Publications by authors named "Rahul Chaudhary"

107 Publications

Timing of venous thromboembolism diagnosis in hospitalized and non-hospitalized patients with COVID-19.

Thromb Res 2021 Oct 7;207:150-157. Epub 2021 Oct 7.

Department of Cardiovascular Diseases, Division of Vascular Medicine, Rochester, MN, United States of America; Department of Internal Medicine, Division of Hematology/Oncology, Mayo Clinic, MN, United States of America. Electronic address:

Background: The reported incidence of venous thromboembolism (VTE) in COVID-19 patients varies widely depending on patient populations sampled and has been predominately studied in hospitalized patients. The goal of this study was to assess the evolving burden of COVID-19 and the timing of associated VTE events in a systems-wide cohort.

Methods: COVID-19 PCR positive hospitalized and non-hospitalized patients ≥18 years of age tested between 1/1/2020 through 12/31/2020 were retrospectively analyzed using electronic medical records from multiple states across the Mayo Clinic enterprise. Radiology reports within 90 days before and after confirmed COVID-19 diagnosis were examined for VTE outcomes using validated Natural Language Processing (NLP) algorithms.

Results: A 29-fold increased rate of VTE compared to the pre-COVID-19 period was noted during the first week following the first positive COVID-19 test (RR: 29.39; 95% CI 21.77-40.03). The rate of VTE steadily decreased and returned to baseline by the 6th week. Among 366 VTE events, most occurred during (n = 243, 66.3%) or after (n = 111, 30.3%) initial hospitalization. Only 11 VTE events were identified in patients who did not require hospitalization (3.0% of total VTE events). VTE and mortality increased with advancing age with a pronounced increased each decade in older patients.

Conclusion: We observed a profoundly increased risk of VTE within the first week after positive testing for COVID-19 that returned to baseline levels after 6 weeks. VTE events occurred almost exclusively in patients who were hospitalized, with the majority of VTE events identified within the first days of hospitalization.
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http://dx.doi.org/10.1016/j.thromres.2021.09.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495042PMC
October 2021

Development and evaluation of phytosome-loaded microsphere system for delivery of ginseng extract.

J Microencapsul 2021 Nov-Dec;38(7-8):496-506. Epub 2021 Oct 13.

Department of Pharmacy, College of Health Sciences, Asella, Ethiopia.

The current research work focuses mainly on evolving a delivery system for ginseng extract (GE), which in turn will ameliorate the neuroprotective potential through enhancing the Ginsenoside Rb1(GRb1) bioavailability (BA). Phytosome complexes (F1, F2, and F3) were prepared by reacting GE with phospholipids in disparate ratios. F3 was chosen for preparing the phytosomes powder (PP) and phytosomes-loaded microspheres (PMs). Extract microspheres (EMs) were prepared by the addition of extract directly into the same polymer mixture. F3 gave enhanced entrapment efficiency (50.61%, ) along with spherical-shaped particle size (42.58 ± 1.4 nm) with the least polydispersity index (0.193 ± 0.01). PM showed an enhanced relative bioavailability (157.94%) of GRb1. It also showed a greater neuroprotective potential exhibiting significant ( < 0.05) augmentation in the nociceptive threshold. It was concluded that the PM system might be an optimistic and feasible strategy to enhance the delivery of GE for the effectual treatment of neuropathy.
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http://dx.doi.org/10.1080/02652048.2021.1982042DOI Listing
October 2021

Dosimetric impact of Acuros XB on cervix radiotherapy using RapidArc technique: a dosimetric study.

Rep Pract Oncol Radiother 2021 12;26(4):582-589. Epub 2021 Aug 12.

Medical Physics Division and Radiation Oncology Department, Rajiv Gandhi Cancer Institute and Research Center, New Delhi, India.

Background: Acuros XB (AXB) may predict better rectal toxicities and treatment outcomes in cervix carcinoma. The aim of the study was to quantify the potential impact of AXB computations on the cervix radiotherapy using the RapidArc (RA ) technique as compared to anisotropic analytical algorithm (AA) computations.

Materials And Methods: A cohort of 30 patients previously cared for cervix carcinoma (stages II-IIIB) was selected for the present analysis. The RA plans were computed using AA and AXB dose computation engines under identical beam setup and MLC pattern.

Results: There was no significant (p > 0.05) difference in D and D to the planning target volume (PTV); moreover, a significant (p < 0.05) rise was noticed for mean dose to the PTV (0.26%), D (0.26%), D (0.80%) and V (44.24%) for AXB computation as compared to AA computations. Further, AXB estimated a significantly (p < 0.05) lower value for maximum and minimum dose to the PTV. Additionally, there was a significant (p < 0.05) reduction observed in mean dose to organs at risk (OARs) for AXB computation as compared to AA, though the reduction in mean dose was non-significant (p > 0.05) for the rectum. The maximum difference observed was 4.78% for the rectum V, 1.72%, 1.15% in mean dose and 2.22%, 1.48% in D of the left femur and right femur, respectively, between AA and AXB dose estimations.

Conclusion: For similar target coverage, there were significant differences observed between the AAA and AXB computations. AA underestimates the V of the rectum and overestimates the mean dose and D for femoral heads as compared to AXB. Therefore, the use of AXB in the case of cervix carcinoma may predict better rectal toxicities and treatment outcomes in cervix carcinoma using the RA technique.
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http://dx.doi.org/10.5603/RPOR.a2021.0074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382073PMC
August 2021

Role of Internal Jugular Venous Ultrasound in suspected or confirmed Heart Failure: A Systematic Review.

J Card Fail 2021 Aug 19. Epub 2021 Aug 19.

UPMC Heart and Vascular Institute, Pittsburgh, Pennsylvania; Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, Pittsburgh, Pennsylvania; Department of Bioengineering, Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.

Background: Few data are available on the use of internal jugular vein (IJV) ultrasound parameters to assess central venous pressure and clinical outcomes among patients with suspected or confirmed heart failure (HF).

Methods: We performed electronic searches on PubMed, The Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases from the inception through January 9, 2021, to identify studies evaluating the accuracy and reliability of the IJV ultrasound parameters and exploring its correlation with central venous pressure and clinical outcomes in adult patients with suspected or confirmed acutely decompensated HF. The studies' report quality was assessed by Quality Assessment of Diagnostic Accuracy Studies-2 scale.

Results: A total of 11 studies were eligible for final analysis (n = 1481 patients with HF). The studies were segregated into 3 groups: (1) the evaluation of patients presenting to the emergency department with dyspnea, (2) the evaluation of patients presenting to the HF clinic for follow-up, and (3) the evaluation of hospitalized patients with acutely decompensated HF or undergoing right heart catheterization. US parameters included IJV height, IJV diameter, IJV diameter ratio, IJV cross-sectional area, respiratory compressibility index, and compression compressibility index.

Conclusions: The findings of this systematic review suggest a significant role for ultrasound interrogation of the IJV in evaluation of patients in the emergency department presenting with dyspnea, in the outpatient clinic for poor clinical outcomes in HF, and in determining the timing of discharge for patients admitted with acutely decompensated HF. Further studies are warranted for testing the reliability of the reported ultrasound indices.
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http://dx.doi.org/10.1016/j.cardfail.2021.08.009DOI Listing
August 2021

Probability Distribution of Pixel Intensities of EBT3 Films and its Application in the Correction of Uncertainty Budget.

J Med Phys 2021 Jan-Mar;46(1):26-32. Epub 2021 May 5.

Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Mumbai, Maharashtra, India.

Background And Aim: Modern radiotherapy modalities, such as Intensity-Modulated Radiotherapy and Volumetric Modulated Arc Therapy involve complex dose delivery. The dose delivery is complex as it involves beam modulation, hence, manual dose calculations for these techniques are not possible. Film dosimetry is commonly used method of dose verification for these modalities because of the advantages associated with it. The quantification of uncertainty associated with a film dosimetry system under clinical use becomes important for accurate dosimetry. The spread in the distribution of the pixel values (PV) of the irradiated film contributes to the uncertainty. The probability distribution (PD) of the PV was studied for the clinical photon beam energies of 6, 10, and 15 MV.

Methods And Materials: Gafchromic EBT3 film and EPSON 10000XL flatbed scanner were used for this purpose and using the resulting PD, the uncertainty budgets for these energies in the red, green and blue color channels were estimated.

Results: The PV of exposed films for the energies studied follows t-distribution, the sum of the squares of the deviation of the measured data from the fitted value was of the order of 10, this indicates the goodness of fit. The "" value corrected combined standard uncertainty (CSU) at 1σ confidence level for exposed film and dose measurement at 200 cGy were 1.42%, 1.48%, and 1.63% and 1.99%, 3.23%, and 5.08% for 6, 10, and 15 MV energies, respectively, in the red colour channel.

Conclusion: In the case of the limited number of measurements of a quantity, the SU values must be corrected using the "t" value to get the correct CSU.
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http://dx.doi.org/10.4103/jmp.JMP_94_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240913PMC
May 2021

Global warming potential and energy dynamics of conservation tillage practices for different rabi crops in the Indo-Gangetic Plains.

J Environ Manage 2021 Oct 3;296:113182. Epub 2021 Jul 3.

Division of Environment Science, NRL Building, Indian Agricultural Research Institute, New Delhi, 110 012, India. Electronic address:

A field experiment was conducted during 2007-2019 under various rabi (winter) crops (viz., wheat, maize, barley and mustard) on a Vertisol in sub-tropical Indo-Gangetic Plains (IGP) with different tillage systems to assess energy indices, greenhouse gas (GHG) emission and carbon sustainability index in assured irrigated fields. The tillage systems were: no tillage sown by a zero till drill (NT), no tillage with retention of previous crop residues at 6 t ha and sowing by a happy turbo seeder (HT), and conventional tillage (CT) where sowing was performed by a multi-crop zero till drill after twice harrowing + twice tilling + once rotavator operations. Significantly higher input energy was observed in wheat followed by maize, barley and mustard. Among tillage systems, CT plots consumed higher input energy that was about 20, 21 to 22, 25 to 26 and 20-22% higher than HT and NT in wheat, maize, barley and mustard, respectively. However, output energy and energy use efficiency were highest in HT. The total GHG emission (kg CO equivalent ha) was highest in wheat (2,351) followed by maize (2,274), barley (1,859) and mustard (1,652). Among tillage systems, CT produced about 31-34%, 33-34%, 37-40% and 28-30% higher GHG emission than HT and NT under wheat, maize, barley and mustard, respectively. The CT plots had lower carbon sustainability index and carbon efficiency than ZT and HT in all crops. In short, HT recorded significantly higher energy use efficiency and lower global warming potential (GWP) than CT in all crops. Thus, HT could be a promising agro-technique for production of rabi crops in the IGP. Among rabi crops, barley production was energy efficient and had less GWP. In rabi crop production, the highest energy sources was mineral fertilizer use (25-49%) and second highest source was irrigation water (14-44%). These can be substituted with use of the organic sources of fertilizers and application of solar and wind power in irrigation, respectively.
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http://dx.doi.org/10.1016/j.jenvman.2021.113182DOI Listing
October 2021

Macrovascular Thrombotic Events in a Mayo Clinic Enterprise-Wide Sample of Hospitalized COVID-19-Positive Compared With COVID-19-Negative Patients.

Mayo Clin Proc 2021 07 4;96(7):1718-1726. Epub 2021 May 4.

Division of Hematology/Oncology, Mayo Clinic, Rochester, MN; Division of Vascular Medicine, Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN.

Objective: To determine the difference in the rate of thromboembolic complications between hospitalized coronavirus disease 2019 (COVID-19)-positive compared with COVID-19-negative patients.

Patients And Methods: Adult patients hospitalized from January 1, 2020, through May 8, 2020, who had COVID-19 testing by polymerase chain reaction assay were identified through electronic health records across multiple hospitals in the Mayo Clinic enterprise. Thrombotic outcomes (venous and arterial) were identified from the hospital problem list.

Results: We identified 3790 hospitalized patients with COVID-19 testing across 19 hospitals, 102 of whom had positive test results. The median age was lower in the COVID-positive patients (62 vs 67 years; P=.03). The median duration of hospitalization was longer in COVID-positive patients (8.5 vs 4 days; P<.001) and more required intensive care unit care (56.9% [58 of 102] vs 26.8% [987 of 3688]; P<.001). Comorbidities, including atrial fibrillation/flutter, heart failure, chronic kidney disease, and malignancy, were observed less frequently with COVID-positive admissions. Any venous thromboembolism was identified in 2.9% of COVID-positive patients (3 of 102) and 4.6% of COVID-negative patients (168 of 3688). The frequency of venous and arterial events was not different between the groups. The unadjusted odds ratio (OR) for COVID-positive-patients for any venous thromboembolism was 0.63 (95% CI, 0.19 to 2.02). A multivariable logistic regression model evaluated death within 30 days of hospital discharge; neither COVID positivity (adjusted OR, 1.12; 95% CI, 0.54 to 2.34) nor thromboembolism (adjusted OR, 0.90; 95% CI, 0.60 to 1.32) was associated with death.

Conclusion: Early experience in patients with COVID-19 across multiple academic and regional hospitals representing different US regions demonstrates a lower than previously reported incidence of thrombotic events. This incidence was not higher than a contemporary COVID-negative hospitalized comparator.
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http://dx.doi.org/10.1016/j.mayocp.2021.04.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096191PMC
July 2021

COVID-19 and clinic workflow optimization using lean six sigma.

Am J Manag Care 2021 06;27(6):225-226

Mayo Clinic, 200 First St SW, Rochester, MN 55905. Email:

Objectives: The COVID-19 pandemic has fundamentally changed the workflow of clinics. We applied Lean Six Sigma processes to optimize clinic workflow to reduce patient wait times and improve the patient experience.

Study Design: Prospective cohort study.

Methods: We implemented (1) pushing most extended wait times to the end of the workflow by rooming the patient directly and (2) using distractions during the waiting process by using educational videos and a timer for physician arrival in the patient exam room. We compared the patient wait times and subcomponents of Press Ganey scores as a surrogate for changes in patient experience and satisfaction from the preimplementation period (n = 277) to the 3-month (September 1, 2020, to November 30, 2020) postimplementation period (n = 218).

Results: There was a significant reduction in overall throughput time (38 vs 35 minutes) and wait before rooming (11 vs 8 minutes), and increased physician time with patients (15 vs 17 minutes) (P < .0001 for all). These results corresponded with a significant improvement in Press Ganey subcomponents of (1) waiting time in the exam room before being seen by the care provider, (2) degree to which you were informed about any delays, (3) wait time at clinic (from arriving to leaving), and (4) length of wait before going to an exam room (P < .001 for all).

Conclusions: Simple, inexpensive measures can improve patient engagement and provide a safe setting for patients for clinic visits in the wake of COVID-19. In the future, clinics' common wait areas could be reappropriated to increase the number of clinic exam rooms.
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http://dx.doi.org/10.37765/ajmc.2021.88661DOI Listing
June 2021

Naltrexone Initiation in the Inpatient Setting for Alcohol Use Disorder: A Systematic Review of Clinical Outcomes.

Mayo Clin Proc Innov Qual Outcomes 2021 Apr 8;5(2):495-501. Epub 2021 Apr 8.

Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.

Alcohol use disorder (AUD) is a highly prevalent health issue in the United States. The number of those receiving medication-assisted treatment (MAT) is limited, despite strong evidence for their effectiveness. The inpatient setting may represent an important opportunity to initiate MAT. The goal of this study was to summarize the data on initiation in the emergency department or inpatient setting for the management of AUDs. We searched ClinicalTrials.gov, Ovid EBM Reviews, Ovid Embase, Ovid Medline, Ovid PsycINFO, Scopus, and Web of Science from inception through October 31, 2019. Search strategies were created using a combination of keywords (Supplemental Appendix 1, available online at http://www.mcpiqojournal.org) and standardized index terms related to naltrexone therapy for medically hospitalized patients with AUD. Two uncontrolled pre-post study designs evaluated naltrexone prescription rates, 30-day readmission rates, and rehospitalization rates. Two authors independently abstracted data on study characteristics, results, and study-level risk of bias. The research team collaborated to assess the strength of evidence across studies. Two studies reported that implementing a protocol for naltrexone initiation increased MAT rates, with one study noting a substantial decrease in 30-day hospital readmissions. Overall, we found that there is a paucity of data on naltrexone initiation in the inpatient setting for AUDs. This likely reflects the nature of current clinical practice and prescriber comfortability. There is a need for further studies evaluating MAT initiation in the inpatient setting. Furthermore, efforts to increase provider knowledge of these therapeutic options are in need of further exploration.
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http://dx.doi.org/10.1016/j.mayocpiqo.2021.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105524PMC
April 2021

Preventing Atrial Fibrillation in Patients After Coronary Artery Bypass Grafting: A Role of Posterior Pericardiotomy-ELECTRAM Investigators.

Am J Ther 2021 Apr 7. Epub 2021 Apr 7.

Division of Cardiology, University of Pittsburgh Medical Centre Heart and Vascular Institute, Pittsburgh, PA Department of Medicine, Mayo Clinic School of Medicine, Rochester, MN Department of Medicine, Brookdale University Hospital Medical Center, New York, NY Department of Cardiology, Helmsley Electrophysiology CenterIcahn School of Medicine at Mount Sinai, New York, NY Division of Cardiology, Cardiac Arrhythmia Service, Kansas City Heart Rhythm Institute and Research Foundation, Kansas City, KS Division of Cardiology, Cardiac Arrhythmia Service, Medical College of Wisconsin, Milwaukee, WI.

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http://dx.doi.org/10.1097/MJT.0000000000001352DOI Listing
April 2021

Improving Outcomes in Cardiovascular Diseases: A Review on Vorapaxar.

Cardiol Rev 2021 Mar 19. Epub 2021 Mar 19.

Mayo Clinic, Rochester, MN Division of Cardiology, University of Pittsburgh Medical Centre Heart and Vascular Institute, Pittsburgh, PA Garden City Hospital, Garden City, MI Sinai Hospital of Baltimore, Baltimore, MD Johns Hopkins University School of Medicine, Baltimore, MD.

Antiplatelet agents are the standard of practice in the management of atherosclerosis and acute coronary syndrome (ACS). In contrast to the available antiplatelet agents, vorapaxar represents a novel mechanism of action. It is an antagonist of the platelet protease-activated receptor-1 (PAR-1) and inhibits thrombin-induced and thrombin receptor agonist peptide (TRAP)- induced platelet aggregation. The TRA2○P-TIMI 50 trial led to the approval of vorapaxar by the Food and Drug Administration and European Medicines Agency for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or peripheral arterial disease. TRA2○P-TIMI 50 trial showed that the use of vorapaxar (2.5 mg once/daily) in addition to standard dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor, was effective in the secondary prevention of recurrent thrombotic events among patients with previous atherothrombosis, particularly in patients with prior MI; at the expense of an increase in major bleeding. Another recently published VORA-PRATIC (Vorapaxar in Patients with Prior Myocardial Infarction Treated with prasugrel and ticagrelor) study showed that among post-MI patients treated with potent P2Y12 inhibitors (prasugrel or ticagrelor), vorapaxar reduced platelet-driven global thrombogenicity, an effect that persisted, albeit attenuated, in the absence of aspirin. The current review summarizes an up to date literature on pharmacokinetics, pharmacodynamics, and clinical efficacy of vorapaxar and proposes future directions of research.
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http://dx.doi.org/10.1097/CRD.0000000000000390DOI Listing
March 2021

Computation of epistemic uncertainty due to limited data samples in small field dosimetry using Fuzzy Set Theory.

Br J Radiol 2021 May 18;94(1121):20190561. Epub 2021 Mar 18.

Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Mumbai, India.

Objective: To estimate the epistemic (or fuzzy) uncertainty, arising due to limited data samples in the measurement of the output factors (OFs) of the small fields using Fuzzy Set Theory (FST).

Methods: EBT3 film samples of size 50 × 50 mm were used for the measurement of the OF of stereotactic radiosurgery (SRS) cones of size 4, 6, 7.5, 10, 12.5 and 15 mm diameter, normalized with respect to the output of 100 × 100 mm open field size. Three measurements were done per cone/field size. Red color channel was chosen for the dosimetry purpose, net optical density (NOD) was converted to the dose using non-linear relation. To estimate the epistemic uncertainty associated with the measured OFs due to limited number of data samples, a triangular fuzzy number (TFN) was assumed as the fuzziness in the dose delivered by the individual SRS cone/field. Uncertainty in the OF was estimated by applying the Fuzzy Vertex Method (FVM). The membership functions of the OF were constructed for each cone size and the nature of the uncertainty in the OF of the cones was expressed in the terms of its fuzziness. For the sake of completeness of the study, the statistical uncertainty involved in the procedure has also been calculated.

Results: The statistical and fuzzy uncertainties in the measurement of OF of cones range from 3.28 to 6.25% and 2.58 to 5.44% respectively. The smallest cone of 4 mm has the largest values of statistical and fuzzy uncertainties. The membership functions of the OF for the studied cones were triangular in nature.

Conclusion: The epistemic uncertainty arising due to limited number of data samples holds a significant fraction of the prescribed dose, and therefore, should not be ignored in the total uncertainty estimation.

Advances In Knowledge: This study highlights the significance of epistemic component of measurement uncertainty arising out due to the insufficient/limited number of measurements of a quantity.
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http://dx.doi.org/10.1259/bjr.20190561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506178PMC
May 2021

Resectional surgery in gallbladder cancer with jaundice-how to improve the outcome?

Langenbecks Arch Surg 2021 May 22;406(3):791-800. Epub 2021 Feb 22.

Department of Surgery, Institute of Gastroenterology, Tokyo Womens' Medical University Hospital, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.

Purpose: To evaluate the surgical outcomes of patients with gallbladder cancer (GBC) with jaundice due to as-yet unelucidated prognostic factors.

Methods: A total of 348 GBC patients underwent resection at our institute between 1985 and 2016. Of these, 67 had jaundice (serum total bilirubin ≥ 2 mg/dL). Preoperative biliary drainage was performed, with portal vein embolization as required. All patients underwent radical surgery. We retrospectively evaluated the outcomes, performed multivariate analysis for overall survival, and compared our findings to those reported in the literature.

Results: The 5-year survival rate of M0 (no distant metastasis) GBC patients with jaundice, who underwent resectional surgery, was 21.9%, versus 68.3% in those without jaundice (p < 0.05). Since 2000, surgical mortality in GBC patients with jaundice has decreased from 12 to 6.8%. Patients with jaundice had more advanced disease and underwent major hepatectomies and vascular resections; however, preoperative jaundice alone was not a prognostic factor. Multivariate analysis of jaundiced patients revealed that percutaneous biliary drainage (PTBD) (vis-à-vis endoscopic drainage [EBD], hazard ratio [HR] 2.82), postoperative morbidity (Clavien-Dindo classification ≥ 3, HR 2.31), and distant metastasis (HR 1.85) were predictors of poor long-term survival. The 5-year survival and peritoneal recurrence rates in M0 patients with jaundice were 16% and 44%, respectively, for patients with PTBD and 39% (p < 0.05) and 13% (p = 0.07) for those with EBD.

Conclusion: M0 GBC patients with jaundice should undergo surgery if R0 resection is possible. Preoperative EBD may be superior to PTBD in M0 GBC patients with jaundice, although further studies are needed.
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http://dx.doi.org/10.1007/s00423-020-02075-8DOI Listing
May 2021

Thromboinflammatory Biomarkers in COVID-19: Systematic Review and Meta-analysis of 17,052 Patients.

Mayo Clin Proc Innov Qual Outcomes 2021 Apr 8;5(2):388-402. Epub 2021 Feb 8.

Division of Vascular Medicine, Mayo Clinic, Rochester, MN.

Objective: To evaluate differences in thromboinflammatory biomarkers between patients with severe coronavirus disease 2019 (COVID-19) infection/death and mild infection.

Patients And Methods: MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, EBSCO, Web of Science, and CINAHL databases were searched for studies comparing thromboinflammatory biomarkers in COVID-19 among patients with severe COVID-19 disease or death (severe/nonsurvivors) and those with nonsevere disease or survivors (nonsevere/survivors) from January 1, 2020, through July 11, 2020. Inclusion criteria were (1) hospitalized patients 18 years or older comparing severe/nonsurvivors vs nonsevere/survivors and (2) biomarkers of inflammation and/or thrombosis. A random-effects model was used to estimate the weighted mean difference (WMD) between the 2 groups of COVID-19 severity.

Results: We included 75 studies with 17,052 patients. The severe/nonsurvivor group was older, had a greater proportion of men, and had a higher prevalence of hypertension, diabetes, cardiac or cerebrovascular disease, chronic kidney disease, malignancy, and chronic obstructive pulmonary disease. Thromboinflammatory biomarkers were significantly higher in patients with severe disease, including D-dimer (WMD, 0.60; 95% CI, 0.49 to 0.71; =83.85%), fibrinogen (WMD, 0.42; 95% CI, 0.18 to 0.67; =61.88%; <.001), C-reactive protein (CRP) (WMD, 35.74; 95% CI, 30.16 to 41.31; =85.27%), high-sensitivity CRP (WMD, 62.68; 95% CI, 45.27 to 80.09; =0%), interleukin 6 (WMD, 22.81; 95% CI, 17.90 to 27.72; =90.42%), and ferritin (WMD, 506.15; 95% CI, 356.24 to 656.06; =52.02%). Moderate to significant heterogeneity was observed for all parameters ( > 25%). Subanalysis based on disease severity, mortality, and geographic region of the studies revealed similar inferences.

Conclusion: Thromboinflammatory biomarkers (D-dimer, fibrinogen, CRP, high-sensitivity CRP, ferritin, and interleukin 6) and marker of end-organ damage (high-sensitivity troponin I) are associated with increased severity and mortality in COVID-19 infection.
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http://dx.doi.org/10.1016/j.mayocpiqo.2021.01.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869679PMC
April 2021

Spiritual Care of Inpatients Focusing on Outcomes and the Role of Chaplaincy Services: A Systematic Review.

J Relig Health 2021 Apr 11;60(2):1406-1422. Epub 2021 Feb 11.

Mayo Clinic, 200 1st St SW, Rochester, MN, 55902, USA.

Objective: To identify demographic trends associated with patient utilization and healthcare provider request for spiritual care services and to describe the impact of spiritual care on the quality of life (QoL), spiritual well-being (SWB) and level of satisfaction (SAT) of hospitalized patients.

Patients And Methods: A systematic search of Ovid MEDLINE, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Scopus, was combined with review of relevant bibliographies. A total of 464 titles and abstracts were reviewed. Data were independently extracted by reviewers according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data on the effects of spiritual interventions on QoL, SWB and SAT were extracted, along with demographic data reflecting chaplain services. The results of the studies are presented narratively and in a qualitative manner.

Results: Observational or experimental studies investigating chaplain utilization demographics (n = 12), patient satisfaction (n = 9) and QoL/SWB (n = 3) were included. Perceived severity of illness, average length of stay and older age were consistently found to be predictors of higher need for spiritual care. Receipt of spiritual care was correlated with increased patient and family satisfaction, independent of clinical outcome. Chaplain interventions were associated with improvement in perceived QoL and SWB. In spite of this, healthcare workers rarely attempt to explore the patient's or family's need for spiritual care, with the majority of chaplaincy consults occurring in the final day of the patient's life, potentially leading to a failure to meet the spiritual needs of non-terminal patients who have spiritual trauma related to their resolving illnesses.

Conclusion: Attention to the spiritual needs of hospitalized patients is an essential yet often overlooked aspect of patient care. Chaplains serve as spiritual care specialists whose services can enhance the hospital experience, improve patient satisfaction and help to bridge potential gaps between the patient and medical providers.
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http://dx.doi.org/10.1007/s10943-021-01191-zDOI Listing
April 2021

Determinants of regeneration and strength of hamstrings after anterior cruciate ligament reconstruction-fate of hamstring tendon.

Int Orthop 2021 07 6;45(7):1751-1760. Epub 2021 Jan 6.

Department of Orthopaedic Surgery, Datta Meghe Institute of Medical Sciences and Jawaharlal Nehru Medical College, Wardha, 442001, India.

Background And Aim: Arthroscopic reconstruction of anterior cruciate ligament (ACL) surgical procedure using hamstring autograft is the most common surgery performed in the arena of sports medicine and arthroscopy. Most studies in literature are ambiguous regarding the fate of hamstrings based on function, regenerative potential, and cross-sectional area (CSA). The aim of this research study is analysis of the fate of hamstring tendons (both semitendinosus and gracilis) during the time course for determinants of regeneration and strength.

Methods: Fifty patients who were operated for unilateral isolated ACL reconstruction from July 2015 to June 2018 were evaluated for the fate of harvested hamstring tendons which included the following: regeneration, cross-sectional area (CSA), strength, and insertion of regenerated hamstrings by isometric torque and isokinetic strength. MRI of knee was performed for both knees concerning the semitendinosus (ST), gracilis (G), Sartorius, biceps femoris, and medial head of gastrocnemius.

Results: Eighty-four percent men and 16% women within a mean patient age of 34 ± 4.12 years were evaluated and all 50 (100%) patients demonstrated hamstring regeneration by the MRI measurements at six months and at one year post-ACL reconstruction. The torque of isometric knee flexion measured in 60° was found to be remarkably lower in the ACL-reconstructed lower extremity compared to that of the contralateral limb (87.13 ± 20.18% of BW), at 90° (49.17 ± 15.09% BW), and at 105° (43.91 ± 13.17% BW), respectively (p < 0.01). However, at 30° flexion and 45° flexion, the difference was insignificant (116.48 ± 21.07% BW for 30° and 100.16 ± 25.12% BW for 45°).

Conclusions: It was found that the properties of musculotendinous units of ST and G were significantly transformed after their harvesting for ACL reconstruction and these weaknesses contribute to the flexion deficit of knee in the deeper range of flexion in the operated limb. Therefore, approaches facilitating tendon regeneration and preservation must be warranted.
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http://dx.doi.org/10.1007/s00264-020-04932-zDOI Listing
July 2021

Effect of serum zinc and copper levels on insulin secretion, insulin resistance and pancreatic β cell dysfunction in US adults: Findings from the National Health and Nutrition Examination Survey (NHANES) 2011-2012.

Diabetes Res Clin Pract 2021 Feb 15;172:108627. Epub 2020 Dec 15.

Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA.

Aim: To compare zinc (Zn) and copper (Cu) levels in US adults with normoglycemia, prediabetes and diabetes, and study the association of serum Zn and Cu levels with pancreatic β cell insulin secretion, pancreatic dysfunction and insulin resistance in US adults with normoglycemia and prediabetes.

Method: Homeostatic Model Assessment (HOMA2) calculator was used to compute estimates of steady state β cell insulin secretion (HOMA2-B), peripheral insulin sensitivity (HOMA2-S), insulin resistance (HOMA-IR), and disposition index (HOMA-DI) in 804 adult individuals from the National Health and Nutrition Examination Survey (NHANES 2011-2012).

Results: There was no significant difference between serum Zn and Cu levels among subjects with normoglycemia, prediabetes, and diabetes. After adjusting for multiple possible confounders, higher serum Zn concentrations were associated with lower β cell insulin secretion (HOMA2-B; p = 0.01) and lower insulin resistance (HOMA-IR; p = 0.04) in the prediabetic subjects. In normoglycemic group, higher serum Zn levels were associated with improved pancreatic function (HOMA-DI; P = 0.02). On the other hand, higher serum Cu levels were associated with increased β cell insulin secretion (HOMA2-B, P = 0.03) only in the subjects with prediabetes.

Conclusion: These findings support the need for further studies to investigate the role of trace elements in diabetes pathogenesis.
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http://dx.doi.org/10.1016/j.diabres.2020.108627DOI Listing
February 2021

Race-Related disparities in COVID-19 thrombotic outcomes: Beyond social and economic explanations.

EClinicalMedicine 2020 Dec 20;29:100647. Epub 2020 Nov 20.

Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Baltimore, MD, United States.

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http://dx.doi.org/10.1016/j.eclinm.2020.100647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678450PMC
December 2020

Telemetry: appropriateness of initial assignment and duration in nonintensive setting.

Am J Manag Care 2020 11;26(11):459-460

Mayo Clinic, 200 First St SW, Rochester, MN 55905. Email:

Objectives: Inappropriate use of telemetry monitoring is associated with alarm fatigue, an increase in health care expenditures, and the potential for patient harm from interventions in clinically inconsequential arrhythmias. We explored adherence to current guidelines for appropriateness of (1) initial telemetry assignment and (2) duration of the assignment.

Study Design: Retrospective study.

Methods: After institutional review board approval, 695 consecutive adult patients (≥ 18 years) who were admitted with any diagnosis to general medical floors and assigned telemetry at the time of admission over 3 months were enrolled. Patients on surgical service and transferred from critical care were excluded. Data were collected from electronic health records (EHRs).

Results: We observed that 155 of 695 (22.3%) patients had been inappropriately assigned telemetry at the time of initial assignment. Of the 540 patients appropriately assigned telemetry, 56.3% of patients had longer than the recommended duration of telemetry monitoring with a median (interquartile range) of 3 (2-4) nonindicated days per patient. The annualized additional cost of telemetry monitoring due to the inefficient utilization was found to be more than $500,000 per year.

Conclusions: Our data further support the need for frequent reassessment of telemetry indication, which can be facilitated by the utilization of EHR-based automated monitoring.
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http://dx.doi.org/10.37765/ajmc.2020.88524DOI Listing
November 2020

Heart Failure Trial Update-Analysis of Recent Data.

J Cardiothorac Vasc Anesth 2021 09 7;35(9):2792-2800. Epub 2020 Sep 7.

Division of Cardiovascular and Thoracic Anesthesiology, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN. Electronic address:

The prevalence of heart failure (HF) continues to increase, and its economic effect is significant in the United States and globally. During the past 2 years, a number of high-quality clinical trials were published with the aim of addressing different stages of the disease process and improving outcomes for patients with preserved and depressed ejection fraction (EF). In this review, data from these trials are summarized and critically appraised. There are several important findings from these studies, including, but not limited to, the benefit of dapagliflozin in HF with reduced EF, sacubitril-valsartan in acute decompensated HF, thoracotomy in left ventricular assist device implantation, and the overall risk-benefit ratios of centrifugal pumps as opposed to continuous flow pumps. Effective therapies for HF with preserved EF continue to evolve for this varied group of high morbidity and mortality conditions.
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http://dx.doi.org/10.1053/j.jvca.2020.09.085DOI Listing
September 2021

First In-Human Experience With Inhaled Acetylsalicylic Acid for Immediate Platelet Inhibition: Comparison With Chewed and Swallowed Acetylsalicylic Acid.

Circulation 2020 09 28;142(13):1305-1307. Epub 2020 Sep 28.

Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, MD (P.A.G., K.P.B., U.S.T.).

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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.047477DOI Listing
September 2020

Carotid access for transcatheter aortic valve replacement: A meta-analysis.

Catheter Cardiovasc Interv 2021 03 5;97(4):723-733. Epub 2020 Sep 5.

Department of Cardiology, Garden City Hospital, Garden City, Michigan, USA.

Objective: We sought to evaluate the feasibility and safety of carotid access transcatheter aortic valve replacement (TAVR) by performing a meta-analysis of published cases.

Background: Several case series and regional data have provided initial basis for carotid access TAVR in patients with prohibitive femoral approach. We performed this meta-analysis to provide further evidence of feasibility and safety of carotid TAVR.

Methods: We searched PubMed, EMBASE, CINAHL, and Cochrane CENTRAL for any study on carotid access TAVR involving ⩾5 patients since inception till March 1, 2020. Random-effects model was used to compute overall effects. The outcomes analyzed were all-cause mortality, Transient ischemic attack (TIA)/stroke, need for permanent pacemaker (PPM) implantation, pericardial tamponade, access site complications, major bleeding, and length of stay.

Results: There was a total of 17 retrospective studies (n = 2082) with a median follow-up of 1 month. Mean age of the patient was 80 years. Mean Euroscore and STS scores were 15 ± 6.2 and 7.9 ± 3.3, respectively. The procedural success rate was 99%. The rate of all-cause mortality was 6.7% (range 4.6-9.7%, p < .001, I = 67%). Incidence of TIA/stroke was 3.9% (range 3.1-4.8%, p < .001, I = 0%) and PPM implantation was 16.7% (range 12.5-21.9%, p < .001, I = 56%). Rate of pericardial tamponade, vascular complication, and major bleeding were 1.7, 2.5, and 7%, respectively. Average length of hospital stay was 7.7 days.

Conclusion: Our results show that transcarotid approach is a feasible option in patients with prohibitive femoral access for TAVR.
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http://dx.doi.org/10.1002/ccd.29244DOI Listing
March 2021

Viscoelastic properties of clot formation and their clinical impact in East Asian versus Caucasian patients with stable coronary artery disease: a COMPARE-RACE analysis.

J Thromb Thrombolysis 2021 Feb;51(2):454-465

Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Baltimore, MD, 21215, USA.

Compared with Caucasian patients, East Asian patients with coronary artery disease (CAD) have demonstrated better clinical outcomes. We sought to compare the viscoelastic properties of clot formation and their impact on clinical outcomes in East Asian vs. Caucasian patients. We analyzed age- and sex-matched East Asian and Caucasian patients with stable CAD (n = 249 each). Viscoelastic properties of clot formation were assessed with thromboelastography (TEG), and 3-year clinical outcomes were recorded. Major adverse cardiovascular events (MACE) were defined as a composite of cardiovascular death, myocardial infarction, or stroke. Compared with Caucasians, East Asians showed lower platelet-fibrin clot strength (PFCS) (maximum amplitude [MA]: 61.8 ± 7.9 vs. 65.4 ± 5.0 mm, p < 0.001). In a multivariate analysis, high PFCS (defined as MA ≥ 68 mm) was significantly associated with MACE occurrence (odds ratio 6.27, 95% CI 2.41 to 16.30, p < 0.001). East Asians vs. Caucasians had lower prevalence of high PFCS (odds ratio 0.50, 95% CI 0.27 to 0.93, p = 0.028). In conclusion, this is the first study to demonstrate different viscoelastic properties of clot between East Asian and Caucasian patients with stable CAD. The platelet-fibrin clot strength was significantly associated with MACE in these patients and was significantly lower in East Asians. Future studies are warranted to further explore the mechanistic explanation and clinical importance of these findings.
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http://dx.doi.org/10.1007/s11239-020-02240-2DOI Listing
February 2021

Personalizing Antithrombotic Therapy in COVID-19: Role of Thromboelastography and Thromboelastometry.

Thromb Haemost 2020 11 17;120(11):1594-1596. Epub 2020 Jul 17.

Sinai Center of Thrombosis Research, Sinai Hospital of Baltimore, Baltimore, Maryland, United States.

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http://dx.doi.org/10.1055/s-0040-1714217DOI Listing
November 2020

Detailed thrombogenicity phenotyping and 1 year outcomes in patients undergoing WATCHMAN implantation: (TARGET-WATCHMAN) a case-control study.

J Thromb Thrombolysis 2020 Oct;50(3):484-498

Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Baltimore, MD, USA.

The relation of device related thrombosis (DRT) and major bleeding after left atrial appendage closure (LAAC) to laboratory thrombosis and hemostasis markers has not been studied. We performed a prospective case control study to identify clinical characteristics and laboratory markers in patients who developed DRT and major bleeding following WATCHMAN LAAC. Thromboelastography, platelet aggregation (PA), urinary 11-dehydrothromboxane B (UTX), fibrinogen, D-dimer, thrombin time and von Willebrand factor activity were determined at baseline, immediately following, and at 45 and 180 days post-LAAC (n = 32) and outcomes were followed for 1 year. Baseline characteristics and thrombogenic profiles of patients with and without DRT and/or BARC bleeding were compared. Mean age was 76 ± 8 years and CHADS2 VASc score was 4.4 ± 1.4. There were 3 DRTs (2 within 6 months, and 1 at 12 months), 4 Type 3A BARC bleeds, and 2 non-cardiac deaths. Patients with DRT had higher baseline thrombin-induced platelet-fibrin clot strength (68.0 ± 1.8 vs. 62.7 ± 4.7 mm, p = 0.06); FCS (35.6 ± 6.0 vs. 24.4 ± 6.6 mm, p = 0.009); and D-dimer (1712 ± 2330 vs. 283 ± 213 ng/mL, p = 0.001). At baseline, 5 patients had all 3 factors associated with high thrombotic risk and 2 experienced a DRT within 6 months. Patients with Type 3A BARC bleeding had lower baseline collagen-induced and 45-day ADP-induced PA (p < 0.01 for both). DRT following LAAC was associated with a baseline prothrombogenic profile whereas bleeding was associated with low platelet reactivity. These preliminary findings warrant further validation and have future implications on patient selection and adjunctive antithrombotic therapy following LAAC.Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03040622 .
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http://dx.doi.org/10.1007/s11239-020-02205-5DOI Listing
October 2020

Investigation on protective effect of Terminalia bellirica (Roxb.) against drugs induced cardiotoxicity in wistar albino rats.

J Ethnopharmacol 2020 Oct 10;261:113080. Epub 2020 Jun 10.

I.T.S College of Pharmacy, Delhi-Meerut Road, Murad Nagar, Ghaziabad, Uttar Pradesh, 201206, India.

Ethnopharmacological Relevance: Various traditional texts like Ayurveda and Materia Medica profoundly mentioned the ethnopharmacological use of Terminalia bellirica fruit for its protective effect on heart and various other vital organs. Hence the present research was focussed to scientifically prove the effect of T. bellirica in support of its traditionally claimed use as cardioprotective agent.

Aim The Study: The aim and objective of the present study was to investigate the protective effect of T. bellirica (Roxb.) against drugs viz. Doxorubicin (DOX) and Isoproterenol (ISO) induced cardiotoxicity in wistar albino rats.

Material And Methods: Cardiotoxicity was induced using DOX (15 mg/kg, i.p.) and ISO (85 mg/kg s.c.) models. Methanolic extract of T. bellirica (METB) was subjected to rats in two different doses (low dose of 250 mg/kg p.o.; and high dose of 500 mg/kg p.o.) for the purpose of investigation of various biochemical markers present in cardiac tissue as well as in blood serum, in order to assess the improvement in drugs induced cardiotoxicity. Also, the histopathological study was carried out in terms of ultrastructural changes occurred in the myocardium during drugs induced cardiomyopathy, to ensure the proposed cardioprotective effect of METB.

Result: Biochemical investigation of cardiac tissue using METB showed significant decrease in CK-MB (creatine kinase-muscle/brain) activity and MDA (malondialdehyde) levels and increase in GSH (reduced glutathione) levels. It also increased the activity of SOD (superoxide dismutase) and CAT (catalase). In serum, METB increased the levels of oxidative stress markers like ALP (alkaline phosphatase), UA (uric acid), ALT (alanine transferase), and AST (aspartate transaminase) near to their normal values as in control group. The use of METB also decreased the levels of total cholesterol and TGs (triglycerides) in serum and significantly increased HDL (high density lipoprotein) levels. Treatment with METB also proved a considerable restoration in histopathological findings of myocardium.

Conclusion: In the present study it was concluded that T. bellirica fruit has profound potential for the treatment of drugs induced cardiotoxicity suggesting the consumption of T. bellirica for cardiac benefits during routine treatment of cardiotoxicity.
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http://dx.doi.org/10.1016/j.jep.2020.113080DOI Listing
October 2020

Rivaroxaban-induced hemorrhagic pericardial tamponade in end-stage renal disease.

J Thromb Thrombolysis 2020 Nov;50(4):982-983

Mayo Clinic, Rochester, MN, USA.

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http://dx.doi.org/10.1007/s11239-020-02164-xDOI Listing
November 2020

DOACs Versus VKAs in Older Adults Treated for Acute Venous Thromboembolism: Systematic Review and Meta-Analysis.

J Am Geriatr Soc 2020 09 22;68(9):2021-2026. Epub 2020 May 22.

Division of Vascular Medicine, Mayo Clinic, Rochester, Minnesota, USA.

Background/objectves: Four direct-acting oral anticoagulants (DOACs) are currently approved by the Food and Drug Administration for the treatment of venous thromboembolism (VTE). Limited efficacy and safety data are available for their use in older adults (aged ≥75 years).

Methods: Medline, Cochrane Central Register of Controlled Trials, Embase, EBSCO, Web of Science, and CINAHL databases were searched for trials comparing DOACs with vitamin K antagonists (VKAs) for the treatment of VTE in older adults from inception through January 1, 2020. Meta-analysis was performed to assess the combined endpoint of recurrent VTE and related deaths and bleeding events (composite of major and clinically relevant nonmajor bleeding). The Mantel-Haenszel relative risk (RR) random effects model was used to pool results across studies.

Results: Six randomized controlled trials at low risk of bias met criteria for inclusion with a total of 3,665 patients aged 75 years and older with follow-up of 24 weeks or longer. Data for bleeding events were not available for dabigatran. Overall, DOACs had an improved efficacy over VKAs (RR = .56; 95% confidence interval [CI] = .38-.82). There was no statistically significant difference in the safety outcomes (RR = .77; 95% CI = .56-1.05). No significant heterogeneity was observed for efficacy outcome, and only moderate heterogeneity was observed for safety outcome.

Conclusion: In older adults with VTE, DOACs appear to improve rates of recurrent VTE and VTE-related deaths compared with VKAs with similar bleeding outcomes.
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http://dx.doi.org/10.1111/jgs.16549DOI Listing
September 2020
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