Highly accelerated submillimeter resolution 3D GRASE with controlled T2 blurring in T2 -weighted functional MRI at 7 Tesla: A feasibility study.

PURPOSE: To achieve highly accelerated submillimeter resolution T2 -weighted functional MRI at 7T by developing a three-dimensional gradient and spin echo imaging (GRASE) with inner-volume selection and variable flip angles (VFA). METHODS: GRASE imaging has disadvantages in that (a) k-space modulation causes T2 blurring by limiting the number of slices and (b) a VFA scheme results in partial success with substantial SNR loss. In this work, accelerated GRASE with controlled T2 blurring is developed to improve a point spread function (PSF) and temporal signal-to-noise ratio (tSNR) with a large number of slices. To this end, the VFA scheme is designed by minimizing a trade-off between SNR and blurring for functional sensitivity, and a new GRASE-optimized random encoding, which takes into account the complex signal decays of T2 and T2∗ weightings, is proposed by achieving incoherent aliasing for constrained reconstruction. Numerical and experimental studies were performed to validate the effectiveness of the proposed method over regular and VFA GRASE (R- and V-GRASE). RESULTS: The proposed method, while achieving 0.8 mm isotropic resolution, functional MRI compared to R- and V-GRASE improves the spatial extent of the excited volume up to 36 slices with 52%-68% full width at half maximum (FWHM) reduction in PSF but approximately 2- to 3-fold mean tSNR improvement, thus resulting in higher BOLD activations. CONCLUSIONS: We successfully demonstrated the feasibility of the proposed method in T2 -weighted functional MRI. The proposed method is especially promising for cortical layer-specific functional MRI.

How are rapid diagnostic tests for infectious diseases used in clinical practice: a global survey by the International Society of Antimicrobial Chemotherapy (ISAC).

Novel rapid diagnostic tests (RDTs) offer huge potential to optimise clinical care and improve patient outcomes. In this study, we aim to assess the current patterns of use around the world, identify issues for successful implementation and suggest best practice advice on how to introduce new tests. An electronic survey was devised by the International Society of Antimicrobial Chemotherapy (ISAC) Rapid Diagnostics and Biomarkers working group focussing on the availability, structure and impact of RDTs around the world. It was circulated to ISAC members in December 2019. Results were collated according to the UN human development index (HDI). 81 responses were gathered from 31 different countries. 84% of institutions reported the availability of any test 24/7. In more developed countries, this was more for respiratory viruses, whereas in high and medium/low developed countries, it was for HIV and viral hepatitis. Only 37% of those carrying out rapid tests measured the impact. There is no 'one-size fits all' solution to RDTs: the requirements must be tailored to the healthcare setting in which they are deployed and there are many factors that should be considered prior to this.

The Association Between Neighborhood Socioeconomic Disadvantage and Readmissions for Patients Hospitalized With Sepsis.

OBJECTIVES: To evaluate associations between a readily availvable composite measurement of neighborhood socioeconomic disadvantage (the area deprivation index) and 30-day readmissions for patients who were previously hospitalized with sepsis. DESIGN: A retrospective study. SETTING: An urban, academic medical institution. PATIENTS: The authors conducted a manual audit for adult patients (18 yr old or older) discharged with an International Classification of Diseases, 10th edition code of sepsis during the 2017 fiscal year to confirm that they met SEP-3 criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The area deprivation index is a publicly available composite score constructed from socioeconomic components (e.g., income, poverty, education, housing characteristics) based on census block level, where higher scores are associated with more disadvantaged areas (range, 1-100). Using discharge data from the hospital population health database, residential addresses were geocoded and linked to their respective area deprivation index. Patient characteristics, contextual-level variables, and readmissions were compared by t tests for continuous variables and Fisher exact test for categorical variables. The associations between readmissions and area deprivation index were explored using logistic regression models. A total of 647 patients had an International Classification of Diseases, 10th edition diagnosis code of sepsis. Of these 647, 116 (17.9%) either died in hospital or were discharged to hospice and were excluded from our analysis. Of the remaining 531 patients, the mean age was 61.0 years (± 17.6 yr), 281 were females (52.9%), and 164 (30.9%) were active smokers. The mean length of stay was 6.9 days (± 5.6 d) with the mean Sequential Organ Failure Assessment score 4.9 (± 2.5). The mean area deprivation index was 54.2 (± 23.8). The mean area deprivation index of patients who were readmitted was 62.5 (± 27.4), which was significantly larger than the area deprivation index of patients not readmitted (51.8 [± 22.2]) (p < 0.001). In adjusted logistic regression models, a greater area deprivation index was significantly associated with readmissions (ß, 0.03; p < 0.001). CONCLUSIONS: Patients who reside in more disadvantaged neighborhoods have a significantly higher risk for 30-day readmission following a hospitalization for sepsis. The insight provided by neighborhood disadvantage scores, such as the area deprivation index, may help to better understand how contextual-level socioeconomic status affects the burden of sepsis-related morbidity.

Comparison of BOLD and CBV using 3D EPI and 3D GRASE for cortical layer functional MRI at 7 T.

PURPOSE: Functional MRI (fMRI) at the mesoscale of cortical layers and columns requires both sensitivity and specificity, the latter of which can be compromised if the imaging method is affected by vascular artifacts, particularly cortical draining veins at the pial surface. Recent studies have shown that cerebral blood volume (CBV) imaging is more specific to the actual laminar locus of neural activity than BOLD imaging using standard gradient-echo EPI sequences. Gradient and spin-echo (GRASE) BOLD imaging has also shown greater specificity when compared with standard gradient-echo EPI BOLD. Here we directly compare CBV and BOLD contrasts in high-resolution imaging of the primary motor cortex for laminar functional MRI in four combinations of signal labeling, CBV using slice-selective slab-inversion vascular space occupancy (VASO) and BOLD, each with 3D gradient-echo EPI and zoomed 3D-GRASE image readouts. METHODS: Activations were measured using each sequence and contrast combination during a motor task. Activation profiles across cortical depth were measured to assess the sensitivity and specificity (pial bias) of each method. RESULTS: Both CBV imaging using gradient-echo 3D-EPI and BOLD imaging using 3D-GRASE show similar specificity and sensitivity and are therefore useful tools for mesoscopic functional MRI in the human cortex. The combination of GRASE and VASO did not demonstrate high levels of sensitivity, nor show increased specificity. CONCLUSION: Three-dimensional EPI with VASO contrast and 3D-GRASE with BOLD contrast both demonstrate sufficient sensitivity and specificity for laminar functional MRI to be used by neuroscientists in a wide range of investigations of depth-dependent neural circuitry in the human brain.

Procalcitonin (PCT)-guided antibiotic stewardship: an international experts consensus on optimized clinical use.

Background Procalcitonin (PCT)-guided antibiotic stewardship (ABS) has been shown to reduce antibiotics (ABxs), with lower side-effects and an improvement in clinical outcomes. The aim of this experts workshop was to derive a PCT algorithm ABS for easier implementation into clinical routine across different clinical settings. Methods Clinical evidence and practical experience with PCT-guided ABS was analyzed and discussed, with a focus on optimal PCT use in the clinical context and increased adherence to PCT protocols. Using a Delphi process, the experts group reached consensus on different PCT algorithms based on clinical severity of the patient and probability of bacterial infection. Results The group agreed that there is strong evidence that PCT-guided ABS supports individual decisions on initiation and duration of ABx treatment in patients with acute respiratory infections and sepsis from any source, thereby reducing overall ABx exposure and associated side effects, and improving clinical outcomes. To simplify practical application, the expert group refined the established PCT algorithms by incorporating severity of illness and probability of bacterial infection and reducing the fixed cut-offs to only one for mild to moderate and one for severe disease (0.25 µg/L and 0.5 µg/L, respectively). Further, guidance on interpretation of PCT results to initiate, withhold or discontinue ABx treatment was included. Conclusions A combination of clinical patient assessment with PCT levels in well-defined ABS algorithms, in context with continuous education and regular feedback to all ABS stakeholders, has the potential to improve the diagnostic and therapeutic management of patients suspected of bacterial infection, thereby improving ABS effectiveness.

Characterization of functional brain connectivity towards optimization of music selection for therapy: a fMRI study.

Background: Music therapy, a nontraditional approach to patient care, has long been used to achieve a wide variety of positive results. To deepen our understanding of the connection and therapeutic potential of music, the effect of music therapy and music medicine (music administered to individuals without an interactive therapeutic relationship) on the brain remains a topic of active research. Objective: This study is aimed at investigating the effect of different music genres and individualized music selection on brain functional connectivity (FC) measured by functional magnetic resonance imaging (fMRI). Methods: Twelve healthy subjects listened to five excerpts: Bach with and without visual guide (unfamiliar), self-selected familiar music, Gagaku (unfamiliar music) and Chaplin (spoken word) while undergoing a block design fMRI study. fMRI datasets were imported into CONN (Matlab toolbox) and graph networks were created for 132 anatomical regions in MNI space. Group connectivity for each soundtrack was quantified and statistically analyzed using the R package. Results: Complex interactions between brain regions, cerebellar regions (713), superior frontal gyrus (178) and parahippocampus (223), were highest for self-selected music. Brain regions involving sound processing, memory retrieval, semantic processing and motor areas were continuously activated for all five excerpts; however, most connections were formed in language processing regions for the Bach excerpt. Conclusion: Functional brain connectivity varied by soundtrack with the largest degree of connectivity found consistently for self-selected and unfamiliar (Bach, Gagaku) music. Incorporating individualized music listening into existing therapy paradigms may positively contribute to standard protocol for stroke rehabilitation and prevention.

Impact of the implementation of a nurse-managed outpatient parenteral antibiotic therapy (OPAT) system in Baltimore: a case study demonstrating cost savings and reduction in re-admission rates.

Objectives: Evidence supports the safety and effectiveness of outpatient parenteral antibiotic therapy (OPAT). A registered nurse (RN)-managed multidisciplinary team OPAT model was implemented at our hospital. We evaluated the impact of the new OPAT model on readmissions during OPAT and other core OPAT processes. Methods: All potential OPAT cases from 1 November 2013 to 31 June 2017 discharged from the Johns Hopkins Bayview Medical Center were followed up in a retrospective cohort study. Relevant clinical and patient characteristics were collected for the first OPAT course per patient. The primary outcome was all-cause readmission to any facility part of the Johns Hopkins Health System within 30 days of OPAT discharge. Proportions of OPAT patients readmitted before and after the implementation of the new OPAT model were compared. A log-binomial regression was used to compare the risk of readmission, adjusted for age, sex, race/ethnicity, site of OPAT care, opioid dependence and OPAT treatment duration. Results: Five hundred and seventeen OPAT patients were included in the analysis; 51.1% were discharged after the implementation of the new OPAT model. Readmission rates decreased from 20.2% to 13.3% following the RN-managed OPAT programme (P = 0.04). The results of the adjusted model indicated that nurse management was associated with a 39% reduction in the risk of readmission (adjusted relative risk 0.61; 95% CI 0.41-0.91; P = 0.01). Our financial evaluation estimated that the reduction in readmissions achieved by the RN-managed model saved the hospital $649 416 over 15 months. Conclusions: The RN-managed OPAT programme was associated with a significant reduction in readmissions.

Hospitalist Infectious Disease Service in Academic Medical Centers: A Win-Win for Hospitalists and Fellows.

Supplemental digital content is available in the text.

A review of congenital lung malformations with a simplified classification system for clinical and research use.

PURPOSE: Congenital lung abnormalities are rare malformations increasingly detected early by prenatal ultrasound. Whether management of these frequently asymptomatic lesions should be surgical or conservative is an unresolved issue. The necessary prospective studies are limited by the absence of a widely accepted practical classification system. Our aim was to develop a simple, clinically relevant system for classifying and studying congenital lung abnormalities. MATERIALS AND METHODS: We based our proposed grouping on a detailed analysis of clinical, radiological, and histological data from well-documented cases, plus an extensive review of the literature. RESULTS: The existence of hybrid lesions and common histological findings suggested a unified embryological mechanism-possibly obstruction of developing airways with distal dysplasia. Malformations could be classified by their anatomical and pathological findings; however, a system based on the prenatal ultrasound plus initial chest X-ray findings had greater clinical relevance: Group 1-Congenital solid/cystic lung malformation, Group 2-Congenital hyperlucent lobe, Group 3-Congenital small lung. CONCLUSIONS: Pathological classification is academically important but is unnecessarily complex for clinical and research use. Our simple radiological-based system allows unambiguous comparison between the results of different studies and also guides the choice of necessary investigations specific to each group.

Differential electrophysiological response during rest, self-referential, and non-self-referential tasks in human posteromedial cortex.

The electrophysiological basis for higher brain activity during rest and internally directed cognition within the human default mode network (DMN) remains largely unknown. Here we use intracranial recordings in the human posteromedial cortex (PMC), a core node within the DMN, during conditions of cued rest, autobiographical judgments, and arithmetic processing. We found a heterogeneous profile of PMC responses in functional, spatial, and temporal domains. Although the majority of PMC sites showed increased broad gamma band activity (30-180 Hz) during rest, some PMC sites, proximal to the retrosplenial cortex, responded selectively to autobiographical stimuli. However, no site responded to both conditions, even though they were located within the boundaries of the DMN identified with resting-state functional imaging and similarly deactivated during arithmetic processing. These findings, which provide electrophysiological evidence for heterogeneity within the core of the DMN, will have important implications for neuroimaging studies of the DMN.

Differences in resting corticolimbic functional connectivity in bipolar I euthymia.

OBJECTIVE: We examined resting state functional connectivity in the brain between key emotion regulation regions in bipolar I disorder to delineate differences in coupling from healthy subjects. METHODS: Euthymic subjects with bipolar I disorder (n = 20) and matched healthy subjects (n = 20) participated in a resting state functional magnetic resonance imaging scan. Low-frequency fluctuations in blood oxygen level-dependent (BOLD) signal were correlated in the six connections between four anatomically defined nodes: left and right amygdala and left and right ventrolateral prefrontal cortex (vlPFC). Seed-to-voxel connectivity results were probed for commonly coupled regions. Following this, an identified region was included in a mediation analysis to determine the potential of mediation. RESULTS: The bipolar I disorder group exhibited significant hyperconnectivity between right amygdala and right vlPFC relative to healthy subjects. The connectivity between these regions in the bipolar I disorder group was partially mediated by activity in the anterior cingulate cortex (ACC). CONCLUSIONS: Greater coupling between right amygdala and right vlPFC and their partial mediation by the ACC were found in bipolar I disorder subjects in remission and in the absence of a psychological task. These findings have implications for a trait-related and clinically important imaging biomarker.

Normal amygdala activation but deficient ventrolateral prefrontal activation in adults with bipolar disorder during euthymia.

Functional neuroimaging studies have implicated the involvement of the amygdala and ventrolateral prefrontal cortex (vlPFC) in the pathophysiology of bipolar disorder. Hyperactivity in the amygdala and hypoactivity in the vlPFC have been reported in manic bipolar patients scanned during the performance of an affective faces task. Whether this pattern of dysfunction persists during euthymia is unclear. Using functional magnetic resonance imaging (fMRI), 24 euthymic bipolar and 26 demographically matched healthy control subjects were scanned while performing an affective task paradigm involving the matching and labeling of emotional facial expressions. Neuroimaging results showed that, while amygdala activation did not differ significantly between groups, euthymic patients showed a significant decrease in activation of the right vlPFC (BA47) compared to healthy controls during emotion labeling. Additionally, significant decreases in activation of the right insula, putamen, thalamus and lingual gyrus were observed in euthymic bipolar relative to healthy control subjects during the emotion labeling condition. These data, taken in context with prior studies of bipolar mania using the same emotion recognition task, could suggest that amygdala dysfunction may be a state-related abnormality in bipolar disorder, whereas vlPFC dysfunction may represent a trait-related abnormality of the illness. Characterizing these patterns of activation is likely to help in understanding the neural changes related to the different mood states in bipolar disorder, as well as changes that represent more sustained abnormalities. Future studies that assess mood-state related changes in brain activation in longitudinal bipolar samples would be of interest.

Emotion processing and regulation in bipolar disorder: a review.

OBJECTIVES: Bipolar disorder (BP) is characterized by a dysfunction of mood, alternating between states of mania/hypomania and depression. Thus, the primary abnormality appears to be an inability to regulate emotion, the result of which is emotional extremes. The purpose of this paper is to review the current functional magnetic resonance imaging (fMRI) literature on adult patients with BP using emotion processing or regulation paradigms. METHODS: A search was conducted on PubMed using the keywords: bipolar disorder, fMRI, mania, bipolar depression, bipolar euthymia, emotion, and amygdala. Only those studies that were conducted in adult patients using an emotion activation task were included in the final review. RESULTS: Using tasks that assess neural functioning during emotion processing and emotion regulation, many fMRI studies have examined BP subjects during mania and euthymia. Fewer fMRI studies have been conducted during depression, and fewer still have included the same subjects in multiple mood states. Despite these limitations, these studies have demonstrated specific abnormalities in frontal-limbic regions. Using a variety of paradigms, investigators have specifically evaluated the amygdala (a structure within the limbic system known to be critical for emotion) and the prefrontal cortex (PFC) (a region known to have a regulatory function over the limbic system). CONCLUSIONS: These investigations reveal that amygdala activation varies as a function of mood state, while the PFC remains persistently hypoactivated across mood states. Emotional dysregulation and lability in mania and depression may reflect disruption of a frontal-limbic functional neuroanatomical network.

The functional neuroanatomy of bipolar disorder: a consensus model.

OBJECTIVES: Functional neuroimaging methods have proliferated in recent years, such that functional magnetic resonance imaging, in particular, is now widely used to study bipolar disorder. However, discrepant findings are common. A workgroup was organized by the Department of Psychiatry, University of Cincinnati (Cincinnati, OH, USA) to develop a consensus functional neuroanatomic model of bipolar I disorder based upon the participants' work as well as that of others. METHODS: Representatives from several leading bipolar disorder neuroimaging groups were organized to present an overview of their areas of expertise as well as focused reviews of existing data. The workgroup then developed a consensus model of the functional neuroanatomy of bipolar disorder based upon these data. RESULTS: Among the participants, a general consensus emerged that bipolar I disorder arises from abnormalities in the structure and function of key emotional control networks in the human brain. Namely, disruption in early development (e.g., white matter connectivity and prefrontal pruning) within brain networks that modulate emotional behavior leads to decreased connectivity among ventral prefrontal networks and limbic brain regions, especially the amygdala. This developmental failure to establish healthy ventral prefrontal-limbic modulation underlies the onset of mania and ultimately, with progressive changes throughout these networks over time and with affective episodes, a bipolar course of illness. CONCLUSIONS: This model provides a potential substrate to guide future investigations and areas needing additional focus are identified.

Deficits in inferior frontal cortex activation in euthymic bipolar disorder patients during a response inhibition task.

OBJECTIVES: The inferior frontal cortical-striatal network plays an integral role in response inhibition in normal populations. While inferior frontal cortex (IFC) impairment has been reported in mania, this study explored whether this dysfunction persists in euthymia. METHODS: Functional magnetic resonance imaging (fMRI) activation was evaluated in 32 euthymic patients with bipolar I disorder and 30 healthy subjects while performing the Go/NoGo response inhibition task. Behavioral data were collected to evaluate accuracy and response time. Within-group and between-group comparisons of activation were conducted using whole-brain analyses to probe significant group differences in neural function. RESULTS: Both groups activated bilateral IFC. However, between-group comparisons showed a significantly reduced activation in this brain region in euthymic patients with bipolar disorder compared to healthy subjects. Other frontal and basal ganglia regions involved in response inhibition were additionally significantly reduced in bipolar disorder patients, in both the medicated and the unmedicated subgroups. No areas of greater activation were observed in bipolar disorder patients versus healthy subjects. CONCLUSIONS: Bipolar disorder patients, even during euthymia, have a persistent reduction in activation of brain regions involved in response inhibition, suggesting that reduced activation in the orbitofrontal cortex and striatum is not solely related to the state of mania. These findings may represent underlying trait abnormalities in bipolar disorder.

Positive Stimulation for Medically Sedated Patients: A Music Therapy Intervention to Treat Sedation-Related Delirium in Critical Care.

Sedation is an essential component of treatment for some patients admitted to the ICU, but it carries a risk of sedation-related delirium. Sedation-related delirium is associated with higher mortality and increased length of stay, but pharmacologic treatments for delirium can lead to oversedation or other adverse effects. Therefore, nonpharmacologic treatments are recommended in the literature; however, these recommendations are quite general and do not provide structured interventions. To establish a structured nonpharmacologic intervention that could improve indications of delirium after sedation, we combined evidence-based interventions including recordings of sensory-rich stories told by the patient's family and patient-specific music into our novel positive stimulation for medically sedated patients (PSMSP) protocol. The positive listening stimulation playlist organized by a board-certified music therapist (MT-BC) within the PSMSP protocol can be used in carefully monitored sessions with the MT-BC potentially to decrease agitation and stabilize arousal, as well as being played by nursing staff throughout the patient's recovery from sedation. Further controlled studies will be necessary, but the PSMSP protocol has the potential to reduce agitation and increase arousal during listening, as highlighted by the case of a patient recovering from sedation during treatment for COVID-19 pneumonia. It is important for the entire critical care team to be aware of nonpharmacologic treatments like PSMSP that are available for delirium mitigation so that, where applicable, these therapies can be incorporated into the patient's treatment regimen.

Amygdala reactivity in healthy adults is correlated with prefrontal cortical thickness.

Recent evidence suggests that putting feelings into words activates the prefrontal cortex (PFC) and suppresses the response of the amygdala, potentially helping to alleviate emotional distress. To further elucidate the relationship between brain structure and function in these regions, structural and functional magnetic resonance imaging (MRI) data were collected from a sample of 20 healthy human subjects. Structural MRI data were processed using cortical pattern-matching algorithms to produce spatially normalized maps of cortical thickness. During functional scanning, subjects cognitively assessed an emotional target face by choosing one of two linguistic labels (label emotion condition) or matched geometric forms (control condition). Manually prescribed regions of interest for the left amygdala were used to extract percentage signal change in this region occurring during the contrast of label emotion versus match forms. A correlation analysis between left amygdala activation and cortical thickness was then performed along each point of the cortical surface, resulting in a color-coded r value at each cortical point. Correlation analyses revealed that gray matter thickness in left ventromedial PFC was inversely correlated with task-related activation in the amygdala. These data add support to a general role of the ventromedial PFC in regulating activity of the amygdala.

Improving antimicrobial prescribing for upper respiratory infections in the emergency department: Implementation of peer comparison with behavioral feedback.

Objective: To reduce inappropriate antibiotic prescribing for acute respiratory infections (ARIs) by employing peer comparison with behavioral feedback in the emergency department (ED). Design: A controlled before-and-after study. Setting: The study was conducted in 5 adult EDs at teaching and community hospitals in a health system. Patients: Adults presenting to the ED with a respiratory condition diagnosis code. Hospitalized patients and those with a diagnosis code for a non-respiratory condition for which antibiotics are or may be warranted were excluded. Interventions: After a baseline period from January 2016 to March 2018, 3 EDs implemented a feedback intervention with peer comparison between April 2018 and December 2019 for attending physicians. Also, 2 EDs in the health system served as controls. Using interrupted time series analysis, the inappropriate ARI prescribing rate was calculated as the proportion of antibiotic-inappropriate ARI encounters with a prescription. Prescribing rates were also evaluated for all ARIs. Attending physicians at intervention sites received biannual e-mails with their inappropriate prescribing rate and had access to a dashboard that was updated daily showing their performance relative to their peers. Results: Among 28,544 ARI encounters, the inappropriate prescribing rate remained stable at the control EDs between the 2 periods (23.0% and 23.8%). At the intervention sites, the inappropriate prescribing rate decreased significantly from 22.0% to 15.2%. Between periods, the overall ARI prescribing rate was 38.1% and 40.6% in the control group and 35.9% and 30.6% in the intervention group. Conclusions: Behavioral feedback with peer comparison can be implemented effectively in the ED to reduce inappropriate prescribing for ARIs.

Development of an antimicrobial stewardship module in an electronic health record: Options to enhance daily antimicrobial stewardship activities.

PURPOSE: The purpose of this manuscript is to describe our experience developing an antimicrobial stewardship (AS) module as a clinical decision support tool in the Epic electronic health record (EHR). SUMMARY: Clinical decision support systems within the EHR can be used to decrease use of broad-spectrum antibiotics, improve antibiotic selection and dosing, decrease adverse effects, reduce antibiotic costs, and reduce the development of antibiotic resistance. The Johns Hopkins Hospital constructed an AS module within Epic. Customized stewardship alerts and scoring systems were developed to triage patients requiring stewardship intervention. This required a multidisciplinary approach with a team comprising AS physicians and pharmacists and Epic information technology personnel, with assistance from clinical microbiology and infection control when necessary. In addition, an intervention database was enhanced with stewardship-specific interventions, and workbench reports were developed specific to AS needs. We herein review the process, advantages, and challenges associated with the development of the Epic AS module. CONCLUSION: Customizing an AS module in an EHR requires significant time and expertise in antimicrobials; however, AS modules have the potential to improve the efficiency of AS personnel in performing daily stewardship activities and reporting through a single system.

Rate of sepsis hospitalizations after misdiagnosis in adult emergency department patients: a look-forward analysis with administrative claims data using Symptom-Disease Pair Analysis of Diagnostic Error (SPADE) methodology in an integrated health system.

OBJECTIVES: Delays in sepsis diagnosis can increase morbidity and mortality. Previously, we performed a Symptom-Disease Pair Analysis of Diagnostic Error (SPADE) "look-back" analysis to identify symptoms at risk for delayed sepsis diagnosis. We found treat-and-release emergency department (ED) encounters for fluid and electrolyte disorders (FED) and altered mental status (AMS) were associated with downstream sepsis hospitalizations. In this "look-forward" analysis, we measure the potential misdiagnosis-related harm rate for sepsis among patients with these symptoms. METHODS: Retrospective cohort study using electronic health record and claims data from Kaiser Permanente Mid-Atlantic States (2013-2018). Patients ≥18 years with ≥1 treat-and-release ED encounter for FED or AMS were included. Observed greater than expected sepsis hospitalizations within 30 days of ED treat-and-release encounters were considered potential misdiagnosis-related harms. Temporal analyses were employed to differentiate case and comparison (superficial injury/contusion ED encounters) cohorts. RESULTS: There were 4,549 treat-and-release ED encounters for FED or AMS, 26 associated with a sepsis hospitalization in the next 30 days. The observed (0.57%) minus expected (0.13%) harm rate was 0.44% (absolute) and 4.5-fold increased over expected (relative). There was a spike in sepsis hospitalizations in the week following FED/AMS ED visits. There were fewer sepsis hospitalizations and no spike in admissions in the week following superficial injury/contusion ED visits. Potentially misdiagnosed patients were older and more medically complex. CONCLUSIONS: Potential misdiagnosis-related harms from sepsis are infrequent but measurable using SPADE. This look-forward analysis validated our previous look-back study, demonstrating the SPADE approach can be used to study infectious disease syndromes.