The article discusses the findings of a study to evaluate the effect of intravenous vitamin C infusion on organ failure scores and biological markers of inflammation and vascular injury in patients ...with sepsis and acute respiratory distress failure (ARDS), which revealed that among these patients, a 96-hour infusion of vitamin C did not significantly improve organ dysfunction scores or alter markers of inflammation and vascular injury. The need is for further research to find an effective therapy for sepsis.
Interrupted time series analysis of a retrospective, electronic health record cohort.
To determine the association between the implementation of Medicare's sepsis reporting measure (SEP-1) and sepsis ...diagnosis rates as assessed in clinical documentation.
The role of health policy in the effort to improve sepsis diagnosis remains unclear.
Adult patients hospitalized with suspected infection and organ dysfunction within 6 hours of presentation to the emergency department, admitted to one of 11 hospitals in a multi-hospital health system from January 2013 to December 2017. Clinician-diagnosed sepsis, as reflected by the inclusion of the terms "sepsis" or "septic" in the text of clinical notes in the first two calendar days following presentation.
Among 44,074 adult patients with sepsis admitted to 11 hospitals over 5 years, the proportion with sepsis documentation was 32.2% just before the implementation of SEP-1 in the third quarter of 2015 and increased to 37.3% by the fourth quarter of 2017. Of the 9 post-SEP-1 quarters, 8 had odds ratios for a sepsis diagnosis >1 (overall range: 0.98-1.26; P value for a joint test of statistical significance = 0.005). The effects were clinically modest, with a maximum effect of an absolute increase of 4.2% (95% CI: 0.9-7.8) at the end of the study period. The effect was greater in patients who did not require vasopressors compared with patients who required vasopressors ( P value for test of interaction = 0.02).
SEP-1 implementation was associated with modest increases in sepsis diagnosis rates, primarily among patients who did not require vasoactive medications.
Clinical and biologic phenotypes of sepsis are proposed in human studies, yet it is unknown whether prognostic or drug response phenotypes are present in animal models of sepsis. Using a ...biotelemetry-enhanced, murine cecal ligation and puncture (CLP) model, we determined phenotypes of polymicrobial sepsis prior to physiologic deterioration, and the association between phenotypes and outcome in a randomized trial of prompt or delayed antibiotics and fluids.
We performed a secondary analysis of male C57BL/6J mice in two observational cohorts and two randomized, laboratory animal experimental trials. In cohort 1, mice (n = 118) underwent biotelemetry-enhanced CLP, and we applied latent class mixed models to determine optimal number of phenotypes using clinical data collected between injury and physiologic deterioration. In cohort 2 (N = 73 mice), inflammatory cytokines measured at 24 h after deterioration were explored by phenotype. In a subset of 46 mice enrolled in two trials from cohort 1, we tested the association of phenotypes with the response to immediate (0 h) vs. delayed (2 to 4 h) antibiotics or fluids initiated after physiologic deterioration.
Latent class mixture modeling derived a two-class model in cohort 1. Class 2 (N = 97) demonstrated a shorter time to deterioration (mean SD 7.3 (0.9) vs. 9.7 (3.2) h, p < 0.001) and lower heart rate at 7 h after injury (mean (SD) 564 (55) vs. 626 (35) beats per minute, p < 0.001). Overall mortality was similar between phenotypes (p = 0.75). In cohort 2 used for biomarker measurement, class 2 mice had greater plasma concentrations of IL6 and IL10 at 24 h after CLP (p = 0.05). In pilot randomized trials, the effects of sepsis treatment (immediate vs. delayed antibiotics) differed by phenotype (p = 0.03), with immediate treatment associated with greater survival in class 2 mice only. Similar differential treatment effect by class was observed in the trial of immediate vs. delayed fluids (p = 0.02).
We identified two sepsis phenotypes in a murine cecal ligation and puncture model, one of which is characterized by faster deterioration and more severe inflammation. Response to treatment in a randomized trial of immediate versus delayed antibiotics and fluids differed on the basis of phenotype.
Oral case presentation is a crucial skill of physicians and a key component of team-based care. However, consistent and objective assessment and feedback on presentations during training are ...infrequent.
To determine the potential value of applying natural language processing, computer software that extracts meaning from text, to transcripts of oral case presentations as a strategy to assess their quality automatically and objectively.
We transcribed a collection of simulated oral case presentations. The presentations were from eight critical care fellows and one critical care attending. They were instructed to review the medical charts of 11 real intensive care unit patient cases and to audio record themselves, presenting each case as if they were doing so on morning rounds. We then used natural language processing to convert the transcripts from human-readable text into machine-readable numbers. These numbers represent details of the presentation style and content. The distance between the numeric representation of two different transcripts negatively correlates with the similarity of those two transcripts. We ranked fellows on the basis of how similar their presentations were to the attending's presentations.
The 99 presentations included 260 minutes of audio (mean length: 2.6 ± 1.24 min per case). On average, 23.88 ± 2.65 sentences were spoken, and each sentence had 14.10 ± 0.67 words, 3.62 ± 0.15 medical concepts, and 0.75 ± 0.09 medical adjectives. When ranking fellows on the basis of how similar their presentations were to the attending's presentation, we found a gap between the five fellows with the most similar presentations and the three fellows with the least similar presentations (average group similarity scores of 0.62 ± 0.01 and 0.53 ± 0.01, respectively). Rankings were sensitive to whether presentation style or content information were weighted more heavily when calculating transcript similarity.
Natural language processing enabled the ranking of case presentations on the basis of how similar they were to a reference presentation. Although additional work is needed to convert these rankings, and underlying similarity scores, into actionable feedback for trainees, these methods may support new tools for improving medical education.
The development of a shared data infrastructure across health systems could improve research, clinical care, and health policy across a spectrum of diseases, including sepsis. Awareness of the ...potential value of such infrastructure has been heightened by COVID-19, as the lack of a real-time, interoperable data network impaired disease identification, mitigation, and eradication. The Sepsis on FHIR collaboration establishes a dynamic, federated, and interoperable system of sepsis data from 55 hospitals using 2 distinct inpatient electronic health record systems. Here we report on phase 1, a systematic review to identify clinical variables required to define sepsis and its subtypes to produce a concept mapping of elements onto Fast Healthcare Interoperability Resources (FHIR). Relevant papers described consensus sepsis definitions, provided criteria for sepsis, severe sepsis, septic shock, or detailed sepsis subtypes. Studies not written in English, published prior to 1970, or "grey" literature were prospectively excluded. We analyzed 55 manuscripts yielding 151 unique clinical variables. We then mapped variables to their corresponding US Core FHIR resources and specific code values. This work establishes the framework to develop a flexible infrastructure for sharing sepsis data, highlighting how FHIR could enable the extension of this approach to other important conditions relevant to public health.
There is wide heterogeneity in sepsis in causative pathogens, host response, organ dysfunction, and outcomes. Clinical and biologic phenotypes of sepsis are proposed, but the role of pathogen data on ...sepsis classification is unknown.
We conducted a secondary analysis of the Recombinant Human Activated Protein C (rhAPC) Worldwide Evaluation in Severe Sepsis (PROWESS) Study. We used latent class analysis (LCA) to identify sepsis phenotypes using, (i) only clinical variables ("host model") and, (ii) combining clinical with microbiology variables (e.g., site of infection, culture-derived pathogen type, and anti-microbial resistance characteristics, "host-pathogen model"). We describe clinical characteristics, serum biomarkers, and outcomes of host and host-pathogen models. We tested the treatment effects of rhAPC by phenotype using Kaplan-Meier curves.
Among 1,690 subjects with severe sepsis, latent class modeling derived a 4-class host model and a 4-class host-pathogen model. In the host model, alpha type (
= 327, 19%) was younger and had less shock; beta type (N=518, 31%) was older with more comorbidities; gamma type (
= 532, 32%) had more pulmonary dysfunction; delta type (
= 313, 19%) had more liver, renal and hematologic dysfunction and shock. After the addition of microbiologic variables, 772 (46%) patients changed phenotype membership, and the median probability of phenotype membership increased from 0.95 to 0.97 (
< 0.01). When microbiology data were added, the contribution of individual variables to phenotypes showed greater change for beta and gamma types. In beta type, the proportion of abdominal infections (from 20 to 40%) increased, while gamma type patients had an increased rate of lung infections (from 50 to 78%) with worsening pulmonary function. Markers of coagulation such as d-dimer and plasminogen activator inhibitor (PAI)-1 were greater in the beta type and lower in the gamma type. The 28 day mortality was significantly different for individual phenotypes in host and host-pathogen models (both
< 0.01). The treatment effect of rhAPC obviously changed in gamma type when microbiology data were added (
-values of log rank test changed from 0.047 to 0.780).
Sepsis host phenotype assignment was significantly modified when microbiology data were added to clinical variables, increasing cluster cohesiveness and homogeneity.
Background
To test the hypothesis that optic nerve sheath diameter (ONSD) correlates with real-time changes in intracranial pressure, we performed ultrasound measurements of the ONSD in ambulatory ...patients undergoing elective lumbar puncture (LP). We conducted a prospective cohort study, including adult patients undergoing LP in a non-emergent setting. We measured ONSD perpendicular to the optic nerve at 3 mm behind the globe in both eyes in the traverse and sagittal planes, with the patient supine. The primary outcome was change in ONSD from pre-LP to post-LP. We calculated association of opening and closing LP pressures with changes in the pre- and post-LP ONSD measurements.
Results
The mean patient age was 49.0 years (SD = 37–61, range 19–67) with 21 females (72.4%) and 26 (89.7%) white American (not Hispanic or Latino). The average opening pressure and closing pressures were 20.4 cm and 13.5 cm with a difference of 6.9 cm, (95% CI 3.9–10.0 cm). Pressures between the participants with baseline ONSD measurement > 5 mm (average opening pressure = 21.3 cm) to those < 5 mm (20.2 cm) differed by 1.1 cm (95% CI − 5.7 to 8.0). Linear regression revealed no association between the sagittal, transverse, average, and change in ONSD measurements with the observed LP opening pressure, change in LP pressure, or volume of cerebral spinal fluid (CSF) drained.
Conclusions
In this study of ambulatory patients undergoing rapid decreases in ICP via elective LP, we detected no acute changes in ultrasonographic measurement of the ONSD.
Although multiple consensus statements have called for large-scale efforts to improve clinicians' communication skills regarding a variety of difficult conversations in medicine, this goal will be ...difficult to attain because there are no readily scalable, validated communication skills training programs for clinicians. However, novel applications of existing technologies and approaches grounded in learning science can overcome the scalability barriers. Moreover, future advances in virtual reality and artificial intelligence are likely to greatly enhance the possibilities for communication skills training programs. The purpose of this paper is to propose a scalable, theoretically grounded method to train clinicians in advanced communication skills in medicine. First, we summarize four key principles of adult learning relevant to communication skills training in medicine. Second, we discuss recommended practices to design effective technology-enhanced educational interventions, with an emphasis on achieving high amounts of user engagement. Third, we synthesize these principles into a framework for a web- and videoconference-based platform for teaching advanced communication skills in medicine. Once developed, this low-cost, scalable training platform has the potential to allow thousands of clinicians to acquire the advanced communication skills needed for difficult conversations in medicine.
Background: Patients with acute illness who receive intravenous (IV) fluids prior to hospital arrival may have a lower in-hospital mortality. To better understand whether this is a direct treatment ...effect or epiphenomenon of downstream care, we tested the association between a prehospital fluid bolus and the change in inflammatory cytokines measured at prehospital and emergency department timepoints in a sample of non-trauma, non-cardiac arrest patients at risk for critical illness. Methods: In a prospective cohort study, we screened 4,013 non-trauma, non-cardiac arrest encounters transported by City of Pittsburgh Emergency Medical Services (EMS) to 2 hospitals from August 2013 to February 2014. In 345 patients, we measured prehospital biomarkers (IL-6, IL-10, and TNF) at 2 time points: the time of prehospital IV access placement by EMS and at ED arrival. We determined the relative change for marker X as: (X
ED
- X
EMS
/X
EMS
). We determined the risk-adjusted association between prehospital IV fluid bolus and relative change for each marker using multivariable linear regression. Results: Among 345 patients, 88 (26%) received a prehospital IV fluid bolus and 257 (74%) did not. Compared to patients who did not receive prehospital fluids, median prehospital IL-6 was greater initially in subjects receiving a prehospital IV fluid bolus (22.3 IQR 6.4-113 vs. 11.5 IQR 5.5-47.6). Prehospital IL-10 and TNF were similar in both groups (IL-10: 3.5 IQR 2.2-25.6 vs. 3.0 IQR 1.9-9.0; TNF: 7.5 IQR 6.4-10.4 vs. 6.9 IQR 6.0-8.3). After adjustment for demographics, illness severity, and prehospital transport time, we observed a relative decrease in IL-6 at hospital arrival in those receiving a prehospital fluid bolus (adjusted β = −10.0, 95% CI: −19.4, −0.6, p = 0.04), but we did not detect a significant change in IL-10 (p = 0.34) or TNF (p = 0.53). Conclusions: Among non-trauma, non-cardiac arrest patients at risk for critical illness, a prehospital IV fluid bolus was associated with a relative decrease in IL-6, but not IL-10 or TNF.
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