Prospective Trial on the Use of Trough Concentration versus Area under the Curve To Determine Therapeutic Vancomycin Dosing.

We hypothesized that dosing vancomycin to achieve trough concentrations of >15 mg/liter overdoses many adults compared to area under the concentration-time curve (AUC)-guided dosing. We conducted a 3-year, prospective study of vancomycin dosing, plasma concentrations, and outcomes. In year 1, nonstudy clinicians targeted trough concentrations of 10 to 20 mg/liter (infection dependent) and controlled dosing. In years 2 and 3, the study team controlled vancomycin dosing with BestDose Bayesian software to achieve a daily, steady-state AUC/MIC ratio of ≥400, with a maximum AUC value of 800 mg · h/liter, regardless of trough concentration. For Bayesian estimation of AUCs, we used trough samples in years 1 and 2 and optimally timed samples in year 3. We enrolled 252 adults who were ≥18 years old with ≥1 available vancomycin concentration. Only 19% of all trough concentrations were therapeutic versus 70% of AUCs (P < 0.0001). After enrollment, median trough concentrations by year were 14.4, 9.7, and 10.9 mg/liter (P = 0.005), with 36%, 7%, and 6% over 15 mg/liter (P < 0.0001). Bayesian AUC-guided dosing in years 2 and 3 was associated with fewer additional blood samples per subject (3.6, 2.0, and 2.4; P = 0.003), shorter therapy durations (8.2, 5.4, and 4.7 days; P = 0.03), and reduced nephrotoxicity (8%, 0%, and 2%; P = 0.01). The median inpatient stay was 20 days among nephrotoxic patients versus 6 days (P = 0.002). There was no difference in efficacy by year, with 42% of patients having microbiologically proven infections. Compared to trough concentration targets, AUC-guided, Bayesian estimation-assisted vancomycin dosing was associated with decreased nephrotoxicity, reduced per-patient blood sampling, and shorter length of therapy, without compromising efficacy. These benefits have the potential for substantial cost savings. (This study has been registered at ClinicalTrials.gov under registration no. NCT01932034.).

Inpatient Neurology Deaths and Factors Associated With Discharge to Hospice.

Background and Purpose: The Neurology Mortality Review Committee at our institution identified variability in location of death for patients on our inpatient neurology services. Hospice may increase the number of patients dying in their preferred locations. This study aimed to characterize patients who die on inpatient neurology services and explore barriers to discharge to hospice. Methods: This retrospective study was completed at a single, quaternary care medical center that is a Level I Trauma Center and Comprehensive Stroke Center. Patients discharged by an inpatient neurology service between 6/2019-1/2021 were identified and electronic medical record review was performed on patients who died in the hospital and who were discharged to hospice. Results: 69 inpatient deaths and 74 discharges to hospice occurred during the study period. Of the 69 deaths, 54 occurred following withdrawal of life sustaining treatment (WLST), of which 14 had a referral to hospice placed. There were 88 "hospice-referred" patients and 40 "hospice-eligible" patients. Hospice-referred patients were less likely to require the intensive care unit than hospice-eligible patients. Hospice-referred patients had their code status changed to Do Not Intubate earlier and were more likely to have advanced directives available. Conclusion: Our data highlight opportunities for further research to improve discharge to hospice including interhospital transfers, advanced directives, earlier goals of care discussions, palliative care consultations, and increased hospice bed availability. Importantly, it highlights the limitations of using in-hospital mortality as a quality indicator in this patient population.

Cost-Effectiveness of Cilostazol Added to Aspirin or Clopidogrel for Secondary Prevention After Noncardioembolic Stroke.

Background The objective of the study was to assess the cost-effectiveness of cilostazol (a selective phosphodiesterase 3 inhibitor) added to aspirin or clopidogrel for secondary stroke prevention in patients with noncardioembolic stroke. Methods and Results A Markov model decision tree was used to examine lifetime costs and quality-adjusted life years (QALYs) of patients with noncardioembolic stroke treated with either aspirin or clopidogrel or with additional cilostazol 100 mg twice daily. Cohorts were followed until all patients died from competing risks or ischemic or hemorrhagic stroke. Probabilistic sensitivity analysis using Monte Carlo simulation was used to model 10 000 cohorts of 10 000 patients. The addition of cilostazol to aspirin or clopidogrel is strongly cost saving. In all 10 000 simulations, the cilostazol strategy resulted in lower health care costs compared with aspirin or clopidogrel alone (mean $13 488 cost savings per patient; SD, $8087) and resulted in higher QALYs (mean, 0.585 more QALYs per patient lifetime; SD, 0.290). This result remained robust across a variety of sensitivity analyses, varying cost inputs, and treatment effects. At a willingness-to-pay threshold of $50 000/QALY, average net monetary benefit from the addition of cilostazol was $42 743 per patient over their lifetime. Conclusions Based on the best available data, the addition of cilostazol to aspirin or clopidogrel for secondary prevention following noncardioembolic stroke results in significantly reduced health care costs and a gain in lifetime QALYs.

Education Research: A novel resident-driven neurology quality improvement curriculum.

OBJECTIVE: To describe and assess the effectiveness of a neurology resident quality improvement curriculum focused on development of practical skills and project experience. METHODS: We designed and implemented a quality improvement curriculum composed of (1) a workshop series and (2) monthly resident-led Morbidity, Mortality, & Improvement conferences focused on case analysis and project development. Surveys were administered precurriculum and 18 months postcurriculum to assess the effect on self-assessed confidence with quality improvement skills, attitudes, and project participation. Scholarship in the form of posters, presentations, and manuscripts was tracked during the course of the study. RESULTS: Precurriculum, 83% of neurology residents felt that instruction in quality improvement was important, but most rated their confidence level with various skills as low. Following implementation of the curriculum, residents were significantly more confident in analyzing a patient case (odds ratio, 95% confidence interval) (2.4, 1.9-3.1), proposing system changes (3.1, 2.3-3.9), writing a problem statement (9.9, 6.2-13.5), studying a process (3.1, 2.3-3.8), identifying resources (3.1, 2.3-3.8), identifying appropriate measures (2.5, 1.9-3.0), collaborating with other providers to make improvements (4.9, 3.5-6.4), and making changes in a system (3.1, 2.3-3.8). Project participation increased from the precurriculum baseline (7/18, 39%) to the postcurriculum period (17/22, 77%; p = 0.023). One hundred percent of residents surveyed rated the curriculum positively. CONCLUSIONS: Our multifaceted curriculum was associated with increased resident confidence with quality improvement skills and increased participation in improvement projects. With adequate faculty mentorship, this curriculum represents a novel template for preparing neurology residents for meeting the expectations of improvement in practice and offers scholarship opportunities.

Blood Pressure Elevation and Risk of Moyamoya Syndrome in Patients With Trisomy 21.

OBJECTIVES: Individuals with Down syndrome (DS) are at risk for the development of moyamoya syndrome (MMS); MMS is often recognized only after a resulting stroke has occurred. Our goal with this study was to determine if elevations in blood pressure (BP) precede acute presentation of MMS in individuals with DS. METHODS: A single-center, retrospective case-control study was performed. Thirty patients with MMS and DS and 116 patients with DS only were identified retrospectively. Three BP recordings were evaluated at set intervals (18-24 months, 12-18 months, and 6-12 months before diagnosis of MMS). These were then compared against control averages from patients with DS only. To assess changes over the time, we used general linear model repeated measures analysis of variance. To identify independent predictors of MMS and DS, we used a multivariable analysis using generalized estimating equations accounting for repeated measures of BP. RESULTS: BP in patients with MMS and DS rose significantly over the 24-month period preceding presentation (34th, 42nd, and 70th percentiles at the 18-24-month, 12-18-month, and 6-12-month periods, respectively). BPs in the patients with both MMS and DS were significantly higher than in the DS-only controls in the 6 to 12 (P < .001) and 12 to 18 months before presentation (P = .016). Higher Suzuki scores, bilateral disease, and posterior circulation involvement were also predictive of BP elevation before presentation. CONCLUSIONS: Elevations in BP may foreshadow presentation of MMS in individuals with DS. This simple, low-cost screening measure may lead to early identification of at-risk patients in the medical home and prevent irreversible neurologic injury.