Publications by authors named "Kyle B Enfield"

46 Publications

Cardiopulmonary Resuscitation in Coronavirus Disease 2019 Patients Experiencing In-Hospital Cardiac Arrest: More Data Are Needed.

Crit Care Med 2021 Apr 2. Epub 2021 Apr 2.

1 Department of Medicine, Division of Pulmonary and Critical Care, University of Virginia, Charlottesville, VA 2 Department of Emergency Medicine, University of Virginia, Charlottesville, VA.

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http://dx.doi.org/10.1097/CCM.0000000000004985DOI Listing
April 2021

Physiologic Improvement in Respiratory Acidosis Using Extracorporeal Co Removal With Hemolung Respiratory Assist System in the Management of Severe Respiratory Failure From Coronavirus Disease 2019.

Crit Care Explor 2021 Mar 9;3(3):e0372. Epub 2021 Mar 9.

Department of Medicine, Louisiana State University Health Sciences Center, Shreveport, LA.

Objectives: About 15% of hospitalized coronavirus disease 2019 patients require ICU admission, and most (80%) of these require invasive mechanical ventilation. Lung-protective ventilation in coronavirus disease 2019 acute respiratory failure may result in severe respiratory acidosis without significant hypoxemia. Low-flow extracorporeal Co removal can facilitate lung-protective ventilation and avoid the adverse effects of severe respiratory acidosis. The objective was to evaluate the efficacy of extracorporeal Co removal using the Hemolung Respiratory Assist System in correcting severe respiratory acidosis in mechanically ventilated coronavirus disease 2019 patients with severe acute respiratory failure.

Design: Retrospective cohort analysis of patients with coronavirus disease 2019 mechanically ventilated with severe hypercapnia and respiratory acidosis and treated with low-flow extracorporeal Co removal.

Setting: Eight tertiary ICUs in the United States.

Patients: Adult patients supported with the Hemolung Respiratory Assist System from March 1, to September 30, 2020.

Interventions: Extracorporeal Co removal with Hemolung Respiratory Assist System under a Food and Drug Administration emergency use authorization for coronavirus disease 2019.

Measurements And Main Results: The primary outcome was improvement in pH and Paco from baseline. Secondary outcomes included survival to decannulation, mortality, time on ventilator, and adverse events. Thirty-one patients were treated with Hemolung Respiratory Assist System with significant improvement in pH and Pco in this cohort. Two patients experienced complications that prevented treatment. Of the 29 treated patients, 58% survived to 48 hours post treatment and 38% to hospital discharge. No difference in age or comorbidities were noted between survivors and nonsurvivors. There was significant improvement in pH (7.24 ± 0.12 to 7.35 ± 0.07; < 0.0001) and Paco (79 ± 23 to 58 ± 14; < 0.0001) from baseline to 24 hours.

Conclusions: In this retrospective case series of 29 patients, we have demonstrated efficacy of extracorporeal Co removal using the Hemolung Respiratory Assist System to improve respiratory acidosis in patients with severe hypercapnic respiratory failure due to coronavirus disease 2019.
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http://dx.doi.org/10.1097/CCE.0000000000000372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994071PMC
March 2021

Effectiveness of Elastomeric Half-Mask Respirators vs N95 Filtering Facepiece Respirators During Simulated Resuscitation: A Nonrandomized Controlled Trial.

JAMA Netw Open 2021 Mar 1;4(3):e211564. Epub 2021 Mar 1.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Virginia School of Medicine, Charlottesville.

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http://dx.doi.org/10.1001/jamanetworkopen.2021.1564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967080PMC
March 2021

Intraarterial Catheter Use Is Associated With Increased Risk of Hospital Onset Bacteremia: A Retrospective Cohort Study.

Chest 2021 Jan 23. Epub 2021 Jan 23.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Virginia Health System, Charlottesville, VA.

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http://dx.doi.org/10.1016/j.chest.2021.01.038DOI Listing
January 2021

Post-ICU COVID-19 Outcomes: A Case Series.

Chest 2021 01 21;159(1):215-218. Epub 2020 Aug 21.

Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Virginia, Charlottesville, VA; Department of Pharmacology, University of Virginia, Charlottesville, VA. Electronic address:

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http://dx.doi.org/10.1016/j.chest.2020.08.2056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442057PMC
January 2021

A comparison of the effect of weather and climate on emergency department visitation in Roanoke and Charlottesville, Virginia.

Environ Res 2020 12 20;191:110065. Epub 2020 Aug 20.

Departments of Public Health Sciences and Orthopaedic Surgery, University of Virginia, Charlottesville, VA, USA. Electronic address:

Compared with mortality, the impact of weather and climate on human morbidity is less well understood, especially in the cold season. We examined the relationships between weather and emergency department (ED) visitation at hospitals in Roanoke and Charlottesville, Virginia, two locations with similar climates and population demographic profiles. Using patient-level data obtained from electronic medical records, each patient who visited the ED was linked to that day's weather from one of 8 weather stations in the region based on each patient's ZIP code of residence. The resulting 2010-2017 daily ED visit time series were examined using a distributed lag non-linear model to account for the concurrent and lagged effects of weather. Total ED visits were modeled separately for each location along with subsets based on gender, race, and age. The relationship between the relative risk of ED visitation and temperature or apparent temperature over lags of one week was positive and approximately linear at both locations. The relative risk increased about 5% on warm, humid days in both cities (lag 0 or lag 1). Cold conditions had a protective effect, with up to a 15% decline on cold days, but ED visits increased by 4% from 2 to 5 days after the cold event. The effect of thermal extremes tended to be larger for non-whites and the elderly, and there was some evidence of a greater lagged response for non-whites in Roanoke. Females in Roanoke were more impacted by winter cold conditions than males, who were more likely to show a lagged response at high temperatures. In Charlottesville, males sought ED attention at lower temperatures than did females. The similarities in the ED response patterns between these two hospitals suggest that certain aspects of the response may be generalizable to other locations that have similar climates and demographic profiles.
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http://dx.doi.org/10.1016/j.envres.2020.110065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658034PMC
December 2020

Adoption of a dedicated multidisciplinary team is associated with improved survival in acute pulmonary embolism.

Respir Res 2020 Jun 22;21(1):159. Epub 2020 Jun 22.

Department of Medicine, Division of Pulmonary and Critical Care, University of Virginia, Charlottesville, USA.

Background: Acute pulmonary embolism remains a significant cause of mortality and morbidity worldwide. Benefit of recently developed multidisciplinary PE response teams (PERT) with higher utilization of advanced therapies has not been established.

Methods: To evaluate patient-centered outcomes and cost-effectiveness of a multidisciplinary PERT we performed a retrospective analysis of 554 patients with acute PE at the university of Virginia between July 2014 and June 2015 (pre-PERT era) and between April 2017 through October 2018 (PERT era). Six-month survival, hospital length-of-stay (LOS), type of PE therapy, and in-hospital bleeding were assessed upon collected data.

Results: 317 consecutive patients were treated for acute PE during an 18-month period following institution of a multidisciplinary PE program; for 120 patients PERT was activated (PA), the remaining 197 patients with acute PE were considered as a separate, contemporary group (NPA). The historical, comparator cohort (PP) was composed of 237 patients. These 3 groups were similar in terms of baseline demographics, comorbidities and risk, as assessed by the Pulmonary Embolism Severity Index (PESI). Patients in the historical cohort demonstrated worsened survival when compared with patients treated during the PERT era. During the PERT era no statistically significant difference in survival was observed in the PA group when compared to the NPA group despite significantly higher severity of illness among PA patients. Hospital LOS was not different in the PA group when compared to either the NPA or PP group. Hospital costs did not differ among the 3 cohorts. 30-day re-admission rates were significantly lower during the PERT era. Rates of advanced therapies were significantly higher during the PERT era (9.1% vs. 2%) and were concentrated in the PA group (21.7% vs. 1.5%) without any significant rise in in-hospital bleeding complications.

Conclusions: At our institution, all-cause mortality in patients with acute PE has significantly and durably decreased with the adoption of a PERT program without incurring additional hospital costs or protracting hospital LOS. Our data suggest that the adoption of a multidisciplinary approach at some institutions may provide benefit to select patients with acute PE.
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http://dx.doi.org/10.1186/s12931-020-01422-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310489PMC
June 2020

Patient Outcomes With Prevented vs Negative Tests Using a Computerized Clinical Decision Support Tool.

Open Forum Infect Dis 2020 Apr 18;7(4):ofaa094. Epub 2020 Mar 18.

Division of Infectious Diseases & International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA.

Background: Overtesting and overdiagnosis of infection are suspected to be common. Reducing inappropriate testing through interventions designed to promote evidence-based diagnostic testing (ie, diagnostic stewardship) may improve test utilization. However, the safety of these interventions is not well understood despite the potential risk for missed or delayed diagnoses.

Methods: This retrospective case-control study examined the outcomes of patients admitted to the University of Virginia Medical Center following introduction of a computerized clinical decision support tool without hard-stops designed to reduce inappropriate tests. Outcomes were compared between patients with a prevented nucleic acid amplification test and those with a negative result. Chart reviews were performed for patients with a subsequent positive within 7 days, as well as those patients who received -active antibiotics after implementation of the computerized clinical decision support tool.

Results: Multivariate analysis of 637 cases (490 negative, 147 prevented) showed that a prevented test was not significantly associated with the primary composite outcome (inpatient mortality or intensive care unit transfer) compared with a negative test (adjusted odds ratio, 0.912;  = .747). Fifty-four of 147 (37%) prevented tests were followed by a completed test within 7 days; 11 of these results were positive, resulting in a potential delay in diagnosis. Individual case reviews found that either clinical changes warranted the delay in testing or no adverse events occurred attributable to infection. treatment without a positive test was not identified.

Conclusions: Diagnostic stewardship of testing using computerized clinical decision support may be both safe and effective for reducing inappropriate inpatient testing.
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http://dx.doi.org/10.1093/ofid/ofaa094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166115PMC
April 2020

Dynamic data in the ED predict requirement for ICU transfer following acute care admission.

J Clin Monit Comput 2020 Mar 19. Epub 2020 Mar 19.

AMP3D, Advanced Medical Predictive Devices, Diagnostics, and Displays, Inc, Charlottesville, VA, USA.

Misidentification of illness severity may lead to patients being admitted to a ward bed then unexpectedly transferring to an ICU as their condition deteriorates. Our objective was to develop a predictive analytic tool to identify emergency department (ED) patients that required upgrade to an intensive or intermediate care unit (ICU or IMU) within 24 h after being admitted to an acute care floor. We conducted a single-center retrospective cohort study to identify ED patients that were admitted to an acute care unit and identified cases where the patient was upgraded to ICU or IMU within 24 h. We used data available at the time of admission to build a logistic regression model that predicts early ICU transfer. We found 42,332 patients admitted between January 2012 and December 2016. There were 496 cases (1.2%) of early ICU transfer. Case patients had 18.0-fold higher mortality (11.1% vs. 0.6%, p < 0.001) and 3.4 days longer hospital stays (5.9 vs. 2.5, p < 0.001) than those without an early transfer. Our predictive analytic model had a cross-validated area under the receiver operating characteristic of 0.70 (95% CI 0.67-0.72) and identified 10% of early ICU transfers with an alert rate of 1.6 per week (162.2 acute care admits per week, 1.9 early ICU transfers). Predictive analytic monitoring based on data available in the emergency department can identify patients that will require upgrade to ICU or IMU if admitted to acute care. Incorporating this tool into ED practice may draw attention to high-risk patients before acute care admit and allow early intervention.
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http://dx.doi.org/10.1007/s10877-020-00500-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223530PMC
March 2020

The Impact of Heat Waves on Emergency Department Visits in Roanoke, Virginia.

Acad Emerg Med 2020 07 12;27(7):614-617. Epub 2020 Feb 12.

Departments of Public Health Sciences and Orthopaedic Surgery, University of Virginia.

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http://dx.doi.org/10.1111/acem.13919DOI Listing
July 2020

Palliative Care and Moral Distress: An Institutional Survey of Critical Care Nurses.

Crit Care Nurse 2019 Oct;39(5):38-49

Alexander T. Wolf is a palliative care nurse practitioner, TriHealth, Cincinnati, Ohio. Kenneth R. White is a professor of nursing and medicine and Associate Dean of Strategic Partnerships and Innovation, School of Nursing, University of Virginia, and a palliative care nurse practitioner, University of Virginia Medical Center, Charlottesville, Virginia. Elizabeth G. Epstein is an associate professor of nursing, University of Virginia, Charlottesville. Kyle B. Enfield is an associate professor of medicine, University of Virginia, and director of the medical intensive care unit, University of Virginia Medical Center, Charlottesville.

Background: The need for palliative care in the intensive care unit is increasing. Whether gaps and variations in palliative care education and use are associated with moral distress among critical care nurses is unknown.

Objectives: To examine critical care nurses' perceived knowledge of palliative care, their recent experiences of moral distress, and possible relationships between these variables.

Methods: In this quantitative, descriptive study, survey questionnaires were distributed to 517 critical care nurses across 7 intensive care units at an academic health center in Virginia. Validated instruments were used to measure participants' perceptions of palliative care in their practice setting and their recent experiences of moral distress.

Results: A total of 167 completed questionnaires were analyzed. Fewer than 40% of respondents reported being highly competent in any palliative care domain. Most respondents had little palliative care education, with 38% reporting none in the past 2 years. Most respondents reported moral distress during the study period, and moral distress levels differed significantly on the basis of perceived use of palliative care ( = .03). Respondents who perceived less frequent use of palliative care tended to experience higher levels of moral distress.

Conclusions: Many critical care nurses do not feel prepared to provide palliative care. When palliative care access is perceived as inadequate, nurses may be more apt to experience moral distress. Health system leaders should prioritize palliative care training for critical care nurses and their colleagues and empower them to reduce barriers to palliative care.
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http://dx.doi.org/10.4037/ccn2019645DOI Listing
October 2019

A Randomized Controlled Trial Comparing Two Lung Expansion Therapies After Upper Abdominal Surgery.

Respir Care 2019 Oct 21;64(10):1181-1192. Epub 2019 May 21.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia.

Background: Lung expansion therapy is often ordered after surgery to improve alveolar ventilation and reduce risks of postoperative pulmonary complications. The impact of lung expansion therapy at altering ventilation in patients who are not intubated has not been described. The primary purpose of this study was to determine if there is a difference in dorsal redistribution of ventilation and incidences of postoperative pulmonary complications when comparing incentive spirometry (IS) with EzPAP lung expansion therapy after upper abdominal surgery. Our a priori null hypothesis was that there are no differences.

Methods: This randomized controlled trial enrolled adult human subjects after upper- abdominal surgery from January 2017 to November 2018. The subjects were allocated to receive IS or EzPAP 3 times a day on postoperative days 1-5. An electrical impedance tomography device was connected to the subjects for a single lung expansion therapy session on postoperative days 1, 3, and 5 to measure the change in post-lung expansion therapy dorsal end-expiratory lung impedance (ΔEELI%). Lung expansion therapy sessions with electrical impedance tomography included 2 min of normal breathing, 3 cycles of 10 breaths, and 2 min of normal breathing after cycle 3. Postoperative pulmonary complications were screened until hospital discharge. Mann-Whitney, chi-square, and Fisher exact tests were applied. Data were reported as count (), percentage, and median (interquartile range) for primary and secondary outcomes. Alpha (2-tailed) was < 0.05.

Results: A total of 112 subjects were enrolled to receive IS ( = 56) or EzPAP ( = 56). Baseline characteristics were equal. Post-lung expansion therapy dorsal ΔEELI% increased for both groups, but the dorsal ΔEELI% for IS versus EzPAP on postoperative day 1 (16% versus 12%, = .39), postoperative day 3 (6% versus 6%, = .68), and postoperative day 5 (9% versus 6%, = .46) was not significantly different. Hospital length of stay (4 d; = .30) and incidence of postoperative pulmonary complications (3.6% versus 7.1%, = .19) were similar.

Conclusions: There was no significant post-lung expansion therapy dorsal ΔEELI% or postoperative pulmonary complications among the adults who received IS or EzPAP 3 times a day after upper abdominal surgery. (ClinicalTrials.gov registration NCT02892773.).
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http://dx.doi.org/10.4187/respcare.06812DOI Listing
October 2019

Initial arterial pH as a predictor of neurologic outcome after out-of-hospital cardiac arrest: A propensity-adjusted analysis.

Resuscitation 2019 06 1;139:76-83. Epub 2019 Apr 1.

Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA. Electronic address:

Background: Lower pH after out-of-hospital cardiac arrest (OHCA) has been associated with worsening neurologic outcome, with <7.2 identified as an "unfavorable resuscitation feature" in consensus treatment algorithms despite conflicting data. This study aimed to describe the relationship between decremental post-resuscitation pH and neurologic outcomes after OHCA.

Methods: Consecutive OHCA patients treated with targeted temperature management (TTM) at multiple US centers from 2008 to 2017 were evaluated. Poor neurologic outcome at hospital discharge was defined as cerebral performance category ≥3. The exposure was initial arterial pH after return of spontaneous circulation (ROSC) analyzed in decremental 0.05 thresholds. Potential confounders (demographics, history, resuscitation characteristics, initial studies) were defined a priori and controlled for via ATT-weighting on the inverse propensity score plus direct adjustment for the linear propensity score.

Results: Of 723 patients, 589 (80%) experienced poor neurologic outcome at hospital discharge. After propensity-adjustment with excellent covariate balance, the adjusted odds ratios for poor neurologic outcome by pH threshold were: ≤7.3: 2.0 (1.0-4.0); ≤7.25: 1.9 (1.2-3.1); ≤7.2: 2.1 (1.3-3.3); ≤7.15: 1.9 (1.2-3.1); ≤7.1: 2.4 (1.4-4.1); ≤7.05: 3.1 (1.5-6.3); ≤7.0: 4.5 (1.8-12).

Conclusions: No increased hazard of progressively poor neurologic outcomes was observed in resuscitated OHCA patients treated with TTM until the initial post-ROSC arterial pH was at least ≤7.1. This threshold is more acidic than in current guidelines, suggesting the possibility that post-arrest pH may be utilized presently as an inappropriately-pessimistic prognosticator.
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http://dx.doi.org/10.1016/j.resuscitation.2019.03.036DOI Listing
June 2019

Human Rabies - Virginia, 2017.

MMWR Morb Mortal Wkly Rep 2019 Jan 4;67(5152):1410-1414. Epub 2019 Jan 4.

On May 9, 2017, the Virginia Department of Health was notified regarding a patient with suspected rabies. The patient had sustained a dog bite 6 weeks before symptom onset while traveling in India. On May 11, CDC confirmed that the patient was infected with a rabies virus that circulates in dogs in India. Despite aggressive treatment, the patient died, becoming the ninth person exposed to rabies abroad who has died from rabies in the United States since 2008. A total of 250 health care workers were assessed for exposure to the patient, 72 (29%) of whom were advised to initiate postexposure prophylaxis (PEP). The total pharmaceutical cost for PEP (rabies immunoglobulin and rabies vaccine) was approximately $235,000. International travelers should consider a pretravel consultation with travel health specialists; rabies preexposure prophylaxis is warranted for travelers who will be in rabies endemic countries for long durations, in remote areas, or who plan activities that might put them at risk for a rabies exposures.
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http://dx.doi.org/10.15585/mmwr.mm675152a2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334827PMC
January 2019

Cost Analysis of Computerized Clinical Decision Support and Trainee Financial Incentive for Clostridioides difficile Testing.

Infect Control Hosp Epidemiol 2019 02 23;40(2):242-244. Epub 2018 Nov 23.

1Division of Infectious Diseases & International Health,Department of Medicine,University of Virginia Health System,Charlottesville,Virginia.

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http://dx.doi.org/10.1017/ice.2018.300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035470PMC
February 2019

Dynamic data monitoring improves predictive analytics for failed extubation in the ICU.

Physiol Meas 2018 07 16;39(7):075005. Epub 2018 Jul 16.

School of Nursing, University of Virginia, Charlottesville, VA, United States of America. School of Medicine, University of Virginia, Charlottesville, VA, United States of America.

Objective: Predictive analytics monitoring that informs clinicians of the risk for failed extubation would help minimize both the duration of mechanical ventilation and the risk of emergency re-intubation in ICU patients. We hypothesized that dynamic monitoring of cardiorespiratory data, vital signs, and lab test results would add information to standard clinical risk factors.

Methods: We report model development in a retrospective observational cohort admitted to either the medical or surgical/trauma ICU that were intubated during their ICU stay and had available physiologic monitoring data (n  =  1202). The primary outcome was removal of endotracheal intubation (i.e. extubation) followed within 48 h by reintubation or death (i.e. failed extubation). We developed a standard risk marker model based on demographic and clinical data. We also developed a novel risk marker model using dynamic data elements-continuous cardiorespiratory monitoring, vital signs, and lab values.

Results: Risk estimates from multivariate predictive models in the 24 h preceding extubation were significantly higher for patients that failed. Combined standard and novel risk markers demonstrated good predictive performance in leave-one-out validation: AUC of 0.64 (95% CI: 0.57-0.69) and 1.6 alerts per week to identify 32% of extubations that will fail. Novel risk factors added significantly to the standard model.

Conclusion: Predictive analytics monitoring models can detect changes in vital signs, continuous cardiorespiratory monitoring, and laboratory measurements in both the hours preceding and following extubation for those patients destined for extubation failure.
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http://dx.doi.org/10.1088/1361-6579/aace95DOI Listing
July 2018

Septic arthritis due to oral streptococci following intra-articular injection: A case series.

Am J Infect Control 2018 11 24;46(11):1301-1303. Epub 2018 May 24.

Department of Medicine, University of Virginia Health System, Charlottesville, VA; Division of Infectious Diseases & International Health, Department of Medicine, University of Virginia Health System, Charlottesville, VA.

Oral streptococcal species are a rare cause of septic arthritis. We describe 4 cases of septic arthritis due to oral streptococcal species following joint injection. The routine use of face masks during joint injection may prevent this rare but serious complication.
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http://dx.doi.org/10.1016/j.ajic.2018.04.227DOI Listing
November 2018

Reduced Clostridium difficile Tests and Laboratory-Identified Events With a Computerized Clinical Decision Support Tool and Financial Incentive.

Infect Control Hosp Epidemiol 2018 06 12;39(6):737-740. Epub 2018 Apr 12.

7Division of Pulmonary and Critical Care Medicine,Department of Medicine,University of Virginia Health System,Charlottesville,Virginia.

We hypothesized that a computerized clinical decision support tool for Clostridium difficile testing would reduce unnecessary inpatient tests, resulting in fewer laboratory-identified events. Census-adjusted interrupted time-series analyses demonstrated significant reductions of 41% fewer tests and 31% fewer hospital-onset C. difficile infection laboratory-identified events following this intervention.Infect Control Hosp Epidemiol 2018;39:737-740.
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http://dx.doi.org/10.1017/ice.2018.53DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6088779PMC
June 2018

Respiratory hospital admissions and weather changes: a retrospective study in Charlottesville, Virginia, USA.

Int J Biometeorol 2018 Jun 7;62(6):1015-1025. Epub 2018 Feb 7.

Division of Pulmonary and Critical Care, Department of Medicine, University of Virginia Health System, Charlottesville, VA, 22908, USA.

In most midlatitude locations, human morbidity and mortality are highly seasonal, with winter peaks driven by respiratory disease and associated comorbidities. But the transition between high and low mortality/morbidity months varies spatially. We use a measure of the thermal biophysical strain imposed on the respiratory system-the Acclimatization Thermal Strain Index (ATSI)-to examine respiratory hospital admissions in Charlottesville, VA. Daily respiratory admissions to the University of Virginia over a 19-year period are compared to ATSI values derived from hourly surface weather data acquired from the Charlottesville airport. Negative ATSI values (associated with transitions from warm (and humid) to cold (and dry) conditions) are related to admission peaks at seasonal and weekly timescales, whereas positive ATSI values (cold to warm) exhibit weaker relationships. This research marks the first application of the ATSI to human morbidity, and results suggest that respiratory strain may account for how people who are acclimated to different climates respond to short-term weather changes.
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http://dx.doi.org/10.1007/s00484-018-1503-9DOI Listing
June 2018

Effect of Ganciclovir on IL-6 Levels Among Cytomegalovirus-Seropositive Adults With Critical Illness: A Randomized Clinical Trial.

JAMA 2017 08;318(8):731-740

Division of Allergy and Infectious Diseases, University of Washington, Seattle.

Importance: The role of cytomegalovirus (CMV) reactivation in mediating adverse clinical outcomes in nonimmunosuppressed adults with critical illness is unknown.

Objective: To determine whether ganciclovir prophylaxis reduces plasma interleukin 6 (IL-6) levels in CMV-seropositive adults who are critically ill.

Design, Setting, And Participants: Double-blind, placebo-controlled, randomized clinical trial (conducted March 10, 2011-April 29, 2016) with a follow-up of 180 days (November 10, 2016) that included 160 CMV-seropositive adults with either sepsis or trauma and respiratory failure at 14 university intensive care units (ICUs) across the United States.

Interventions: Patients were randomized (1:1) to receive either intravenous ganciclovir (5 mg/kg twice daily for 5 days), followed by either intravenous ganciclovir or oral valganciclovir once daily until hospital discharge (n = 84) or to receive matching placebo (n = 76).

Main Outcomes And Measures: The primary outcome was change in IL-6 level from day 1 to 14. Secondary outcomes were incidence of CMV reactivation in plasma, mechanical ventilation days, incidence of secondary bacteremia or fungemia, ICU length of stay, mortality, and ventilator-free days (VFDs) at 28 days.

Results: Among 160 randomized patients (mean age, 57 years; women, 43%), 156 patients received 1or more dose(s) of study medication, and 132 patients (85%) completed the study. The mean change in plasma IL-6 levels between groups was -0.79 log10 units (-2.06 to 0.48) in the ganciclovir group and -0.79 log10 units (-2.14 to 0.56) in the placebo group (point estimate of difference, 0 [95% CI, -0.3 to 0.3]; P > .99). Among secondary outcomes, CMV reactivation in plasma was significantly lower in the ganciclovir group (12% [10 of 84 patients] vs 39% [28 of 72 patients]); absolute risk difference, -27 (95% CI, -40 to -14), P < .001. The ganciclovir group had more median VFDs in both the intention-to-treat (ITT) group and in the prespecified sepsis subgroup (ITT group: 23 days in ganciclovir group vs 20 days in the placebo group, P = .05; sepsis subgroup, 23 days in the ganciclovir group vs 20 days in the placebo group, P = .03). There were no significant differences between the ganciclovir and placebo groups in duration of mechanical ventilation (5 days for the ganciclovir group vs 6 days for the placebo group, P = .16), incidence of secondary bacteremia or fungemia (15% for the ganciclovir group vs 15% for the placebo group, P = .67), ICU length of stay (8 days for the ganciclovir group vs 8 days for the placebo group, P = .76), or mortality (12% for the ganciclovir group vs 15% for the placebo group, P = .54).

Conclusions And Relevance: Among CMV-seropositive adults with critical illness due to sepsis or trauma, ganciclovir did not reduce IL-6 levels and the current study does not support routine clinical use of ganciclovir as a prophylactic agent in patients with sepsis. Additional research is necessary to determine the clinical efficacy and safety of CMV suppression in this setting.

Trial Registration: clinicaltrials.gov Identifier: NCT01335932.
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http://dx.doi.org/10.1001/jama.2017.10569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817487PMC
August 2017

Cardiorespiratory dynamics measured from continuous ECG monitoring improves detection of deterioration in acute care patients: A retrospective cohort study.

PLoS One 2017 3;12(8):e0181448. Epub 2017 Aug 3.

Department of Medicine, Division of Cardiovascular Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.

Background: Charted vital signs and laboratory results represent intermittent samples of a patient's dynamic physiologic state and have been used to calculate early warning scores to identify patients at risk of clinical deterioration. We hypothesized that the addition of cardiorespiratory dynamics measured from continuous electrocardiography (ECG) monitoring to intermittently sampled data improves the predictive validity of models trained to detect clinical deterioration prior to intensive care unit (ICU) transfer or unanticipated death.

Methods And Findings: We analyzed 63 patient-years of ECG data from 8,105 acute care patient admissions at a tertiary care academic medical center. We developed models to predict deterioration resulting in ICU transfer or unanticipated death within the next 24 hours using either vital signs, laboratory results, or cardiorespiratory dynamics from continuous ECG monitoring and also evaluated models using all available data sources. We calculated the predictive validity (C-statistic), the net reclassification improvement, and the probability of achieving the difference in likelihood ratio χ2 for the additional degrees of freedom. The primary outcome occurred 755 times in 586 admissions (7%). We analyzed 395 clinical deteriorations with continuous ECG data in the 24 hours prior to an event. Using only continuous ECG measures resulted in a C-statistic of 0.65, similar to models using only laboratory results and vital signs (0.63 and 0.69 respectively). Addition of continuous ECG measures to models using conventional measurements improved the C-statistic by 0.01 and 0.07; a model integrating all data sources had a C-statistic of 0.73 with categorical net reclassification improvement of 0.09 for a change of 1 decile in risk. The difference in likelihood ratio χ2 between integrated models with and without cardiorespiratory dynamics was 2158 (p value: <0.001).

Conclusions: Cardiorespiratory dynamics from continuous ECG monitoring detect clinical deterioration in acute care patients and improve performance of conventional models that use only laboratory results and vital signs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0181448PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542430PMC
September 2017

: A Validated Scoring System for Early Stratification of Neurologic Outcome After Out-of-Hospital Cardiac Arrest Treated With Targeted Temperature Management.

J Am Heart Assoc 2017 May 20;6(5). Epub 2017 May 20.

Department of Cardiovascular Medicine, University of Virginia, Charlottesville, VA

Background: Out-of-hospital cardiac arrest (OHCA) results in significant morbidity and mortality, primarily from neurologic injury. Predicting neurologic outcome early post-OHCA remains difficult in patients receiving targeted temperature management.

Methods And Results: Retrospective analysis was performed on consecutive OHCA patients receiving targeted temperature management (32-34°C) for 24 hours at a tertiary-care center from 2008 to 2012 (development cohort, n=122). The primary outcome was favorable neurologic outcome at hospital discharge, defined as cerebral performance category 1 to 2 (poor 3-5). Patient demographics, pre-OHCA diagnoses, and initial laboratory studies post-resuscitation were compared between favorable and poor neurologic outcomes with multivariable logistic regression used to develop a simple scoring system (). The score ranges 0 to 5 using equally weighted variables: (): coronary artery disease, known pre-OHCA; (): glucose ≥200 mg/dL; (): rhythm of arrest not ventricular tachycardia/fibrillation; (): age >45; (): arterial pH ≤7.0. A validation cohort (n=344) included subsequent patients from the initial site (n=72) and an external quaternary-care health system (n=272) from 2012 to 2014. The c-statistic for predicting neurologic outcome was 0.82 (0.74-0.90, <0.001) in the development cohort and 0.81 (0.76-0.87, <0.001) in the validation cohort. When subdivided by score, similar rates of favorable neurologic outcome were seen in both cohorts, 70% each for low (0-1, n=60), 22% versus 19% for medium (2-3, n=307), and 0% versus 2% for high (4-5, n=99) scores in the development and validation cohorts, respectively.

Conclusions: stratifies neurologic outcomes following OHCA in patients receiving targeted temperature management (32-34°C) using objective data available at hospital presentation, identifying patient subsets with disproportionally favorable ( ≤1) and poor ( ≥4) prognoses.
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http://dx.doi.org/10.1161/JAHA.116.003821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524053PMC
May 2017

New-Onset Atrial Fibrillation in the Critically Ill.

Crit Care Med 2017 May;45(5):790-797

1Division of Cardiovascular Medicine, Department of Medicine, University of Virginia Health System, Charlottesville, VA. 2Department of Surgery, University of Virginia Health System, Charlottesville, VA. 3Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Virginia Health System, Charlottesville, VA. 4University of Virginia School of Medicine, Charlottesville, VA.

Objective: To determine the association of new-onset atrial fibrillation with outcomes, including ICU length of stay and survival.

Design: Retrospective cohort of ICU admissions. We found atrial fibrillation using automated detection (≥ 90 s in 30 min) and classed as new-onset if there was no prior diagnosis of atrial fibrillation. We identified determinants of new-onset atrial fibrillation and, using propensity matching, characterized its impact on outcomes.

Setting: Tertiary care academic center.

Patients: A total of 8,356 consecutive adult admissions to either the medical or surgical/trauma/burn ICU with available continuous electrocardiogram data.

Interventions: None.

Measurements And Main Results: From 74 patient-years of every 15-minute observations, we detected atrial fibrillation in 1,610 admissions (19%), with median burden less than 2%. Most atrial fibrillation was paroxysmal; less than 2% of admissions were always in atrial fibrillation. New-onset atrial fibrillation was subclinical or went undocumented in 626, or 8% of all ICU admissions. Advanced age, acute respiratory failure, and sepsis were the strongest predictors of new-onset atrial fibrillation. In propensity-adjusted regression analyses, clinical new-onset atrial fibrillation was associated with increased hospital mortality (odds ratio, 1.63; 95% CI, 1.01-2.63) and longer length of stay (2.25 d; CI, 0.58-3.92). New-onset atrial fibrillation was not associated with survival after hospital discharge (hazard ratio, 0.99; 95% CI, 0.76-1.28 and hazard ratio, 1.11; 95% CI, 0.67-1.83, respectively, for subclinical and clinical new-onset atrial fibrillation).

Conclusions: Automated analysis of continuous electrocardiogram heart rate dynamics detects new-onset atrial fibrillation in many ICU patients. Though often transient and frequently unrecognized, new-onset atrial fibrillation is associated with poor hospital outcomes.
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http://dx.doi.org/10.1097/CCM.0000000000002325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389601PMC
May 2017

Preparedness planning and care of patients under investigation for or with Ebola virus disease: A survey of physicians in North America.

Am J Infect Control 2017 01;45(1):65-68

Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia Health System, Charlottesville, VA; Office of Hospital Epidemiology/Infection Prevention and Control, University of Virginia Health System, Charlottesville, VA. Electronic address:

The West African Ebola virus disease (EVD) epidemic of 2014-2015 required North American hospitals to undertake comprehensive planning and training for the potential need to care for patients with EVD. Here we describe physician contributions to EVD preparedness planning and the care of persons under investigation for or patients with EVD.
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http://dx.doi.org/10.1016/j.ajic.2016.09.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132729PMC
January 2017

Reduced health care-associated infections in an acute care community hospital using a combination of self-disinfecting copper-impregnated composite hard surfaces and linens.

Am J Infect Control 2016 12 28;44(12):1565-1571. Epub 2016 Sep 28.

Office of Hospital Epidemiology/Infection Prevention & Control, University of Virginia Health System, Charlottesville, VA; Division of Pulmonary & Critical Care Medicine, Department of Medicine, University of Virginia Health System, Charlottesville, VA.

Background: The purpose of this study was to determine the effectiveness of copper-impregnated composite hard surfaces and linens in an acute care hospital to reduce health care-associated infections (HAIs).

Methods: We performed a quasiexperimental study with a control group, assessing development of HAIs due to multidrug resistant organisms (MDROs) and Clostridium difficile in the acute care units of a community hospital following the replacement of a 1970s-era clinical wing with a new wing outfitted with copper-impregnated composite hard surfaces and linens.

Results: The study was conducted over a 25.5-month time period that included a 3.5-month washout period. HAI rates obtained from the copper-containing new hospital wing (14,479 patient-days; 72 beds) and the unmodified hospital wing (19,177 patient-days) were compared with those from the baseline period (46,391 patient-days). The new wing had 78% (P = .023) fewer HAIs due to MDROs or C difficile, 83% (P = .048) fewer cases of C difficile infection, and 68% (P = .252) fewer infections due to MDROs relative to the baseline period. No changes in rates of HAI were observed in the unmodified hospital wing.

Conclusions: Copper-impregnated composite hard surfaces and linens may be useful technologies to prevent HAIs in acute care hospital settings. Additional studies are needed to determine whether reduced HAIs can be attributed to the use of copper-containing antimicrobial hard and soft surfaces.
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http://dx.doi.org/10.1016/j.ajic.2016.07.007DOI Listing
December 2016

Signatures of Subacute Potentially Catastrophic Illness in the ICU: Model Development and Validation.

Crit Care Med 2016 Sep;44(9):1639-48

1Division of Cardiovascular Medicine, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA.2Department of Statistics, University of Virginia, Charlottesville, VA.3Division of Acute Care and Trauma Surgery, Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA.4Division of Pulmonary and Critical Care, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA.5Department of Physics, College of William and Mary, Williamsburg, VA.6Division of Neonatology, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA.7Department of Biomedical Engineering, University of Virginia, Charlottesville, VA.8Department of Molecular Physiology, University of Virginia, Charlottesville, VA.

Objectives: Patients in ICUs are susceptible to subacute potentially catastrophic illnesses such as respiratory failure, sepsis, and hemorrhage that present as severe derangements of vital signs. More subtle physiologic signatures may be present before clinical deterioration, when treatment might be more effective. We performed multivariate statistical analyses of bedside physiologic monitoring data to identify such early subclinical signatures of incipient life-threatening illness.

Design: We report a study of model development and validation of a retrospective observational cohort using resampling (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis type 1b internal validation) and a study of model validation using separate data (type 2b internal/external validation).

Setting: University of Virginia Health System (Charlottesville), a tertiary-care, academic medical center.

Patients: Critically ill patients consecutively admitted between January 2009 and June 2015 to either the neonatal, surgical/trauma/burn, or medical ICUs with available physiologic monitoring data.

Interventions: None.

Measurements And Main Results: We analyzed 146 patient-years of vital sign and electrocardiography waveform time series from the bedside monitors of 9,232 ICU admissions. Calculations from 30-minute windows of the physiologic monitoring data were made every 15 minutes. Clinicians identified 1,206 episodes of respiratory failure leading to urgent unplanned intubation, sepsis, or hemorrhage leading to multi-unit transfusions from systematic individual chart reviews. Multivariate models to predict events up to 24 hours prior had internally validated C-statistics of 0.61-0.88. In adults, physiologic signatures of respiratory failure and hemorrhage were distinct from each other but externally consistent across ICUs. Sepsis, on the other hand, demonstrated less distinct and inconsistent signatures. Physiologic signatures of all neonatal illnesses were similar.

Conclusions: Subacute potentially catastrophic illnesses in three diverse ICU populations have physiologic signatures that are detectable in the hours preceding clinical detection and intervention. Detection of such signatures can draw attention to patients at highest risk, potentially enabling earlier intervention and better outcomes.
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http://dx.doi.org/10.1097/CCM.0000000000001738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4987175PMC
September 2016

Hidden Reservoir: An Outbreak of Tuberculosis in Hospital Employees with No Patient Contact.

Infect Control Hosp Epidemiol 2016 09 9;37(9):1111-3. Epub 2016 Jun 9.

3Division of Infectious Diseases & International Health,University of Virginia Health System,Charlottesville,Virginia.

We describe an outbreak of tuberculosis (TB) in the food preparation area of a hospital, which demonstrates that employees in healthcare settings may serve as potential risks for spread of TB even if they have no direct patient contact. Infect Control Hosp Epidemiol 2016;37:1111-1113.
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http://dx.doi.org/10.1017/ice.2016.126DOI Listing
September 2016

Humidity: A review and primer on atmospheric moisture and human health.

Environ Res 2016 Jan 21;144(Pt A):106-116. Epub 2015 Nov 21.

Division of Pulmonary and Critical Care, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22908, USA. Electronic address:

Research examining associations between weather and human health frequently includes the effects of atmospheric humidity. A large number of humidity variables have been developed for numerous purposes, but little guidance is available to health researchers regarding appropriate variable selection. We examine a suite of commonly used humidity variables and summarize both the medical and biometeorological literature on associations between humidity and human health. As an example of the importance of humidity variable selection, we correlate numerous hourly humidity variables to daily respiratory syncytial virus isolates in Singapore from 1992 to 1994. Most water-vapor mass based variables (specific humidity, absolute humidity, mixing ratio, dewpoint temperature, vapor pressure) exhibit comparable correlations. Variables that include a thermal component (relative humidity, dewpoint depression, saturation vapor pressure) exhibit strong diurnality and seasonality. Humidity variable selection must be dictated by the underlying research question. Despite being the most commonly used humidity variable, relative humidity should be used sparingly and avoided in cases when the proximity to saturation is not medically relevant. Care must be taken in averaging certain humidity variables daily or seasonally to avoid statistical biasing associated with variables that are inherently diurnal through their relationship to temperature.
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http://dx.doi.org/10.1016/j.envres.2015.10.014DOI Listing
January 2016