Methods Used to Obtain Pediatric Patient Weights, Their Accuracy and Associated Drug Dosing Errors in 142 Simulated Prehospital Pediatric Patient Encounters.

Background: Prehospital pediatric drug dosing errors occur at a high rate. Multiple factors contribute to these errors. The contribution of weight estimation errors to drug dosing errors is unknown. We describe methods used to obtain weights and resulting drug dosing errors. Methods: As part of a quality improvement study in 16 EMS agencies, we conducted four simulated pediatric scenarios: seizing, hypoglycemic infant, infant cardiac arrest, 18-month old burn and a 5-year old with anaphylactic shock. Crews used their regular drug bags and equipment. Simulations were observed by study team members with video review and scored on a standardized scoring sheet. Results: 142 scenarios were completed. Methods to obtain patient weights were: asking parent 17/142 (12.0%), patient age 35/142 (24.8%) and Broselow-Luten Tape (BLT) 89/142 (63.1%). There were 19 (13.4% 95% CI 8.5, 20.0) incorrect weight estimations resulting in 18 (12.7% 95% CI 8.2, 19.2) dosing errors (1 asking parent, 9 patient age and 8 BLT). Ten dosing errors were directly caused by weight estimation errors. In 41/89 (46.1% 95%CI 36.1, 56.4) BLT uses there was a near-miss error that did not result in a dosing error. One pound to kilogram conversion error occurred. Conclusions: BLT is the most frequently used method to obtain a patient weight. Drug dosing errors were most frequent with patient age, followed by BLT and asking the parent. System-based solutions-weight determination hierarchy, not using the BLT on seated patients, and more frequent training and practice with the BLT-are needed to improve drug-dosing accuracy.

The Volume-Outcome Relationship and Traveling for Hepatobiliary and Pancreatic Surgery: A Quantitative Analysis of Patient Perspectives.

Despite the well-established relationship between volume and outcomes, patients continue to have procedures performed at low-volume hospitals. The factors patients use to make the complex decision of where to have hepatopancreaticobiliary (HPB) surgery remain poorly characterized. A novel survey instrument was administered to all patients who had undergone HPB surgery at two university-affiliated community hospitals. 76 patients participated in the study (89% response rate). The majority of patients were unaware of the volume-outcome relationship (58.8%). No demographic factors differed between patients who were or were not aware except for patient research. Physician factors were the most important selection category (64.4%). Only 28.9% of patients were willing to travel more than two hours to have an operation performed at a hospital with a high volume/improved quality. Despite many voices calling for regionalization, patient decision-making factors should be considered before any realistic implementation.

Assessment of antibiotic use and concordance with practice guidelines within 3 diverse ambulatory clinic systems.

OBJECTIVES: The objectives of this study were (1) to determine the rate of antibiotic prescribing at ambulatory clinics, and (2) to assess the concordance of antibiotic prescriptions with published guidelines and Food and Drug Administration-approved indications in terms of drug choices and dosing regimen. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Patients of all ages receiving at least 1 prescription during ambulatory visits in 2016 to 2017 were observed. OUTCOME MEASURES: For each of the 3 clinic systems included in this study, oral antibiotic prescribing rates were estimated per patient and per ambulatory visit. Then, the concordance of oral antibiotic prescribing was assessed with respect to (1) choice of agent and (2) the dosing regimen by comparing it to the recommended therapeutic regimen (RTR). RESULTS: A total of 284,348 patients receiving at least 1 prescription were included in the analysis. Between clinics, 17.4 to 43.7 per 100 patients received antibiotics. Of the antibiotics prescribed, 48.9% in Clinic A, 48.0% in Clinic B, and 60.7% in Clinic C were considered to be discordant in terms of drug choice. When the dosing regimen was taken into account in addition to the choice of agent, 72.6% in Clinic A, 76.7% in Clinic B, and 81.6% in Clinic C were discordant based on drug choice or dosing regimen. Of the prescriptions written with a discordant dosing regimen, 91.2% in Clinic A, 79.6% in Clinic B, and 91.0% in Clinic C were at a higher dosage than RTR. CONCLUSION: Antibiotic prescribing rates vary by clinics, whereas discordant prescribing is consistently prevalent across clinics. More efforts should be put into ambulatory care to address antibiotic misuse problems, and our method could improve ambulatory antimicrobial stewardship programs.

Synchronization of the Normal Human Peripheral Immune System: A Comprehensive Circadian Systems Immunology Analysis.

In this study, we sought to fill an important gap in fundamental immunology research by conducting a comprehensive systems immunology analysis of daily variation in the normal human peripheral immune system. Although variation due to circadian rhythmicity was not a significant source of variation in daily B-cell levels or any CD4+ functional subset, it accounted for more than 25% of CD4+ regulatory T-cell variation and over 50% of CD8+ central memory variation. Circadian rhythmicity demonstrated phase alignment within functional phenotypes. In addition, we observed that previously-described mechanistic relationships can also appear in the peripheral system as phase shifting in rhythmic patterns. We identified a set of immune factors which are ubiquitously correlated with other factors and further analysis also identified a tightly-correlated "core" set whose relational structure persisted after analytically removing circadian-related variation. This core set consisted of CD8+ and its subpopulations and the NK population. In sum, the peripheral immune system can be conceptualized as a dynamic, interconnected wave-field repeating its pattern on a daily basis. Our data provide a comprehensive inventory of synchronization and correlation within this wave-field and we encourage use of our data to discover unknown mechanistic relationships which can then be tested in the laboratory.

Dosing Errors Made by Paramedics During Pediatric Patient Simulations After Implementation of a State-Wide Pediatric Drug Dosing Reference.

Background: Drug dosing errors occur at a high rate for prehospital pediatric patients. To reduce errors, Michigan implemented a state-wide pediatric dosing reference (PDR), with doses listed in milliliters, the requirement that doses be drawn into a smaller syringe from a pre-loaded syringe using a stopcock, and dilution of certain drugs to different concentrations.Purpose: To evaluate the rate of medication errors, including errors of omission and commission, after implementation of a state-wide PDR.Methods: EMS crews from 15 agencies completed 4 validated, simulation scenarios: an infant seizing, an infant cardiac arrest, an 18-month-old with a burn, and 5-year-old with anaphylactic shock. Agencies were private, public, not-for-profit, for-profit, urban, rural, fire-based, and third service. EMS crews used their regular equipment and were required to carry out all the steps to administer a drug dose. Two evaluators scored crew performance via direct observation and video review. An error was defined as [Formula: see text]20% difference compared to the weight-appropriate dose. Descriptive statistics were utilized.Results: A total of 142 simulations were completed. The majority of crews were (58.3%) Emergency Medical Technician-Paramedic (EMTP)/EMTP. For the cardiac arrest scenario, 51/70 (72.9%; 95% CI: 60.9%, 82.8%) epinephrine doses were correct. There were 6 (8.6%, 95% CI: 2.0%, 15.1%) 10-fold overdoses and one (1.4%; 95% CI: -1.4%, 4.2%), 10-fold under dose. In the seizure scenario, 28/50 (56.0%; 95% CI: 42.2%, 69.8%) benzodiazepine doses were correct; 6/18 (33.3%; 95% CI: 11.5%, 55.1%) drug dilutions were incorrect resulting in dosing errors. Unrecognized air was frequently entrained into the administration syringe resulting in under doses. Overall, 31.2% (95% CI: 25.5%, 36.6%) of drug doses were incorrect. Obtaining an incorrect weight led to a drug dosing error in 18/142 (12.7%, 95% CI: 7.2%, 18.2%) cases. Errors of omission included failure to check blood sugar in the seizure scenario and failure to administer epinephrine and a fluid bolus in anaphylactic shock.Conclusion: Despite implementation of a PDR, dosing errors, including 10-fold errors, still occur at a high rate. Errors occur with dilution and length-based tape use. Further error reduction strategies, beyond a PDR and that target errors of omission, are needed for pediatric prehospital drug administration.

Effectiveness of instructor-guided independent learning in comparison to traditional didactic lecture in the preclinical medical curriculum: A retrospective cohort study.

Introduction: To create time for learner-centered forms of active learning in the classroom, didactic lectures are being replaced with instructor-guided independent learning (IGIL) assignments that students complete on their own outside of the formal educational setting. The effectiveness of IGIL assignments in supporting learning across the preclinical medical curriculum when applied to all learners in the same class of students has not been examined. Further, we have examined this performance across three class cohorts. Methods: In this retrospective cohort study, we compared student performance on questions from both IGIL assignments and didactic lectures that were items on the end-of-course summative examinations. Data were analyzed from three classes of graduating students in each of the 14 courses that comprise our preclinical medical curriculum. Results: The results of this study suggest that IGIL assignments were as effective as didactic lectures in supporting student learning in our preclinical medical curriculum. Importantly, IGIL assignments supported learning for both low and high performing students. Conclusions: Students can effectively learn from IGIL assignments when the assignments are well-designed and their importance in the curriculum is emphasized.

Prevalence and Scope of Point-of-Care Ultrasound Education in Internal Medicine, Pediatric, and Medicine-Pediatric Residency Programs in the United States.

OBJECTIVES: The purpose of this study was to determine the prevalence and scope of point-of-care ultrasound (US) education in internal medicine, pediatric, and medicine-pediatric residency programs nationwide. METHODS: Program directors were surveyed between January and June 2016 with a 15-item online questionnaire to assess the state of point-of-care US training in their programs. The survey aimed to identify whether programs had an established point-of-care US curriculum and, if not, what reasons may have existed for a lack of point-of-care US training in their programs. RESULTS: The survey was distributed to 685 program directors, and the response rate was 19.2%. Only 31.5% of respondents reported having a formal point-of-care US curriculum in their program, and in 12.4% of programs, there was no US training at all. The presence of point-of-care US training as reported by internal medicine (n = 64) and medicine-pediatric (n = 24) respondents showed formal point-of-care US curriculum rates of 37.5% and 43.5%, respectively. Pediatric programs (n = 24) reported limited point-of-care US training, with formal curriculum in only 12.4% of programs and 27.3% having no point-of-care US training at all. The most common reasons for lack of a point-of-care US curriculum among program directors were lack of trained faculty/instructors (70.4%), lack of guidelines/standards by governing societies (44.4%), and lack of the necessary technology (33.3%). CONCLUSIONS: Less than half of residents with internal medicine training will have trained at a program with a point-of-care US curriculum, and point-of-care US training in pediatrics is even more limited. The major reason for the lack of point-of-care US education is a lack of trained faculty or instructors.

Treatment of type 1 diabetes with teplizumab: clinical and immunological follow-up after 7 years from diagnosis.

AIMS/HYPOTHESIS: The long-term effects of successful immune therapies for treatment of type 1 diabetes have not been well studied. The Autoimmunity-Blocking Antibody for Tolerance (AbATE) trial evaluated teplizumab, an Fc receptor non-binding humanised anti-CD3 monoclonal antibody in individuals with new-onset type 1 diabetes, and ended in 2011. Clinical drug-treated responders showed an increased frequency of 'partially exhausted' CD8+ T cells. We studied the clinical, immunological and metabolic status of participants after an average follow-up of 7 years. METHODS: Participants with detectable C-peptide at year 2 of AbATE returned for follow-up. C-peptide responses were assessed by 4 h mixed-meal tolerance test. Autoantibodies and HbA1c levels were measured and average daily insulin use was obtained from patient logs. Peripheral blood mononuclear cells were analysed by flow cytometry and cytokine release. RESULTS: Fifty-six per cent of the original participants returned. Three of the original control group who did not return had lost all detectable C-peptide by the end of the 2 year trial. The C-peptide responses to a mixed-meal tolerance test were similar overall in the drug vs control group of participants but were significantly improved, with less loss of C-peptide, in drug-treated responders identified at 1 year. However, the improvements in C-peptide response were not associated with lower HbA1c levels or insulin use. Drug-treated responders showed a significantly increased frequency of programmed cell death protein 1-positive central memory and anergic CD8+ T cells at follow-up. CONCLUSIONS/INTERPRETATION: These findings suggest there is reduced decline in C-peptide and persistent immunological responses up to 7 years after diagnosis of diabetes in individuals who respond to teplizumab. TRIAL REGISTRATION: ClinicalTrials.gov NCT02067923; the protocol is available at www.immunetolerance.org (ITN027AI).

Autoreactive T effector memory differentiation mirrors ß cell function in type 1 diabetes.

In type 1 diabetes, cytotoxic CD8+ T cells with specificity for ß cell autoantigens are found in the pancreatic islets, where they are implicated in the destruction of insulin-secreting ß cells. In contrast, the disease relevance of ß cell-reactive CD8+ T cells that are detectable in the circulation, and their relationship to ß cell function, are not known. Here, we tracked multiple, circulating ß cell-reactive CD8+ T cell subsets and measured ß cell function longitudinally for 2 years, starting immediately after diagnosis of type 1 diabetes. We found that change in ß cell-specific effector memory CD8+ T cells expressing CD57 was positively correlated with C-peptide change in subjects below 12 years of age. Autoreactive CD57+ effector memory CD8+ T cells bore the signature of enhanced effector function (higher expression of granzyme B, killer-specific protein of 37 kDa, and CD16, and reduced expression of CD28) compared with their CD57- counterparts, and network association modeling indicated that the dynamics of ß cell-reactive CD57+ effector memory CD8+ T cell subsets were strongly linked. Thus, coordinated changes in circulating ß cell-specific CD8+ T cells within the CD57+ effector memory subset calibrate to functional insulin reserve in type 1 diabetes, providing a tool for immune monitoring and a mechanism-based target for immunotherapy.

Coagulation profile following liver resection: Does liver cirrhosis affect thromboelastography?

BACKGROUND: Thromboelastography has called into question the coagulopathy seen following partial hepatectomy. However the coagulation profile in cirrhotic livers has not been studied. Our objective was to determine the coagulation profile following partial hepatectomy in normal and cirrhotic livers. METHODS: Patients undergoing liver resection were prospectively enrolled in the study. The prothrombin time and international normalized ratio, as well as the thromboelastogram, were obtained preoperatively, post-operatively, and on post-operative days 1, 3, and 5. RESULTS: 22 noncirrhotic and 11 cirrhotic patients undergoing liver resection were enrolled. Postoperatively the thromboelastogram demonstrated a hypercoagulable profile in 64%, 33%, 39% and 36% of patients on post-operative days 0, 1, 3 and 5 respectively. There was no difference between patients with cirrhosis and those without underlying liver disease. CONCLUSION: Patients appear to have a similar coagulation profile after liver resection regardless of underlying cirrhosis with many having a hypercoagulable profile.

Assessment of ß Cell Mass and Function by AIRmax and Intravenous Glucose in High-Risk Subjects for Type 1 Diabetes.

Context: There is little information regarding ß cell mass in individuals at early stages of type 1 diabetes (T1D). Objective: To investigate both acute insulin response to arginine at hyperglycemia (AIRmax), as a correlate of ß cell mass, and ß cell function by the intravenous glucose tolerance test (IVGTT) in subjects at early stages of T1D. Design/Setting/Participants: Forty subjects were enrolled: (1) low-risk group: relatives of patients with T1D with 0 to 1 antibody (n = 21) and (2) high-risk group: relatives with ≥2 antibodies (n = 19). Main Outcome Measure: Acute insulin and C-peptide responses to IVGTT and to AIRmax. Participants underwent two IVGTT and AIRmax procedures on different days. Results: AIRmax was reproducible, well tolerated, and correlated to first-phase insulin response (FPIR) from IVGTT (r = 0.779). The high-risk group had greater impaired ß cell function compared with the low-risk group, determined both by lower mean FPIR and a greater number of subjects below an established threshold for abnormal function [10 of 19 (52.6%) versus 4 of 21 (19%)]. There was a heterogeneous AIRmax response in these subjects with low FPIR, ranging from 38 to 250 µU/mL. Conclusions: There is significant variation in insulin secretory reserve as assessed by AIRmax in family members with low ß cell function assessed by FPIR. As AIRmax is a functional measure of ß cell mass, these data suggest heterogeneity in disease pathogenesis in which mass is preserved in relation to function in some individuals. The tolerability and reproducibility of AIRmax suggest it could be a useful stratification measure in clinical trials of disease-modifying therapy.