Jeffrey A. Kline
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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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Item The use of qualitative methods in venous thromboembolism research(Elsevier, 2021-09-12) Hernandez-Nino, Jackeline; Thomas, Mary; Alexander, Andreia B.; Ott, Mary A.; Kline, Jeffrey A.; Emergency Medicine, School of MedicineIntroduction: Qualitative research has been increasingly used in health care research to allow in-depth insights and understanding of patients' lived experiences for poorly understood phenomena. The psychological stress mechanisms underlying fear, dyspnea, and pain after venous thromboembolism (VTE) remain poorly understood. However, novice VTE researchers may not be familiar with the process of undertaking qualitative research. Objective: The aim of this article is to describe the planning, methodology and execution of qualitative methods, using the example of patients' lived experiences during and after the diagnosis of VTE. We discuss challenges and solutions in implementing qualitative research methods in health care research. Methods: Patients were recruited from the emergency department and clinic using in-person and phone contact. We used both in-person and video format to interview 24 patients. Interviews were guided by a set of questions to be explored but conducted to elucidate unique thoughts and opinions from patients. Results: For recruitment, "cold-calling" was found to be largely unsuccessful. Many patients have preexisting diagnoses of anxiety and depression. Video interviews were found to be at least as effective as in-person interviews. Interviews revealed unique post-VTE experiences from all participants, with a wide range of impact on quality of life. Themes that were most common included perceptions of physician communication, fear of recurrence, and concerns of death. Conclusion: A qualitative research approach can reveal individual experiences and psychosocial impact in patients diagnosed with VTE, which allow the researchers to better comprehend the complexity of this phenomenon and its impact in health care.Item Metabolic Syndrome Increases Risk of Venous Thromboembolism Recurrence after Acute Pulmonary Embolism(American Thoracic Society, 2020-07) Stewart, Lauren K.; Kline, Jeffrey A.; Emergency Medicine, School of MedicineRationale: Metabolic syndrome (MetS), the clinical clustering of hypertension, dyslipidemia, insulin resistance, and abdominal obesity, has been associated with a prothrombotic and hypofibrinolytic state, although data linking MetS with venous thromboembolism (VTE) remain limited. Objectives: The aim of this study was to measure the prevalence of MetS in patients with pulmonary embolism (PE) across a large population and to examine its impact on VTE recurrence. Methods: This was a retrospective, population-based analysis using deidentified information from a large statewide database, the Indiana Network for Patient Care. All patients with an International Classification of Diseases-defined diagnosis of PE from 2004 to 2017 were included. We measured the frequency with which patients with PE carried a comorbid diagnosis of each MetS component. Multiple logistic regression analysis was performed with VTE recurrence as the dependent variable to test the independent effect of MetS diagnosis, with a statistical model using a directed acyclic graph to account for potential confounders and mediators. Kaplan-Meier curves were constructed to compare rates of VTE recurrence over time based on the presence or absence of MetS and its individual components. Results: A total of 72,936 patients were included in this analysis. The most common MetS component was hypertension with a prevalence of 59%, followed by hyperlipidemia (41%), diabetes mellitus (24%), and obesity (22%). Of these patients, 69% had at least one comorbid component of MetS. The overall incidence of VTE recurrence was 17%, increasing stepwise with each additional MetS component and ranging from 6% in patients with zero components to 37% in those with all four. Logistic regression analysis yielded an adjusted odds ratio of 3.03 (95% CI, 2.90-3.16) for the effect of composite diagnosis requiring at least three of the four components of MetS diagnosis on VTE recurrence. Conclusions: The presence of comorbid MetS in patients with PE is associated with significantly higher rates of VTE recurrence, supporting the importance of recognizing these risk factors and initiating appropriate therapies to reduce recurrence risk.Item 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 MedicineIntroduction: 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.Item Systematic review and meta-analysis of outcomes in patients with suspected pulmonary embolism(American Society of Hematology, 2021-04-27) Patel, Parth; Patel, Payal; Bhatt, Meha; Braun, Cody; Begum, Housne; Nieuwlaat, Robby; Khatib, Rasha; Martins, Carolina C.; Zhang, Yuan; Etxeandia-Ikobaltzeta, Itziar; Varghese, Jamie; Alturkmani, Hani; Bahaj, Waled; Baig, Mariam; Kehar, Rohan; Mustafa, Ahmad; Ponnapureddy, Rakesh; Sethi, Anchal; Thomas, Merrill; Wooldridge, David; Lim, Wendy; Bates, Shannon M.; Lang, Eddy; Le Gal, Grégoire; Haramati, Linda B.; Kline, Jeffrey A.; Righini, Marc; Wiercioch, Wojtek; Schünemann, Holger; Mustafa, Reem A.; Emergency Medicine, School of MedicinePrompt evaluation and therapeutic intervention of suspected pulmonary embolism (PE) are of paramount importance for improvement in outcomes. We systematically reviewed outcomes in patients with suspected PE, including mortality, incidence of recurrent PE, major bleeding, intracranial hemorrhage, and postthrombotic sequelae. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. We included 22 studies with 15 865 patients. Among patients who were diagnosed with PE and discharged with anticoagulation, 3-month follow-up revealed that all-cause mortality was 5.69% (91/1599; 95% confidence interval [CI], 4.56-6.83), mortality from PE was 1.19% (19/1597; 95% CI, 0.66-1.72), recurrent venous thromboembolism (VTE) occurred in 1.38% (22/1597; 95% CI: 0.81-1.95), and major bleeding occurred in 0.90% (2/221%; 95% CI, 0-2.15). In patients with a low pretest probability (PTP) and negative D-dimer, 3-month follow-up revealed mortality from PE was 0% (0/808) and incidence of VTE was 0.37% (4/1094; 95% CI: 0.007-0.72). In patients with intermediate PTP and negative D-dimer, 3-month follow-up revealed that mortality from PE was 0% (0/2747) and incidence of VTE was 0.46% (14/3015; 95% CI: 0.22-0.71). In patients with high PTP and negative computed tomography (CT) scan, 3-month follow-up revealed mortality from PE was 0% (0/651) and incidence of VTE was 0.84% (11/1302; 95% CI: 0.35-1.34). We further summarize outcomes evaluated by various diagnostic tests and diagnostic pathways (ie, D-dimer followed by CT scan).Item Derivation and Validation of a 4-Level Clinical Pretest Probability Score for Suspected Pulmonary Embolism to Safely Decrease Imaging Testing(JAMA, 2021-06-01) Roy, Pierre-Marie; Friou, Emilie; Germeau, Boris; Douillet, Delphine; Kline, Jeffrey A.; Righini, Marc; Le Gal, Grégoire; Moumneh, Thomas; Penaloza, Andrea; Emergency Medicine, School of MedicineImportance: In patients with suspected pulmonary embolism (PE), overuse of diagnostic imaging is an important point of concern. Objective: To derive and validate a 4-level pretest probability rule (4-Level Pulmonary Embolism Clinical Probability Score [4PEPS]) that makes it possible to rule out PE solely on clinical criteria and optimized D-dimer measurement to safely decrease imaging testing for suspected PE. Design, setting, and participants: This study included consecutive outpatients suspected of having PE from US and European emergency departments. Individual data from 3 merged management studies (n = 11 114; overall prevalence of PE, 11%) were used for the derivation cohort and internal validation cohort. The external validation cohorts were taken from 2 independent studies, the first with a high PE prevalence (n = 1548; prevalence, 21.5%) and the second with a moderate PE prevalence (n = 1669; prevalence, 11.7%). A prior definition of pretest probability target values to achieve a posttest probability less than 2% was used on the basis of the negative likelihood ratios of D-dimer. Data were collected from January 2003 to April 2016, and data were analyzed from June 2018 to August 2019. Main outcomes and measures: The rate of PE diagnosed during the initial workup or during follow-up and the rate of imaging testing. Results: Of the 5588 patients in the derivation cohort, 3441 (61.8%) were female, and the mean (SD) age was 52 (18.5) years. The 4PEPS comprises 13 clinical variables scored from -2 to 5. It results in the following strategy: (1) very low probability of PE if 4PEPS is less than 0: PE ruled out without testing; (2) low probability of PE if 4PEPS is 0 to 5: PE ruled out if D-dimer level is less than 1.0 μg/mL; (3) moderate probability of PE if 4PEPS is 6 to 12: PE ruled out if D-dimer level is less than the age-adjusted cutoff value; (4) high probability of PE if 4PEPS is greater than 12: PE ruled out by imaging without preceding D-dimer test. In the first and the second external validation cohorts, the area under the receiver operator characteristic curves were 0.79 (95% CI, 0.76 to 0.82) and 0.78 (95% CI, 0.74 to 0.81), respectively. The false-negative testing rates if the 4PEPS strategy had been applied were 0.71% (95% CI, 0.37 to 1.23) and 0.89% (95% CI, 0.53 to 1.49), respectively. The absolute reductions in imaging testing were -22% (95% CI, -26 to -19) and -19% (95% CI, -22 to -16) in the first and second external validation cohorts, respectively. The 4PEPS strategy compared favorably with all recent strategies in terms of imaging testing. Conclusions and relevance: The 4PEPS strategy may lead to a substantial and safe reduction in imaging testing for patients with suspected PE. It should now be tested in a formal outcome study.Item Inhaled nitric oxide to control platelet hyper-reactivity in patients with acute submassive pulmonary embolism(Elsevier, 2020-03-01) Kline, Jeffrey A.; Puskarich, Michael A.; Pike, Jonathan; Zagorski, John; Alves, Nathan J.; Emergency Medicine, School of MedicineBackground: We test if inhaled nitric oxide (NO) attenuates platelet functional and metabolic hyper-reactivity in subjects with submassive pulmonary embolism (PE). Methods: Participants with PE were randomized to either 50 ppm NO + O2 or O2 only for 24 h with blood sampling at enrollment and after treatment; results were compared with healthy controls. Platelet metabolic activity was assessed by oxygen consumption (basal and uncoupled) and reactivity was assessed with agonist-stimulated thromboelastography (TEG) and fluorometric measurement of agonist-stimulated cytosolic [Ca++] without and with pharmacological soluble guanylate (sGC) modulation. Results: Participants (N = 38 per group) were well-matched at enrollment for PE severity, comorbidities as well as TEG parameters and platelet O2 consumption. NO treatment doubled the mean plasma [NO3-] (P < 0.001) indicating successful delivery, but placebo treatment produced no change. After 24 h, neither TEG nor O2 consumption parameters differed significantly between treatment groups. Platelet cytosolic [Ca++] was elevated with PE versus controls, and was decreased by treatment with cinaciguat (an sGC activator), but not riociguat (an sGC stimulator). Stimulated platelet lysate sGC activity was increased with PE compared with controls. Conclusions: In patients with acute submassive PE, despite evidence of adequate drug delivery, inhaled NO had no major effect on platelet O2 consumption or agonist-stimulated parameters on TEG. Pharmacological activation, but not stimulation, of sGC effectively decreased platelet cytosolic [Ca++], and platelet sGC activity was increased with PE, confirming the viability of sGC as a therapeutic target.Item Effect of metabolic syndrome on mean pulmonary arterial pressures in patients with acute pulmonary embolism treated with catheter-directed thrombolysis(Elsevier, 2020-03-01) Stewart, Lauren K.; Beam, Daren M.; Casciani, Thomas; Cameron, Scott J.; Kline, Jeffrey A.; Emergency Medicine, School of MedicineBackground: Metabolic syndrome (MetS) has been associated with a procoagulant and hypofibrinolytic state. Current data exploring the role of MetS in venous thromboembolism (VTE) are limited. The objective was to measure the prevalence of MetS in patients with acute PE receiving catheter-directed thrombolysis (CDT) and to investigate its effect on mean pulmonary arterial pressure and overall treatment success. Methods: We used a 3-year prospective registry of ED patients with acute PE with severity qualifying for activation of a PE response team (PERT). All patients had CDT with catheter-measured mPAP and angiography. The presence or absence of MetS components were extracted from chart review based on the following criteria: 1. body mass index (BMI) >30 kg/m2; 2. diagnosed hypertension; 3. diabetes mellitus (including HbA1c >6.5%) and; 4. dyslipidemia (including triglycerides >150 mg/dL or high-density lipoprotein <40 mg/dL). Results: Of the 134 patients, 85% met the criteria for at least one of four MetS components, with obesity being most common, present in 71%. Results demonstrated a positive concordance between the number of criteria for MetS and MPAP, both pre- and post-fibrinolysis, as pressures tended to increase with each additional MetS criterion. Multivariate regression analysis determined age (-), BMI (+) and hypertension (+) to be significant independent predictor variables for mPAP. Conclusions: MetS was common in patients with more severe manifestations of PE and was associated with higher mPAP values both at diagnosis and following treatment with CDT.Item Pulmonary vasodilation in acute pulmonary embolism - a systematic review(Sage, 2020-03-04) Lyhne, Mads Dam; Kline, Jeffrey A.; Nielsen-Kudsk, Jens Erik; Andersen, Asger; Emergency Medicine, School of MedicineAcute pulmonary embolism is the third most common cause of cardiovascular death. Pulmonary embolism increases right ventricular afterload, which causes right ventricular failure, circulatory collapse and death. Most treatments focus on removal of the mechanical obstruction caused by the embolism, but pulmonary vasoconstriction is a significant contributor to the increased right ventricular afterload and is often left untreated. Pulmonary thromboembolism causes mechanical obstruction of the pulmonary vasculature coupled with a complex interaction between humoral factors from the activated platelets, endothelial effects, reflexes and hypoxia to cause pulmonary vasoconstriction that worsens right ventricular afterload. Vasoconstrictors include serotonin, thromboxane, prostaglandins and endothelins, counterbalanced by vasodilators such as nitric oxide and prostacyclins. Exogenous administration of pulmonary vasodilators in acute pulmonary embolism seems attractive but all come with a risk of systemic vasodilation or worsening of pulmonary ventilation-perfusion mismatch. In animal models of acute pulmonary embolism, modulators of the nitric oxide-cyclic guanosine monophosphate-protein kinase G pathway, endothelin pathway and prostaglandin pathway have been investigated. But only a small number of clinical case reports and prospective clinical trials exist. The aim of this review is to give an overview of the causes of pulmonary embolism-induced pulmonary vasoconstriction and of experimental and human investigations of pulmonary vasodilation in acute pulmonary embolism.Item Inter-rater reliability and prospective validation of a clinical prediction rule for SARS-CoV-2 infection(Wiley, 2021-07) Nevel, Adam E.; Kline, Jeffrey A.; Emergency Medicine, School of MedicineObjectives Accurate estimation of the risk of SARS-CoV-2 infection based on bedside data alone has importance to Emergency Department (ED) operations and throughput. The 13 item CORC (COVID [or coronavirus] Rule-out Criteria) rule had good overall diagnostic accuracy in retrospective derivation and validation. The objective of this study was to prospectively test the inter-rater-reliability and diagnostic accuracy of the CORC score and rule (score ≤0 negative, >0 positive), and compare the CORC rule performance with physician gestalt. Methods This non-interventional study was conducted at an urban academic ED from February-March 2021. Two practitioners were approached by research coordinators and asked to independently complete a form capturing the CORC criteria for their shared patient, and their gestalt binary prediction of the SARS-CoV-2 test result and confidence (0-100%). The criterion standard for SARS-CoV-2 was from rt-PCR performed on a nasopharyngeal swab. The primary analysis was from weighted Cohen’s K and likelihood ratios (LR). Results For 928 patients, agreement between observers was good for the total CORC score, K = 0.613 (0.579-0.646) and for the CORC rule K = 0.644 (0.591-0.697). The agreement for clinician gestalt binary determination of SARs-CoV-2 status was K = 0.534, (95% CI 0.437-0.632) with median confidence of 76% (1st-3rd quartile: 66-88.5). For 425 patients who had the criterion standard, a negative CORC rule (both observers scored CORC <0), the sensitivity was 88%, specificity 51%, with a LR(-) = 0.24 (95% CI 0.10-0.50). Among patients with a mean CORC score >4, the prevalence of a positive SARS-CoV-2 test was 58% (28-85%) and LR(+) = 13.1 (4.5-37.2). Clinician gestalt demonstrated a sensitivity of 51%, specificity of 86% with a LR(-) = 0.57 (0.39-0.74). Conclusion In this prospective study, the CORC score and rule demonstrated good inter-rater reliability and reproducible diagnostic accuracy for estimating the pretest probability of SARs-CoV-2 infection.Item 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 MedicineObjective 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.