OBJECTIVE:This study evaluated weight-based dosing of antithymocyte globulin, or ATG, using ideal body weight (IBW) in kidney transplant patients with and without obesity. METHODS:This was a single-center, retrospective cohort study of adult kidney transplant recipients who received ATG for induction from 8/2022 to 8/2023. Patients were divided into groups based on obesity status (i.e., body mass index [BMI] ≥ 30). The primary comparative endpoint was the average absolute lymphocyte count (ALC) across post-operative days (POD) 1 through 4. Secondary comparative endpoints included total ATG dose, hematologic outcomes, graft function, infection, rejection, malignancy, graft survival, and overall survival. Continuous data was assessed for normality, then compared using either the Student t-test or the Mann-Whitney U test and presented as averages ± standard deviation or median (interquartile range). Categorical data were compared using the chi-square or Fisher's exact test and presented as counts (%). An a priori power calculation demonstrated that 126 patients (63 per group) were required to detect a 0.1 k/uL difference between groups with alpha = 0.05 and 80% power. RESULTS:Baseline characteristics were similar between groups; however, the group with obesity had more Black patients and fewer Hispanic and Asian/Pacific Islander patients. Patients with obesity more frequently had HTN and DM as their ESRD etiologies and experienced more delayed graft function. En bloc transplants were more common in the group without obesity. The average ALC POD1-4 was similar across groups. The total ATG dose, expressed as mg/kg IBW, was the same between groups. The total ATG dose, expressed as mg/kg actual body weight (ABW), was significantly lower in the obese group. In the group with obesity, the average WBC count POD1- 4 was higher, eGFR was lower, and the incidence of CMV viremia was higher. Rejection rate, graft survival, and patient survival were similar between groups. CONCLUSIONS:Dosing ATG based on IBW results in similar ALC depletion in patients with and without obesity. There were similar allograft and safety findings observed between groups. Compared with theoretical ABW dosing, this IBW dosing strategy resulted in significantly less ATG use, potentially leading to substantial cost savings.
Maribavir is a well-tolerated option for drug-resistant CMV, though there is no available guidance for dosing in patients on continuous renal replacement therapy (CRRT). This study aimed to determine maribavir clearance and hemofilter adsorption during CRRT to inform dosing recommendations. Maribavir pharmacokinetic profiles were quantified using an in vitro model. Total clearance during CRRT (CLCRRT) in addition to sieving (SC), and saturation (SA) coefficients were calculated based on these experiments. Optimal maribavir doses were then estimated from the in vitro parameters. The mean SA was 0.853 and did not differ by filter type (P = 0.831). The SC was higher with the M150 filter (0.102) than for the HF1400 filter (0.080; P = 0.040). Across all experiments, the mean maribavir CLCRRT ranged from 0.19 to 0.49 L/hr and did not significantly differ between continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD) (P = 0.853) but was higher at 4 vs. 2 L/hr (P = 0.007). The mean CLCRRT was lower with the M150 filter compared to the HF1400 filter (P = 0.063), which was attributed to the higher adsorption with HF1400. Filter type and effluent flow rate were independently associated with CLCRRT for CVVH whereas only effluent flow rate was independently associated with CLCRRT for CVVHD. The package insert dose of 400 mg twice daily would lead to adequate concentrations across the most common flow rates (1–4 L/hr) with either modality or filter type. Maribavir clearance during CRRT was relatively low, though it adsorbed significantly more to the HF1400 filter. At typical CRRT flow rates, standard dosing of 400 mg twice daily is predicted to provide adequate exposures.
Background/Objectives: Perioperative hypotension during kidney transplantation poses a risk to graft function and survival. Angiotensin II (AngII) is an endogenous vasoconstrictor targeting the renin–angiotensin–aldosterone system (RAAS) to increase blood pressure. Black patients may have a different response to synthetic angiotensin II (AT2S) compared to non-Black patients, given differential expressions in renin profiles. The purpose of this study is to assess the difference between Black and non-Black patients in total vasopressor duration and usage when AT2S is first line for hypotension during kidney transplantation. Methods: A single-center, retrospective cohort study comparing Black and non-Black patients who required AT2S as a first-line vasopressor for hypotension during the perioperative period of kidney transplantation. Results: The primary outcome evaluating total usage of vasopressors found that Black patients required longer durations of vasopressors (36.9 ± 66.8 h vs. 23.7 ± 31.7 h; p = 0.022) but no difference in vasopressor amount (0.07 ± 0.1 NEE vs. 0.05 ± 0.1 NEE; p = 0.128) compared to non-Black patients. Regression analysis found that body weight was associated with the duration of vasopressors (p < 0.05), while baseline systolic blood pressure was inversely associated with it. Longer duration of vasopressors and duration of transplant surgery were associated with delayed graft function in regression analysis (p < 0.05). Conclusions: Black patients had a longer duration of vasopressors, but this was not driven by differences in usage of AT2S. As baseline weight was significantly higher in Black patients and associated with duration of usage, perhaps the metabolic differences in our Black patients led to the observed differences. Regardless, longer durations of vasopressors were associated with delayed graft function, making this an area of utmost importance for continued investigation.
Background/Objectives: The use of angiotensin II (AT2S) as a vasopressor in patients receiving angiotensin receptor blockers (ARBs) prior to kidney transplant (KT) raises theoretical concerns. At our center, AT2S is the first-line vasopressor during KT. This study evaluated the hemodynamic and clinical effects of pre-transplant ARBs on AT2S use in KT. Methods: This single-center, retrospective cohort trial included patients with hypertension ≥ 18 years old on antihypertensive therapy who received AT2S as the first-line vasopressor peri-transplant. Patients were divided into ARB and non-ARB cohorts. Primary outcomes included total AT2S duration, time with SBP < 120 mmHg, and need for additional vasopressor support. Results: A total of 65 patients were analyzed: 22 in the ARB group and 43 in the non-ARB group. There were no significant differences in the frequency or duration of SBP < 120 mmHg or additional vasopressor requirements between groups (p > 0.05). Hospital and ICU stay length, safety, and adverse drug events were also similar. Conclusions: Contrary to theoretical concerns and observations in other distributive shock populations, no significant hemodynamic or clinical differences were observed in the response to AT2S in patients with pre-transplant ARB use.
Objective: The purpose of this study was to evaluate the utility of end-tidal carbon dioxide (ETCO2) values as a predictive marker of in-hospital cardiac arrest (IHCA). This was achieved by comparing the trends of ETCO2 values in mechanically ventilated ICU patients that experienced an IHCA versus patients that did not. Methods: A single-center, retrospective, observational, and comparative cohort study at an academic medical center. Mechanically ventilated adults in the ICU who received continuous ETCO2 monitoring were included. Patients who were transferred to our facility already intubated, experienced an out-of-hospital cardiac arrest, or had a do-not-resuscitate order were excluded. Extracted data points included demographics, comorbidities, vitals, labs, and outcomes. Patients were grouped into IHCA and non-IHCA cohorts, and the trends of ETCO2 values were compared at multiple time points for 48 h before the IHCA or after intubation (time zero) for the groups, respectively. An ROC curve was constructed to determine the predictive value of ETCO2 for IHCA. Results: A total of 207 patients were included, of which 104 (50.2%) had an IHCA and 103 (49.8%) did not. There were no differences in the mean SOFA scores at the initiation of mechanical ventilation (8.5 vs. 7.6). The ETCO2 values were decreased in the IHCA cohort, and significantly different at each time point analyzed from 300 min until immediately prior to the arrest (p < 0.001). The ETCO2 values were a mean of 20.0 mmHg in the IHCA cohort at the index time vs. 34.7 mmHg in the non-IHCA cohort (p < 0.001). The ROC analysis demonstrated moderate reliability, with an AUC = 0.687 (p < 0.0001, 95% CI 0.613–0.761) and with an ETCO2 of less than 23 mmHg, demonstrating a 67% sensitivity and a 71% specificity, as well as a 70% PPV for predicting the IHCA from our sample. Conclusions: Patients typically have rapid clinical deteriorations prior to cardiac arrest, and monitoring ETCO2 is easily achieved at the bedside while aiding in clinical decision making. The ETCO2 values in our study were significantly decreased in the IHCA cohort prior to cardiac arrest compared to the stable values in those that did not experience an IHCA, indicating that ETCO2 monitoring may have utility in predicting cardiac arrest. Further study is warranted to evaluate if predictive models utilizing ETCO2 can be constructed to predict IHCAs in mechanically ventilated ICU patients.
Objective: To determine the impact of item-writing flaws and cognitive level on student performance metrics in 1 course series across 2 semesters at a single institution. Methods: Four investigators reviewed 928 multiple-choice items from an integrated therapeutics course series. Differences in performance metrics were examined between flawed and standard items, flawed stems and flawed answer choices, and cognitive levels. Results: Reviewers found that 80% of the items were flawed, with the most common types being implausible distractors and unfocused stems. Flawed items were generally easier than standard ones, but the type of flaw significantly impacted the difficulty. Items with flawed stems had the same difficulty as standard items; however, those with flawed answer choices were significantly easier. Most items tested lower-level skills and have more flaws than higher-level items. There was no significant difference in difficulty between lower- and higher-level cognitive items, and higher-level items were more likely to have answer flaws than item flaws. Conclusion: Item-writing flaws differently impact student performance. Implausible distractors artificially lower the difficulty of questions, even those designed to assess higher-level skills. This effect contributes to a lack of significant difference in difficulty between higher- and lower-level items. Unfocused stems, on the other hand, likely increase confusion and hinder performance, regardless of the question's cognitive complexity.
OBJECTIVE:The purpose of this analysis was to identify, analyze, and report patterns (or themes) of planning and preparation considerations of students that scored less than the historic average score on the Pre-NAPLEX® exam. METHODS:This qualitative study was a retrospective, inductive thematic analysis of de-identified semi-structured interview field notes collected from student interviews for those students that scored less than the historic average score on the Pre-NAPLEX® exam. RESULTS:Ninety-one students were initially contacted based on their score on the Pre-NAPLEX® exam to participate in one-on-one virtual discussions (i.e., interviews) with faculty members. Fifty-two responded and participated with their responses analyzed and included in thematic categorization. Four major themes were identified during the analysis. These include 1) Organization and Messaging of NAPLEX® Preparation Efforts, 2) Time Management during Competing Obligations, 3) Test Taking Experience, and 4) Curricular Disconnect. CONCLUSION:Student performance on the NAPLEX licensing exam is of great concern to many colleges of pharmacy. As a result, many institutions are looking at root-causes for poor performance and working to implement structural changes at their institution to address these concerns. This investigation identified four major themes surrounding the preparation and planning for the Pre-NAPLEX® for students that scored less than the historic average score on the Pre-NAPLEX®. These include 1) Organization and Messaging of NAPLEX® Preparation Efforts, 2) Time Management during Competing Obligations, 3) Test Taking Experience, and 4) Curricular Disconnect. Each of these themes provides potentially actionable items to improve how students prepare and plan for the Pre-NAPLEX®, which may be translatable to informing actions to improve results on the actual NAPLEX exam itself.
INTRODUCTION:Angiotensin II (ATII) maintains blood pressure via RAAS with a beneficial adverse effect profile versus catecholamines and phenylephrine. Head-to-head data comparing ATII to phenylephrine are lacking regarding renal allograft function, hemodynamic efficacy, and safety within the perioperative period of kidney transplantation. METHODS:This single-center, retrospective study included adult kidney transplant recipients who received continuous infusions of ATII or phenylephrine within a 24-h perioperative period as a first-line vasopressor according to an institutional algorithm. The primary endpoint was allograft function. Secondary endpoints were hemodynamic efficacy and adverse effects. RESULTS:Among 105 patients, there was no significant difference in IGF (p = 0.545), SGF (p = 0.557), or DGF (p = 0.878) between patient cohorts. In the 34 patients with cold ischemia time (CIT) > 14-h, IGF was higher (p = 0.013) and DGF (p = 0.045) was lower in the ATII cohort versus phenylephrine. In all patients, ATII was associated with a decreased need for additional vasopressor agents (p < 0.001). Adverse effect profiles were similar between cohorts (p > 0.05). CONCLUSION:Among kidney transplant recipients, ATII may be a suitable first-line alternative compared with phenylephrine in the perioperative period for hypotension management with a reduced need for additional vasopressor support. Allograft benefits were observed in patients with prolonged CIT.
Introduction: Glycemic management in the intensive care unit is an evolving practice area. This evolution has included the refinement of blood glucose targets, matching glycemic management to premorbid status, and investigations into the impact of glycemic variability and relative hypoglycemia on ICU outcomes. The interplay between these phenomena and absolute hypoglycemia has yet to be investigated in hyperglycemic emergencies. Objectives: To examine the incidence of and risk factors for relative hypoglycemia and absolute hypoglycemia in patients admitted to an intensive care unit for the management of hyperglycemic emergencies. Methods: This was a retrospective, single-center, exploratory analysis of adults admitted to the medical intensive care unit for diabetic ketoacidosis or hyperosmolar hyperglycemic syndrome. The primary outcome was the incidence of relative hypoglycemia, defined as a blood glucose level 30% lower than baseline. The baseline was determined by the estimated average blood glucose calculated from hemoglobin A1c within 3 months of index admission. Secondary outcomes were ICU length of stay, glycemic variability, and incidence of absolute hypoglycemia.Results: Relative hypoglycemia was observed in 60% of patients in the cohort. Longer insulin infusion duration and higher hemoglobin A1c levels were found to statistically increase the risk of developing relative hypoglycemia. Higher glycemic variability and longer ICU length of stay were associated with the risk of developing absolute hypoglycemia. Conclusions: Relative hypoglycemia is a frequent occurrence in this patient population. Hemoglobin A1c and duration of the insulin infusion statistically influenced the risk of developing relative hypoglycemia. Higher glycemic variability and longer ICU stay were significantly associated with developing absolute hypoglycemia. While relative hypoglycemia is common in hyperglycemic emergencies, the clinical impact remains uncertain and warrants additional investigation.