Longitudinal accuracy analysis of ultrasound performed during a four-year emergency medicine residency.

BACKGROUND: The objective of this study was to analyze patterns of point-of-care ultrasound (POCUS) performance over 4 years of emergency medicine (EM) residency. Specifically, we aimed to study how accuracy and adherence to standards of scanning changed by postgraduate year (PGY). METHODS: This was a retrospective observational study of resident-performed POCUS at an academic emergency department over 6 years. We reviewed records of POCUS scans performed by PGY-1 to -4 residents that had been collected for quality assurance purposes. Data that were collected about EM residents' performance included the total number and type of scans per year, rate of technically limited scans (TLS), and accuracy on interpreting ultrasound images. Resident performances in each year (PGY-1 to -4) were independently evaluated and reported. RESULTS: During a 6-year period, 137 different EM residents performed 50,815 ultrasound scans. The median number of scans was 177 for PGY-1, 124 for PGY-2, 118 for PGY-3, and 76 for residents in PGY-4. The accuracy of scan interpretations were high across all PGY levels (>97%), but slight degradation was observed as residents progressed through residency. The TLS rate increased from 4.7% among PGY-1s to 13.6% as PGY-4s. CONCLUSIONS: In this large cohort of POCUS studies by EM residents, POCUS accuracy rates decreased and rates of TLS significantly increased as residents progressed through residency.

Prospective validation of the bedside sonographic acute cholecystitis score in emergency department patients.

BACKGROUND: Acute cholecystitis can be difficult to diagnose in the emergency department (ED); no single finding can rule in or rule out the disease. A prediction score for the diagnosis of acute cholecystitis for use at the bedside would be of great value to expedite the management of patients presenting with possible acute cholecystitis. The 2013 Tokyo Guidelines is a validated method for the diagnosis of acute cholecystitis but its prognostic capability is limited. The purpose of this study was to prospectively validate the Bedside Sonographic Acute Cholecystitis (SAC) Score utilizing a combination of only historical symptoms, physical exam signs, and point-of-care ultrasound (POCUS) findings for the prediction of the diagnosis of acute cholecystitis in ED patients. METHOD: This was a prospective observational validation study of the Bedside SAC Score. The study was conducted at two tertiary referral academic centers in Boston, Massachusetts. From April 2016 to March 2019, adult patients (≥18 years old) with suspected acute cholecystitis were enrolled via convenience sampling and underwent a physical exam and a focused biliary POCUS in the ED. Three symptoms and signs (post-prandial symptoms, RUQ tenderness, and Murphy's sign) and two sonographic findings (gallbladder wall thickening and the presence of gallstones) were combined to calculate the Bedside Sonographic Acute Cholecystitis (SAC) Score. The final diagnosis of acute cholecystitis was determined from chart review or patient follow-up up to 30 days after the initial assessment. In patients who underwent operative intervention, surgical pathology was used to confirm the diagnosis of acute cholecystitis. Sensitivity, specificity, PPV and NPV of the Bedside SAC Score were calculated for various cut off points. RESULTS: 153 patients were included in the analysis. Using a previously defined cutoff of ≥ 4, the Bedside SAC Score had a sensitivity of 88.9% (95% CI 73.9%-96.9%), and a specificity of 67.5% (95% CI 58.2%-75.9%). A Bedside SAC Score of < 2 had a sensitivity of 100% (95% CI 90.3%-100%) and specificity of 35% (95% CI 26.5%-44.4%). A Bedside SAC Score of ≥ 7 had a sensitivity of 44.4% (95% CI 27.9%-61.9%) and specificity of 95.7% (95% CI 90.3%-98.6%). CONCLUSION: A bedside prediction score for the diagnosis of acute cholecystitis would have great utility in the ED. The Bedside SAC Score would be most helpful as a rule out for patients with a low Bedside SAC Score < 2 (sensitivity of 100%) or as a rule in for patients with a high Bedside SAC Score ≥ 7 (specificity of 95.7%). Prospective validation with a larger study is required.

Clinical Integration of Point-of-care Ultrasound by Emergency Medicine Residents: A Single-center Mixed-methods Study.

BACKGROUND: Point-of-care ultrasound (POCUS) competence consists of image acquisition, image interpretation, and clinical integration. Limited data exist on POCUS usage patterns and clinical integration by emergency medicine (EM) residents. We sought to determine actual POCUS usage and clinical integration patterns by EM residents and to explore residents' perspectives on POCUS clinical integration. METHODS: We conducted an explanatory sequential mixed-methods study at a 4-year EM residency program. In phase 1, EM ultrasound (US) attendings observed PGY-4 EM residents' clinical integration of POCUS in real time while on shift in the emergency department (ED). EM US attendings evaluated residents on their intent to perform POCUS, actual POCUS usage, and competence per patient encounter. We used logistic regression to analyze these parameters. In phase 2, we conducted semi-structured interviews with the observed PGY-4 residents regarding POCUS usage and clinical integration in the ED. We analyzed qualitative data for themes. RESULTS: Emergency medicine US attendings observed 10 PGY-4 EM residents during 254 high-acuity patient encounters from December 2018 to March 2019. EM US attendings considered POCUS indicated for 26% (66/254) of patients, possibly indicated for 12% (30/254) and not indicated for 62% (158/254). Of the 66 patients for whom EM US attendings considered POCUS indicated, PGY-4s intended to perform POCUS for patient management 61% (40/66) of the time. PGY-4s subsequently incorporated POCUS into patient management 73% (48/66) of the time. EM US attendings considered PGY-4s entrustable to perform POCUS independently 81% (206/254) of the time. We did not find a statistically significant association between shift volume, shift type, or POCUS application, and resident intent to perform POCUS nor competence. Interviews identified three factors that influence PGY-4's POCUS clinical integration: motivations to use POCUS, barriers to utilization, and POCUS educational methods. CONCLUSIONS: This mixed-methods study identified a significant gap in POCUS utilization and clinical integration by PGY-4 EM residents for clinically indicated cases identified by EM US attendings. As clinical integration is a cornerstone of POCUS competence, it is important to ensure that EM resident POCUS curricula emphasize training on clinical utilization and indications for POCUS while on shift in the ED.

Interdisciplinary approach to enhance trauma residents education of Extended-Focused Assessment for Sonography in Trauma in the emergency department.

BACKGROUND: Despite the utilization of point-of-care ultrasound (POCUS) by trauma surgeons, formal POCUS requirements do not exist for general surgery residents. We sought to evaluate surgery resident comfort with performing and interpreting of Extended-Focused Assessment for Sonography in Trauma (E-FAST) scans after a brief educational session. METHODS: A pre-survey, sent to PGY-2 and -3 surgical residents before their trauma rotation, evaluated comfort with eight components of the E-FAST. Residents were then required to watch a 15-min online video and attend a 1-h bedside training session moderated by emergency medicine ultrasound fellows during which residents practised E-FAST image acquisition and interpretation. After the rotation, residents completed a post-survey evaluating their comfort with the E-FAST. RESULTS: All 27 residents rotating on the trauma service during the 2017-2018 academic year were eligible and, therefore, approached by the study team. Twenty-one (77.78%) residents completed the pre-survey, training and post-survey. Initially, only 52% (13/25) of residents reported feeling confident in performing the E-FAST. After the session, all (100%) reported feeling confident in their training in E-FAST. Self-reported mean comfort with each of the eight components of the E-FAST showed a statistically significant (P < 0.01) increase from pre-post survey for all residents. Isolating only the residents who initially reported feeling confident in E-FAST still showed a statistically significant (P < 0.01) increase in mean comfort. CONCLUSION: A single POCUS training programme has been shown to improve surgical residents' comfort in performing and interpreting the E-FAST. This interdisciplinary approach can enhance collaboration and bridge gaps between emergency medicine and surgery residency programmes.

Increased Sensitivity of Focused Cardiac Ultrasound for Pulmonary Embolism in Emergency Department Patients With Abnormal Vital Signs.

BACKGROUND: Focused cardiac ultrasound (FOCUS) is insensitive for pulmonary embolism (PE). Theoretically, when a clot is large enough to cause vital sign abnormalities, it is more likely to show signs of right ventricular dysfunction on FOCUS, although this has not been well quantified. A rapid bedside test that could quickly and reliably exclude PE in patients with abnormal vital signs could be of high utility in emergency department (ED) patients. We hypothesized that in patients with tachycardia or hypotension, the sensitivity of FOCUS for PE would increase substantially. METHODS: We performed a prospective observational multicenter cohort study involving a convenience sample of patients from six urban academic EDs. Patients suspected to have PE with tachycardia (heart rate [HR] ≥ 100 beats/min) or hypotension (systolic blood pressure [sBP] < 90 mm Hg) underwent FOCUS before computed tomography angiography (CTA). FOCUS included assessment for right ventricular dilation, McConnell's sign, septal flattening, tricuspid regurgitation, and tricuspid annular plane systolic excursion. If any of these were abnormal, FOCUS was considered positive, while if all were normal, FOCUS was considered negative. We a priori planned a subgroup analysis of all patients with a HR ≥ 110 beats/min (regardless of their sBP). We then determined the diagnostic test characteristics of FOCUS for PE in the entire patient population and in the predefined subgroup, based on CTA as the criterion standard. Inter-rater reliability of FOCUS was determined by blinded review of images by an emergency physician with fellowship training in ultrasound. RESULTS: A total of 143 subjects were assessed for enrollment and 136 were enrolled; four were excluded because they were non-English-speaking and three because of inability to obtain any FOCUS windows. The mean (±SD) age of enrolled subjects was 56 (±7) years, mean (±SD) HR was 114 (±12) beats/min, and 37 (27.2%) subjects were diagnosed with PE on CTA. In all subjects, FOCUS was 92% (95% confidence interval [CI] = 78% to 98%) sensitive and 64% specific (95% CI = 53% to 73%) for PE. In the subgroup of 98 subjects with a HR ≥ 110 beats/min, FOCUS was 100% sensitive (95% CI = 88% to 100%) and 63% specific (95% CI = 51% to 74%) for PE. There was substantial interobserver agreement for FOCUS (κ = 1.0, 95% CI = 0.31 to 1.0). CONCLUSIONS: A negative FOCUS examination may significantly lower the likelihood of the diagnosis of PE in most patients who are suspected of PE and have abnormal vital signs. This was especially true in those patients with a HR ≥ 110 beats/min. Our results suggest that FOCUS can be an important tool in the initial evaluation of ED patients with suspected PE and abnormal vital signs.

Generalized Pain Sensitization and Endogenous Oxytocin in Individuals With Symptoms of Migraine: A Cross-Sectional Study.

OBJECTIVE: The current study examined pain and neurogenic inflammation responses to topical capsaicin during the interictal period (between headache) and their relationship with plasma oxytocin in individuals with migraine. BACKGROUND: Individuals with migraine can experience generalized (extracephalic) hyperalgesia, which can persist even between headache attacks. Elevated levels of plasma and cerebrospinal fluid oxytocin have been observed during migraine attacks, oxytocin levels being positively associated with the intensity of migraine symptoms. However, whether oxytocin plays a role in the mechanisms of generalized pain sensitization and neurogenic inflammation during the interictal period has not been studied yet. Understanding migraineurs' interictal pain phenotype and endogenous oxytocin might help identify individuals who would benefit from intranasal oxytocin treatment. METHODS: Thirty-two subjects with migraine and 26 healthy controls underwent pain testing. The current study compared capsaicin-induced pain, central sensitization (areas of secondary mechanical allodynia and hyperalgesia), and neurogenic inflammation (capsaicin-induced flare) responses on the nondominant volar forearm between migraineurs and healthy controls. Additionally, we studied plasma oxytocin levels and their relationship to migraine symptoms, experimental pain and affect. RESULTS: The results indicated a significant group effect (P = .019): Migraineurs reported greater capsaicin-induced pain unpleasantness (M = 1.2, SD = 1.4) on a 0-10 scale and showed larger areas of flare (LnM = 2.8, SD = 0.4) than healthy controls (M = 0.5, SD = 0.8; LnM = 2.6, SD = 0.4; ps < .032). In a subgroup analysis, enhanced capsaicin-induced pain unpleasantness was found in the chronic (P = .007), but not the episodic (Ps > .200), migraineurs. The oxytocin levels were elevated in migraineurs and accounted for 18% of the group difference in capsaicin-induced pain unpleasantness. Within migraineurs, interictal oxytocin levels were negatively associated with psychological distress (Ps < .030). However, during the interictal period, pain sensitivity in extracephalic regions and plasma oxytocin levels were unrelated to migraine symptom parameters (Ps > .074). Lastly, the results found no group difference in areas of secondary mechanical allodynia and hyperalgesia (Ps >.298). CONCLUSION: The current study revealed that individuals with migraine exhibit enhanced extracephalic capsaicin-induced pain unpleasantness and flare responses during interictal periods. In addition, migraineurs, especially those with chronic migraine, had slightly elevated interictal oxytocin levels compared to controls, which was associated with their affective component of experimental pain. Therefore, treatment targeting affective pain during the interictal period may help to reduce generalized pain in migraine. Furthermore, endogenous increases in oxytocin may be a compensatory mechanism that may help decrease affective distress in migraineurs. The therapeutic effects of intranasal oxytocin may benefit migraineurs by reducing their affective distress.

Consequences of perinatal bisphenol A exposure in a mouse model of multiple sclerosis.

Multiple sclerosis (MS) is a complex disease influenced by genetic and environmental contributing factors. Endocrine disrupting compounds (EDCs) such as bisphenol A (BPA) affect gene expression and hormone-regulated systems throughout the body. We investigated the effects of BPA on Theiler's-virus induced demyelination (TVID), a mouse model of MS. Perinatal BPA exposure, combined with viral infection, resulted in a decreased level of viral antibodies, accelerated the onset of TVID symptoms, increased inflammation in both the spinal cord and digestive tract, and amplified immune-related gene expression changes induced by viral infection. These results demonstrate the effect of BPA on the trajectory of TVID, and illustrate how multiple factors collectively influence autoimmune disease.

Membrane insertion of the FYVE domain is modulated by pH.

The FYVE domain associates with phosphatidylinositol 3-phosphate [PtdIns(3)P] in membranes of early endosomes and penetrates bilayers. Here, we detail principles of membrane anchoring and show that the FYVE domain insertion into PtdIns(3)P-enriched membranes and membrane-mimetics is substantially increased in acidic conditions. The EEA1 FYVE domain binds to POPC/POPE/PtdIns(3)P vesicles with a Kd of 49 nM at pH 6.0, however associates approximately 24 fold weaker at pH 8.0. The decrease in the affinity is primarily due to much faster dissociation of the protein from the bilayers in basic media. Lowering the pH enhances the interaction of the Hrs, RUFY1, Vps27p and WDFY1 FYVE domains with PtdIns(3)P-containing membranes in vitro and in vivo, indicating that pH-dependency is a general function of the FYVE finger family. The PtdIns(3)P binding and membrane insertion of the FYVE domain is modulated by the two adjacent His residues of the R(R/K)HHCRXCG signature motif. Mutation of either His residue abolishes the pH-sensitivity. Both protonation of the His residues and nonspecific electrostatic contacts stabilize the FYVE domain in the lipid-bound form, promoting its penetration and increasing the membrane residence time.

Molecular mechanism of membrane targeting by the GRP1 PH domain.

The general receptor for phosphoinositides isoform 1 (GRP1) is recruited to the plasma membrane in response to activation of phosphoinositide 3-kinases and accumulation of phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P(3)]. GRP1's pleckstrin homology (PH) domain recognizes PtdIns(3,4,5)P(3) with high specificity and affinity, however, the precise mechanism of its association with membranes remains unclear. Here, we detail the molecular basis of membrane anchoring by the GRP1 PH domain. Our data reveal a multivalent membrane docking involving PtdIns(3,4,5)P(3) binding, regulated by pH and facilitated by electrostatic interactions with other anionic lipids. The specific recognition of PtdIns(3,4,5)P(3) triggers insertion of the GRP1 PH domain into membranes. An acidic environment enhances PtdIns(3,4,5)P(3) binding and increases membrane penetration as demonstrated by NMR and monolayer surface tension and surface plasmon resonance experiments. The GRP1 PH domain displays a 28 nM affinity for POPC/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine/PtdIns(3,4,5)P(3) vesicles at pH 6.0, but binds 22-fold weaker at pH 8.0. The pH sensitivity is attributed in part to the His355 residue, protonation of which is required for the robust interaction with PtdIns(3,4,5)P(3) and significant membrane penetration, as illustrated by mutagenesis data. The binding affinity of the GRP1 PH domain for PtdIns(3,4,5)P(3)-containing vesicles is further amplified (by approximately 6-fold) by nonspecific electrostatic interactions with phosphatidylserine/phosphatidylinositol. Together, our results provide new insight into the multivalent mechanism of the membrane targeting and regulation of the GRP1 PH domain.