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

High‐dose Cholecalciferol Supplementation in Adults with Cystic Fibrosis

Introduction Despite the availability of consensus guidelines for the treatment of vitamin D deficiency, prospective trials are lacking to examine alternative dosing strategies for adult patients with cystic fibrosis (CF) who do not meet therapeutic goals with standard regimens. Objectives The primary objective of this study was to determine the efficacy of high‐dose cholecalciferol supplementation in increasing serum vitamin D (25‐OHD) levels in adult patients with CF. Methods Patients were eligible for inclusion if they were 18 years or older, had baseline 25‐OHD levels lower than 30 ng/ml, and were diagnosed with CF and pancreatic insufficiency. Patients were given a single dose of cholecalciferol 300,000 or 500,000 IU based on baseline 25‐OHD levels. Response was defined by 25‐OHD and ionized calcium levels at 3 months. At 6 months, responders received a second dose of the same strength, and nonresponders were given a weekly supplement of cholecalciferol 50,000 IU in addition to cholecalciferol 500,000 IU. A second 25‐OHD level was obtained at 9 months. Results Of the 46 patients enrolled, 32 patients (70%) completed the study. Baseline levels of 25‐OHD significantly increased over time in the per protocol population at 3 and 9 months. A total of 16 patients (50%) were considered nonresponders and required weekly supplementation. Conclusion A protocol using high‐dose cholecalciferol or high‐dose plus weekly cholecalciferol is safe and effective in treating adult patients with CF and pancreatic insufficiency

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

Using Debates to Mimic Clinical Discussion in Experiential Education

Critical thinking and application of knowledge to an ambiguous patient care scenario are often difficult skills to cultivate in learners. Use of traditional teaching techniques (e.g. topic discussions and journal clubs) helps to develop these competencies within learners. However, alternative teaching strategies may help develop critical thinking and direct application. Debates have been used in healthcare education for decades with positive results. This paper provides supporting evidence for use of debates in pharmacy education and is designed to serve as a general guide for preceptors interested in implementing debates into the experiential setting. Specifically, the objectives are to: 1) highlight the pedagogical outcomes as reported in the literature, 2) offer practical considerations to implement debates as a teaching tool in experiential education, and 3) encourage future research and scholarship in this area.   Type: Idea Pape

Diverse aging rates in ectothermic tetrapods provide insights for the evolution of aging and longevity

Comparative studies of mortality in the wild are necessary to understand the evolution of aging; yet, ectothermic tetrapods are underrepresented in this comparative landscape, despite their suitability for testing evolutionary hypotheses. We present a study of aging rates and longevity across wild tetrapod ectotherms, using data from 107 populations (77 species) of nonavian reptiles and amphibians. We test hypotheses of how thermoregulatory mode, environmental temperature, protective phenotypes, and pace of life history contribute to demographic aging. Controlling for phylogeny and body size, ectotherms display a higher diversity of aging rates compared with endotherms and include phylogenetically widespread evidence of negligible aging. Protective phenotypes and life-history strategies further explain macroevolutionary patterns of aging. Analyzing ectothermic tetrapods in a comparative context enhances our understanding of the evolution of aging

Management of coronary disease in patients with advanced kidney disease

BACKGROUND Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease. METHODS We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P=0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P=0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P=0.03). CONCLUSIONS Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction

Health status after invasive or conservative care in coronary and advanced kidney disease

BACKGROUND In the ISCHEMIA-CKD trial, the primary analysis showed no significant difference in the risk of death or myocardial infarction with initial angiography and revascularization plus guideline-based medical therapy (invasive strategy) as compared with guideline-based medical therapy alone (conservative strategy) in participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease (an estimated glomerular filtration rate of <30 ml per minute per 1.73 m2 or receipt of dialysis). A secondary objective of the trial was to assess angina-related health status. METHODS We assessed health status with the Seattle Angina Questionnaire (SAQ) before randomization and at 1.5, 3, and 6 months and every 6 months thereafter. The primary outcome of this analysis was the SAQ Summary score (ranging from 0 to 100, with higher scores indicating less frequent angina and better function and quality of life). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate the treatment effect with the invasive strategy. RESULTS Health status was assessed in 705 of 777 participants. Nearly half the participants (49%) had had no angina during the month before randomization. At 3 months, the estimated mean difference between the invasive-strategy group and the conservative-strategy group in the SAQ Summary score was 2.1 points (95% credible interval, 120.4 to 4.6), a result that favored the invasive strategy. The mean difference in score at 3 months was largest among participants with daily or weekly angina at baseline (10.1 points; 95% credible interval, 0.0 to 19.9), smaller among those with monthly angina at baseline (2.2 points; 95% credible interval, 122.0 to 6.2), and nearly absent among those without angina at baseline (0.6 points; 95% credible interval, 121.9 to 3.3). By 6 months, the between-group difference in the overall trial population was attenuated (0.5 points; 95% credible interval, 122.2 to 3.4). CONCLUSIONS Participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease did not have substantial or sustained benefits with regard to angina-related health status with an initially invasive strategy as compared with a conservative strategy

Initial invasive or conservative strategy for stable coronary disease

BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, 121.8 percentage points; 95% CI, 124.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used