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ACS pharmacology & translational science. 2025:8(11):3844-3871.DOI: 10.1021/acsptsci.5c00029

Quinoline-Based Neuropilin‑1 Antagonists Exhibit a Pure Antagonist Profile and Block Vascular Endothelial Growth Factor-Induced Pain

Hestehave, Sara; Dragoni, Silvia; Fallon, Philip; Mota, Filipa; Calderon-Rivera, Aida; Gomez, Kimberly; Powell, Jonathan; Patsiarika, Anastasia; Reisinger, Tifelle; Crosby, Stuart; Chan, A W Edith; Steadman, David; Winfield, Natalie; Jarvis, Ashley; Martin, John; Zachary, Ian C; Frankel, Paul; Djordjevic, Snezana; Ruhrberg, Christiana; Khanna, Rajesh; Selwood, David L
Nociceptive pain, resulting from tissue injury or inflammation, affects a large portion of the global population. This type of pain is commonly treated by small molecules that are associated with a variety of drawbacks, including addiction and potential liver or kidney damage, highlighting the need for new therapeutic strategies. Here, we report the design, synthesis, and characterization of EG01449 (12h), a quinoline-based neuropilin-1 (NRP1) antagonist with analgesic effects in vascular endothelial growth factor (VEGF)-induced pain models. Neuropilin-1 is a critical coreceptor mediating VEGF signaling. In models of VEGF-induced pain, the VEGFA165a isoform increases currents through voltage-gated sodium and calcium channels in dorsal root ganglia sensory neurons. Notably, this effect was mitigated upon the inhibition of NRP1 by 12h, while 12h alone showed no discernible impact on sodium currents. Compound 12h also attenuated sensitivity to mechanical stimuli and cold-induced allodynia. Unlike the previously reported NRP1-targeting compounds that may activate intracellular signaling, 12h did not activate p38 mitogen-activated protein kinase and exhibited a purely inhibitory pharmacological profile. Structural comparison using X-ray crystallography revealed an additional hydrogen bond that contributes to the increased stabilization of the 12h/NRP1 complex. These findings demonstrate that the NRP1 inhibitor 12h elicits an antinociceptive effect and highlight the impact of subtle structural modifications on biological outcomes. NRP1 antagonism thus represents a promising new modality for the treatment of chronic pain conditions.
PMCID:12624434
PMID: 41262564
ISSN: 2575-9108
CID: 6041712
Canadian journal of surgery = Journal canadien de chirurgie. 2025:68(6suppl3):S58-S132.DOI: 10.1503/cjs.020125

Canadian Spine Society: 25th Annual Scientific Conference, February 25 to 28, 2025, Fairmont Le Manoir Richelieu, La Malbaie, Charlevoix, Que., Canada

Chan, Vivien; Gausper, Adeesya; Liu, Andy; Andras, Lindsay M; Illingworth, Kenneth D; Skaggs, David L; Imbeault, Rachelle; Dufresne, Justin; Parent, Stefan; Deschênes, Sylvain; Roy-Beaudry, Marjolaine; Legler, Jack; Benaroch, Lee; Pirshahid, Ali Ahmadi; Serhan, Olivia; Cheng, Draydon; Bartley, Debra; Carey, Timothy; Rasoulinejad, Parham; Singh, Supriya; Thornley, Patrick; Skaik, Khaled; Belanger, Genevieve; Phan, Philippe; Stratton, Alexandra; Matthew, Coyle; Kingwell, Stephen; Tsai, Eve; Wai, Eugene; Fonteyne, Hannah; Hryniuk, Sarah Southon; Parent, Eric; Huang, Eric; Stampe, Kyle; Beaulieu, Marie J; Chan, Monica; Thevasagayam, Gloria; Marino-Merlo, Gabriela; Malhotra, Armaan K; Lozano, Christopher S; Salaheen, Zaid; Malvea, Anahita; Shakil, Husain; Yefet, Leeor; Moghaddamjou, Ali; Molot-Toker, Sam; Witiw, Christopher D; Wilson, Jefferson R; Christian, Eisha; Quon, Jennifer L; Dirks, Peter B; Drake, James M; Rutka, James T; Kulkarni, Abhaya V; Zeller, Reinhard; Lebel, David E; Ibrahim, George M; Dionne, Antoine; Joncas, Julie; Barchi, Soraya; Parent, Stefan; Mac-Thiong, Jean-Marc; Yoon, Samuel; Aboelmagd, Karim; Sivakuganandan, Archana; Zulfiqar, Amna; Murphy, Anne; Moll, Stanley; Sorbara, Julia; Rocos, Brett; Lebel, David; Camp, Mark; Chan, Vivien; Shumilak, Geoffrey; Malhotra, Armaan K; Dansby, Jalen; Liu, Andy M; Chan-Tai-Kong, Andrew Michael; Lebel, David E; Illingworth, Kenneth D; Skaggs, David L; Lu, Daisy A; Wang, Zhi; Clar, Monique; Al-Shakfa, M Fidaa; Shen, Jesse; Rasoulinejad, Parham; Miyanji, Firoz; Kantar, Karim; Carey, Timothy; Bailey, Chris; Ghag, Ravi; Lanting, Brent; Singh, Supriya; Urquhart, Jennifer; Lung, Tiffany; Sardar, Zeeshan; Basu, Saumayajit; Gupta, Manish; Lewis, Stephen; Eissa, Abdullah T; Kato, So; Lenke, Lawrence; Jones, Kristen; Nielsen, Christopher; Basu, Saumyajit; Kelly, Michael; Smith, Justin; Strantzas, Samuel; Qiu, Yong; Pellise, Ferran; Alanay, Ahmet; Quraishi, Nasir; Gray, Randolph; Yoshida, Go; Aziz, Amer; Lewis, Stephen; Chaves, Jennyfer Paulla Galdino; Hsu, Brian; Sima, Stone; Singh, Bhisham; Kulkarni, Vinay; Diwan, Ashish; Ludwig, Taryn; Moghaddam, Farbod; Aminghafari, Mina; Choi, May; Nicholls, Fred; Seider, Eliana; Daunt, Lauren; Vashishth, Vanessa; Abbas, Aazad; Cadieux, Chloe; Lewis, Stephen; Ahmadi, Ali; Brzozowski, Pawel; Toobaie, Asra; Rasoulinejad, Parham; Fernandes, Renan Rodrigues; Young, James J; Urquhart, Jennifer; Bailey, Chris; McIntosh, Greg; Glennie, Andrew; Fisher, Charles; Perruccio, Anthony V; Rampersaud, Raja; Glennie, Andrew; Urquhart, Jennifer; Mishreky, Amir; Fisher, Charles; Rampersaud, Raja; Bailey, Chris; MacLean, Mark A; Julien, Lisa; Patriquin, Glenn; Leblanc, Jason; Greene, Ryan; Alant, Jacob; Barry, Sean; Glennie, R Andrew; Oxner, William; Christie, Sean D; Pedro, Karlo; Abbas, Aazad; Bailey, Christopher; Urquhart, Jennifer; MacIntosh, Greg; Glennie, Andrew; Fisher, Charles; Phan, Philippe; Rampersaud, Y Raja; Smith, Daniel P; Bigney, Erin E; Hebert, Jeffrey; Richardson, Eden A; Manson, Neil A; Abraham, Edward; Zein, Abdullah; Holt, Kyra; Isaac, Hannah; Kearney, Jill; Small, Chris; Evaniew, Nathan; Alduwaisan, Abdullah; Smith, Victoria; Whittaker, Tara; Eckenswiller, Denise; Soumbasis, Elias; Tanguay, Robert; Jacobs, W Bradley; Thomas, Kenneth C; Nicholls, Fred; Soroceanu, Alex; Swamy, Ganesh; Nahanni, Celina; Lung, Tiffany S; Young, James J; Cadieux, Chloe N; Du, Jin Tong; Rampersaud, Raja; Glennie, Andrew; Dunning, Cynthia; Jones, Emma; Oxner, William; Lobo, Kaike; Łajczak, Paweł; Santos, Claudia; Rajab, Numa; Oliveira, Rafael; Silva, Yasmin Picanco; Barbosa, Ramon Guerra; Silva, Yan G M D; Abbas, Aazad; Sahi, Gurjovan; Du, Jin Tong; Johnson, Michael; Buchel, Edward; Toor, Jay; Kulkarni, Ronit; Bertolino, Melanie; Walton, Chase; Rivas, Gabriella; Glaser, John; Reitman, Charles A; Lawrence, James; Ravinsky, Robert; Pedro, Karlo; Fehlings, Michael; Alvi, Mohammed; Essa, Ahmad; Shakil, Husain; Malhotra, Armaan K; Nathens, Avery B; Badhiwala, Jetan; Yuan, Eva Y; He, Yingshi; Mathieu, Francois; Sklar, Michael C; Wilson, Jefferson; Witiw, Christopher D; Yoon, Samuel; Reda, Luke A; Malhotra, Armaan; Shakil, Hussain; Fehlings, Michael G; Witiw, Christopher D; Wilson, Jefferson R; Badhiwala, Jetan H; Sadiqi, Said; Muijs, Sander P J; Dandurand, Charlotte; Dvorak, Marcel F; Oner, F Cumhur; ,; Dionne, Antoine; Richard-Denis, Andréane; Phan, Philippe; Mputu, Pascal Mputu; Mac-Thiong, Jean-Marc; Le, Vivian Huong Hoang Thien; Mputu, Pascal Mputu; Richard-Denis, Andreane; Bernard, Francis; Cavayas, Yiorgos Alexandros; Dionne, Antoine; Mac-Thiong, Jean-Marc; Attabib, Najmedden A; Hong, Heather A; Kurban, Dilnur; Yang, Tianyu; Fallah, Nader; Cheng, Christiana L; Humphreys, Suzanne; Noonan, Vanessa K; El-Mughayyar, Dana; Craig, Michael; O'Connell, Colleen; ,; Shakil, Husain; Hu, Zixuan; Smith, Christopher W; Malhotra, Armaan K; Essa, Ahmad; Ling, Hui M; Khan, Zakariya M; Sejdic, Ervin; Colak, Errol; Witiw, Christopher D; Duguay, Maude; Hernandez, Juan David Cifuentes; Mac-Thiong, Jean-Marc; Dionne, Antoine; Bensoussan, Natan; Richard-Denis, Andreane; Carrier, Louis; Blanchard, Jocelyn; LaRue, Bernard; Paquette, Ariane; Silva, Yan Gabriel Morais; Nielsen, Christopher J; Bhatt, Vaidehi; Lewis, Stephen J; Rampersaud, Y Raja; Rosenstein, Brent; Montpetit, Chanelle; Vaillancourt, Nicolas; Dover, Geoffrey; Weiss, Christina; Papula, Lee Ann; Melek, Antonys; Fortin, Maryse; Fazlollahi, Ali M; Barak, Uri; Kalhor, Samira; Nguyen, Joshua Hien; Santaguida, Carlo; Raj, Ruheksh; Lewkonia, Peter; Rogan, Kyle; Marchuk, Allison; Barrett, Erin; Masson, Anand; Pratt, Brandy; Michaud, Danielle; Skyrda, Kateryna; Simms, Sierra; Yang, Michael; Herrington, Brandon J; Urquhart, Jennifer C; Rasoulinejad, Parham; Siddiqi, Fawaz; Gurr, Kevin; Bailey, Christopher S; Chayer, Mathieu; Phan, Philippe; Arnoux, Pierre-Jean; Wang, Zhi; Rawlinson, Jeremy; Aruwajoye, Olumide; Aubin, Carl-Éric; Samhat, Hussein; Pedro, Karlo M; Pirshahid, Ali Ahmadi; Charest-Morin, Raphaële; Gore, Genevieve; Filion, Kristian B; Lasry, Oliver; Levett, Jordan J; Dea, Nicolas; Evanview, Nathan; McIntosh, Greg; Weber, Michael H; Rinott, Nadav; Laflamme, Mathieu; McIntosh, Greg; Evaniew, Nathan; Weber, Michael H; Dea, Nicolas; Liu, Andy; Tuchman, Alexander; Mikhail, Christopher; Chan, Vivien; McDonald, James; Zaldivar, Julien; Dea, Nicolas; Koegl, Nikolaus; McIntosh, Greg; Evaniew, Nathan; Lonjon, Guillaume; Vassal, Matthieu; Dhenin, Alexandre; Perez, Alexis; Dupuy, Martin; Challier, Vincent; Castelain, Jean-Etienne; Ghailane, Soufiane; Campana, Matthieu; Lebhar, Jonathan; Guerin, Gilles; Pellet, Nicolas; Sabah, Yann; Chevillotte, Thomas; Darnis, Alice; Cristini, Joseph; Ferracci, François-Xavier; Delambre, Jérôme; Queinnec, Steffen; Delmotte, Alexandre; Marinho, Paulo; Gauthe, Rémi; Hannequin, Pierre; Gilard, Vianney; Meyblum, Jean; Perrin, Alexis; Pietton, Raphaël; Lonjon, Nicolas; Gennari, Antoine; Malhotra, Armaan K; Shakil, Husain; Essa, Ahmad; Evaniew, Nathan; ,; Witiw, Christopher D; Wilson, Jefferson R; Dea, Nicolas; Al-Shawwa, Abdul; Craig, Michael; Ost, Kalum; Jacobs, W Bradley; Evaniew, Nathan; Lewkonia, Peter; Nicholls, Fred; Soroceanu, Alex; Swamy, Ganesh; Thomas, Kenneth C; Yang, Michael M H; Adad, Julien-Cohen; Cadotte, David W; Wangai, Isaac; Nataraj, Andrew; Hojanepesov, Osman; Cadotte, David; Skarsgard, Matthew; Evaniew, Nathan; Paquet, Jerome; Dhaliwal, Perry; Attabib, Najmedden; Urquhart, Jennifer; Dea, Nicolas; Bailey, Chris; Karthikeyan, Vishwathsen; Shakil, Husain; Malhotra, Armaan; Lozano, Christopher; Wilson, Jefferson; Fehlings, Michael; Badhiwala, Jetan; Koegl, Nikolaus; McIntosh, Greg; Dea, Nicolas; Evaniew, Nathan; Charest-Morin, Raphaële; Kurtz, Daniel; Phan, Philippe; Sun, Christopher; Cho, Newton; Al-Shawwa, Abdul; Jacobs, Bradley; Evaniew, Nathan; Bouchard, Jacques; Casha, Steven; duPlessis, Stephan; Lewkonia, Peter; Nicholls, Fred; Soroceanu, Alex; Swamy, Ganesh; Thomas, Kenneth; Yang, Michael; Cohen-Adad, Julien; Cadotte, David; Charest-Morin, Raphaële; Hansen, Landon; Yip, Stephen; Dea, Nicolas; Goodwin, Rory C; Fisher, Charles G; Bettegowda, Chetan; Versteeg, Anne L; Sahgal, Arjun; Laufer, Ilya; Rhines, Laurence; Sciubba, Daniel; Schuster, James; Weber, Michael; Lazary, Aron; Boriani, Stefano; Bettegowda, Chetan; Fehlings, Michael; Clarke, Michelle; Arnold, Paul; Gokaslan, Ziya; Fisher, Charles; Versteeg, Anne; Weber, Michael; De La Garza Ramos, Rafael; Shin, John; Pahuta, Mark; Luzatti, Alessandro; Disch, Alexander; Gasbarrini, Alessandro; Verlaan, Jorrit-Jan; Teixeira, William; Sahgal, Arjun; Laufer, Ilya; Lazary, Aron; Chou, Dean; Fisher, Charles; Gokaslan, Ziya; Fehlings, Michael; Rhines, Laurence; Mesfin, Addisu; Sciubba, Daniel; Bettegowda, Chetan; Goldschlager, Tony; Netzer, Cordula; Clarke, Michelle; O'Toole, John; Boriani, Stefano; Barzilai, Ori; Kawahara, Nori; Kumar, Naresh; Dea, Nicolas; Reynolds, Jeremy; Goodwin, Rory; Charest-Morin, Raphaële; ,; Shakil, Husain; Malhotra, Armaan K; Essa, Ahmad; Karthikeyan, Vishwathsen; Lozano, Christopher S; Badhiwala, Jetan H; Sahgal, Arjun; Dea, Nicolas; Fehlings, Michael G; Kiss, Alex; Witiw, Christopher D; Redelmeier, Donald A; Wilson, Jefferson R; Kwan, William Chu; Koegl, Nikolaus; Dea, Nicolas; Fisher, Charles; Charest-Morin, Raphaële; Rocha, Alexandra; Renaud, Matthew; Urquhart, Jennifer; Singh, Supriya; Caceres, Marco Perez; Ahmed, Omer; Freire, Véronique; Shen, Jesse; Al-Shakfa, Fidaa; Boulé, Danielle; Wang, Zhi; Lozano, Christopher S; Malhotra, Armaan K; Karthikeyan, Vishwathsen; Shakil, Husain; Balasubramaniam, Neevya; Wilson, Jefferson R; Witiw, Christopher; Jacobs, W Bradley; Wang, Zhi; Dhaliwal, Perry; Santaguida, Carlo; Bailey, Chris; Bangsboll, Emily; Roach, Koren; Duncan, Neil; Salo, Paul; Bouchard, Jacques; Ronsky, Janet; Swamy, Ganesh; Ngana, Germain Sophie; Nassrullah, Zain; Alhantoobi, Mohamed; Al-Assiri, Suhail S; Al-Zailaie, Abdulaziz; Ngetich, Geofrey; Kwok, Desmond; Pahuta, Markian; Martinyuk, Amanda; Guha, Daipayan; Evaniew, Nathan; Malholtra, Armaan K; Charest-Morin, Raphaële; Soroceanu, Alex; Jacobs, W Bradley; Cadotte, David W; Dea, Nicolas; Halabian, Negeen; Deng, Jiawen; Alvi, Mohammed Ali; Pedro, Karlo M; Fehlings, Michael G; Cho, Newton; Al-Shawwa, Abdul; Jacobs, Bradley; Evaniew, Nathan; Lewkonia, Peter; Nicholls, Fred; Soroceanu, Alex; Swamy, Ganesh; Thomas, Kenneth; Yang, Michael; Cadotte, David; Siddiqi, Omar; Urquhart, Jennifer; Fernandes, Renan Rodrigues; Wangai, Isaac; Walker, Taryn; Alanezi, Turki; Raj, Ruheksh; Bailey, Chris; Barbosa, Ramon Guerra; Pimenta, Newton; Silva, Yan; Tobin, Jacqueline; Martin, John; Kouame, Mark; Rivas, Gabriella; Reitman, Charles; Glaser, John; Lawrence, James; Ravinsky, Robert; Alfawaz, Thamer; Zhang, Tinghua; Dea, Nicolas; Evaniew, Nathan; Phan, Philippe; Outcomes, Canadian Spine; Network, Research; Karthikeyan, Vishwathsen; Shakil, Husain; Malhotra, Armaan; Lozano, Christopher; Wilson, Jefferson; Silva, Yan G M D; Barbosa, Ramon; de Souza Rodrigues Júnior, Erenaldo; Filho, Carlos Alberto Assunção; Gomes, Rodrigo; de Oliveira, Luis Fernando Weber; Fay, Mary; Christie, Sean; Barry, Sean; Lethbridge, Lynn; Oxner, William; Johnston, Emily; Glennie, Andrew; Belanger, Geneviève L; Wai, Eugene K; Skaik, Khaled; Smith-Forrester, Jenna; Rowicki, Michelle; Gillis, Justina; Jones, Karen; Freeman, Jason; Mitchell, Matt; MacLean, Emily; Hollahan, Renee; Hardy, Leslie; MacDonald, Christina; Decker, Alissa; Barry, Sean; Glennie, Andrew; Oxner, William; Weise, Lutz; Christie, Sean; Barter, Lauren; Glennie, Andrew; Christie, Sean; Zwicker, Cynthia Dunning; Oxner, Bill; Jaffe, Rachael; Malhotra, Armaan; Shakil, Husain; Witiw, Christopher; Bradley, Sarah; Martin, John; Rivas, Gabriella; Seeger, Sydney; Glaser, John; Reitman, Charles; Lawrence, James; Ravinsky, Robert; Daunt, Lauren I; Vashishth, Vanessa; Seider, Eliana; Abbas, Aazad; Daziano, Mauricio Campos; Rienmüller, Anna C; Ames, Christopher; Lewis, Stephen J; Kow, Chien Yew; Moghaddam, Farbod; Choi, May; Nicholls, Fred; Cadieux, Chloe; Rienmüller, Anna C; Kwan, Kenny Yat Hong; Qiu, Yong; Pellise, Ferran; Alanay, Ahmet; Smith, Justin; Quraishi, Nasir; Gray, Randolph; Basu, Saumyajii; Yoshida, Go; Lenke, Lawrence; Lewis, Stephen J; Nielsen, Christopher J; Alavi, Fatemeh; Dantas, Francois; Rampersaud, Y Raja; Lewis, Stephen J; Łajczak, Paweł; Silva, Yasmin Picanco; Ayesha, Ayesha; Von Quednow, Enzo; Jabbar, Rabbia; Zottele, Mariana Zamprogno; Nascimento, Gabriela Fonseca; Rocha, Fabio Victor Vieira; Sahin, Oguz Kagan; Sharma, Eshita; Barbosa, Ramon; Fagundes, Walter; Silva, Yan G M D; Kow, Chien Yew; Moghaddam, Farbod; Choi, May; Nicholls, Fred; Chaves, Jennyfer Paulla Galdino; Hsu, Brian; Sima, Stone; Singh, Bhisham; Diwan, Ashish; Smith, Victoria; Evaniew, Nathan; Soroceanu, Alex; Lewis, Steve; Nicholls, Fred; Swamy, Ganesh; Abdelnour, Mark; Cierson, Tanya; Mumtaz, Rohail; Zhang, TingHua; Alhowsawi, Mamdoh; Swamy, Ganesh; Thomas, Kenneth; Soroceanu, Alex; Wang, Zhi; Stratton, Alexandra; Kingwell, Stephen; Wai, Eugene; Tsai, Eve; Phan, Philippe Tran Nhut; Cadieux, Chloe; Kato, So; Klineberg, Eric; Yilgor, Caglar; Kelly, Michael; Lenke, Lawrence; Shaffrey, Christopher; Cheung, Kenneth; Berven, Sigurd; Matsuyama, Yukihiro; Pellise, Ferran; Dahl, Benny N; Spruit, Maarten; Alanay, Ahmet; Lewis, Stephen J; Eissa, Abdullah T; Kato, So; Lenke, Lawrence; Jones, Kristen; Nielsen, Christopher; Basu, Saumyajit; Kelly, Michael; Strantzas, Samuel; Qiu, Yong; Pellise, Ferran; Alanay, Ahmet; Quraishi, Nasir; Gray, Randolph; Yoshida, Go; Aziz, Amer; Lewis, Stephen; Chan, Vivien; Etigunta, Suhas; Malhotra, Armaan K; Shumilak, Geoffrey; Lebel, David E; Illingworth, Kenneth D; Skaggs, David L; Zohar, Ariel; Loomans, Janneke; Pellise, Ferran; Kato, So; Sardar, Zeeshan; Lenke, Lawrence G; Lewis, Stephen J; Switzer, Lily; Aboelmagd, Karim; Anthony, Alison; Nadler, Emma; Dermott, Jennifer A; Camp, Mark; Lebel, David E; Aboelmagd, Karim; Versteeg, Anne; Camp, Mark; Zeller, Reinhard; Lebel, David; Batista, Nuno M; Liu, Taylor; Romeo, Jessica; Tice, Andrew; Jarvis, James; Smit, Kevin; Imbeault, Rachelle; Shen, Jesse; Parent, Stefan; Alzakri, Abdulmajeed; Turcot, Olivier; Beauséjour, Marie; Roy-Beaudry, Marjolaine; Barchi, Soraya; Turgeon, Isabelle; Yoon, Samuel; Rutz, Erich; Percival, Mia; Johnson, Michael B; Lundine, Kris; Chan, Vivien; Shumilak, Geoffrey; Malhotra, Armaan K; Lebel, David E; Illingworth, Kenneth D; Skaggs, David L; Nielsen, Christopher J; Alavi, Fatemeh; Dantas, Francois; Rampersaud, Y Raja; Lewis, Stephen J; Chan, Vivien; Kong, Andrew Michael Chan Tai; Gausper, Adeesya; Etigunta, Suhas; Liu, Andy M; Illingworth, Kenneth D; Skaggs, David L; Łajczak, Paweł; Sharma, Eshita; Petry, Iago Nathan Simon; Jabbar, Rabbia; Silva, Yasmin Picanço; Rocha, Fabio Victor Vieira; Sahin, Oguz Kagan; da Silva Lobo, Kaike Eduardo; Ayesha, Ayesha; Ahmed, Aisha Rizwan; Fagundes, Walter; Silva, Yan G M D; Abbas, Aazad; Pedro, Karlo; Bailey, Christopher; Phan, Philippe; Uruqhurt, Jennifer; McIntosh, Greg; Rampersaud, Y Raja; Cadieux, Chloe; Lung, Tiffany; Du, Jin Tong; Nahanni, Celina; Nielsen, Christopher; Lewis, Stephen J; Rampersaud, Raja Y; Ross, Nicolas; Aleman, Carlos; Dhenin, Alexandre; Vassal, Matthieu; Lonjon, Guillaume; Salimi, Hamidullah; Terai, Hidetomi; Tamai, Koji; Uematsu, Masato; Katsuda, Hiroshi; Sharma, Eshita; Ayesha, Ayesha; Lobo, Kaike Eduardo Silva; Pomianoski, Beatriz Westphalen; Kotochinsky, Jose Martin; Silva, Yan G M D; Barbosa, Ramon Guerra; Pimenta, Newton; Silva, Yan; Kim, Jieun; Roberts, Richard; Kortbeek, Frank; MacLean, Mark A; Rampersaud, Y Raja; Bailey, Chris; Fisher, Charles; Glennie, R Andrew; Lonjon, Guillaume; Dhenin, Alexandre; Vassal, Matthieu; Van Brenk, Hannah; Bigney, Erin E; Manson, Neil A; Small, Chris; Abraham, Edward; Attabib, Najmedden; Kearney, Jill; Richardson, Eden A; deVries, Gwyneth; Dombrowski, Stephan; ,; Hebert, Jeffrey; Barbosa, Ramon Guerra; Pimenta, Newton; Silva, Yan; Fernandes, Renan Rodrigues; Jacobs, Bradley; Witiw, Christopher; Wang, Zhi; Dhaliwal, Perry; Santaguida, Carlo; Bailey, Christopher; Faridi, Sufyan; Bigney, Erin; Hebert, Jeffrey; Manson, Neil; Abraham, Edward; Small, Chris; Richardson, Eden; Kearney, Jill; Attabib, Najmedden; Rampersaud, Y Raja; Power, J Denise; Kapoor, Mohit; Perruccio, Anthony V; Sharma, Eshita; Lobo, Kaike Eduardo Silva; Ayesha, Ayesha; Łajczak, Paweł; Pomianoski, Beatriz Westphalen; Silva, Yan G M D; Wang, Zhi; Jacobs, Bradley; Witiw, Christopher; Dhaliwal, Perry; Santaguida, Carlo; Bailey, Chris; Wright, Alicia; Rosenstein, Brent; Montpetit, Chanelle; Vaillancourt, Nicolas; Fortin, Maryse; Rosenstein, Brent; Bergevin, Maxime; Bobeuf, Florian; Bherer, Louis; Pageaux, Benjamin; Roy, Mathieu; Fortin, Maryse; Wolfe, Daniel; Dover, Geoffrey; Boily, Mathieu; Fortin, Maryse; Nadler, Emma; Lebel, David E; Kim, Dorothy J; Dermott, Jennifer A; Wagman, Emma; Kim, Dorothy J; Nadler, Emma; Lebel, David E; Dermott, Jennifer A; Provost, Myriam; Cobetto, Nikita; Beausejour, Marie; Joncas, Julie; Rojas, Francisca; Tran, Shi-Jia; Sharma, Dhawal; Balondona, Aurelien; Labelle, Hubert; Aubin, Carl-Eric; Chan, Vivien; Michael, George; Illingworth, Kenneth D; Skaggs, David L; Thibault, Jérémie; Dionne, Antoine; Mac-Thiong, Jean-Marc; Olijnyk, Leonardo; Le, Vivian Huong Hoang Thien; Al-Shakfa, Fidaa; Florial, Edisond; Shedid, Daniel; Yuh, Sung-Joo; Boubez, Ghassan; Shen, Jesse; Wang, Zhi; Le, Vivian Huong Hoang Thien; Olijnyk, Leonardo; Al-Shakfa, Fidaa; Florial, Edisond; Shedid, Daniel; Yuh, Sunj-Joo; Boubez, Ghassan; Wang, Zhi; Truong, Van Tri; Dang, The Khanh; Osman, Galil; Al-Shakfa, Fidaa; Boulé, Danielle; Phan, Philippe; Shen, Jesse; Wang, Zhi; Versteeg, Anne; Abdoelmagd, Karim; Camp, Mark; Lebel, David; Hopyan, Sevan; Lewis, Stephen; Essa, Ahmad; Shakil, Husain; Malhotra, Armaan K; Nathens, Avery B; Yuan, Eva Y; He, Yingshi; Jack, Andrew S; Mathieu, Francois; Anekstien, Yoram; Azad, Tej D; Wilson, Jefferson R; Witiw, Christopher D; Bond, Michael; Beresford, Aidan; Noonan, Vanessa K; Rotem-Kohavi, Naama; Dvorak, Marcel F; Kwon, Brian K; Liu, Guiping; Sutherland, Jason M; Ryan, Gareth; Smith, Victoria; Nicholls, Fred; Lischynski, Jennifer R; Brar, Karnvir; Siddiqui, Aasiyah; Galdino, Jennyfer; Ajoku, Uchenna; Vega, Miguel; Alizadeh, Arsilan; Siddiqui, Faisal; Zeiler, Frederick; Dhaliwal, Perry; Whitten, Tara A; Rotem-Kohavi, Naama; Thorogood, Nancy; Humphreys, Suzanne P; Noonan, Vanessa K; Ho, Chester; Bakal, Jeffrey A; Pedro, Karlo; Fehlings, Michael; Alvi, Mohammed; Pedro, Karlo; Fehlings, Michael; Alvi, Mohammed; Essa, Ahmad; Malhotra, Armaan K; Shakil, Husain; Nathens, Avery B; Yuan, Eva Y; He, Yingshi; Jack, Andrew S; Mathieu, Francois; Wilson, Jefferson R; Witiw, Christopher D; Fehlings, Michael; Pedro, Karlo; Alvi, Mohammed; Dionne, Antoine; Richard-Denis, Andréane; Brouillard, Émile; Lassassy, Ismail; Bourassa-Moreau, Etienne; Khoueir, Paul; Wang, Zhi; Mac-Thiong, Jean-Marc; Bond, Michael; Beresford, Aidan; Noonan, Vanessa K; Rotem-Kohavi, Naama; Dvorak, Marcel F; Kwon, Brian K; Liu, Guiping; Sutherland, Jason M; Essa, Ahmad; Malhotra, Armaan K; Shakil, Husain; Nathens, Avery B; Yuan, Eva Y; He, Yingshi; Mathieu, Francois; Sklar, Michael C; Wilson, Jefferson R; Witiw, Christopher D; Badhiwala, Jetan; Sharma, Ojasvi; Levett, Jordan J; Weber, Michael H; Barbosa, Ramon Guerra; Lages, Gustavo; Alencar, Johmeson; Sadiqi, Said; Hakbijl-van der Wind, Aline J; Egberts, Sylvia; Stolwijk, Janneke; Osterthun, Rutger; van Diemen, Tijn; Oner, F Cumhur; Post, Marcel W M; ,; Hong, Heather A; Parsons, Jessica; Xu, Jijie; Walden, Kristen; Fallah, Nader; Cheng, Christiana L; Attabib, Najmedden; Christie, Sean D; Craven, Cathy B; Fehlings, Michael; Fourney, Daryl R; Kainth, Hardeep S; Kwon, Brian K; Linassi, Gary A; Moganathas, Saranjan; Paquet, Jerome; Mac-Thiong, Jean-Marc; Townson, Andrea F; Urquhart, Jennifer; Tsai, Eve; Whelan, Alex J; Noonan, Vanessa K; ,; Ye, Vincent C; Malhotra, Armaan K; Shakil, Husain; Essa, Ahmad; Witiw, Christopher D; Bond, Michael; Beresford, Aidan; Noonan, Vanessa K; Rotem-Kohavi, Naama; Dvorak, Marcel F; Kwon, Brian K; Liu, Guiping; Sutherland, Jason M; Karthikeyan, Vishwathsen; Lozano, Christopher; Malhotra, Armaan; Shakil, Husain; Wilson, Jefferson; Witiw, Christopher; Badhiwala, Jetan; Chenevert, Alexandre; Lanoue, Charlotte; Couture, Jérôme; Bédard, Sonia; Gammel, Juliette; Silvestre, Jason; Rivas, Gabrielle; Lawrence, James; Ravinsky, Robert; Dermott, Jennifer A; Jaakkimainen, Liisa; To, Teresa; Bouchard, Maryse; Howard, Andrew W; Lebel, David E; Ostertag, Curtis A; Whittaker, Tara; Nicholls, Fred H; Dukkipati, Siril Teja; Driscoll, Mark; Lu, Daisy A; Sahraoui, Oussama; Danino, Alain; Wang, Zhi; Sahi, Gurjovan; Du, Jin Tong; Abbas, Aazad; Hanna, Sager; Berrington, Neil; Almojuela, Alysa; Johnson, Michael; Lewis, Stephen; Goytan, Michael; Toor, Jay; Du, Jin Tong; Lung, Tiffany; Nahanni, Celina; Cadieux, Chloe; Dandal, Gavin; Anderson, Nicola; Lewis, Stephen; Nielsen, Christopher; Massicote, Eric; Rampersaud, Raja; Skaik, Khaled; Phan, Philippe; Belanger, Genevieve; Kingwell, Stephen; Stratton, Alexandra; Coyle, Matthew; Wai, Eugene; Olijnyk, Leonardo; Kaiser, Paul; Brunette-Clément, Tristan; Shedid, Daniel; Yuh, Sung-Joo; Barbosa, Ramon Guerra; Lages, Gustavo; Pimenta, Newton; Murray, Sean A; Driscoll, Mark; Lung, Tiffany; Cadieux, Chloe; Du, Jin Tong; Lazarus, Jed; Nahanni, Celina; Nielsen, Christopher; Rampersaud, Raja; Yoo, Arim; Gandhi, Pranjan; Rajapaksege, Nathasha; Hart, Shannon L; Shi, Victoria; Pahuta, Markian; Guha, Daipayan; Lu, Daisy A; Wang, Zhi; Al-Shakfa, M Fidaa; Shen, Jesse; Mulhall, Drew; Kow, Chien Yew; Masson, Anand Oliveira; Veilleux, Catherine; du Plessis, Stephan; Casha, Steve; Thomas, Ken; Yang, Michael; Valošek, Jan; Bouthillier, Maxime; Cohen-Adad, Julien; ,; Li, Ling Jing; Dukkipati, Siril Teja; Driscoll, Mark; Ludwig, Taryn; Mina, Mina; Gibbon, Stephanie; Bello, Oluwakanyinsola; Anderson, Sarah J; Willetts, Lian; Lewkonia, Peter; Deprato, Andy; Chalmers, Kieran; Tice, Andrew; Romeo, Jessica; Carsen, Sasha; Smit, Kevin; Hadi, Ayesha; Kim, Dorothy J; Doria, Andrea S; Khalvati, Farzad; Chen, Chaojun; Dermott, Jennifer A; Lebel, David E; Dufresne, Justin; Aubert, Benjamin; Imbeault, Rachelle; Roy-Beaudry, Marjolaine; Cresson, Thierry; Parent, Stefan; Liu, Taylor; Tice, Andrew; Romeo, Jessica; Smit, Kevin
PMID: 41386990
ISSN: 1488-2310
CID: 5978112
BMC health services research. 2019:19(1).DOI: 10.1186/s12913-019-4018-0

Association of in-hospital resource utilization with post-acute spending in Medicare beneficiaries hospitalized for acute myocardial infarction: a cross-sectional study

Nuti, Sudhakar V; Li, Shu-Xia; Xu, Xiao; Ott, Lesli S; Lagu, Tara; Desai, Nihar R; Murugiah, Karthik; Duan, Michael; Martin, John; Kim, Nancy; Krumholz, Harlan M
BACKGROUND:Efforts to decrease hospitalization costs could increase post-acute care costs. This effect could undermine initiatives to reduce overall episode costs and have implications for the design of health care under alternative payment models. METHODS:Among Medicare fee-for-service beneficiaries aged ≥65 years hospitalized with acute myocardial infarction (AMI) between July 2010 and June 2013 in the Premier Healthcare Database, we studied the association of in-hospital and post-acute care resource utilization and outcomes by in-hospital cost tertiles. RESULTS:Among patients with AMI at 326 hospitals, the median (range) of each hospital's mean per-patient in-hospital risk-standardized cost (RSC) for the low, medium, and high cost tertiles were $16,257 ($13,097-$17,648), $18,544 ($17,663-$19,875), and $21,831 ($19,923-$31,296), respectively. There was no difference in the median (IQR) of risk-standardized post-acute payments across cost-tertiles: $5014 (4295-6051), $4980 (4349-5931) and $4922 (4056-5457) for the low (n = 90), medium (n = 98), and high (n = 86) in-hospital RSC tertiles (p = 0.21), respectively. In-hospital and 30-day mortality rates did not differ significantly across the in-hospital RSC tertiles; however, 30-day readmission rates were higher at hospitals with higher in-hospital RSCs: median = 17.5, 17.8, and 18.0% at low, medium, and high in-hospital RSC tertiles, respectively (p = 0.005 for test of trend across tertiles). CONCLUSIONS:In our study of patients hospitalized with AMI, greater resource utilization during the hospitalization was not associated with meaningful differences in costs or mortality during the post-acute period. These findings suggest that it may be possible for higher cost hospitals to improve efficiency in care without increasing post-acute care utilization or worsening outcomes.
PMCID:6432744
PMID: 30909904
ISSN: 1472-6963
CID: 5429802