Collaborative drug therapy modification (CDTM): Facilitators, barriers, and perceptions of individual pharmacist participation in Georgia.

BACKGROUND: Georgia Board of Pharmacy (BOP) regulations permit pharmacists to engage in collaborative drug therapy modification (CDTM) with physicians, allowing them to perform patient assessments, adjust pharmacotherapy, and order laboratory tests. Pharmacist-led CDTM can positively affect health outcomes leading to reduced healthcare expenditures. CDTM is underutilized, with < 1% of Georgia pharmacists holding an active license to practice CDTM. OBJECTIVE(S): The objective of this study was to examine CDTM licensed pharmacists' perceptions of facilitators and barriers in providing CDTM. METHODS: Georgia-licensed CDTM pharmacists were invited to participate in a 60-minute qualitative interview. Interview questions were developed from electronic survey responses. The interview was designed to elicit information regarding perceived benefits and barriers to CDTM implementation. Guided by the Consolidated Framework for Implementation Research, thematic analysis was applied to identify themes using ATLAS.ti software to code. Themes were described qualitatively and prevalence of each was reported. RESULTS: Nine interviews were conducted, and data saturation was achieved at interview 6. After resolution of discrepancies, 100% coding agreement was reached among 2 independent researchers. Nine themes were identified, and each was categorized as a facilitator or barrier to establishing pharmacist-led CDTM in Georgia. Themes associated with facilitating were (prevalence %) (1) practice autonomy (100), (2) personal attributes (100), (3) having support (100), and (4) institutional logistics (88). Barrier themes included issues concerning (5) the Georgia BOP (100), (6) pharmacist autonomy (88), (7) lack of provider status (88), (8) institutional restrictions (75), and (9) personal development (e.g., confidence) (22). CONCLUSION: Facilitators to the establishment of pharmacist-led CDTM exist and pharmacists can capitalize on these to create successful CDTM programs. Barriers are varied, and it may be difficult to systematically address individual barriers such as pharmacist autonomy and personal development. Barriers associated with institutional restrictions, the Georgia BOP, and lack of provider status can likely be removed or addressed by policy.

The impact of synchronous hybrid instruction on students' engagement in a pharmacotherapy course.

Background: Synchronous hybrid instruction offers flexible learning opportunities by allowing a portion of students to attend class sessions on campus while simultaneously allowing the remaining students to attend remotely. Although such flexibility may offer a number of advantages for pharmacy students, one area of concern is whether online participation options within synchronous hybrid courses can promote similar levels of engagement as courses that are designed entirely for face-to-face (FTF) participation. Objectives: The objective of this study was to evaluate the impact of synchronous hybrid instruction on pharmacy students' engagement in a pharmacotherapy course. An evaluation was completed to determine if students were more likely to actively engage in class when they were participating remotely via teleconferencing technology or when FTF. Additionally, students' perspectives were evaluated to determine their views of the benefits and challenges of the hybrid model for engagement in learning. Methods: The course utilizes team-based learning to apply critical thinking skills and develop a comprehensive care plan. A mixed methods approach was used to examine students' engagement in the hybrid learning environment by quantitatively analyzing students' responses to likert-scale survey items and qualitatively analyzing their responses to open-ended survey questions. Results: Students reported they were more likely to actively listen (p=0.004), avoid distractions (p=0.008), and react emotionally to a topic or instruction (p=0.045) when FTF. There were no significant differences found in student reported note taking, asking questions, responding to questions, or engaging in group work between the two modes of participation. Content analysis identified other benefits that supported student engagement, including perceived flexibility and enhanced ability to interact during class via the teleconferencing technology. For some students, challenges that negatively impacted engagement included difficulties with internet connectivity and a sense of dislocation or isolation in the course. Conclusion: This study demonstrated that when participating in a synchronous hybrid course, students participating remotely were less likely (compared to in-person attendance) to pay close attention and react emotionally, but were just as likely to take notes and communicate with teachers and groups. Key benefits of the hybrid approach were increased flexibility and the usefulness of online communication tools, while key challenges focused on technical and psychological isolation from others. The principles of flexible learning environments and self-regulated learning provide opportunities for pharmacy educators who are interested in improving hybrid instruction in the future.

A Scoping Review Evaluating the Effect of SGLT-2 Inhibitors on Insulin Dose Requirements in Insulin-Dependent Patients With Type 2 Diabetes.

OBJECTIVE: Assess evidence describing the effect of Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors on total daily insulin (TDI) requirements in insulin-dependent patients with type 2 diabetes. DATA SOURCES: A scoping review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Protocols and Scoping Reviews (PRISMA-ScR) guidelines. The search was conducted in PubMed; citation mapping was completed in Web of Science. Filters for human studies, English language, and a publication date, from January 1, 2005 to April 12, 2021, were applied. STUDY SELECTION AND DATA EXTRACTION: Studies assessing insulin dose requirements with concurrent use of an SGLT2 inhibitor for patients with type 2 diabetes were included. DATA SYNTHESIS: Sixteen studies were included and demonstrated that addition of an SGLT2 inhibitor typically reduced TDI requirements. Insulin reductions were often statistically significant, occurring in studies evaluating (1) within subjects who received SGLT2 inhibitors, and (2) between subjects receiving SGLT2 inhibitors versus placebo. Compared with placebo, insulin dose reduction ranged from -0.72 to -19.2 units. However, studies were relatively small, not designed to assess TDI change, and some utilized fixed dose insulin protocols or empiric insulin dose reductions. CONCLUSIONS: Lowering insulin requirements may have benefits, such as decreased hypoglycemia risk, insulin resistance, and cost. Addition of an SGLT2 inhibitor may modestly reduce TDI requirements for patients with type 2 diabetes. Evidence indicating SGLT2 inhibitor use reduces TDI may lead to additional implementation in practice and inform future research. Further research is needed to clarify insulin type (i.e., basal or prandial) and degree of TDI reduction expected with addition of an SGLT2 inhibitor.

The impact of synchronous hybrid instruction on students’ engagement in a pharmacotherapy course

Background: Synchronous hybrid instruction offers flexible learning opportunities by allowing a portion of students to attend class sessions on campus while simultaneously allowing the remaining students to attend remotely. Although such flexibility may offer a number of advantages for pharmacy students, one area of concern is whether online participation options within synchronous hybrid courses can promote similar levels of engagement as courses that are designed entirely for face-to-face (FTF) participation. Objectives: The objective of this study was to evaluate the impact of synchronous hybrid instruction on pharmacy students’ engagement in a pharmacotherapy course. An evaluation was completed to determine if students were more likely to actively engage in class when they were participating remotely via teleconferencing technology or when FTF. Additionally, students’ perspectives were evaluated to determine their views of the benefits and challenges of the hybrid model for engagement in learning. Methods: The course utilizes team-based learning to apply critical thinking skills and develop a comprehensive care plan. A mixed methods approach was used to examine students’ engagement in the hybrid learning environment by quantitatively analyzing students’ responses to likert-scale survey items and qualitatively analyzing their responses to open-ended survey questions. (AU)

Evaluation of GLP-1 Receptor Agonists in Combination With Multiple Daily Insulin Injections for Type 2 Diabetes.

OBJECTIVE: To assess the available literature evaluating the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with multiple daily insulin injections (MDII). DATA SOURCES: A literature search of MEDLINE and Embase was performed (2004 to May 2020) using the following search terms: glucagon-like 1 receptor agonist, liraglutide, albiglutide, dulaglutide, exenatide, semaglutide, diabetes mellitus, and prandial insulin or bolus insulin. Additional references were obtained from cross-referencing the bibliographies of selected articles. STUDY SELECTION AND DATA EXTRACTION: All information obtained from the searches were reviewed. All relevant trials are included in this review. DATA SYNTHESIS: Eight studies met criteria for inclusion. The addition of a GLP-1 RA to multiple daily insulin injections was associated with a reduction in A1c in 7 out of 8 studies, and weight loss in 5 studies. In studies that allowed insulin adjustment after the addition of GLP-1 RA, the average total daily insulin dose was reduced in 3 studies. When evaluated, hypoglycemia frequency or other adverse events were not increased when GLP-1 RAs were added to MDII. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Guidelines do not offer recommendations regarding the use of GLP-1 RAs in combination with MDII regimens. This review evaluates current studies demonstrating efficacy and safety considerations of this combination. CONCLUSIONS: While some studies did demonstrate an improvement in A1c and reduction in insulin doses without increased hypoglycemia, larger randomized controlled trials are needed to adequately assess the benefit and safety of GLP-1 RAs in combination with MDII.

Team feedback: A missing piece of the interprofessional education puzzle.

INTRODUCTION: The ambulatory care practice model has long embraced interprofessional collaboration, well before it was formalized by the Interprofessional Education Collaborative. Establishing a mechanism to gather insight from other members of the interprofessional team may facilitate further development of interprofessional education (IPE). COMMENTARY: There is limited evidence investigating non-pharmacy trainees and medical provider perceptions of advanced pharmacy practice experience (APPE) student involvement in IPE. Most available evidence evaluates the satisfaction of non-pharmacy trainees and other health care professionals with APPE student recommendations. IMPLICATIONS: Emphasis on IPE, such as formalizing feedback from other health care professionals during experiential rotations, may assist preceptors in adapting interactions, strengthening interprofessional collaborations, and ensuring that students are valued team members who contribute to providing quality patient care.

Pharmacy Student Performance in a Capstone Course Utilizing the Pharmacists' Patient Care Process.

Objective. To develop, implement, and assess student performance and confidence in a pharmacy capstone course that used case-based instruction and the Pharmacist's Patient Care Process (PPCP) to develop patient work-up skills in third-year Doctor of Pharmacy (PharmD) students. Methods. A skills-based capstone course was developed by a team of faculty members and instructional designers that focused on patient evaluation skills and applying the steps of the PPCP to complex patient cases housed in a simulated electronic health record (SEHR). The acuity of the cases increased over the course of the semester. For each patient case, students were expected to identify drug-related problems and develop an assessment and plan based on the information provided in the SEHR. Results. Students (n=134) were assessed through weekly quizzes and two practical examinations. The average score for all quizzes was 81%. A significant correlation was found between average quiz scores and performance on the end-of-course practical examination. Student scores significantly improved from the first to the second practical examination (10.4 vs 12.9, respectively), and student confidence with regard to all course objectives significantly improved from the beginning to the end of the semester. Conclusion. A capstone course that applied the PPCP framework successfully taught third-year PharmD students the patient care skills they would need in advanced pharmacy practice experiences.

Evaluation of affective domain elements in a new pharmacy practice course.

INTRODUCTION: In 2016, new Accreditation Standards were implemented that required integration of affective domain elements (ADEs) into the Doctor of Pharmacy (PharmD) curriculum and admissions interview process. The purpose of this study is to analyze the relationship between admissions variables and performance in a new course, and to analyze the relationship between student self-assessment and faculty evaluation of their development and performance in ADEs. METHODS: Pre-pharmacy admission variables were evaluated for correlations with student performance in ADEs. Student self-assessments and faculty evaluations of performance in ADEs were also analyzed. RESULTS: Statistically significant positive correlations were found between student age and completion of at least a bachelor's degree with student self-assessment in communication and leadership. When evaluating faculty assessment, significant positive correlations were found for female performance in the areas of leadership and team readiness. There was a positive association between the Pharmacy College Admission Test (PCAT) quantitative score and performance in professionalism; while negative associations were seen between the PCAT comprehensive score and student self-assessment in self-awareness and professionalism, and between the PCAT quantitative score and student self-assessment in self-awareness (p < 0.05 for all). Median evaluation ranks by faculty members were significantly lower than the median self-evaluation ranks done by students. DISCUSSION AND CONCLUSION: This study suggests careful analysis of admissions variables in relation to ADEs may offer PharmD programs insight into how they design educational activities related to the affective domain. Additionally, evaluating multiple observations by both students and faculty members may identify patterns of growth and development in ADEs.

Impact of health literacy level on aspects of medication nonadherence reported by underserved patients with type 2 diabetes.

BACKGROUND: Medication adherence can be affected by many factors, including health literacy. The purpose of this study is to determine (1) if a relationship exists between health literacy and self-reported or objectively measured medication adherence and (2) which aspect or aspects of medication nonadherence are most associated with health literacy. SUBJECTS AND METHODS: This is a multicenter, cross-sectional survey study of adult patients with type 2 diabetes mellitus (T2DM), taking one or more antidiabetes medication for ≥6 months with a hemoglobin A1c (HbA1c) measure on record. Data collected included patient demographics (age, gender, race, language, highest level of education, injectable diabetes medication use, last HbA1c, and diabetes medication refill history) and two survey instruments (the Morisky eight-item Medication Adherence Scale [MMAS-8] and the short-form Test of Functional Health Literacy in Adults [s-TOFHLA]). Descriptive statistics and bivariate correlations were assessed, along with linear and logistic regression. RESULTS: One hundred ninety-two patients with an average HbA1c level of 8.1% were included. Of these subjects, 32.8% had limited health literacy as measured by the s-TOFHLA, 58.9% had low adherence as measured by MMAS-8, and 65.1% were nonadherent based on cumulative medication gap (CMG) analysis. Age was associated with s-TOFHLA (-0.411; P<0.01) and MMAS-8 (0.157; P<0.05) scores. HbA1c was associated with MMAS-8 (-0.209; P<0.01) and CMG (0.152; P<0.05) scores. There was no significant association between s-TOFHLA and MMAS-8 or CMG. However, s-TOFHLA was positively related to MMAS-8 question 8, assessing difficulty remembering to take medications (P=0.017). CONCLUSIONS: Health literacy level is not associated with self-reported or objectively measured medication adherence in underserved patients with T2DM. Lower health literacy scores are associated with a patient experiencing difficulty remembering to take medications.

Safety and efficacy of allopurinol in chronic kidney disease.

OBJECTIVE: To review the evidence surrounding the use of allopurinol in chronic kidney disease (CKD) and discuss safety and efficacy considerations of such use. DATA SOURCES: A literature search was conducted through MEDLINE (1950-July 2013), PubMed (1965-July 2013), and International Pharmaceutical Abstracts (1970-July 2013) using the search terms allopurinol and kidney or renal. In addition, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles in English identified from the data sources were evaluated for inclusion. DATA SYNTHESIS: Gout management with allopurinol in patients with CKD can be challenging because of the risk of adverse events and uncertain efficacy. Not all gout treatment guidelines provide recommendations for allopurinol use specifically in patients with CKD. Literature regarding the safety and efficacy of dosing allopurinol in CKD has shown inconsistent results and is based primarily on retrospective, case cohort or observational data. Some trials have demonstrated an increased risk of allopurinol-induced adverse reactions in patients with CKD, whereas others have not confirmed renal insufficiency as a risk factor. More CKD patients achieved a target uric acid level in studies where the allopurinol dose was titrated to effect as compared with those studies in which patients were given renally adjusted or untitrated allopurinol doses. CONCLUSIONS: Studies evaluating allopurinol use in patients with CKD have reported inconsistent findings relative to safety and efficacy. Providers should be aware of the potential risk of allopurinol hypersensitivity syndrome as well as the need for reducing the initiation dose and gradual titration of allopurinol to safely achieve a target serum urate level in this population.

Implementation of a pharmacy residency in a Veterans Affairs community-based outpatient clinic.

PURPOSE: The implementation of an innovative ambulatory care pharmacy residency program at a Veterans Affairs (VA) outpatient clinic is described. SUMMARY: Community-based outpatient clinics (CBOCs) are a largely underutilized resource for pharmacy residency training. Through a collaboration of the University of Georgia College of Pharmacy in Athens and Charlie Norwood VA Medical Center in Augusta, a postgraduate year 2 (PGY2) pharmacy residency program was established at the CBOC in Athens. The program graduated its first resident in 2009; components of training included (1) disease state management at an anticoagulation clinic and a newly created disease state-focused pharmacotherapy clinic, (2) participation in the planning and implementation of a new lipid management service, (3) a variety of didactic, laboratory, and experiential teaching activities at the college of pharmacy, and (4) management experiences such as completing requests for nonformulary medications, management of drug shortages, adverse drug reaction reporting, and participation in meetings of local and regional VA pharmacy and therapeutics committees. The demonstrated value of the ongoing program led to position upgrades for two CBOC clinical pharmacists and the addition of a clinical faculty member, enabling the program to offer additional learning experiences and preceptorship opportunities. CONCLUSION: A PGY2 ambulatory care residency program established in a CBOC provided a novel practice setting for the resident, helped improve patient care and pharmacy student education, and assisted in the professional development of preceptors and providers at the training site.

Rosiglitazone, myocardial ischemic risk, and recent regulatory actions.

OBJECTIVE: To review the evidence surrounding rosiglitazone and ischemic cardiovascular risk and discuss the Food and Drug Administration (FDA) decision to revise safety information and restrict access to the drug. DATA SOURCES: A literature search was conducted through MEDLINE (1950-January 2012), PubMed (1966-January 2012), and International Pharmaceutical Abstracts (1970-December 2011) using the search terms rosiglitazone and cardiovascular risk. Regulatory documents from the FDA and the Center for Drug Evaluation and Research, as well as reference citations from publications identified, were reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles in English identified from the data sources were evaluated for inclusion. DATA SYNTHESIS: Literature regarding rosiglitazone and ischemic cardiovascular risk has shown inconsistent results. Meta-analyses by the FDA, GlaxoSmithKline, and several independent research groups suggest an increased risk for myocardial infarction (MI), while others have not. Long-term, controlled trials not designed to evaluate cardiovascular outcomes did not find a significant increase in cardiovascular events and had low event rates overall. The RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes in Oral Agent Combination Therapy for Type 2 Diabetes) trial is the only prospective randomized trial to date designed to evaluate cardiovascular outcomes of rosiglitazone; the results were limited because of issues with study design and event adjudication. The only direct comparisons between rosiglitazone and pioglitazone are observational studies in which pioglitazone had a more favorable MI risk profile. CONCLUSIONS: Data involving rosiglitazone and an association with ischemic cardiovascular risk have yielded variable results. The FDA made the decision to restrict access to rosiglitazone in September 2010 by requiring GlaxoSmithKline to submit a risk evaluation and mitigation strategy (REMS). Drug labeling was revised in February 2011, and the rosiglitazone REMS program took full effect in November 2011.

Academic pharmacy and patient-centered health care: a model to prepare the next generation of pharmacists.

OBJECTIVE: To provide evidence regarding existing partnerships between academic pharmacy and primary care that focus on training practitioners in patient-centered health care (PCHC). DATA SOURCES: The report of the 2009-10 American Association of Colleges of Pharmacy Professional Affairs Committee identified 25 current U.S.-based examples of PCHC that incorporate the training and preparation of both student pharmacists and pharmacy residents. SUMMARY: The most frequently reported health care delivery model was an ambulatory care clinic followed by a Department of Veterans Affairs or military hospital clinic. Pharmacists worked alongside a variety of other health care providers in these settings. Collaboration occurred most commonly with family and internal medicine physicians but also with specialists such as psychiatrists, obstetricians/gynecologists, hematologists/oncologists, and other health care providers (e.g., nurses, physician assistants, dieticians, social workers). CONCLUSION: In light of the increasing demand for primary care services, pharmacists' documented ability to address these needs and the resulting benefits to patients, providers, and systems in these models, developing strategies for promoting pharmacist integration into PCHC is essential. Academic pharmacy provides a valuable platform for this integration through its expert faculty clinician involvement in care and practice-based research and student pharmacist and pharmacy residency training.

Calcium supplementation in postmenopausal women to reduce the risk of osteoporotic fractures.

PURPOSE: The most recent large-scale studies evaluating the effects of calcium supplementation for prevention of osteoporosis-related fractures in postmenopausal women are reviewed. SUMMARY: Osteoporosis is a very common disease associated with significant morbidity and mortality. For many years, use of a calcium supplement (preferably in combination with vitamin D to optimize calcium absorption) has been recommended for postmenopausal women to decrease fracture risk. However, five large-scale, randomized, controlled trials have called into question the benefits of calcium in reducing fracture risk, and four of the studies indicated that calcium users may be at increased risk for renal stones and gastrointestinal problems. However, all five studies had one or more important limitations, including possible selection bias and study participants' relatively high baseline calcium intake and generally low adherence to treatment regimens. Moreover, in some of the studies, vitamin D was not included in the treatment protocol or was not used at levels sufficient to optimize calcium absorption. In three of the five trials, subgroup analysis of the most treatment-adherent participants indicated significant reductions in osteoporotic fracture risk with calcium supplement use. CONCLUSION: Results of recent clinical trials indicate that calcium supplementation does not significantly reduce fracture risk in postmenopausal women. However, evidence from the same studies suggests that beneficial effects on fracture risk may be seen in women who are adherent to therapy. Postmenopausal women should continue calcium supplementation to reduce osteoporosis risk.

Instruments assessing capacity to manage medications.

OBJECTIVE: To review literature on instruments available for assessing the physical and cognitive ability to take medications as prescribed, which serve as a way to rule out reasons for nonadherence. DATA SOURCES: A PubMed search (1950-February 2008) was conducted to identify relevant articles. Additional references were obtained from cross-referencing the bibliographies of selected articles. Only journals containing English-language articles were selected for review. STUDY SELECTION AND DATA EXTRACTION: Articles that described a simulated assessment of medication management were obtained, irrespective of whether the assessment also contained data about medication adherence or was focused on older adults. DATA SYNTHESIS: Fifteen instruments were identified. Six instruments required 5 minutes or less to administer, 5 required 6-30 minutes, and 4 had no administration time data reported. A possible advantage of 3 of the instruments is that they use a subject's own medications and may therefore provide a more authentic assessment. Only 2 instruments have been tested by subjects other than the drug developers and only one has been used in 2 different populations, thereby affording some insight into generalizability. These studies have used a variety of other validated surveys/assessments to provide an indication of construct validity, including neuropsychological batteries, caregiver reports, prospective outcomes, instrumental activities of daily living, and levels of care. One instrument determined whether individuals could tell if refills existed, whom to contact, and resources to obtain medications. Three assessed numeracy literacy. CONCLUSIONS: Five instruments that measure medication management capacity should be compared for potential further use, including Beckman's tasks, due to their brevity and assessment of numeracy literacy; the Medication Management Ability Assessment, Drug Regimen Unassisted Grading Scale, and Hopkins Medication Schedule because of the evidence supporting their use; and the Medication Management Instrument for Deficiencies in the Elderly because it includes an assessment of the patient's knowledge of how to obtain more medications. No brief tool is available for the primary care setting to identify individuals with medication management problems or to guide the type and amount of support required to manage medications.

Evaluation of anticoagulation in patients with antiphospholipid syndrome.

PURPOSE: The quality of anticoagulation therapy in patients with antiphospholipid syndrome (APS) was evaluated. SUMMARY: The high risk of unnecessary anticoagulation and recent changes in the recommended International Normalized Ratio (INR) target range prompted a performance-improvement initiative to improve the care of patients with APS within the University of Iowa Hospitals and Clinics internal medicine and family medicine anticoagulation clinics. Twenty-three patients with an initial diagnosis of APS were evaluated through chart review to determine the anticoagulation indication, occurrence of thromboembolic events, and INR target range. Confirmation of APS diagnosis was made using Sapporo criteria. Recommendations were made to the patients' physicians for confirmatory APS testing and changes in the anticoagulation regimen. INR target ranges were 2.0-3.0, 2.5-3.5, and 2.5-3.0 for 57%, 39%, and 4% of patients, respectively. Only 6 (26%) of the 23 patients met Sapporo criteria for a definite diagnosis of APS. Of the 17 patients (74%) who did not meet these criteria, 8 (47%) had another indication for indefinite anticoagulation. Repeat APS testing was indicated for 7 patients, 5 of whom met Sapporo criteria for APS. A lower target INR range of 2.0-3.0 was determined appropriate for 6 (26%) of the 23 patients evaluated. CONCLUSION: A majority of patients with an initial diagnosis of APS did not meet criteria for a definite diagnosis of APS. Of those patients, approximately half had another indication for long-term anticoagulation, and one third were receiving warfarin dosages based on an INR target range that was higher than clinically indicated.

Hepatitis associated with low-dose venlafaxine for postmenopausal vasomotor symptoms.

OBJECTIVE: To report a case of drug-induced hepatitis associated with low-dose venlafaxine. CASE SUMMARY: A 60-year-old white woman receiving venlafaxine 75 mg daily for vasomotor symptoms presented after one month of therapy with nonspecific complaints, including abdominal pain. A series of diagnostic and laboratory tests revealed an enlarged liver and elevated alanine aminotransferase (ALT) up to 372 U/L, aspartate aminotransferase (AST) up to 99 U/L, gamma-glutamyltransferase (GGT) up to 962 U/L, and alkaline phosphatase up to 758 U/L. All potential hepatotoxic medications were discontinued. Within one week after stopping venlafaxine, her liver function test results showed marked improvement. Almost 4 weeks after discontinuing therapy, venlafaxine 37.5 mg was reinitiated. Her ALT, AST, GGT, and alkaline phosphatase again increased to 269, 49, 256, and 263 U/L, respectively, 6 days after resuming therapy. Upon discontinuation of venlafaxine, her liver function abnormalities resolved. DISCUSSION: This case is significant due to the severity of symptoms and consequent liver function test results involved in diagnosing drug-induced hepatitis. It is also remarkable because of the hepatotoxicity that occurred initially and on rechallenge with low-dose venlafaxine. The hepatotoxic effects of venlafaxine have been characterized as rare and idiosyncratic. The Naranjo probability scale revealed that the adverse drug event was probable. CONCLUSIONS: Venlafaxine therapy can lead to drug-induced hepatitis, even when used at low doses. Clinicians should be aware of this possible adverse effect of venlafaxine therapy and monitor patients closely after initiation of therapy.

Comparative antihypertensive effects of hydrochlorothiazide and chlorthalidone on ambulatory and office blood pressure.

Low-dose thiazide-type diuretics are recommended as initial therapy for most hypertensive patients. Chlorthalidone has significantly reduced stroke and cardiovascular end points in several landmark trials; however, hydrochlorothiazide remains favored in practice. Most clinicians assume that the drugs are interchangeable, but their antihypertensive effects at lower doses have not been directly compared. We conducted a randomized, single-blinded, 8-week active treatment, crossover study comparing chlorthalidone 12.5 mg/day (force-titrated to 25 mg/day) and hydrochlorothiazide 25 mg/day (force-titrated to 50 mg/day) in untreated hypertensive patients. The main outcome, 24-hour ambulatory blood pressure (BP) monitoring, was assessed at baseline and week 8, along with standard office BP readings every 2 weeks. Thirty patients completed the first active treatment period, whereas 24 patients completed both. An order-drug-time interaction was observed with chlorthalidone; therefore, data from only the first active treatment period was considered. Week 8 ambulatory BPs indicated a greater reduction from baseline in systolic BP with chlorthalidone 25 mg/day compared with hydrochlorothiazide 50 mg/day (24-hour mean = -12.4+/-1.8 mm Hg versus -7.4+/-1.7 mm Hg; P=0.054; nighttime mean = -13.5+/-1.9 mm Hg versus -6.4+/-1.8 mm Hg; P=0.009). Office systolic BP reduction was lower at week 2 for chlorthalidone 12.5 mg/day versus hydrochlorothiazide 25 mg/day (-15.7+/-2.2 mm Hg versus -4.5+/-2.1 mm Hg; P=0.001); however, by week 8, reductions were statistically similar (-17.1+/-3.7 versus -10.8+/-3.5; P=0.84). Within recommended doses, chlorthalidone is more effective in lowering systolic BPs than hydrochlorothiazide, as evidenced by 24-hour ambulatory BPs. These differences were not apparent with office BP measurements.

Reducing clinically significant gastrointestinal toxicity associated with nonsteroidal antiinflammatory drugs.

OBJECTIVE: To evaluate the efficacy of treatment strategies to reduce clinically significant gastrointestinal adverse effects associated with nonsteroidal antiinflammatory drugs (NSAIDs). DATA SOURCES: A MEDLINE search (1966-November 2003) was performed to identify relevant articles. Key search terms included proton-pump inhibitors, histamine H2 antagonists, misoprostol, cyclooxygenase-2 (COX-2) selective inhibitors, nonsteroidal antiinflammatory agents, stomach ulcer, prevention, and economics. Additional references were obtained from cross-referencing the bibliographies of selected articles. STUDY SELECTION AND DATA EXTRACTION: All information obtained from the MEDLINE search was reviewed. To provide the most clinically relevant information, only randomized controlled trials are included in this review. DATA SYNTHESIS: Clinically significant upper gastrointestinal adverse events, such as ulcers and ulcer complications, associated with NSAIDs are a cause of significant morbidity and mortality in the US. Interest in strategies to reduce the risk of these adverse events is high among clinicians and patients. Misoprostol, high-dose H2-receptor antagonists, proton-pump inhibitors, and COX-2 inhibitors have been shown to reduce this risk. Misoprostol and proton-pump inhibitors are more effective than H2-receptor antagonists; dose-related diarrhea limits the clinical utility of misoprostol. These strategies may not provide enough protection in patients taking concomitant low-dose aspirin therapy or patients with a history of ulcer complications. CONCLUSIONS: COX-2 inhibitors and proton-pump inhibitors are effective and well-tolerated therapies to reduce clinically significant upper gastrointestinal adverse events associated with NSAIDs.