Gina Daubney Garrison

Varenicline: A first-line treatment option for smoking cessation

BACKGROUND Varenicline acts as a partial agonist/antagonist with affinity and selectivity for alpha(4) beta(2) nicotinic acetylcholine receptors. This activity at the nicotine-receptor level may help patients achieve smoking cessation by reducing cravings/withdrawal symptoms and smoking satisfaction. OBJECTIVE This article reviews the literature on the pharmacologic properties, therapeutic efficacy, and tolerability of varenicline for smoking cessation. METHODS Pertinent controlled clinical trials, meta-analyses, meeting abstracts, case reports, and review articles published in English between 1966 and May 2008 were identified through searches of MEDLINE and OVID using the terms varenicline, smoking, tobacco cessation, and CP 526555. RESULTS Eight clinical trials were identified that compared <or=12 weeks of varenicline treatment with placebo and/or bupropion sustained release (SR); one of the trials reported follow-up data to 24 weeks, and the remainder reported data to 52 weeks. During treatment with oral varenicline titrated to 1 mg BID, CO-confirmed 4-week continuous quit rates/continuous abstinence rates (CQRs/CARs) in weeks 9 through 12 ranged from 43.9% (odds ratio [OR] = 3.85 [95% CI, 2.69-5.50; P < 0.001 vs placebo]; OR = 1.90 [95% CI, 1.38-2.62; P < 0.001 vs bupropion SR]) to 65.4% (OR = 2.98 [95% CI, 1.78-4.99; P < 0.001 vs placebo]). In 4 of these trials, varenicline 1 mg BID was associated with significantly higher CQRs/CARs compared with placebo at week-52 follow-up, ranging from 21.9% (P < 0.001) to 34.6% (P = 0.036). One trial reported a significantly higher CAR at 52 weeks with varenicline compared with bupropion SR (23.0% vs 14.6%, respectively; P = 0.004), and another reported a significantly higher CAR at 52 weeks with varenicline compared with nicotine replacement therapy (25.9% vs 19.8%, respectively; P = 0.040). In a relapse-prevention study that included a 12-week extension period for participants who were abstinent after the initial 12 weeks of treatment, CARs were significantly improved at 24 weeks with varenicline relative to placebo (70.5% vs 49.6%, respectively; OR = 2.48; 95% CI, 1.95-3.16; P < 0.001). Treatment with varenicline was generally well tolerated in study populations with no major comorbidities. In a pooled analysis of 2 Phase III trials, the most commonly reported adverse events (AEs) with varenicline, bupropion SR, and placebo were nausea (28.8%, 9.9%, and 9.1%, respectively), insomnia (14.2%, 21.5%, and 12.6%), and headache (14.2%, 11.1%, and 12.4%). In a pooled analysis of 2 identically designed Phase III trials, bupropion SR was associated with the highest overall rates of discontinuation due to all-cause AEs compared with varenicline and placebo (13.9%, 9.5%, and 8.2%, respectively) and due to AEs considered related to study drug (12.1%, 7.9%, and 6.4%). In double-blind clinical trials of varenicline, nausea was the most frequently reported AE (16.3%-41.9%). Varenicline treatment should begin 7 days before the proposed smoking quit date; dose titration is recommended to minimize dose-related nausea. Based on postmarketing reports of serious AEs in vareniclinetreated patients, caution is recommended when operating vehicles or heavy machinery. Patient education and monitoring for potential AEs are also recommended, particularly in patients with a history of psychiatric illness. CONCLUSIONS Varenicline has a unique mechanism of action compared with other first-line options for smoking cessation. Available clinical-trial data support its use as an effective and generally well-tolerated therapy for smoking cessation in healthy adult smokers, although there is a need for further efficacy and safety evaluation in the general population, particularly those with comorbid conditions.

Factors Affecting Prescribing of the Newer Antidepressants

OBJECTIVE: To survey various prescriber types and specialties to determine whether differences exist in prescribing patterns for the newer antidepressants. DESIGN, SETTING, AND PARTICIPANTS: A survey about prescribing of the newer antidepressants was mailed to 1500 New York state licensed prescribers who were randomly selected from membership rosters. Nurse practitioners; physician assistants and physicians in family medicine, primary care, general practice, and internal medicine; and psychiatrists were included. MAIN OUTCOME MEASURES: Prescriber responses regarding factors involved with choosing among the newer antidepressants. RESULTS: A total of 508 surveys (36%) were returned, of which 398 (29%) were acceptable for analysis. In choosing among the newer antidepressants, most prescribers ranked patient diagnosis and past success as a high priority, and free drug samples and drug-representative detailing as a low priority. The majority of each prescriber type preferred fluoxetine for major depression and depression associated with fatigue; paroxetine for concomitant anxiety and depression, as well as for panic disorder; and sertraline for geriatric patients and patients with suicidal ideation. Differences existed between the prescriber groups when asked whether prescribing habits for the newer antidepressants were based on familiarity with a particular agent (p = 0.0009) and on labeled indications (p = 0.002). CONCLUSIONS: This is the first study to demonstrate prescribing preferences for the newer antidepressants among different prescriber groups. Additional studies are needed to determine predictors of patient response to newer antidepressants and clinical guidelines for their use.

Comparison of Natural Product Use Between Primary Care and Nephrology Patients

BACKGROUND: The use of natural products is increasing, but healthcare professionals may underestimate the use of these agents by patients. It is unknown whether natural product use differs between primary care and specialty clinic patients, such as those in a nephrology clinic. OBJECTIVE: To compare patterns of natural product use between primary care and nephrology clinic patients. METHODS: One thousand adult patients from each clinic were randomly mailed an anonymous questionnaire to determine current and past use of natural products. RESULTS: A total of 491 surveys were returned, for an overall response rate of 26% (25% primary care; 28% nephrology clinic). Current use of natural products was similar between the primary care and nephrology groups (34% vs 29%, respectively; p = NS). Primary care patients were more likely to have taken a natural product in the past (57% vs 45%; p < 0.05); Echinacea was the most common product taken by those patients (26%). Green tea was the most common natural product taken by nephrology clinic patients (18%). More primary care patients took Echinacea compared with nephrology clinic patients (26% vs 12%; p < 0.01). Adverse reactions led to discontinuation of the natural product in 7% of respondents. CONCLUSIONS: Active use of natural products was similar between the survey respondents. Documentation and monitoring of natural product use by healthcare professionals working with primary care and nephrology clinic patients are recommended.

Finding Time for Faculty Development

Faculty members are responsible for demonstrating excellence in the tripartite mission of teaching, scholarship, and service, yet few faculty members have formal training in these areas.1-5 Faculty development programs can help close this educational gap by promoting desirable teaching, leadership, and scholarly behaviors, but they are often plagued by low attendance and participation by faculty members.1,6 This may be attributable largely to the limited “free time” available for professional development, a reason commonly cited by faculty members at academic health centers or health-related universities.7 Many colleges and schools of pharmacy have explored ways of increasing attendance and participation in faculty development by using online or on-demand programs such as Education Scholar (Western University of Health Sciences, Pomona, CA, and American Association of Colleges of Pharmacy, Alexandria, VA), Mediasite Education Grand Rounds (Sonic Foundry, Inc, Madison, WI) presentations, and Webinars.8 The popularity of social networking sites also presents a new, innovative opportunity for “virtual” faculty development. The impact of using online book clubs to increase participation in faculty development is largely undocumented in the literature. The American Association of Colleges of Pharmacy (AACP) Women Faculty Special Interest Group (SIG) has begun offering an online book club focused on academic and leadership skills to engage its members in faculty development. Since spring 2009, the SIG Networking Committee has sponsored a series of 4 online book discussions using a social networking site (www.ning.com). Book titles relevant to faculty members were selected to promote self-development in the areas of teaching, communication, and leadership, while stimulating opportunities for networking among members. While reading and reflecting on new knowledge are important first steps in professional development, active learning and peer collaboration were structured in this forum to improve learning and accountability. Assessment of the outreach achieved by the book club series was evaluated informally. Reading and discussing professional literature about academic and leadership skills appeared to be an attractive self-development and networking opportunity for SIG members, with over 100 members registering on the book club Website. The level of interest in this innovative form of faculty development was evident and promising, so it was surprising to see an inverse relationship between member interest and level of participation in the online book club discussion. The conundrum and concern is that while SIG members want the book club to continue, and they remain interested in participating in future book club offerings, few have taken the opportunity to actively engage in the book club discussions. Data from an informal survey of SIG members suggest 2 main reasons for the low level of participation in the online book club. First, members indicated that they did not know how to register for or access the online book club to participate. This feedback suggests that the level of e-mail communication about registering and accessing the book club was insufficient and requires modification. Second, members reported lack of time to read books. The SIG appreciated such time constraints after the first year of the book club, and limited the 2010 selections to “quick read” books with a length of approximately 100 pages. Despite this change, few faculty members acquired the books and even fewer commented on the postings. Various attempts to increase discussion, via e-mail reminders and the development of a readers guide, also had little impact on participation. The Women Faculty SIG online book club will continue to offer an intentional way of growing academic and leadership skills while inviting a virtual dialogue among faculty members with varying experience and expertise. The challenge faced by any group using this format is to optimally stimulate and continually engage participation, thereby fostering a more meaningful form of professional development. We continue to review and test methods for improving member engagement in meaningful use of the professional development and networking opportunities offered in a virtual book club environment. Individual faculty development takes time and deliberate attention. Time always will be a limited commodity, so the question becomes what form of professional development faculty members prefer. Furthermore, this begs the question in the academy why we struggle to make time for faculty development and networking opportunities. Many educators and clinicians are challenged to find time in our busy schedules to read, reflect, discuss, and network, yet we encourage and expect students, residents, and fellows to engage in these very activities. Should we not step back and secure “protected time” to advance our personal and professional development to complement that being developed in those we teach and mentor? Have we become too busy for our own good?

High-Dose Versus Standard-Dose Amoxicillin for Acute Otitis Media

BACKGROUND: Emergence of drug-resistant bacteria has led to a recommendation to use high-dose (HD) amoxicillin (80–90 mg/kg/d) rather than standard-dose (SD) amoxicillin (40–45 mg/kg/d) to treat children with acute otitis media (AOM). OBJECTIVE: To compare the efficacy and tolerability of HD versus SD amoxicillin among children with AOM who were considered at low risk for infection with antibiotic-resistant bacteria. METHODS: A double-blind, randomized, 3-year clinical trial was conducted using participants who met the following criteria: age >3 mo, weight ≤18 kg, diagnosed with AOM, and candidates for treatment with amoxicillin. The primary endpoint was treatment success at a 3- to 4-day follow-up visit based on the clinical decision to continue the prescribed antibiotic therapy for AOM. Other endpoints included duration of illness, number of office visits and telephone calls related to illness, total number of subsequent AOM episodes, and number of adverse effects. RESULTS: The absolute difference in antibiotic failure rate with SD versus HD amoxicillin at the follow-up visit was nonsignificant (95% CI–1.5% to 3.4%; p = 0.78). The mean duration of illness was similar for both doses of amoxicillin (3 ± 2 d). The number of office visits and telephone calls related to illness and the number of subsequent AOM episodes did not differ between the 2 treatment groups. HD amoxicillin did not result in a greater incidence of adverse effects than SD amoxicillin. CONCLUSIONS: HD amoxicillin had neither benefit nor detriment compared with SD for AOM in children at low risk for infection with antibiotic-resistant bacteria.

An asynchronous learning approach for the instructional component of a dual-campus pharmacy resident teaching program.

Objective. To describe the shift to an asynchronous online approach for pedagogy instruction within a pharmacy resident teaching program offered by a dual-campus college. Design. The pedagogy instruction component of the teaching program (Part I) was redesigned with a focus on the content, delivery, and coordination of the learning environment. Asynchronous online learning replaced distance technology or lecture capture. Using a pedagogical content knowledge framework, residents participated in self-paced online learning using faculty recordings, readings, and discussion board activities. A learning management system was used to assess achievement of learning objectives and participation prior to progressing to the teaching experiences component of the teaching program (Part II). Assessment. Evaluation of resident pedagogical knowledge development and participation in Part I of the teaching program was achieved through the learning management system. Participant surveys and written reflections showed general satisfaction with the online learning environment. Future considerations include addition of a live orientation session and increased faculty presence in the online learning environment. Conclusion. An online approach framed by educational theory can be an effective way to provide pedagogy instruction within a teaching program.

High-dose versus standard-dose amoxicillin/clavulanate for clinically-diagnosed acute bacterial sinusitis: A randomized clinical trial

Background The recommended treatment for acute bacterial sinusitis in adults, amoxicillin with clavulanate, provides only modest benefit. Objective To see if a higher dose of amoxicillin will lead to more rapid improvement. Design, setting, and participants Double-blind randomized trial in which, from November 2014 through February 2017, we enrolled 315 adult outpatients diagnosed with acute sinusitis in accordance with Infectious Disease Society of America guidelines. Interventions Standard-dose (SD) immediate-release (IR) amoxicillin/clavulanate 875 /125 mg (n = 159) vs. high-dose (HD) (n = 156). The original HD formulation, 2000 mg of extended-release (ER) amoxicillin with 125 mg of IR clavulanate twice a day, became unavailable half way through the study. The IRB then approved a revised protocol after patient 180 to provide 1750 mg of IR amoxicillin twice a day in the HD formulation and to compare Time Period 1 (ER) with Time Period 2 (IR). Main measure The primary outcome was the percentage in each group reporting a major improvement—defined as a global assessment of sinusitis symptoms as “a lot better” or “no symptoms”—after 3 days of treatment. Key results Major improvement after 3 days was reported during Period 1 by 38.8% of ER HD versus 37.9% of SD patients (P = 0.91) and during Period 2 by 52.4% of IR HD versus 34.4% of SD patients, an effect size of 18% (95% CI 0.75 to 35%, P = 0.04). No significant differences in efficacy were seen at Day 10. The major side effect, severe diarrhea at Day 3, was reported during Period 1 by 7.4% of HD and 5.7% of SD patients (P = 0.66) and during Period 2 by 15.8% of HD and 4.8% of SD patients (P = 0.048). Conclusions Adults with clinically diagnosed acute bacterial sinusitis were more likely to improve rapidly when treated with IR HD than with SD but not when treated with ER HD. They were also more likely to suffer severe diarrhea. Further study is needed to confirm these findings. Trial registration ClinicalTrials.gov Identifier: NCT02340000.

Varenicline for 4 weeks prior to target quit date reduces prequit date smoking and increases 12-week abstinence

Commentary on: HajekPMcRobbieHJMyersKE. Use of varenicline for 4 weeks before quitting smoking: decrease in ad lib smoking and increase in smoking cessation rates. Arch Intern Med 2011;171:770–7.