Multicenter Comparison of the Safety and Efficacy of Clopidogrel Versus Ticagrelor for Neuroendovascular Stents.

BACKGROUND: Dual antiplatelet therapy (DAPT) is commonly employed for neuroendovascular stenting due to the significant risk of thromboembolism. Clopidogrel and aspirin are most often selected as initial DAPTs; however, there is limited literature available to support guidance of DAPT in this setting. The objective of this study was to evaluate safety and efficacy in patients whose final regimen included either DAPT with aspirin and clopidogrel (DAPT-C) or DAPT with aspirin and ticagrelor (DAPT-T). METHODS: This was a multicenter, retrospective cohort of patients who underwent neuroendovascular stenting and received DAPT between July 1, 2017, and October 31, 2020. Study participants were allocated into groups based on discharge DAPT regimen. The primary outcome was incidence of stent thrombosis at 3-6 months on DAPT-C versus DAPT-T, as defined by the presence of thrombus on imaging or new onset stroke. Secondary outcomes included major and minor bleeding and death within 3-6 months after the procedure. RESULTS: Five hundred and seventy patients were screened across 12 sites. Of those, 486 were included (DAPT-C n = 360, DAPT-T n = 126). There was no difference in the primary outcome of stent thrombosis between the DAPT-C and DAPT-T groups (8% vs. 8%, p = 0.97) and no difference in any of the secondary safety outcomes. CONCLUSIONS: Using DAPT-C or DAPT-T regimens in a broad population of neuroendovascular stenting procedures appears to have similar safety and efficacy profiles. Further prospective evaluation is warranted to streamline the practice of DAPT selection and monitoring to determine the impact on clinical outcomes.

Evaluation of a decentralized investigational drug service pharmacist in a cancer clinical trial infusion unit.

INTRODUCTION: Investigational drug service (IDS) oversees and manages use of investigational products. There is limited data on utility of pharmacy services in clinical trial conduct and outcomes, specifically on the value of a decentralized IDS pharmacist. METHODS: This is a quasi-experimental study conducted in an oncology clinical trial infusion unit. A retrospective chart review was done to reflect current practice from January through June 2022. A decentralized IDS pharmacist was piloted in December 2022. Data collected included number and types of consults, personnel requesting the consult, and intervention performed. A satisfaction questionnaire was conducted after the pilot program. RESULTS: A total of 16.3% (173 of 1062 patient visits) of pharmacy consults were completed in the centralized IDS pharmacy model, while 44.5% (81 of 182 patient visits) of pharmacy consults were completed during the decentralized IDS pharmacist pilot, p < .001. Decentralized IDS pharmacist completed 77% (62/81) of the consults during the pilot period. Most common types of consults were toxicity management (20%), electronic medical record issues (17%), and tubing and drug administration issues (16%). More than 80% of respondents to the satisfaction questionnaire responded that implementation of a decentralized IDS pharmacist is acceptable, appropriate, and feasible. CONCLUSION: This pilot study demonstrated that a decentralized IDS pharmacist in an oncology clinical trial infusion unit improved accessibility to an IDS pharmacist, increased pharmacy consults relevant to patient care and optimized centralized pharmacists medication distribution workflow. Further studies are needed to evaluate patient benefits from implementing decentralized IDS pharmacist in direct patient care activities.

Multicenter comparison of antiplatelet treatment strategies for urgent/emergent neuroendovascular stenting.

BACKGROUND: Emergent neuroendovascular stenting presents challenges for the utilization of antiplatelet agents. METHODS: This was a multicenter, retrospective cohort of patients who underwent emergent neuroendovascular stenting. The primary endpoints were thrombotic and bleeding events in relation to the timing of antiplatelet administration, route of administration, and choice of intravenous (IV) agent and the study investigated practice variability in antiplatelet utilization. RESULTS: Five-hundred and seventy patients were screened across 12 sites. Of those, 167 were included for data analysis. For patients who presented with ischemic stroke, artery dissection and emergent internal carotid artery (ICA) stenting who received an antiplatelet agent prior to or during the procedure, 57% were given an IV antiplatelet agent; for patients who were given an antiplatelet agent after the procedure, 96% were given an oral agent. For patients who presented for aneurysm repair and received an antiplatelet agent prior to or during the procedure, 74% were given an IV agent; patients who were given an antiplatelet agent after the completion of the procedure were given an oral antiplatelet agent 90% of the time. In patients who presented with ischemic stroke, artery dissection and emergent ICA stenting who received oral antiplatelet agents post-procedure were more likely to have thrombotic events compared to those who received oral antiplatelet agents prior to or during the procedure (29% vs 9%; p = 0.04). There were no differences in the primary outcomes observed when comparing other antiplatelet treatment strategies. CONCLUSION: The optimal timing of antiplatelet administration in relation to stent placement and route of administration of antiplatelet agents is unclear. Timing and route of administration of antiplatelet agents may have an effect on thrombosis in emergent neuroendovascular stenting. Significant practice variation exists in antiplatelet agent utilization in emergent neuroendovascular stenting.

Comparison of nimodipine formulations and administration techniques via enteral feeding tubes in patients with aneurysmal subarachnoid hemorrhage: A multicenter retrospective cohort study.

BACKGROUND: Nimodipine improves outcomes following aneurysmal subarachnoid hemorrhage (aSAH) and current guidelines suggest that patients with aSAH receive nimodipine for 21 days. Patients with no difficulty swallowing will swallow the whole capsules or tablets; otherwise, nimodipine liquid must be drawn from capsules, tablets need to be crushed, or the commercially available liquid product be used to facilitate administration through an enteral feeding tube (FT). It is not clear whether these techniques are equivalent. The goal of the study was to determine if different nimodipine formulations and administration techniques were associated with the safety and effectiveness of nimodipine in aSAH. METHODS: This was a retrospective multicenter observational cohort study conducted in 21 hospitals across North America. Patients admitted with aSAH and received nimodipine by FT for ≥3 days were included. Patient demographics, disease severity, nimodipine administration, and study outcomes were collected. Safety end points included the prevalence of diarrhea and nimodipine dose reduction or discontinuation secondary to blood pressure reduction. Predictors of the study outcomes were analyzed using regression modeling. RESULTS: A total of 727 patients were included. Administration of nimodipine liquid product was independently associated with higher prevalence of diarrhea compared to other administration techniques/formulations (Odds ratio [OR] 2.28, 95% confidence interval [CI] 1.41-3.67, p-value = 0.001, OR 2.76, 95% CI 1.37-5.55, p-value = 0.005, for old and new commercially available formulations, respectively). Bedside withdrawal of liquid from nimodipine capsules prior to administration was significantly associated with higher prevalence of nimodipine dose reduction or discontinuation secondary to hypotension (OR 2.82, 95% CI 1.57-5.06, p-value = 0.001). Tablet crushing and bedside withdrawal of liquid from capsules prior to administration were associated with increased odds of delayed cerebral ischemia (OR 6.66, 95% CI 3.48-12.74, p-value <0.0001 and OR 3.92, 95% CI 2.05-7.52, p-value <0.0001, respectively). CONCLUSIONS: Our findings suggest that enteral nimodipine formulations and administration techniques might not be equivalent. This could be attributed to excipient differences, inconsistency and inaccuracy in medication administration, and altered nimodipine bioavailability. Further studies are needed.

Intravenous Versus Oral Acetaminophen Use in Febrile Neurocritical Care Patients.

The use of intravenous (IV) acetaminophen (APAP) for fever has not been thoroughly studied in neurocritical care (NCC) patients, in whom a temperature of ≥38°C is associated with poor outcomes and treatment to normothermia is common practice. This retrospective study evaluated NCC patients admitted between May 1, 2012, and April 30, 2013, and received at least one dose of IV or oral (PO) APAP for a body temperature of ≥38°C. The primary aim of this study was to compare the reduction in body temperature (RIT) between IV and PO APAP, calculated as the change in temperature before and 0.5, 1, 2, 3, and 6 hours after administration. Descriptive statistics were used to assess use characteristics, and Kruskal-Wallis and Mann-Whitney U tests were used for between-group differences. There were 142 NCC patients who received a total of 405 IV APAP and 253 PO APAP doses. Seventy percent of all APAP doses resulted in a temperature of <38°C within 6 hours. The median oral body temperature before APAP was 38.8°C and 38.6°C for IV and PO APAP, respectively (p < 0.01). The median RIT at 0.5 (IV 0.25°C vs. PO 0.2°C), 1 (IV 0.4°C vs. PO 0.2°C), 2 (IV 0.7°C vs. PO 0.5°C), 3 (IV 0.9°C vs. PO 0.6°C), and 6 (IV 1°C vs. PO 0.8°C) hours was significantly greater for IV APAP than for PO APAP at all time points (p < 0.05). Patients with an acute ischemic stroke and patients with an intracerebral hemorrhage had a statistically significantly greater RIT with IV APAP therapy. IV APAP administered to febrile NCC patients was associated with a significantly greater RIT than PO, but 70% of all APAP doses resulted in a body temperature of <38°C within 6 hours. Further prospective studies are needed to determine if IV APAP improves clinical outcomes.

Time Is Brain: Acute Control of Repetitive Seizures and Status Epilepticus Using Alternative Routes of Administration of Benzodiazepines.

Time plays a major role in seizure evaluation and treatment. Acute repetitive seizures and status epilepticus are medical emergencies that require immediate assessment and treatment for optimal therapeutic response. Benzodiazepines are considered the first-line agent for rapid seizure control. Thus, various routes of administration of benzodiazepines have been studied to facilitate a quick, effective, and easy therapy administration. Choosing the right agent may vary based on the drug and route properties, patient's environment, caregiver's skills, and drug accessibility. The pharmacokinetic and pharmacodynamic aspects of benzodiazepines are essential in the decision-making process. Ultimately, agents and routes that give the highest bioavailability, fastest absorption, and a modest duration are preferred. In the outpatient setting, intranasal and buccal routes appear to be equally effective and more rapidly administered than rectal diazepam. On the other hand, in the inpatient setting, if available, the IV route is ideal for benzodiazepine administration to avoid any potential absorption delay. In this article, we will provide an overview and comparison of the various routes of benzodiazepine administration for acute control of repetitive seizures and status epilepticus.

Effect of bodyweight on VerifyNow Aspirin platelet function test: a retrospective review.

BACKGROUND: Antiplatelet therapy is used to prevent stent thrombosis in intracranial stents, but the optimal dose of aspirin is unknown. This study sought to determine whether the degree of platelet inhibition with aspirin is affected by bodyweight as observed through a platelet reactivity assay. METHODS: This is a retrospective review of patients who underwent neurovascular stent placement and had a VerifyNow Aspirin assay result. The primary outcome was the correlation between the VerifyNow Aspirin result, bodyweight, and the initial dose of aspirin. Secondary outcomes included the impact of the VerifyNow P2Y12 result and of weight on the incidence of bleeding or a thrombotic event. RESULTS: Of the 142 included patients, 62.7% weighed ≥70 kg and 88.7% were initiated on aspirin 300-325 mg daily. 83.8% achieved a therapeutic VerifyNow Aspirin result. There was minimal correlation between the VerifyNow Aspirin result, bodyweight, and aspirin dose (R2=0.02). Between patients who weighed <70 kg versus ≥70 kg, there was no difference in the mean aspirin reaction units (ARU) (449 vs 435, p=0.32) or in the incidence of bleeding (28% vs 17.1%, p=0.14) or a thrombotic event (4% vs 5.3%, p=0.59). No patient experienced stent thrombosis and eight patients experienced in-stent stenosis. In a multivariate analysis, only the VerifyNow P2Y12 result predicted the development of either bleeding or a thrombotic event (p<0.01). CONCLUSIONS: Bodyweight did not influence the likelihood of obtaining a therapeutic VerifyNow Aspirin result. The clinical utility of obtaining VerifyNow Aspirin assays for this patient population is unknown.

Management of an i.v. fluid shortage through use of electronic medical record alerts.

PURPOSE: Evaluation of mechanisms used to cope with an i.v. fluid shortage to determine if prescribing habits were changed and if substitution of an i.v. dose of magnesium with an oral dose impacted patient outcomes. METHODS: A single-center, retrospective analysis of electronic medical record (EMR) alerts and medical records covering 6-month periods before and during an i.v. fluid shortage was conducted. Records of adult medical and surgical inpatients admitted during these periods who had an order for i.v. or oral magnesium were screened for inclusion. The primary outcome of part 1 of the study was the percent acceptance of drug shortage-related EMR alert recommendations associated with i.v. magnesium. The primary outcome of part 2 of the study was the change in serum magnesium concentration (SMC) after an i.v. or oral dose of magnesium was administered. RESULTS: Of the 7,476 EMR alerts generated during provider ordering of i.v. magnesium products, 4.8% resulted in the provider accepting the recommendation to switch to an oral alternative, 89% resulted in continuation of an i.v. magnesium order, and 6.2% resulted in order cancellation. Among patients who received magnesium doses, SMC values increased by a mean (SD) of 0.135 (0.08) mg/dL per gram of i.v. magnesium sulfate administered (n = 251), compared to an increase of 0.058 (0.08) mg/dL per 400-mg tablet of magnesium oxide administered (n = 42). CONCLUSION: Acceptance of the EMR alert recommendations was low. Both i.v. magnesium sulfate and oral magnesium oxide are viable options for increasing SMC.