Jeffrey A. Kline

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https://hdl.handle.net/1805/6677

Facial Expression as a Diagnostic Tool for Pulmonary Embolism

Jeffrey Kline studies blood clots, the people they affect, and the providers who care for those people. His diagnostic research interests focus on human affect analysis, pretest probability, and novel breath-based instruments to reduce medical imaging. His human treatment research includes randomized trials of fibrinolysis and inhaled nitric oxide to reduce heart damage from blood clots in the lungs. He derived and validated a decision rule to help emergency physicians reduce unnecessary diagnostic tests for low-risk patients with symptoms of blood clots in the lungs.

Dr. Kline’s current work focuses on using the human face as a diagnostic instrument to further help doctors make informed decisions about diagnostic testing for blood clots. His laboratory work focuses on mechanisms and treatment of acute pulmonary hypertension from pulmonary embolism (PE), animal models of pulmonary embolism, and a nanoparticle-delivered enzyme, plasmin, to promote clot lysis without increasing risk. He helped set up an advanced hospital treatment program to treat patients with severe PE, and he also created and runs a clinic specifically to allow patients diagnosed with blood clots in the emergency department to treat themselves at home, rather than in the hospital.

Dr. Kline’s work using the human face as a diagnostic instrument is another example of how IUPUI’s faculty members are TRANSLATING their RESEARCH INTO PRACTICE.

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1-year mortality following contrast-induced nephropathy
(2013) Mitchell, Alice M; Jones, Alan E; Tumlin, James A; Kline, Jeffrey A.
Objective: The aim of this study was to determine the 1-year mortality risk subsequent to Contrast-Induced Nephropathy (CIN) following CECT imaging, relative to other well-recognized predictors of mortality. Methods: We followed a prospective, consecutive cohort of ambulatory patients who received intravenous contrast for CECT for the outcome of death from any cause within 1 year. In a multivariate analysis, we compared CIN with other predictors of mortality: active malignancy, coronary artery disease (CAD), congestive heart failure (CHF) and age ≥70 years. Anticipating that terminal cancers would account for the majority of deaths in this population, we also analyzed the subset of patients without an active malignancy at the time of enrollment. Results: We followed 633 patients and 46 died (7%, 95%CI: 5-9%) within 1 year. The incidence of CIN was 11% (95%CI: 8-14%). Active malignancy (HR 9.2, 95%CI: 5.1-16.8), CIN (HR 2.4, 95%CI: 1.3-4.6), CHF (HR 2.1, 95%CI: 1.0-4.2), CAD (HR 2.2, 95%CI: 1.0-5.5) and age ≥70 years (HR 1.8, 95%CI: 1.0-3.8) were significant predictors of all-cause mortality. Among patients without active malignancies, the mortality rate was 4% (25/580, 95%CI: 3-6%) and CIN (HR 4.0, 95%CI: 1.7-9.6) and age ≥70 years (HR 3.7, 95%CI: 1.4-9.7) were significantly associated with death, whereas CAD (HR 2.5, 95%CI: 0.8-7.7) and CHF (HR 1.8, 95%CI: 0.6-5.3) were not. Conclusions: The development of CIN following CECT is associated with an increased likelihood of death at 1 year among patients with and without active malignancies, comparable to CAD, CHF and advanced age.
2-Hour Accelerated Diagnostic Protocol to Assess Patients With Chest Pain Symptoms Using Contemporary Troponins as the Only Biomarker
(2012-06) Than, Martin; Cullen, Louise; Aldous, Sally; Parsonage, William A; Reid, Christopher M; Greenslade, Jaimi; Flaws, Dylan; Hammett, Christopher J; Beam, Daren M; Ardagh, Michael W; Troughton, Richard; Brown, Anthony FT; George, Peter; Florkowski, Christopher M; Kline, Jeffrey A.; Peacock, W Frank; Maisel, Alan S; Lim, Swee Han; Lamanna, Arvin; Richards, A Mark
Objectives The purpose of this study was to determine whether a new accelerated diagnostic protocol (ADP) for possible cardiac chest pain could identify low-risk patients suitable for early discharge (with follow-up shortly after discharge). Background Patients presenting with possible acute coronary syndrome (ACS), who have a low short-term risk of adverse cardiac events may be suitable for early discharge and shorter hospital stays. Methods This prospective observational study tested an ADP that included pre-test probability scoring by the Thrombolysis In Myocardial Infarction (TIMI) score, electrocardiography, and 0 + 2 h values of laboratory troponin I as the sole biomarker. Patients presenting with chest pain due to suspected ACS were included. The primary endpoint was major adverse cardiac event (MACE) within 30 days. Results Of 1,975 patients, 302 (15.3%) had a MACE. The ADP classified 392 patients (20%) as low risk. One (0.25%) of these patients had a MACE, giving the ADP a sensitivity of 99.7% (95% confidence interval [CI]: 98.1% to 99.9%), negative predictive value of 99.7% (95% CI: 98.6% to 100.0%), specificity of 23.4% (95% CI: 21.4% to 25.4%), and positive predictive value of 19.0% (95% CI: 17.2% to 21.0%). Many ADP negative patients had further investigations (74.1%), and therapeutic (18.3%) or procedural (2.0%) interventions during the initial hospital attendance and/or 30-day follow-up. Conclusions Using the ADP, a large group of patients was successfully identified as at low short-term risk of a MACE and therefore suitable for rapid discharge from the emergency department with early follow-up. This approach could decrease the observation period required for some patients with chest pain. (An observational study of the diagnostic utility of an accelerated diagnostic protocol using contemporary central laboratory cardiac troponin in the assessment of patients presenting to two Australasian hospitals with chest pain of possible cardiac origin; ACTRN12611001069943)
41: Health Insurance and Duration of Symptoms Prior to Emergency Department Visit: An Analysis of 19,850 Patients With Suspected COVID-19
(Elsevier, 2021-08) Gunn, A.H.; Neptune, N.; Cunningham, H.M.; Conner, D.; Adkins, L.; Tait, S.D.; Pung, L.; Courtney, D.M.; Kline, Jeffrey A.; Purakal, J.D.; Emergency Medicine, School of Medicine
Study Objectives The COVID-19 pandemic has emphasized disparities in health outcomes across social and economic strata. The mechanisms of this relationship are poorly understood, but the length of time patients exhibit symptoms prior to getting tested for COVID-19 increases the opportunity for community transmission. We hypothesized that there is a relationship between insurance coverage and the duration of COVID-19 symptoms prior to seeking care at the emergency department (ED). Methods A national, multi-institution (n=45 sites) registry collected information on ED visits in which patients were tested for suspected COVID-19. Demographics and clinical characteristics were summarized for the total cohort. Insurance was categorized into private (private or commercial), public (Medicare, Medicaid, or dual-eligible), worker’s compensation or unknown, or no health insurance. Negative binomial regression was used to analyze both the unadjusted and adjusted relationship between insurance and the time from symptom onset to ED presentation. Adjustments included age, sex, race, ethnicity, medical history, smoking status, drug use, and number of COVID symptoms. Results Baseline demographic and clinical characteristics of included patients (n=19,850) are displayed in Table 1. The average time from symptom onset to ED presentation among patients with suspected COVID-19 was 5.4 days. In unadjusted analysis, patients with private insurance had significantly longer time of symptom onset prior to ED presentation than patients with public insurance (5.6 vs. 5.3 days, p=0.007). After multivariate adjustment, increased duration of symptoms prior to ED presentation was significantly associated with private insurance [rate ratio (RR) 1.07, 95% confidence interval (CI): 1.03 – 1.10] and no health insurance (RR 1.06, 95% CI: 1.07 – 1.13) compared to public insurance (Figure 1). Patients residing in states with Medicaid expansion were not independently associated with the increased time to ED presentation (RR 1.03, 95% CI: 1.00 – 1.07). Conclusion Patients with private insurance or no insurance waited significantly longer to present to the ED. The extended duration of symptoms prior to presentation increases the opportunities for community transmission. The results from this study can be used by health systems to target the patients at increased risk for delayed ED presentation.
Acceptability of Contraceptive Services in the Emergency Department: A Cross-sectional Survey
(University of California, 2021-05-24) Alexander, Andreia B.; Chernoby, Kimberly; VanderVinne, Nathan; Doos, Yancy; Kaur, Navneet; Bernard, Caitlin; Kline, Jeffrey A.; Emergency Medicine, School of Medicine
Introduction: Unintended pregnancy disproportionately affects marginalized populations and has significant negative health and financial impacts on women, their families, and society. The emergency department (ED) is a promising alternative setting to increase access to sexual and reproductive health (SRH) services including contraception, especially among marginalized populations. The primary objective of this study was to determine the extent to which adult women of childbearing age who present to the ED would be receptive to receiving contraception and/or information about contraception in the ED. As a secondary objective, we sought to identify the barriers faced in attempting to obtain SRH care in the past. Methods: We conducted a quantitative, cross-sectional, assisted, in-person survey of women aged 18-50 in the ED setting at two large, urban, academic EDs between June 2018-September 2019. The survey was approved by the institutional review board. Survey items included demographics, interest in contraception initiation and/or receiving information about contraception in the ED, desire to conceive, prior SRH care utilization, and barriers to SRH. Results: A total of 505 patients participated in the survey. Participants were predominantly single and Black, with a mean age of 31 years, and reporting not wanting to become pregnant in the next year. Of those participants, 55.2% (n = 279) stated they would be interested in receiving information about birth control AND receiving birth control in the ED if it were available. Of those who reported the ability to get pregnant, and not desiring pregnancy in the next year (n = 279, 55.2%), 32.6% were not currently using anything to prevent pregnancy (n = 91). Only 10.5% of participants stated they had experienced barriers to SRH care in the past (n = 53). Participants who experienced barriers to SRH reported higher interest in receiving information and birth control in the ED (74%, n = 39) compared to those who had not experienced barriers (53%, n = 240); (P = 0.004, 95% confidence interval, 1.30-4.66). Conclusion: The majority of women of childbearing age indicated the desire to access contraception services in the ED setting. This finding suggests favorable patient acceptability for an implementation study of contraception services in emergency care.
Agricultural workers in meatpacking plants presenting to an emergency department with suspected COVID-19 infection are disproportionately Black and Hispanic
(Wiley, 2021-09) House, Hans R.; Vakkalanka, J. Priyanka; Behrens, Nathan G.; Haan, Jessica De; Halbur, Christopher R.; Harrington, Elaine M.; Patel, Pooja H.; Rawwas, Lulua; Camargo, Carlos A.; Kline, Jeffrey A.; Emergency Medicine, School of Medicine
Objective Facilities that process and package meat for consumer sale and consumption (meatpacking plants) were early sites of coronavirus disease 2019 (COVID-19) outbreaks. The aim of this study was to characterize the association between meatpacking plant exposure and clinical outcomes among emergency department (ED) patients with COVID-19 symptoms. Methods This was a retrospective cohort study of patients presenting to a single ED, from March 1 to May 31, 2020, who had: 1) symptoms consistent with COVID-19 and 2) a COVID-19 test performed. The primary outcome was COVID-19 positivity, and secondary outcomes included hospital admission from the ED, ventilator use, intensive care unit (ICU) admission, hospital length of stay (LOS; <48 or ≥48 h), and mortality. Results Patients from meatpacking plants were more likely to be Black or Hispanic than the ED patients without this occupational exposure. Patients with a meatpacking plant exposure were more likely to test positive for COVID-19 (adjusted relative risk [aRR] = 2.37, 95% confidence interval [CI] = 1.59 to 3.53) but had similar rates of hospital admission (aRR = 0.94, 95% CI = 0.82 to 1.07) and hospital LOS (aRR = 0.76, 95% CI = 0.45 to 1.23). There was no significant difference in ventilator use among patients with meatpacking and nonmeatpacking plant exposure (8.2% vs. 11.1%, p = 0.531), ICU admissions (4.1% vs. 12.0%, p = 0.094), and mortality (2.0% vs. 4.1%, p = 0.473). Conclusions Workers in meatpacking plants in Iowa had a higher rate of testing positive for COVID-19 but were not more likely to be hospitalized for their illness. These patients were disproportionately Black and Hispanic.
Anxiety Associated With Increased Risk for Emergency Department Recidivism in Patients With Low-Risk Chest Pain
(Elsevier, 2018) Musey, Paul I., Jr.; Patel, Roma; Fry, Colin; Jimenez, Guadalupe; Koene, Rachael; Kline, Jeffrey A.; Emergency Medicine, School of Medicine
Anxiety contributes to the chest pain symptom complex in 30% to 40% of patients with low-risk chest pain seen in the emergency department (ED). The validated Hospital Anxiety Depression Scale-Anxiety subscale (HADS-A) has been used as an anxiety screening tool in this population. The objective was to determine the prevalence of abnormal HADS-A scores in a cohort of low-risk chest pain patients and test the association of HADS-A score with subsequent healthcare utilization and symptom recurrence. In a single-center, prospective, observational cohort study of adult ED subjects with low-risk chest pain, the HADS-A was used to stratify participants into 2 groups: low anxiety (score <8) and high anxiety (score ≥8). At 45-day follow-up, chest pain recurrence was assessed by patient report, whereas ED utilization was assessed through chart review. Of the 167 subjects enrolled, 78 (47%) were stratified to high anxiety. The relative risk for high anxiety being associated with at least one 30-day ED return visit was 2.6 (95% confidence interval 1.4 to 4.7) and this relative risk increased to 9.1 (95% confidence interval 2.18 to 38.6) for 2 or more ED return visits. Occasional chest pain recurrence was reported by more subjects in the high anxiety group, 68% vs 47% (p = 0.029). In conclusion, 47% of low-risk chest pain cohort had abnormal levels of anxiety. These patients were more likely to have occasional recurrence of their chest pain and had an increased risk multiple ED return visits.
Assessing Risk of Future Suicidality in Emergency Department Patients
(Wiley, 2020-04-02) Brucker, Krista; Duggan, Carter; Niezer, Joseph; Roseberry, Kyle; Le-Niculescu, Helen; Niculescu, Alexander B.; Kline, Jeffrey A.; Emergency Medicine, School of Medicine
Background. Emergency Departments (ED) are the first line of evaluation for patients at risk and in crisis, with or without overt suicidality (ideation, attempts). Currently employed triage and assessments methods miss some of the individuals who subsequently become suicidal. The Convergent Functional Information for Suicidality (CFI-S) 22 item checklist of risk factors, that does not ask directly about suicidal ideation, has demonstrated good predictive ability for suicidality in previous studies in psychiatric outpatients, but has not been tested in the real world-setting of emergency departments (EDs). Methods. We administered CFI-S prospectively to a convenience sample of consecutive ED patients. Median administration time was 3 minutes. Patients were also asked at triage about suicidal thoughts or intentions per standard ED suicide clinical screening (SCS), and the treating ED physician was asked to fill a physician gestalt visual analog scale (VAS) for likelihood of future suicidality spectrum events (SSE) (ideation, preparatory acts, attempts, completed suicide). We performed structured chart review and telephone follow-up at 6 months post index visit. Results. The median time to complete the CFI-S was three minutes (1st to 3rd quartile 3–6 minutes). Of the 338 patients enrolled, 45 (13.3%) were positive on the initial SCS, and 32 (9.5%) experienced a SSE in the 6 months follow-up. Overall, across genders, SCS had a modest diagnostic discrimination for future SSE (ROC AUC 0.63,). The physician VAS was better (AUC 0.76 CI 0.66–0.85), and the CFI-S was slightly higher (AUC 0.81, CI 0.76–0.87). The top CFI-S differentiating items were psychiatric illness, perceived uselessness, and social isolation. The top CFI-S items were family history of suicide, age, and past history of suicidal acts. Conclusions. Using CFI-S, or some of its items, in busy EDs may help improve the detection of patients at high risk for future suicidality.
Assessment of Right Ventricular Function in the Research Setting: Knowledge Gaps and Pathways Forward. An Official American Thoracic Society Research Statement
(American Thoracic Society, 2018-08-15) Lahm, Tim; Douglas, Ivor S.; Archer, Stephen L.; Bogaard, Harm J.; Chesler, Naomi C.; Haddad, Francois; Hemnes, Anna R.; Kawut, Steven M.; Kline, Jeffrey A.; Kolb, Todd M.; Mathai, Stephen C.; Mercier, Olaf; Michelakis, Evangelos D.; Naeije, Robert; Tuder, Rubin M.; Ventetuolo, Corey E.; Vieillard-Baron, Antoine; Voelkel, Norbert F.; Vonk-Noordegraaf, Anton; Medicine, School of Medicine
BACKGROUND: Right ventricular (RV) adaptation to acute and chronic pulmonary hypertensive syndromes is a significant determinant of short- and long-term outcomes. Although remarkable progress has been made in the understanding of RV function and failure since the meeting of the NIH Working Group on Cellular and Molecular Mechanisms of Right Heart Failure in 2005, significant gaps remain at many levels in the understanding of cellular and molecular mechanisms of RV responses to pressure and volume overload, in the validation of diagnostic modalities, and in the development of evidence-based therapies. METHODS: A multidisciplinary working group of 20 international experts from the American Thoracic Society Assemblies on Pulmonary Circulation and Critical Care, as well as external content experts, reviewed the literature, identified important knowledge gaps, and provided recommendations. RESULTS: This document reviews the knowledge in the field of RV failure, identifies and prioritizes the most pertinent research gaps, and provides a prioritized pathway for addressing these preclinical and clinical questions. The group identified knowledge gaps and research opportunities in three major topic areas: 1) optimizing the methodology to assess RV function in acute and chronic conditions in preclinical models, human studies, and clinical trials; 2) analyzing advanced RV hemodynamic parameters at rest and in response to exercise; and 3) deciphering the underlying molecular and pathogenic mechanisms of RV function and failure in diverse pulmonary hypertension syndromes. CONCLUSIONS: This statement provides a roadmap to further advance the state of knowledge, with the ultimate goal of developing RV-targeted therapies for patients with RV failure of any etiology.
Association Between Early Hyperoxia Exposure After Resuscitation From Cardiac Arrest and Neurological Disability: Prospective Multicenter Protocol-Directed Cohort Study
(American Heart Association, 2018-05-15) Roberts, Brian W.; Kilgannon, J. Hope; Hunter, Benton R.; Puskarich, Michael A.; Pierce, Lisa; Donnino, Michael; Leary, Marion; Kline, Jeffrey A.; Jones, Alan E.; Shapiro, Nathan I.; Abella, Benjamin S.; Trzeciak, Stephen; Emergency Medicine, School of Medicine
BACKGROUND: Studies examining the association between hyperoxia exposure after resuscitation from cardiac arrest and clinical outcomes have reported conflicting results. Our objective was to test the hypothesis that early postresuscitation hyperoxia is associated with poor neurological outcome. METHODS: This was a multicenter prospective cohort study. We included adult patients with cardiac arrest who were mechanically ventilated and received targeted temperature management after return of spontaneous circulation. We excluded patients with cardiac arrest caused by trauma or sepsis. Per protocol, partial pressure of arterial oxygen (Pao2) was measured at 1 and 6 hours after return of spontaneous circulation. Hyperoxia was defined as a Pao2 >300 mm Hg during the initial 6 hours after return of spontaneous circulation. The primary outcome was poor neurological function at hospital discharge, defined as a modified Rankin Scale score >3. Multivariable generalized linear regression with a log link was used to test the association between Pao2 and poor neurological outcome. To assess whether there was an association between other supranormal Pao2 levels and poor neurological outcome, we used other Pao2 cut points to define hyperoxia (ie, 100, 150, 200, 250, 350, 400 mm Hg). RESULTS: Of the 280 patients included, 105 (38%) had exposure to hyperoxia. Poor neurological function at hospital discharge occurred in 70% of patients in the entire cohort and in 77% versus 65% among patients with versus without exposure to hyperoxia respectively (absolute risk difference, 12%; 95% confidence interval, 1-23). Hyperoxia was independently associated with poor neurological function (relative risk, 1.23; 95% confidence interval, 1.11-1.35). On multivariable analysis, a 1-hour-longer duration of hyperoxia exposure was associated with a 3% increase in risk of poor neurological outcome (relative risk, 1.03; 95% confidence interval, 1.02-1.05). We found that the association with poor neurological outcome began at ≥300 mm Hg. CONCLUSIONS: Early hyperoxia exposure after resuscitation from cardiac arrest was independently associated with poor neurological function at hospital discharge.
Association Between Elevated Mean Arterial Blood Pressure and Neurologic Outcome After Resuscitation From Cardiac Arrest: Results From a Multicenter Prospective Cohort Study
(Wolters Kluwer, 2019-01) Roberts, Brian W.; Kilgannon, J. Hope; Hunter, Benton R.; Puskarich, Michael A.; Shea, Lisa; Donnino, Michael; Jones, Christopher; Fuller, Brian M.; Kline, Jeffrey A.; Jones, Alan E.; Shapiro, Nathan I.; Abella, Benjamin S.; Trzeciak, Stephen; Department of Emergency Medicine
Objective: Laboratory studies suggest elevated blood pressure after resuscitation from cardiac arrest may be protective; however, clinical data are limited. We sought to test the hypothesis that elevated post-resuscitation mean arterial blood pressure (MAP) is associated with neurological outcome. Design: Pre-planned analysis of a prospective cohort study. Setting: Six academic hospitals in the United States. Patients: Adult, non-traumatic cardiac arrest patients treated with targeted temperature management after return of spontaneous circulation (ROSC). Interventions: MAP was measured non-invasively after ROSC and every hour during the initial six hours after ROSC. Measures and Main Results: We calculated the mean MAP and a priori dichotomized subjects into two groups: mean MAP 70–90 and > 90 mmHg. The primary outcome was good neurological function, defined as a modified Rankin Scale (mRS) ≤ 3. The mRS was prospectively determined at hospital discharge. Of the 269 patients included, 159 (59%) had a mean MAP > 90 mmHg. Good neurological function at hospital discharge occurred in 30% of patients in the entire cohort, and was significantly higher in patients with a mean MAP > 90 mmHg (42%) as compared to MAP 70–90 mmHg (15%) [absolute risk difference 27% (95% CI 17%−37%)]. In a multivariable Poisson regression model adjusting for potential confounders, mean MAP > 90 mmHg was associated with good neurological function, adjusted relative risk 2.46 (95% CI 2.09–2.88). Over ascending ranges of mean MAP, there was a dose-response increase in probability of good neurological outcome, with mean MAP > 110 mmHg having the strongest association, adjusted relative risk 2.97 (95% CI 1.86 – 4.76). Conclusions: Elevated blood pressure during the initial six hours after resuscitation from cardiac arrest was independently associated with good neurological function at hospital discharge. Further investigation is warranted to determine if targeting an elevated MAP would improve neurologic outcome after cardiac arrest.

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