Comprehensive Approach to Opioid Management in a Primary Care Network.

In response to the opioid epidemic, the Centers for Disease Control and Prevention released best practice recommendations for prescribing, yet adoption of these guidelines has been fragmented and frequently met with uncertainty by both patients and providers. This study aims to describe the development and implementation of a comprehensive approach to improving opioid stewardship in a large network of primary care providers. The authors developed a 3-tier approach to opioid management: (1) establishment and implementation of best practices for prescribing opioids, (2) development of a weaning process to decrease opioid doses when the risk outweighs benefits, and (3) support for patients when opioid use disorders were identified. Across 44 primary care practices caring for >223,000 patients, the total number of patients prescribed a chronic opioid decreased from 4848 patients in 2018 to 3106 patients in 2021, a decrease of 36% (P < 0.001). The percent of patients with a controlled substance agreement increased from 13% to 83% (P < 0.001) and the percent of patients completing an annual urine drug screen increased from 17% to 53% (P < 0.001). The number of patients coprescribed benzodiazepines decreased from 1261 patients at baseline to 834 at completion. A total of 6.5% of patients were referred for additional support from a certified alcohol and substance abuse counselor embedded within the program. Overall, the comprehensive opioid management program provided the necessary structure to support opioid prescribing and resulted in improved adherence to best practices, facilitated weaning of opioids when medically appropriate, and enhanced support for patients with opioid use disorders.

Real-world Impact of 3 and 4.5 mg Doses of Dulaglutide on Weight and Hemoglobin A1c in Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Limited real-world data on the benefits and risks associated with 3 and 4.5 mg doses of dulaglutide currently exists, making it difficult to determine the impact of dose titration for patients currently managed with dulaglutide 1.5 mg weekly. OBJECTIVE: To determine the impact of dulaglutide 3 and 4.5 mg doses on weight and hemoglobin A1c (HbA1c) in patients with type 2 diabetes mellitus (T2DM), in clinical practice. METHODS: Retrospective, observational study of adult T2DM patients receiving dulaglutide 3 or 4.5 mg weekly within a large, university-affiliated, primary care network. The primary outcome was change in weight and HbA1c from baseline to 24 weeks. Secondary outcomes included incremental changes in weight and HbA1c, and describing trends related to dose reductions. RESULTS: Ninety-five patients were included, 62 in the dulaglutide 3 mg group and 33 in the dulaglutide 4.5 mg group. After 24 weeks, the mean changes in weight and HbA1c from baseline were -1.8 kg (P < 0.01) and -0.4% (P < 0.01) in the 3 mg group, and -4.2 kg (P < 0.01) and -0.4% (P = 0.119) in the 4.5 mg group. Incremental change in weight and HbA1c among patients who were titrated from dulaglutide 3 to 4.5 mg weekly were -2.6 kg (P < 0.01) and -0.2% (P = 0.04), respectively. CONCLUSION AND RELEVANCE: Titration from dulaglutide 1.5 to 3 mg resulted in significant reductions in weight and HbA1c after 24 weeks. Additional, statistically significant, reductions in weight and HbA1c were seen when patients were further titrated to dulaglutide 4.5 mg weekly.

Stinging Nettle (Urtica dioica): An Unusual Case of Galactorrhea.

BACKGROUND The increasing popularity and availability of herbal supplements among patients necessitates a better understanding of their mechanism of action and the effects they have on the body, both intended and unintended. Stinging nettle (Urtica dioica) is an herbaceous shrub found throughout the world that has been used for medicinal purposes for centuries. CASE REPORT A 30-year-old woman with obesity and GERD presented to a primary care clinic with new-onset galactorrhea. A urine pregnancy test was negative. Prolactin, thyroid-stimulating hormone (TSH), and a metabolic panel were all within normal limits. A mammogram demonstrated scattered areas of fibroglandular density and benign-appearing calcifications in the left breast. The breast ultrasound showed no suspicious findings. Her medications included intermittent Echinacea, etonogestrel implant 68 mg subdermal, and the supplement stinging nettle 500 mg, which she had been taking over the past month for environmental allergies. After consultation with a clinical pharmacist, the stinging nettle was discontinued. No additional changes to her medications or supplements were made. One week after discontinuation, she returned to the clinic with complete resolution of the galactorrhea. CONCLUSIONS Stinging nettle (Urtica dioica) is a common supplement and has effects on (1) sex hormone-binding globulin, (2) histamine-induced prolactin release, and (3) serotonin-induced release of thyrotropin-releasing hormone. The local estrogen bioactivity in breast tissue may subsequently lead to gynecomastia and/or galactorrhea. Supplements are an often overlooked but a critical component of medication reconciliation and potential clinical adverse effects.

Addressing Medication Costs During Primary Care Visits: A Before-After Study of Team-Based Training.

Background: Medications contribute to patients' out-of-pocket costs, yet most clinicians do not routinely screen for patients' cost-of-medication (COM) concerns. Objective: To assess whether a single training session improves COM conversations. Design: Before-after cross-sectional surveys of patients and qualitative interviews with clinicians and staff. Setting: 7 primary care practices in 3 U.S. states. Participants: In total, 700 patients were surveyed from May 2017 to January 2018: 50 patients per practice before the intervention and another 50 patients per practice after the intervention. Eligibility criteria included age 18 years or older and taking 1 or more long-term medications. Qualitative interviews with 45 staff members were conducted. Intervention: A single 60-minute training session for clinicians and staff from each practice on COM importance, team-based screening, and cost-saving strategies. Measurements: Patient data (demographics, number of long-term medications, total monthly out-of-pocket medication costs, and history of cost-related medication nonadherence) were obtained immediately before and 3 months after the intervention. Practice staff were interviewed 3 months after the intervention. Results: A total of 700 patient surveys were completed. Frequency of COM discussion improved in 6 of the 7 practices and remained unchanged in 1 practice. Overall, COM conversations with patients increased from 17% at baseline to 32% postintervention (P = 0.00). There was substantial heterogeneity among sites in before-after differences in patient-reported out-of-pocket COM. Qualitative analyses from key informant interviews showed wide variation in implementation of screening approaches, workflow, adoption of a team-based approach, and strategies for addressing COM. Limitation: It is not known whether improvements in COM conversations were sustained beyond 3 months. Conclusion: A single team training to screen and address patients' medication cost concerns improved COM discussions over the short term. Further research is needed to assess sustained effects and impact on patient costs and medication adherence and to determine whether more intensive, scalable interventions are needed. Primary Funding Source: Robert Wood Johnson Foundation.

Safety of Popular Herbal Supplements in Lactating Women.

The increasing popularity and use of dietary supplements has required health care professionals to become more knowledgeable of their properties, interactions, and adverse effects. The objectives of this review were to evaluate the safety of popular dietary supplements in breastfeeding mothers and the effects on the infants. Nine of the most popular herbal dietary supplements were identified based on the 2011 US market report of the top 10 selling botanicals and the most frequently received inquiries by the Ruth A. Lawrence Lactation Study Center at the University of Rochester Medical Center. Relevant publications were identified through June 2014 using PubMed and EMBASE; tertiary references, including the Drugs and Lactation Database and Natural Medicine Comprehensive Database, were also reviewed. These herbals include black cohosh, cranberry, echinacea, evening primrose, garlic, ginseng, melatonin, milk thistle, and St John's wort. Studies varied greatly with regard to study design, herbal intervention, and outcome measures. Findings suggested that dietary/herbal supplements have not been evaluated in high-quality clinical trials, and there is limited evidence supporting safety of use, particularly among lactating women. Therefore, it is essential for physicians to provide counseling for nursing mothers seeking information on dietary supplements, highlighting reliable safety profiles, inquiring about the potential benefits the patient is seeking, and assessing the patient's perception of this supplement during breastfeeding. More research and clinical trials are required in this area to guide the recommendations and expand our current knowledge of these products.

Tasimelteon (Hetlioz™): A New Melatonin Receptor Agonist for the Treatment of Non-24-Hour Sleep-Wake Disorder.

In January 2014, the US Food and Drug Administration approved tasimelteon (Hetlioz™), a melatonin-receptor agonist for the treatment of non-24-hour sleep-wake disorder. This article provides an overview of the mechanism of action, pharmacokinetic properties, as well as the clinical efficacy, safety, and tolerability of tasimelteon. Relevant information was identified through a comprehensive literature search of several databases using the key words tasimelteon, Non-24-hour Sleep-Wake disorder, Non-24, and melatonin. Further information was obtained from the tasimelteon package insert, fda.gov, clinicaltrials.gov, briefing materials provided by Vanda Pharmaceuticals, and posters from scientific meetings.

Levomilnacipran (Fetzima): A New Serotonin-Norepinephrine Reuptake Inhibitor for the Treatment of Major Depressive Disorder.

In July 2013, the US Food and Drug Administration approved levomilnacipran extended release (ER; Fetzima), a serotonin-norepinephrine reuptake inhibitor, for the treatment of adults with major depressive disorder. Levomilnacipran is an active enantiomer of the racemic drug milnacipran that is currently approved in the United States for the treatment of fibromyalgia. This article provides an overview of the mechanism of action, pharmacokinetic properties, clinical efficacy, safety, and tolerability of levomilnacipran ER. Relevant information was identified through a search of databases using the key word levomilnacipran. Additional information was obtained from fda.gov, by a review of the reference lists of identified articles, and from posters and abstracts from scientific meetings. Levomilnacipran ER, dosed once daily, is generally well tolerated and has demonstrated favorable effects compared to placebo in clinical trials of patients with major depressive disorder. The increased potency for norepinephrine reuptake inhibition is a characteristic that may represent a novel contribution for levomilnacipran. Additional studies comparing levomilnacipran ER to other commonly prescribed antidepressants are needed to further evaluate its place in therapy.

Dimethyl fumarate (Tecfidera): a new oral agent for multiple sclerosis.

OBJECTIVE: To describe the clinical evidence supporting the safety, efficacy, and clinical utility of oral dimethyl fumarate for the treatment of multiple sclerosis (MS). DATA SOURCES: A comprehensive PubMed search was conducted in July 2013 using the search terms dimethyl fumarate and Tecfidera. Reference lists of abstracted publications were reviewed to identify relevant works that were not retrieved via the electronic search. Additional information was obtained from the FDA Web site, manufacturer prescribing information, and Clinicaltrials.gov. STUDY SELECTION AND DATA ABSTRACTION: Clinical trials and review articles that included the use of dimethyl fumarate in the treatment of MS and were available in English were abstracted for review. DATA SYNTHESIS: The safety and efficacy of dimethyl fumarate for the treatment of relapsing remitting MS was confirmed in 2 phase III trials, DEFINE and CONFIRM. Relative to placebo, twice-daily dimethyl fumarate was found to reduce the proportion of patients with relapses at 2 years by 34% to 49% and the annualized relapse rate by 44% to 53%. Although the incidence of serious adverse effects did not differ from that of placebo, intolerable flushing and gastrointestinal adverse effects prompted discontinuation in 3% and 4% of patients, respectively. CONCLUSIONS: In March 2013, dimethyl fumarate was approved as a third oral option for patients with relapsing forms of MS. Although no head-to-head trials have been conducted, a comparison of data from phase III trials suggests that the efficacy of dimethyl fumarate is comparable to that of existing oral agents and may offer a preferable safety profile.

Pharmacokinetic simulation of fatal carbamazepine intoxication in 23-month old child following phenytoin discontinuation.

The antiepileptic, carbamazepine, is extensively metabolized via hepatic enzymes in the cytochrome P450 family and is therefore subject to a myriad of drug interactions. Concomitant administration with phenytoin enhances carbamazepine metabolism thus reducing serum concentrations and necessitating the use of a higher maintenance dose. Removal of phenytoin therapy in the absence of anticipatory dose adjustments and careful monitoring of serum concentrations may result in catastrophic outcomes. Reported herein are the events leading to the death of a 23-month old child who suffered a fatal carbamazepine overdose following withdrawal of phenytoin therapy.

Improving the success of mailed letter intervention programs to influence prescribing behaviors: a review.

BACKGROUND: Educational interventions have long been used as a means of influencing prescribing behavior. Various techniques including educational mailings, academic detailing, prescriber feedback with or without disclosing patient-identifying data, and supplemental patient information have been used to promote appropriate prescribing habits, reduce costs, and optimize patient care. While the effects of educational intervention programs are widely reported, little information is available regarding the effectiveness of various mailed intervention techniques. OBJECTIVE: To review the effectiveness of mailed intervention programs and identify factors that may promote successful outcomes. METHODS: A literature search was conducted via PubMed for reports of mailed intervention programs published through May 2012. Specific search terms included "drug utilization review," "drug utilization," "Medicaid," "prescribing feedback," "mailed physician intervention," and "mailed physician communications." Identified publications that met the following criteria were selected for inclusion: (a) evaluated printed educational materials disseminated via postal mail, (b) occurred in an outpatient setting, and (c) measured intervention impact on prescribing patterns, health care utilization, or economic outcomes. Publications that met all 3 criteria were abstracted for intervention strategy, follow-up period, data source, intervention target, prescriber acceptance of intervention, and effect on prescribing patterns, health care utilization, and economic outcomes. RESULTS: A total of 40 published reports regarding 39 unique interventions met inclusion criteria. The majority (34/39 [87.2%]) of studies were conducted in state or federally funded programs; only 5 programs involved private insurers. All programs used follow-up periods of ≤12 months after final intervention mailing. A total of 26 of the 39 unique interventions reported a positive impact on at least 1 target outcome. Programs that included a second recipient such as pharmacists (n = 4) reported a greater impact as compared with interventions mailed to prescribers alone. Programs that provided patient-identifying data had a higher success rate than those that supplied prescriber feedback and/or educational materials (21/25 [84.0%] vs. 5/14 [35.7%]); it should be noted that 2 of the 5 successful programs that provided nonpatient-identifying materials also used academic detailing. Programs that sent education material and/or prescriber feedback pertaining to multiple medication classes or disease states had minimal impact on prescribing patterns (n = 4). However, targeting 1 specific disease or medication supported by appropriate evidence resulted in favorable change in a short period of time. Additionally, providing recommendations that were supported by widely accepted clinical guidelines or literature were also associated with a high rate of success. A subset of programs that sought to evaluate health care utilization (n=5) and economic impact (n = 9) observed little change in measured outcomes. Evaluation of prescriber response forms conducted by 7 programs revealed that changes in therapy occurred in approximately 50% of patients with prescribers who intended to accept intervention recommendations. CONCLUSIONS: Though the degree of heterogeneity between articles prevents provision of definite results, it appears that a well-constructed mailed intervention program has the potential to evoke significant changes in prescribing patterns. Prescribers appear to be receptive to mailed interventions; however, there are limited data to determine the association between acceptance and actual prescribing change. Future research should focus on identifying barriers that may prohibit acceptance of recommendations from translating into changes in therapy. Additionally, future projects should include longer assessment periods to determine the duration of impact following final intervention mailing and potential effect on health care and economic outcomes.