Canagliflozin, a New Sodium-Glucose Co-Transporter 2 Inhibitor, in the Treatment of Diabetes

Purpose. The published evidence on the pharmacology, pharmacodynamics, pharmacokinetics, safety, and efficacy of a promising investigational agent for managing type 2 diabetes is evaluated. Summary. Canagliflozin belongs to a class of agents—the sodium–glucose cotransporter 2 (SGLT2) inhibitors—whose novel mechanism of action offers potential advantages over other antihyperglycemic agents, including a relatively low hypoglycemia risk and weight loss-promoting effects. Canagliflozin has dose-dependent pharmacokinetics, and research in laboratory animals demonstrated high oral bioavailability (85%) and rapid effects in lowering glycosylated hemoglobin (HbA1c) values. In four early-stage clinical trials involving a total of over 500 patients, the use of canagliflozin for varying periods was associated with significant mean reductions in HbA1c (absolute reductions of 0.45–0.92%) and fasting plasma glucose (decreases ranged from 16.2% to 42.4%) and weight loss ranging from 0.7 to 3.5 kg. More than a dozen Phase II or III clinical trials of canagliflozin in adults are ongoing or were recently completed, but the final results of most of those studies have not been published. Adverse effects reported in clinical trials of canagliflozin include urinary tract and genital infections, occurring in about 10% of patients. Additional and larger Phase III clinical trials to delineate the potential role of canagliflozin and other SGLT2 inhibitors in the management of diabetes (including studies involving the elderly, children, and patients with renal or hepatic dysfunction) are planned or currently underway. Conclusion. Canagliflozin and other investigational SGLT2 inhibitors have a novel mechanism of action that may offer a future alternative treatment pathway for managing type 2 diabetes

Student-generated e-learning for clinical education

Background Within clinical education, e-learning facilitates a standardised learning experience to augment the clinical experience while enabling learner and teacher flexibility. With the shift of students from consumers to creators, student-generated content is expanding within higher education; however, there is sparse literature evaluating the impact of student-developed e-learning within clinical education. The aim of this study was to implement and evaluate a student-developed e-learning clinical module series within ambulatory care clinical pharmacy experiences. Methods Three clinical e-learning modules were developed by students for use prior to clinical experiences. E-learning modules were created by fourth-year professional pharmacy students and reviewed by pharmacy faculty members. A pre-/post-assessment was performed to evaluate knowledge comprehension before and after participating in the e-learning modules. Additionally, a survey on student perceptions of this educational tool was performed at the end of the clinical experience. There is sparse literature evaluating the impact of student-developed e-learning within clinical education Results Of the 31 students eligible for study inclusion, 94 per cent participated in both the pre- and post-assessments. The combined post-assessment score was significantly improved after participating in the student-developed e-learning modules (p = 0.008). The student perception survey demonstrated positive perceptions of e-learning within clinical education. Discussion Student-generated e-learning was able to enhance knowledge and was positively perceived by learners. As e-learning continues to expand within health sciences education, students can be incorporated into the development and execution of this educational tool

Numerical Regularization of Electromagnetic Quantum Fluctuations in Inhomogeneous Dielectric Media

Electromagnetic Casimir stresses are of relevance to many technologies based on mesoscopic devices such as MEMS embedded in dielectric media, Casimir induced friction in nano-machinery, micro-fluidics and molecular electronics. Computation of such stresses based on cavity QED generally require numerical analysis based on a regularization process. A new scheme is described that has the potential for wide applicability to systems involving realistic inhomogeneous media. From a knowledge of the spectrum of the stationary modes of the electromagnetic field the scheme is illustrated by estimating numerically the Casimir stress on opposite faces of a pair of perfectly conducting planes separated by a vacuum and the change in this result when the region between the plates is filled with an incompressible inhomogeneous non-dispersive dielectric.Comment: 5 pages, 2 figures, submitted to PR

Design of Drug-Induced Diseases Elective Utilizing Active Learning

Objectives To describe active learning utilized in a drug-induced diseases (DID) elective and determine inter-rater reliability of the assessment rubric for oral case-based presentations. Methods The design of this DID elective focuses on problem-based learning to enhance students’ critical thinking and problem-solving skills pertaining to the treatment of inducible diseases and general medicine. Each class incorporates active learning, utilization of drug information resources, and group work. The primary course assessment is student developed oral case-based presentations evaluated with a standard rubric. Results The intra-class correlation coefficient (ICC) was calculated amongst evaluators to assess the inter-rater reliability of the DID rubric for 21 case-based presentations during the Fall 2013 semester. Composite scores for the case-based presentations demonstrated good inter-rater reliability with an ICC of 0.628. Conclusions Teaching methods utilizing active learning are described for this DID elective. The rubric for the student developed oral case-based presentations demonstrated good inter-rater reliability amongst evaluators and could be modified for use in other professional courses

Survey of Pharmacist-Managed Primary Care Clinics Using Healthcare Failure Mode and Effect Analysis (HFMEA)

Objectives: The primary objective was to expand upon results of a previously piloted patient perception survey with Healthcare Failure Mode and Effect Analysis (HFMEA), to identify areas within pharmacist-managed clinics needing improvement. Methods: The survey was adapted for use in pharmacist-managed clinics. Patients completed the survey following regularly scheduled pharmacist appointments. Data were analyzed with a method adapted from HFMEA. Product scores could range from five to 25. A product of five indicates that pharmacists are doing a good job on the items that patients place the most value on, while a product score of 25 indicates that pharmacists are doing a poor job. A score greater than or equal to ten was used to identify areas for improvement. Results: Seventy-one patients completed surveys. Thirteen components were assessed and no item achieved a mean product greater than or equal to ten. The survey item with the highest mean product pertained to discussion of potential medication side effects (mean: 7.06; interquartile range: 5-10). Analysis of each survey item found that all survey items had multiple individual responses that provided a product score of greater than or equal to ten. The survey items most frequently listed in the overall population as being most valued were “Told you the name of each of your medicines and what they are used for”, “Answered your questions fully,” and “Explained what your medicines do”. Conclusions: Educational components provided during pharmacist-managed clinic appointments are aligned with patients’ needs and are successfully incorporating the components that patients value highly in a patient-healthcare provider interaction. The HFMEA model can be an important teaching tool to identify specific processes in need of improvement and to help enhance pharmacists’ self-efficacy, which may further improve patient care

Retuning the Catalytic Bias and Overpotential of a [NiFe]-Hydrogenase via a Single Amino Acid Exchange at the Electron Entry/Exit Site

The redox chemistry of the electron entry/exit site in Escherichia coli hydrogenase-1 is shown to play a vital role in tuning biocatalysis. Inspired by nature, we generate a HyaA-R193L variant to disrupt a proposed Arg-His cation-π interaction in the secondary coordination sphere of the outermost, "distal", iron-sulfur cluster. This rewires the enzyme, enhancing the relative rate of H 2 production and the thermodynamic efficiency of H 2 oxidation catalysis. On the basis of Fourier transformed alternating current voltammetry measurements, we relate these changes in catalysis to a shift in the distal [Fe 4S 4] 2+/1+ redox potential, a previously experimentally inaccessible parameter. Thus, metalloenzyme chemistry is shown to be tuned by the second coordination sphere of an electron transfer site distant from the catalytic center

Teaching residents to teach: preparing faculty and clinical educators

Abstract from the 114th Annual Meeting of the American Association of Colleges of Pharmacy, Chicago, IL, July 13-17, 2013

Health impact assessment for air pollution in the presence of regional variation in effect sizes: the implications of using different meta-analytic approaches

The estimated health effects of air pollution vary between studies, and this variation is caused by factors associated with the study location, hereafter termed regional heterogeneity. This heterogeneity raises a methodological question as to which studies should be used to estimate risks in a specific region in a health impact assessment. Should one use all studies across the world, or only those in the region of interest? The current study provides novel insight into this question in two ways. Firstly, it presents an up-to-date analysis examining the magnitude of continent-level regional heterogeneity in the short-term health effects of air pollution, using a database of studies collected by Orellano et al. (2020). Secondly, it provides in-depth simulation analyses examining whether existing meta-analyses are likely to be underpowered to identify statistically significant regional heterogeneity, as well as evaluating which meta-analytic technique is best for estimating region-specific estimates. The techniques considered include global and continent-specific (sub-group) random effects meta-analysis and meta-regression, with omnibus statistical tests used to quantify regional heterogeneity. We find statistically significant regional heterogeneity for 4 of the 8 pollutant-outcome pairs considered, comprising NO2, O3 and PM2.5 with all-cause mortality, and PM2.5 with cardiovascular mortality. From the simulation analysis statistically significant regional heterogeneity is more likely to be identified as the number of studies increases (between 3 and 30 in each region were considered), between region heterogeneity increases and within region heterogeneity decreases. Finally, while a sub-group analysis using Cochran's Q test has a higher median power (0.71) than a test based on the moderators' coefficients from meta-regression (0.59) to identify regional heterogeneity, it also has an inflated type-1 error leading to more false positives (median errors of 0.15 compared to 0.09)

Life in 2.5D: Animal Movement in the Trees

The complex, interconnected, and non-contiguous nature of canopy environments present unique cognitive, locomotor, and sensory challenges to their animal inhabitants. Animal movement through forest canopies is constrained; unlike most aquatic or aerial habitats, the three-dimensional space of a forest canopy is not fully realized or available to the animals within it. Determining how the unique constraints of arboreal habitats shape the ecology and evolution of canopy-dwelling animals is key to fully understanding forest ecosystems. With emerging technologies, there is now the opportunity to quantify and map tree connectivity, and to embed the fine-scale horizontal and vertical position of moving animals into these networks of branching pathways. Integrating detailed multi-dimensional habitat structure and animal movement data will enable us to see the world from the perspective of an arboreal animal. This synthesis will shed light on fundamental aspects of arboreal animals’ cognition and ecology, including how they navigate landscapes of risk and reward and weigh energetic trade-offs, as well as how their environment shapes their spatial cognition and their social dynamics