Incretin Analogs for Weight Management in Adults Without Diabetes.

OBJECTIVE: This is a narrative review of incretin analogs and their effect on weight management in adult without diabetes. DATA SOURCES: Randomized controlled trials were identified by English language. PubMed/MEDLINE, Scopus, and Embase databases were searched from inception through June 2023 to identify all pertinent trials reporting outcomes on efficacy and safety search using the terms: tirzepatide, semaglutide, liraglutide, and obesity. STUDY SELECTION AND DATA EXTRACTION: Selected studies were included if the study population was composed of adults without diabetes being treated by glucagon-like peptide 1 (GLP-1) receptor agonists or glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 agonists for weight management, and weight loss was assessed as a primary outcome. DATA SYNTHESIS: Fifteen studies involving 3 pharmacotherapies (liraglutide, semaglutide, and tirzepatide) were identified. Efficacy data supporting the use of these agents for weight management were promising when compared to placebo and/or other behavioral therapies. Percent weight loss ranged from 5.7% to 11.8%, 14.9% to 17.4%, and 15% to 20.9% for liraglutide, semaglutide, and tirzepatide, respectively. Safety data were relatively similar across all trials and identified gastrointestinal adverse effects as most common. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Glucagon-like peptide 1 agonists are preferred for overweight or obese patients by the American Gastroenterological Association. Future guidelines may address tirzepatides' place in therapy as new evidence comes forth. Providers should consider patient-specific factors such as cost, adverse effects, drug interactions, and comorbidities when prescribing these agents and provide education regarding the need for concurrent diet and exercise modifications. CONCLUSIONS: All incretin analogs in this review are superior to placebo when used for weight management in adults without diabetes.

The Struggle is Real: Facilitating Pharmacy Student Success on Rotations When Challenges Arise.

Pharmacy preceptors are pivotal to facilitating and maximizing student learning on experiential rotations. However, preceptors may encounter a variety of behaviors or barriers that can hinder student success. Although some guidance exists for preceptors, emerging learner challenges along with new educational outcomes call for an updated practical approach to promoting student success on rotations. This paper provides preceptors with a structured approach to facilitate success for students who exhibit challenges on rotations. Four categories that preceptors can use to identify behaviors and barriers to learning are outlined - knowledge, skills, professional attitudes and behaviors, and external factors including the Social Determinants of Learning™. We describe strategies to help preceptors identify and categorize these challenges and provide a stepwise approach to facilitate student success.

Tezepelumab in the Treatment of Uncontrolled Severe Asthma.

OBJECTIVE: To review the pharmacology, efficacy, and safety of subcutaneous tezepelumab in the treatment of severe uncontrolled asthma. DATA SOURCES: The PubMed database and ClinicalTrials.gov were searched using the following terms: tezepelumab, Tezspire, AMG157, and MEDI9929. STUDY SELECTION AND DATA EXTRACTION: Articles published in English between January 2000 and March 2022 related to pharmacology, safety, and clinical trials were assessed. DATA SYNTHESIS: In a phase 2 trial, tezepelumab at low, medium, and high doses reduced the annualized asthma exacerbation rate by 62%, 71%, and 66%, respectively, when compared with placebo (P < 0.001). In addition to significant reduction of asthma exacerbation rate in the overall treatment population, a phase 3 trial showed significant reduction of asthma exacerbation across all subgroups analyzed regardless of serum eosinophil count (EOS), fractionated exhaled nitric oxide (FeNO) level, or allergic status as determined by IgE sensitivity. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Tezepelumab is indicated to treat nonallergic and noneosinophilic severe uncontrolled asthma phenotypes in addition to type 2 inflammatory asthma. When selecting the most appropriate biologic agent, consider the risks, benefits, and costs. There is a paucity of data on the efficacy of tezepelumab in patients with comorbid conditions. In the case of a patient presenting with uncontrolled severe asthma with such comorbid conditions, it may be prudent to consider a biologic therapy that can target both. CONCLUSION: Tezepelumab has shown clinical utility in severe uncontrolled asthma regardless of phenotype, fulfilling the need for treatment options in individuals with severe, uncontrolled, noneosinophilic, and nonallergic asthma.

Intranasal Olopatadine-Mometasone in the Treatment of Seasonal Allergic Rhinitis.

OBJECTIVE: To review the pharmacology, efficacy, and safety of intranasal olopatadine hydrochloride-mometasone furoate (OM) combination in the treatment of seasonal allergic rhinitis (SAR). DATA SOURCES: The PubMed database and ClinicalTrials.gov were searched using the following terms: mometasone + olopatadine, GSP301, mometasone furoate, and olopatadine hydrochloride. STUDY SELECTION AND DATA EXTRACTION: Articles published in English between January 1987 and August 2022 related to pharmacology, safety, and clinical trials were assessed. DATA SYNTHESIS: In 2 phase II clinical trials, twice-daily (BID) and once-daily (QDay) intranasal OM demonstrated significant improvements in reflective total nasal symptom score (rTNSS) (BID P < 0.001 and QDay P < 0.001) and instantaneous total nasal symptom score (iTNSS) (BID P < 0.001 and P < 0.0001; QDay P < 0.001 and P < 0.0001). In 2 phase III clinical trials, BID OM showed significant improvements in rTNSS vs. placebo (P < 0.001), olopatadine monotherapy (P = 0.03 and P = 0.003), and mometasone monotherapy (P = 0.02 and P = 0.059). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: OM is indicated for treatment of SAR symptoms. Caution with use must be considered for certain high-risk patients, existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. Due to its quick and sustained onset of action, OM may be an ideal agent for initial treatment of moderate-severe SAR for patients 12 years and older. CONCLUSION: OM significantly improves SAR symptoms and is a viable treatment option in short-term SAR.

Dual- Versus Mono-Bronchodilator Therapy in Moderate to Severe COPD: A Meta-analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) guidelines recommend both long-acting and dual bronchodilator therapy. It is unclear if there are differences in efficacy and safety. OBJECTIVE: This meta-analysis evaluates the efficacy of dual therapy with long-acting ß-agonist (LABA) + long acting muscarinic antagonist (LAMA) compared with monotherapy with LAMA for COPD. METHODS: We searched PubMed, CINAHL, and Web of Science databases from inception through March 2020 to identify English-language, prospective randomized controlled trials (RCTs) that compared dual therapy with monotherapy in adult patients with COPD. Risk of bias was assessed using the Jadad score. Overall analysis was performed using Review Manager 5.3. Treatment effect was determined with the random-effects model using the Mantel-Haenszel method and was reported as mean difference (MD) with 95% CI. RESULTS: A total of 18 RCTs were included (n = 6086; median Jadad score 5/5) that compared LAMA + LABA with LAMA. There was a greater improvement in forced expiratory volume at 1 s (FEV1) with dual therapy compared with LAMA: MD = 0.08; 95% CI = [0.05, 0.11]. There was no difference in St George Respiratory Questionnaire (SGRQ) scores between groups: OR = -0.85; 95% CI = [-1.83, 0.13]. There were no differences in overall adverse events (OR = 1.00; 95% CI = 0.92, 1.09), serious adverse events (OR = 1.01; 95% CI = 0.86, 1.18), or cardiovascular events (OR = 0.88; 95% CI = 0.58, 1.34). CONCLUSION AND RELEVANCE: Dual therapy improves FEV1 and is as safe as LAMA. Dual therapy does not improve SGRQ scores more than LAMA.

Teduglutide for the Treatment of Short Bowel Syndrome.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and safety of the newly approved drug, teduglutide, for the treatment of short bowel syndrome (SBS). DATA SOURCES: Literature was retrieved through PubMed (1966-March 2014) using the search term teduglutide. The authors applied the filters Humans and English language, resulting in 47 publications. STUDY SELECTION AND DATA EXTRACTION: The authors reviewed the 47 citations to extract those that were published clinical trials. Bibliographies of recent review articles and editorials were evaluated for additional pertinent publications for inclusion. The methods and results from each of the trials were extracted. DATA SYNTHESIS: Teduglutide has been studied in SBS in 3 phase III trials. Teduglutide decreases parenteral nutrition (PN) volume requirements, with 1 study showing a reduction of 4.4 ± 3.8 L/wk with teduglutide 0.05 mg/kg versus 2.3 ± 2.7 L/wk with placebo; P < 0.001. In another study, teduglutide improved graded response scores, which are based on the intensity and duration of the reduction of PN use (16/35 assigned to teduglutide 0.05 mg/kg vs 1/16 assigned to placebo; P = 0.007). The dosing range studies have indicated that the optimal dose of teduglutide is 0.05 mg/kg daily subcutaneously. There are a number of adverse effects reported in the trials, including abdominal pain or distention, injection site reactions, nausea, headaches, and fluid overload among others. There is also a concern for the development of malignancy with teduglutide, and therefore, it is not recommended in patients with active gastrointestinal malignancies. CONCLUSIONS: Overall, teduglutide appears to be a promising agent for the treatment of SBS.

Pharmacist perceptions of delivering patient care through telehealth.

PURPOSE: To evaluate pharmacists' perceptions of the benefits of and barriers to telehealth as experienced in actual telehealth visits with patients. METHODS: This qualitative study used virtual focus groups and a validated questionnaire (the Health Optimum Telemedicine Acceptance [HOTA] survey) to assess telehealth facilitators and barriers. Participants were included if they were licensed pharmacists utilizing telehealth in the outpatient setting. Pharmacist focus group responses were transcribed and analyzed using Miles and Huberman's qualitative data analysis model. RESULTS: Six pharmacists participated in this study. Their responses were placed into 2 categories: clinical effectiveness and patient experience. All participants had performed at least 20 virtual visits, and all agreed that telehealth improved patients' health status. Respondents agreed that telehealth results in more frequent patient interactions and allows for provision of multiple types of care virtually. However, technological difficulties and the inability to provide physical examinations and obtain laboratory values were identified limitations. The surveyed pharmacists agreed that the main benefit that patients gained from telehealth was the elimination of transportation concerns, allowing increased access to care. However, pharmacists voiced their concern for patient privacy and barriers to educating patients on proper use of medical devices. CONCLUSION: Pharmacists felt that telehealth was useful in several clinical scenarios. However, they also identified opportunities to improve its development in clinical practice. Further investigation must be done to better grasp impediments to telehealth in order to provide the most effective patient care.

Donor-Site Complication of Severe Valgus Ankle Deformity in an Adult With Ehlers-Danlos Syndrome Following Free Vascularized Fibular Grafting.

Valgus deformity of the ankle joint is a well-known and relatively common donor-site complication of free vascularized fibular graft harvest in children. Due to children having naturally greater ligamentous laxity than adults, the tibiofibular syndesmosis can be compromised with the loss of the fibular shaft, leading to valgus ankle deformity (VAD). Syndesmotic stabilization with screws is commonly recommended in subsets of pediatric patients at the greatest risk of this complication. In adults, the occurrence of VAD is seldom reported in the literature following fibular graft harvest. As such, no recommendation for syndesmotic stabilization exists in the adult population. We present a case of end-stage VAD in an adult patient with Ehlers-Danlos syndrome (EDS) following free vascularized fibular graft harvest. We hypothesize that other patients with generalized joint hypermobility may face the same complication and, thus, recommend the consideration of syndesmotic stabilization or primary syndesmotic fusion at the time of graft harvest in this patient population.

Corticosteroid Exposure in the Treatment of Severe COPD Exacerbations.

BACKGROUND: Recent literature and guidelines support treatment of severe acute exacerbation of COPD (AECOPD) with prednisone 40 mg (or equivalent) for 5 days. OBJECTIVE: The purpose of this study was to determine whether systemic corticosteroids were being prescribed at the appropriate dose and duration in the treatment of severe AECOPD at a large academic medical institution. METHODS: This was a single-center, retrospective, observational study conducted to evaluate corticosteroid prescribing patterns for adults admitted for severe AECOPD from March to May 2019 at a large academic medical institution. Appropriate therapy was defined as: prednisone 40 mg (or equivalent) for 5 days. The primary outcome was to determine the frequency of appropriate dose and duration. The secondary outcomes were to identify the frequency of appropriate dose or duration, compare the prevalence of adverse effects, such as new/worsening hyperglycemia or hypertension, and compare 30- and 90-day readmission rates. RESULTS: Of the 190 patients included, 16 (8.4%) had an appropriate duration and 8 (4.2%) an appropriate dose. Only 4 patients (2.1%) had both appropriate corticosteroid dose and duration. New/worsening hyperglycemia occurred in 96 (50.5%), and hypertension developed in 13 (6.8%). Thirty-day readmission occurred in 46 (24.2%) and 90-day readmission in 78 (41.1%). These were more likely in those without appropriate dose and duration. CONCLUSION: Systemic corticosteroids for the treatment of severe AECOPD are not prescribed in accordance with evidence-based recommendations at this institution. This might result in a greater incidence of adverse effects and readmissions.

A scaffolded problem-based learning course for first-year pharmacy students.

BACKGROUND AND PURPOSE: There has been an increased use of active learning pedagogies in pharmacy curricula. Structured, complex pedagogies such as problem-based learning (PBL) may require rigorous training for students to be successful. We aim to describe the development and implementation of an introductory PBL course for first-year pharmacy students. We describe the theoretical framework for course development, including the educational philosophies informing the course design. Development of PBL skills and professional behavior were evaluated using student self-assessment throughout the course. EDUCATIONAL ACTIVITY AND SETTING: This introductory PBL course was developed using educational philosophies to scaffold student learning of the pedagogy and development of PBL skills. A student self-assessment was administered at two time points throughout the course. The self-assessment contained items related to PBL skills and professional behaviors. Self-assessment scores were compared with facilitator evaluations of student performance to determine reliability of self-assessment results. FINDINGS: Eighty-eight students completed both self-assessments (93.6% response rate). Self-assessment of PBL skills increased significantly. There was no improvement in self-assessed professional behaviors. Self-assessment scores did not correlate with facilitator assessment of student performance in a small group. SUMMARY: Integrating a scaffolded, theoretically sound educational approach to introduce students to the PBL pedagogy improves students' self-assessed PBL skills but not professional behavior.

Incorporating verbal defense into problem-based learning.

INTRODUCTION: The objective of this project was to evaluate the effect of adjusting the solution reporting phase of problem-based learning (PBL) while keeping core components of the pedagogy constant. METHODS: A PBL course for third year pharmacy students changed delivery of the problem solution from a written format to a verbal defense. Comparisons were made between the written format and verbal defense groups. The primary outcome was the change in the motivation domain of the Motivated Strategies for Learning Questionnaire (MSLQ). Secondary outcomes included evaluation of the learning strategies domain of the MSLQ, changes in MSLQ scores within each group, exam scores, and themes identified using focus groups. RESULTS: There was no difference in the change of motivation and learning domains between the groups. However, scores in both groups increased significantly from the beginning to the end of the semester for both motivation and learning. There was no difference in exam scores and facilitator confidence between groups. Themes from focus groups who used the written format were appreciation of PBL outcomes, discomfort with the pedagogy, and disconnect of assessments. Themes from the verbal format group were realism, increased confidence, and comments with course logistics. CONCLUSIONS: No difference in motivation and learning was observed between the groups, although both groups improved over the course of the semester. Changes to PBL approach within the confines of the pedagogy may not impact motivation and learning.

Ambulatory care practice in the COVID-19 era: Redesigning clinical services and experiential learning.

The coronavirus disease (COVID-19) has created a variety of challenges for health care professionals, including ambulatory care clinical pharmacists. High-quality remote and minimal-contact care has become a necessity. Ambulatory care clinical pharmacists around the nation have adjusted their practice. In many cases, this included implementation of telehealth programs for comprehensive medication management. The redesign of ambulatory care Advanced Pharmacy Practice Experiences (APPE) also required quick adaptation. In this paper, we describe the clinical practice and experiential education challenges encountered by an ambulatory care clinical pharmacist workgroup in a COVID-19 "hotspot," with an emphasis on solutions and guidance. We discuss how to adapt ambulatory care clinical pharmacy practices including methods of minimal-contact care, reimbursement opportunities, tracking outcomes, and restructuring ambulatory care APPE. As ambulatory care clinical pharmacists continue to expand the services they provide in response to COVID-19, we also describe opportunities to promote pharmacists as providers during times of pandemic and into the future.

Understandability, actionability, and readability of online patient education materials about diabetes mellitus.

PURPOSE: The purpose of this study was to assess the understandability, actionability, and readability of online diabetes education materials. SUMMARY: This was a descriptive study that identified printable diabetes education materials through an online search. Materials were included from the following sources: national organizations with materials approved by expert panels, corporations with materials subject to FDA approval, and not-for-profit organizations with inter-professional advisory boards to approve materials. Topics included were basic knowledge of diabetes, hypoglycemia, insulin, and blood sugar goals. Materials were excluded if they were non-printable, contained active links, had a publication date prior to January 2011, were greater than 2 pages in length, or were pediatric focused. Understandability and actionability of the patient education materials were evaluated using the Patient Education Materials Assessment Tool (PEMAT). Descriptive statistics and inter-rater reliability analysis using the kappa statistic were utilized. Readability was assessed using the Flesch-Kincaid Grade Level and Simple Measure of Gobbledygook (SMOG) formula. Pearson correlation coefficient was calculated to assess the relationship between reading grade level and PEMAT scores. In total, 25 websites were identified, 5 of which met the inclusion criteria; 13 patient education materials were included, PEMAT scoring revealed that 4 of these met the criteria for understandability and only 1 met the criteria for actionability. There was no correlation found between PEMAT scores and reading grade levels (Pearson correlation coefficient = -0.30, p = 0.325). CONCLUSION: The majority of diabetes patient education materials reviewed scored poorly using the PEMAT. Future development of diabetes patient education materials should be designed with the goal of increasing understandability and actionability.

Adherence to GOLD Guidelines in the Inpatient COPD Population.

PURPOSE: The Global Initiative for Chronic Obstructive Lung Disease guidelines provide recommendations to manage chronic obstructive lung disease (COPD) exacerbations. This study assessed the management of inpatient COPD exacerbations at an urban teaching hospital. METHODS: A retrospective cohort analysis of adults admitted between December 2010 and August 2012 with a COPD exacerbation was conducted. Patient demographics, length of stay (LOS), Charlson comorbidity score, inpatient pulmonary medications, and 30-day readmission were collected. Descriptive statistics characterized guideline adherence and readmission. RESULTS: 94 patients were included with median LOS of 3 days (interquartile range [IQR]: 1-5 days) and median Charlson comorbidity score of 6 (IQR: 5-8). All patients received an inhaled short-acting beta agonist, and 52 (55.3%) also received an inhaled short-acting anticholinergic. Seventy-eight (83%) received systemic corticosteroids, of which 3 received guideline-recommended doses. Sixty-four (68.1%) received antibiotics for a pulmonary indication, of which 71.9% received appropriate antibiotics per indication. Of the 94 patients, 2 were managed in complete adherence with GOLD recommendations. A total of 24 (25.5%) patients were readmitted within 30 days of discharge, 9 of these for COPD. CONCLUSION: COPD exacerbation treatment deviated from GOLD recommendations. This provides opportunities for further optimization of treatment of COPD exacerbations.

As-needed intravenous antihypertensive therapy and blood pressure control.

BACKGROUND: Hospitalized patients with elevated blood pressure (BP) in most cases should be treated with intensification of oral regimens, but are often given intravenous (IV) antihypertensives. OBJECTIVE: To determine frequency of prescribing and administering episodic IV antihypertensives and outcomes. DESIGN: Retrospective review. SETTING: Urban academic hospital. PATIENTS: Non-critically ill, hospitalized patients with an IV antihypertensive order for enalaprilat, labetalol, hydralazine, or metoprolol. MEASUREMENTS: We analyzed BP thresholds for ordering and administering IV antihypertensives, the types and frequencies of IV antihypertensives administered, and the effect of IV antihypertensive use on short-term BP and adverse outcomes. The BP change during hospitalization was contrasted in those receiving IV antihypertensives between those who did and did not receive subsequent intensification of chronic oral antihypertensive regimens. RESULTS: Two hundred forty-six patients had an episodic IV antihypertensive order. One hundred seventy-two patients received 458 doses, with 48% receiving a single dose. Over 98% of episodic IV antihypertensive doses were administered for systolic blood pressure (SBP) <200 mm Hg and 84.5% for SBP <180 mm Hg. Within 6 hours of administration, there was a statistically significant decline in average SBP and diastolic BP in patients receiving IV hydralazine and labetolol. After administration of IV antihypertensives, the oral inpatient medication regimen was adjusted in 52% of patients; these patients had a greater reduction in SBP from admission to discharge than patients with no change to their oral regimens. A total of 32.6% of patients receiving treatment experienced a BP reduction of more than 25% within 6 hours. CONCLUSIONS: IV antihypertensive drugs are ordered and administered in patients with asymptomatic, uncontrolled BP for levels unassociated with substantive immediate cardiovascular risk, which may cause adverse effects.

Vulnerable COPD patients with comorbidities: the role of roflumilast.

Roflumilast is a selective phosphodiesterase-4 (PDE-4) inhibitor that was approved by the US Food and Drug Administration in February 2011 for the management of chronic obstructive pulmonary disease (COPD). Literature was retrieved through PubMed using the terms "roflumilast" and "COPD". Reference citations from publications identified were also reviewed. All articles published in English using the terms "roflumilast" and "COPD" were retrieved. For evaluation of clinical efficacy, published Phase III studies and pooled analyses of Phase III trials were included. In seven published Phase III trials, roflumilast at 500 µg daily showed improvements in lung function as measured by pre- and post-bronchodilator forced expiratory volume in 1 second. Roflumilast appears to be useful in vulnerable patients who are at high risk for exacerbations. Roflumilast was found to be effective when administered alone and with concomitant long-acting bronchodilator therapy in the Caucasian and Asian population. Patients with severe-to-very severe COPD, chronic bronchitis, and frequent history of exacerbations derived the greatest benefit with roflumilast. Compared to the standard of care therapies, roflumilast is more cost-prohibitive. Roflumilast was well tolerated, with the most common adverse events observed in clinical trials being diarrhea, nausea, and headache. Weight loss and increased risk of psychiatric events have also been observed with roflumilast in clinical trials. Roflumilast is a safe and effective option for the treatment of COPD.

Roflumilast in the management of chronic obstructive pulmonary disease.

PURPOSE: The pharmacology, pharmacokinetics, efficacy, and safety of roflumilast-the first in a new class of agents for managing chronic obstructive pulmonary disease (COPD)-are reviewed. SUMMARY: Roflumilast (Daliresp, Forest Pharmaceuticals) is an oral phosphodiesterase-4 (PDE-4) inhibitor that targets inflammatory cells involved in triggering COPD exacerbations. The only PDE-4 inhibitor approved by the Food and Drug Administration, roflumilast is available in 500-µg tablets to be administered once daily. In six placebo-controlled trials involving nearly 4500 patients with COPD of varying severity, the use of roflumilast was associated with reduced COPD exacerbations and improved lung function, as determined by spirometry, with the greatest benefits observed in patients with severe COPD who had chronic bronchitis and a history of frequent exacerbations; clinical efficacy was demonstrated in patients receiving roflumilast alone as well as those receiving concomitant inhaled long-acting ß2-agonist (LABA) therapy. The most common adverse events in clinical trials of roflumilast were diarrhea, nausea, and headache. Weight loss and an increased risk of psychiatric events have also been reported in association with roflumilast use. As roflumilast is rapidly converted to its active metabolite via cytochrome P-450 (CYP) isoenzymes, coadministration with strong CYP inducers is not recommended. Research to better define roflumilast's role in COPD management, including a study to determine whether it confers additive benefits when used in combination with standard inhaled therapies other than LABAs, is ongoing. CONCLUSION: Roflumilast is a safe and effective option for controlling COPD exacerbations in a defined subset of patients for whom the available treatment alternatives are very limited.