Browsing by Author "Boyle, Stephen H"

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    A population-based analysis on the use of therapeutic plasma exchange and intravenous immunoglobulin in heparin-induced thrombocytopenia.
    (Thrombosis research, 2021-05) Soares Ferreira Júnior, Alexandre; Boyle, Stephen H; Kuchibhatla, Maragatha; Onwuemene, Oluwatoyosi A

    Introduction

    In heparin-induced thrombocytopenia (HIT), selected patients are treated with therapies directed at the immune response, intravenous immunoglobulin (IVIG) and therapeutic plasma exchange (TPE). To determine IVIG and TPE characteristics and outcomes in HIT, we analyzed the National Inpatient Sample (NIS) database.

    Methods

    In a population-based analysis of the NIS, we identified hospital discharges of adult patients with a HIT diagnosis. A two-level statistical analysis was performed comparing cases as follows 1) IVIG or TPE vs. none; and 2) IVIG vs. TPE. For each analysis, the primary outcome was in-hospital mortality. Secondary outcomes were thrombotic events, major bleeding, infections, hospital length of stay, and total charges.

    Results

    Among 22,152 discharges with a HIT diagnosis, 77 (0.34%) and 52 (0.23%) received TPE and IVIG, respectively. In the first level analysis of TPE or IVIG vs. no treatment, TPE or IVIG treatment was associated with a higher likelihood of in-hospital mortality (OR = 1.85; 95%CI: 1.13-3.03, p = 0.0104), major bleeding (OR = 1.91; 95%CI: 1.25-2.93, p = 0.0030), gastrointestinal bleeding (OR = 1.89; 95%CI: 1.08-3.30, p = 0.0259), and infection (OR = 1.65; 95% CI:1.13-2.41, p = 0.0095). In the second-level analysis comparing IVIG vs. TPE, there were no significant differences in patient characteristics or outcomes in both unadjusted and adjusted analyses.

    Conclusions

    In this population-based analysis of HIT, we found similar outcomes of IVIG and TPE-treated cases. Given the small sample size, future studies are needed to confirm this observation.
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    Bleeding is associated with intravenous immunoglobulin and therapeutic plasma exchange use in heparin-induced thrombocytopenia: A propensity matched analysis.
    (EJHaem, 2021-08) Soares Ferreira Júnior, Alexandre; Boyle, Stephen H; Kuchibhatla, Maragatha; Onwuemene, Oluwatoyosi A
    Intravenous immunoglobulin (IVIG) and therapeutic plasma exchange (TPE) are used in select cases with heparin-induced thrombocytopenia (HIT). In a cross-sectional analysis, a propensity matched sample was generated by IVIG or TPE treatment status to assess the primary outcome of mortality. In 500 HIT cases, IVIG or TPE was not associated with increased mortality (OR = 1.46; 95% CI: 0.81-2.63, p = 0.2052) but was associated with a higher likelihood of major bleeding (OR = 1.75; 95% CI: 1.03-2.96, p = 0.0376). The use of IVIG or TPE in HIT cases with bleeding contraindications to standard therapies should be further investigated.
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    Bleeding outcomes of inpatients receiving therapeutic plasma exchange: A propensity-matched analysis of the National Inpatient Sample.
    (Transfusion, 2022-02) Soares Ferreira Júnior, Alexandre; Boyle, Stephen H; Kuchibhatla, Maragatha; Onwuemene, Oluwatoyosi A

    Background

    Although therapeutic plasma exchange (TPE) is associated with hemostatic abnormalities, its impact on bleeding outcomes is unknown. Therefore, the main study objective was to determine bleeding outcomes of inpatients treated with TPE.

    Study design and methods

    In a cross-sectional analysis of the National Inpatient Sample (NIS), discharges were identified with 10 common TPE-treated conditions. A 1:3 propensity-matched analysis of TPE- to non-TPE-treated discharges was performed. The primary outcome was major bleeding and secondary outcomes were packed red blood cell (PRBC) transfusion, mortality, disposition, hospital length of stay (LOS), and charges. Multivariable regression analyses were used to examine the association between TPE and study outcomes.

    Results

    The study population was 15,964 discharges, of which 3991 were TPE- treated. The prevalence of major bleeding was low (5.4%). When compared to non-TPE discharges, TPE had a significant and positive association with major bleeding (OR = 1.37, 95% CI: 1.16-1.63, p = .0003). TPE was also associated with PRBC transfusion (OR = 1.66, 95% CI: 1.42-1.94, p < .0001), in-hospital mortality (OR = 1.45, 95% CI: 1.10-1.90, p = .0008), hospital length of stay (12.45 [95% CI: 11.95-12.97] vs. 7.38 [95% CI: 7.12-7.65] days, p < .0001) and total charges, ($125,123 [95% CI: $119,220-$131,317] vs. $61,953 [95% CI: $59,391-$64,625], p < .0001), and disposition to non-self-care (OR = 1.29, 95% CI: 1.19-1.39, p < .0001).

    Discussion

    The use of TPE in the inpatient setting is positively associated with bleeding; however, with low prevalence. Future studies should address risk factors that predispose patients to TPE-associated bleeding.
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    Central venous catheters are associated with thrombosis among adult inpatients undergoing therapeutic plasma exchange.
    (Journal of clinical apheresis, 2022-08) Soares Ferreira Júnior, Alexandre; Boyle, Stephen H; Kuchibhatla, Maragatha; Onwuemene, Oluwatoyosi A

    Background

    For inpatients undergoing therapeutic plasma exchange (TPE) in the United States, the primary mode of venous access is the central venous catheter (CVC). To evaluate the impact of CVC on thrombosis outcomes of patients undergoing TPE, we analyzed the National Inpatient Sample (NIS) database.

    Study design and methods

    In a cross-sectional analysis of the NIS, we identified hospital discharges of adult patients treated with TPE. Cases were classified into two groups based on CVC status. The primary outcome was thrombosis. Secondary outcomes were major bleeding, packed red blood cell (PRBC) transfusion, in-hospital mortality, hospital length of stay (LOS), and charges.

    Results

    Among 9863 TPE-treated discharges, CVC was used in 5988 (60%). These numbers correspond to weighted national estimates of 49 315 and 29 940, respectively. There was a positive and significant association between CVC and thrombosis (OR = 1.23, 95% 1.04-1.46, P = 0.0174), PRBC transfusion (OR = 1.15, 95% 1.03-1.29, P = 0.0121), in-hospital mortality (OR = 1.36, 95% 1.10-1.68, P = 0.0043), hospital LOS (15.63 vs 12.45 days, P < 0.0001) and hospital charges ($166 387 vs. $132 655, P < 0.0001).

    Conclusion

    In hospitalized patients undergoing TPE, CVC use is associated with increased rates of thrombosis. Future studies are needed to investigate strategies to decrease CVC use and/or prevent CVC-associated complications in TPE-treated inpatients.
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    Pharmacometabolomics of response to sertraline and to placebo in major depressive disorder - possible role for methoxyindole pathway.
    (PloS one, 2013-01) Zhu, Hongjie; Bogdanov, Mikhail B; Boyle, Stephen H; Matson, Wayne; Sharma, Swati; Matson, Samantha; Churchill, Erik; Fiehn, Oliver; Rush, John A; Krishnan, Ranga R; Pickering, Eve; Delnomdedieu, Marielle; Kaddurah-Daouk, Rima; Pharmacometabolomics Research Network
    Therapeutic response to selective serotonin (5-HT) reuptake inhibitors in Major Depressive Disorder (MDD) varies considerably among patients, and the onset of antidepressant therapeutic action is delayed until after 2 to 4 weeks of treatment. The objective of this study was to analyze changes within methoxyindole and kynurenine (KYN) branches of tryptophan pathway to determine whether differential regulation within these branches may contribute to mechanism of variation in response to treatment. Metabolomics approach was used to characterize early biochemical changes in tryptophan pathway and correlated biochemical changes with treatment outcome. Outpatients with MDD were randomly assigned to sertraline (n = 35) or placebo (n = 40) in a double-blind 4-week trial; response to treatment was measured using the 17-item Hamilton Rating Scale for Depression (HAMD17). Targeted electrochemistry based metabolomic platform (LCECA) was used to profile serum samples from MDD patients. The response rate was slightly higher for sertraline than for placebo (21/35 [60%] vs. 20/40 [50%], respectively, χ(2)(1)  = 0.75, p = 0.39). Patients showing a good response to sertraline had higher pretreatment levels of 5-methoxytryptamine (5-MTPM), greater reduction in 5-MTPM levels after treatment, an increase in 5-Methoxytryptophol (5-MTPOL) and Melatonin (MEL) levels, and decreases in the (KYN)/MEL and 3-Hydroxykynurenine (3-OHKY)/MEL ratios post-treatment compared to pretreatment. These changes were not seen in the patients showing poor response to sertraline. In the placebo group, more favorable treatment outcome was associated with increases in 5-MTPOL and MEL levels and significant decreases in the KYN/MEL and 3-OHKY/MEL; changes in 5-MTPM levels were not associated with the 4-week response. These results suggest that recovery from a depressed state due to treatment with drug or with placebo could be associated with preferential utilization of serotonin for production of melatonin and 5-MTPOL.
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    Platelet aggregation and mental stress induced myocardial ischemia: Results from the Responses of Myocardial Ischemia to Escitalopram Treatment (REMIT) study.
    (Am Heart J, 2015-04) Jiang, Wei; Boyle, Stephen H; Ortel, Thomas L; Samad, Zainab; Velazquez, Eric J; Harrison, Robert W; Wilson, Jennifer; Kuhn, Cynthia; Williams, Redford B; O'Connor, Christopher M; Becker, Richard C
    BACKGROUND: Mental stress-induced myocardial ischemia (MSIMI) is common in patients with ischemic heart disease (IHD) and associated with a poorer cardiovascular prognosis. Platelet hyperactivity is an important factor in acute coronary syndrome. This study examined associations between MSIMI and resting and mental stress-induced platelet activity. METHODS: Eligible patients with clinically stable IHD underwent a battery of 3 mental stress tests during the recruitment phase of REMIT study. MSIMI was assessed by echocardiography and electrocardiography. Ex vivo platelet aggregation in response to ADP, epinephrine, collagen, serotonin, and combinations of serotonin plus ADP, epinephrine, and collagen were evaluated as was platelet serotonin transporter expression. RESULTS: Of the 270 participants who completed mental stress testing, and had both resting and post-stress platelet aggregation evaluation , 43.33% (n=117) met criteria for MSIMI and 18.15% (n=49) had normal left ventricular response to stress (NLVR). The MSIMI group, relative to the NLVR groups, demonstrated heightened mental stress-induced aggregation responses, as measured by area under the curve, to collagen 10μM (6.95[5.54] vs. -14.23[8.75].; P=0.045), epinephrine 10μM (12.84[4.84] vs. -6.40[7.61].; P=0.037) and to serotonin 10 μM plus ADP 1 μM (6.64[5.29] vs. -27.34[8.34]; P<.001). The resting platelet aggregation and serotonin transporter expression, however, were not different between the two groups. CONCLUSIONS: These findings suggest that the dynamic change of platelet aggregation caused by mental stress may underlie MSIMI. While the importance of these findings requires additional investigation, they raise concern given the recognized relationship between mental stress-induced platelet hyperactivity and cardiovascular events in patients with IHD.
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    Use of therapeutic plasma exchange in heparin-induced thrombocytopenia: A population-based study.
    (Journal of clinical apheresis, 2021-06) Soares Ferreira Júnior, Alexandre; Boyle, Stephen H; Kuchibhatla, Maragatha; Akinyemiju, Tomi; Onwuemene, Oluwatoyosi A

    Background

    Heparin-induced thrombocytopenia (HIT) is characterized by anti-heparin/platelet factor 4 immune complexes, which are removed by therapeutic plasma exchange (TPE). Our main objective was to study TPE outcomes in HIT using a large administrative claims database.

    Study design and methods

    We used the National Inpatient Sample (NIS) to identify hospital discharges of adult patients (≥18) with a primary or secondary diagnosis of HIT. Cases were classified into two groups based on TPE use. The primary outcome was in-hospital mortality. Secondary outcomes were thrombotic events, major bleeding, hospital length of stay (LOS), and charges. Multivariable regression analysis, controlling for age and medical comorbidities, was used to examine the association of TPE with study outcomes.

    Results

    A HIT diagnosis was made in 22 165 discharges, of which 90 (0.4%) received TPE. Corresponding national estimates are 106 435 and 439, respectively. TPE was not associated with decreased in-hospital mortality (OR = 1.72; 95%CI: 0.93-3.17, P = .085). However, TPE was associated with a higher likelihood of major bleeding (OR = 2.35; 95%CI: 1.40-3.68, P = .0009), primarily driven by gastrointestinal bleeding (OR = 2.21; 95%CI: 1.17-4.17, P = .015). TPE was also associated with higher hospital LOS (20.5 vs 10 day, P < .0001) and charges (USD 211181 vs USD 81654, P < .0001).

    Conclusion

    TPE's association with increased bleeding and a prolonged hospital course indicates that it is being used in HIT cases with a severe clinical phenotype. Future studies are needed to better characterize the HIT phenotype that will most benefit from TPE.