Maximizing Adherence and Minimizing Time to Antibiotics: A Multidisciplinary Institutional Trauma Bay Protocol for Single Antibiotic Prophylaxis in Open Fractures.

OBJECTIVES: To determine if a multidisciplinary institutional protocol can optimize the time to antibiotic (Abx) administration for open fractures (openFx) and improve compliance with the administration of Abx prophylaxis during trauma activation. DESIGN: Retrospective pre-post study design. SETTING: Single Level II Trauma Center. PATIENT SELECTION CRITERIA: All patients who triggered a trauma activation with suspected openFx and were treated according to the institutional single antibiotic regimen were eligible for inclusion. Patients were excluded if fractures did not involve the appendicular skeleton. Patients treated before implementation of a standardized institutional protocol where premixed IV bags of antibiotics were stocked in automated dispensing systems within ED trauma bays (January 2021-October 2022) were defined as the "pre" group and those treated following implementation the "post" group. OUTCOME MEASURES AND COMPARISONS: The primary outcome was time from trauma bay arrival to antibiotic aministration, measured in minutes, with comparisons made between preprotocol and postprotocol implementation. Secondary outcomes for comparison included rates (%) of time to Abx <60 minutes, allergic reactions, acute kidney injury, ototoxicity, surgical site infection, multi-drug-resistant organisms identified in blood or biopsy cultures in cases requiring reoperation, and Clostridium difficile infection in the gastrointestinal system, confirmed by stool test results, within 30 days. RESULTS: Twenty-four patients (mean age 39.5 ± 16.3 years) met the criteria after protocol implementation compared with 72 patients (mean age 34.3 ± 14.8 years) before implementation. Implementation of the institutional protocol resulted in a significant reduction in the time to Abx administration for openFx from 87.9 ± 104.6 minutes to 22.2 ± 12.8 minutes in the postprotocol group ( P < 0.001). In addition, only 53% in the preprotocol group received Abx within 60 minutes compared with 96% in postprotocol group ( P < 0.001). Post hoc power analysis revealed that the study was powered at 92% (effect size = 0.72) to detect a significant difference between the preprotocol and postprotocol groups. CONCLUSION: This study provides evidence that a multidisciplinary institutional protocol for the administration of Abx prophylaxis can be an effective strategy for optimizing the time to Abx administration in cases of suspected openFx. This protocol may be implemented in other trauma centers to optimize time to Abx administration for openFx. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Selection, optimization and validation of ten chronic disease polygenic risk scores for clinical implementation in diverse US populations.

Polygenic risk scores (PRSs) have improved in predictive performance, but several challenges remain to be addressed before PRSs can be implemented in the clinic, including reduced predictive performance of PRSs in diverse populations, and the interpretation and communication of genetic results to both providers and patients. To address these challenges, the National Human Genome Research Institute-funded Electronic Medical Records and Genomics (eMERGE) Network has developed a framework and pipeline for return of a PRS-based genome-informed risk assessment to 25,000 diverse adults and children as part of a clinical study. From an initial list of 23 conditions, ten were selected for implementation based on PRS performance, medical actionability and potential clinical utility, including cardiometabolic diseases and cancer. Standardized metrics were considered in the selection process, with additional consideration given to strength of evidence in African and Hispanic populations. We then developed a pipeline for clinical PRS implementation (score transfer to a clinical laboratory, validation and verification of score performance), and used genetic ancestry to calibrate PRS mean and variance, utilizing genetically diverse data from 13,475 participants of the All of Us Research Program cohort to train and test model parameters. Finally, we created a framework for regulatory compliance and developed a PRS clinical report for return to providers and for inclusion in an additional genome-informed risk assessment. The initial experience from eMERGE can inform the approach needed to implement PRS-based testing in diverse clinical settings.

Selection, optimization, and validation of ten chronic disease polygenic risk scores for clinical implementation in diverse populations.

Polygenic risk scores (PRS) have improved in predictive performance supporting their use in clinical practice. Reduced predictive performance of PRS in diverse populations can exacerbate existing health disparities. The NHGRI-funded eMERGE Network is returning a PRS-based genome-informed risk assessment to 25,000 diverse adults and children. We assessed PRS performance, medical actionability, and potential clinical utility for 23 conditions. Standardized metrics were considered in the selection process with additional consideration given to strength of evidence in African and Hispanic populations. Ten conditions were selected with a range of high-risk thresholds: atrial fibrillation, breast cancer, chronic kidney disease, coronary heart disease, hypercholesterolemia, prostate cancer, asthma, type 1 diabetes, obesity, and type 2 diabetes. We developed a pipeline for clinical PRS implementation, used genetic ancestry to calibrate PRS mean and variance, created a framework for regulatory compliance, and developed a PRS clinical report. eMERGE's experience informs the infrastructure needed to implement PRS-based implementation in diverse clinical settings.

Evaluation of the Access Bio CareStart rapid SARS-CoV-2 antigen test in asymptomatic individuals tested at a community mass-testing program in Western Massachusetts.

Point-of-care antigen-detecting rapid diagnostic tests (RDTs) to detect Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) represent a scalable tool for surveillance of active SARS-CoV-2 infections in the population. Data on the performance of these tests in real-world community settings are paramount to guide their implementation to combat the COVID-19 pandemic. We evaluated the performance characteristics of the CareStart COVID-19 Antigen test (CareStart) in a community testing site in Holyoke, Massachusetts. We compared CareStart to a SARS-CoV-2 reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) reference, both using anterior nasal swab samples. We calculated the sensitivity, specificity, and the expected positive and negative predictive values at different SARS-CoV-2 prevalence estimates. We performed 666 total tests on 591 unique individuals. 573 (86%) were asymptomatic. There were 52 positive tests by RT-qPCR. The sensitivity of CareStart was 49.0% (95% Confidence Interval (CI) 34.8-63.4) and specificity was 99.5% (95% CI 98.5-99.9). Among positive RT-qPCR tests, the median cycle threshold (Ct) was significantly lower in samples that tested positive on CareStart. Using a Ct ≤ 30 as a benchmark for positivity increased the sensitivity of the test to 64.9% (95% CI 47.5-79.8). Our study shows that CareStart has a high specificity and moderate sensitivity. The utility of RDTs, such as CareStart, in mass implementation should prioritize use cases in which a higher specificity is more important, such as triage tests to rule-in active infections in community surveillance programs.

Systematic review of risk and protective factors associated with substance use and abuse in individuals with autism spectrum disorders.

LAY ABSTRACT: Symptoms characteristic of autism spectrum disorder were initially believed to protect individuals with autism spectrum disorder from developing substance abuse. However, recent studies suggest that up to 36% of individuals with autism spectrum disorder may have a co-occurring issue with substance abuse. In addition, substance abuse may worsen the difficulties with daily functioning some individuals with autism spectrum disorder experience. It is important to understand occurrence rates, and risk, protective and positive treatment factors of co-occurring autism spectrum disorder and substance abuse in order to promote the best possible support for this special population. This review aimed to find and synthesize evidence regarding risk, protective and treatment factors, and determine a general prevalence rate of co-occurring autism spectrum disorder and substance abuse from all studies on substance use and abuse in individuals with autism spectrum disorder. The review also aimed to assess study quality and identify a diagnostic measure for substance abuse in individuals with autism spectrum disorder. Twenty-six studies on substance use and abuse in autism spectrum disorder were included in the review. The rates of substance abuse among those with autism spectrum disorder identified by included studies ranged from 1.3% to 36%, but due to large differences in study methods, a general prevalence rate could not be determined. Risk and protective factors, recognized in the general population, such as familial substance abuse and co-occurring mental health issues, and factors which may be more likely to occur in individuals with autism spectrum disorder, such as limited social resources and low sensation-seeking, were identified. No diagnostic measures specific to individuals with autism spectrum disorder and substance abuse were identified. This review identified only one exploratory study on an adapted intervention for co-occurring autism spectrum disorder and substance abuse. However, there were many methodological challenges in this study that limit the conclusions that can be drawn from the data. More research, using consistent methods, is needed to understand risk and protective factors and to determine the prevalence of substance abuse among individuals with autism spectrum disorder. The potential for co-occurring autism spectrum disorder and substance abuse should be considered by professional working in both autism spectrum disorder and substance abuse services, as finding suggests substance abuse is possible among individuals with autism spectrum disorder and may occur more frequently than previously believed. In addition, autism spectrum disorder and substance abuse service providers should be sensitive to specific risk and protective factors identified by the review that may impact substance abuse course and outcomes.

Characterization of the response of taurine protons to PRESS at 9.4 T for Resolving choline and Determining taurine T2.

Point-resolved spectroscopy (PRESS), characterized by two TEs (TE1 and TE2 ), can be employed to perform animal magnetic resonance spectroscopy (MRS) studies at 9.4 T. Taurine (Tau) and choline (Cho) are relevant metabolites that can be measured by MRS. In this work, the response of the J-coupled protons of Tau as a function of PRESS TE1 and TE2 was characterized at 9.4 T to achieve two objectives. The first was to determine two TE1 and TE2 combinations that could be used to obtain T2 -corrected measures of Tau (3.42 ppm) that were minimally influenced by J coupling. The second was to exploit the Tau J coupling to find a timing combination that minimized the 3.25-ppm Tau signal to enable the Cho (3.22 ppm) resonance to be resolved from the overlapping Tau signal. The response of Tau protons was investigated both numerically and experimentally. It was numerically determined that the timings {TE1 , TE2 } = {17 ms, 10 ms} and {TE1 , TE2 } = {80 ms, 70 ms} yielded similar 3.42-ppm Tau resonance areas (5% difference), rendering them suitable for Tau T2 determination. {TE1 , TE2 } = {25 ms, 50 ms} was found to yield minimal 3.25-ppm Tau signal, reducing its interference with Cho. The efficacy of the timings was demonstrated on phantom solutions and in vivo in four Sprague Dawley rats. LCModel was employed to analyse the in vivo spectra and Tau T2 values were estimated by fitting the Tau peak areas obtained with {TE1 , TE2 } = {17 ms, 10 ms} and {TE1 , TE2 } = {80 ms, 70 ms} to a monoexponentially decaying function. An average Tau T2 of 106 ms (standard deviation, 12 ms) was obtained. LCModel analysis of rat spectra obtained with {TE1 , TE2 } = {25 ms, 50 ms} demonstrated negligible levels of Tau signal, compared with that obtained with short TE.