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1. Intravenously administered interleukin-7 to reverse lymphopenia in patients with septic shock: a double-blind, randomized, placebo-controlled trial [2023]

  • Daix, Thomas, Mathonnet, Armelle, Brakenridge, Scott, Dequin, Pierre-François, Mira, Jean-Paul, Berbille, Frederique, Morre, Michel, Jeannet, Robin, Blood, Teresa, Unsinger, Jacqueline, Blood, Jane, Walton, Andrew, Moldawer, Lyle L., Hotchkiss, Richard, and Francois, Bruno
  • Annals of Intensive Care. December, 2023, Vol. 13 Issue 1

2. Patient‐reported outcome measures and patient engagement in heart failure clinical trials: multi‐stakeholder perspectives. [2023]

  • Zannad, Faiez, Alikhaani, Jacqueline, Alikhaani, Sadegh, Butler, Javed, Gordon, Jason, Jensen, Klaus, Khatib, Rani, Mantovani, Lorenzo, Martinez, Robin, Moore, Wanda F., Murakami, Masahiro, Roessig, Lothar, Stockbridge, Norman, Van Spall, Harriette G.C., Yancy, Clyde, and Spertus, John A.
  • European Journal of Heart Failure. Mar2023, p1. 10p. 2 Illustrations, 4 Charts.
Abstract
There are many consequences of heart failure (HF), including symptoms, impaired health‐related quality of life (HRQoL), and physical and social limitations (functional status). These have a substantial impact on patients' lives, yet are not routinely captured in clinical trials. Patient‐reported outcomes (PROs) can quantify patients' experiences of their disease and its treatment. Steps can be taken to improve the use of PROs in HF trials, in regulatory and payer decisions, and in patient care. Importantly, PRO measures (PROMs) must be developed with involvement of patients, family members, and caregivers from diverse demographic groups and communities. PRO data collection should become more routine not only in clinical trials but also in clinical practice. This may be facilitated by the use of digital tools and interdisciplinary patient advocacy efforts. There is a need for standardization, not only of the PROM instruments, but also in procedures for analysis, interpretation and reporting PRO data. More work needs to be done to determine the degree of change that is important to patients and that is associated with increased risks of clinical events. This ‘minimal clinically important difference’ requires further research to determine thresholds for different PROMs, to assess consistency across trial populations, and to define standards for improvement that warrant regulatory and reimbursement approvals. PROs are a vital part of patient care and drug development, and more work should be done to ensure that these measures are both reflective of the patient experience and that they are more widely employed. [ABSTRACT FROM AUTHOR]

3. Patterns of failure in pediatric medulloblastoma and implications for hippocampal sparing. [2023]

  • Baliga, Sujith, Adams, Judith A., Bajaj, Benjamin V. M., Van Benthuysen, Liam, Daartz, Juliane, Gallotto, Sara L., Lewy, Jacqueline R., DeNunzio, Nicholas, Weyman, Elizabeth A., Lawell, Miranda P., Palmer, Joshua D., Yeap, Beow Y., Ebb, David H., Huang, Mary S., Perry, Alisa F., MacDonald, Shannon M., Jones, Robin M., Tarbell, Nancy J., and Yock, Torunn I.
  • Cancer (0008543X). Mar2023, Vol. 129 Issue 5, p764-770. 7p.
Subjects
MEDULLOBLASTOMA, HIPPOCAMPUS (Brain), CHILD patients, VOLUMETRIC-modulated arc therapy, BRAIN tumors, and SUBSTANCE abuse relapse
Abstract
Background: Hippocampal avoidance (HA) has been shown to preserve cognitive function in adult patients with cancer treated with whole‐brain radiation therapy for brain metastases. However, the feasibility of HA in pediatric patients with brain tumors has not been explored because of concerns of increased risk of relapse in the peri‐hippocampal region. Our aim was to determine patterns of recurrence and incidence of peri‐hippocampal relapse in pediatric patients with medulloblastoma (MB). Methods and materials: We identified pediatric patients with MB treated with protons between 2002 and 2016 and who had recurrent disease. To estimate the risk of peri‐hippocampal recurrence, three hippocampal zones (HZs) were delineated corresponding to ≤5 mm (HZ‐1), 6 to 10 mm (HZ‐2), and >10 mm (HZ‐3) distance of the recurrence from the contoured hippocampi. To determine the feasibility of HA, three standard‐risk patients with MB were planned using either volumetric‐modulated arc therapy (VMAT) or intensity‐modulated proton therapy (IMPT) plans. Results: Thirty‐eight patients developed a recurrence at a median of 1.6 years. Of the 25 patients who had magnetic resonance imaging of the recurrence, no patients failed within the hippocampus and only two patients failed within HZ‐1. The crude incidence of peri‐hippocampal failure was 8%. Both HA‐VMAT and HA‐IMPT plans were associated with significantly reduced mean dose to the hippocampi (p <.05). HA‐VMAT and HA‐IMPT plans were associated with decreased percentage of the third and lateral ventricles receiving the prescription craniospinal dose of 23.4 Gy. Conclusions: Peri‐hippocampal failures are uncommon in pediatric patients with MB. Hippocampal avoidance should be evaluated in a prospective cohort of pediatric patients with MB. Plain Language Summary: In this study, the patterns of disease recurrence in patients with a pediatric brain tumor known as medulloblastoma treated with proton radiotherapy were examined. The majority of failures occur outside of an important structure related to memory formation called the hippocampus. Hippocampal sparing radiation plans using proton radiotherapy were generated and showed that dose to the hippocampus was able to be significantly reduced. The study provides the rationale to explore hippocampal sparing in pediatric medulloblastoma in a prospective clinical trial. The incidence of peri‐hippocampal failures in patients treated with proton radiotherapy for pediatric medulloblastoma was 8%.Hippocampal sparing plans were associated with significant reduction in the mean dose to the right and left hippocampi. [ABSTRACT FROM AUTHOR]

4. Evaluation of left cardiac chamber function with cardiac magnetic resonance and association with outcome in patients with systemic sclerosis. [2023]

  • Butcher, Steele C, Vos, Jacqueline L, Fortuni, Federico, Galloo, Xavier, Liem, Sophie I E, Bax, Jeroen J, Delgado, Victoria, Vonk, Madelon C, Leuven, Sander I van, Snoeren, Miranda, Messaoudi, Saloua El, Vries-Bouwstra, Jeska K de, Nijveldt, Robin, and Marsan, Nina Ajmone
  • Rheumatology. 2023 Supplement, Vol. 62, pSI20-SI31. 12p.
Subjects
LEFT heart ventricle, PATIENT aftercare, CAUSES of death, CONFIDENCE intervals, MAGNETIC resonance imaging, GLOBAL longitudinal strain, SYSTEMIC scleroderma, TERTIARY care, DESCRIPTIVE statistics, RESEARCH funding, LOGISTIC regression analysis, ODDS ratio, LEFT heart atrium, HEART failure, and PROPORTIONAL hazards models
Abstract
Objective This study aimed to determine whether lower values of feature-tracking cardiovascular magnetic resonance (CMR)-derived left atrial reservoir strain (LARS) and impaired left ventricular (LV) global longitudinal strain (GLS) were associated with the presence of symptoms and long-term prognosis in patients with SSc. Methods A total of 100 patients {54 [interquartile range (IQR) 46–64] years, 42% male} with SSc who underwent CMR imaging at two tertiary referral centres were included. All patients underwent analysis of LARS and LV GLS using feature-tracking on CMR and were followed-up for the occurrence of all-cause mortality. Results The median LV GLS was –21.8% and the median LARS was 36%. On multivariable logistic regression, LARS [odds ratio (OR) 0.964 per %, 95% CI 0.929, 0.998, P  = 0.049] was independently associated with New York Heart Association (NYHA) class II–IV heart failure symptoms. Over a median follow-up of 37 (21–62) months, a total of 24 (24%) patients died. Univariable Cox regression analysis demonstrated that LARS [hazard ratio (HR) 0.94 per 1%, 95% CI 0.91, 0.97, P  < 0.0001) and LV GLS (HR 1.10 per %, 95% CI 1.03, 1.17, P  = 0.005) were associated with all-cause mortality, while LV ejection fraction was not. Likelihood ratio tests demonstrated that LARS provided incremental value over prognostically important clinical and imaging parameters, including late gadolinium enhancement. Conclusion In patients with SSc, LARS was independently associated with the presence of NYHA class II–IV heart failure symptoms. Although both LARS and LV GLS were associated with all-cause mortality, only LARS provided incremental value over all evaluated variables known to be prognostically important in patients with SSc. [ABSTRACT FROM AUTHOR]

5. A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes [2023]

  • Zeidan, Amer M., Borate, Uma, Pollyea, Daniel A., Brunner, Andrew M., Roncolato, Fernando, Garcia, Jacqueline S., Filshie, Robin, Odenike, Olatoyosi, Watson, Anne Marie, Krishnadasan, Ravitharan, Bajel, Ashish, Naqvi, Kiran, Zha, Jiuhong, Cheng, Wei-Han, Zhou, Ying, Hoffman, David, Harb, Jason G., Potluri, Jalaja, and Garcia-Manero, Guillermo
  • American Journal of Hematology. February, 2023, Vol. 98 Issue 2, p272, 10 p.

6. 6-month antibody kinetics and durability after four doses of a SARS-CoV-2 vaccine in solid organ transplant recipients [2023]

  • Mitchell, Jonathan, Chiang, Teresa PY, Alejo, Jennifer L., Kim, Jake D., Chang, Amy, Abedon, Aura T., Avery, Robin K., Tobian, Aaron A. R., Levan, Macey L., Warren, Daniel S., Garonzik-Wang, Jacqueline M., Segev, Dorry L., Massie, Allan B., and Werbel, William A.
  • Clinical Transplantation. January, 2023, Vol. 37 Issue 1, pn/a, 3 p.

7. Vergence/accommodative therapy for symptomatic convergence insufficiency in children: Time course of improvements in convergence function [2023]

  • Jenewein, Erin C., Cotter, Susan, Roberts, Tawna, Kulp, Marjean, Mitchell, G. Lynn, Jones-Jordan, Lisa A., Chen, Angela M., Hopkins, Kristine, Huang, Kristine, Amster, Deborah, Fecho, Gregory, Tyler, Julie, Meiyeppen, Shivakhaami, Scheiman, Mitchell, Scheiman, Mitchell, Cooper, Jeffrey, Schulman, Erica, Hamian, Kimberly, Iacono, Danielle, Larson, Steven, Leung, Valerie, Meeder, Sara, Ramos, Elaine, Ritter, Steven, Steiner, Audra, Stormann, Alexandria, Vricella, Marilyn, Zhu, Xiaoying, Tamkins, Susanna, Aguilera, Naomi, Brafman, Elliot, Capo, Hilda, Cavuoto, Kara, Crespo, Isaura, Dowling, Monica, Draskovic, Kristie, Farag, Miriam, Fischer, Vicky, Grace, Sara, Gutierrez, Ailen, Manchola-Orozco, Carolina, Martinez, Maria, McKeown, Craig, Osigian, Carla, Pham, Tuyet-Suong, Small, Leslie, Townsend, Natalie, Gallaway, Michael, Boas, Mark, Calvert, Christine, Franz, Tara, Gerrouge, Amanda, Hayden, Donna, Margolies, Zachary, Myung, Jenny, Pollack, Karen, Shoge, Ruth, Tang, Andrew, Tannen, Noah, Trieu, Lynn, Trujillo, Luis, Buckland, Michelle, Ellis, Allison, Fogt, Jennifer, McDaniel, Catherine, McGann, Taylor, Morrison, Ann, Mulvihill, Shane, Peiffer, Adam, Plaumann, Maureen, Pierce, Gil, Preston, Julie, Reuter, Kathleen, Stevens, Nancy, Teeny, Jake, Toole, Andrew, Widmer, Douglas, Zimmerman, Aaron, Barnhardt, Carmen, Borsting, Eric, Chu, Raymond, Parker, Susan, Retnasothie, Dashaini, Wu, Judith, Hertle, Richard, Clark, Penny, Culp, Kelly, Fraley, Kathy, Grant, Drusilla, Hanna, Nancy, Knox, Stephanie, Lawhon, William, Li, Lan, Mitcheff, Sarah, Ricker, Isabel, Solis, Casandra, Wall, Palak, Zaczyk, Samantha, Marsh-Tootle, Wendy, Bowen, Michelle, Call, Terri, Domnanovich, Kristy, Frazier, Marcela, Guyette, Nicole, Hayes, Oakley, Houser, John, Lee, Sarah, Montejo, Jenifer, Oechslin, Tamara, Turner, Candace, Weise, Katherine, Coulter, Rachel, Bade, Annette, Bansal, Surbhi, Falco, Laura, Green, Katherine, Irizarry, Gabriela, Jhajj, Jasleen, Patterson, Nicole, Rodena, Jacqueline, Tea, Yin, Weiss, Dana, Zakaib, Lauren, Lorenzana, Ingryd, Meza, Yesena, Mann, Ryan, Quezada, Mariana, Rein, Scott, Rudaitis, Indre, Stepleton, Susan, Wajs, Beata, Redford, Maryann, Hertle, Richard, Redford, Maryann, Denton, Carolyn, Arnold, Eugene, Borsting, Eric, Chase, Christopher, Denton, Carolyn, Wee, Sharyl, Dahl-Leonard, Katlynn, Powers, Kenneth, Alaniz, Amber, Diener-West, Marie, Good, William V., Grisham, David, Kratochvil, Christopher J., Revicki, Dennis, Wanzek, Jeanne, Pollack, Karen, Abraham, Mustafa, Dangelo, Julianne, Hegedus, Jordan, Jones, Ian, Junglas, Alexander, Lee, Jihyun, Nettles, Jadin, Mitchell, Curtis, Osman, Mawada, Scott-Tibbs, Gloria, Sinnott, Loraine, Teasley, Chloe, Vang, Victor, and Varghese, Robin
  • Ophthalmic and Physiological Optics. January, 2023, Vol. 43 Issue 1, p105, 11 p.

8. Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis [2022]

  • Kanoni, Stavroula, Graham, Sarah E., Wang, Yuxuan, Surakka, Ida, Ramdas, Shweta, Zhu, Xiang, Clarke, Shoa L., Bhatti, Konain Fatima, Vedantam, Sailaja, Winkler, Thomas W., Locke, Adam E., Marouli, Eirini, Zajac, Greg J. M., Wu, Kuan-Han H., Ntalla, Ioanna, Hui, Qin, Klarin, Derek, Hilliard, Austin T., Wang, Zeyuan, Xue, Chao, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F., Holm, Hilma, Olafsson, Isleifur, Hwang, Mi Yeong, Han, Sohee, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M., Rasheed, Humaira, Havulinna, Aki S., Veturi, Yogasudha, Pacheco, Jennifer Allen, Rosenthal, Elisabeth A., Lingren, Todd, Feng, QiPing, Kullo, Iftikhar J., Narita, Akira, Takayama, Jun, Martin, Hilary C., Hunt, Karen A., Trivedi, Bhavi, Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E., Campbell, Archie, Lin, Kuang, Millwood, Iona Y., Rasheed, Asif, Hindy, George, Faul, Jessica D., Zhao, Wei, Weir, David R., Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Choudhury, Ananyo, Sengupta, Dhriti, Mahajan, Anubha, Brown, Michael R., Zhang, Weihua, Yu, Ketian, Schmidt, Ellen M., Pandit, Anita, Gustafsson, Stefan, Yin, Xianyong, Luan, Jian'an, Zhao, Jing-Hua, Matsuda, Fumihiko, Jang, Hye-Mi, Yoon, Kyungheon, Medina-Gomez, Carolina, Pitsillides, Achilleas, Hottenga, Jouke Jan, Wood, Andrew R., Ji, Yingji, Gao, Zishan, Haworth, Simon, Yousri, Noha A., Mitchell, Ruth E., Chai, Jin Fang, Aadahl, Mette, Bjerregaard, Anne A., Yao, Jie, Manichaikul, Ani, Hwu, Chii-Min, Hung, Yi-Jen, Warren, Helen R., Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L., Goel, Anuj, Sabater-Lleal, Maria, Noordam, Raymond, Mauro, Pala, Matteo, Floris, McDaid, Aaron F., Marques-Vidal, Pedro, Wielscher, Matthias, Trompet, Stella, Sattar, Naveed, Mallehave, Line T., Munz, Matthias, Zeng, Lingyao, Huang, Jianfeng, Yang, Bin, Poveda, Alaitz, Kurbasic, Azra, Lamina, Claudia, Forer, Lukas, Scholz, Markus, Galesloot, Tessel E., Bradfield, Jonathan P., Ruotsalainen, Sanni E., Daw, EWarwick, Zmuda, Joseph M., Mitchell, Jonathan S., Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A., Vazquez-Moreno, Miguel, Feitosa, Mary F., Wojczynski, Mary K., Wang, Zhe, Preuss, Michael H., Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W., Engmann, Jorgen, Tsao, Noah L., Verma, Anurag, Slieker, Roderick C., Lo, Ken Sin, Zilhao, Nuno R., Le, Phuong, Kleber, Marcus E., Delgado, Graciela E., Huo, Shaofeng, Ikeda, Daisuke D., Iha, Hiroyuki, Yang, Jian, Liu, Jun, Demirkan, AyÅe, Leonard, Hampton L., Marten, Jonathan, Frank, Mirjam, Schmidt, Börge, Smyth, Laura J., Caéadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kähönen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlos, Lyssenko, Valeriya, Nongmaithem, Suraj S., Bayyana, Swati, Stringham, Heather M., Irvin, Marguerite R., Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul R. H. J., Arbeeva, Liubov, Dorajoo, Rajkumar, Lange, Leslie A., Prasad, Gauri, Lorés-Motta, Laura, Pauper, Marc, Long, Jirong, Li, Xiaohui, Theusch, Elizabeth, Takeuchi, Fumihiko, Spracklen, Cassandra N., Loukola, Anu, Bollepalli, Sailalitha, Warner, Sophie C., Wang, Ya Xing, Wei, Wen B., Nutile, Teresa, Ruggiero, Daniela, Sung, Yun Ju, Chen, Shufeng, Liu, Fangchao, Yang, Jingyun, Kentistou, Katherine A., Banas, Bernhard, Nardone, Giuseppe Giovanni, Meidtner, Karina, Bielak, Lawrence F., Smith, Jennifer A., Hebbar, Prashantha, Farmaki, Aliki-Eleni, Hofer, Edith, Lin, Maoxuan, Concas, Maria Pina, Vaccargiu, Simona, van der Most, Peter J., Pitkänen, Niina, Cade, Brian E., van der Laan, Sander W., Chitrala, Kumaraswamy Naidu, Weiss, Stefan, Bentley, Amy R., Doumatey, Ayo P., Adeyemo, Adebowale A., Lee, Jong Young, Petersen, Eva R. B., Nielsen, Aneta A., Choi, Hyeok Sun, Nethander, Maria, Freitag-Wolf, Sandra, Southam, Lorraine, Rayner, Nigel W., Wang, Carol A., Lin, Shih-Yi, Wang, Jun-Sing, Couture, Christian, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Cuellar-Partida, Gabriel, Vestergaard, Henrik, Hidalgo, Bertha, Giannakopoulou, Olga, Cai, Qiuyin, Obura, Morgan O., van Setten, Jessica, Li, Xiaoyin, Liang, Jingjing, Tang, Hua, Terzikhan, Natalie, Shin, Jae Hun, Jackson, Rebecca D., Reiner, Alexander P., Martin, Lisa Warsinger, Chen, Zhengming, Li, Liming, Kawaguchi, Takahisa, Thiery, Joachim, Bis, Joshua C., Launer, Lenore J., Li, Huaixing, Nalls, Mike A., Raitakari, Olli T., Ichihara, Sahoko, Wild, Sarah H., Nelson, Christopher P., Campbell, Harry, Jäger, Susanne, Nabika, Toru, Al-Mulla, Fahd, Niinikoski, Harri, Braund, Peter S., Kolcic, Ivana, Kovacs, Peter, Giardoglou, Tota, Katsuya, Tomohiro, de Kleijn, Dominique, de Borst, Gert J., Kim, Eung Kweon, Adams, Hieab H. H., Ikram, M. Arfan, Zhu, Xiaofeng, Asselbergs, Folkert W., Kraaijeveld, Adriaan O., Beulens, Joline W. J., Shu, Xiao-Ou, Rallidis, Loukianos S., Pedersen, Oluf, Hansen, Torben, Mitchell, Paul, Hewitt, Alex W., Kähönen, Mika, Pérusse, Louis, Bouchard, Claude, Tönjes, Anke, Chen, Yii-Der Ida, Pennell, Craig E., Mori, Trevor A., Lieb, Wolfgang, Franke, Andre, Ohlsson, Claes, Mellström, Dan, Cho, Yoon Shin, Lee, Hyejin, Yuan, Jian-Min, Koh, Woon-Puay, Rhee, Sang Youl, Woo, Jeong-Taek, Heid, Iris M., Stark, Klaus J., Zimmermann, Martina E., Völzke, Henry, Homuth, Georg, Evans, Michele K., Zonderman, Alan B., Polasek, Ozren, Pasterkamp, Gerard, Hoefer, Imo E., Redline, Susan, Pahkala, Katja, Oldehinkel, Albertine J., Snieder, Harold, Biino, Ginevra, Schmidt, Reinhold, Schmidt, Helena, Bandinelli, Stefania, Dedoussis, George, Thanaraj, Thangavel Alphonse, Kardia, Sharon L. R., Peyser, Patricia A., Kato, Norihiro, Schulze, Matthias B., Girotto, Giorgia, Böger, Carsten A., Jung, Bettina, Joshi, Peter K., Bennett, David A., De Jager, Philip L., Lu, Xiangfeng, Mamakou, Vasiliki, Brown, Morris, Caulfield, Mark J., Munroe, Patricia B., Guo, Xiuqing, Ciullo, Marina, Jonas, Jost B., Samani, Nilesh J., Kaprio, Jaakko, Pajukanta, Päivi, Tusié-Luna, Teresa, Aguilar-Salinas, Carlos A., Adair, Linda S., Bechayda, Sonny Augustin, de Silva, H. Janaka, Wickremasinghe, Ananda R., Krauss, Ronald M., Wu, Jer-Yuarn, Zheng, Wei, Hollander, Anneke Iden, Bharadwaj, Dwaipayan, Correa, Adolfo, Wilson, James G., Lind, Lars, Heng, Chew-Kiat, Nelson, Amanda E., Golightly, Yvonne M., Wilson, James F., Penninx, Brenda, Kim, Hyung-Lae, Attia, John, Scott, Rodney J., Rao, D. C., Arnett, Donna K., Hunt, Steven C., Walker, Mark, Koistinen, Heikki A., Chandak, Giriraj R., Mercader, Josep M., Costanzo, Maria C., Jang, Dongkeun, Burtt, Noël P., Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, EShyong, van Dam, Rob M., Lehtimäki, Terho, Chaturvedi, Nish, Yokota, Mitsuhiro, Liu, Jianjun, Reilly, Dermot F., McKnight, Amy Jayne, Kee, Frank, Jöckel, Karl-Heinz, McCarthy, Mark I., Palmer, Colin N. A., Vitart, Veronique, Hayward, Caroline, Simonsick, Eleanor, van Duijn, Cornelia M., Jin, Zi-Bing, Qu, Jia, Hishigaki, Haretsugu, Lin, Xu, März, Winfried, Gudnason, Vilmundur, Tardif, Jean-Claude, Lettre, Guillaume, Hart, Leen M.'t, Elders, Petra J. M., Damrauer, Scott M., Kumari, Meena, Kivimaki, Mika, van der Harst, Pim, Spector, Tim D., Loos, Ruth J. F., Province, Michael A., Parra, Esteban J., Cruz, Miguel, Psaty, Bruce M., Brandslund, Ivan, Pramstaller, Peter P., Rotimi, Charles N., Christensen, Kaare, Ripatti, Samuli, Widén, Elisabeth, Hakonarson, Hakon, Grant, Struan F. A., Kiemeney, Lambertus A. L. M., de Graaf, Jacqueline, Loeffler, Markus, Kronenberg, Florian, Gu, Dongfeng, Erdmann, Jeanette, Schunkert, Heribert, Franks, Paul W., Linneberg, Allan, Jukema, J. Wouter, Khera, Amit V., Männikkö, Minna, Jarvelin, Marjo-Riitta, Kutalik, Zoltan, Francesco, Cucca, Mook-Kanamori, Dennis O., van Dijk, Ko Willems, Watkins, Hugh, Strachan, David P., Grarup, Niels, Sever, Peter, Poulter, Neil, Chuang, Lee-Ming, Rotter, Jerome I., Dantoft, Thomas M., Karpe, Fredrik, Neville, Matt J., Timpson, Nicholas J., Cheng, Ching-Yu, Wong, Tien-Yin, Khor, Chiea Chuen, Li, Hengtong, Sabanayagam, Charumathi, Peters, Annette, Gieger, Christian, Hattersley, Andrew T., Pedersen, Nancy L., Magnusson, Patrik K. E., Boomsma, Dorret I., Willemsen, Allegonda H. M., Cupples, LAdrienne, van Meurs, Joyce B. J., Ghanbari, Mohsen, Gordon-Larsen, Penny, Huang, Wei, Kim, Young Jin, Tabara, Yasuharu, Wareham, Nicholas J., Langenberg, Claudia, Zeggini, Eleftheria, Kuusisto, Johanna, Laakso, Markku, Ingelsson, Erik, Abecasis, Goncalo, Chambers, John C., Kooner, Jaspal S., de Vries, Paul S., Morrison, Alanna C., Hazelhurst, Scott, Ramsay, Michèle, North, Kari E., Daviglus, Martha, Kraft, Peter, Martin, Nicholas G., Whitfield, John B., Abbas, Shahid, Saleheen, Danish, Walters, Robin G., Holmes, Michael V., Black, Corri, Smith, Blair H., Baras, Aris, Justice, Anne E., Buring, Julie E., Ridker, Paul M., Chasman, Daniel I., Kooperberg, Charles, Tamiya, Gen, Yamamoto, Masayuki, van Heel, David A., Trembath, Richard C., Wei, Wei-Qi, Jarvik, Gail P., Namjou, Bahram, Hayes, M. Geoffrey, Ritchie, Marylyn D., Jousilahti, Pekka, Salomaa, Veikko, Hveem, Kristian, Ãsvold, Bjarn Olav, Kubo, Michiaki, Kamatani, Yoichiro, Okada, Yukinori, Murakami, Yoshinori, Kim, Bong-Jo, Thorsteinsdottir, Unnur, Stefansson, Kari, Zhang, Jifeng, Chen, YEugene, Ho, Yuk-Lam, Lynch, Julie A., Rader, Daniel J., Tsao, Philip S., Chang, Kyong-Mi, Cho, Kelly, O'Donnell, Christopher J., Gaziano, John M., Wilson, Peter W. F., Frayling, Timothy M., Hirschhorn, Joel N., Kathiresan, Sekar, Mohlke, Karen L., Sun, Yan V., Morris, Andrew P., Boehnke, Michael, Brown, Christopher D., Natarajan, Pradeep, Deloukas, Panos, Willer, Cristen J., Assimes, Themistocles L., and Peloso, Gina M.
  • Genome Biology (Online Edition). December 27, 2022, Vol. 23 Issue 1

9. PART is part of SNAP‐MCI. [2022]

  • Wisse, Laura EM, Xie, Long, Lyu, Xueying, Das, Sandhitsu R., de Flores, Robin, Lane, Jacqueline, Yushkevich, Paul A., Wolk, David A., and Initiative, Disease Neuroimaging
  • Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Dec2022 Supplement 6, Vol. 18 Issue 6, p1-4, 4p
Abstract
Background: Mild Cognitive Impairment with Suspected non‐Alzheimer's Pathophysiology (SNAP‐MCI) represents a group of patients with Alzheimer's disease (AD) like neurodegeneration without beta‐amyloid pathology. While this group likely has a heterogeneous etiology, tau pathology, as in Primary Age‐Related Tauopathy (PART), has been hypothesized to play a major role. We investigate tau positron emission tomography (PET) uptake in the medial temporal lobe (MTL) in SNAP‐MCI and the association of MTL Tau‐PET uptake with structural measures and delayed recall in beta‐amyloid negative (A‐) MCI patients. Method: 237 MCI patients and 301 A‐ controls with available beta‐amyloid and tau PET and magnetic resonance images (within 200 days) were included. Baseline hippocampal volume and entorhinal cortex (ERC) and Brodmann areas (BA)35 thickness were obtained using an in‐house developed pipeline and annualized atrophy rates were estimated in an unbiased fashion using follow‐up MRIs within 4.5 years. Βeta‐amyloid status (A+/‐) was determined by a standard cut‐off (Florbetapir: 1.11; Florbetaben: 1.08) and neurodegeneration status (N+/‐) by hippocampal volumes, corrected for intracranial volume, using the 90th percentile of A+ AD patients as the cut‐off. Tau‐PET standardized uptake value ratio (SUVR) in the ERC/BA35 was calculated. A composite z‐score of delayed recall at baseline and change over 2 years was obtained. Result: SNAP‐MCI had significantly higher ERC/BA35 Tau‐PET SUVR than A‐ controls (Table 1, corrected for age) and qualitatively higher than A‐N‐ MCI (p=0.10). ERC/BA35 Tau‐PET SUVR in A‐N‐ MCI was not significantly different from A‐ controls. In A‐ MCI patients, ERC/BA35 Tau‐PET SUVR was significantly associated with BA35 thickness and hippocampal, ERC and BA35 atrophy rates, corrected for beta‐amyloid PET SUVR (Table 2; Figure 1). MTL structural measures, but not ERC/BA35 Tau‐PET SUVR, were associated with cross‐sectional and longitudinal delayed recall measures (Table 3; Figure 2). Conclusion: SNAP‐MCI had elevated ERC/BA35 Tau‐PET SUVR and ERC/BA35 Tau‐PET SUVR was associated with MTL structural measures in A‐ MCI patients. This indicates that tau pathology might be an important driver of neurodegeneration in the absence of beta‐amyloid pathology, supporting the notion that PART contributes to SNAP‐MCI. Additionally, MTL structure was associated with memory performance, consistent with SNAP not being a benign condition. [ABSTRACT FROM AUTHOR]

10. Drug therapy, imaging, and other aspects of clinical management change after Alzheimer's biomarker testing in routine practice: Findings from the IMPACT‐AD BC study. [2022]

  • Yang, David, Best, John R., Chambers, Colleen, Feldman, Howard H., Pettersen, Jacqueline A, Henri‐Bhargava, Alexander, Lee, Philip E, Nygaard, Haakon B., Funnell, Clark R, Foti, Dean J, Hsiung, Ging‐Yuek Robin, and DeMarco, Mari L.
  • Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Dec2022 Supplement 6, Vol. 18 Issue 6, p1-2, 2p
Abstract
Background: While previous studies have demonstrated the effect of Alzheimer's disease (AD) CSF testing in changing diagnosis, we lack an understanding of how this testing affects clinical management. Therefore, we assessed changes in clinical management associated with AD CSF biomarker testing when ordered as part of routine clinical management. Method: The 'Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia' (IMPACT‐AD BC) study (NCT05002699) is a longitudinal study examining the impact of AD CSF testing on clinical management, personal utility and health care economics in British Columbia, Canada. After AD CSF testing was ordered as part of routine care (where the clinical scenario met the appropriate use criteria), the patient and their physician were eligible to participate in the study. The primary outcome was the change in management (pre‐ v. post‐biomarker results) in a composite measure including 1) AD drug therapy, 2) other relevant drug therapy, 3) other diagnostic procedures, and 4) referral or counselling. Result: Participants (n = 129) had a median age of 63 (IQR:58‐68); 49% were female. Cognitive impairment at baseline consisted of 7% with subjective cognitive impairment, 53% with mild cognitive impairment, and 40% with dementia. CSF biomarker profiles were consistent with an amyloid‐beta pathology (i.e., A+) in 72% of cases. Changes in clinical management because of testing occurred in 83% of cases including: referrals and counseling (57%), imaging (47%) and other diagnostic procedures (e.g., neuropsychological testing) (42%), and use of AD drug therapies (40%). For those with a non‐AD pre‐biomarkers diagnosis, 42% were changed to AD post‐biomarkers; for those with an AD pre‐biomarkers diagnosis, 18% were changed to non‐AD post‐biomarkers. Conclusion: This study has revealed substantial changes in clinical management as a direct result of AD CSF biomarker testing in routine care. An understanding of the implications of biomarker testing will in turn help us: improve appropriate utilization, understand the broader impacts on persons living with dementia and on the health care system, and prepare for expanded use of this testing with the availability of disease‐modifying therapeutics. [ABSTRACT FROM AUTHOR]

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