Proactive Polypharmacy Management Using Large Language Models: Opportunities to Enhance Geriatric Care.

Polypharmacy remains an important challenge for patients with extensive medical complexity. Given the primary care shortage and the increasing aging population, effective polypharmacy management is crucial to manage the increasing burden of care. The capacity of large language model (LLM)-based artificial intelligence to aid in polypharmacy management has yet to be evaluated. Here, we evaluate ChatGPT's performance in polypharmacy management via its deprescribing decisions in standardized clinical vignettes. We inputted several clinical vignettes originally from a study of general practicioners' deprescribing decisions into ChatGPT 3.5, a publicly available LLM, and evaluated its capacity for yes/no binary deprescribing decisions as well as list-based prompts in which the model was prompted to choose which of several medications to deprescribe. We recorded ChatGPT responses to yes/no binary deprescribing prompts and the number and types of medications deprescribed. In yes/no binary deprescribing decisions, ChatGPT universally recommended deprescribing medications regardless of ADL status in patients with no overlying CVD history; in patients with CVD history, ChatGPT's answers varied by technical replicate. Total number of medications deprescribed ranged from 2.67 to 3.67 (out of 7) and did not vary with CVD status, but increased linearly with severity of ADL impairment. Among medication types, ChatGPT preferentially deprescribed pain medications. ChatGPT's deprescribing decisions vary along the axes of ADL status, CVD history, and medication type, indicating some concordance of internal logic between general practitioners and the model. These results indicate that specifically trained LLMs may provide useful clinical support in polypharmacy management for primary care physicians.

Heart rate outcomes with concomitant parenteral calcium channel blockers and beta blockers in rapid atrial fibrillation or flutter.

BACKGROUND: Patients who present with atrial fibrillation (AF) or flutter with rapid ventricular response (RVR) and hemodynamic stability may be managed with either an intravenous (IV) nondihydropyridine calcium channel blocker (CCB) or a beta-blocker (BB). Patients without improved heart rates may need to switch to, or add, a second AV nodal blocker. OBJECTIVE: To evaluate the incidence of rate control achievement and bradycardia in patients in AF or atrial flutter with RVR who receive both an intravenous CCB and a BB. METHODS: A retrospective chart review of patients who received concomitant intravenous CCB or BB for the treatment of rapid AF or atrial flutter from April 2016 through July 2018 in the emergency department. Patients were excluded if the second agent was ordered but not administered, or if they received IV amiodarone or digoxin. RESULTS: A total of 136 patients were included in the analysis, and of those, 46% (n = 62) of patients achieved a heart rate <110 bpm without bradycardia, and 3.7% (n = 5) developed bradycardia. Age, initial heart rate, time between CCB and BB administration, addition of an oral CCB or BB administration, or administration of IV magnesium did not impact target heart rate achievement. CONCLUSION: Adding a second nodal blocker in patients who did not achieve rate control with the first agent resulted in heart rate control 46% of the time. The development of symptomatic bradycardia was uncommon.

Reversal of Oral Anticoagulants for Intracerebral Hemorrhage Patients: Best Strategies.

In patients with acute intracerebral hemorrhage (ICH), one of the major concerns is ongoing bleeding or ICH expansion. Anticoagulated patients are at higher risk of ongoing expansion and worse outcome. It may be that rapid anticoagulation reversal can reduce the risk of expansion and improve clinical outcome. For those taking coumarins, the best available evidence suggests that intravenous vitamin K combined with four-factor prothrombin complex concentrate (4F-PCC) is the most rapid and effective regimen to restore hemostasis. For those on dabigatran, the highest quality data available for reversal are for idarucizumab, although it is not yet clear whether patients derive clinical benefit from this reversal. In the absence or failure of idarucizumab, activated prothrombin complex concentrate (aPCC) is recommended. For those on factor Xa inhibitors, the ideal reversal agent is not clear. Many providers use 4F-PCC or aPCC, but more specific agents are in clinical trials and may soon be available. In addition, the half-lives of the non-vitamin K antagonists are relatively short compared with warfarin, and so some patients may not have a clinically relevant coagulopathy at the time of presentation. Overall, the optimal reversal agent, when one is required, is a function of which anticoagulant the patient is taking.

Reduced-dose intramuscular ketamine for severe agitation in an academic emergency department.

Introduction: Rapid sedation of severely agitated patients is often necessary to ensure the safety of patients and healthcare workers. Intramuscular (IM) ketamine 4-6 mg/kg was previously studied but may carry an increased risk of intubation and other adverse effects. Therefore, the purpose of this case series was to describe the efficacy and safety of a reduced-dose (2 mg/kg) IM ketamine guideline.Methods: Consecutive patients receiving IM ketamine for agitation in the emergency department via our reduced-dose guideline were included. Successful sedation of the agitated patient was defined as documentation from a healthcare provider, a lack of additional sedating medication administration for 30 min following administration of IM ketamine, or ability to complete necessary procedure.Results: Of 15 patients included in this case series, 13 (87%) were adequately sedated with no subsequent intubations due to excess ketamine. The median total dose administered was 157.5 mg and the median weight-based dose was 2 mg/kg. In 11 of the 15 cases, reduced-dose ketamine was used as a second-line agent.Conclusion: Reduced-dose IM ketamine may be effective for severe agitation, particularly when used as a second-line agent.

Beta-lactam antibiotic test doses in the emergency department.

BACKGROUND: Facilitating beta-lactam antibiotic use in patients reporting beta-lactam allergies in acute care settings is important to individual patient outcomes and public health; however, few initiatives have targeted the Emergency Department (ED) setting. METHODS: We implemented pathways for patients reporting prior penicillin and/or cephalosporin hypersensitivity as part of a hospital guideline in the ED of a large academic medical center in the United States. We described beta-lactam test doses, pathway compliance, hypersensitivity reactions (HSRs), and allergy record updating associated with ED-administered beta-lactam test doses from October 2016 to June 2018. RESULTS: 310 beta-lactam antibiotic test doses were administered to patients with penicillin and/or cephalosporin allergy histories in the study period (average volume 15/month [standard deviation 4]). Test doses were to cephalosporins (85%), penicillins (12%), and carbapenems (4%). 219 (71%) of test doses were compliant with the pathways. Ten patients (3.2%; 95% CI 1.6%-5.9%) had HSRs; five HSR patients (50%) had beta-lactams administered that were not pathway compliant. The allergy record was updated in 146 (47%) of patients, with improvement over the study period (p < 0.001). CONCLUSIONS: Inpatient approaches to prescribing beta-lactams in patients reporting beta-lactam allergies can be operationalized in the ED. Additional efforts are required to ensure guideline compliance and appropriate allergy documentation.

Evaluation of andexanet alfa and four-factor prothrombin complex concentrate (4F-PCC) for reversal of rivaroxaban- and apixaban-associated intracranial hemorrhages.

BACKGROUND/OBJECTIVE: Before approval of andexanet alfa, off-label treatment with 4-factor prothrombin complex concentrate (4F-PCC) was often utilized for the management of life-threatening hemorrhages associated with oral factor Xa inhibitors. We evaluated the operational processes and outcomes of patients with oral factor Xa inhibitor-associated intracranial hemorrhages (ICH) treated with andexanet alfa or 4F-PCC. METHODS: We performed a retrospective, single-center case series of rivaroxaban or apixaban-associated ICH between 2016-2019 treated with andexanet alfa or 4F-PCC. Good or excellent hemostatic effectiveness, good functional outcome (Glasgow Outcome Score [GOS]> 3) at hospital discharge, and incidence of thrombosis within 30 days were reported. RESULTS: Eighteen patients were included in the andexanet alfa cohort and 11 in the 4F-PCC cohort. Excellent or good hemostasis occurred in 88.9% of andexanet alfa-treated patients and 60% of 4F-PCC-treated patients. Good functional outcome on discharge occurred in 55.6% of andexanet alfa-treated patients and 9.1% of 4F-PCC-treated patients. Thrombotic complications occurred in 16.7% of andexanet alfa-treated patients and 9.1% of 4F-PCC-treated patients. Median order-to-administration time was 1.1 hours [0.8-1.4] versus 0.5 hours [0.1-0.8] in the andexanet alfa and 4F-PCC group, respectively. The median cost of therapy was $29970/patient versus $6925/patient in the andexanet alfa and 4F-PCC group, respectively. CONCLUSIONS: We observed higher rates of occurrence of good or excellent hemostasis and GOS > 3 on hospital discharge and increased incidence of thrombosis in patients who received andexanet alfa compared to 4F-PCC for oral factor Xa inhibitor reversal. However, patients receiving 4F-PCC had lower pre-reversal Glasgow Coma Scale (GCS)score and larger pre-reversal ICH volume.

Thromboembolic Risk of 4-Factor Prothrombin Complex Concentrate versus Fresh Frozen Plasma for Urgent Warfarin Reversal in the Emergency Department.

INTRODUCTION: Warfarin is a potent anticoagulant used for the prevention and treatment of venous and arterial thrombosis. Occasionally, patients require emergent warfarin reversal due to active bleeding, supratherapeutic international normalized ratio, or emergent diagnostic or therapeutic interventions. Various agents can be used for emergent warfarin reversal, including fresh frozen plasma (FFP) and 4-factor prothrombin complex concentrate (4F-PCC). Both FFP and 4F-PCC are generally considered safe; however, both agents contain coagulation factors and have the potential to provoke a thromboembolic event. Although clinical trials have compared the efficacy and safety of FFP and 4F-PCC, data are limited comparing the risk of thromboembolism between the two agents. METHODS: A retrospective chart review was performed at a single, urban, academic medical center comparing the incidence of thromboembolism with FFP or 4F-PCC for warfarin reversal during a three-year period in the emergency department (ED) at Massachusetts General Hospital. Patients were included in the study if they were at least 18 years of age and were on warfarin per electronic health records. Patients were excluded if they had received both FFP and 4F-PCC during the same visit. The primary outcome was the frequency of thromboembolism within 30 days of 4F-PCC or FFP. Secondary outcomes included time to thromboembolic event and in-hospital mortality. RESULTS: Three hundred and thirty-six patients met the inclusion criteria. Thromboembolic events within 30 days of therapy occurred in seven patients (2.7%) in the FFP group and 14 patients (17.7%) in the 4F-PCC group (p=<0.001). Death occurred in 39 patients (15.2%) who received FFP and 18 patients (22.8%) who received 4F-PCC (p=0.115). Since the 4F-PCC group was treated disproportionately for central nervous system (CNS) bleeding, a subgroup analysis was performed including patients requiring reversal due to CNS bleeds that received vitamin K. The primary outcome remained statistically significant, occurring in four patients (4.1%) in the FFP group and nine patients (14.1%) in the 4F-PCC group (p=0.02). CONCLUSION: Our study found a significantly higher risk of thromboembolic events in patients receiving 4F-PCC compared to FFP for urgent warfarin reversal. This difference remained statistically significant when controlled for CNS bleeds and administration of vitamin K.

Impact of a Pharmacist-Driven Prothrombin Complex Concentrate Protocol on Time to Administration in Patients with Warfarin-associated Intracranial Hemorrhage.

INTRODUCTION: Advancements in the treatment of warfarin-associated intracranial hemorrhage (ICH) include the use of four-factor prothrombin complex concentrate (4F-PCC), which has demonstrated more rapid reversal of the international normalized ratio (INR) when compared with fresh frozen plasma. A pharmacist-driven protocol for 4F-PCC was implemented within our institution, which allows for pharmacist approval of 4F-PCC in patients diagnosed with warfarin-associated ICH and an INR ≥2. The pharmacist is responsible for determining the appropriate dose of 4F-PCC, preparation, bedside delivery, and order entry into the electronic medical record. Prior to implementation of the new protocol, the blood bank was responsible for 4F-PCC approval, dosing, product preparation, and arranging delivery with emergency department (ED) staff. The purpose of this study was to evaluate the impact of a pharmacist-driven protocol on time to 4F-PCC administration in warfarin-associated ICH. METHODS: We performed a retrospective review of consecutive patients who received 4F-PCC in a single ED from September 2015 through February 2017. Patients ≥18 years old were eligible for inclusion based on three criteria: confirmed diagnosis of ICH; confirmed warfarin use; and INR ≥2. Secondary outcomes included dose of 4F-PCC in concordance with INR and weight-based dosing recommendations and hospital protocol, as well as concomitant intravenous vitamin K administration. RESULTS: A total of 48 patients met inclusion criteria for the study with 24 patients in each protocol group. The median time to administration of 4F-PCC in the pharmacist-driven protocol group was 35 minutes (interquartile range [IQR] [25-62]; range, 11-133) compared with 70 minutes (IQR [34-89]; range, 14-244) in the pre-protocol group (p=0.034). We saw no differences for appropriate 4F-PCC dosing based on INR and patient weight between the two groups. CONCLUSION: Implementation of a pharmacist-driven protocol for 4F-PCC in the ED at our institution significantly reduced time to administration in patients presenting with warfarin-associated ICH.

Characterization of drug overdoses in an Ohio incarcerated population.

CONTEXT: Literature exists about drug overdose following release of recently incarcerated individuals and mortality among prisoners in the United States, but little information exists about drug overdoses in the imprisoned population. OBJECTIVE: This study aims to quantify and describe prisoner medication overdose requiring inpatient admission or assessment at a tertiary care facility and to assess the associated hospital charges. MATERIALS AND METHODS: A single-center, retrospective cohort study was conducted on all Ohio Department of Rehabilitation and Correction inmates who presented to The Ohio State University Wexner Medical Center with drug overdose between 15 October 2011 and 14 October 2014. Demographic information, overdose substances, exposure reason, clinical effects, lengths of stay, outcomes, and hospital charges were collected. RESULTS: Of the 130 patients included in the study, there were 100 intentional overdoses, 7 unintentional overdoses, 3 adverse drug reactions, and 20 unknown intentions. The most common drug in prisoner overdose was phenytoin (n = 29, 22%). While anticonvulsants were the most common drug class overall, anticonvulsants, antidepressants, and cardiovascular medications accounted for equal numbers of intensive care unit (ICU) admissions. Most patients exhibited multiple symptoms on arrival, most commonly neurologic, cardiovascular, and gastrointestinal symptoms. Patients were seen from 21 of the 28 Ohio Department of Rehabilitation and Correction facilities, of which five facilities, that largely house minimum and medium security prisoners, accounted for 61% of patients sent to our institution. The total sum of charges was $2,606,942 with 55% of charges from ICU stays. CONCLUSION: Our study shows that drug overdoses within our incarcerated population were largely intentional overdoses of anticonvulsants, cardiovascular drugs, and antidepressants. Opportunities exist to target intentional drug overdoses that accounted for 80% of prisoner overdoses for potential cost-savings.