Prevalence and Source Tracing of PFAS in Shallow Groundwater Used for Drinking Water in Wisconsin, USA.

Samples from 450 homes with shallow private wells throughout the state of Wisconsin (USA) were collected and analyzed for 44 individual per- and polyfluoroalkyl substances (PFAS), general water quality parameters, and indicators of human waste as well as agricultural influence. At least one PFAS was detected in 71% of the study samples, and 22 of the 44 PFAS analytes were detected in one or more samples. Levels of PFOA and/or PFOS exceeded the proposed Maximum Contaminant Levels of 4 ng/L, put forward by the U.S. Environmental Protection Agency (EPA) in March 2023, in 17 of the 450 samples, with two additional samples containing PFHxS ≳ 9 ng/L (the EPA-proposed hazard index reference value). Those samples above the referenced PFAS levels tend to be associated with developed land and human waste indicators (artificial sweeteners and pharmaceuticals), which can be released to groundwater via septic systems. For a few samples with levels of PFOA, PFOS, and/or PFHxS > 40 ng/L, application of wastes to agricultural land is a possible source. Overall, the study suggests that human waste sources, septic systems in particular, are important sources of perfluoroalkyl acids, especially ones with ≤8 perfluorinated carbons, in shallow groundwater.

Diagnosing and Treating an Acute Anterior Shoulder Dislocation Using Point-of-Care Ultrasound in an Urgent Care Setting.

IntroductionAcute shoulder dislocations are a commonly encountered injury in the acute care setting. Time restrictions and limited availability of diagnostic and therapeutic resources are barriers to attempting reduction in the urgent care setting. Use of point-of-care ultrasound (POCUS) can expediate diagnosis, offer a means for safe and effective analgesia, and provide bedside confirmation of reduction. Case presentationA 54-year-old woman stumbled while dismounting from a bicycle, bracing herself with an abducted externally rotated left arm so as not to fall. Following the incident, she had shoulder pain and immobility of her left arm. Handheld POCUS was used to diagnose an anterior shoulder dislocation. Analgesia was achieved with ultrasound-guided intra-articular lidocaine injection. The shoulder was reduced using the Cunningham technique. POCUS was then used to confirm reduction. ConclusionThis case illustrates the efficiency, effectiveness, and safety of POCUS-guided shoulder dislocation diagnosis and treatment in the urgent care setting.

Phase III Trial of Avelumab Maintenance After First-Line Induction Chemotherapy Versus Continuation of Chemotherapy in Patients With Gastric Cancers: Results From JAVELIN Gastric 100.

PURPOSE: The role of maintenance therapy for gastric (GC) or gastroesophageal junction cancer (GEJC) is unclear. We investigated avelumab (anti-programmed death ligand-1 [PD-L1]) maintenance after first-line induction chemotherapy for GC/GEJC. PATIENTS AND METHODS: JAVELIN Gastric 100 was a global, open-label, phase III trial. Eligible patients had untreated, unresectable, human epidermal growth factor receptor 2-negative, locally advanced or metastatic GC or GEJC. Patients without progressive disease after 12 weeks of first-line chemotherapy with oxaliplatin plus a fluoropyrimidine were randomly assigned 1:1 to avelumab 10 mg/kg every 2 weeks or continued chemotherapy, stratified by region (Asia v non-Asia). The primary end point was overall survival (OS) after induction chemotherapy in all randomly assigned patients or the PD-L1-positive randomly assigned population (≥ 1% of tumor cells; 73-10 assay). RESULTS: A total of 805 patients received induction; 499 were randomly assigned to avelumab (n = 249) or continued chemotherapy (n = 250). Median OS was 10.4 months (95% CI, 9.1 to 12.0 months) versus 10.9 months (95% CI, 9.6 to 12.4 months) and 24-month OS rate was 22.1% versus 15.5% with avelumab versus chemotherapy, respectively (hazard ratio [HR], 0.91; 95% CI, 0.74 to 1.11; P = .1779). In the PD-L1-positive population (n = 54), the HR for OS was 1.13 (95% CI, 0.57 to 2.23; P = .6352). In an exploratory analysis of the PD-L1-positive population, defined as combined positive score ≥ 1 (22C3 assay; n = 137), median OS was 14.9 months (95% CI, 8.7 to 17.3 months) with avelumab versus 11.6 months (95% CI, 8.4 to 12.6 months) with chemotherapy (unstratified HR, 0.72; 95% CI, 0.49 to 1.05). With avelumab and chemotherapy, treatment-related adverse events (TRAEs) occurred in 149 (61.3%) and 184 (77.3%) patients, including grade ≥ 3 TRAEs in 31 (12.8%) and 78 (32.8%) patients, respectively. CONCLUSION: JAVELIN Gastric 100 did not demonstrate superior OS with avelumab maintenance versus continued chemotherapy in patients with advanced GC or GEJC overall or in a prespecified PD-L1-positive population.

The Standardized Video Interview: How Does It Affect the Likelihood to Invite for a Residency Interview?

BACKGROUND: The Association of American Medical Colleges instituted a standardized video interview (SVI) for all applicants to emergency medicine (EM). It is unclear how the SVI affects a faculty reviewer's decision on likelihood to invite an applicant (LTI) for an interview. OBJECTIVES: The objective was to determine whether the SVI affects the LTI. METHODS: Nine Accreditation Council of Graduate Medication Education (ACGME)-accredited EM residency programs participated in this prospective, observational study. LTI was defined on a 5-point Likert scale as follows: 1 = definitely not invite, 2 = likely not invite, 3 = might invite, 4 = probably invite, 5 = definitely invite. LTI was recorded at three instances during each review: 1) after typical screening (blinded to the SVI), 2) after unblinding to the SVI score, and 3) after viewing the SVI video. RESULTS: Seventeen reviewers at nine ACGME-accredited residency programs participated. We reviewed 2,219 applications representing 1,424 unique applicants. After unblinding the SVI score, LTI did not change in 2,065 (93.1%), increased in 85 (3.8%) and decreased in 69 (3.1%; p = 0.22). In subgroup analyses, the effect of the SVI on LTI was unchanged by United States Medical Licensing Examination score. However, when examining subgroups of SVI scores, the percentage of applicants in whom the SVI score changed the LTI was significantly different in those that scored in the lower and upper subgroups (p < 0.0001). The SVI video was viewed in 816 (36.8%) applications. Watching the video did not change the LTI in 631 (77.3%); LTI increased in 106 (13.0%) and decreased in 79 (9.7%) applications (p = 0.04). CONCLUSIONS: The SVI score changed the LTI in 7% of applications. In this group, the score was equally likely to increase or decrease the LTI. Lower SVI scores were more likely to decrease the LTI than higher scores were to increase the LTI. Watching the SVI video was more likely to increase the LTI than to decrease it.

Standardized Video Interviews Do Not Correlate to United States Medical Licensing Examination Step 1 and Step 2 Scores.

INTRODUCTION: In 2017, the Standardized Video Interview (SVI) was required for applicants to emergency medicine (EM). The SVI contains six questions highlighting professionalism and interpersonal communication skills. The responses were scored (6-30). As it is a new metric, no information is available on correlation between SVI scores and other application data. This study was to determine if a correlation exists between applicants' United States Medical Licensing Examination (USMLE) and SVI scores. We hypothesized that numeric USMLE Step 1 and Step 2 Clinical Knowledge (CK) scores would not correlate with the SVI score, but that performance on the Step 2 Clinical Skills (CS) portion may correlate with the SVI since both test communication skills. METHODS: Nine EM residency sites participated in the study with data exported from an Electronic Residency Application Service (ERAS®) report. All applicants with both SVI and USMLE scores were included. We studied the correlation between SVI scores and USMLE scores. Predetermined subgroup analysis was performed based on applicants' USMLE Step 1 and Step 2 CK scores as follows: (≥ 200, 201-220, 221-240, 241-260, >260). We used linear regression, the Kruskal-Wallis test and Mann-Whitney U test for statistical analyses. RESULTS: 1,325 applicants had both Step 1 and SVI scores available, with no correlation between the overall scores (p=0.58) and no correlation between the scores across all Step 1 score ranges, (p=0.29). Both Step 2 CK and SVI scores were available for 1,275 applicants, with no correlation between the overall scores (p=0.56) and no correlation across all ranges, (p=0.10). The USMLE Step 2 CS and SVI scores were available for 1,000 applicants. Four applicants failed the CS test without any correlation to the SVI score (p=0.08). CONCLUSION: We found no correlation between the scores on any portion of the USMLE and the SVI; therefore, the SVI provides new information to application screeners.

First-in-Human Phase I Trial of a Tumor-Targeted Cytokine (NHS-IL12) in Subjects with Metastatic Solid Tumors.

PURPOSE: The NHS-IL12 immunocytokine is composed of two IL12 heterodimers fused to the NHS76 antibody. Preclinical studies have shown that this antibody targets IL12 to regions of tumor necrosis by binding histones on free DNA fragments in these areas, resulting in enhanced antitumor activity. The objectives of this phase I study were to determine the maximum tolerated dose (MTD) and pharmacokinetics of NHS-IL12 in subjects with advanced solid tumors. PATIENTS AND METHODS: Subjects (n = 59) were treated subcutaneously with NHS-IL12 in a single ascending-dose cohort followed by a multiple ascending-dose cohort (n = 37 with every 4-week dosing). RESULTS: The most frequently observed treatment-related adverse events (TRAE) included decreased circulating lymphocytes, increased liver transaminases, and flu-like symptoms. Of the grade ≥3 TRAEs, all were transient and only one was symptomatic (hyperhidrosis). The MTD is 16.8 µg/kg. A time-dependent rise in IFNγ and an associated rise in IL10 were observed following NHS-IL12. Of peripheral immune cell subsets evaluated, most noticeable were increases in frequencies of activated and mature natural killer (NK) cells and NKT cells. Based on T-cell receptor sequencing analysis, increases in T-cell receptor diversity and tumor-infiltrating lymphocyte density were observed after treatment where both biopsies and peripheral blood mononuclear cells were available. Although no objective tumor responses were observed, 5 subjects had durable stable disease (range, 6-30+ months). CONCLUSIONS: NHS-IL12 was well tolerated up to a dose of 16.8 µg/kg, which is the recommended phase II dose. Early clinical immune-related activity warrants further studies, including combination with immune checkpoint inhibitors.See related commentary by Lyerly et al., p. 9.

Novel methods reveal that parallelism contributes to the functional vertical slot dimension in ceramic and metal brackets.

OBJECTIVES:: To validate a novel method for measuring the clinically relevant bracket slot and use these methods to test the hypothesis that various metal injection molded (MIM) and esthetic ceramic injection molded (CIM) brackets have a bracket slot accuracy within 1 mil (0.001") of their reported slot dimension. MATERIALS AND METHODS:: A Nikon iNEXIV-VMA-2520 laser microscope was used to measure slots of six series of CIM brackets and two series of MIM brackets via a vision measuring system of 256 gray levels to capture each edge of the slot, largely taking out human subjectivity. This system had a maximum permissible error of 2 + 8 L/1000 µm with a point resolution of 0.1 µm and was estimated to be more accurate than previous methods by a factor of 10. The video image for each bracket was autofocused by a blinded operator, and 40 point-to-line measurements were calculated along the clinical slot and averaged. RESULTS:: Vertical slot dimension varied from series to series and within the series of brackets. Three of six CIM and two of three MIM brackets had a statistically significant mean slot size 0.001 inches larger than reported. The reported precision of these CIM brackets, as determined from standard deviation, varied from series to series. CONCLUSIONS:: A novel system that incorporates parallelism into analysis of vertical bracket slot dimension was described. When the entire clinically relevant slot was considered, MIM and CIM brackets had similar precision but were significantly oversized, with contribution from a nonparallel, likely diverging, vertical slot dimension.

Fate of five pharmaceuticals under different infiltration conditions for managed aquifer recharge.

Infiltration of treated wastewater (TWW) to recharge depleted aquifers, often referred to as managed aquifer recharge, is a solution to replenish groundwater resources in regions facing water scarcity. We present a mass balance approach to infer the amounts of five pharmaceuticals (carbamazepine, diclofenac, fenoprofen, gemfibrozil, and naproxen) degraded in column experiments based on concentrations of pharmaceuticals in the aqueous and solid (sorbed) phases. Column experiments were conducted under three different conditions: continuous infiltration, wetting and drying cycles, and wetting and drying cycles with elevated concentrations of antibiotics (which may reduce microbially aided degradation of other compounds). A mass balance comparing pharmaceutical mass in the water phase over the 16-month duration of the experiments to mass sorbed to the soil was used to infer the mass of pharmaceuticals degraded. Results show sorption as the main attenuation mechanism for carbamazepine. About half of the mass of diclofenac was degraded with wetting and drying cycles, but no significant degradation was found for continuous infiltration, while 32% of infiltrated mass sorbed. Fenoprofen was degraded in the shallow and aerobic part of the soil, but degradation appeared to cease beyond 27 cm depth. Gemfibrozil attenuated through a combination of degradation and sorption, with slight increases in attenuation with depth from both mechanisms. Naproxen degraded progressively with depth, resulting in attenuation of >90% of the mass. In the column with elevated concentrations of antibiotics, the antibiotics attenuated to about 50% or less of inflow concentrations by 27 cm depth and within this zone, less degradation of the other compounds was observed.

Comparison of Medical Therapy Alone to Medical Therapy with Surgical Treatment of Peritonsillar Abscess.

Objective This study was performed to determine whether the efficacy and safety of medical management of uncomplicated peritonsillar abscess (PTA) presenting in the emergency department is equivalent to medical plus surgical therapy. Study Design Case series with chart review. Setting Southern California Permanente Medical Group (SCPMG). Subjects and Methods Upon successful completion of a prospective study comparing medical treatment (MT) to surgical treatment (ST) of PTA in 2008, MT was adopted by 12 SCPMG centers while 7 centers continued standard surgical drainage. Clinical outcomes are now reviewed on a random sampling of 211 patients with PTA treated with MT and 96 patients treated with ST between 2008 and 2013 at the respective medical centers. Patients were treated with intravenous (IV) fluids, weight-appropriate IV ceftriaxone, clindamycin, and dexamethasone, and then discharged on clindamycin × 10 days (MT). Patients in the ST group received MT but also surgical drainage. Primary end points were complication rates and failure rates. Results MT and ST resulted in no significant difference in treatment success or complications. However, patients in the MT group obtained significantly less liquid opioid prescriptions (MT, 30.8 ± 5.65; ST, 77.75 ± 13.41; P < .0001), reported fewer sore days (MT, 4.48 ± 0.27; ST, 5.77 ± 0.49; P = .0004), and required less days off from work (MT, 3.4 ± 0.44; ST, 4.9 ± 0.82; P = .044). Conclusions Compared to ST, MT appears to be equally safe and efficacious, with less pain, opioid use, and days off work, especially if patients with PTA present without trismus. MT for PTAs reduces the possibility of surgical complications, as well as the cost and inconvenience associated with ST.

Outpatient Management of Emergency Department Patients With Acute Pulmonary Embolism: Variation, Patient Characteristics, and Outcomes.

STUDY OBJECTIVE: Outpatient management of emergency department (ED) patients with acute pulmonary embolism is uncommon. We seek to evaluate the facility-level variation of outpatient pulmonary embolism management and to describe patient characteristics and outcomes associated with home discharge. METHODS: The Management of Acute Pulmonary Embolism (MAPLE) study is a retrospective cohort study of patients with acute pulmonary embolism undertaken in 21 community EDs from January 2013 to April 2015. We gathered demographic and clinical variables from comprehensive electronic health records and structured manual chart review. We used multivariable logistic regression to assess the association between patient characteristics and home discharge. We report ED length of stay, consultations, 5-day pulmonary embolism-related return visits and 30-day major hemorrhage, recurrent venous thromboembolism, and all-cause mortality. RESULTS: Of 2,387 patients, 179 were discharged home (7.5%). Home discharge varied significantly between EDs, from 0% to 14.3% (median 7.0%; interquartile range 4.2% to 10.9%). Median length of stay for home discharge patients (excluding those who arrived with a new pulmonary embolism diagnosis) was 6.0 hours (interquartile range 4.6 to 7.2 hours) and 81% received consultations. On adjusted analysis, ambulance arrival, abnormal vital signs, syncope or presyncope, deep venous thrombosis, elevated cardiac biomarker levels, and more proximal emboli were inversely associated with home discharge. Thirteen patients (7.2%) who were discharged home had a 5-day pulmonary embolism-related return visit. Thirty-day major hemorrhage and recurrent venous thromboembolism were uncommon and similar between patients hospitalized and those discharged home. All-cause 30-day mortality was lower in the home discharge group (1.1% versus 4.4%). CONCLUSION: Home discharge of ED patients with acute pulmonary embolism was uncommon and varied significantly between facilities. Patients selected for outpatient management had a low incidence of adverse outcomes.

Teaching the Emergency Department Patient Experience: Needs Assessment from the CORD-EM Task Force.

INTRODUCTION: Since the creation of Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) patient satisfaction (PS) scores, patient experience (PE) has become a metric that can profoundly affect the fiscal balance of hospital systems, reputation of entire departments and welfare of individual physicians. While government and hospital mandates demonstrate the prominence of PE as a quality measure, no such mandate exists for its education. The objective of this study was to determine the education and evaluation landscape for PE in categorical emergency medicine (EM) residencies. METHODS: This was a prospective survey analysis of the Council of Emergency Medicine Residency Directors (CORD) membership. Program directors (PDs), assistant PDs and core faculty who are part of the CORD listserv were sent an email link to a brief, anonymous electronic survey. Respondents were asked their position in the residency, the name of their department, and questions regarding the presence and types of PS evaluative data and PE education they provide. RESULTS: We obtained 168 responses from 139 individual residencies, representing 72% of all categorical EM residencies. This survey found that only 27% of responding residencies provide PS data to their residents. Of those programs, 61% offer simulation scores, 39% provide third-party attending data on cases with resident participation, 37% provide third-party acquired data specifically about residents and 37% provide internally acquired quantitative data. Only 35% of residencies reported having any organized PE curricula. Of the programs that provide an organized PE curriculum, most offer multiple modalities; 96% provide didactic lectures, 49% small group sessions, 47% simulation sessions and 27% specifically use standardized patient encounters in their simulation sessions. CONCLUSION: The majority of categorical EM residencies do not provide either PS data or any organized PE curriculum. Those that do use a heterogeneous set of data collection modalities and educational techniques. American Osteopathic Association and Accreditation Council for Graduate Medical Education residencies show no significant differences in their resident PS data provision or formal curricula. Further work is needed to improve education given the high stakes of PS scores in the emergency physician's career.

Computed Tomography Use for Adults With Head Injury: Describing Likely Avoidable Emergency Department Imaging Based on the Canadian CT Head Rule.

BACKGROUND: Millions of head computed tomography (CT) scans are ordered annually, but the extent of avoidable imaging is poorly defined. OBJECTIVES: The objective was to determine the prevalence of likely avoidable CT imaging among adults evaluated for head injury in 14 community emergency departments (EDs) in Southern California. METHODS: We conducted an electronic health record (EHR) database and chart review of adult ED trauma encounters receiving a head CT from 2008 to 2013. The primary outcome was discordance with the Canadian CT Head Rule (CCHR) high-risk criteria; the secondary outcome was use of a neurosurgical intervention in the discordant cohort. We queried systemwide EHRs to identify CCHR discordance using criteria identifiable in discrete data fields. Explicit chart review of a subset of discordant CTs provided estimates of misclassification bias and assessed the low-risk cases who actually received an intervention. RESULTS: Among 27,240 adult trauma head CTs, EHR data classified 11,432 (42.0%) discordant with CCHR recommendation. Subsequent chart review showed that the designation of discordance based on the EHR was inaccurate in 12.2% (95% confidence interval [CI] = 5.6% to 18.8%). Inter-rater reliability for attributing CCHR concordance was 95% (κ = 0.86). Thus, we estimate that 36.8% of trauma head CTs were truly likely avoidable (95% CI = 34.1% to 39.6%). Among the likely avoidable CT group identified by EHR, only 0.1% (n = 13) received a neurosurgical intervention. Chart review showed none of these were actually "missed" by the CCHR, as all 13 were misclassified. CONCLUSION: About one-third of head CTs currently performed on adults with head injury may be avoidable by applying the CCHR. Avoidance of CT in such patients is unlikely to miss any important injuries.

Low-value care for acute sinusitis encounters: who's choosing wisely?

OBJECTIVES: To assess acute sinusitis (AS) encounters in primary care (PC), urgent care (UC), and emergency department (ED) settings for adherence to recommendations to avoid low-value care. STUDY DESIGN: A retrospective, observational study of adult AS encounters (2010-2012) within a large integrated healthcare system. METHODS: We compared ED and UC encounters with PC visits, adjusting for differences in patient characteristics. PRIMARY OUTCOMES: adherence to recommendations to avoid antibiotics and a computed tomography (CT) scan of the face, head, or sinuses. SECONDARY OUTCOMES: length of symptoms and adherence with AS recommendations. RESULTS: Of 152,774 AS encounters, 89.2% resulted in antibiotics and 1.1% resulted in a CT scan. Compared with PC encounters, ED encounters were less likely to result in antibiotics (adjusted odds ratio [AOR], 0.57; 95% CI, 0.50-0.65) but more likely to result in a CT scan (AOR, 59.4; 95% CI, 51.3-68.7), while UC encounters were more likely to result in both antibiotics (AOR, 1.12; 95% CI, 1.08-1.17) and CT imaging (AOR, 2.4; 95% CI, 2.1-2.7). Chart review of encounters resulting in antibiotics found that 50% were inappropriately prescribed for symptoms of ≤7 days' duration (95% CI, 41%-58%), while 35% were appropriately prescribed for symptoms of ≥14 days' duration (95% CI, 27%-44%). Only 29% (95% CI, 22%-36%) of encounters were consistent with guideline-adherent care. CONCLUSIONS: AS encounters in an integrated health system infrequently result in CT imaging, but antibiotic treatment is common. Differences exist across acute care settings, but improved antibiotic stewardship is needed in all settings.

PD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer.

Programmed death 1 ligand 1 (PD-L1) is an immune regulatory molecule that limits antitumor immune activity. Targeting of PD-L1 and other immune checkpoint proteins has shown therapeutic activity in various tumor types. The expression of PD-L1 and its correlation with response to neoadjuvant chemotherapy in breast cancer has not been studied extensively. Our goal was to assess PD-L1 expression in a cohort of breast cancer patients treated with neoadjuvant chemotherapy. Pretreatment biopsies from 105 patients with breast cancer from Yale New Haven Hospital that subsequently received neoadjuvant chemotherapy were assessed for PD-L1 protein expression by automated quantitative analysis with a rabbit monoclonal antibody (E1L3N) to the cytoplasmic domain of PD-L1. In addition, tumor-infiltrating lymphocytes (TIL) were assessed on hematoxylin and eosin slides. PD-L1 expression was observed in 30% of patients, and it was positively associated with hormone-receptor-negative and triple-negative status and high levels of TILs. Both TILs and PD-L1 measured in the epithelium or stroma predicted pathologic complete response (pCR) to neoadjuvant chemotherapy in univariate and multivariate analyses. However, because they are strongly associated, TILs and PD-L1 cannot both be included in a significant multivariate model. PD-L1 expression is prevalent in breast cancer, particularly hormone-receptor-negative and triple-negative patients, indicating a subset of patients that may benefit from immune therapy. Furthermore, PD-L1 and TILs correlate with pCR, and high PD-L1 predicts pCR in multivariate analysis.