Evelyn R. Hermes-DeSantis

The Role of Colesevelam Hydrochloride in Hypercholesterolemia and Type 2 Diabetes Mellitus

Objective: To evaluate the safety and efficacy of colesevelam hydrochloride for the treatment of hypercholesterolemia and type 2 diabetes mellitus. Data Sources: Literature retrieval was accessed through MEDLINE/PubMed (1950–March 2010), Web of Science (1980–March 2010), and International Pharmaceutical Abstracts (1977–March 2010) using the terms colesevelam, dyslipidemia, hypercholesterolemia, and type 2 diabetes mellitus. References from publications identified were reviewed for additional resources. In addition, abstracts presented at the most recent (2009) American Diabetes Association, American Association of Clinical Endocrinologists, and European Association for the Study of Diabetes annual meetings were searched for relevant original research. Study Selection and Data Extraction: All articles in English identified from the data sources were evaluated. All relevant studies evaluating the safety and efficacy of colesevelam in hypercholesterolemia and/or type 2 diabetes mellitus were included. Priority was placed on data obtained from human randomized controlled trials. Data Synthesis: Seventeen clinical trials were reviewed and evaluated. Of the clinical trials evaluating colesevelam in hypercholesterolemia, 3 evaluated monotherapy, 4 evaluated combination therapy with hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, and 6 evaluated combination therapy with other lipid-lowering therapies. In the type 2 diabetes mellitus trials, colesevelam was evaluated in combination with metformin, sulfonylureas, insulin, and rosiglitazone and sitagliptin. A review of the clinical trials provided evidence that colesevelam monotherapy effectively reduces low-density lipoprotein cholesterol (LDL-C). Additionally, the use of colesevelam in combination with other lipid-lowering therapies further reduces LDL-C. Colesevelam also effectively reduces hemoglobin A1c in patients with type 2 diabetes mellitus. The safety and tolerability of colesevelam appear to be improved from that of older-generation bile acid sequestrants, with adverse effects similar to those with placebo in monotherapy and type 2 diabetes mellitus trials. Conclusions: Colesevelam is a safe and effective option for the treatment of hypercholesterolemia and type 2 diabetes mellitus. It can fulfill a useful role in combination with HMG-CoA reductase inhibitors for hypercholesterolemia and should be considered in patients with type 2 diabetes mellitus with concomitant hypercholesterolemia.

Anaphylaxis to medications containing meat byproducts in an alpha-gal sensitized individual

Delayed anaphylaxis to red meat is an allergy that has been increasingly recognized over the last few years. The mechanism involves an IgE reaction to an oligosaccharide, galactose-alpha1,3-galactose (alpha-gal), found in nonprimate mammals and tick glycoproteins. The reaction can consist of anaphylaxis, urticaria, or angioedema and occurs in response to ingestion of mammalian meat, such as beef, lamb, pork, or venison. The mechanism of sensitization has been found to be associated with bites from Amblyomma americanum, the lone star tick. The proposed mechanism of sensitization is that the tick bite stimulates production of IgE to alpha-gal, and the IgE then binds to high-affinity IgE receptors on mast cells and basophils. When mammalian meat is later ingested by a sensitized individual, the alpha-gal antigen in the meat binds the IgE, which results in the release of mediators, such as histamine, from these cells. Magnesium stearate is a pharmaceutical excipient, which is added to tablets to facilitate lubrication during powder particle molding in the manufacturing process. This inactive ingredient can be synthesized from organic fatty acids of either bovine or vegetable origin. It is produced by a chemical reaction of magnesium chloride with sodium stearate or by a reaction of magnesium oxide, hydroxide, or carbonate with stearic acid at elevated temperatures. Stearic acid has a chain length with a beneficial friction coefficient reduction, which allows multilayers to form on the surface of medication and facilitates lubrication. Although it is a theoretical concern, there have not yet been any reports of a cross-reaction between allergy to alpha-gal and medications that contain magnesium stearate, a meat byproduct. Our case presents a patient with alpha-gal allergy as well as allergic reactions to numerous medications that contain magnesium stearate. The correlation between his reactions to meat and to these medications suggests that the medication reactions may have been due to alpha-gal in the magnesium stearate. Alpha-gal has not been definitively found in magnesium stearate, as this study has yet to be conducted. The correlation is theoretical. Our patient is a 48-year-old man with hypertension, Keinboch’s disease with chronic pain, and recurrent anaphylaxis who presented for evaluation of allergy to red meat. He had no personal or family history of asthma, allergic rhinitis, or other food allergy. He reported that for the last 25 years, he has had episodes of edema of the larynx and tongue, diffuse hives, dyspnea, wheezing, abdominal cramping, diarrhea, edematous testicles, and a sense of impending doom approximately 4 to 5 hours after eating hamburger, steak, or venison. Reactions typically required treatment with epinephrine. The delay in time between eating dinner and the reaction caused a delay in diagnosis for many years. Notably, he had been a hunter since the age of 11 and had sustained countless tick bites over the years. He was evaluated by an allergist and had an alpha-gal IgE of 95.90 (Labcorp: normal <0.35) and a tryptase level of 9 ng/mL (Quest: normal 2-10). He also had a venison IgE of 0.35, pork and lamb IgE of 0.14, but beef, chicken, and turkey IgE of <0.08. It is important to note that his negative beef immunoassay in the setting of a positive immunoassay to alpha-gal is not consistent with the literature on alpha-gal. However in our evaluation, and similar to what has been described in related reports, he was originally negative to milk and meats on commercially available percutaneous skin testing, but subsequent prick-prick skin testing with fresh meats revealed positive responses to beef, lamb, and pork. With avoidance of red meats, he has experienced no reactions; however, he has had symptoms with medications that contain magnesium stearate. After taking medications prescribed as a gelatin capsule, including acetaminophen (Tylenol, McNeil Consumer Healthcare, Fort Washington, Pa) and naproxen (Aleve, Bayer HealthCare LLC, Whippany, NJ), he experienced immediate onset diarrhea and chest tightness, which resolved with the use of diphenhydramine (Benadryl, McNeil Consumer Healthcare, Fort Washington, Pa). With lisinopril tablets (Aurobindo Pharma Limited, Hyderbad, India), he experienced laryngeal edema, abdominal cramping, nausea, and diarrhea, which resolved after stopping lisinopril. Approximately 3 to 4 hours after taking hydrocodone bitartrate and/or acetaminophen (Vicodin, AbbVie Inc, North Chicago, Ill), he experienced hives, which were relieved 4 hours after the use of diphenhydramine (Benadryl). Similarly, he experienced hives after the use of clonidine. Each of these medications has one inactive ingredient in common: magnesium stearate, a potential meat byproduct. According to the manufacturers, magnesium stearate in the patient’s medications was derived from either bovine or vegetable sources. The possibility that alpha-gal may be present in the patient’s medications warrants consideration. Ever since he identified magnesium stearate as the common denominator, he has avoided medications that contain magnesium stearate and has had no further reactions. He currently tolerates compounded oral suspensions of clonidine and oxycodone. Our case highlights the possible cross-reaction between allergy to alpha-gal and meat byproducts, such as magnesium stearate, which has yet to be described in the literature. Because patients with alpha-gal allergy can experience life-threatening anaphylaxis to mammalian meat, it is exceedingly important to recognize the

Evidence for the Use of Epoprostenol to Treat Raynaud’s Phenomenon With or Without Digital Ulcers:

Objective: To review the evidence for using intravenous (IV) epoprostenol to treat Raynaud’s phenomenon (RP). Data Sources: The databases MEDLINE (1946 to March 2016), PubMed, and International Pharmaceutical Abstracts were searched using the terms epoprostenol, Flolan, Raynaud’s disease, and CREST syndrome. Further literature sources were identified by reviewing article citations. Study Selection and Data Extraction: All English-language, clinical trials and case series evaluating IV epoprostenol for the management or treatment of RP were included. Lower-quality evidence were incorporated due to limited information. Data Synthesis: Seven small uncontrolled studies/case series, 1 small placebo controlled study, and 1 larger randomized trial were identified and included. There was no consistent measurement of efficacy utilized, but improvements in hand temperature, RP attack duration and frequency were commonly associated with IV epoprostenol treatment (5 trials). There were conflicting data regarding effect sustainability, with 5 trials showing long-term effects and 3 showing immediate effects. Fewer ischemic ulcers developed during treatment with IV epoprostenol in 1 trial compared to conventional treatment. Ulcer healing ocurred in 2 trials. Common adverse effects included hypotension, headache, flushing, gastrointestinal symptoms, and jaw pain. Conclusions: Available evidence supports the use of IV epoprostenol for treatment of severe RP in patients refractory or intolerant to standard therapies. The dose, titration schedule, and duration of IV epoprostenol utilized in studies varied, but a conservative approach to initiation should be considered. Patients who do not respond to intermittent infusions and have severe digital ischemia may require more aggressive regimens.

Analysis of Social Media Interactions Between Pharmaceutical Companies and Consumers: The Power of the ''Like''

Background: The way in which pharmaceutical companies are using social media is vitally important in staying competitive, but the way social media users respond is equally if not more important. This study aimed to evaluate the use of social media by the top 20 pharmaceutical companies and to determine how much consumers interacted with these posts. Results: The top 20 pharmaceutical companies included in this study were present in varying degrees on Twitter, YouTube, and Facebook (90%, 70%, and 50%, respectively). A linear regression analysis between pharmaceutical company interactions and corresponding consumer interactions for each social media platform did not find a statistically significant association (r 2 = 0.44, 0.49, and 0.22, respectively). Conclusion: In a descriptive review of the social media posts analyzed, this study found pharmaceutical company posts to relate to disease state awareness, business updates, and community outreach projects.

The Power of Genes A Case of Unusually Severe Systemic Toxicity After Localized Hepatic Chemoembolization With Irinotecan-Eluted Microspheres for Metastatic Colon Cancer

Objective: To report a case of systemic irinotecan toxicity following regional transarterial chemoembolization with drug-eluting beads loaded with irinotecan (DEBIRI-TACE) in a patient later found to have a homozygous mutation for UGT1A1*28. Case Summary: An 80-year-old woman presented with a cecal colon cancer with synchronous metastases to the liver. After resection of the primary tumor, the patient underwent DEBIRI-TACE with 100 mg of irinotecan to treat the residual disease in the liver. A week after this procedure, the patient developed grade 4 neutropenia, and later, alopecia. Eventually, it was found that the patient had a mutation of UDP glucuronosyltransferase 1 family polypeptide A1 (UGT1A1), which provided a reasonable explanation for the observed reaction. Discussion: The toxic effects of irinotecan are well understood. Patients with genetic polymorphisms of the genes encoding for the enzyme UGT1A1 may have increased incidence of irinotecan-associated toxicities because of decreased clearance of the active metabolite SN38 via the glucuronidation pathway. To date, there have been limited publications describing systemic adverse events following TACE or DEBIRI-TACE and, based on a thorough literature search, none following these procedures in patients with UGT1A1 polymorphisms. Based on the scoring results of the Naranjo algorithm (7), we are confident in attributing the observed reaction to the patient’s genetic polymorphism. Conclusion: Although genetic testing prior to the initiation of irinotecan therapy is not currently recommended, assessment of UGT1A1 polymorphism is warranted when severe adverse events typical of systemic therapy manifest following DEBIRI-TACE.

Differentiating predatory scholarship: best practices in scholarly publication

The intent of this article is to define predatory publishing, identify the risks and costs associated with publishing scholarship with these types of organizations and to provide recommendations for best practices how a potential author can protect themselves against predatory organizations.

Comparison of Postdoctoral Pharmacy Training Programs: Drug Information Residencies and Medical Information Fellowships

Pharmacy graduates interested in postdoctoral training opportunities in drug information or Medical Information have the option to pursue either a fellowship within the pharmaceutical industry or a clinical residency. Limited resources exist for pharmacy students to gain insight into the differences between drug information (DI) and medical information (MI) training programs. The purpose of this project is to identify available opportunities for postdoctoral training in DI or MI disciplines and to identify similarities and differences between them. DI residencies and MI fellowships were identified by examination of the American Society of Health-System Pharmacists (ASHP) and the American College of Clinical Pharmacy (ACCP) residency directories, the ASHP Personal Placement Service (PPS) index, and online keyword searching for nonindexed programs. The authors investigated individual programs via publicly available information to classify core responsibilities and skill sets developed; a total of 24 DI residency programs and 33 MI fellowships focusing or containing at least 1 component in medical information were evaluated. All ASHP-accredited DI residencies offered teaching, formulary management, adverse drug reaction and medication error reporting, drug utilization evaluation, and policy development as professional growth opportunities. The most commonly encountered development activities in MI fellowships were creating standard response documents, collaborating with cross functional teams, teaching or precepting, and reviewing promotional materials. Institutions and health care providers (HCPs) are the primary recipients of DI services whereas MI services respond to consumers, payors, HCPs, and external organizations. Employment prospects commonly overlap between the 2 training programs.

Use of nitroglycerin ointment to treat primary and secondary Raynaud’s phenomenon: a systematic literature review

Raynaud’s phenomenon (RP) is a microvascular condition in which reversible ischemic attacks occur in the extremities. Due to the unpredictable nature of these attacks, pharmacologic agents that can be administered on as-needed basis are currently being sought after. Topical nitrates are well suited for as-needed use, and several different formulations have been studied for the treatment of RP, including ointments, gels, patches, and tapes. However, these different dosage forms are not all equal in terms of safety and efficacy, and not every one is commercially available for use in clinical practice. Nitroglycerin ointment is commercially available, and it has less systemic side effects than other topical formulations. Since its role in the treatment of RP has not yet been completely established, we performed a systematic search of Medline, Embase, and the Cochrane Central Register of Controlled Trials to evaluate its safety and efficacy. A total of 1125 studies were identified, and 7 were included in our review. Although the included studies used different measures of efficacy, the majority reported positive responses to nitroglycerin ointment. The benefit of nitroglycerin ointment in the treatment of RP may be further realized through more robust investigation.

Disaster Preparedness: Biological Threats and Treatment Options

Biological disasters can be natural, accidental, or intentional. Biological threats have made a lasting impact on civilization. This review focuses on agents of clinical significance, bioterrorism, and national security, specifically Category A agents (anthrax, botulism, plague, tularemia, and smallpox), as well as briefly discusses other naturally emerging infections of public health significance, Ebola virus (also a Category A agent) and Zika virus. The role of pharmacists in disaster preparedness and disaster response is multifaceted and important. Their expertise includes clinical knowledge, which can aid in drug information consultation, patient‐specific treatment decision making, and development of local treatment plans. To fulfill this role, pharmacists must have a comprehensive understanding of medical countermeasures for these significant biological threats across all health care settings. New and reemerging infectious disease threats will continue to challenge the world. Pharmacists will be at the forefront of preparedness and response, sharing knowledge and clinical expertise with responders, official decision makers, and the general public.

Publish or perish: Success with publication in pharmacy residency training

BACKGROUND AND PURPOSE Pharmacy residency training standards require development of medical writing skills. These skills are fundamental to pharmacy clinicians and scholars alike. Despite this requirement, new practitioners and seasoned clinicians frequently struggle with scholarly development and manuscript generation for a variety of reasons, ranging from lack of experience or familiarity with the process of peer-review submission to time constraints. EDUCATIONAL ACTIVITY AND SETTING We describe a process for fostering pharmacy resident scholarship and publication utilized at Robert Wood Johnson University Hospital, including the stages of the project development process and corresponding responsibilities during each phase of the manuscript submission process. From identification of interest, to project and manuscript development, review, submission, revision, and reflection, our postgraduate pharmacy residents receive guidance and structure from a preceptor mentor to usher them through this experience for the first time. FINDINGS The program has had success utilizing this structured approach to supporting residency publication efforts, with the preparation of 23 manuscripts that have resulted in peer-reviewed publications from 28 residents graduating between 2013 and 2017. This results in a resident authorship rate of 82%. SUMMARY Although medical writing and manuscript development may not be an intuitive process, it is imperative that preceptors and individuals interacting with postgraduate pharmacy trainees consider exposing their trainees to this process, with foresight into thinking about a structured approach to publication at the onset of project development.