusion, iron, erythropoiesisstimulating agents, and erythropoietin. Study Selection and Data Extraction: All English-language prospective and retrospective human studies and meta-analyses evaluating oral iron, IV iron, or ESA alone or in combination in elective orthopedic surgery patients were evaluated, provided they reported blood transfusion outcomes. Data Synthesis: A total of 9 prospective and retrospective studies and 1 meta-analysis were identified and included. In the preoperative setting, administration of oral iron, IV iron, or ESA alone or in combination to correct underlying anemia led to significantly reduced transfusion rates. Transfusion requirements were generally less with combination therapy (ESA + oral or IV iron). In the short-term perioperative or postoperative period, use of oral or IV iron led to conflicting results, with some reporting a statistically significant reduction in blood transfusions, whereas others reported none. Conclusions: In elective orthopedic surgery, IV or oral iron with or without an ESA may provide benefit in prevention of postoperative anemia and results in blood transfusion reduction without significantly increasing the risk of adverse events. These agents should be considered at the lowest effective dose with emphasis on administration prior to planned surgery

The Impact of an International Interprofessional Experience on Perceptions of Pharmacist-Physician Relationships

Objective. To assess the impact of this international interprofessional learning experience on perceptions of pharmacist-physician relationships and interprofessional teams. Methods. Medical and pharmacy students completed a one-week interprofessional medical mission experience in the Dominican Republic. Anonymous surveys were administered to 17 students before and after completion to measure perceptions of pharmacist-physician relationships and interprofessional teams. Responses were matched and changes in perceptions were analyzed using the Wilcoxon Signed Rank test. The SPICE-R2 instrument was administered after the experience to measure attitudes toward interprofessional teams. Results. Of the 17 participants, 100% responded to all surveys. Significant improvements were seen in the perception of pharmacists as an integral part of medical mission trips (P=0.035) and confidence in the ability to communicate with other healthcare disciplines (P=0.033). All students stated they would recommend this experience, and agreed that interprofessional experiences enhance their team work skills and should be incorporated into their education. Student comments supported that this was a meaningful and effective interprofessional experience. The results of the SPICE-R2 demonstrated positive attitudes about interprofessional teams, with all questions having a median score of “agree” or “strongly agree.” Conclusions. An international interprofessional experience improved the perception of pharmacist-physician relationships. The experience provided understanding of the other healthcare discipline, an appreciation for the importance of interprofessional teamwork, increased student confidence in communicating with the other discipline, and cultivated interest in future interprofessional collaboration

Hybrid Online Delivery of a Pharmacy Residency and Fellowship Elective Course

  Objective: To describe and evaluate the transition of a pharmacy residency and fellowship (PRF) elective course to a hybrid online platform. Innovation: In 2016, the 1-credit hour PRF elective was transitioned from a live, synchronous course to a hybrid online platform. Over the course of the semester, students completed eight modules along with assignments that pertained to a different component of PRF. Course grades and evaluations, as well as PRF placement rates, were compared between 2015 (live, synchronous course) and 2016 (hybrid online course). There were no differences in overall course grades or student evaluations of individual relevant course objectives between the two course formats. However, more students rated the course as excellent during the 2015 live, synchronous course. Placement rates were similar between students who took the course in 2015 and 2016. Critical Analysis: Following the transition of a PRF elective to a hybrid online platform, course grades, evaluation of individual relevant course objectives, and PRF placement rates remained similar to previous years. Creative educational venues can help meet the student demand while simultaneously allowing faculty to manage their time. However, instructors should balance this with desire of students to have more face-to-face in class time.     Type: Not

Determinants of synaptic integration and heterogeneity in rebound firing explored with data-driven models of deep cerebellar nucleus cells

Significant inroads have been made to understand cerebellar cortical processing but neural coding at the output stage of the cerebellum in the deep cerebellar nuclei (DCN) remains poorly understood. The DCN are unlikely to just present a relay nucleus because Purkinje cell inhibition has to be turned into an excitatory output signal, and DCN neurons exhibit complex intrinsic properties. In particular, DCN neurons exhibit a range of rebound spiking properties following hyperpolarizing current injection, raising the question how this could contribute to signal processing in behaving animals. Computer modeling presents an ideal tool to investigate how intrinsic voltage-gated conductances in DCN neurons could generate the heterogeneous firing behavior observed, and what input conditions could result in rebound responses. To enable such an investigation we built a compartmental DCN neuron model with a full dendritic morphology and appropriate active conductances. We generated a good match of our simulations with DCN current clamp data we recorded in acute slices, including the heterogeneity in the rebound responses. We then examined how inhibitory and excitatory synaptic input interacted with these intrinsic conductances to control DCN firing. We found that the output spiking of the model reflected the ongoing balance of excitatory and inhibitory input rates and that changing the level of inhibition performed an additive operation. Rebound firing following strong Purkinje cell input bursts was also possible, but only if the chloride reversal potential was more negative than −70 mV to allow de-inactivation of rebound currents. Fast rebound bursts due to T-type calcium current and slow rebounds due to persistent sodium current could be differentially regulated by synaptic input, and the pattern of these rebounds was further influenced by HCN current. Our findings suggest that active properties of DCN neurons could play a crucial role for signal processing in the cerebellum