Biosimilars and Novel Insulins Background: Insulin therapy is the mainstay of treatment for type 1 diabetes and may be necessary in type 2 diabetes. Current insulin analogues present a more physiological profile, are effective, and with less risk of hypoglycemia, but they are expensive. Biosimilar insulins should offer the advantages of insulin analogues at reduced costs. In addition, current rapid-acting insulin analogues are not fast enough to control excessive postprandial glucose excursions in many patients. Areas of Uncertainty: Biosimilar insulins demonstrated that are safe and effective, but interchangeability and automatic substitution remain an issue. Ultrafast-acting insulins should reduce postprandial hyperglycemia and improve flexibility in insulin dosing. Data sources: This systematic review was conducted following widely recommended methods. We searched for each topic in Medline, Embase, the Cochrane Library, and SCISEARCH for relevant citations for the appropriate period. Therapeutic Advances: LY2963016 and MK-1293 are biosimilar insulins of insulin glargine, and SAR342434 is a biosimilar of insulin lispro. The abbreviated developed program demonstrated comparable efficacy and safety and supports their use for treatment of people with diabetes but no interchangeability. Faster-acting insulin aspart is a new formulation of insulin aspart with accelerated subcutaneous absorption. Faster aspart demonstrated noninferiority in reducing HbA1c as compared to insulin aspart with superiority in controlling postprandial hyperglycemia without increasing hypoglycemia, and flexible insulin dosing. Conclusions: Biosimilar insulins have comparable PK-PD profiles and equivalent efficacy and safety to original insulins at a lower price, making them available for more people with diabetes. Faster aspart is the first ultrafast-acting insulin. New upcoming clinical trials and more clinical experience with faster aspart will show the real potential of this new insulin. Address for correspondence: Section Chief, Diabetes Reference Unit, Endocrinology and Nutrition Department, Clinic University Hospital Valencia, Av. da. Blasco Ibáñez, 17, 46010 Valencia, Spain. E-mail: francisco.j.ampudia@uv.es The author has no conflicts of interest to declare. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Comparing Nonopioids Versus Opioids for Acute Pain in the Emergency Department: A Literature Review Background: Pain is the most common reason for patient visits in the emergency department (ED). Opioids have been long considered the standard of care for acute pain in the ED. Because of the opioid crisis, investigation and implementation of novel practices to manage pain is needed. The use of various nonopioids has been suggested as a plausible alternative to opioids, with emerging literature to support its use for acute pain in the ED. Study Question: To evaluate the safety, efficacy, opioid-sparing effects of nonopioids in patients who present with acute pain in the ED. Data Sources: We systematically searched PubMed and EMBASE (July 1970 to January 2019). Study Design: Randomized controlled trials that evaluated nonopioids versus opioids in the ED were eligible. The clinical outcomes measured were change in pain scores compared with baseline, the incidence of adverse events, and use of rescue analgesia. Results: Twenty-five randomized controlled trials that evaluated the use of nonopioids in 2323 patients [acetaminophen (APAP) (n = 651), diclofenac (n = 547), ketamine (n = 272), ketorolac (n = 225), lidocaine (n = 219), ibuprofen (n = 162), ibuprofen & APAP (n = 162), hydroxyzine & dihydroergotamine (n = 85)] met inclusion criteria. Four trials found significant greater reductions in pain scores, favoring nonopioids. In all trials, the duration of pain relief provided by nonopioids was not sustained over an extended period. Eighteen trials reported no significant differences in reduction of pain scores. Two trials reported improved pain reduction with opioids and one trial reported noninferiority. Conclusions: Evidence from primary literature suggests that nonopioids could be a feasible alternative to opioids for management of acute pain in the ED as it is effective, safe, and decreases the need for rescue analgesia. Address for correspondence: Assistant Director of Pharmacy, Mount Sinai Queens, Long Island City, Queens NY, 25–10 30th Avenue, Long Island City, NY 11102. E-mail: billy.sin@mountsinai.org The authors have no conflicts of interest to declare. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.americantherapeutics.com). Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Acetazolamide-Associated Hyperosmolar Hyperglycemic Nonketotic Syndrome No abstract available

Carfilzomib-Induced Pulmonary Hypertension No abstract available

Inappropriate Use of Aztreonam Background: Aztreonam is not a preferred empiric antibiotic because of variable susceptibilities compared with alternative agents. In addition, it has no Gram-positive activity, necessitating coadministration with vancomycin when used empirically, and is more costly when compared with other Gram-negative active agents. Aztreonam is often given to patients with a reported penicillin allergy without further investigation into the reaction or other relevant allergy information. Study Question: How frequently is aztreonam being used inappropriately? Study Design: We conducted a retrospective chart review at an academic medical center to assess the appropriateness of our aztreonam use. Measures and Outcomes: Our primary outcome was frequency of appropriate aztreonam use, based on a true IgE-mediated allergy reported for each patient. We evaluated whether the patients had tolerated a beta-lactam in the past, and what the reported allergic reaction was. Results: We included 165 patients and found that 46.7% of our aztreonam use was inappropriate, based on previous use of a beta-lactam, or no documentation of an IgE-mediated response. Of the patients with a documented beta-lactam allergy, 63 (38.2%) patients had no allergy manifestation listed, and 37 (22.4%) patients had a non–IgE-mediated allergy manifestation. Of the total population, 61 (37%) patients had tolerated a beta-lactam in the past. Conclusions: Aztreonam should be avoided, except in the case of a true IgE-mediated allergic reaction. Our goal was to reduce the inappropriate use of aztreonam at our institution by one or more of the following: educating providers, reviewing aztreonam orders, requiring answering of order questions, or requiring an indication for use. Penicillin skin testing and desensitization are options as well. Address for correspondence: 600 S 43rd Street, 108T, Philadelphia, PA 19104. E-mail: mking3509@gmail.com L. Rose is on the speakers' bureau for Allergan. M. King is on the speakers' bureau for Tetraphase. The remaining authors have no conflicts of interest to declare. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Hundred Years of Insulin Therapy: Purified Early Insulins Background: The discovery of insulin has changed dramatically the outcome of patients with type 1 diabetes, giving them the possibility to survive. This is of particular concern due to the fact that type 1 diabetes most frequently occurs in children who were destined to die in ketoacidosis coma. Areas of Uncertainty: From insulin discovery to the availability of human insulin and human insulin analogs to be used in diabetes therapy, a series of problems have arisen as the difficulty of insulin purifications, the animal insulin used by the first researches were in fact contaminated by proteins, fats, and other impurities, and the presence of side effects such as allergy, antibodies generation, and lipoatrophy. Data Source Literature: Data strictly related to the argument have been searched in Pub Med and used. Results: Starting from insulin discovery in 1921 to nowadays, significant efforts have been made by a series of researches to purify animal insulin, discover the molecular structure of human insulin, and develop methods to synthetize human insulin and then insulin analogs. Conclusions: The history of insulin discovery here reported is fascinating; insulin is a hormone, a product of biotechnology, a field of research that saved and save the life of many diabetic patients. Address for correspondence: E-mail: annunziata.lapolla@unipd.it The authors have no conflicts of interest to declare. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Examining the Causes and Consequences of Increasing Insulin Costs With Prospective Interventions No abstract available

Paliperidone-Associated Priapism in an Autistic Child No abstract available

Cefepime-Associated Myoclonic Seizures No abstract available

Angioedema in an Immunocompromised Patient No abstract available