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

Impact of a Modified Jigsaw Method for Learning an Unfamiliar, Complex Topic

Objective: The aim of this study was to use the jigsaw method with an unfamiliar, complex topic and to evaluate the effectiveness of the jigsaw teaching method on student learning of assigned material (“jigsaw expert”) versus non-assigned material (“jigsaw learner”). Innovation: The innovation was implemented in an advanced cardiology elective. Forty students were assigned a pre-reading and one of four valvular heart disorders, a topic not previously taught in the curriculum. A pre-test and post-test evaluated overall student learning. Student performance on pre/post tests as the “jigsaw expert” and “jigsaw learner” was also compared. Critical Analysis: Overall, the post-test mean score of 85.75% was significantly higher than that of the pre-test score of 56.75% (p<0.05). There was significant improvement in scores regardless of whether the material was assigned (“jigsaw experts” pre=58.8% and post=82.5%; p<0.05) or not assigned (“jigsaw learners” pre= 56.25% and post= 86.56%, p<0.05) for pre-study. Next Steps: The use of the jigsaw method to teach unfamiliar, complex content helps students to become both teachers and active listeners, which are essential to the skills and professionalism of a health care provider. Further studies are needed to evaluate use of the jigsaw method to teach unfamiliar, complex content on long-term retention and to further examine the effects of expert vs. non-expert roles. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received), employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties.   Type: Not

Osteopoikilosis and multiple exostoses caused by novel mutations in LEMD3 and EXT1 genes respectively - coincidence within one family

<p>Abstract</p> <p>Background</p> <p>Osteopoikilosis is a rare autosomal dominant genetic disorder, characterised by the occurrence of the hyperostotic spots preferentially localized in the epiphyses and metaphyses of the long bones, and in the carpal and tarsal bones <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. Heterozygous <it>LEMD3 </it>gene mutations were shown to be the primary cause of the disease <abbrgrp><abbr bid="B2">2</abbr></abbrgrp>. Association of the primarily asymptomatic osteopokilosis with connective tissue nevi of the skin is categorized as Buschke-Ollendorff syndrome (BOS) <abbrgrp><abbr bid="B3">3</abbr></abbrgrp>. Additionally, osteopoikilosis can coincide with melorheostosis (MRO), a more severe bone disease characterised by the ectopic bone formation on the periosteal and endosteal surface of the long bones <abbrgrp><abbr bid="B4">4</abbr><abbr bid="B5">5</abbr><abbr bid="B6">6</abbr></abbrgrp>. However, not all MRO affected individuals carry germ-line <it>LEMD3 </it>mutations <abbrgrp><abbr bid="B7">7</abbr></abbrgrp>. Thus, the genetic cause of MRO remains unknown. Here we describe a familial case of osteopoikilosis in which a novel heterozygous <it>LEMD3 </it>mutation coincides with a novel mutation in <it>EXT1</it>, a gene involved in aetiology of multiple exostosis syndrome. The patients affected with both <it>LEMD3 </it>and <it>EXT1 </it>gene mutations displayed typical features of the osteopoikilosis. There were no additional skeletal manifestations detected however, various non-skeletal pathologies coincided in this group.</p> <p>Methods</p> <p>We investigated <it>LEMD3 </it>and <it>EXT1 </it>in the three-generation family from Poland, with 5 patients affected with osteopoikilosis and one child affected with multiple exostoses.</p> <p>Results</p> <p>We found a novel c.2203C > T (p.R735X) mutation in exon 9 of <it>LEMD3</it>, resulting in a premature stop codon at amino acid position 735. The mutation co-segregates with the osteopoikilosis phenotype and was not found in 200 ethnically matched controls. Another new substitution G > A was found in <it>EXT1 </it>gene at position 1732 (cDNA) in Exon 9 (p.A578T) in three out of five osteopoikilosis affected family members. Evolutionary conservation of the affected amino acid suggested possible functional relevance, however no additional skeletal manifestations were observed other then those specific for osteopoikilosis. Finally in one member of the family we found a splice site mutation in the <it>EXT1 </it>gene intron 5 (IVS5-2 A > G) resulting in the deletion of 9 bp of cDNA encoding three evolutionarily conserved amino acid residues. This child patient suffered from a severe form of exostoses, thus a causal relationship can be postulated.</p> <p>Conclusions</p> <p>We identified a new mutation in <it>LEMD3 </it>gene, accounting for the familial case of osteopoikilosis. In the same family we identified two novel <it>EXT1 </it>gene mutations. One of them A598T co-incided with the <it>LEMD3 </it>mutation. Co-incidence of <it>LEMD3 </it>and <it>EXT1 </it>gene mutations was not associated with a more severe skeletal phenotype in those patients.</p

2019 Update to the American College of Clinical Pharmacy Pharmacotherapy Didactic Curriculum Toolkit

Introduction: The American College of Clinical Pharmacy (ACCP) Pharmacotherapy Didactic Curriculum Toolkit was created by the 2008 ACCP Educational Affairs Committee to provide guidance to schools and colleges of pharmacy for didactic pharmacotherapy curricular development. The toolkit was revised and updated by the 2016 ACCP Educational Affairs Committee. Objectives: In accordance with the ACCP Board of Regents decision to update the toolkit every 3 years, the 2019 ACCP Publications Committee was charged with updating the 2016 toolkit to guide adequate disease state inclusion and depth of pharmacotherapy coverage in pharmacy curricula. Methods: The committee retained the competency-based tier definitions and organization of the 2016 toolkit. Multiple literature resources were reviewed to assess medical conditions responsive to drug therapy for inclusion in the 2019 toolkit. The committee also reviewed the tier designation for all toolkit entries for appropriateness, given recent advances in medical care and evolving patient care responsibilities of clinical pharmacists. Updates to the toolkit were made by consensus with electronic voting when required. Results: The 2019 toolkit contains 302 topics, including 94 (31%) tier 1, 133 (44%) tier 2, and 75 (25%) tier 3 entries. There are 26 additional topics in the updated toolkit, including 12 new tier 1 topics that are generally treated with nonprescription medications. Eleven new topics were added to tier 2, and 20 topics were added to tier 3 (including 11 topics in the Oncologic Disorders section). The tier classification of some conditions was changed to reflect current pharmacy practice expectations. Conclusion: As with the 2016 toolkit, the large number of tier 1 topics will require schools and colleges to employ creative teaching strategies to achieve practice competence in all graduates. The large number of tier 2 topics highlights the importance of postgraduate training and experience for pharmacy graduates desiring to provide direct patient care