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1. Safety of treating acute pulmonary embolism at home: an individual patient data meta-analysis.

Author

Luijten, Dieuwke, Douillet, Delphine, Luijken, Kim, Tromeur, Cecile, Penaloza, Andrea, Hugli, Olivier, Aujesky, Drahomir, Barco, Stefano, Bledsoe, Joseph, Chang, Kyle, Couturaud, Francis, den Exter, Paul, Font, Carme, Huisman, Menno, Jimenez, David, Kabrhel, Christopher, Kline, Jeffrey, Konstantinides, Stavros, van Mens, Thijs, Otero, Remedios, Peacock, W, Sanchez, Olivier, Stubblefield, William, Valerio, Luca, Vinson, David, Wells, Philip, van Smeden, Maarten, Roy, Pierre-Marie, and Klok, Frederikus

Subjects
Clinical decision-making, Early discharge, Emergency care, Outpatient care, Pulmonary embolism, Humans, Pulmonary Embolism, Acute Disease, Home Care Services, Hemorrhage, Male, Female, Anticoagulants, Randomized Controlled Trials as Topic, Prospective Studies, Aged, Natriuretic Peptide, Brain, Middle Aged
Abstract

BACKGROUND AND AIMS: Home treatment is considered safe in acute pulmonary embolism (PE) patients selected by a validated triage tool (e.g. simplified PE severity index score or Hestia rule), but there is uncertainty regarding the applicability in underrepresented subgroups. The aim was to evaluate the safety of home treatment by performing an individual patient-level data meta-analysis. METHODS: Ten prospective cohort studies or randomized controlled trials were identified in a systematic search, totalling 2694 PE patients treated at home (discharged within 24 h) and identified by a predefined triage tool. The 14- and 30-day incidences of all-cause mortality and adverse events (combined endpoint of recurrent venous thromboembolism, major bleeding, and/or all-cause mortality) were evaluated. The relative risk (RR) for 14- and 30-day mortalities and adverse events is calculated in subgroups using a random effects model. RESULTS: The 14- and 30-day mortalities were 0.11% [95% confidence interval (CI) 0.0-0.24, I2 = 0) and 0.30% (95% CI 0.09-0.51, I2 = 0). The 14- and 30-day incidences of adverse events were 0.56% (95% CI 0.28-0.84, I2 = 0) and 1.2% (95% CI 0.79-1.6, I2 = 0). Cancer was associated with increased 30-day mortality [RR 4.9; 95% prediction interval (PI) 2.7-9.1; I2 = 0]. Pre-existing cardiopulmonary disease, abnormal troponin, and abnormal (N-terminal pro-)B-type natriuretic peptide [(NT-pro)BNP] at presentation were associated with an increased incidence of 14-day adverse events [RR 3.5 (95% PI 1.5-7.9, I2 = 0), 2.5 (95% PI 1.3-4.9, I2 = 0), and 3.9 (95% PI 1.6-9.8, I2 = 0), respectively], but not mortality. At 30 days, cancer, abnormal troponin, and abnormal (NT-pro)BNP were associated with an increased incidence of adverse events [RR 2.7 (95% PI 1.4-5.2, I2 = 0), 2.9 (95% PI 1.5-5.7, I2 = 0), and 3.3 (95% PI 1.6-7.1, I2 = 0), respectively]. CONCLUSIONS: The incidence of adverse events in home-treated PE patients, selected by a validated triage tool, was very low. Patients with cancer had a three- to five-fold higher incidence of adverse events and death. Patients with increased troponin or (NT-pro)BNP had a three-fold higher risk of adverse events, driven by recurrent venous thromboembolism and bleeding.

Published
2024

4. Transcriptome-wide association study and Mendelian randomization in pancreatic cancer identifies susceptibility genes and causal relationships with type 2 diabetes and venous thromboembolism

Author

Lindstrom, Sara, Wang, Lu, Smith, Erin, Gordon, William, Van Hylckama Vlieg, Astrid, De Andrade, Mariza, Brody, Jennifer, Pattee, Jack, Haessler, Jeffrey, Brumpton, Ben, Chasman, Daniel, Suchon, Pierre, Chen, Ming-Huei, Turman, Constance, Germain, Marine, Wiggins, Kerri, MacDonald, James, Braekkan, Sigrid, Armasu, Sebastian, Pankratz, Nathan, Jackson, Rabecca, Nielsen, Jonas, Giulianini, Franco, Puurunen, Marja, Ibrahim, Manal, Heckbert, Susan, Bammler, Theo, Frazer, Kelly, McCauley, Bryan, Taylor, Kent, Pankow, James, Reiner, Alexander, Gabrielsen, Maiken, Deleuze, Jean-François, O'Donnell, Chris, Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John-Bjarne, Rosendaal, Frits, Heit, John, Psaty, Bruce, Tang, Weihong, Kooperberg, Charles, Hveem, Kristian, Ridker, Paul, Morange, Pierre-Emmanuel, Johnson, Andrew, Kabrhel, Christopher, Trégouët, David-Alexandre, Smith, Nicholas, Tan, Marcus C.B., Isom, Chelsea A., Liu, Yangzi, Wu, Lang, Zhou, Dan, and Gamazon, Eric R.

Published
2024
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5. Genome-wide investigation of exogenous female hormones, genetic variation, and venous thromboembolism risk

Author

Hasser, Emily K., Brody, Jennifer A., Bartz, Traci M., Thibord, Florian, Li-Gao, Ruifang, Kauko, Anni, Wiggins, Kerri L., Teder-Laving, Maris, Kim, Jihye, Munsch, Gaëlle, Haile, Helen G., Deleuze, Jean-Francois, van Hylckama Vlieg, Astrid, Wolberg, Alisa S., Boland, Anne, Morange, Pierre-Emmanuel, Kraft, Peter, Lowenstein, Charles J., Emmerich, Joseph, Sitlani, Colleen M., Suchon, Pierre, Rosendaal, Frits R., Niiranen, Teemu, Kabrhel, Christopher, Trégouët, David-Alexandre, and Smith, Nicholas L.

Published
2024
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7. A genetic association study of circulating coagulation factor VIII and von Willebrand factor levels

Author

Abe, Namiko, Abecasis, Gonçalo, Aguet, Francois, Albert, Christine, Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Ardlie, Kristin, Arking, Dan, Arnett, Donna K, Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Ayas, Najib, Balasubramanian, Adithya, Barnard, John, Barnes, Kathleen, Barr, R. Graham, Barron-Casella, Emily, Barwick, Lucas, Beaty, Terri, Beck, Gerald, Becker, Diane, Becker, Lewis, Beer, Rebecca, Beitelshees, Amber, Benjamin, Emelia, Benos, Takis, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Blue, Nathan, Boerwinkle, Eric, Bowden, Donald W., Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Brown, Deborah, Bunting, Karen, Burchard, Esteban, Bustamante, Carlos, Buth, Erin, Cade, Brian, Cardwell, Jonathan, Carey, Vincent, Carrier, Julie, Carson, April P., Carty, Cara, Casaburi, Richard, Casas Romero, Juan P, Casella, James, Castaldi, Peter, Chaffin, Mark, Chang, Christy, Chang, Yi-Cheng, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Ida Chen, Yii-Der, Cho, Michael, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Chung, Ren-Hua, Clish, Clary, Comhair, Suzy, Conomos, Matthew, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L. Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, de las Fuentes, Lisa, de Vries, Paul, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Dinh, Huyen, Doddapaneni, Harsha, Duan, Qing, Dugan-Perez, Shannon, Duggirala, Ravi, Durda, Jon Peter, Dutcher, Susan K., Eaton, Charles, Ekunwe, Lynette, El Boueiz, Adel, Ellinor, Patrick, Emery, Leslie, Erzurum, Serpil, Farber, Charles, Farek, Jesse, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Frazar, Chris, Fu, Mao, Fullerton, Stephanie M., Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Shanshan, Gao, Yan, Gass, Margery, Geiger, Heather, Gelb, Bruce, Geraci, Mark, Germer, Soren, Gerszten, Robert, Ghosh, Auyon, Gibbs, Richard, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Graw, Sharon, Gray, Kathryn J., Grine, Daniel, Gross, Colin, Gu, C. Charles, Guan, Yue, Guo, Xiuqing, Gupta, Namrata, Haessler, Jeff, Hall, Michael, Han, Yi, Hanly, Patrick, Harris, Daniel, Hawley, Nicola L., He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hobbs, Brian, Hokanson, John, Hong, Elliott, Hoth, Karin, Hsiung, Chao (Agnes), Hu, Jianhong, Hung, Yi-Jen, Huston, Haley, Hwu, Chii Min, Irvin, Marguerite Ryan, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Khan, Ziad, Kim, Wonji, Kimoff, John, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Kramer, Holly, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Jiwon, Lee, Sandra, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Dan, Lewis, Joshua, Li, Xiaohui, Li, Yun, Lin, Henry, Lin, Honghuang, Lin, Xihong, Liu, Simin, Liu, Yongmei, Liu, Yu, Loos, Ruth J. F., Lubitz, Steven, Lunetta, Kathryn, Luo, James, Magalang, Ulysses, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manning, Alisa, Manson, JoAnn, Martin, Lisa, Marton, Melissa, Mathai, Susan, Mathias, Rasika, May, Susanne, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, McGoldrick, Daniel, McHugh, Caitlin, McNeil, Becky, Mei, Hao, Meigs, James, Menon, Vipin, Mestroni, Luisa, Metcalf, Ginger, Meyers, Deborah A, Mignot, Emmanuel, Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L, Mitchell, Braxton D., Moll, Matt, Momin, Zeineen, Montasser, May E., Montgomery, Courtney, Muzny, Donna, Mychaleckyj, Josyf C, Nadkarni, Girish, Naik, Rakhi, Naseri, Take, Natarajan, Pradeep, Nekhai, Sergei, Nelson, Sarah C., Neltner, Bonnie, Nessner, Caitlin, Nickerson, Deborah, Nkechinyere, Osuji, North, Kari, O'Connell, Jeff, O'Connor, Tim, Ochs-Balcom, Heather, Okwuonu, Geoffrey, Pack, Allan, Paik, David T., Palmer, Nicholette, Pankow, James, Papanicolaou, George, Parker, Cora, Peloso, Gina, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Lawrence S, Pleiness, Jacob, Pollin, Toni, Post, Wendy, Becker, Julia Powers, Boorgula, Meher Preethi, Preuss, Michael, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Rajendran, Mahitha, Ramachandran, Vasan S., Rao, D. C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Reeves, Catherine, Regan, Elizabeth, Reiner, Alex, Reupena, Muagututi‘a Sefuiva, Rice, Ken, Rich, Stephen, Robillard, Rebecca, Robine, Nicolas, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Runnels, Alexi, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sabino, Ester Cerdeira, Saleheen, Danish, Salimi, Shabnam, Salvi, Sejal, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay G., Santibanez, Jireh, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Seidman, Jonathan, Sériès, Frédéric, Sheehan, Vivien, Sherman, Stephanie L., Shetty, Amol, Shetty, Aniket, Hui-Heng Sheu, Wayne, Shoemaker, M. Benjamin, Silver, Brian, Silverman, Edwin, Skomro, Robert, Smith, Albert Vernon, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Snyder, Michael, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne M., Storm, Garrett, Streeten, Elizabeth, Su, Jessica Lasky, Sung, Yun Ju, Sylvia, Jody, Szpiro, Adam, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent D., Taylor, Matthew, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Threlkeld, Machiko, Tinker, Lesley, Tirschwell, David, Tishkoff, Sarah, Tiwari, Hemant, Tong, Catherine, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, Van Den Berg, David, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wang, Fei Fei, Wang, Heming, Wang, Jiongming, Watson, Karol, Watt, Jennifer, Weeks, Daniel E., Weinstock, Joshua, Weir, Bruce, Weiss, Scott T, Weng, Lu-Chen, Wessel, Jennifer, Willer, Cristen, Williams, Kayleen, Williams, L. Keoki, Wilson, Carla, Wilson, James, Winterkorn, Lara, Wong, Quenna, Wu, Joseph, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yu, Ketian, Zekavat, Seyedeh Maryam, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zhu, Xiaofeng, Ziv, Elad, Zody, Michael, Zoellner, Sebastian, Lindstrom, Sara, Wang, Lu, Smith, Erin N., Gordon, William, van Hylckama Vlieg, Astrid, Brody, Jennifer A., Pattee, Jack W., Haessler, Jeffrey, Brumpton, Ben M., Chasman, Daniel I., Suchon, Pierre, Chen, Ming-Huei, Turman, Constance, Germain, Marine, Wiggins, Kerri L., MacDonald, James, Braekkan, Sigrid K., Armasu, Sebastian M., Pankratz, Nathan, Jackson, Rabecca D., Nielsen, Jonas B., Giulianini, Franco, Puurunen, Marja K., Ibrahim, Manal, Heckbert, Susan R., Bammler, Theo K., Frazer, Kelly A., McCauley, Bryan M., Taylor, Kent, Pankow, James S., Reiner, Alexander P., Gabrielsen, Maiken E., Deleuze, Jean-François, O'Donnell, Chris J., Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John-Bjarne, Rosendaal, Frits R., Heit, John A., Psaty, Bruce M., Tang, Weihong, Hveem, Kristian, Ridker, Paul M., Morange, Pierre-Emmanuel, Johnson, Andrew D., Kabrhel, Christopher, AlexandreTrégouët, David, Smith, Nicholas L., de Vries, Paul S., Reventun, Paula, Brown, Michael R., Heath, Adam S., Huffman, Jennifer E., Le, Ngoc-Quynh, Bebo, Allison, Temprano-Sagrera, Gerard, Raffield, Laura M., Ozel, Ayse Bilge, Thibord, Florian, Lewis, Joshua P., Rodriguez, Benjamin A. T., Polasek, Ozren, Yanek, Lisa R., Carrasquilla, German D., Marioni, Riccardo E., Kleber, Marcus E., Trégouët, David-Alexandre, Yao, Jie, Li-Gao, Ruifang, Joshi, Peter K., Trompet, Stella, Martinez-Perez, Angel, Ghanbari, Mohsen, Howard, Tom E., Reiner, Alex P., Arvanitis, Marios, Ryan, Kathleen A., Bartz, Traci M., Rudan, Igor, Faraday, Nauder, Linneberg, Allan, Davies, Gail, Delgado, Graciela E., Klaric, Lucija, Noordam, Raymond, van Rooij, Frank, Curran, Joanne E., Wheeler, Marsha M., Osburn, William O., O'Connell, Jeffrey R., Beswick, Andrew, Kolcic, Ivana, Souto, Juan Carlos, Becker, Lewis C., Hansen, Torben, Doyle, Margaret F., Harris, Sarah E., Moissl, Angela P., Rich, Stephen S., Campbell, Harry, Stott, David J., Soria, Jose Manuel, de Maat, Moniek P. M., Brody, Lawrence C., Auer, Paul L., Ben-Shlomo, Yoav, Hayward, Caroline, Mathias, Rasika A., Kilpeläinen, Tuomas O., Lange, Leslie A., Cox, Simon R., März, Winfried, Rotter, Jerome I., Mook-Kanamori, Dennis O., Wilson, James F., van der Harst, Pim, Jukema, J. Wouter, Ikram, M. Arfan, Desch, Karl C., Sabater-Lleal, Maria, Lowenstein, Charles J., and Morrison, Alanna C.

Published
2024
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11. A clinical decision framework to guide the outpatient treatment of emergency department patients diagnosed with acute pulmonary embolism or deep vein thrombosis: Results from a multidisciplinary consensus panel

Author

Kabrhel, Christopher, Vinson, David R, Mitchell, Alice Marina, Rosovsky, Rachel P, Chang, Anna Marie, Hernandez‐Nino, Jackeline, and Wolf, Stephen J

Subjects
Patient Safety, Lung, Clinical Research, Cardiovascular, Emergency Care, Hematology, Health Services, Management of diseases and conditions, 7.3 Management and decision making, Good Health and Well Being, deep vein thrombosis, outpatient, pulmonary embolism, treatment, venous thromboembolism
Abstract

The outpatient treatment of select emergency department patients with acute pulmonary embolism (PE) or deep vein thrombosis (DVT) has been shown to be safe, cost effective and associated with high patient satisfaction. Despite this, outpatient PE and DVT treatment remains uncommon. To address this, the American College of Emergency Physicians assembled a multidisciplinary team of content experts to provide evidence-based recommendations and practical advice to help clinicians safely treat patients with low-risk PE and DVT without hospitalization. The emergency clinician must stratify the patient's risk of clinical decompensation due to their PE or DVT as well as their risk of bleeding due to anticoagulation. The clinician must also select and start an anticoagulant and ensure that the patient has access to the medication in a timely manner. Reliable follow-up is critical, and the patient must also be educated about signs or symptoms that should prompt a return to the emergency department. To facilitate access to these recommendations, the consensus panel also created 2 web-based "point-of-care tools."

Published
2021

13. Authors’ reply

Author

Lyhne, Mads Dam, Giordano, Nicholas, Dudzinski, David, Torrey, Jasmine, Wang, Grace, Zheng, Hui, Parry, Blair Alden, Kalra, Mannudeep K., and Kabrhel, Christopher

Published
2023
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14. Rare Genetic Variants Associated With Sudden Cardiac Death in Adults

Author

Khera, Amit V, Mason-Suares, Heather, Brockman, Deanna, Wang, Minxian, VanDenburgh, Martin J, Senol-Cosar, Ozlem, Patterson, Candace, Newton-Cheh, Christopher, Zekavat, Seyedeh M, Pester, Julie, Chasman, Daniel I, Kabrhel, Christopher, Jensen, Majken K, Manson, JoAnn E, Gaziano, J Michael, Taylor, Kent D, Sotoodehnia, Nona, Post, Wendy S, Rich, Stephen S, Rotter, Jerome I, Lander, Eric S, Rehm, Heidi L, Ng, Kenney, Philippakis, Anthony, Lebo, Matthew, Albert, Christine M, and Kathiresan, Sekar

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Prevention, Genetics, Clinical Research, Heart Disease, Cardiovascular, 4.2 Evaluation of markers and technologies, Aetiology, Detection, screening and diagnosis, 2.4 Surveillance and distribution, 2.1 Biological and endogenous factors, Good Health and Well Being, Aged, Aged, 80 and over, Case-Control Studies, Death, Sudden, Cardiac, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Exome Sequencing, gene sequencing, genomic medicine, sudden cardiac death, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundSudden cardiac death occurs in ∼220,000 U.S. adults annually, the majority of whom have no prior symptoms or cardiovascular diagnosis. Rare pathogenic DNA variants in any of 49 genes can pre-dispose to 4 important causes of sudden cardiac death: cardiomyopathy, coronary artery disease, inherited arrhythmia syndrome, and aortopathy or aortic dissection.ObjectivesThis study assessed the prevalence of rare pathogenic variants in sudden cardiac death cases versus controls, and the prevalence and clinical importance of such mutations in an asymptomatic adult population.MethodsThe authors performed whole-exome sequencing in a case-control cohort of 600 adult-onset sudden cardiac death cases and 600 matched controls from 106,098 participants of 6 prospective cohort studies. Observed DNA sequence variants in any of 49 genes with known association to cardiovascular disease were classified as pathogenic or likely pathogenic by a clinical laboratory geneticist blinded to case status. In an independent population of 4,525 asymptomatic adult participants of a prospective cohort study, the authors performed whole-genome sequencing and determined the prevalence of pathogenic or likely pathogenic variants and prospective association with cardiovascular death.ResultsAmong the 1,200 sudden cardiac death cases and controls, the authors identified 5,178 genetic variants and classified 14 as pathogenic or likely pathogenic. These 14 variants were present in 15 individuals, all of whom had experienced sudden cardiac death-corresponding to a pathogenic variant prevalence of 2.5% in cases and 0% in controls (p

Published
2019

15. A large‐scale exome array analysis of venous thromboembolism

Author

Lindström, Sara, Brody, Jennifer A, Turman, Constance, Germain, Marine, Bartz, Traci M, Smith, Erin N, Chen, Ming‐Huei, Puurunen, Marja, Chasman, Daniel, Hassler, Jeffrey, Pankratz, Nathan, Basu, Saonli, Guan, Weihua, Gyorgy, Beata, Ibrahim, Manal, Empana, Jean‐Philippe, Olaso, Robert, Jackson, Rebecca, Brækkan, Sigrid K, McKnight, Barbara, Deleuze, Jean‐Francois, O’Donnell, Cristopher J, Jouven, Xavier, Frazer, Kelly A, Psaty, Bruce M, Wiggins, Kerri L, Taylor, Kent, Reiner, Alexander P, Heckbert, Susan R, Kooperberg, Charles, Ridker, Paul, Hansen, John‐Bjarne, Tang, Weihong, Johnson, Andrew D, Morange, Pierre‐Emmanuel, Trégouët, David A, Kraft, Peter, Smith, Nicholas L, Kabrhel, Christopher, and Consortium, on behalf of the INVENT

Subjects
Prevention, Clinical Research, Biotechnology, Human Genome, Genetics, 2.1 Biological and endogenous factors, Aetiology, Black or African American, Alleles, Case-Control Studies, Exome, Female, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, High-Throughput Nucleotide Sequencing, Humans, Male, Microarray Analysis, Odds Ratio, Polymorphism, Single Nucleotide, Sample Size, Venous Thromboembolism, exome, genetic association, venous thromboembolism, INVENT Consortium, Public Health and Health Services, Epidemiology
Abstract

Although recent Genome-Wide Association Studies have identified novel associations for common variants, there has been no comprehensive exome-wide search for low-frequency variants that affect the risk of venous thromboembolism (VTE). We conducted a meta-analysis of 11 studies comprising 8,332 cases and 16,087 controls of European ancestry and 382 cases and 1,476 controls of African American ancestry genotyped with the Illumina HumanExome BeadChip. We used the seqMeta package in R to conduct single variant and gene-based rare variant tests. In the single variant analysis, we limited our analysis to the 64,794 variants with at least 40 minor alleles across studies (minor allele frequency [MAF] ~0.08%). We confirmed associations with previously identified VTE loci, including ABO, F5, F11, and FGA. After adjusting for multiple testing, we observed no novel significant findings in single variant or gene-based analysis. Given our sample size, we had greater than 80% power to detect minimum odds ratios greater than 1.5 and 1.8 for a single variant with MAF of 0.01 and 0.005, respectively. Larger studies and sequence data may be needed to identify novel low-frequency and rare variants associated with VTE risk.

Published
2019

16. Multi‐phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations

Author

Temprano‐Sagrera, Gerard, Sitlani, Colleen M., Bone, William P., Martin‐Bornez, Miguel, Voight, Benjamin F., Morrison, Alanna C., Damrauer, Scott M., de Vries, Paul S., Smith, Nicholas L., Sabater‐Lleal, Maria, Dehghan, Abbas, Heath, Adam S, Morrison, Alanna C, Reiner, Alex P, Johnson, Andrew, Richmond, Anne, Peters, Annette, van Hylckama Vlieg, Astrid, McKnight, Barbara, Psaty, Bruce M, Hayward, Caroline, Ward‐Caviness, Cavin, O’Donnell, Christopher, Chasman, Daniel, Strachan, David P, Tregouet, David A, Mook‐Kanamori, Dennis, Gill, Dipender, Thibord, Florian, Asselbergs, Folkert W, Leebeek, Frank W.G., Rosendaal, Frits R, Davies, Gail, Homuth, Georg, Temprano, Gerard, Campbell, Harry, Taylor, Herman A, Bressler, Jan, Huffman, Jennifer E, Rotter, Jerome I, Yao, Jie, Wilson, James F, Bis, Joshua C, Hahn, Julie M, Desch, Karl C, Wiggins, Kerri L, Raffield, Laura M, Bielak, Lawrence F, Yanek, Lisa R, Kleber, Marcus E, Mueller, Martina, Kavousi, Maryam, Mangino, Massimo, Liu, Melissa, Brown, Michael R, Conomos, Matthew P, Jhun, Min‐A, Chen, Ming‐Huei, de Maat, Moniek P.M., Pankratz, Nathan, Smith, Nicholas L, Peyser, Patricia A, Elliot, Paul, de Vries, Paul S, Wei, Peng, Wild, Philipp S, Morange, Pierre E, van der Harst, Pim, Yang, Qiong, Le, Ngoc‐Quynh, Marioni, Riccardo, Li, Ruifang, Damrauer, Scott M, Cox, Simon R, Trompet, Stella, Felix, Stephan B, Völker, Uwe, Tang, Weihong, Koenig, Wolfgang, Jukema, J. Wouter, Guo, Xiuqing, Lindstrom, Sara, Wang, Lu, Smith, Erin N, Gordon, William, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Haessler, Jeffrey, Brumpton, Ben M, Chasman, Daniel I, Suchon, Pierre, Turman, Constance, Germain, Marine, MacDonald, James, Braekkan, Sigrid K, Armasu, Sebastian M, Jackson, Rabecca D, Nielsen, Jonas B, Giulianini, Franco, Puurunen, Marja K, Ibrahim, Manal, Heckbert, Susan R, Bammler, Theo K, Frazer, Kelly A, McCauley, Bryan M, Taylor, Kent, Pankow, James S, Reiner, Alexander P, Gabrielsen, Maiken E, Deleuze, Jean‐François, O’Donnell, Chris J, Kim, Jihye, Kraft, Peter, Hansen, John‐Bjarne, Heit, John A, Kooperberg, Charles, Hveem, Kristian, Ridker, Paul M, Morange, Pierre‐Emmanuel, Johnson, Andrew D, Kabrhel, Christopher, Trégouët, David‐Alexandre, Malik, Rainer, Chauhan, Ganesh, Traylor, Matthew, Sargurupremraj, Muralidharan, Okada, Yukinori, Mishra, Aniket, Rutten‐Jacobs, Loes, Giese, Anne‐Katrin, van der Laan, Sander W, Gretarsdottir, Solveig, Anderson, Christopher D, Chong, Michael, Adams, Hieab HH, Ago, Tetsuro, Almgren, Peter, Amouyel, Philippe, Ay, Hakan, Bartz, Traci M, Benavente, Oscar R, Bevan, Steve, Boncoraglio, Giorgio B, Brown, Robert D, Butterworth, Adam S, Carrera, Caty, Carty, Cara L, Chen, Wei‐Min, Cole, John W, Correa, Adolfo, Cotlarciuc, Ioana, Cruchaga, Carlos, Danesh, John, de Bakker, Paul IW, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gottesman, Rebecca F, Grewal, Raji P, Gudnason, Vilmundur, Gustafsson, Stefan, Harris, Tamara B, Hassan, Ahamad, Havulinna, Aki S, Holliday, Elizabeth G, Howard, George, Hsu, Fang‐Chi, Hyacinth, Hyacinth I, Arfan Ikram, M, Ingelsson, Erik, Irvin, Marguerite R, Jian, Xueqiu, Jiménez‐Conde, Jordi, Johnson, Julie A, Jukema, J Wouter, Kanai, Masahiro, Keene, Keith L, Kissela, Brett M, Kleindorfer, Dawn O, Kubo, Michiaki, Lange, Leslie A, Langefeld, Carl D, Langenberg, Claudia, Launer, Lenore J, Lee, Jin‐Moo, Lemmens, Robin, Leys, Didier, Lewis, Cathryn M, Lin, Wei‐Yu, Lindgren, Arne G, Lorentzen, Erik, Magnusson, Patrik K, Maguire, Jane, Manichaikul, Ani, McArdle, Patrick F, Meschia, James F, Mitchell, Braxton D, Mosley, Thomas H, Nalls, Michael A, Ninomiya, Toshiharu, O’Donnell, Martin J, Pulit, Sara L, Rannikmäe, Kristiina, Rexrode, Kathryn M, Rice, Kenneth, Rich, Stephen S, Rost, Natalia S, Rothwell, Peter M, Rundek, Tatjana, Sacco, Ralph L, Sakaue, Saori, Sale, Michele M, Salomaa, Veikko, Sapkota, Bishwa R, Schmidt, Reinhold, Schmidt, Carsten O, Schminke, Ulf, Sharma, Pankaj, Slowik, Agnieszka, Sudlow, Cathie LM, Tanislav, Christian, Tatlisumak, Turgut, Taylor, Kent D, Thijs, Vincent NS, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tiedt, Steffen, Tzourio, Christophe, van Duijn, Cornelia M, Walters, Matthew, Wareham, Nicholas J, Wassertheil‐Smoller, Sylvia, Wilson, James G, Yusuf, Salim, Amin, Najaf, Aparicio, Hugo S, Arnett, Donna K, Attia, John, Beiser, Alexa S, Berr, Claudine, Buring, Julie E, Bustamante, Mariana, Caso, Valeria, Cheng, Yu‐Ching, Hoan Choi, Seung, Chowhan, Ayesha, Cullell, Natalia, Dartigues, Jean‐François, Delavaran, Hossein, Delgado, Pilar, Dörr, Marcus, Engström, Gunnar, Ford, Ian, Gurpreet, Wander S, Hamsten, Anders, Heitsch, Laura, Hozawa, Atsushi, Ibanez, Laura, Ilinca, Andreea, Ingelsson, Martin, Iwasaki, Motoki, Jackson, Rebecca D, Jood, Katarina, Jousilahti, Pekka, Kaffashian, Sara, Kalra, Lalit, Kamouchi, Masahiro, Kitazono, Takanari, Kjartansson, Olafur, Kloss, Manja, Koudstaal, Peter J, Krupinski, Jerzy, Labovitz, Daniel L, Laurie, Cathy C, Levi, Christopher R, Li, Linxin, Lind, Lars, Lindgren, Cecilia M, Lioutas, Vasileios, Mei Liu, Yong, Lopez, Oscar L, Makoto, Hirata, Martinez‐Majander, Nicolas, Matsuda, Koichi, Minegishi, Naoko, Montaner, Joan, Morris, Andrew P, Muiño, Elena, Müller‐Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Reddy Peddareddygari, Leema, Pedersen, Nancy L, Pera, Joanna, Perola, Markus, Pezzini, Alessandro, Pileggi, Silvana, Rabionet, Raquel, Riba‐Llena, Iolanda, Ribasés, Marta, Romero, Jose R, Roquer, Jaume, Rudd, Anthony G, Sarin, Antti‐Pekka, Sarju, Ralhan, Sarnowski, Chloe, Sasaki, Makoto, Satizabal, Claudia L, Satoh, Mamoru, Sattar, Naveed, Sawada, Norie, Sibolt, Gerli, Sigurdsson, Ásgeir, Smith, Albert, Sobue, Kenji, Soriano‐Tárraga, Carolina, Stanne, Tara, Colin Stine, O, Stott, David J, Strauch, Konstantin, Takai, Takako, Tanaka, Hideo, Tanno, Kozo, Teumer, Alexander, Tomppo, Liisa, Torres‐Aguila, Nuria P, Touze, Emmanuel, Tsugane, Shoichiro, Uitterlinden, Andre G, Valdimarsson, Einar M, van der Lee, Sven J, Völzke, Henry, Wakai, Kenji, Weir, David, Williams, Stephen R, Wolfe, Charles DA, Wong, Quenna, Xu, Huichun, Yamaji, Taiki, Sanghera, Dharambir K, Melander, Olle, Jern, Christina, Strbian, Daniel, Fernandez‐Cadenas, Israel, Longstreth, W T, Rolfs, Arndt, Hata, Jun, Woo, Daniel, Rosand, Jonathan, Pare, Guillaume, Hopewell, Jemma C, Saleheen, Danish, Stefansson, Kari, Worrall, Bradford B, Kittner, Steven J, Seshadri, Sudha, Fornage, Myriam, Markus, Hugh S, Howson, Joanna MM, Kamatani, Yoichiro, Debette, Stephanie, and Dichgans, Martin

Published
2022
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18. Ruling out Pulmonary Embolism in Patients with High Pretest Probability

Author

Akhter, Murtaza, Kline, Jeffrey, Bhattarai, Bikash, Courtney, Mark, and Kabrhel, Christopher

Abstract

Introduction: The American College of Emergency Physicians guidelines recommend more aggressive workup beyond imaging alone in patients with a high pretest probability (PTP) of pulmonary embolism (PE). However, the ability of multiple tests to safely rule out PE in high PTP patients is not known. We sought to measure the ability of negative computed tomography pulmonary angiography (CTPA) along with negative D-dimer to rule out PE in these high-risk patients.Methods: We analyzed data from a previous prospective observational study conducted in 12 emergency departments (ED). Wells score criteria were entered by providers before final PE testing. PE was diagnosed by imaging on the index ED visit, or within 45 days, demonstrating either PE ordeep vein thrombosis (DVT), or if the patient died of PE during the 45-day, follow-up period. Testing threshold was set at 1.8%.Results: A total of 7,940 patients were enrolled and tested for PE, and 257 had high PTP (Wells >6). Sixteen of these high-risk patients had negative CTPA and negative D-dimer, of whom two were positive for PE (12.5% [95% confidence interval 2.2%-40.0%]). One of these patients had a DVT on CT venogram and the other was diagnosed at follow-up.Conclusion: Our analysis suggests that in patients with high PTP of PE, neither negative CTPA by itself nor a negative CTPA plus a negative D-dimer are sufficient to rule out PE. More aggressive workup strategies may be required for these patients.

Published
2018

22. Quality of life after pharmacomechanical catheter-directed thrombolysis for proximal deep venous thrombosis

Author

Sichlau, Michael, Vlahos, Athanasios, Smith, Steven, Thalheimer, Quinn, Singh, Nisha, Harting, Rekha, Gocke, John, Guth, Scott, Shah, Neel, Brady, Paul, Schatz, Marvin, Horrow, Mindy, Markazi, Peyman, Forouzan, Leli, Matalon, Terence A.S., Hertzog, David, Goday, Swapna, Kennedy, Margaret, Kaplan, Robert, Campbell, Thomas, Hartman, Jamie, Nahum, Elmer, Venkat, Arvind, Krishnamurthy, Venkataramu, Rectenwald, John, Henke, Peter, Eliason, Jonathan, Willatt, Jonathon, Escobar, Guillermo, Samuels, Shaun, Katzen, Barry, Benenati, James, Powell, Alex, Pena, Constantino, Wallach, Howard, Gandhi, Ripal, Schneider, Joseph, Kim, Stanley, Hashemi, Farrah, Boyle, Joseph, Patel, Nilesh, Verta, Michael, Leung, Daniel, Garcia, Marc, Blatt, Phillip, Khatri, Jamil, Epstein, Dave, Ryan, Randall, Sweeny, Tom, Stillabower, Michael, Kimbiris, George, Raman, Tuhina, Sierzenski, Paul, Getto, Lelia, Dignazio, Michael, Horvath, Mark, Gornik, Heather, Bartholomew, John, Shishehbor, Mehdi, Peacock, Frank, Joseph, Douglas, Kim, Soo Hyum, Mahlay, Natalia Fendrikova, Clair, Daniel, Lyden, Sean, Kapoor, Baljendra, McLennon, Gordon, Pierce, Gregory, Newman, James, Spain, James, Gill, Amanjiit, Hamilton, Aaron, Rizzo, Anthony, Park, Woosup, Dietzek, Alan, Galin, Ira, Plummer, Dahlia, Hsu, Richard, Broderick, Patrick, Keller, Andrew, Sayeed, Sameer, Slater, Dennis, Lustberg, Herb, Akus, Jan, Sidman, Robert, Dhami, Mandeep, Kohanski, Phillip, Bulgaru, Anca, Dulala, Renuka, Burch, James, Kapur, Dinesh, Yang, Jie, Ranson, Mark, Wladis, Alan, Varnagy, David, Mekhail, Tarek, Winter, Robert, Perez-Izquierdo, Manuel, Motew, Stephen, Royd-Kranis, Robin, Workman, Raymond, Kribbs, Scott, Hogsette, Gerald, Moore, Phillip, Thomason, Bradley, Means, William, Bonsall, Richard, Stewart, John, Golwya, Daniel, Azene, Ezana, Bottner, Wayne, Bishop, William, Clayton, Dave, Gundersen, Lincoln, Riherd, Jody, Shakhnovich, Irina, Ziegelbein, Kurt, Chang, Thomas, Sharma, Karun, Allison, Sandra, Banovac, Fil, Cohen, Emil, Furlong, Brendan, Kessler, Craig, McCullough, Mike, Spies, Jim, Lin, Judith, Kaatz, Scott, Getzen, Todd, Miller, Joseph, Schwartz, Scott, Kabbani, Loay, McVinnie, David, Rundback, John, Manno, Joseph, Schwab, Richard, Cole, Randolph, Herman, Kevin, Singh, David, Barkama, Ravit, Patel, Amish, Comerota, Anthony, Pigott, John, Seiwert, Andrew, Whalen, Ralph, Russell, Todd, Assi, Zakaria, Kazanjian, Sahira, Yobbagy, Jonathan, Kaminski, Brian, Kaufman, Allan, Begeman, Garett, DiSalle, Robert, Thakur, Subash, Kim, Paul, Jacquet, Marc, Dykes, Thomas, Gerding, Joseph, Baker, Christopher, Debiasto, Mark, Mittleider, Derek, Higgins, George, III, Amberson, Steven, Pezzuti, Roger, Gallagher, Thomas, Schainfeld, Robert, Wicky, Stephan, Kalva, Sanjeeva, Walker, Gregory, Salazar, Gloria, Pomerantz, Benjamin, Patel, Virenda, Kabrhel, Christopher, Iqbal, Shams, Gangull, Suvranu, Oklu, Rahmi, Brannan, Scott, Misra, Sanjay, Bjarnason, Haraldur, Ashrani, Aneel, Caccavale, Michael, Fleming, Chad, Friese, Jeremy, Heit, John, Kalra, Manju, Macedo, Thanila, McBane, Robert, McKusick, Michael, Stockland, Andrew, Woodrum, David, Wysokinski, Waldemar, Verma, Adarsh, Davis, Andrew, Chung, Jerry, Nicker, David, Anderson, Brian, Stein, Robert, Weiss, Michael, Patel, Parag, Rilling, William, Tutton, Sean, Hieb, Robert, Hohenwalter, Eric, Colella, M. Riccardo, Gosset, James, White, Sarah, Lewis, Brian, Brown, Kellie, Rossi, Peter, Seabrook, Gary, Guimaraes, Marcelo, Selby, J. Bayne, McGary, William, Hannegan, Christopher, Robison, Jacob, Brothers, Thomas, Elliott, Bruce, Garg, Nitin, Anderson, M. Bret, Uflacker, Renan, Schonholz, Claudio, Raney, Laurence, Greenberg, Charles, Kaufman, John, Keller, Frederick, Kolbeck, Kenneth, Landry, Gregory, Mitchell, Erica, Barton, Robert, DeLoughery, Thomas, Kalbfleisch, Norman, Minjarez, Renee, Lakin, Paul, Liem, Timothy, Moneta, Gregory, Farsad, Khashayar, Fleischman, Ross, French, Loren, Marques, Vasco, Al−Hassani, Yasir, Sawar, Asad, Taylor, Frank, Patel, Rajul, Malhotra, Rahul, Hashemi, Farah, Padnick, Marvin, Gurley, Melissa, Cucher, Fred, Sterrenberg, Ronald, Deepthi, G. Reshmaal, Cumaranatunge, Gomes, Bhatla, Sumit, Jacobs, Darick, Dolen, Eric, Gamboa, Pablo, Dean, L. Mark, Davis, Thomas, Lippert, John, Khanna, Sanjeev, Schirf, Brian, Silber, Jeffrey, Wood, Donald, McGraw, J. Kevin, LaPerna, Lucy, Willette, Paul, Murphy, Timothy, Cerezo, Joselyn, Dhangana, Rajoo, Ahn, Sun Ho, Dubel, Gregory, Haas, Richard, Jay, Bryan, Prince, Ethan, Soares, Gregory, Klinger, James, Lambiase, Robert, Jay, Gregory, Tubbs, Robert, Beland, Michael, Hampson, Chris, O'Hara, Ryan, Thompson, Chad, Frodsham, Aaron, Gardiner, Fenwick, Jaffan, Abdel, Keating, Lawrence, Zafar, Abdul, Alicic, Radica, Raabe, Rodney, Brower, Jayson, McClellan, David, Pellow, Thomas, Zylak, Christopher, Davis, Joseph, Reilly, M. Kathleen, Symington, Kenneth, Seibold, Camerson, Nachreiner, Ryan, Murray, Daniel, Murray, Stephen, Saha, Sandeep, Luna, Gregory, Hodgson, Kim, McLafferty, Robert, Hood, Douglas, Moore, Colleen, Griffen, David, Hurst, Darren, Lubbers, David, Kim, Daniel, Warren, Brent, Engel, Jeremy, Suresh, D.P., VanderWoude, Eric, Razdan, Rahul, Hutchins, Mark, Rounsborg, Terry, Midathada, Madhu, Moravec, Daniel, Tilford, Joni, Beckman, Joni, Razavi, Mahmood, Openshaw, Kurt, Flanigan, D. Preston, Loh, Christopher, Dorne, Howard, Chan, Michael, Thomas, Jamie, Psaila, Justin, Ringold, Michael, Fisher, Jay, Lipcomb, Any, Oskin, Timothy, Wible, Brandt, Coleman, Brendan, Elliott, David, Gaddis, Gary, Cochran, C. Doug, Natarajan, Kannan, Bick, Stewart, Cooke, Jeffrey, Hedderman, Ann, Greist, Anne, Miller, Lorrie, Martinez, Brandon, Flanders, Vincent, Underhill, Mark, Hofmann, Lawrence, Sze, Daniel, Kuo, William, Louie, John, Hwang, Gloria, Hovsepian, David, Kothary, Nishita, Berube, Caroline, Schreiber, Donald, Jeffrey, Brooke, Schor, Jonathan, Deitch, Jonathan, Singh, Kuldeep, Hahn, Barry, Ardolic, Brahim, Gupta, Shilip, Bashir, Riyaz, Rao, Angara Koneti, Garg, Manish, Patil, Pravin, Zack, Chad, Cohen, Gary, Schmieder, Frank, Lakhter, Valdimir, Sacks, David, Guay, Robert, Scott, Mark, Cunningham, Karekin, Sigal, Adam, Cescon, Terrence, Leasure, Nick, Dhurairaj, Thiruvenkatasamy, Muck, Patrick, Knochel, Kurt, Lohr, Joann, Barreau, Jose, Recht, Matthew, Bhaskaran, Jayapandia, Brahmamdam, Ranga, Draper, David, Mehta, Apurva, Maher, James, Sharafuddin, Melhem, Lentz, Steven, Nugent, Andrew, Sharp, William, Kresowik, Timothy, Nicholson, Rachel, Sun, Shiliang, Youness, Fadi, Pascarella, Luigi, Ray, Charles, Knuttinen, Martha-Gracia, Bui, James, Gaba, Ron, Dobiesz, Valerie, Shamim, Ejaz, Nimmagadda, Sangeetha, Peace, David, Zain, Aarti, Palumto, Alison, Haskal, Ziv, Hirshon, Jon Mark, Richard, Howard, Verceles, Avelino, Wong-You-Chong, Jade, Othee, Bertrand, Patel, Rahul, Iliescu, Bogdan, Williams, David, Gemmete, Joseph, Cwikiel, Wojciech, Cho, Kyung, Schields, James, Vellody, Ranjith, Novelli, Paula, Dasika, Narasimham, Wakefield, Thomas, Desmond, Jeffrey, Froehlich, James, Khaja, Minhajuddin, Hunter, David, Golzarian, Jafar, Cressman, Erik, Dotta, Yvonne, Schmiechen, Nate, Marek, John, Garcia, David, Tawil, Isaac, Langsfeld, Mark, Moll, Stephan, Mauro, Matthew, Stavas, Joseph, Burke, Charles, Dixon, Robert, Yu, Hyeon, Keagy, Blair, Kim, Kyuny, Kasthuri, Raj, Key, Nigel, Chaer, Rabih, Makaroun, Michael, Rhee, Robert, Cho, Jae−Sung, Baril, Donald, Marone, Luke, Hseih, Margaret, Feterik, Kristian, Smith, Roy, Jeyabalan, Geetha, Rogers, Jennifer, Vinik, Russel, Kinikini, Dan, Kraiss, Larry, Mueller, Michelle, Pendleton, Robert, Rondina, Matthew, Sarfati, Mark, Wanner, Nathan, Johnson, Stacy, Hopkins, Christy, Ihnat, Daniel, Angle, John, Matsumoto, Alan, Harthun, Nancy, Turba, Ulku, Saad, Wael, Uthlaut, Brian, Nannapaneni, Srikant, Ling, David, Sabri, Saher, Kern, John, Macik, B. Gail, Hoke, George, Park, Auh Wahn, Stone, James, Sneed, Benjamin, Syverud, Scott, Davidson, Kelly, Sharma, Aditya, Wilkins, Luke, Black, Carl, Asay, Mark, Hatch, Daniel, Smilanich, Robert, Patten, Craig, Brown, S. Douglas, Nielsen, Ryan, Alward, William, Collins, John, Nokes, Matthew, Geary, Randolph, Edwards, Matthew, Godshall, Christopher, Levy, Pavel, Winokur, Ronald, Sista, Akhilesh, Madoff, David, Lee, Kyungmouk, Pua, Bradley, DeSancho, Maria, Milizia, Raffaele, Gao, Jing, McLean, Gordon, Khalid, Sanualah, Vedantham, Suresh, Lewis, Larry, Saad, Nael, Thoelke, Mark, Pallow, Robert, Klein, Seth, Sicard, Gregorio, Cohen, David J., Comerota, Anthony J., Gornik, Heather L., Jaff, Michael R., Julian, Jim, Kahn, Susan R., Kearon, Clive, Kee, Stephen, Kindzelski, Andrei L., Lewis, Lawrence, Magnuson, Elizabeth, Razavi, Mahmood K., Murphy, Timothy P., Julian, Jim A., Gu, Chu-Shu, Magnuson, Elizabeth A., Goldhaber, Samuel Z., Schneider, Joseph R., Sista, Akhilesh K., McLafferty, Robert B., Kaufman, John A., Wible, Brandt C., and Blinder, Morey

Published
2020
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23. Associations of Trauma Exposure and Posttraumatic Stress Symptoms With Venous Thromboembolism Over 22 Years in Women.

Author

Sumner, Jennifer A, Kubzansky, Laura D, Kabrhel, Christopher, Roberts, Andrea L, Chen, Qixuan, Winning, Ashley, Gilsanz, Paola, Rimm, Eric B, Glymour, Maria M, and Koenen, Karestan C

Subjects
Humans, Pulmonary Embolism, Venous Thrombosis, Incidence, Proportional Hazards Models, Stress Disorders, Post-Traumatic, Adult, Middle Aged, United States, Female, Venous Thromboembolism, Psychological Trauma, deep vein thrombosis, posttraumatic stress disorder, pulmonary embolism, trauma, venous thromboembolism, Anxiety Disorders, Cardiovascular, Prevention, Post-Traumatic Stress Disorder (PTSD), Mental Health, Clinical Research, Violence Research, Hematology, Brain Disorders, Cardiorespiratory Medicine and Haematology
Abstract

BackgroundTrauma exposure and posttraumatic stress disorder (PTSD) have been linked to myocardial infarction and stroke in women, with biological and behavioral mechanisms implicated in underlying risk. The third most common cardiovascular illness, venous thromboembolism (VTE), is a specific health risk for women. Given previous associations with other cardiovascular diseases, we hypothesized that high levels of trauma and PTSD symptoms would be associated with higher risk of incident VTE in younger and middle-aged women.Methods and resultsWe used proportional hazards models to estimate hazard ratios (HRs) and 95% CIs for new-onset VTE (960 events) over 22 years in 49 296 women in the Nurses' Health Study II. Compared to no trauma exposure, both trauma exposure and PTSD symptoms were significantly associated with increased risk of developing VTE, adjusting for demographics, family history, and childhood adiposity. Women with the most PTSD symptoms exhibited the greatest risk elevation: trauma/6 to 7 symptoms: HR=2.42 (95% CI, 1.83-3.20); trauma/4 to 5 symptoms: HR=2.00 (95% CI, 1.55-2.59); trauma/1 to 3 symptoms: HR=1.44 (95% CI, 1.12-1.84); trauma/no symptoms: HR=1.72 (95% CI, 1.43-2.08). Results were similar, although attenuated, when adjusting for VTE-relevant medications, medical conditions, and health behaviors.ConclusionsWomen with the highest PTSD symptom levels had nearly a 2-fold increased risk of VTE compared to women without trauma exposure in fully adjusted models. Trauma exposure alone was also associated with elevated VTE risk. Trauma and PTSD symptoms may be associated with a hypercoagulable state. Treatment providers should be aware that women with trauma exposure and PTSD symptoms may be vulnerable to VTE.

Published
2016

28. Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism

Author

Lindström, Sara, Wang, Lu, Smith, Erin N., Gordon, William, van Hylckama Vlieg, Astrid, de Andrade, Mariza, Brody, Jennifer A., Pattee, Jack W., Haessler, Jeffrey, Brumpton, Ben M., Chasman, Daniel I., Suchon, Pierre, Chen, Ming-Huei, Turman, Constance, Germain, Marine, Wiggins, Kerri L., MacDonald, James, Braekkan, Sigrid K., Armasu, Sebastian M., Pankratz, Nathan, Jackson, Rebecca D., Nielsen, Jonas B., Giulianini, Franco, Puurunen, Marja K., Ibrahim, Manal, Heckbert, Susan R., Damrauer, Scott M., Natarajan, Pradeep, Klarin, Derek, de Vries, Paul S., Sabater-Lleal, Maria, Huffman, Jennifer E., Bammler, Theo K., Frazer, Kelly A., McCauley, Bryan M., Taylor, Kent, Pankow, James S., Reiner, Alexander P., Gabrielsen, Maiken E., Deleuze, Jean-François, O'Donnell, Chris J., Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John-Bjarne, Rosendaal, Frits R., Heit, John A., Psaty, Bruce M., Tang, Weihong, Kooperberg, Charles, Hveem, Kristian, Ridker, Paul M., Morange, Pierre-Emmanuel, Johnson, Andrew D., Kabrhel, Christopher, Trégouët, David-Alexandre, and Smith, Nicholas L.

Published
2019
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33. Addressing the rising trend of high‐risk pulmonary embolism mortality: Clinical and research priorities.

Author

Casey, Scott D., Stubblefield, William B., Luijten, Dieuwke, Klok, Frederikus A., Westafer, Lauren M., Vinson, David R., and Kabrhel, Christopher

Subjects
PULMONARY embolism, RISK assessment, POLICY sciences, ANTICOAGULANTS, THROMBOLYTIC therapy, RESEARCH evaluation, HEALTH policy, PSYCHOLOGICAL adaptation, PRIORITY (Philosophy), PHYSICIANS, QUALITY assurance, HEALTH equity, DISEASE risk factors
Abstract

Background: Deaths from high‐risk pulmonary embolism (PE) appear to have increased in the US over the last decade. Modifiable risks contributing to this worrisome trend present opportunities for physicians, researchers, and healthcare policymakers to improve care. Methods: We sought to contextualize contemporary, high‐risk PE epidemiology and examine clinical trials, quality improvement opportunities, and healthcare policy initiatives directed at reducing mortality. Results: We observed significant and modifiable excess mortality due to high‐risk PE. We identified several opportunities to improve care including: (1) rapid translation of forthcoming data on reperfusion strategies into clinical practice; (2) improved risk stratification tools; (3) quality improvement initiatives to address presumptive anticoagulation practice gaps; and (3) adoption of health policy initiatives to establish pulmonary embolism response teams and address the social determinants of health. Conclusion: Addressing knowledge and practice gaps in intermediate and high‐risk PE management must be prioritized and informed by forthcoming high‐quality data. Implementation efforts are needed to improve acute PE management and resolve treatment disparities. [ABSTRACT FROM AUTHOR]

Published
2024
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38. Emergency department diagnosis and management of acute pulmonary embolism.

Author

Wrenn, Jesse O. and Kabrhel, Christopher

Subjects
*CLINICAL decision support systems, *PULMONOLOGY, *THROMBOEMBOLISM, *EMERGENCY medicine, *HOSPITAL emergency services, *PULMONARY embolism
Abstract

Summary Despite advances in clinical decision support, the diagnosis, prognostic risk stratification, treatment and disposition of emergency department patients with pulmonary embolism remain challenging. The use of diagnostic risk stratification tools and D‐dimer can decrease unnecessary exposure to radiation and intravenous contrast; however, D‐dimer is elevated in many conditions including normal pregnancy, so imaging is often indicated. Once diagnosed, prognostic risk stratification tools can inform treatment decisions across the risk spectrum, including identifying low‐risk patients with pulmonary embolism who can safely be treated at home. For patients requiring hospitalization, alternatives to unfractionated heparin can improve time to therapeutic anticoagulation and reduce treatment‐related bleeding risk. [ABSTRACT FROM AUTHOR]

Published
2024
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40. Barriers and facilitators to interhospital transfer of acute pulmonary embolism: An inductive qualitative analysis

Author

DeBerry, Jacob, Rali, Parth, McDaniel, Michael, Kabrhel, Christopher, Rosovsky, Rachel, Melamed, Roman, Friedman, Oren, Elwing, Jean M., Balasubramanian, Vijay, Sahay, Sandeep, Bossone, Eduardo, Farmer, Mary Jo S., Klein, Andrew J. P., Hamm, Megan E., Ross, Charles B., Rivera-Lebron, Belinda N., Deberry, Jacob, Rali, Parth, Mcdaniel, Michael, Kabrhel, Christopher, Rosovsky, Rachel, Melamed, Roman, Friedman, Oren, Elwing, Jean M, Balasubramanian, Vijay, Sahay, Sandeep, Bossone, Eduardo, Farmer, Mary Jo S, Klein, Andrew J P, Hamm, Megan E, Ross, Charles B, and Rivera-Lebron, Belinda N

Subjects
catheter–directed thrombolysi, interhospital transfer, pulmonary embolism response team, pulmonary embolism, surgical embolectomy, General Medicine
Abstract

BackgroundInterhospital transfer (IHT) of patients with acute life-threatening pulmonary embolism (PE) is necessary to facilitate specialized care and access to advanced therapies. Our goal was to understand what barriers and facilitators may exist during this transfer process from the perspective of both receiving and referring physicians.MethodsThis qualitative descriptive study explored physician experience taking care of patients with life threatening PE. Subject matter expert physicians across several different specialties from academic and community United States hospitals participated in qualitative semi-structured interviews. Interview transcripts were subsequently analyzed using inductive qualitative description approach.ResultsFour major themes were identified as barriers that impede IHT among patients with life threatening PE. Inefficient communication which mainly pertained to difficulty when multiple points of contact were required to complete a transfer. Subjectivity in the indication for transfer which highlighted the importance of physicians understanding how to use standardized risk stratification tools and to properly triage these patients. Delays in data acquisition were identified in regards to both obtaining clinical information and imaging in a timely fashion. Operation barriers which included difficulty finding available beds for transfer and poor weather conditions inhibiting transportation. In contrast, two main facilitators to transfer were identified: good communication and reliance on colleagues and dedicated team for transferring and treating PE patients.ConclusionThe most prominent themes identified as barriers to IHT for patients with acute life-threatening PE were: (1) inefficient communication, (2) subjectivity in the indication for transfer, (3) delays in data acquisition (imaging or clinical), and (4) operational barriers. Themes identified as facilitators that enable the transfer of patients were: (1) good communication and (2) a dedicated transfer team. The themes presented in our study are useful in identifying opportunities to optimize the IHT of patients with acute PE and improve patient care. These opportunities include instituting educational programs, streamlining the transfer process, and formulating a consensus statement to serve as a guideline regarding IHT of patients with acute PE.

Published
2023

47. Life expectancy associated with different ages at diagnosis of type 2 diabetes in high-income countries : 23 million person-years of observation

Author

Kaptoge, Stephen, Sun, Luanluan, Walker, Matthew, Spackman, Sarah, Pennells, Lisa, Seshasai, Sreenivasa Rao Kondapally, Bolton, Thomas, Ataklte, Feven, Willeit, Peter, Bell, Steven, Burgess, Steven, Altay, Servet, Assmann, Gerd, Ben-Shlomo, Yoav, Best, Lyle G., Bjorkelund, Cecilia, Blazer, Dan G., Brenner, Hermann, Brunner, Eric J., Dagenais, Gilles R., Cooper, Jackie A., Cooper, Cyrus, Crespo, Carlos J., Cushman, Mary, D'Agostino, Ralph B., Sr., Daimon, Makoto, Daniels, Lori B., Dankner, Rachel, Davidson, Karina W., de Jongh, Renate T., Donfrancesco, Chiara, Ducimetiere, Pierre, Elders, Petra J. M., Engstrom, Gunnar, Ford, Ian, Gallacher, John, Bakker, Stephan J. L., Goldbourt, Uri, de la Camara, Agustin Gomez, Grimsgaard, Sameline, Gudnason, Vilmundur, Hansson, Per-Olof, Imano, Hironori, Jukema, J. Wouter, Kabrhel, Christopher, Kauhanen, Jussi, Kavousi, Maryam, Kiechl, Stefan, Knuiman, Matthew W., Kromhout, Daan, Krumholz, Harlan M., Kuller, Lewis H., Laatikainen, Tiina, Lawlor, Debbie A., Meyer, Haakon E., Mukamal, Kenneth, Nietert, Paul J., Ninomiya, Toshiharu, Nitsch, Dorothea, Nordestgaard, Borge G., Palmieri, Luigi, Price, Jackie F., Ridker, Paul M., Sun, Qi, Rosengren, Annika, Roussel, Ronan, Sakurai, Masaru, Salomaa, Veikko, Schottker, Ben, Shaw, Jonathan E., Strandberg, Timo E., Sundström, Johan, Tolonen, Hanna, Tverdal, Aage, Verschuren, W. M. Monique, Volzke, Henry, Wagenknecht, Lynne, Wallace, Robert B., Wannamethee, S. Goya, Wareham, Nicholas J., Wassertheil-Smoller, Sylvia, Yamagishi, Kazumasa, Yeap, Bu B., Harrison, Seamus, Thompson, Simon G., Inouye, Michael, Griffin, Simon, Butterworth, Adam S., Wood, Angela M., Sattar, Naveed, Danesh, John, Di Angelantonio, Emanuele, Kaptoge, Stephen, Sun, Luanluan, Walker, Matthew, Spackman, Sarah, Pennells, Lisa, Seshasai, Sreenivasa Rao Kondapally, Bolton, Thomas, Ataklte, Feven, Willeit, Peter, Bell, Steven, Burgess, Steven, Altay, Servet, Assmann, Gerd, Ben-Shlomo, Yoav, Best, Lyle G., Bjorkelund, Cecilia, Blazer, Dan G., Brenner, Hermann, Brunner, Eric J., Dagenais, Gilles R., Cooper, Jackie A., Cooper, Cyrus, Crespo, Carlos J., Cushman, Mary, D'Agostino, Ralph B., Sr., Daimon, Makoto, Daniels, Lori B., Dankner, Rachel, Davidson, Karina W., de Jongh, Renate T., Donfrancesco, Chiara, Ducimetiere, Pierre, Elders, Petra J. M., Engstrom, Gunnar, Ford, Ian, Gallacher, John, Bakker, Stephan J. L., Goldbourt, Uri, de la Camara, Agustin Gomez, Grimsgaard, Sameline, Gudnason, Vilmundur, Hansson, Per-Olof, Imano, Hironori, Jukema, J. Wouter, Kabrhel, Christopher, Kauhanen, Jussi, Kavousi, Maryam, Kiechl, Stefan, Knuiman, Matthew W., Kromhout, Daan, Krumholz, Harlan M., Kuller, Lewis H., Laatikainen, Tiina, Lawlor, Debbie A., Meyer, Haakon E., Mukamal, Kenneth, Nietert, Paul J., Ninomiya, Toshiharu, Nitsch, Dorothea, Nordestgaard, Borge G., Palmieri, Luigi, Price, Jackie F., Ridker, Paul M., Sun, Qi, Rosengren, Annika, Roussel, Ronan, Sakurai, Masaru, Salomaa, Veikko, Schottker, Ben, Shaw, Jonathan E., Strandberg, Timo E., Sundström, Johan, Tolonen, Hanna, Tverdal, Aage, Verschuren, W. M. Monique, Volzke, Henry, Wagenknecht, Lynne, Wallace, Robert B., Wannamethee, S. Goya, Wareham, Nicholas J., Wassertheil-Smoller, Sylvia, Yamagishi, Kazumasa, Yeap, Bu B., Harrison, Seamus, Thompson, Simon G., Inouye, Michael, Griffin, Simon, Butterworth, Adam S., Wood, Angela M., Sattar, Naveed, Danesh, John, and Di Angelantonio, Emanuele

Abstract

Background The prevalence of type 2 diabetes is increasing rapidly, particularly among younger age groups. Estimates suggest that people with diabetes die, on average, 6 years earlier than people without diabetes. We aimed to provide reliable estimates of the associations between age at diagnosis of diabetes and all-cause mortality, cause-specific mortality, and reductions in life expectancy. Methods For this observational study, we conducted a combined analysis of individual-participant data from 19 high income countries using two large-scale data sources: the Emerging Risk Factors Collaboration (96 cohorts, median baseline years 1961-2007, median latest follow-up years 1980-2013) and the UK Biobank (median baseline year 2006, median latest follow-up year 2020). We calculated age-adjusted and sex-adjusted hazard ratios (HRs) for all-cause mortality according to age at diagnosis of diabetes using data from 1 515 718 participants, in whom deaths were recorded during 23 center dot 1 million person-years of follow-up. We estimated cumulative survival by applying age-specific HRs to age-specific death rates from 2015 for the USA and the EU. Findings For participants with diabetes, we observed a linear dose-response association between earlier age at diagnosis and higher risk of all-cause mortality compared with participants without diabetes. HRs were 2 center dot 69 (95% CI 2 center dot 43-2 center dot 97) when diagnosed at 30-39 years, 2 center dot 26 (2 center dot 08-2 center dot 45) at 40-49 years, 1 center dot 84 (1 center dot 72-1 center dot 97) at 50-59 years, 1 center dot 57 (1 center dot 47-1 center dot 67) at 60-69 years, and 1 center dot 39 (1 center dot 29-1 center dot 51) at 70 years and older. HRs per decade of earlier diagnosis were similar for men and women. Using death rates from the USA, a 50-year-old individual with diabetes died on average 14 years earlier when diagnosed aged 30 years, 10 years earlier when diagnosed aged 40 years, or 6 years earlier

Published
2023
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