Successful Treatment of Confirmed Severe Bupropion Cardiotoxicity With Veno-Arterial Extracorporeal Membrane Oxygenation Initiation Prior to Cardiac Arrest.

Bupropion is a substituted cathinone (ß-keto amphetamine) norepinephrine/dopamine reuptake inhibitor andnoncompetitive nicotinic acetylcholine receptor antagonist that is frequently used to treat major depressive disorder. Bupropion overdose can cause neurotoxicity and cardiotoxicity, the latter of which is thought to be secondary to gap junction inhibition and ion channel blockade. We report a patient with a confirmed bupropion ingestion causing severe cardiotoxicity, for whom prophylactic veno-arterial extracorporeal membrane oxygenation (ECMO) was successfully implemented. The patient was placed on the ECMO circuit several hours before he experienced multiple episodes of hemodynamically unstable ventricular tachycardia, which were treated with multiple rounds of electrical defibrillation and terminated after administration of lidocaine. Despite a neurological examination notable for fixed and dilated pupils after ECMO cannulation, the patient completely recovered without neurological deficits. Multiple bupropion and hydroxybupropion concentrations were obtained and appear to correlate with electrocardiogram interval widening and toxicity.

Quality and rapidity of anticoagulation in patients with acute pulmonary embolism undergoing mechanical thrombectomy.

The primary objective of our study was to determine the proportion of intermediate-risk PE patients undergoing mechanical thrombectomy (MT) who achieved therapeutic anticoagulation (AC) at the time of the procedure. The salient findings of our study showed that only a minority of patients (14.3%) were in the therapeutic range by ACT at the time of MT (primary outcome). Furthermore, in this higher-risk PE cohort selected for MT, 18.2% of patients were subtherapeutic after initially reaching therapeutic AC, 43% experienced supratherapeutic AC at some point before MT, and less than half (43%) attained therapeutic AC at 6 hours, highlighting the necessity for optimizing anticoagulation practices in acute PE.

Toward Personalized DAPT: Is There an Inter-Manufacturer Difference in Generic Clopidogrel Response?

OBJECTIVE: To compare rates of clopidogrel response among patients receiving medication produced by 2 different manufacturers after acute coronary syndrome (ACS) and/or percutaneous coronary intervention. METHODS: This quality-improvement project included 515 adult patients receiving clopidogrel for ACS or ischemic heart disease and referred for coronary angiography/ percutaneous coronary intervention. The project was divided into 2 phases: (1) retrospective collection of baseline data (April 2019-October 2020); and (2) two 12-week, prospective phases in which all clopidogrel in the hospital was restricted to a single manufacturer at a time (November 2020-May 2021). The primary outcome was clopidogrel response measured by platelet function testing, defined as adenosine diphosphate (ADP) response <40% on light transmission aggregometry. RESULTS: Of 515 total patients included in both phases (mean age, 64.5 ± 11.4 years; 351 men [68.2%]; 450 with ACS [87.4%]), 52% were found to be clopidogrel responders based on results of platelet function testing. Among 135 patients in the prospective phase, there was a significantly lower proportion of patients who were clopidogrel responders in the Manufacturer 1 group compared with the Manufacturer 2 group (34.8% vs 55.1%, respectively; P=.03). After adjustment for age, sex, body mass index, aspirin response, therapeutic hypothermia, left heart catheterization indication, clopidogrel loading dose, time between loading dose and lab measurement, and manufacturer, aspirin response (odds ratio 0.96; 95% confidence interval, 0.95-0.97; P<.001) and manufacturer (odds ratio, 2.45; 95% confidence interval, 1.18-5.22; P=.02) were associated with clopidogrel response. CONCLUSIONS: In a large public hospital, we observed that pharmacodynamic response to clopidogrel varied by drug manufacturer. Further investigation and/or regulation is needed to minimize inter-manufacturer variability.

The Contribution of Patient, Primary Care Physician, and Primary Care Clinic Factors to Good Bone Health Care.

BACKGROUND/OBJECTIVE: Patient, provider, and system factors can contribute to chronic care management and outcomes. Few studies have examined these multilevel associations with osteoporosis care and outcomes. We examined how key process and structural factors at the patient, primary care physician (PCP), and primary care clinic (PCC) levels were associated with guideline concordant osteoporosis pharmacotherapy, daily calcium intake, vitamin D supplementation, and weekly exercise sessions at 52 weeks following enrollment in a cluster randomized controlled trial. METHODS: We conducted a secondary analysis of observational data from 1 site of the trial. The study sample included 1996 men and women ≥ 50 years of age at the time of recruitment following completion of a dual-energy x-ray absorptiometry (DXA) scan and who had complete data at baseline and 52 weeks. Our primary independent variable was "relationship continuity": the DXA-ordering provider was the patient's PCP. Hierarchical linear and logistic regression accounted for patient, provider, and primary care clinic characteristics. RESULTS: In multivariable regression analyses, relationship continuity (ie, the PCP ordered the study DXA) was associated with higher average daily calcium intake and likelihood of vitamin D supplementation at 52 weeks. No PCP or primary care clinic factors were associated with osteoporosis care. CONCLUSIONS: The relationship continuity, in which the provider ordering a DXA is the patient's PCP and therefore also presents the results of a DXA, may help to promote patient behaviors associated with good bone health.

Evaluation of a hospital-wide vancomycin-dosing nomogram in patients with continuous-flow left ventricular assist devices.

INTRODUCTION: Hemodynamic derangements due to heart failure are associated with alterations in pharmacokinetics. Although use of mechanical circulatory support mitigates such derangements, little evidence is available regarding pharmacokinetics in patients with LVADs. A previous pharmacokinetic analysis of vancomycin among patients with LVADs observed a reduced volume of distribution and clearance compared with estimates based on population kinetics. METHODS: A total of 28 adult patients with LVADs hospitalized between January 2014 and May 2018 who received vancomycin through a pharmacist dosing consult were included. Internal medicine patients without heart failure receiving vancomycin were enrolled in a 2:1 fashion to make a control group. Exclusion criteria were unstable renal function, ESRD, acute decompensation, cardiac surgery within the preceding 5 days, or weight >110 kg. RESULTS: No difference was observed in the proportion achieving goal trough (64% of LVAD patients vs 71% control patients, p = 0.50). However, mean trough was significantly higher among LVAD patients (23.4 mg/L vs 17.7 mg/L, p = 0.017). Furthermore, there was a significant difference in the distribution of trough levels (p = 0.025) with LVAD patients being more likely to attain levels >25 mg/L (32% vs 14%) and less likely to have troughs <10 mg/L (4% vs 14%). A numerically greater number of LVAD patients experienced nephrotoxicity but this did not reach statistical significance (32% vs 18%, p = 0.14). CONCLUSION: The use of vancomycin in LVAD patients may result in higher trough levels when compared to internal medicine patients. Increased monitoring or conservative dosing may be warranted to improve safety and efficacy.

The prevalence of overtreatment of osteoporosis: results from the PAADRN trial.

Overtreatment of osteoporosis increases costs and puts patients at unnecessary risk of experiencing adverse drug events. In the Patient Activation After DXA Receipt Notification (PAADRN) trial, we found that 8% of individuals with no indication for therapy were recommended a new osteoporosis medication or continuation of an existing medication. PURPOSE: There is a robust body of literature addressing undertreatment in osteoporosis, but limited data addressing overtreatment. Understanding overtreatment is important to minimize harm and decrease costs. METHODS: One of the pre-specified post hoc analyses of the PAADRN trial, a randomized, controlled, pragmatic clinical trial, was to quantify and identify risk factors associated with osteoporosis overtreatment. PAADRN included patients ≥ 50 years of age presenting for bone density testing between February, 2012, and August, 2014, at three US healthcare systems. We assessed 20,397 patients for eligibility and randomized 7749. Intervention patients received a tailored letter containing their dual-energy X-ray absorptiometry (DXA) results and an educational osteoporosis brochure. Control patients received usual care. Using the National Osteoporosis Foundation treatment guidelines, we defined overtreatment as the receipt of osteoporosis pharmacotherapy 12 weeks after DXA when treatment was not indicated. We evaluated the relationship between the following baseline variables-sex, race/ethnicity, educational attainment, and differences across health systems-and overtreatment using a series of multivariable logistic regression models. RESULTS: Among 3602 patients with no apparent indication for osteoporosis treatment, 292 (8.1%; 95% CI, 7.22 to 9.00%) received a new prescription for osteoporosis pharmacotherapy or were instructed to continue an existing medication (presumed overtreatment). Presumed overtreatment was more common among participants with prior DXA history, those who reported a history of osteoporosis or low bone mass, and those referred for testing by family medicine providers. CONCLUSION: In our sample of older adults, overuse of osteoporosis pharmacotherapy was only 8.1%. Nevertheless, overtreatment exposes patients to possible risk with negligible chance of benefit and should be minimized. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01507662.

Pharmacokinetics and Clinical Implications of Semaglutide: A New Glucagon-Like Peptide (GLP)-1 Receptor Agonist.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) came to market in the year 2005, as a new therapeutic classification, for clinical use in the management of type 2 diabetes mellitus (T2DM). Since 2005, there have been six approved products on the market, with the newest product being semaglutide (Novo Nordisk). Several studies have been conducted and completed evaluating its pharmacokinetics as a once-weekly subcutaneous injection. As a dose of 0.5 or 1 mg, semaglutide has a half-life of 7 days; therefore, it would reach steady state in 4-5 weeks. There are few drug interactions and dose adjustments are not necessary. However, similar to other GLP-1 RAs, semaglutide can delay gastric emptying and may impact the absorption of oral medications. Based on clinical trials, semaglutide has been compared with placebo, sitagliptin, exenatide extended release, and insulin glargine as monotherapy or add-on therapy. Semaglutide has resulted in a 1.5-1.9% glycosylated hemoglobin A1c reduction after 30-56 weeks. It also produced 5-10% weight reduction from baseline in clinical efficacy studies. Semaglutide can be another acceptable option for patients with T2DM, and it has a potential role among patients who require weight loss with a low risk of hypoglycemia. This article evaluates the pharmacokinetics of semaglutide and summarizes its application to clinical practice based on efficacy and safety data.

Diet and exercise changes following bone densitometry in the Patient Activation After DXA Result Notification (PAADRN) study.

Calcium and vitamin D intake and exercise are suboptimal among older adults. Following bone densitometry, a letter communicating individualized fracture risk accompanied by an educational brochure improved participants' lifestyle-but no more than existing communication strategies-over 52 weeks. Simple communication strategies are insufficient for achieving optimal levels of bone health behaviors. PURPOSE: The Patient Activation After DXA Result Notification (PAADRN) study was designed to evaluate whether a letter with individualized fracture risk and an educational brochure mailed to patients soon after their DXA might improve bone health behaviors (daily calcium intake, vitamin D supplementation, and weekly exercise sessions) compared to slower, less individualized communication characterizing usual care. METHODS: Participants ≥ 50 years were recruited, at three sites, following their DXA and randomized with 1:1 allocation to intervention and control (usual care only) groups. Data were collected at enrollment interview and by phone survey at 12 and 52 weeks thereafter. Intention-to-treat analyses were conducted on 7749 of the 20,397 eligible participants who enrolled. Changes in bone health behaviors were compared within and between study groups. Average treatment effects and heterogeneity of treatment effects were estimated with multivariable linear and logistic regression models. RESULTS: In unadjusted analyses, calcium intake, vitamin D supplementation, and weekly exercise sessions increased significantly over 52 weeks within both the intervention and control groups (all p < 0.001). In unadjusted analyses and multivariable models, increases in each behavior did not significantly differ between the intervention and control groups. Intervention group participants with a > 20% 10-year fracture risk at enrollment did, however, have a significantly greater increase in calcium intake compared to other study participants (p = 0.031). CONCLUSIONS: Bone health behaviors improved, on average, over 52 weeks among all participants following a DXA. Receipt of the PAADRN letter and educational brochure did not directly improve bone health behaviors compared to usual care. TRIAL REGISTRATION: The Patient Activation after DXA Result Notification (PAADRN) Study is registered at ClinicalTrials.Gov: NCT01507662, https://clinicaltrials.gov/ct2/show/NCT01507662.

Patient-reported reasons for nonadherence to recommended osteoporosis pharmacotherapy.

OBJECTIVES: As many as one-half of patients recommended for osteoporosis pharmacotherapy do not take their medications. To identify intervention targets, we examined patient characteristics associated with nonadherence to recommended pharmacotherapy and their reasons for nonadherence. METHODS: Data come from the Patient Activation after DXA Result Notification (PAADRN) study, a randomized controlled trial of 7749 patients aged 50 years or older presenting for dual-energy X-ray absorptiometry (DXA) at 3 health centers in the United States. We focused on the 790 patients who reported receiving a recommendation for new pharmacotherapy at baseline. Using Pearson chi-squared tests for categorical variables, 2-sample t tests for continuous variables, and multivariable multinomial logistic regression, we compared those who reported starting the recommended medication (adherers) with temporary nonadherers and nonadherers on demographics, health habits, DXA impression, 10-year probability of fracture using the assessment tool, and osteoporosis knowledge, and we examined their stated reasons for nonadherence. RESULTS: Mean age was 66.8 years (SD = 8.9); 87.2% were women, and 84.2% were white. One-fourth of patients (24.8%) reported that they did not start their recommended pharmacotherapy. In the unadjusted analyses, the only factor significantly associated with nonadherence was osteoporosis knowledge, with those having better knowledge being less likely to take their medications (P < 0.05). The most common reasons for nonadherence were fear of adverse effects (53.3%), a dislike of taking medicine (25.3%), and the belief that the medication would not help their condition (16.7%). CONCLUSION: One in 4 patients recommended for osteoporosis pharmacotherapy declined treatment because they feared potential adverse effects, did not like taking medicine, or believed that the medication would not help their condition. Improved patient counseling on the potential adverse effects of osteoporosis treatment and the risk-benefit ratio for these medications may increase adherence.

Racial Differences and Disparities in Osteoporosis-related Bone Health: Results From the PAADRN Randomized Controlled Trial.

BACKGROUND: Determining whether observed differences in health care can be called disparities requires persistence of differences after adjustment for relevant patient, provider, and health system factors. We examined whether providing dual-energy x-ray absorptiometry (DXA) test results directly to patients might reduce or eliminate racial differences in osteoporosis-related health care. DESIGN, SUBJECTS, AND MEASURES: We analyzed data from 3484 white and 1041 black women who underwent DXA testing at 2 health systems participating in the Patient Activation after DXA Result Notification (PAADRN) pragmatic clinical trial (ClinicalTrials.gov NCT-01507662) between February 2012 and August 2014. We examined 7 outcomes related to bone health at 12 weeks and 52 weeks post-DXA: (1) whether the patient correctly identified their DXA baseline results; (2) whether the patient was on guideline-concordant osteoporosis pharmacotherapy; (3) osteoporosis-related satisfaction; (4) osteoporosis knowledge; (5 and 6) osteoporosis self-efficacy for exercise and for diet; and (7) patient activation. We examined whether unadjusted differences in outcomes between whites and blacks persisted after adjusting for patient, provider, and health system factors. RESULTS: Mean age was 66.5 years and 29% were black. At baseline black women had less education, poorer health status, and were less likely to report a history of osteoporosis (P<0.001 for all). In unadjusted analyses black women were less likely to correctly identify their actual DXA results, more likely to be on guideline-concordant therapy, and had similar patient activation. After adjustment for patient demographics, baseline health status and other factors, black women were still less likely to know their actual DXA result and less likely to be on guideline-concordant therapy, but black women had greater patient activation. CONCLUSIONS: Adjustment for patient and provider level factors can change how racial differences are viewed, unmasking new disparities, and providing explanations for others.

Activating Patients With a Tailored Bone Density Test Results Letter and Educational Brochure: the PAADRN Randomized Controlled Trial.

In cross-sectional studies, patient activation has been associated with better health behaviors, health outcomes, and health-care experiences. Moreover, tailored interventions have led to clinically meaningful improvements in patient activation, as well as health outcomes over time. We tested whether a tailored patient-activation letter communicating bone mineral density (BMD) test results plus an educational brochure improved patient activation scores and levels at 12 and 52 wk post-baseline as the mechanism leading to enhanced bone healthcare. In a randomized, controlled, double-blinded, multicenter pragmatic clinical trial, we randomized 7749 patients ≥50 yr old and presenting for BMD testing at 3 medical centers in the United States between February 2012 and August 2014. The outcome measures were patient activation scores and levels based on 6 items taken from the Patient Activation Measure (PAM) that were administered at the baseline, 12-wk, and 52-wk follow-up interviews. Mean age was 66.6 yr, 83.8% were women, and 75.3% were Non-Hispanic-Whites. Overall, PAM activation scores improved from 58.1 at baseline to 76.4 by 12 wk (p < 0.001) and to 77.2 (p = 0.002) by 52 wk post-baseline. These improvements, however, were not significantly different between the intervention and usual care groups (18.7 vs 18.1, p = 0.176, at 12 wk) in intention-to-treat analyses. PAM activation scores and levels substantially improved at 12 wk and 52 wk, but no differences were observed in these improvements between the intervention and usual care groups. These null findings may have occurred because the tailoring focused on the patient's BMD and fracture risk results, rather than on the patient's BMD and fracture risk results as well as the patient's baseline PAM activation scores or levels.

Dying means suffocating: perceptions of people living with severe COPD facing the end of life.

AIM: The purpose of this research was to describe the perceptions of people living with severe chronic obstructive pulmonary disease (COPD) with respect to the end of life. METHOD: For this descriptive exploratory qualitative study, semi-structured interviews were conducted with six participants suffering from severe COPD hospitalized in the past year following an exacerbation episode. The data were analyzed using the method developed by Miles and Huberman (2003), which comprises three main steps: data reduction, data display, and conclusion drawing/verification. RESULTS: The analysis yielded four themes that reflect the perceptions of participants with respect to the end of life, namely: living and seeing oneself decline, living and preparing to die, dying of COPD means suffocating, and dying in hospital surrounded by family and friends. What emerges from the study is that persons living with severe COPD wish to die without suffocating, in hospital, surrounded by family and friends, all the while hoping to go on living. CONCLUSION: This study contributes to a more comprehensive understanding of the end-of-life experience. It shows the importance of accompanying these persons properly towards the end of life and at the moment of dying. The study proposes a series of avenues for future research and makes recommendations for practice.