Physician experiences with sodium-glucose cotransporter (SGLT2) inhibitors, a new class of medications in type 2 diabetes, and adverse effects.

AIM: The primary aim of our study is to identify physicians who have witnessed a complication attributed to sodium-glucose cotransporter (SGLT2) inhibitors. The secondary aim is to determine the type, severity, and setting of the event (inpatient versus outpatient). BACKGROUND: Diabetes is an increasing public health burden with 9.9% of Canadians expected to be diagnosed with it in 2020. A prominent change with respect to treatment options since the publication of the revised Diabetes Canada guidelines in May 2016 concerned the SGLT2 inhibitors. Their favorable clinical profile has increased interest among clinicians, but there is still reason for caution. Because these drugs are new, the balance of benefits versus risks is not well understood. METHODS: We conducted a cross-sectional survey of all in-practice physicians (excluding pediatricians). Data were collected through an online survey. FINDINGS: Our survey identified 154 physicians who have identified one or more adverse drug reactions (ADRs) related to SGLT2 inhibitor use. A total of 173 ADRs were identified. In total, 20.6% of family physician respondents had witnessed one or more ADRs. The most common complication is mycotic infection (82 cases) with 47% identified as a low level of severity and occurring mostly in the outpatient setting. The second most common complication is diabetic ketoacidosis (43 cases) with 67% identified as a high level of severity and occurring mostly in the inpatient setting. Other identified complications include hyperkalemia (6 cases), renal insufficiency (15 cases), and even amputation (2 cases). Our survey is the first to document real-world complications from SGLT2 inhibitors. In the outpatient setting, mycotic infections are most common and most often benign. In the inpatient setting, diabetic ketoacidosis is the most common and is severe. This is an important take-home message for family physicians to tailor their practice and vigilance according to the practice setting.

Intraosseous administration of antidotes - a systematic review.

CONTEXT: Intraosseous (IO) access is an established route of administration in resuscitation situations. Patients with serious poisoning presenting to the emergency department may require urgent antidote therapy. However, intravenous (IV) access is not always readily available. OBJECTIVE: This study reviews the current evidence for IO administration of antidotes that could be used in poisoning. The primary outcome was mortality as a surrogate of efficacy. Secondary outcomes included hemodynamic variables, electrocardiographic variables, neurological status, pharmacokinetics outcomes, and adverse effects as defined by each article. METHODS: A medical librarian created a systematic search strategy for Medline, subsequently translated to Embase, BIOSIS, PubMed, Web of Science, Cochrane, Database of Abstracts of Reviews of Effects (DARE), and the CENTRAL clinical trial register, all of which we searched from inception to 30 June 2016. Interventions included IO administration of selected antidotes. Articles included volunteer studies, poisoning, or other resuscitation contexts such as cardiac arrest, burns, dehydration, seizure, hemorrhagic shock, or undifferentiated shock. We considered all human studies and animal experiments to the exception of in vitro studies. Two reviewers independently selected studies, and a third adjudicated in case of disagreement. Three reviewers extracted all relevant data. Three reviewers evaluated the risk of bias and quality of the articles using specific scales according to each type of study design. RESULTS: A total of 47 publications (46 articles and one abstract) met our inclusion criteria and described IO administration of 13 different antidotes. These included one case series and 21 case reports describing 26 patients, and 25 animal experiments. Of those, seven human case reports and four animal experiments specifically reported the use of antidotes in poisoning. Human case reports suggested favorable outcomes with IO use of atropine, diazepam, hydroxocobalamin, insulin, lipid emulsion, methylene blue, phentolamine, prothrombin complex concentrate, and sodium bicarbonate. Clinical outcomes varied according to the antidote used. The only reported adverse event was ventricular tachycardia following IO naloxone. Regarding the animal experiments, IO administration of lipid emulsion and of hydroxocobalamin showed improved survival in bupivacaine-poisoned rats and in cyanide-intoxicated swine, respectively. Animal data also suggested an equivalent bio-availability between IO and IV administration for atropine, calcium chloride, dextrose 50%, diazepam, methylene blue, pralidoxime, and sodium bicarbonate. Adverse effect reporting of fat emboli after IO administration of sodium bicarbonate, for example, was conflicting due to the significant heterogeneity in the timing of lung examination across studies. CONCLUSION: The evidence supporting the use of IO route for the administration of antidotes in a context of poisoning is scarce. The majority of the evidence consists of case reports and animal experiments. Common antidotes such as acetylcysteine, fomepizole, and digoxin-specific antibody fragments have not been studied or reported with the use of the IO route. Despite the low-quality evidence available, IO access is a potential option for antidotal treatments in toxicological resuscitation when IV access is unavailable.

Educating medical trainees on medication reconciliation: a systematic review.

BACKGROUND: Effective medication reconciliation is critical in reducing the risk of preventable adverse drug events. Medical trainees are often responsible for medication reconciliation on admission, transfer and discharge of the most vulnerable patients; therefore, it is important that trainees are educated on this aspect of quality care. METHODS: We conducted a systematic review using MEDLINE and EMBASE databases to identify education initiatives targeted at improving trainee skill and knowledge in carrying out medication reconciliation. Studies published in English or French between July 1980 and July 2013, where the primary focus of the article was the role of medical trainees in conducting medication reconciliation, and where trainee-specific data was reported, were included. Included articles must have reported trainee-specific data. Given the anticipated heterogeneity and array of outcomes, we were unable to employ a specific tool in assessing the risk of bias across studies. RESULTS: Seven studies met pre-specified eligibility criteria, indicating the lack of published education initiatives targeted towards improving trainee knowledge and experience. Four described an education intervention targeted towards students completing internal medicine clerkship, while the remaining 3 were implemented among residents. Although no two interventions were the same, 5 out of 7 included an experiential component. CONCLUSIONS: Varying success was achieved with medication reconciliation education interventions. While some noted improved competence and/or confidence amongst trainees, namely undergraduate medical students, others noted little effect resulting from the intervention.