Katy E. Trinkley

QT interval prolongation and the risk of torsades de pointes: essentials for clinicians

Abstract Objective: QT interval prolongation signifies an increased risk of the life-threatening arrhythmia torsades de pointes (TdP). The purpose of this paper is to review the diverse methods for assessing and monitoring the risk of TdP, discuss risk factors for TdP, and recommend interventions that may mitigate the risk of TdP. Methods: A non-systematic search of PubMed (through March 2013) was conducted to determine the optimal approach to assessing and monitoring QT interval, prevention of TdP, and to identify risks factors for TdP. Papers known to the authors were included, as were scientific statements. Articles were chosen based on the judgment of the authors. Results: Risk factors for drug-induced TdP include hypokalemia, female sex, drug–drug interactions, advancing age, genetic predisposition, hypomagnesemia, heart failure, bradycardia, and corrected QT (QTc) interval prolongation. Many risk factors, including hypokalemia, use of QT-interval-prolonging drugs, and drug interactions are potentially modifiable and should be corrected in persons at risk for QT interval prolongation. Given the variable onset of TdP following initiation of QT-interval-prolonging drugs, careful and regular monitoring of electrocardiography (EKG) and electrolytes are necessary. Patients at risk for QT interval prolongation should be educated to go directly to the emergency room if they experience palpitations, lightheadedness, dizziness or syncope. When the QTc interval is 470–500 ms for males, or 480–500 ms for females, or the QTc interval increases 60 ms or more from pretreatment values, dose reduction or discontinuation of the offending drug should be considered where possible, and electrolytes corrected as needed. Furthermore, if the QTc interval is ≥500 ms, the offending drug should be discontinued, and continuous EKG telemetry monitoring should be performed, or the 12-lead EKG should be repeated every 2–4 hours, until the QT interval has normalized. Conclusions: Close monitoring for QTc prolongation is necessary to prevent TdP. The recommendations in this paper are limited by the available evidence and additional studies are needed to better define the approach to monitoring.

Medication management of irritable bowel syndrome.

Background: Irritable bowel syndrome (IBS) is a complex syndrome that is difficult to manage. Here we present the evidence supporting medication treatments for specific IBS symptoms, discuss evidence-based management of IBS with medications including dose regimens and adverse effects and review progress on research for new IBS treatments. Summary: Currently, there is evidence to support improvements in specific IBS symptoms following treatment with loperamide, psyllium, bran, lubiprostone, linaclotide, amitriptyline, trimipramine, desipramine, citalopram, fluoxetine, paroxetine, dicyclomine, peppermint oil, rifaximin, ketotifen, pregabalin, gabapentin and octreotide and there are many new medications being investigated for the treatment of IBS. Key Message: Of the medications with demonstrated improvements for IBS symptoms, rifaximin, lubiprostone, linaclotide, fiber supplementation and peppermint oil have the most reliable evidence supporting their use for the treatment of IBS. Onset of efficacy for the various medications has been noted to be as early as 6 days after initiation; however, the efficacy of most medications was not assessed prospectively at predefined periods. Additional studies of currently available and new medications are ongoing and are needed to better define their place in therapy and expand therapeutic options for the treatment of IBS. The most promising new medications for IBS include a variety of novel pharmacologic approaches, most notably the dual μ-opioid receptor agonist and δ-opioid antagonist, JNJ-27018966.

Phentermine/Topiramate for the Treatment of Obesity:

OBJECTIVE To review the pharmacology, efficacy, and safety of phentermine/topiramate (PHEN/TPM) in the management of obese patients. DATA SOURCES MEDLINE (1966-July 2012) was searched using the terms weight loss, obesity, phentermine and topiramate, phentermine, topiramate, Qnexa, Qsymia, and VI-0521. Additionally, the new drug application and prescribing information for PHEN/TPM were retrieved. STUDY SELECTION/DATA EXTRACTION All studies considering the pharmacology, efficacy, and safety of PHEN/TPM were reviewed with a focus on efficacy and safety data from Phase 3 trials. DATA SYNTHESIS In 3 Phase 3 trials (EQUIP, CONQUER, and SEQUEL), treatment with PHEN/TPM consistently demonstrated statistically significant weight loss compared with placebo. After 56 weeks of treatment, percent weight loss achieved with PHEN/TPM was 10.6%, 8.4%, and 5.1% with 15/92 mg, 7.5/46 mg, and 3.75/23 mg, respectively (p < 0.0001). The 52-week extension study (SEQUEL) showed maintained weight loss over 2 years with 9.3% and 10.5% weight loss from baseline for 7.5/46 mg and 15/92 mg PHEN/TPM (p < 0.0001). A significantly higher proportion of patients achieved greater than 5%, 10%, or 15% weight loss with PHEN/TPM compared with placebo. Significant reductions in waist circumference, fasting triglycerides, and fasting glucoses were also attributable to PHEN/TPM. The drug was generally well tolerated in clinical trials. Adverse reactions occurring in 5% or more of study subjects included paresthesia, dizziness, dysgeusia, insomnia, constipation, and dry mouth. CONCLUSIONS PHEN/TPM is a new, once-daily, controlled-release, combination weight-loss product approved as an adjunct to diet and exercise for chronic weight management of obese or overweight patients with weight-related comorbidities. PHEN/TPM is modestly effective and a viable option for patients interested in losing weight, although long-term safety data are lacking.

A systematic review of the efficacy of venlafaxine for the treatment of fibromyalgia

Fibromyalgia is a painful disease affecting 1–2% of the United States population. Serotonin and norepinephrine reuptake inhibitors (SNRIs), such as duloxetine and milnacipran, are well studied and frequently used for treating this disorder. However, efficacy data are limited for the SNRI venlafaxine despite its use in nearly a quarter of patients with fibromyalgia. Accordingly, we systematically reviewed the efficacy of venlafaxine for treatment of fibromyalgia.

A Pharmacist-Physician Collaboration to Optimize Benzodiazepine Use for Anxiety and Sleep Symptom Control in Primary Care.

Introduction: Benzodiazepines are prescribed inappropriately in up to 40% of outpatients. The purpose of this study is to describe a collaborative team-based care model in which clinical pharmacists work with primary care providers (PCPs) to improve the safe use of benzodiazepines for anxiety and sleep disorders and to assess the preliminary results of the impact of the clinical service on patient outcomes. Methods: Adult patients were eligible if they received care from the academic primary care clinic, were prescribed a benzodiazepine chronically, and were not pregnant or managed by psychiatry. Outcomes included baseline PCP confidence and knowledge of appropriate benzodiazepine use, patient symptom severity, and medication changes. Results: Twenty-five of 57 PCPs responded to the survey. PCPs reported greater confidence in diagnosing and treating generalized anxiety and panic disorders than sleep disorder and had variable knowledge of appropriate benzodiazepine prescribing. Twenty-nine patients had at least 1 visit. Over 44 total patient visits, 59% resulted in the addition or optimization of a nonbenzodiazepine medication and 46% resulted in the discontinuation or optimization of a benzodiazepine. Generalized anxiety symptom severity scores significantly improved (−2.0; 95% confidence interval (CI): −3.57 to −0.43). Conclusion: Collaborative team-based models that include clinical pharmacists in primary care can assist in optimizing high-risk benzodiazepine use. Although these findings suggest improvements in safe medication use and symptoms, additional studies are needed to confirm these preliminary results.

Variations in Metformin Prescribing for Type 2 Diabetes

Background: Reasons for suboptimal metformin prescribing are unclear, but may be due to perceived risk of lactic acidosis. The purpose of this study is to describe provider attitudes regarding metformin prescribing in various patient situations. Methods: An anonymous, electronic survey was distributed electronically to 76 health care providers across the nation. The 14-item survey contained demographic questions and questions related to prescribing of metformin for T2DM in various patient situations, including suboptimal glycemic control, alcohol use, history of lactic acidosis, and varying degrees of severity for certain health conditions, including renal and hepatic dysfunction, chronic obstructive pulmonary disease, and heart failure. Results: There were a total of 100 respondents. For suboptimal glycemic control, most providers (75%) would increase metformin from 1500 to 2000 mg daily; however, 25% would add an alternate agent, such as a sulfonylurea (18%) or dipeptidyl peptidase-4 inhibitor (7%). Although 51% of providers would stop metformin based on serum creatinine thresholds, the remainder would rely on glomerular filtration rate thresholds of <60 mL/min (15%), <30 mL/min (33%), or <15 mL/min (1%) to determine when to stop metformin. For heart failure, 45% of providers would continue metformin as currently prescribed regardless of severity. Most providers would adjust metformin for varying severity of hepatic dysfunction (74%) and alcohol abuse (40%). Conclusions: Despite evidence supporting the cardiovascular benefits of metformin, provider attitudes toward prescribing metformin are suboptimal in certain patient situations and vary greatly by provider.

Physician Acceptance of a Physician‐Pharmacist Collaborative Treatment Model for Hypertension Management in Primary Care

Physician‐pharmacist collaborative care (PPCC) is effective in improving blood pressure (BP) control, but primary care provider (PCP) engagement in such models has not been well‐studied. The authors analyzed data from PPCC referrals to 108 PCPs, for patients with uncontrolled hypertension, assessing the proportion of referral requests approved, disapproved, and not responded to, and reasons for disapproval. Of 2232 persons with uncontrolled hypertension, PPCC referral requests were sent for 1516 (67.9%): 950 (62.7%) were approved, 406 (26.8%) were disapproved, and 160 (10.6%) received no response. Approval rates differed widely by PCP with a median approval rate of 75% (interquartile range, 41%–100%). The most common reasons for disapproval were: PCP prefers to manage hypertension (19%), and BP controlled per PCP (18%); 8% of cases were considered too complex for PPCC. Provider acceptance of a PPCC hypertension clinic was generally high and sustained but varied widely among PCPs. No single reason for disapproval predominated.

Integrating virtual reality to expand the public health role of community pharmacists

OBJECTIVES To describe a potential future role of the community pharmacist in public health using virtual centers that provide immediate feedback to patients regarding behavior changes. SUMMARY Community pharmacists would provide a comprehensive standardized patient-centered interview to collect pertinent information regarding patients that, together with a computerized body scan of the individual, would be fed into the virtual center to create a baseline likeness of the person. The virtual center then would predict the persons appearance and overall body health at a predetermined interval in the future, as well as provide feedback to the patient, engaging multiple senses and using an advanced body suit to represent changes in body mass and exercise tolerance as the person moves in the center. Pharmacists would work with the patient to identify patient-centered behavior changes, which would be programmed into the virtual center to demonstrate to the person how their new lifestyle goal may change their future appearance and health. Achievements and social networking in the virtual world would be incorporated to motivate patients to continue to make positive decisions regarding their health. CONCLUSION Virtual reality technology can be a powerful motivational tool that community pharmacists can use in a variety of ways to help patients implement and sustain positive lifestyle changes.

Clinical pharmacists in primary care: Provider satisfaction and perceived impact on quality of care provided:

Purpose: The purpose of this study is to evaluate primary care provider satisfaction and perceived impact of clinical pharmacy services on the disease state management in primary care. Methods: A cross-sectional survey with 24 items and 4 domains was distributed anonymously to pharmacy residency program directors across the United States who were requested to forward the survey to their primary care provider colleagues. Primary care providers were asked to complete the survey. Results: A total of 144 primary care providers responded to the survey, with 130 reporting a clinical pharmacist within their primary care practice and 114 completing the entire survey. Primary care providers report pharmacists positively impact quality of care (mean = 5.5 on Likert scale of 1–6; standard deviation = 0.72), high satisfaction with pharmacy services provided (5.5; standard deviation = 0.79), and no increase in workload as a result of clinical pharmacists (5.5; standard deviation = 0.77). Primary care providers would recommend clinical pharmacists to other primary care practices (5.7; standard deviation = 0.59). Primary care providers perceived specific types of pharmacy services to have the greatest impact on patient care: medication therapy management (38.6%), disease-focused management (29.82%), and medication reconciliation (11.4%). Primary care providers indicated the most valuable disease-focused pharmacy services as diabetes (58.78%), hypertension (9.65%), and pain (11.4%). Conclusion: Primary care providers report high satisfaction with and perceived benefit of clinical pharmacy services in primary care and viewed medication therapy management and disease-focused management of diabetes, hypertension, and pain as the most valuable clinical pharmacy services. These results can be used to inform development or expansion of clinical pharmacy services in primary care.

Integration of Community Pharmacists in Transition of Care (TOC) Services: Current Trends and Pharmacist Perceptions.

Background: Barriers exist for patients transitioning from one health-care setting to another, or to home, and health-care systems are falling short of meeting patient needs during this time. Community pharmacist incorporation poses a solution to the current communication breakdown and high rates of medication errors during transitions of care (TOC). The purpose of this study was to determine community pharmacists’ involvement in and perceptions of TOC services. Methods: Cross-sectional study using electronic surveys nationwide to pharmacists employed by a community pharmacy chain. Results: Of 7236 pharmacists surveyed, 546 (7.5%) responded. Only 33 (6%) pharmacists reported their pharmacy participates in TOC services. Most pharmacists (81.5%) reported receiving discharge medication lists. The most common reported barrier to TOC participation is lack of electronic integration with surrounding hospitals (51.1%). Most pharmacists agreed that (1) it is valuable to receive discharge medication lists (83.3%), (2) receiving discharge medication lists is beneficial for patients’ health (89.1%), (3) discharge medication list receipt improves medication safety (88.8%). Conclusions: Most pharmacists reported receiving discharge medication lists and reported discharge medication lists are beneficial, but less than half purposefully used medication lists. To close TOC gaps, health-care providers must collaborate to overcome barriers for successful TOC services.