335 results on '"A. Berinstein"'
Search Results
2. Methotrexate, cytarabine, thiotepa and rituximab (MATRix) chemoimmunotherapy for primary central nervous system lymphoma: a Toronto experience
- Author
-
Adam, Suleman, Jiajia, Liu, Lisa K, Hicks, Adi Klil, Drori, Michael, Crump, Robert, Kridel, Anca, Prica, and Neil, Berinstein
- Subjects
Hematology - Abstract
Not available.
- Published
- 2022
3. Inflammatory bowel disease patient concerns and experiences on transition to home-based infusions during the COVID-19 pandemic
- Author
-
Janson Jacob, Daniel Aintabi, Melissa DeJonckheere, Shirley A. Cohen-Mekelburg, John I. Allen, David N. Irani, A. Mark Fendrick, Akbar K. Waljee, Peter D.R. Higgins, and Jeffrey A. Berinstein
- Subjects
Chronic Disease ,Humans ,COVID-19 ,Pharmaceutical Science ,Pharmacy ,Inflammatory Bowel Diseases ,Pandemics ,Infliximab - Abstract
In response to the COVID-19 pandemic, the CDC issued guidance advising patients and providers to adopt social distancing practices such as home-based infusions (H-BI).We performed a mixed methods evaluation to summarize perceptions, concerns, and experiences with H-BI among all inflammatory bowel disease patients 18-90 years of age who transitioned to home-based infliximab or vedolizumab infusions between March to July 2020 at a tertiary care center. Semi-structured interviews were conducted and analyzed using an iterative, inductive thematic approach. Baseline characteristics and outcome on safety, COVID-19 transmission, delays in infusions, and H-BI persistence were collected.Of the 57 participants who transitioned to H-BI, 20 (33%) responded. Four major categories and six major themes related to expectations, experience, perceived safety, and logistical factors were identified. Initial perceptions were mixed, however these resolved. One patient developed COVID-19, one patient experienced an adverse event, 12 (21%) patients experienced an infusion delay, and 6 (11%) patients transitioned from H-BI.Despite mixed initial perceptions, respondents had a positive experience with most respondents planning to continue H-BI after the pandemic resolves. Several real-world actionable barriers were identified related to scheduling, communication between stakeholders, and nursing quality. No major safety concerns were identified.
- Published
- 2022
4. Comparative Study of the Immune Response Induced by an Argentinian Classical Strain of IBDV in Two Chicken Breeds
- Author
-
Juan Jaton, María Soledad Lucero, Matías Richetta, Silvina Pinto, María José Gravisaco, Analía Berinstein, Evangelina Gómez, and Silvina Chimeno Zoth
- Subjects
Article Subject ,General Veterinary - Abstract
The hybrid chicken Negra INTA, which originated at the National Institute of Agricultural Technology (INTA), is the product of the cross between Barred Plymouth Rock females and Rhode Island Red males, and it is used as a laying hen for egg consumption. It has been characterized by productive parameters, but the characterization from an immunological perspective has not been done yet. Infectious bursal disease virus (IBDV) causes a highly contagious viral disease that affects the bursa of Fabricius. Although most chickens are regularly vaccinated against IBDV, this virus still generates negative impacts on production with significant economic losses. The aim of the present work was to compare the immune responses of the Negra INTA hybrid and the White Leghorn layer line to the infection with a field isolate of IBDV. Four-week-old chickens were infected with a single dose of IBDV and at 3, 5, 7, and 30 days postinfection (dpi), bursae were removed, and different parameters were evaluated. Results showed that the reduction of the bursa body (BB) ratio and the histopathological damage were maximum on day 7 postinfection (pi). The viral load was greater in the hybrid Negra INTA at 5 dpi. The humoral immune response between both breeds was similar, although more animals from the commercial line showed higher titers of neutralizing antibodies. Flow cytometry analysis revealed that Bu+ bursal lymphocytes reached a minimum at 7 dpi. Meanwhile, T cell infiltration measured by the percentage of CD3+, CD4+, and CD8+ cells in the bursa was at its maximum at 5 dpi. To our knowledge, this work describes for the first time the pathogenesis and the immune response caused by an Argentinian IBDV isolate in two different chicken lines.
- Published
- 2022
5. IL-15 promotes inflammatory Th17 cells in the intestine
- Author
-
Jonathan G. Golob, Guoqing Hou, Allen Lee, Helmut Grassberger, Elliott M Berinstein, Mohamed El Zataari, Valerie Khaykin, Christopher Fry, Jeff B. Berinstein, Jean Nemzek, Nobuhiko Kamada, John Y Kao, and Shrinivas Bishu
- Abstract
Ulcerative Colitis (UC) is a chronic gastrointestinal condition with high morbidity. While modern medical therapies have revolutionized the care of UC, 10-25% of patients fail medications and still progress to surgery. Thus, developing new treatments is a core problem in UC. T-cells, especially Th17 cells, are strongly linked with UC and are major targets of medications in UC. Tissue-resident memory T-cells (TRM) are a distinct class of T-cells that are highly enriched in the intestine, closely aligned with the microbiota, and are implicated in the pathogenesis of UC. Unlike circulating T-cells, TRMare difficult to target because they do not recirculate. Thus, we focused on cytokines like IL-15 which act as a tissue danger signal and regulate T-cellsin situ. We found that theIL15axis is upregulated in UC and predicts treatment response. IL-15 was redundant for Th17 differentiation but could activate terminally differentiated Th17 cells to promote intestinal inflammation. Finally, in CD4+TRMfrom patients with UC, IL-15 upregulatedRORC, the master transcription factor for Th17 cells, via a Janus Kinase (JAK)1 pathway. Thus, IL-15 promotes terminally differentiated inflammatory Th17 cells in the intestine raising the possibility that IL-15 may be a target for UC treatments.
- Published
- 2023
6. The Relationship Between Opioid Use and Healthcare Utilization in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis
- Author
-
Jessica L Sheehan, Janson Jacob, Elliot M Berinstein, LaVana Greene-Higgs, Calen A Steiner, Sameer K Berry, Carol Shannon, Shirley A Cohen-Mekelburg, Peter D R Higgins, and Jeffrey A Berinstein
- Subjects
Analgesics, Opioid ,Hospitalization ,Clinical Review ,Gastroenterology ,Humans ,Immunology and Allergy ,Patient Acceptance of Health Care ,Inflammatory Bowel Diseases ,Emergency Service, Hospital - Abstract
Background Pain is commonly experienced by patients with inflammatory bowel disease (IBD). Unfortunately, pain management is a challenge in IBD care, as currently available analgesics are associated with adverse events. Our understanding of the impact of opioid use on healthcare utilization among IBD patients remains limited. Methods A systematic search was completed using PubMed, Embase, the Cochrane Library, and Scopus through May of 2020. The exposure of interest was any opioid medication prescribed by a healthcare provider. Outcomes included readmissions rate, hospitalization, hospital length of stay, healthcare costs, emergency department visits, outpatient visits, IBD-related surgeries, and IBD-related medication utilization. Meta-analysis was conducted on study outcomes reported in at least 4 studies using random-effects models to estimate pooled relative risk (RR) and 95% confidence interval (CI). Results We identified 1969 articles, of which 30 met inclusion criteria. Meta-analysis showed an association between opioid use and longer length of stay (mean difference, 2.25 days; 95% CI, 1.29-3.22), higher likelihood of prior IBD-related surgery (RR, 1.72; 95% CI, 1.32-2.25), and higher rates of biologic use (RR, 1.38; 95% CI, 1.13-1.68) but no difference in 30-day readmissions (RR, 1.17; 95% CI, 0.86-1.61), immunomodulator use (RR, 1.13; 95% CI, 0.89-1.44), or corticosteroid use (RR, 1.36; 95% CI, 0.88-2.10) in patients with IBD. On systematic review, opioid use was associated with increased hospitalizations, healthcare costs, emergency department visits, outpatient visits, and polypharmacy. Discussion Opioids use among patients with IBD is associated with increased healthcare utilization. Nonopioid alternatives are needed to reduce burden on the healthcare system and improve patient outcomes.
- Published
- 2022
7. Incidence of Delayed Vitreous Hemorrhage in Patients With Retinal Tears Associated With Bridging Vessels
- Author
-
Travis J, Peck, Dylan J, Sadowsky, Asma, Ullah, Daniel M, Berinstein, Alexander, Melamud, and Joshua D, Levinson
- Subjects
Case-Control Studies ,Incidence ,Humans ,Retinal Perforations ,Retrospective Studies ,Vitreous Hemorrhage - Abstract
BACKGROUND AND OBJECTIVE: The purpose of this article is to determine if outcomes in patients presenting with retinal tears with bridging vessels (BVs) differ from those without BVs. PATIENTS AND METHODS: A case control study of all patients presenting with retinal tears during a 3-year period was completed. Comparisons were made between patients with and without BVs. Variables included vitreous hemorrhage (VH) at presentation, delayed VH, initial and final visual acuity, need for surgery, and retinal detachment. RESULTS: There was a significant increase in the number of patients with a VH at presentation (75% vs 28%; P < .0001), delayed VH (31% vs 7.5%; P = .001), and incidence of pars plana vitrectomy (16% vs 1.3%; P = .002) in the BV cohort. There was no significant difference in time to VH (9.4 vs 38.8 days; P = .32) or final visual acuity (20/25 vs 20/25; P = .45) between the two groups. CONCLUSIONS: The presence of a BV is an important prognostic indicator for risk of delayed VH. Documenting the presence of a BV allows for appropriate patient counseling. [ Ophthalmic Surg Lasers Imaging Retina 2022;53:502–505.]
- Published
- 2022
8. The Fecal Microbiome in Quiescent Crohn’s Disease with Persistent Gastrointestinal Symptoms Show Enrichment of Oral Microbes But Depletion of Butyrate and Indole Producers
- Author
-
Jonathan Golob, Krishna Rao, Jeffrey Berinstein, William Chey, Chung Owyang, Nobuhiko Kamada, Peter Higgins, Vincent Young, Shrinivas Bishu, and Allen Lee
- Subjects
Article - Abstract
Background and AimsEven in the absence of inflammation, persistent symptoms in Crohn’s disease (CD) are prevalent and negatively impact quality of life. We aimed to determine whether quiescent CD patients with persistent symptoms (qCD+symptoms) have changes in microbial structure and functional potential compared to those without symptoms (qCD-symptoms).MethodsWe performed a prospective multi-center observational study nested within the SPARC IBD study. CD patients were included if they had evidence of quiescent disease as defined by fecal calprotectin level < 150 mcg/g. Persistent symptoms were defined by the CD-PRO2 questionnaire. Active CD (aCD), diarrhea-predominant irritable bowel syndrome (IBS-D), and healthy controls (HC) were included as controls. Stool samples underwent whole genome shotgun metagenomic sequencing.ResultsA total of 424 patients were analyzed, including 39 qCD+symptoms, 274 qCD-symptoms, 21 aCD, 40 IBS-D, and 50 HC. Patients with qCD+symptoms had a less diverse microbiome, including significant reductions in Shannon diversity (PPKlebsiella pneumoniae(q=.003) as well as depletion of important butyrate and indole producers, such asEubacterium rectale(q=.001),Lachnospiraceae spp. (qFaecalibacterium prausnitzii(qtnaAgenes, which mediate tryptophan metabolism, as well as significanttnaAallelic variation, compared with qCD-symptoms.ConclusionThe microbiome in patients with qCD+symptoms show significant changes in diversity, community profile, and composition compared with qCD-symptoms. Future studies will focus on the functional significance of these changes.What You Need to KnowBackgroundPersistent symptoms in quiescent Crohn’s disease (CD) are prevalent and lead to worse outcomes. While changes in the microbial community have been implicated, the mechanisms by which altered microbiota may lead to qCD+symptoms remain unclear.FindingsQuiescent CD patients with persistent symptoms demonstrated significant differences in microbial diversity and composition compared to those without persistent symptoms. Specifically, quiescent CD patients with persistent symptoms were enriched in bacterial species that are normal inhabitants of the oral microbiome but depleted in important butyrate and indole producers compared to those without persistent symptoms.Implications for Patient CareAlterations in the gut microbiome may be a potential mediator of persistent symptoms in quiescent CD. Future studies will determine whether targeting these microbial changes may improve symptoms in quiescent CD.
- Published
- 2023
9. <scp>PD‐L1</scp> expression predicts efficacy in the phase <scp>II SPiReL</scp> trial with <scp>MVP‐S</scp> , pembrolizumab, and low‐dose <scp>CPA</scp> in R/R <scp>DLBCL</scp>
- Author
-
Irina Amitai, Kim Roos, Iran Rashedi, Yidi Jiang, Kathryn Mangoff, Gail Klein, Nicholas Forward, Douglas Stewart, Pierre Laneuville, Isabelle Bence‐Bruckler, Joy Mangel, George Tomlinson, and Neil L. Berinstein
- Subjects
Hematology ,General Medicine - Published
- 2023
10. Characteristics of Facilities with Early and Rapid Ustekinumab Adoption for Patients with Inflammatory Bowel Disease
- Author
-
Shirley Cohen-Mekelburg, Tony Van, Jeffrey A. Berinstein, Xianshi Yu, Deena Kelly Costa, Beth I. Wallace, Sameer Saini, Andrew J. Admon, Peter D. R. Higgins, Ji Zhu, and Akbar K. Waljee
- Subjects
Hepatology ,Gastroenterology - Published
- 2023
11. Profiles of Web-based Portal Users with Inflammatory Bowel Disease
- Author
-
Mohamed Noureldin, Kira L Newman, Peter D R Higgins, John D Piette, Kenneth Resnicow, Jeremy Louissaint, Brooke Kenney, Jeffrey Berinstein, Akbar K Waljee, Ji Zhu, and Shirley Cohen-Mekelburg
- Subjects
Gastroenterology ,Immunology and Allergy - Abstract
Background Web-based portals can enhance communication between patients and providers to support IBD self-management and improve care. We aimed to identify portal use patterns of patients with inflammatory bowel disease (IBD) to inform future web portal-based interventions and portal design. Methods Patients with IBD receiving care at the University of Michigan between 2012 and 2021 were identified. Meta-data from electronic logs of each patient’s most recent year of portal use were abstracted. Portal engagement was characterized in terms of intensity (ie, frequency of use); comprehensiveness (ie, number of portal functions used); and duration (ie, quarters per year of portal use). We used k-means clustering, a machine-learning technique, to identify groupings of portal users defined in terms of engagement features. Results We found 5605 patients with IBD who had accessed their portal account at least once. The average age was 41.2 years (SD 16.7), 3035 (54.2%) were female, and 2214 (39.5%) received immune-targeted therapies. We identified 3 patterns of portal engagement: (1) low intensity users (29.5%); (2) moderate intensity, comprehensive, and sustained users (63.3%); and (3) high intensity, comprehensive, sustained users (7.2%). Patients with more intense, comprehensive, and sustained use of the portal were older, female, with more comorbidities, and were more likely to receive immune-targeted therapies. Conclusion Understanding distinct patterns of portal use can inform portal-based interventions and portal design. Patient portals may be particularly helpful in delivering assistance to those with comorbidities and those receiving immune-targeted therapies—many of whom demonstrate more intense, comprehensive, and sustained portal use.
- Published
- 2023
12. Self-Efficacy and the Impact of Inflammatory Bowel Disease on Patients’ Daily Lives
- Author
-
Jessica L. Sheehan, LaVana Greene-Higgs, Linnea Swanson, Peter D.R. Higgins, Sarah L. Krein, Akbar K. Waljee, Sameer D. Saini, Jeffrey A. Berinstein, Jessica L. Mellinger, John D. Piette, Ken Resnicow, and Shirley Cohen-Mekelburg
- Subjects
Gastroenterology - Published
- 2023
13. A Predictive Model to Identify ComplicatedClostridiodes difficileInfection
- Author
-
Jeffrey A Berinstein, Calen A Steiner, Samara Rifkin, D Alexander Perry, Dejan Micic, Daniel Shirley, Peter D R Higgins, Vincent B Young, Allen Lee, and Krishna Rao
- Subjects
Infectious Diseases ,Oncology - Abstract
BackgroundClostridioides difficile infection (CDI) is a leading cause of health care–associated infection and may result in organ dysfunction, colectomy, and death. Published risk scores to predict severe complications from CDI demonstrate poor performance upon external validation. We hypothesized that building and validating a model using geographically and temporally distinct cohorts would more accurately predict risk for complications from CDI.MethodsWe conducted a multicenter retrospective cohort study of adults diagnosed with CDI. After randomly partitioning the data into training and validation sets, we developed and compared 3 machine learning algorithms (lasso regression, random forest, stacked ensemble) with 10-fold cross-validation to predict disease-related complications (intensive care unit admission, colectomy, or death attributable to CDI) within 30 days of diagnosis. Model performance was assessed using the area under the receiver operating curve (AUC).ResultsA total of 3646 patients with CDI were included, of whom 217 (6%) had complications. All 3 models performed well (AUC, 0.88–0.89). Variables of importance were similar across models, including albumin, bicarbonate, change in creatinine, non-CDI-related intensive care unit admission, and concomitant non-CDI antibiotics. Sensitivity analyses indicated that model performance was robust even when varying derivation cohort inclusion and CDI testing approach. However, race was an important modifier, with models showing worse performance in non-White patients.ConclusionsUsing a large heterogeneous population of patients, we developed and validated a prediction model that estimates risk for complications from CDI with good accuracy. Future studies should aim to reduce the disparity in model accuracy between White and non-White patients and to improve performance overall.
- Published
- 2023
14. Prediction for 2-Year Vision Outcomes Using Early Morphologic and Functional Responses in the Comparison of Age-related Macular Degeneration Treatments Trials
- Author
-
Katie Xue, Peiying Hua, Maureen G. Maguire, Ebenezer Daniel, Glenn J. Jaffe, Juan E. Grunwald, Gui-shuang Ying, David F. Williams, Sara Beardsley, Steven Bennett, Herbert Cantrill, Carmen Chan-Tram, Holly Cheshier, Kathyrn Damato, John Davies, Sundeep Dev, Julianne Enloe, Gennaro Follano, Peggy Gilbert, Jill Johnson, Tori Jones, Lisa Mayleben, Robert Mittra, Martha Moos, Ryan Neist, Neal Oestreich, Polly Quiram, Robert Ramsay, Edwin Ryan, Stephanie Schindeldecker, John Snater, Trenise Steele, Dwight Selders, Jessica Tonsfeldt, Shelly Valardi, Gary Edd Fish, Hank A. Aguado, Sally Arceneaux, Jean Arnwine, Kim Bell, Tina Bell, Bob Boleman, Patricia Bradley, David Callanan, Lori Coors, Jodi Creighton, Timothy Crew, Kimberly Cummings, Christopher Dock, Karen Duignan, Dwain Fuller, Keith Gray, Betsy Hendrix, Nicholas Hesse, Diana Jaramillo, Bradley Jost, Sandy Lash, Laura Lonsdale, Michael Mackens, Karin Mutz, Michael Potts, Brenda Sanchez, William Snyder, Wayne Solley, Carrie Tarter, Robert Wang, Patrick Williams, Stephen L. Perkins, Nicholas Anderson, Ann Arnold, Paul Blais, Joseph Googe, Tina T. Higdon, Cecile Hunt, Mary Johnson, James Miller, Misty Moore, Charity K. Morris, Christopher Morris, Sarah Oelrich, Kristina Oliver, Vicky Seitz, Jerry Whetstone, Bernard H. Doft, Jay Bedel, Robert Bergren, Ann Borthwick, Paul Conrad, Amanda Fec, Christina Fulwylie, Willia Ingram, Shawnique Latham, Gina Lester, Judy Liu, Louis Lobes, Nicole M. Lucko, Holly Mechling, Lori Merlotti, Keith McBroom, Karl Olsen, Danielle Puskas, Pamela Rath, Maria Schmucker, Lynn Schueckler, Christina Schultz, Heather Shultz, David Steinberg, Avni Vyas, Kim Whale, Kimberly Yeckel, David H. Orth, Linda S. Arredondo, Susan Brown, Barbara J. Ciscato, Joseph M. Civantos, Celeste Figliulo, Sohail Hasan, Belinda Kosinski, Dan Muir, Kiersten Nelson, Kirk Packo, John S. Pollack, Kourous Rezaei, Gina Shelton, Shannya Townsend-Patrick, Marian Walsh, H. Richard McDonald, Nina Ansari, Amanda Bye, Arthur D. Fu, Sean Grout, Chad Indermill, Robert N. Johnson, J. Michael Jumper, Silvia Linares, Brandon J. Lujan, Ames Munden, Meredith Persons, Rosa Rodriguez, Jennifer M. Rose, Brandi Teske, Yesmin Urias, Stephen Young, Richard F. Dreyer, Howard Daniel, Michele Connaughton, Irvin Handelman, Stephen Hobbs, Christine Hoerner, Dawn Hudson, Marcia Kopfer, Michael Lee, Craig Lemley, Joe Logan, Colin Ma, Christophe Mallet, Amanda Milliron, Mark Peters, Harry Wohlsein, Joel A. Pearlman, Margo Andrews, Melissa Bartlett, Nanette Carlson, Emily Cox, Robert Equi, Marta Gonzalez, Sophia Griffin, Fran Hogue, Lance Kennedy, Lana Kryuchkov, Carmen Lopez, Danny Lopez, Bertha Luevano, Erin McKenna, Arun Patel, Brian Reed, Nyla Secor, Iris R. Sison, Tony Tsai, Nina Varghis, Brooke Waller, Robert Wendel, Reina Yebra, Daniel B. Roth, Jane Deinzer, Howard Fine, Flory Green, Stuart Green, Bruce Keyser, Steven Leff, Amy Leviton, Amy Martir, Kristin Mosenthine, Starr Muscle, Linda Okoren, Sandy Parker, Jonathan Prenner, Nancy Price, Deana Rogers, Linda Rosas, Alex Schlosser, Loretta Studenko, Thea Tantum, Harold Wheatley, Michael T. Trese, Thomas Aaberg, Denis Bezaire, Craig Bridges, Doug Bryant, Antonio Capone, Michelle Coleman, Christina Consolo, Cindy Cook, Candice DuLong, Bruce Garretson, Tracy Grooten, Julie Hammersley, Tarek Hassan, Heather Jessick, Nanette Jones, Crystal Kinsman, Jennifer Krumlauf, Sandy Lewis, Heather Locke, Alan Margherio, Debra Markus, Tanya Marsh, Serena Neal, Amy Noffke, Kean Oh, Clarence Pence, Lisa Preston, Paul Raphaelian, Virginia R. Regan, Peter Roberts, Alan Ruby, Ramin Sarrafizadeh, Marissa Scherf, Sarita Scott, Scott Sneed, Lisa Staples, Brad Terry, Matthew T. Trese, Joan Videtich, George Williams, Mary Zajechowski, Daniel P. Joseph, Kevin Blinder, Lynda Boyd, Sarah Buckley, Meaghan Crow, Amanda Dinatale, Nicholas Engelbrecht, Bridget Forke, Dana Gabel, Gilbert Grand, Jennifer Grillion-Cerone, Nancy Holekamp, Charlotte Kelly, Ginny Nobel, Kelly Pepple, Matt Raeber, P. Kumar Rao, Tammy Ressel, Steven Schremp, Merrilee Sgorlon, Shantia Shears, Matthew Thomas, Cathy Timma, Annette Vaughn, Carolyn Walters, Rhonda Weeks, Jarrod Wehmeier, Tim Wright, Daniel M. Berinstein, Aida Ayyad, Mohammed K. Barazi, Erica Bickhart, Tracey Brady, Lisa Byank, Alysia Cronise, Vanessa Denny, Courtney Dunn, Michael Flory, Robert Frantz, Richard A. Garfinkel, William Gilbert, Michael M. Lai, Alexander Melamud, Janine Newgen, Shamekia Newton, Debbie Oliver, Michael Osman, Reginald Sanders, Manfred von Fricken, Pravin Dugel, Sandra Arenas, Gabe Balea, Dayna Bartoli, John Bucci, Jennifer A. Cornelius, Scheleen Dickens, Don Doherty, Heather Dunlap, David Goldenberg, Karim Jamal, Norma Jimenez, Nicole Kavanagh, Derek Kunimoto, John Martin, Jessica Miner, Sarah Mobley, Donald Park, Edward Quinlan, Jack Sipperley, Carol Slagle, Danielle Smith, Miguelina Yafchak, Rohana Yager, Christina J. Flaxel, Steven Bailey, Peter Francis, Chris Howell, Thomas Hwang, Shirley Ira, Michael Klein, Andreas Lauer, Teresa Liesegang, Ann Lundquist, Sarah Nolte, Susan K. Nolte, Scott Pickell, Susan Pope, Joseph Rossi, Mitchell Schain, Peter Steinkamp, Maureen D. Toomey, Debora Vahrenwald, Kelly West, Baker Hubbard, Stacey Andelman, Chris Bergstrom, Judy Brower, Blaine Cribbs, Linda Curtis, Jannah Dobbs, Lindreth DuBois, Jessica Gaultney, Deborah Gibbs, Debora Jordan, Donna Leef, Daniel F. Martin, Robert Myles, Timothy Olsen, Bryan Schwent, Sunil Srivastava, Rhonda Waldron, Andrew N. Antoszyk, Uma Balasubramaniam, Danielle Brooks, Justin Brown, David Browning, Loraine Clark, Sarah Ennis, Susannah Held, Jennifer V. Helms, Jenna Herby, Angie Karow, Pearl Leotaud, Caterina Massimino, Donna McClain, Michael McOwen, Jennifer Mindel, Candace Pereira, Rachel Pierce, Michele Powers, Angela Price, Jason Rohrer, Jason Sanders, Robert L. Avery, Kelly Avery, Jessica Basefsky, Liz Beckner, Alessandro Castellarin, Stephen Couvillion, Jack Giust, Matthew Giust, Maan Nasir, Dante Pieramici, Melvin Rabena, Sarah Risard, Robert See, Jerry Smith, Lisha Wan, Sophie J. Bakri, Nakhleh Abu-Yaghi, Andrew Barkmeier, Karin Berg, Jean Burrington, Albert Edwards, Shannon Goddard, Shannon Howard, Raymond Iezzi, Denise Lewison, Thomas Link, Colin A. McCannel, Joan Overend, John Pach, Margaret Ruszczyk, Ryan Shultz, Cindy Stephan, Diane Vogen, Reagan H. Bradford, Vanessa Bergman, Russ Burris, Amanda Butt, Beth Daniels, Connie Dwiggins, Stephen Fransen, Tiffany Guerrero, Darin Haivala, Amy Harris, Sonny Icks, Ronald Kingsley, Lena Redden, Rob Richmond, Brittany Ross, Kammerin White, Misty Youngberg, Trexler M. Topping, Steve Bennett, Sandy Chong, Mary Ciotti, Tina Cleary, Emily Corey, Dennis Donovan, Albert Frederick, Lesley Freese, Margaret Graham, Natalya Gud, Taneika Howard, Mike Jones, Michael Morley, Katie Moses, Jen Stone, Robin Ty, Torsten Wiegand, Lindsey Williams, Beth Winder, Carl C. Awh, Michelle Amonette, Everton Arrindell, Dena Beck, Brandon Busbee, Amy Dilback, Sara Downs, Allison Guidry, Gary Gutow, Jackey Hardin, Sarah Hines, Emily Hutchins, Kim LaCivita, Ashley Lester, Larry Malott, MaryAnn McCain, Jayme Miracle, Kenneth Moffat, Lacy Palazzotta, Kelly Robinson, Peter Sonkin, Alecia Travis, Roy Trent Wallace, Kelly J. Winters, Julia Wray, April E. Harris, Mari Bunnell, Katrina Crooks, Rebecca Fitzgerald, Cameron Javid, Corin Kew, Erica Kill, Patricia Kline, Janet Kreienkamp, Maricruz Martinez, Roy Ann Moore, Egbert Saavedra, LuAnne Taylor, Mark Walsh, Larry Wilson, Thomas A. Ciulla, Ellen Coyle, Tonya Harrington, Charlotte Harris, Cindi Hood, Ingrid Kerr, Raj Maturi, Dawn Moore, Stephanie Morrow, Jennifer Savage, Bethany Sink, Tom Steele, Neelam Thukral, Janet Wilburn, Joseph P. Walker, Jennifer Banks, Debbie Ciampaglia, Danielle Dyshanowitz, Jennifer Frederick, A. Tom Ghuman, Richard Grodin, Cheryl Kiesel, Eileen Knips, Jonathan McCue, Maria Ortiz, Crystal Peters, Paul Raskauskas, Etienne Schoeman, Ashish Sharma, Glenn Wing, Rebecca Youngblood, Suresh R. Chandra, Michael Altaweel, Barbara Blodi, Kathryn Burke, Kristine A. Dietzman, Justin Gottlieb, Gene Knutson, Denise Krolnik, T. Michael Nork, Shelly Olson, John Peterson, Sandra Reed, Barbara Soderling, Guy Somers, Thomas Stevens, Angela Wealti, Srilaxmi Bearelly, Brenda Branchaud, Joyce W. Bryant, Sara Crowell, Sharon Fekrat, Merritt Gammage, Cheala Harrison, Sarah Jones, Noreen McClain, Brooks McCuen, Prithvi Mruthyunjaya, Jeanne Queen, Neeru Sarin, Cindy Skalak, Marriner Skelly, Ivan Suner, Ronnie Tomany, Lauren Welch, Susanna S. Park, Allison Cassidy, Karishma Chandra, Idalew Good, Katrina Imson, null Sashi, null Kaur, Helen Metzler, Lawrence Morse, Ellen Redenbo, Marisa Salvador, David Telander, Mark Thomas, Cindy Wallace, Charles C. Barr, Amanda Battcher, Michelle Bottorff, Mary Chasteen, Kelly Clark, Diane Denning, Debra Schoen, Amy Schultz, Evie Tempel, Lisa Wheeler, Greg K. Whittington, Thomas W. Stone, Todd Blevins, Michelle Buck, Lynn Cruz, Wanda Heath, Diana Holcomb, Rick Isernhagen, Terri Kidd, John Kitchens, Cathy Sears, Ed Slade, Jeanne Van Arsdall, Brenda VanHoose, Jenny Wolfe, William Wood, John Zilis, Carol Crooks, Larry Disney, Mimi Liu, Stephen Petty, Sandra Sall, James C. Folk, Tracy Aly, Abby Brotherton, Douglas Critser, Connie J. Hinz, Stefani Karakas, Valerie Kirschner, Cheyanne Lester, Cindy Montague, Stephen Russell, Heather Stockman, Barbara Taylor, Randy Verdick, Jean Walshire, John T. Thompson, Barbara Connell, Maryanth Constantine, John L. Davis, null Gwen Holsapple, Lisa Hunter, C. Nicki Lenane, Robin Mitchell, Leslie Russel, Raymond Sjaarda, David M. Brown, Matthew Benz, Llewellyn Burns, JoLene G. Carranza, Richard Fish, Debra Goates, Shayla Hay, Theresa Jeffers, Eric Kegley, Dallas Kubecka, Stacy McGilvra, Beau Richter, Veronica Sneed, Cary Stoever, Isabell Tellez, Tien Wong, Ivana Kim, Christopher Andreoli, Leslie Barresi, Sarah Brett, Charlene Callahan, Karen Capaccioli, William Carli, Matthew Coppola, Nicholas Emmanuel, Claudia Evans, Anna Fagan, Marcia Grillo, John Head, Troy Kieser, Elaine Lee, Ursula Lord, Edward Miretsky, Kate Palitsch, Todd Petrin, Liz Reader, Svetlana Reznichenko, Mary Robertson, Justin Smith, Demetrios Vavvas, John Wells, Cassie Cahill, W. Lloyd Clark, Kayla Henry, David Johnson, Peggy Miller, LaDetrick Oliver, Robbin Spivey, Tiffany Swinford, Mallie Taylor, Michael Lambert, Kris Chase, Debbie Fredrickson, Joseph Khawly, Valerie Lazarte, Donald Lowd, Pam Miller, Arthur Willis, Philip J. Ferrone, Miguel Almonte, Rachel Arnott, Ingrid Aviles, Sheri Carbon, Michael Chitjian, Kristen DAmore, Christin Elliott, David Fastenberg, Barry Golub, Kenneth Graham, AnnMarie Lavorna, Laura Murphy, Amanda Palomo, Christina Puglisi, David Rhee, Juan Romero, Brett Rosenblatt, Glenda Salcedo, Marianne Schlameuss, Eric Shakin, Vasanti Sookhai, Richard Kaiser, Elizabeth Affel, Gary Brown, Christina Centinaro, Deborah Fine, Mitchell Fineman, Michele Formoso, Sunir Garg, Lisa Grande, Carolyn Herbert, Allen Ho, Jason Hsu, Maryann Jay, Lisa Lavetsky, Elaine Liebenbaum, Joseph Maguire, Julia Monsonego, Lucia O’Connor, Lisa Pierce, Carl Regillo, Maria Rosario, Marc Spirn, James Vander, Jennifer Walsh, Frederick H. Davidorf, Amanda Barnett, Susie Chang, John Christoforidis, Joy Elliott, Heather Justice, Alan Letson, Kathryne McKinney, Jeri Perry, Jill A. Salerno, Scott Savage, Stephen Shelley, Lawrence J. Singerman, Joseph Coney, John DuBois, Kimberly DuBois, Gregg Greanoff, Dianne Himmelman, Mary Ilc, Elizabeth McNamara, Michael Novak, Scott Pendergast, Susan Rath, Sheila Smith-Brewer, Vivian Tanner, Diane E. Weiss, Hernando Zegarra, Lawrence Halperin, Patricia Aramayo, Mandeep Dhalla, Brian Fernandez, Cindy Fernandez, Jaclyn Lopez, Monica Lopez, Jamie Mariano, Kellie Murphy, Clifford Sherley, Rita Veksler, Firas Rahhal, Razmig Babikian, David Boyer, Sepideh Hami, Jeff Kessinger, Janet Kurokouchi, Saba Mukarram, Sarah Pachman, Eric Protacio, Julio Sierra, Homayoun Tabandeh, Adam Zamboni, Michael Elman, Jennifer Belz, Tammy Butcher, Theresa Cain, Teresa Coffey, Dena Firestone, Nancy Gore, Pamela Singletary, Peter Sotirakos, JoAnn Starr, Travis A. Meredith, Cassandra J. Barnhart, Debra Cantrell, RonaLyn Esquejo-Leon, Odette Houghton, Harpreet Kaur, Fatoumatta NDure, Ronald Glatzer, Leonard Joffe, and Reid Schindler
- Subjects
Ophthalmology - Published
- 2023
15. Predictors of 90-Day Colectomy in Hospitalized Patients Receiving Infliximab for Acute Severe Ulcerative Colitis at a Tertiary Care Center
- Author
-
Jeffrey A. Berinstein, Neelakanta Anurag Atkuri, Elliot M. Berinstein, Jessica L. Sheehan, Laura A. Johnson, Shirley A. Cohen-Mekelburg, Hui Jiang, Nicole I. Wakim, Kelley M. Kidwell, Inbal Billie Nahum-Shani, null Robert, Akbar K. Waljee, and Peter D.R. Higgins
- Abstract
BACKGROUND & AIMSAcute severe ulcerative colitis (ASUC) is a life-threatening presentation of ulcerative colitis requiring prompt treatment. Infliximab (IFX) rescue therapy can prevent colectomy in patients with ASUC.METHODSWe performed a cohort study of adult patients hospitalized with ASUC between 01/2014 – 02/2021 who received infliximab rescue therapy. Using multivariable logistic regression, baseline and longitudinal laboratory predictors of colectomy within 90 days of index hospitalization were identified and used to develop a risk prediction model and prognostic scoring system to identifying patients at risk for colectomy. Model performance was assessed using area under the receiver operator characteristic curve (AUC) analysis.RESULTS166 patients with ASUC who received infliximab rescue therapy were identified. Overall, 24.7% (n=41) underwent colectomy within 90 days. Multivariate analysis revealed that colectomy within 90 days could be predicted by having a calculated IFX clearance of >53L/d (OR 2.28, 95% CI 0.99, 5.22), a day 0 absolute C-reactive protein (CRP) > 91mg/L (OR 3.49, 95% CI 1.58 to 8.08), a decrease in CRP of < 43% from day 0 to day 3 (OR 4.13, 95% CI 1.84 to 9.94), and a decrease in CRP of < 9% from the day of IFX administration to one day post-IFX administration (OR 4.20, 95% CI 1.74 to 10.4). Using these predictors, two highly accurate prognostic scoring system were developed to identify patients at risk for requiring colectomy both prior to administering infliximab (AUC 0.76) and after administer infliximab rescue therapy (AUC 0.81).CONCLUSIONWe identified important baseline and longitudinal laboratory predictors of colectomy within 90-days among patients with ASUC receiving infliximab rescue therapy and developed accurate prognostic scores to determine risk of colectomy. These scores can be used risk-stratify patients and facilitate personalized management.
- Published
- 2022
16. Topic: AS07-Singular Entities/Subtypes/AS07a-ARCH, CCUS, ICUS: THE IMPACT OF CHIP ON CHEMOTHERAPY-RELATED OUTCOMES AND CLONAL DYNAMICS IN OLDER LYMPHOMA PATIENTS
- Author
-
R. Buckstein, M. Cheung, L. Mozessohn, L. Chodirker, K. Imrie, N. Berinstein, S. Chow, O. Lopes, G. Kupakuwana-Suk, A. Fu, A. Mcnaughton, A. Parmentier, P. Sasitharakumar, H. Tsui, L. Zhang, and M. Rauh
- Subjects
Cancer Research ,Oncology ,Hematology - Published
- 2023
17. The Perfect Storm: An Unusual Cause of Intestinal Perforation in a Solid Organ Transplant Patient
- Author
-
Karan Joseph, Daniel Aintabi, Eun-Young K. Choi, and Jeffrey A. Berinstein
- Subjects
General Medicine - Published
- 2023
18. Next Generation BTK Inhibitor Acalabrutinib with Bendamustine-Rituximab in First Line Waldenstrom's Macroglobulinemia: The Brawm Study
- Author
-
Neil L Berinstein, Gail Klein, Katerina Welsh, Rebecca McClure, Nicholas Allen Forward, Mona Shafey, Anna Nikonova, David MacDonald, Diego Villa, Irwindeep Sandhu, Mohammed A Aljama, and Jean-François Larouche
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
19. S1464 Participation in a Community-Based Weight Loss Program Showed Significant Improvement in Patient Reported Outcomes of Their Mental and Physical Health
- Author
-
Elliot Berinstein, Ann Saliares, Daniel Aintabi, and Naresh Gunaratnam
- Subjects
Hepatology ,Gastroenterology - Published
- 2022
20. A Predictive Model to Identify Complicated Clostridiodes difficile Infection
- Author
-
Jeffrey A. Berinstein, Calen A. Steiner, Samara Rifkin, D. Alexander Perry, Dejan Micic, Daniel Shirley, Peter D.R. Higgins, Vincent B. Young, Allen Lee, and Krishna Rao
- Abstract
BackgroundClostridioides difficile infection (CDI) is a leading cause of healthcare-associated infections and may result in organ dysfunction, colectomy, and death. We recently showed that published risk scores to predict severe complications from CDI demonstrate poor performance upon external validation. We hypothesized that building and validating a model using geographically and temporally distinct cohorts would more accurately identify patients at risk for complicated CDI.MethodsWe conducted a multi-center retrospective cohort study of adult subjects diagnosed with CDI in the US. After randomly partitioning the data into training/validation set, we developed and compared three machine learning algorithms (Lasso regression, random forest, stacked ensemble models) with 10-fold cross-validation that used structured EHR data collected within 48 hours of CDI diagnosis to predict disease-related complications from CDI (intensive care unit admission, colectomy, or death attributable to CDI within 30 days of diagnosis). Model performance was assessed using area under the receiver operating curve (AUC).ResultsA total of 3,762 patients with CDI were included of which 218 (5.8%) had complications. Lasso regression, random forest, and stacked ensemble models all performed well with AUC ranging between 0.89-0.9. Variables of importance were similar across models, including albumin, bicarbonate, change in creatinine, systolic blood pressure, non-CDI-related ICU admission, and concomitant non-CDI antibiotics. Sensitivity analyses indicated that model performance was robust even when varying derivation cohort inclusion and CDI testing approach.ConclusionUsing a large heterogeneous population of patients, we have developed and validated a prediction model based on structured EHR data that accurately estimates risk for complications from CDI.Key PointsMachine learning models using structured electronic health records can be leveraged to accurately predict risk of severe complications related to Clostridiodes difficile infection, including intensive care unit admission, colectomy, and/or death.
- Published
- 2022
21. Social Network Diversity and the Daily Burden of Inflammatory Bowel Disease
- Author
-
LaVana Greene-Higgs, Ariel Jordan, Jessica Sheehan, Jeffrey Berinstein, Andrew J. Admon, Akbar K. Waljee, Megan Riehl, John Piette, Kenneth Resnicow, Peter D. Higgins, and Shirley Cohen-Mekelburg
- Subjects
Gastroenterology - Published
- 2023
22. The Association Between Nonsteroidal Anti-Inflammatory Drug Use and Inflammatory Bowel Disease Exacerbations: A True Association or Residual Bias?
- Author
-
Shirley Cohen-Mekelburg, Tony Van, Beth Wallace, Jeff Berinstein, Xianshi Yu, James Lewis, Jason Hou, Jason A. Dominitz, and Akbar K. Waljee
- Subjects
Cohort Studies ,Hepatology ,Risk Factors ,Anti-Inflammatory Agents, Non-Steroidal ,Gastroenterology ,Disease Progression ,Humans ,Analgesics, Non-Narcotic ,Inflammatory Bowel Diseases ,Proportional Hazards Models - Abstract
Studies suggest that nonsteroidal anti-inflammatory drugs (NSAID) may contribute to inflammatory bowel disease (IBD) exacerbations. We examined whether variation in the likelihood of IBD exacerbations is attributable to NSAID.In a cohort of patients with IBD (2004-2015), we used 3 analytic methods to examine the likelihood of an exacerbation after an NSAID exposure. First, we matched patients by propensity for NSAID use and examined the association between NSAID exposure and IBD exacerbation using an adjusted Cox proportional hazards model. To assess for residual confounding, we estimated a previous event rate ratio and used a self-controlled case series analysis to further explore the relationship between NSAID and IBD exacerbations.We identified 15,705 (44.8%) and 19,326 (55.2%) IBD patients with and without an NSAID exposure, respectively. Findings from the Cox proportional hazards model suggested an association between NSAID and IBD exacerbation (hazard ratio 1.24; 95% confidence interval 1.16-1.33). However, the likelihood of an IBD exacerbation in the NSAID-exposed arm preceding NSAID exposure was similar (hazard ratio 1.30; 95% confidence interval 1.21-1.39). A self-controlled case series analysis of 3,968 patients who had both an NSAID exposure and IBD exacerbation demonstrated similar exacerbation rates in the 1 year preceding exposure, 2-6 weeks postexposure, and 6 weeks to 6 months postexposure, but a higher incidence in 0-2 weeks postexposure, suggesting potential confounding by reverse causality.While we see an association between NSAID and IBD exacerbations using traditional methods, further analysis suggests this may be secondary to residual bias. These findings may reassure patients and clinicians considering NSAID as a nonopioid pain management option.
- Published
- 2022
23. Mapping the relationships between inflammatory bowel disease and comorbid diagnoses to identify disease associations
- Author
-
Brahmajee K. Nallamothu, Jeffrey A. Berinstein, Kelly C. Cushing, Beth I Wallace, David A. Hanauer, Mohamed Noureldin, Shirley Cohen-Mekelburg, Akbar K. Waljee, Peter D.R. Higgins, and Toby P Keeney-Bonthrone
- Subjects
Erythema nodosum ,medicine.medical_specialty ,Hepatology ,business.industry ,Medical record ,Gastroenterology ,MEDLINE ,Disease ,Colitis ,Inflammatory Bowel Diseases ,medicine.disease ,digestive system ,Parametritis ,Inflammatory bowel disease ,Pyoderma Gangrenosum ,Article ,Cross-Sectional Studies ,Erythema Nodosum ,Internal medicine ,medicine ,Humans ,Female ,Medical diagnosis ,business ,Pyoderma gangrenosum - Abstract
Background Massive amounts of patient data are captured daily in electronic medical records (EMR). Utilizing the power of such large data may help identify disease associations and generate hypotheses that can lead to a better understanding of disease associations and mechanisms. We aimed to comprehensively identify and validate associations between inflammatory bowel disease (IBD) and concurrent comorbid diagnoses. Methods We performed a cross-sectional study using EMR data collected between 1986 and 2009 at a large tertiary referral center to identify associations with a diagnosis of IBD. The resulting associations were externally validated using the Truven MarketScan database, a large nationwide dataset of private insurance claims. Results A total of 6225 IBD patients and 31 125 non-IBD controls identified using EMR data were used to abstract 41 comorbid diagnoses associated with an IBD diagnosis. The strongest associations included Clostridiodes difficile infection, pyoderma gangrenosum, parametritis, pernicious anemia, erythema nodosum, and cytomegalovirus infection. Two IBD association clusters were found, including diagnoses of nerve conduction abnormalities and nonspecific inflammatory conditions of organs outside the gut. These associations were validated in a national cohort of 80 907 patients with IBD and 404 535 age- and sex-matched controls. Conclusion We leveraged a big data approach to identify several associations between IBD and concurrent comorbid diagnoses. EMR and big data provide the opportunity to explore disease associations with large sample sizes. Further studies are warranted to refine the characterization of these associations and evaluate their usefulness for increasing our understanding of disease associations and mechanisms.
- Published
- 2020
24. Analysis of Emergent Nonhospital-Based Retina Consultation Requests in an Academic Nonhospital-Associated Retina Practice
- Author
-
Daniel M. Berinstein, D. Wilkin Parke, Brice Hwang, Kevin J. Blinder, Justin Shortell, Kevin Broderick, Gaurav K. Shah, Barton L. Blackorby, Peter J. Belin, and Sabin Dang
- Subjects
medicine.medical_specialty ,Visual acuity ,Eye pain ,Specialty ,Private Practice ,Appointments and Schedules ,03 medical and health sciences ,0302 clinical medicine ,Retinal Diseases ,Ophthalmology ,Chart review ,Humans ,Medicine ,Referral and Consultation ,Ocular pain ,Retrospective Studies ,030304 developmental biology ,0303 health sciences ,business.industry ,Retrospective cohort study ,Emergency department ,Private practice ,Emergency medicine ,030221 ophthalmology & optometry ,medicine.symptom ,Emergency Service, Hospital ,business - Abstract
Purpose To evaluate the outcomes of after-hour encounters concerning patients referred by eye physicians to on-call retina services for emergent evaluation not seen in or referred by an emergency department. Design Retrospective study. Participants Patients seeking treatment at 3 private practice institutions over a 2-year period between 2017 and 2018. Methods A retrospective chart review was conducted comprising all patients who sought treatment emergently and after clinic hours from 3 academic nonhospital-associated retina-only private practice institutions over a 2-year period. Main Outcome Measures Patient presenting symptoms, diagnosis given at time of after-hours appointment, duration of symptoms, source of after-hours consultation (patient or provider), procedure performed at appointment, and appointments that led to surgery. Results Nine hundred eighty-seven charts were reviewed. Provider referrals accounted for 49.13% (n = 485) and patient-derived referrals accounted for 50% (n = 493) of appointments. New patients accounted for 27.6% (n = 146) of patient-derived and 85.2% (n = 413) of provider-derived referrals. The most common presenting symptoms were flashes and floaters (42.5%; n = 420), decrease in visual acuity (32.1%; n = 317), generalized eye pain (7.4%; n = 73), visual field disturbance (4.3%; n = 42), and postoperative ocular pain (3.4%; n = 34). An in-office procedure was performed at the time of examination in 18% of encounters (n = 178), with most of these being laser retinopexy. Surgery was performed within 24 hours in 18% (n = 180), within 48 hours in 20.6% (n = 203), within 72 hours in 21.7% (n = 214), and within 96 hours in 22.6% (n = 223) of the appointment. When combined with procedures, 36.2% (n = 358) of encounters led to urgent intervention within 24 hours. If a provider called about an existing patient, 37.5% of these appointments (n = 27) led to surgery versus 12.8% (n = 49) if an existing patient self-referred. If a provider called about a new patient, 31.7% of these appointments (n = 131) led to surgery versus 10% (n = 14) if a new patient self-referred. Conclusions At these 3 private practice retinal specialty clinics, 41% of after-hours appointment requests resulted in an intervention within 96 hours, and 36% of these patients underwent an intervention within 24 hours.
- Published
- 2020
25. AXL Is a Potential Target for the Treatment of Intestinal Fibrosis
- Author
-
Peter D.R. Higgins, Sha Huang, Laura A. Johnson, Kelly C. Cushing, Calen A. Steiner, Jeffrey A. Berinstein, Eva S. Rodansky, and Jason R. Spence
- Subjects
0301 basic medicine ,Inflammatory bowel disease ,Receptor tyrosine kinase ,Intestinal Failure ,Transforming Growth Factor beta1 ,03 medical and health sciences ,0302 clinical medicine ,Crohn Disease ,Fibrosis ,In vivo ,Proto-Oncogene Proteins ,medicine ,Humans ,Immunology and Allergy ,biology ,business.industry ,Gastroenterology ,Receptor Protein-Tyrosine Kinases ,Transforming growth factor beta ,Triazoles ,medicine.disease ,Axl Receptor Tyrosine Kinase ,Intestines ,Organoids ,Benzocycloheptenes ,030104 developmental biology ,Cell culture ,Apoptosis ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Leading Off ,business ,Myofibroblast - Abstract
Background Fibrosis is the final common pathway to intestinal failure in Crohn’s disease, but no medical therapies exist to treat intestinal fibrosis. Activated myofibroblasts are key effector cells of fibrosis in multiple organ systems, including the intestine. AXL is a receptor tyrosine kinase that has been implicated in fibrogenic pathways involving myofibroblast activation. We aimed to investigate the AXL pathway as a potential target for the treatment of intestinal fibrosis. Methods To establish proof of concept, we first analyzed AXL gene expression in 2 in vivo models of intestinal fibrosis and 3 in vitro models of intestinal fibrosis. We then tested whether pharmacological inhibition of AXL signaling could reduce fibrogenesis in 3 in vitro models of intestinal fibrosis. In vitro testing included 2 distinct cell culture models of intestinal fibrosis (matrix stiffness and TGF-β1 treatment) and a human intestinal organoid model using TGF-β1 cytokine stimulation. Results Our findings suggest that the AXL pathway is induced in models of intestinal fibrosis. We demonstrate that inhibition of AXL signaling with the small molecule inhibitor BGB324 abrogates both matrix-stiffness and transforming growth factor beta (TGF-β1)–induced fibrogenesis in human colonic myofibroblasts. AXL inhibition with BGB324 sensitizes myofibroblasts to apoptosis. Finally, AXL inhibition with BGB324 blocks TGF-β1-induced fibrogenic gene and protein expression in human intestinal organoids. Conclusions The AXL pathway is active in multiple models of intestinal fibrosis. In vitro experiments suggest that inhibiting AXL signaling could represent a novel approach to antifibrotic therapy for intestinal fibrosis such as in Crohn’s disease.
- Published
- 2020
26. Anti-tumour necrosis factor-α therapy and recurrent or new primary cancers in patients with inflammatory bowel disease, rheumatoid arthritis, or psoriasis and previous cancer in Denmark: a nationwide, population-based cohort study
- Author
-
Camilla B. Jensen, Jeffrey A. Berinstein, Marie Villumsen, Shirley Cohen-Mekelburg, Akbar K. Waljee, Tine Jess, Peter D.R. Higgins, Beth I Wallace, and Kristine H. Allin
- Subjects
Adult ,Male ,medicine.medical_specialty ,Denmark ,Clinical Decision-Making ,Population ,Disease ,Arthritis, Rheumatoid ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Neoplasms ,Internal medicine ,Outcome Assessment, Health Care ,medicine ,Humans ,Psoriasis ,Prospective Studies ,Registries ,education ,Prospective cohort study ,Aged ,education.field_of_study ,Hepatology ,Tumor Necrosis Factor-alpha ,business.industry ,Incidence ,Hazard ratio ,Gastroenterology ,Case-control study ,Cancer ,Middle Aged ,Inflammatory Bowel Diseases ,medicine.disease ,Cancer registry ,Case-Control Studies ,030220 oncology & carcinogenesis ,Female ,Tumor Necrosis Factor Inhibitors ,030211 gastroenterology & hepatology ,business ,Cohort study - Abstract
BACKGROUND: Safety of anti-tumour necrosis factor-α (TNFα) therapy in people with a history of cancer and with an immune-mediated disease is unknown. We aimed to assess the risk of recurrence of initial cancer or development of a new primary cancer after treatment with anti-TNFα therapy.METHODS: In this Danish, population-based cohort study we recruited adults (≥18 years) with inflammatory bowel disease (IBD), rheumatoid arthritis, or psoriasis and a primary cancer diagnosed between Jan 1, 1999 and Dec 31, 2016. Patients were recruited from the prospectively recorded Danish National Patient Registry and the Danish Cancer Registry. Participants were matched 1:10 between the treatment group who received anti-TNFα therapy and the control group (no anti-TNFα therapy) and we excluded individuals with a cancer diagnosed before their first anti-TNFα treatment (or before matching date for controls), individuals diagnosed with IBD, rheumatoid arthritis, or psoriasis after anti-TNFα initiation (or respective match date for controls), and individuals who received anti-TNFα with fewer than five matched controls. Using adjusted Cox proportional hazards regression, we estimated the primary outcome of development of recurrent or new primary cancer in patients who received anti-TNFα therapy compared with patients who did not receive this therapy, matched by sex, immune-mediated disease type, cancer type, and time from initial cancer diagnosis to first anti-TNFα registration.FINDINGS: Overall, 25 738 patients with immune-mediated disease and a history of cancer were identified. 434 patients who received anti-TNFα therapy after their initial cancer were matched to 4328 patients in the control group. During 18 752 person-years (median 5·6 years [IQR 2·8-7·9]) of follow up, 635 individuals developed recurrent or new primary cancer, 72 of whom had received anti-TNFα therapy and 563 of whom were in the control group. The median time between anti-TNFα treatment and recurrent or new primary cancer diagnosis was 2·8 years (IQR 1·7-5·4). The incidence of recurrent or new primary cancer development was 30·3 cases (95% CI 24·0-38·2) per 1000 person-years in the anti-TNFα treatment group and 34·4 cases (31·7-37·3) per 1000 person-years in the control group, yielding an adjusted hazard ratio of 0·82 (95% CI 0·61-1·11).INTERPRETATION: Use of anti-TNFα therapy was not associated with recurrent or new primary cancer development in patients with previous cancer. Timing of anti-TNFα therapy after an initial cancer diagnosis did not influence recurrent or new primary cancer development. This observation might guide clinical decision making among providers treating immune-mediated diseases with anti-TNFα medications.FUNDING: None.
- Published
- 2020
27. Association of Household Pets, Common Dietary Factors, and Lifestyle Factors with Clostridium difficile Infection
- Author
-
Emily Briggs, Peter D.R. Higgins, Krishna Rao, Calen A. Steiner, Katelin Roth, and Jeffrey A. Berinstein
- Subjects
Adult ,Male ,medicine.medical_specialty ,Allergy ,Adolescent ,genetic structures ,Physiology ,Dietary factors ,Article ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Hospital-acquired infection ,Epidemiology ,Animals ,Humans ,Medicine ,Life Style ,Aged ,Retrospective Studies ,Aged, 80 and over ,Response rate (survey) ,business.industry ,Gastroenterology ,Feeding Behavior ,Pets ,Middle Aged ,Clostridium difficile ,Hepatology ,medicine.disease ,Lifestyle factors ,Case-Control Studies ,030220 oncology & carcinogenesis ,Clostridium Infections ,Female ,030211 gastroenterology & hepatology ,business - Abstract
BACKGROUND: Clostridium difficile infection (CDI) is one of the most common hospital-acquired infections and is associated with significant morbidity and mortality. Since owning a cat or dog could enrich the gut microbiome, we hypothesized that it would be protective against CDI. AIMS: We conducted a survey study on patients tested for CDI in order to assess whether living in the presence of a pet is associated with a decreased risk of CDI. METHODS: We surveyed subjects aged 18–90 over a 14-month period using a retrospective case–control design. Subjects with CDI were matched by gender and age to patients who tested negative and had no prior history of CDI. A web-based survey was provided to subjects by mail or assisted by phone. Conditional logistic regression was used to assess for associations between CDI and the various risk factors. RESULTS: 205 CDI positive and 205 CDI negative subjects (response rate of 50.2%) were included. After matching for age and sex, living with a cat or dog was not associated with negative CDI testing. Exploratory multivariable modeling identified an unexpected association between positive CDI testing and high meat intake (OR 2.13, 95% CI 1.21–3.77) as well as between positive CDI testing and cat allergies (OR 1.88, 95% CI 1.02–3.46). CONCLUSION: Living with a cat or dog was not associated with negative CDI testing. Several novel risk factors for CDI have been identified including high meat intake and cat allergies.
- Published
- 2020
28. Tofacitinib for Biologic-Experienced Hospitalized Patients With Acute Severe Ulcerative Colitis: A Retrospective Case-Control Study
- Author
-
Laura A. Johnson, Ryan W. Stidham, Jeffrey A. Berinstein, Elliot M. Berinstein, Jami Kinnucan, Michael Dias, Shirley Cohen-Mekelburg, John I. Allen, Shrinivas Bishu, Akbar K. Waljee, Peter D.R. Higgins, Calen A. Steiner, Randolph E. Regal, Jessica L. Sheehan, and Kelly C. Cushing
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,03 medical and health sciences ,0302 clinical medicine ,Piperidines ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Colectomy ,Janus kinase inhibitor ,Retrospective Studies ,Biological Products ,Tofacitinib ,Hepatology ,Proportional hazards model ,business.industry ,Hazard ratio ,Gastroenterology ,Case-control study ,medicine.disease ,Ulcerative colitis ,Pyrimidines ,030220 oncology & carcinogenesis ,Concomitant ,Case-Control Studies ,030211 gastroenterology & hepatology ,Colitis, Ulcerative ,business - Abstract
Background & Aims Despite rescue therapy, more than 30% of patients with acute severe ulcerative colitis (ASUC) require colectomy. Tofacitinib is a rapidly acting Janus kinase inhibitor with proven efficacy in ulcerative colitis. Tofacitinib may provide additional means for preventing colectomy in patients with ASUC. Methods A retrospective case-control study was performed evaluating the efficacy of tofacitinib induction in biologic-experienced patients admitted with ASUC requiring intravenous corticosteroids. Tofacitinib patients were matched 1:3 to controls according to gender and date of admission. Using Cox regression adjusted for disease severity, we estimated the 90-day risk of colectomy. Rates of complications and steroid dependence were examined as secondary outcomes. Results Forty patients who received tofacitinib were matched 1:3 to controls (n = 113). Tofacitinib was protective against colectomy at 90 days compared with matched controls (hazard ratio [HR], 0.28, 95% confidence interval [CI], 0.10–0.81; P = .018). When stratifying according to treatment dose, 10 mg three times daily (HR, 0.11; 95% CI, 0.02–0.56; P = .008) was protective, whereas 10 mg twice daily was not significantly protective (HR, 0.66; 95% CI, 0.21–2.09; P = .5). Rate of complications and steroid dependence were similar between tofacitinib and controls. Conclusions Tofacitinib with concomitant intravenous corticosteroids may be an effective induction strategy in biologic-experienced patients hospitalized with ASUC. Prospective trials are needed to identify the safety, optimal dose, frequency, and duration of tofacitinib for ASUC.
- Published
- 2021
29. Use of Accelerated Induction Strategy of Infliximab for Ulcerative Colitis in Hospitalized Patients at a Tertiary Care Center
- Author
-
Jeffrey A. Berinstein, Shail M. Govani, Karin M. Hardiman, Ryan W. Stidham, Akbar K. Waljee, and Peter D.R. Higgins
- Subjects
Adult ,Male ,medicine.medical_specialty ,Physiology ,Hospitalized patients ,medicine.medical_treatment ,Tertiary care ,Drug Administration Schedule ,Tertiary Care Centers ,03 medical and health sciences ,0302 clinical medicine ,Gastrointestinal Agents ,Risk Factors ,Internal medicine ,medicine ,Humans ,In patient ,Dosing ,Colectomy ,Retrospective Studies ,business.industry ,Gastroenterology ,Middle Aged ,Hepatology ,medicine.disease ,Ulcerative colitis ,Infliximab ,030220 oncology & carcinogenesis ,Colitis, Ulcerative ,Female ,030211 gastroenterology & hepatology ,business ,medicine.drug - Abstract
Infliximab can prevent colectomy in patients hospitalized with acute severe ulcerative colitis (ASUC). In cases of ASUC, fecal losses of infliximab may lead to low drug levels and reduced efficacy. To determine 90-day colectomy risk and postoperative complications in patients receiving single-dose and accelerated induction of infliximab for ASUC. We conducted a retrospective review of patients hospitalized with ASUC requiring infliximab therapy between 2013 and 2017 at the University of Michigan. Patients were excluded if they had an enteric infection, received an anti-TNF previously, or received cyclosporine during the same admission. The primary outcome was colectomy within 90 days of admission. Patients receiving single-dose induction infliximab were compared to those receiving accelerated rescue induction with two doses of infliximab prior to day 14. Administration of accelerated induction was guided by a protocol, suggesting administering a second dose of infliximab to those with only a partial response in CRP 3 days after the initial dose. Postoperative outcomes including 30-day readmission rates and complications were compared using descriptive statistics. From 2013 to 2017, 66 patients with ASUC met our criteria. Thirty-three received accelerated induction (50.0%). The colectomy rate in the accelerated induction group was 30.3% versus 24.2% in the single-dose induction group (p = 0.58). There was no detected difference in postoperative outcomes between the accelerated and single-dose rescue induction. In this retrospective review, 69.7% of those failing to respond to single-dose infliximab were able to avoid colectomy with an accelerated rescue induction strategy without worsening postoperative outcomes. Larger studies of accelerated dosing infliximab are needed.
- Published
- 2019
30. S2846 Liquid Nitrogen Cryoablation Alone Is an Effective Palliative Treatment for Metastatic Esophageal Squamous Cell Carcinoma
- Author
-
Daniel Aintabi, Ann Saliares, Elliot Berinstein, and Naresh Gunaratnam
- Subjects
Hepatology ,Gastroenterology - Published
- 2022
31. S2761 Crohn's Disease Presenting as Diffuse Granulomatous Mesenteric Adenitis
- Author
-
Michael W. Song, Suraj Pai, Fadi Hawa, and Jeffrey Berinstein
- Subjects
Hepatology ,Gastroenterology - Published
- 2022
32. S1794 Pleomorphic Sarcoma Presenting as Pancreatitis, Panniculitis and Polyarthritis Syndrome
- Author
-
Ann Saliares, Elliot Berinstein, Wael Al-Yaman, and Naresh Gunaratnam
- Subjects
Hepatology ,Gastroenterology - Published
- 2022
33. Editorial: estimating the costs of care in irritable bowel syndrome—a necessary step to enhance value‐based care for a high‐prevalence, low‐cost condition
- Author
-
Jeffrey Berinstein and Mark Fendrick
- Subjects
Hepatology ,Gastroenterology ,Pharmacology (medical) - Published
- 2022
34. A Patient Perspective on Contemporary Risk of Surgery in Patients With Ulcerative Colitis and Crohn’s Disease
- Author
-
Jeffrey A. Berinstein and Katelin Roth
- Subjects
Crohn's disease ,medicine.medical_specialty ,Hepatology ,business.industry ,Internal medicine ,Perspective (graphical) ,Gastroenterology ,medicine ,In patient ,medicine.disease ,business ,Ulcerative colitis - Published
- 2022
35. Institutionalizing Precarious Immigration Status in Canada
- Author
-
Judith K. Bernhard, Carolina Berinstein, and Luin Goldring
- Subjects
Social and Behavioral Sciences - Abstract
This paper analyzes the institutionalized production of precarious migration status in Canada. Building on recent work on the legal production of illegality and non-dichotomous approaches to migratory status, we review Canadian immigration and refugee policy, and analyze pathways to loss of migratory status and the implications of less than full status for access to social services. In Canada, policies provide various avenues of authorized entry, but some entrants lose work and/or residence authorization and end up with variable forms of less-than-full immigration status. We argue that binary conceptions of migration status (legal/illegal) do not reflect this context, and advocate the use of ‘precarious status’ to capture variable forms of irregular status and illegality, including documented illegality. We find that elements of Canadian policy routinely generate pathways to multiple forms of precarious status, which is accompanied by precarious access to public services. Our analysis of the production of precarious status in Canada is consistent with approaches that frame citizenship and illegality as historically produced and changeable. Considering variable pathways to and forms of precarious status supports theorizing citizenship and illegality as having blurred rather than bright boundaries. Identifying differences between Canada and the US challenges binary and tripartite models of illegality, and supports conducting contextually specific and comparative work.
- Published
- 2021
36. Biomarkers for the Prediction and Diagnosis of Fibrostenosing Crohn's Disease: A Systematic Review
- Author
-
Brian G. Feagan, Jeremy Louissaint, Mark E. Baker, Cathy Lu, Florian Rieder, Ryan W. Stidham, Jason R. Spence, Dominik Bettenworth, Carol Shannon, Joel G. Fletcher, Jeffrey A. Berinstein, Peter D.R. Higgins, Calen A. Steiner, Vipul Jairath, Stenosis Therapy, and David H. Bruining
- Subjects
medicine.medical_specialty ,Constriction, Pathologic ,Cochrane Library ,Cartilage Oligomeric Matrix Protein ,Inflammatory bowel disease ,Gastroenterology ,Article ,Crohn Disease ,Intestinal Stricture ,Internal medicine ,medicine ,Humans ,Crohn's disease ,Hepatology ,biology ,business.industry ,Serine Endopeptidases ,Anti–Saccharomyces cerevisiae antibody ,Odds ratio ,medicine.disease ,Clinical trial ,MicroRNAs ,biology.protein ,Biomarker (medicine) ,business ,Biomarkers ,Intestinal Obstruction - Abstract
Background and Aims Intestinal strictures are a common complication of Crohn’s disease (CD). Biomarkers of intestinal strictures would assist in their prediction, diagnosis, and monitoring. Herein we provide a comprehensive systematic review of studies assessing biomarkers that may predict or diagnose CD-associated strictures. Methods We performed a systematic review of PubMed, EMBASE, ISI Web of Science, Cochrane Library, and Scopus to identify citations pertaining to biomarkers of intestinal fibrosis through July 6, 2020, that used a reference standard of full-thickness histopathology or cross-sectional imaging or endoscopy. Studies were categorized based on the type of biomarker they evaluated (serum, genetic, histopathologic, or fecal). Results Thirty-five distinct biomarkers from 3 major groups were identified: serum (20 markers), genetic (9 markers), and histopathology (6 markers). Promising markers include cartilage oligomeric matrix protein, hepatocyte growth factor activator, and lower levels of microRNA-19-3p (area under the curves were 0.805, 0.738, and 0.67, respectively), and multiple anti-flagellin antibodies (A4-Fla2 [odds ratio, 3.41], anti Fla-X [odds ratio, 2.95], and anti-CBir1 [multiple]). Substantial heterogeneity was observed and none of the markers had undergone formal validation. Specific limitations to acceptance of these markers included failure to use a standardized definition of stricturing disease, lack of specificity, and insufficient relevance to the pathogenesis of intestinal strictures or incomplete knowledge regarding their operating properties. Conclusions There is a lack of well-defined studies on biomarkers of intestinal stricture. Development of reliable and accurate biomarkers of stricture is a research priority. Biomarkers can support the clinical management of CD patients and aid in the stratification and monitoring of patients during clinical trials of future antifibrotic drug candidates.
- Published
- 2021
37. Review of Bruton Tyrosine Kinase Inhibitors for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma
- Author
-
Carolyn Owen, A. Christofides, Laurie H. Sehn, and N.L. Berinstein
- Subjects
mantle cell lymphoma ,Antineoplastic Agents ,Review Article ,Lymphoma, Mantle-Cell ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Refractory ,Recurrence ,immune system diseases ,hemic and lymphatic diseases ,Agammaglobulinaemia Tyrosine Kinase ,medicine ,Humans ,Bruton's tyrosine kinase ,030212 general & internal medicine ,Bruton tyrosine kinase inhibitors ,Protein Kinase Inhibitors ,biology ,business.industry ,acalabrutinib ,medicine.disease ,Lymphoma ,Clinical trial ,chemistry ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Ibrutinib ,Refractory Mantle Cell Lymphoma ,Cancer research ,biology.protein ,Acalabrutinib ,Mantle cell lymphoma ,Neoplasm Recurrence, Local ,business - Abstract
Mantle cell lymphoma (MCL) is a rare subtype of aggressive B-cell non-Hodgkin lymphoma that remains incurable with standard therapy. Patients typically require multiple lines of therapy, and those with relapsed or refractory (R/R) disease have a very poor prognosis. The Bruton tyrosine kinase (BTK) inhibitor ibrutinib has proven to be an effective agent for patients with R/R MCL. Although usually well tolerated, ibrutinib can be associated with unique toxicities, requiring discontinuation in some patients. Effective and well-tolerated alternatives to ibrutinib for patients with R/R MCL are therefore needed. Novel btk inhibitors such as acalabrutinib, zanubrutinib, and tirabrutinib are designed to improve on the safety and efficacy of first-generation btk inhibitors such as ibrutinib. Data from single-arm clinical trials suggest that, compared with ibrutinib, second-generation btk inhibitors have comparable efficacy and might have a more favourable toxicity profile. Those newer btk inhibitors might therefore provide a viable treatment option for patients with R/R MCL.
- Published
- 2019
38. Abstract P2-09-12: Perilymphatic IRX-2 cytokine therapy to enhance tumor infiltrating lymphocytes (TILs) and PD-L1 expression preceding curative-intent therapy in early stage breast cancer (ESBC)
- Author
-
Walter J. Urba, M Campbell, Neil L Berinstein, Joanna Pucilowska, Maritza Martel, A Acheson, M Shah, Zhaoyu Sun, David B. Page, K Massimino, William L. Redmond, S Aliabadi-Wahle, Nicole Moxon, JH Imatani, Yaping Wu, Alison Conlin, and JE Egan
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Tumor microenvironment ,Cyclophosphamide ,Cytokine Therapy ,business.industry ,Tumor-infiltrating lymphocytes ,medicine.medical_treatment ,Cancer ,Immunotherapy ,medicine.disease ,Immune system ,Breast cancer ,Internal medicine ,Medicine ,business ,medicine.drug - Abstract
Background: Cytokines are being explored as a therapeutic strategy to modulate the tumor microenvironment and facilitate immunotherapy benefit in breast cancer. Here, we investigate a locoregional therapeutic approach whereby cytokines (IRX-2) are administered into the subcutaneous peri-areolar tissue (in an anatomic distribution similar to sentinel lymph node mapping) to facilitate immune cell recruitment/activation within the draining lymph nodes and tumor in ESBC. IRX-2 is derived from ex vivo phytohemagglutinin-stimulated lymphocytes and contains multiple cytokines including IL-1β, IL-2, TNF-α, IFN-γ, IL-6, IL-8, and GM-CSF, with stable concentrations from lot to lot. Preclinically, IRX-2 activates T-cells and natural killer (NK) cells, facilitates antigen presentation, and enhances activity of anti-PD-1/L1 in a SCC7 model. In a preceding head/neck squamous cell carcinoma phase I trial, perilymphatic IRX-2 was safe and increased TILs. Here, we report the final clinical results of a phase Ib trial evaluating the feasibility and immunologic activity of IRX-2 in ESBC. Methods: Beginning 21 days prior to surgical resection, enrolled operable patients with stage I-III ESBC (all subtypes) received the pre-operative IRX-2 regimen consisting of a single low-dose cyclophosphamide (300 mg/m2 to facilitate T-regulatory cell depletion), followed by 10 days of subcutaneous peri-areolar IRX-2 injections into the affected breast (1 mL × 2 at tumor axis and at 90°). Endpoints were feasibility (primary endpoint), stromal TIL (sTIL) count (pre-treatment versus post-treatment, blinded average of two pathologist reads using San Antonio H&E sTIL guidelines), PD-L1 expression (Nanostring) and enumeration of peripheral immune cells by flow cytometry. Results: All patients (n=16/16) completed and tolerated the regimen with no surgical delays or treatment-attributed grade III/IV toxicities. Common adverse events (occurring in >15% subjects) attributed to IRX-2 injections were: injection site reaction (grade 1, n=8/16), bruising (grade 1, n=7/16), and pain (grade 1, n=3/16). Common adverse events attributed to low-dose cyclophosphamide were: fatigue (grade 1, n=5/16) and nausea (grade 1/2, n=3/16). Treatment was associated with an increase in sTIL score (Wilcoxon signed-rank p=.04), with 4/10 sTIL-low tumors (0-10% score) re-categorized to sTIL-moderate (11-50% score). Increases in PD-L1 RNA expression were observed (Wilcoxon signed-rank p=.04) in 12/16 tumors (median 57% increase, range: -53% to 185% increase), as well as increases in Nanostring NK and Th1 cell signatures. In blood, increases in CD4 and CD8 effector T-cell activation (ICOS, HLA-DR, and CD38) and T-reg depletion were observed. Conclusions: IRX-2 was well tolerated with preliminary evidence of sTIL increase, PD-L1 upregulation, and peripheral lymphocyte activation. Based upon these data and preclinical evaluations demonstrating synergy with checkpoint inhibition, the IRX-2 regimen is being evaluated for clinical efficacy in conjunction with pembrolizumab and neoadjuvant chemotherapy (doxorubicin, cyclophosphamide, paclitaxel) in patients with stage II-III triple negative breast cancer. Citation Format: Pucilowska J, Egan JE, Berinstein NL, Moxon N, Aliabadi-Wahle S, Imatani JH, Conlin A, Acheson A, Massimino K, Martel M, Campbell M, Wu Y, Sun Z, Redmond W, Shah M, Urba WJ, Page DB. Perilymphatic IRX-2 cytokine therapy to enhance tumor infiltrating lymphocytes (TILs) and PD-L1 expression preceding curative-intent therapy in early stage breast cancer (ESBC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-09-12.
- Published
- 2019
39. Natural History of Drusenoid Pigment Epithelial Detachment Associated with Age-Related Macular Degeneration
- Author
-
Jeannette J. Yu, Elvira Agrón, Traci E. Clemons, Amitha Domalpally, Freekje van Asten, Tiarnan D. Keenan, Catherine Cukras, Emily Y. Chew, Frederick L. Ferris, John Paul SanGiovanni, Traci Clemons, Anne Lindblad, Robert Lindblad, Nilay Shah, Robert Sperduto, Wendy McBee, Gary Gensler, Molly Harrington, Alice Henning, Katrina Jones, Kumar Thotapally, Diana Tull, Valerie Watson, Kayla Williams, Christina Gentry, Francine Kaufman, Chris Morrison, Elizabeth Saverino, Sherrie Schenning, Barbara Blodi, Ronald P. Danis, Matthew Davis, Kathy Glander, Gregory Guilfoil, Larry D. Hubbard, Kristine Johnson, Ronald Klein, Barbara Nardi, Michael Neider, Nancy Robinson, Eileen Rosensteel, Hugh Wabers, Grace Zhang, Alan J. Ruby, Antonio Capone, Bawa Dass, Kimberly Drenser, Bruce R. Garretson, Tarek S. Hassan, Michael Trese, George A. Williams, Jeremy Wolfe, Tina Bell, Mary Zajechowski, Dennis Bezaire, Fran McIver, Anthony Medina, Jackie Pagett, Stephanie Hatch Smith, Lynn Swartz, Tom Treuter, Andrew Antoszyk, Justin Brown, David J. Browning, Walter Holland, Angella Karow, Kelly Stalford, Angela Price, Sarah Ennis, Sherry Fredenberg, Jenna Herby, Uma Balasubramaniam, Loraine Clark, Donna McClain, Michael McOwen, Lynn Watson, Michael Klein, Steven T. Bailey, Thomas J. Hwang, Andreas Lauer, J. Timothy Stout, Patty McCollum, Milt Johnson, Patrick B. Rice, Ivana Kim, John Loewenstein, Joan Miller, Lucia Sobrin, Lucy Young, Jacqueline Sullivan, Patricia Houlihan, Linda Merry, Ann Marie Lane, Ursula Lord Bator, Claudia Evans, Sarah Brett, Charleen Callahan, Marcia Grillo, David Walsh, Kamella Lau Zimmerman, Gary Edd Fish, Rajiv Anand, Lori E. Coors, Dwain G. Fuller, Rand Spencer, Robert C. Wang, Karen Duignan, Sally Arceneaux, Hank Aguado, Nicholas Hesse, Michael Mackens, Brian Swan, Wai T. Wong, Monica Dalal, Naima Jacobs-El, Catherine Meyerle, Benjamin Nicholson, Henry Wiley, Katherine Hall Shimel, Angel Garced, Janice Oparah, Greg Short, Alana Temple, Babilonia Ayukawa, Guy Foster, Darryl Hayes, Dessie Koutsandreas, Roula Nashwinter, John Rowan, Michael Bono, Denise Cunningham, Marilois Palmer, Alicia Zetina, David H. Orth, Kourous Rezaei, Joseph Civantos, Sohail Hasan, Kirk Packo, Celeste Figliulo, Pam Stanberry, Tara Farmer, Kiersten Nelson, Shannya Townsend-Patrick, Philip Rosenfeld, Royce Chen, Rishi Doshi, Sander Dubovy, Brian T. Kim, Matthew Lowrance, Andrew Moshfeghi, Zayna Nahas, Gary Schienbaum, John Vishak, Christina Weng, Zohar Yehoshua, Belen Rodriguez, Jose Rebimbas, Jane Gleichauf, Mike Kicak, Jason Mena, Tim Odem, Elizabeth Sferza-Camp, Alicia Disgdiertt, Jim Oramas, Isabel Rams, Stephanie Thatcher, Susan B. Bressler, Neil M. Bressler, Daniel Finkelstein, Steven H. Sherman, Sharon Solomon, Howard S. Ying, Rita Denbow, Deborah Phillips, Elizabeth Radcliffe, Judy Belt, Dennis Cain, David Emmert, Mark Herring, Jacquelyn McDonald, G. Baker Hubbard, Chris S. Bergstrom, Blaine Cribbs, Andrew Hendrick, Brandon Johnson, Philip Laird, Sonia Mehta, Timothy Olsen, Justin Townsend, Jion Yan, Steven Yeh, Linda Curtis, Judy Brower, Hannah Yi, Jannah Rutter Dobbs, Debbie Jordan, Michael J. Elman, Robert A. Liss, JoAnn Starr, Jennifer Belz, Charlene Putzulo, Teresa Coffey, Ashley Davis, Pamela Singletary, Giorya Shabi Andreani, Theresa Cain, Daniel Ketner, Peter Sotirakos, Suresh Chandra, Barbara A. Blodi, Michael M. Altaweel, Justin L. Gottlieb, Michael Ip, T. Michael Nork, Thomas S. Stevens, Kathryn Burke, Shelly Olson, Kristine Dietzman, Barbara Soderling, Guy Somers, Angie Wealti, Denise Krolnik, John Peterson, Sandra Reed, Thomas Friberg, Andrew Eller, Denise Gallagher, Leanne Labriola, Melissa Pokrifka, Aron Gedansky, Natalie Anthony, Cassandra Grzybowski, Dawn Matthews, Sharon Murajda-Jumba, Jessica Toro, David G. Callanan, Wayne A. Solley, Patrick Williams, Sandy Lash, Bob Boleman, Chris Dock, Michel Shami, Brenda Arrington, Ashaki Meeks, Alan R. Margherio, Paul Raphaelian, Debra Markus, Justin Langdon, Elizabeth Truax, Sandy Lewis, Brad Terry, Amy Noffke, Kean Oh, Ramin Sarrafizadeh, Scott Sneed, Julie Hammersley, Serena Neal, Mary Doran, Nan Jones, Lisa Preston, Heather Jessick, Tanya Tracy Marsh, Michael Tolentino, Adam Berger, Richard Hamilton, David Misch, Suk Jin Moon, Dawn Sutherland, Vera Dilts, Sara Henderson, Esmeralda Medina, Donald Trueman, Laura Holm, Jason Strickland, Darmakusuma Ie, Jeffrey L. Lipkowitz, Kekul B. Shah, Susan Geraghty, Beverly Sannazzaro, Morgan Harper, Krista Bayer, Mary B. Lansing, Lauren B. Fox, Rebecca Lee, Jay B. Stallman, Michael Jacobson, Sean Koh, Scott Lampert, John Miller, Mark Rivellese, Atul Sharma, Robert A. Stoltz, Stephanie Vanderveldt, Leslie Marcus, Starr Hendricks, Ryan Hollman, Grethel Betanzos, Leslie Ellorin, Shelly Fulbright, Debbie McCormick, Paul A. Edwards, Julianne Hall, Mary Monk, Melanie Gutkowski, Melina Mazurek, Janet Murphy, Katherine Gusas, Crystal Moffett, David Burley, Nicole Chesney, Katie Kilgo, Brian Rusinek, Bradley Stern, Tracy Troszak, Rhonda Baker-Levingston, Carl W. Baker, Tracey Caldwell, Tammy Walker, Lynnette F. Lambert, Tracey Martin, Mary Jill Palmer, Tana Williams, Michael A. Novak, Joseph Coney, David G. Miller, Scott Pendergast, Lawrence Singerman, Nicholas Zakov, Hernando Zegarra, Kim DuBois, Susan Rath, Lori Revella, Tammy Brink, Kim Drury, Lisa Hogue, Mary Ilc, Connie Keller, Elizabeth McNamara, Vivian Tanner, Tamara Cunningham, John DuBois, Gregg Greanoff, Trina Nitzsche, Sheila Smith-Brewer, Ricky D. Isernhagen, John W. Kitchens, Thomas W. Stone, William J. Wood, Diana Holcomb, Virginia Therrien, Michelle Buck, Jeanne Van Arsdall, Edward Slade, Todd E. Schneiderman, David J. Spinak, Jackie Gaedke, Heather Davis Brown, Dan Helgren, Jenifer Garrison Pangelinan, Lawrence Halperin, Scott Anagnoste, Mandeep Dhalla, Krista Rosenberg, Barry Taney, W. Scott Thompson, Jaclyn Lopez, Monica Hamlin, Monica Lopez, Jamie Mariano, Evelyn Quinchia, Patricia Aramayo, Rita Veksler, Michael Lee, Richard Dreyer, Irvin Handelman, Colin Ma, Mark Peters, Stephen Hobbs, Amanda Milliron, Marcia Kopfer, Michele Connaughton, A. Christine Hoerner, R. Joseph Logan, Harry J. Wohlsein, David Boyer, Thomas G. Chu, Pouya Dayani, David Liao, Roger L. Novack, Firas M. Rahhal, Richard Roe, Homayoun Tabandeh, Janet Bayramyan, Tammy Gasparyan, Connie Hoang, Janet Kurokouchi, Tammy Eileen Lo, Richard Ngo, Mary Ann Nguyen, Michael Peyton, Charles Yoon, Julio Sierra, Adam Zamboni, Jeff Kessinger, Eric Protacio, Adam Smucker, Pamela Rath, Robert Bergren, Bernard Doft, Judy Liu, Karl Olsen, Lori Merlotti, Willia Ingram, Kellianne Marfisi, Kimberly Yeckel, Heather Schultz Carmelo, Amanda Fec, Keith McBroom, David Steinberg, Marc Levy, Jody Abrams, Melvin Chen, Waldemar Torres, Peggy Jelemensky, Mark Prybylski, Tara Raphael, Diana Appleby, Charlotte Rodman, Mark Sneath, Robert H. Rosa, Vanessa Hoelscher, Adelia Castano, Jocelyn Parker, John Hoskins, Nicholas Anderson, Joseph Googe, Tod A. McMillan, James Miller, Stephen Perkins, Kristina Oliver, Jennifer Beerbower, Bruce Gilliland, Cecile Hunt, Mike Jacobus, Raul Lince, Christopher Morris, Sarah Oelrich, Jerry Whetstone, Clement K. Chan, Steven Lin, Kim Walther, Tiana Gonzales, Lenise Myers, Kenneth Huff, David M. Brown, Eric Chen, Matthew S. Benz, Richard H. Fish, Rosa Y. Kim, James Major, Tien Pei Wong, Charles Wycoff, Cassandra Cone, Debbie Goates Gilaspia, Nubia Landaverde, Robert Smith, Deneva Zamora, Veronica Sneed, Melina Vela, Eric Kegley, Craig Greven, Shree Kurup, Charles Richards, Madison Slusher, Cara Everhart, Joan Fish, Mark Clark, David Miller, Marshall Tyler, J. Michael Jumper, Arthur D. Fu, Robert N. Johnson, Brandon Lujan, H. Richard McDonald, Rosa Rodriguez, Nina Ansari, Jeanifer Joaquin, Silvia Linares, Lizette Lopez, Jessica Sabio, Sean Grout, Chad Indermill, Yesmin Urias, Roberto Zimmerman, Linda Margulies, Sara J. Schmidt, Joy L. Meier, Sherry L. Hadley, William Rosenthal, Barbara Johnson, Lois Swafford, Richard Shields, R. Scott Varner, Richard Rosen, Ronald Gentile, Melissa Rivas, Katy W. Tai, Wanda Carrasquillo-Boyd, Robert Masini, Glenn Stoller, Ken Carnevale, Diane M. LaRosa, Barbara Burger, Tereza Conway, Carla Del Castillo, Julissa Diaz, Susan Jones, Nina Mondoc, Charlene Balfour, C.H. Vitha, Jennifer Lutz, Barbara McGinley, Fadi El Baba, Ann Marie Lavorna, Renee Jones, Jean Lewis, Ruth Tenzler, Mary Salvas-Mladek, Diane Van Kesteren, W. Copley McLean, W. Zachery Bridges, Cameron Stone, Denise Ammons, Mary Lamy, Andrea Menzel, Lea Doll Raymer, Barbara Campbell, Lisa Hawkins, Leslie Rickman, Lorraine Sherlin, Paula Price, Albert Sinyai, Ronald Kingsley, Reagan H. Bradford, Robert E. Leonard, Sonny Icks, Vanessa Bergman, Brittany Ross, Russ Burris, Amanda Butt, Rob Richmond, Alice Lyon, Manjot Gill, Lee Jampol, Rukhsana Mizra, Zuzanna Rozenbajgier, Jeremy Chapman, Lori Kaminski, Andrea Degillio, Evica Simjanoski, Jeffrey Heier, Hyung Cho, Tina Scheufele Cleary, Darin Goldman, Chirag Shah, Trexler Topping, Marissa Weber, Torsten Wiegand, Jeremy Schindelheim, Joy Bankert, Jennifer Stone, Alison Nowak, Sandy Chong, Lindsay Williams, Steven Bennett, Dennis Donovan, Margaret Graham, Cullen Jones, Anne Fung, Jan-Kristine Bayabo, Razelda Bosch, Esperanza Cruz, Ashley Emerson, Alycia Fleming, Denice Barsness, Jorge Rodriguez, Marina Soboleva, Ingrid U. Scott, Esther Bowie, Kimberly A. Neely, David A. Quillen, Laura Walter, Timothy Bennett, James Strong, John Wells, Lloyd Clark, David Johnson, Peggy Miller, Mallie Taylor, Tiffany Swinford, Robbin Spivey, Michael Banach, Lawrence Ho, Richard Lanning, Thomas R. Pheasant, Jay G. Prensky, Steven Truong, Julia Teatsworth, Michelle Dietrich, Ann Wasilus, Ann Miller, Megan Rakes, Teresa Slagle, Michelle Richards, Patricia Schuessler, Lacy Stover, Paul Beer, Naomi S. Falk, Mary Beth Shannon, Jeannie Olmeda, Don Berdeen, Joseph F. Fisher, James Folk, Stephen Russell, Barbara Taylor, Connie Hinz, Jean Walshire, Heather Stockman, Bruce Critser, Stefani Karakas, Cindy Montague, Randy Verdick, Omesh Gupta, Joseph Maguire, Christopher Brady, Francis Char DeCroos, Michael Dollin, Sunir Garg, Adam Gerstenblith, Julia Haller, Allen C. Ho, Jason Hsu, Richard Kaiser, John Pitcher, Carl Regillo, Rajiv Shah, Marc Spirn, William Tasman, James Vander, Noga Senderowitsch, Michele Formoso, Michelle Markun, Cedric George, Christina Centinaro, Lisa Grande, Stefanie Carey, Elaine Liebenbaum, SriniVas Sadda, Mark Humayun, Rachel Sierra, Elizabeth Corona, Margaret Padilla, Moonseok Nu, Sylvia Ramos, Cullen Barnett, Glenn Currie, Cornelia Gottlieb, Richard Garfinkel, Daniel Berinstein, Marcus Colyer, William Deegan, Michael Min-Shyue Lai, Robert Murphy, Michael Osman, Michael Rivers, Reginald Sanders, Manfred A. von Fricken, Debbie Oliver, Jeanne Kirshon, Tanya Alexander Snowden, Thomas Blondo, Alysia Cronise, Vanessa Denny, Kylie Mendez, Janine Newgen, Justin Davis, Mike Flory, Robert Frantz, Bryan Murphy, Steve Rauch, Judy E. Kim, Jane Bachman, Thomas B. Connor, Dennis P. Han, Kimberly Stepian, David V. Weinberg, William J. Wirostko, Krissa Packard, Tracy Kaczanowski, Vesper Williams, Vicki Barwick, Judy Flanders, Dennis Backes, Joe Beringer, Kristy Keller, Kathy Selchert, Paul Bernstein, Michael Teske, Albert Vitale, Susan Allman, Bonnie Carlstrom, Kimberley Wegner, Anne Haroldsen, Deborah Harrison, Cyrie Fry, James Gilman, Glen Jenkins, Paula Morris, Michael Rauser, Joseph Fan, Mukesh Suthar, Gisela Santiago, Kara Rollins Halsey, Christy Quesada, William Kiernan, Jesse Knabb, Richard Alan Lewis, Cindy Dorenbach, Steven Spencer, Dana Barnett, Joseph Morales, Barron C. Fishburne, Jeffrey G. Gross, Michael A. Magee, Amy Flowers, Angie McDowell, Randall Price, Suber Huang, Johnny Tang, Shawn Wilker, Cherie Hornsby, Lisa Ferguson, Kirk Krogstad, Riva Adamovsky, Peggy Allchin, Kathleen Carlton, Claudia Clow, Kelly Sholtis, Stephanie Burke, Mark Harrod, Stacie Hrvatin, Geoffrey Pankhurst, Nelson R. Sabates, Michael Cassell, Komal Desai, Abraham Poulose, Felix Sabates, Yin Chen, Gary Gallimore, Yolanda Konior, Nicola Kim, Sami Uwaydat, Deborah Troillett, Karen Aletter, Robert N. Frank, Gary Abrams, James Puklin, Asheesh Tewari, Cheryl Milanovic, Melanie Bailey, David Griffith, Dena McDonald, Kit Morehead, Zlatan Sadikovic, Lisa Schillace, Elizabeth Silvis, Brian Joondeph, Nancy Christmas, Alan Kimura, Mimi Liu, Stephen Petty, John Zilis, Jenny Benitez, Cassandra Berryman Catlett, Eric Fluegel, Shane Mowry, Hoang Nguyen, David Reflow, Odette M. Houghton, Seema Garg, Maurice B. Landers, Travis Meredith, Sandy Barnhart, Megha Karmalkar, Debra Cantrell, Rona Lyn Esquejo-Leon, Linda Manor, Sue Pope, David Stines, Amelia Stokely, Dean Hainsworth, Dyann Helming, Debbie Eichelberger, Mary Paige Leaton, Chuck Hamm, Edward Chaum, Alessandro Iannaccone, Barbara Jennings, Tracy Murray, Joe Mastellone, Robert Millay, Brian Kim, Theresa Goddard, Liza Jarrett Beaudette, Nina Changelian-Aitken, Fernando Corrada, Jason Dubuque, Raymond Iezzi, Sophie J. Bakri, Jose S. Pulido, Diane Vogen, Rebecca Nielsen, Karin Berg, Jean Burrington, Shannon Howard, Joan Overend, Zbigniew Krason, Denise Lewison, Thomas Link, Kevin J. Blinder, Nicholas E. Engelbrecht, M. Gilbert Grand, Daniel P. Joseph, Gaurav K. Shah, Bradley Smith, Matthew Thomas, Rhonda Weeks, Lynda Boyd, Dana Gabel, Ron Adelman, John Huang, James Kempton, Aaron Parnes, Jennifer Dupont, Elizabeth Perotti, Victoria Donaldson, Kenneth Fong, Pamela Ossorio, Anita Agarwal, Paul Sternberg, Sandy Owings, Tony Adkins, Elaine Lok, Garvin Munn, Buddy Skellie, Neelakshi Bhagat, Monique S. Roy, Marco Zarbin, Catherine Fay, Michael Lazar, Beth Malpica, Tatiana Mikheyav, Lawrence Ulanski, Jennifer Lim, Marcia Niec, Tametha Johnson, Yesenia Ovando, Catherine Nail Carroll, Mark Janowicz, Steven Schwartz, David Cupp, Michael Gorin, Gad Heilweil, Hamid Hosseini, Jean-Pierre Hubschman, Allan Kreiger, Tara Young McCannel, Carolyn Pan, David Sarraf, Irena Tsui, Joshua Udoetek, Vinad Voleti, Logan Hitchcock, Rosaleen Ostrick, Melissa Chun, Jennie Kageyama, Nilo Davila, Kristin Lipka, Christina Shin, Cynthia Owsley, Michael Albert, Richard Feist, John Mason, Martin Thomley, Angelia Johnson, Tracy Emond, Joanna Hamela, Angela Marsh, Karen Searcey, Kia Rookard, Yu-Guang He, Rafael L. Ufret-Vincenty, Mike Molai, William Anderson, John Horna, Alan Letson, Colleen Cebulla, Susie Chang, Fred Davidorf, Jill Salerno, Laura Sladoje, Christina Stetson, Jeri Perry, Scott Savage, Cynthia Toth, Glenn Jaffe, Stefanie Schuman, Neeru Sarin, Jim Crowell, Tiffanie Keaton, Michael Kelly, Brian Lutman, Marriner Skelly, Lauren Welch, Lawrence Morse, Allan Hunter, Susanna Soon-Chun Park, Cynthia Wallace, Ember Dhillon, Marisa Salvador, Barbara Holderreed, Karishma Chandra, Sashi Kaur, Ellen Redenbo, Smiley Hom, Michael Cooney, Irene Barbazetto, James M. Klancnik, John A. Sorenson, Lawrence Yannuzzi, Maria Scolaro, Eugene Agresta, Nancy Gonzalez, Sandeep Grover, K.V. Chalam, Shailesh Gupta, Christopher Lyons, Wenhua Li, Chirag Patel, Jose Carrion, Henry Ferreyra, Amberly Rodriguez, Iliana Molina, Gabriel Balea, Pam Emory, Marlene Rico, Giorgio Siqueiros, Alexander J. Brucker, Joshua Dunaief, Juan Grunwald, Benjamin Kim, Albert M. Maguire, Brian VanderBeek, Sheri Drossner, Joan DuPont, Rebecca Salvo, Jim Berger, Cheryl Devine, Bill Nyberg, Laurel Weeney, David DiLoreto, Mina Chung, Valerie Davis, Peter MacDowell, George O. Gara, Daniel Castillo, Andrea Czubinski, Melissa Keim, Brandi Hardy, Rachel Grunhaus Hollar, Lynn Schueckler, Alice T. Lyon, Aaron Weinberg, Mira Shiloach, Nicole Pelkofer, Qin Zhou, Laura McPoland, Rajendra Apte, P. Kumar Rao, Sam Pistorius, Jamie Kambarian, Eve Adcock, Sarah Gould, Melanie Quinn, Rhonda Curtis, Amy Frost, Charla Meyer, and Greg Rathert
- Subjects
0303 health sciences ,medicine.medical_specialty ,Visual acuity ,genetic structures ,business.industry ,Eye disease ,Hazard ratio ,Age-Related Eye Disease Study ,Retrospective cohort study ,Fundus (eye) ,Macular degeneration ,medicine.disease ,eye diseases ,03 medical and health sciences ,Ophthalmology ,0302 clinical medicine ,030221 ophthalmology & optometry ,medicine ,sense organs ,medicine.symptom ,Prospective cohort study ,business ,030304 developmental biology - Abstract
Purpose To investigate the natural history and genetic associations of drusenoid pigment epithelial detachment (DPED) associated with age-related macular degeneration (AMD). Design Retrospective analysis of a prospective cohort study. Participants Of the 4203 Age-Related Eye Disease Study 2 (AREDS2) participants, 391 eyes (325 participants) had DPED without late AMD at the time of DPED detection. Genetic analyses included 120 white AREDS2 participants and 145 Age-Related Eye Disease Study (AREDS) participants with DPED. Methods Baseline and annual stereoscopic fundus photographs were graded centrally to detect DPED, a well-defined yellow elevated mound of confluent drusen ≥433 μm in diameter, and to evaluate progression rates to late AMD: geographic atrophy (GA) and neovascular (NV)-AMD. Five single nucleotide polymorphisms (CFH [rs10611670], C3 [rs2230199], CFI [rs10033900], C2/CFB [rs114254831], ARMS2 [rs10490924]) and genetic risk score (GRS) group were investigated for association with DPED development. Kaplan–Meier analyses and multivariable proportional hazard regressions were performed. Main Outcome Measures Progression rates to late AMD and decrease of ≥3 lines in visual acuity (VA) from the time of DPED detection; association of rate of DPED development with genotype. Results Mean (standard deviation [SD]) follow-up time from DPED detection was 4.7 (0.9) years. DPED was associated with increased risk of progression to late AMD (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.98–2.82; P Conclusions This study replicates the results of previous natural history studies of eyes with DPED including the high rates of progression to late AMD and vision loss (regardless of progression to late AMD). The genetic associations are consistent with genes associated with AMD progression.
- Published
- 2019
40. S804 Identifying Targets for Improving Inflammatory Bowel Disease Medication Adherence
- Author
-
LaVana Greene-Higgs, Jeff Berinstein, Peter D.R. Higgins, Akbar K. Waljee, Shirley Cohen-Mekelburg, Linnea Swanson, and Jessica L. Sheehan
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,Internal medicine ,Gastroenterology ,Medication adherence ,Medicine ,business ,medicine.disease ,Inflammatory bowel disease - Published
- 2021
41. 321: SELF-EFFICACY AS A TARGET FOR IMPROVING INFLAMMATORY BOWEL DISEASE SELF-MANAGEMENT AND OUTCOMES
- Author
-
Jessica L. Sheehan, LaVana Greene-Higgs, Linnea Swanson, Peter D. Higgins, Sarah Krein, Akbar K. Waljee, Sameer D. Saini, Jeffrey Berinstein, Jessica L. Mellinger, John Piette, Kenneth Resnicow, and Shirley Cohen-Mekelburg
- Subjects
Hepatology ,Gastroenterology - Published
- 2022
42. 976: THE IMPACT OF CANNABIS LEGALIZATION ON OPIOIDS IN PATIENTS WITH IBD: A DIFFERENCE-IN-DIFFERENCE ANALYSIS
- Author
-
Mohamed Noureldin, Jeffrey Berinstein, Frank I. Scott, Peter D. Higgins, Ryan Stidham, Shirley Cohen-Mekelburg, Jason K. Hou, and Akbar K. Waljee
- Subjects
Hepatology ,Gastroenterology - Published
- 2022
43. A Care Coordination Intervention Improves Symptoms But Not Charges in High-Risk Patients With Inflammatory Bowel Disease
- Author
-
Daniel Wray, Sameer K. Berry, Akbar K. Waljee, Sameer D. Saini, Megan A. Adams, Shirley Cohen-Mekelburg, A. Mark Fendrick, Gillian M. Greenberg, Jeffrey A. Berinstein, and Peter D.R. Higgins
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,Gastroenterology ,Health Care Costs ,Odds ratio ,Emergency department ,Inflammatory Bowel Diseases ,Article ,Confidence interval ,law.invention ,Indirect costs ,Quality of life (healthcare) ,Randomized controlled trial ,law ,Chronic Disease ,Health care ,Emergency medicine ,Humans ,Medicine ,Patient-reported outcome ,Health Expenditures ,business ,Delivery of Health Care - Abstract
Background Inflammatory bowel disease (IBD) is associated with substantial symptom burden, variability in clinical outcomes, and high direct costs. We sought to determine if a care coordination–based strategy was effective at improving patient symptom burden and reducing healthcare costs for patients with IBD in the top quintile of predicted healthcare utilization and costs. Methods We performed a randomized controlled trial to evaluate the efficacy of a patient-tailored multicomponent care coordination intervention composed of proactive symptom monitoring and care coordinator–triggered algorithms. Enrolled patients with IBD were randomized to usual care or to our care coordination intervention over a 9-month period (April 2019 to January 2020). Primary outcomes included change in patient symptom scores throughout the intervention and IBD-related charges at 12 months. Results Eligible IBD patients in the top quintile for predicted healthcare utilization and expenditures were identified. A total of 205 patients were enrolled and randomized to our intervention (n = 100) or to usual care (n = 105). Patients in the care coordinator arm demonstrated an improvement in symptoms scores compared with usual care (coefficient, –0.68, 95% confidence interval, –1.18 to –0.18; P = .008) without a significant difference in median annual IBD-related healthcare charges ($10,094 vs $9080; P = .322). Conclusions In this first randomized controlled trial of a patient-tailored care coordination intervention, composed of proactive symptom monitoring and care coordinator–triggered algorithms, we observed an improvement in patient symptom scores but not in healthcare charges. Care coordination programs may represent an effective value-based approach to improving symptoms scores without added direct costs in a subgroup of high-risk patients with IBD. ( ClinicalTrials.gov , Number: NCT04796571 ).
- Published
- 2022
44. Progression of Geographic Atrophy in Age-related Macular Degeneration
- Author
-
Tiarnan D. Keenan, Elvira Agrón, Amitha Domalpally, Traci E. Clemons, Freekje van Asten, Wai T. Wong, Ronald G. Danis, SriniVas Sadda, Philip J. Rosenfeld, Michael L. Klein, Rinki Ratnapriya, Anand Swaroop, Frederick L. Ferris, Emily Y. Chew, John Paul SanGiovanni, Traci Clemons, Anne Lindblad, Robert Lindblad, Nilay Shah, Robert Sperduto, Wendy McBee, Gary Gensler, Molly Harrington, Alice Henning, Katrina Jones, Kumar Thotapally, Diana Tull, Valerie Watson, Kayla Williams, Christina Gentry, Francine Kaufman, Chris Morrison, Elizabeth Saverino, Sherrie Schenning, Barbara Blodi, Ronald P. Danis, Matthew Davis, Kathy Glander, Gregory Guilfoil, Larry D. Hubbard, Kristine Johnson, Ronald Klein, Barbara Nardi, Michael Neider, Nancy Robinson, Eileen Rosensteel, Hugh Wabers, Grace Zhang, Alan J. Ruby, Antonio Capone, Bawa Dass, Kimberly Drenser, Bruce R. Garretson, Tarek S. Hassan, Michael Trese, George A. Williams, Jeremy Wolfe, Tina Bell, Mary Zajechowski, Dennis Bezaire, Fran McIver, Anthony Medina, Jackie Pagett, Stephanie Hatch Smith, Lynn Swartz, Tom Treuter, Andrew Antoszyk, Justin Brown, David J. Browning, Walter Holland, Angella Karow, Kelly Stalford, Angela Price, Sarah Ennis, Sherry Fredenberg, Jenna Herby, Uma Balasubramaniam, Loraine Clark, Donna McClain, Michael McOwen, Lynn Watson, Michael Klein, Steven T. Bailey, Thomas J. Hwang, Andreas Lauer, J. Timothy Stout, Patty McCollum, Milt Johnson, Patrick B. Rice, Ivana Kim, John Loewenstein, Joan Miller, Lucia Sobrin, Lucy Young, Jacqueline Sullivan, Patricia Houlihan, Linda Merry, Ann Marie Lane, Ursula Lord Bator, Claudia Evans, Sarah Brett, Charleen Callahan, Marcia Grillo, David Walsh, Kamella Lau Zimmerman, Gary Edd Fish, Rajiv Anand, Lori E. Coors, Dwain G. Fuller, Rand Spencer, Robert C. Wang, Karen Duignan, Sally Arceneaux, Hank Aguado, Nicholas Hesse, Michael Mackens, Brian Swan, Catherine Cukras, Monica Dalal, Naima Jacobs-El, Catherine Meyerle, Benjamin Nicholson, Henry Wiley, Katherine Hall Shimel, Angel Garced, Janice Oparah, Greg Short, Alana Temple, Babilonia Ayukawa, Guy Foster, Darryl Hayes, Dessie Koutsandreas, Roula Nashwinter, John Rowan, Michael Bono, Denise Cunningham, Marilois Palmer, Alicia Zetina, David H. Orth, Kourous Rezaei, Joseph Civantos, Sohail Hasan, Kirk Packo, Celeste Figliulo, Pam Stanberry, Tara Farmer, Kiersten Nelson, Shannya Townsend-Patrick, Philip Rosenfeld, Royce Chen, Rishi Doshi, Sander Dubovy, Brian T. Kim, Matthew Lowrance, Andrew Moshfeghi, Zayna Nahas, Gary Schienbaum, John Vishak, Christina Weng, Zohar Yehoshua, Belen Rodriguez, Jose Rebimbas, Jane Gleichauf, Mike Kicak, Jason Mena, Tim Odem, Elizabeth Sferza-Camp, Alicia Disgdiertt, Jim Oramas, Isabel Rams, Stephanie Thatcher, Susan B. Bressler, Neil M. Bressler, Daniel Finkelstein, Steven H. Sherman, Sharon Solomon, Howard S. Ying, Rita Denbow, Deborah Phillips, Elizabeth Radcliffe, Judy Belt, Dennis Cain, David Emmert, Mark Herring, Jacquelyn McDonald, G. Baker Hubbard, Chris S. Bergstrom, Blaine Cribbs, Andrew Hendrick, Brandon Johnson, Philip Laird, Sonia Mehta, Timothy Olsen, Justin Townsend, Jion Yan, Steven Yeh, Linda Curtis, Judy Brower, Hannah Yi, Jannah Rutter Dobbs, Debbie Jordan, Michael J. Elman, Robert A. Liss, JoAnn Starr, Jennifer Belz, Charlene Putzulo, Teresa Coffey, Ashley Davis, Pamela Singletary, Giorya Shabi Andreani, Theresa Cain, Daniel Ketner, Peter Sotirakos, Suresh Chandra, Barbara A. Blodi, Michael M. Altaweel, Justin L. Gottlieb, Michael Ip, T. Michael Nork, Thomas S. Stevens, Kathryn Burke, Shelly Olson, Kristine Dietzman, Barbara Soderling, Guy Somers, Angie Wealti, Denise Krolnik, John Peterson, Sandra Reed, Thomas Friberg, Andrew Eller, Denise Gallagher, Leanne Labriola, Melissa Pokrifka, Aron Gedansky, Natalie Anthony, Cassandra Grzybowski, Dawn Matthews, Sharon Murajda-Jumba, Jessica Toro, David G. Callanan, Wayne A. Solley, Patrick Williams, Sandy Lash, Bob Boleman, Chris Dock, Michel Shami, Brenda Arrington, Ashaki Meeks, Alan R. Margherio, Paul Raphaelian, Debra Markus, Justin Langdon, Elizabeth Truax, Sandy Lewis, Brad Terry, Amy Noffke, Kean Oh, Ramin Sarrafizadeh, Scott Sneed, Julie Hammersley, Serena Neal, Mary Doran, Nan Jones, Lisa Preston, Heather Jessick, Tanya Tracy Marsh, Michael Tolentino, Adam Berger, Richard Hamilton, David Misch, Suk Jin Moon, Dawn Sutherland, Vera Dilts, Sara Henderson, Esmeralda Medina, Donald Trueman, Laura Holm, Jason Strickland, Darmakusuma Ie, Jeffrey L. Lipkowitz, Kekul B. Shah, Susan Geraghty, Beverly Sannazzaro, Morgan Harper, Krista Bayer, Mary B. Lansing, Lauren B. Fox, Rebecca Lee, Jay B. Stallman, Michael Jacobson, Sean Koh, Scott Lampert, John Miller, Mark Rivellese, Atul Sharma, Robert A. Stoltz, Stephanie Vanderveldt, Leslie Marcus, Starr Hendricks, Ryan Hollman, Grethel Betanzos, Leslie Ellorin, Shelly Fulbright, Debbie McCormick, Paul A. Edwards, Julianne Hall, Mary Monk, Melanie Gutkowski, Melina Mazurek, Janet Murphy, Katherine Gusas, Crystal Moffett, David Burley, Nicole Chesney, Katie Kilgo, Brian Rusinek, Bradley Stern, Tracy Troszak, Rhonda Baker-Levingston, Carl W. Baker, Tracey Caldwell, Tammy Walker, Lynnette F. Lambert, Tracey Martin, Mary Jill Palmer, Tana Williams, Michael A. Novak, Joseph Coney, David G. Miller, Scott Pendergast, Lawrence Singerman, Nicholas Zakov, Hernando Zegarra, Kim DuBois, Susan Rath, Lori Revella, Tammy Brink, Kim Drury, Lisa Hogue, Mary Ilc, Connie Keller, Elizabeth McNamara, Vivian Tanner, Tamara Cunningham, John DuBois, Gregg Greanoff, Trina Nitzsche, Sheila Smith-Brewer, Ricky D. Isernhagen, John W. Kitchens, Thomas W. Stone, William J. Wood, Diana Holcomb, Virginia Therrien, Michelle Buck, Jeanne Van Arsdall, Edward Slade, Todd E. Schneiderman, David J. Spinak, Jackie Gaedke, Heather Davis Brown, Dan Helgren, Jenifer Garrison Pangelinan, Lawrence Halperin, Scott Anagnoste, Mandeep Dhalla, Krista Rosenberg, Barry Taney, W. Scott Thompson, Jaclyn Lopez, Monica Hamlin, Monica Lopez, Jamie Mariano, Evelyn Quinchia, Patricia Aramayo, Rita Veksler, Michael Lee, Richard Dreyer, Irvin Handelman, Colin Ma, Mark Peters, Stephen Hobbs, Amanda Milliron, Marcia Kopfer, Michele Connaughton, A. Christine Hoerner, R. Joseph Logan, Harry J. Wohlsein, David Boyer, Thomas G. Chu, Pouya Dayani, David Liao, Roger L. Novack, Firas M. Rahhal, Richard Roe, Homayoun Tabandeh, Janet Bayramyan, Tammy Gasparyan, Connie Hoang, Janet Kurokouchi, Tammy Eileen Lo, Richard Ngo, Mary Ann Nguyen, Michael Peyton, Charles Yoon, Julio Sierra, Adam Zamboni, Jeff Kessinger, Eric Protacio, Adam Smucker, Pamela Rath, Robert Bergren, Bernard Doft, Judy Liu, Karl Olsen, Lori Merlotti, Willia Ingram, Kellianne Marfisi, Kimberly Yeckel, Heather Schultz Carmelo, Amanda Fec, Keith McBroom, David Steinberg, Marc Levy, Jody Abrams, Melvin Chen, Waldemar Torres, Peggy Jelemensky, Mark Prybylski, Tara Raphael, Diana Appleby, Charlotte Rodman, Mark Sneath, Robert H. Rosa, Vanessa Hoelscher, Adelia Castano, Jocelyn Parker, John Hoskins, Nicholas Anderson, Joseph Googe, Tod A. McMillan, James Miller, Stephen Perkins, Kristina Oliver, Jennifer Beerbower, Bruce Gilliland, Cecile Hunt, Mike Jacobus, Raul Lince, Christopher Morris, Sarah Oelrich, Jerry Whetstone, Clement K. Chan, Steven Lin, Kim Walther, Tiana Gonzales, Lenise Myers, Kenneth Huff, David M. Brown, Eric Chen, Matthew S. Benz, Richard H. Fish, Rosa Y. Kim, James Major, Tien Pei Wong, Charles Wycoff, Cassandra Cone, Debbie Goates Gilaspia, Nubia Landaverde, Robert Smith, Deneva Zamora, Veronica Sneed, Melina Vela, Eric Kegley, Craig Greven, Shree Kurup, Charles Richards, Madison Slusher, Cara Everhart, Joan Fish, Mark Clark, David Miller, Marshall Tyler, J. Michael Jumper, Arthur D. Fu, Robert N. Johnson, Brandon Lujan, H. Richard McDonald, Rosa Rodriguez, Nina Ansari, Jeanifer Joaquin, Silvia Linares, Lizette Lopez, Jessica Sabio, Sean Grout, Chad Indermill, Yesmin Urias, Roberto Zimmerman, Linda Margulies, Sara J. Schmidt, Joy L. Meier, Sherry L. Hadley, William Rosenthal, Barbara Johnson, Lois Swafford, Richard Shields, R. Scott Varner, Richard Rosen, Ronald Gentile, Melissa Rivas, Katy W. Tai, Wanda Carrasquillo-Boyd, Robert Masini, Glenn Stoller, Ken Carnevale, Diane M. LaRosa, Barbara Burger, Tereza Conway, Carla Del Castillo, Julissa Diaz, Susan Jones, Nina Mondoc, Charlene Balfour, C.H. Vitha, Jennifer Lutz, Barbara McGinley, Fadi El Baba, Ann Marie Lavorna, Renee Jones, Jean Lewis, Ruth Tenzler, Mary Salvas-Mladek, Diane Van Kesteren, W. Copley McLean, W. Zachery Bridges, Cameron Stone, Denise Ammons, Mary Lamy, Andrea Menzel, Lea Doll Raymer, Barbara Campbell, Lisa Hawkins, Leslie Rickman, Lorraine Sherlin, Paula Price, Albert Sinyai, Ronald Kingsley, Reagan H. Bradford, Robert E. Leonard, Sonny Icks, Vanessa Bergman, Brittany Ross, Russ Burris, Amanda Butt, Rob Richmond, Alice Lyon, Manjot Gill, Lee Jampol, Rukhsana Mizra, Zuzanna Rozenbajgier, Jeremy Chapman, Lori Kaminski, Andrea Degillio, Evica Simjanoski, Jeffrey Heier, Hyung Cho, Tina Scheufele Cleary, Darin Goldman, Chirag Shah, Trexler Topping, Marissa Weber, Torsten Wiegand, Jeremy Schindelheim, Joy Bankert, Jennifer Stone, Alison Nowak, Sandy Chong, Lindsay Williams, Steven Bennett, Dennis Donovan, Margaret Graham, Cullen Jones, Anne Fung, Jan-Kristine Bayabo, Razelda Bosch, Esperanza Cruz, Ashley Emerson, Alycia Fleming, Denice Barsness, Jorge Rodriguez, Marina Soboleva, Ingrid U. Scott, Esther Bowie, Kimberly A. Neely, David A. Quillen, Laura Walter, Timothy Bennett, James Strong, John Wells, Lloyd Clark, David Johnson, Peggy Miller, Mallie Taylor, Tiffany Swinford, Robbin Spivey, Michael Banach, Lawrence Ho, Richard Lanning, Thomas R. Pheasant, Jay G. Prensky, Steven Truong, Julia Teatsworth, Michelle Dietrich, Ann Wasilus, Ann Miller, Megan Rakes, Teresa Slagle, Michelle Richards, Patricia Schuessler, Lacy Stover, Paul Beer, Naomi S. Falk, Mary Beth Shannon, Jeannie Olmeda, Don Berdeen, Joseph F. Fisher, James Folk, Stephen Russell, Barbara Taylor, Connie Hinz, Jean Walshire, Heather Stockman, Bruce Critser, Stefani Karakas, Cindy Montague, Randy Verdick, Omesh Gupta, Joseph Maguire, Christopher Brady, Francis Char DeCroos, Michael Dollin, Sunir Garg, Adam Gerstenblith, Julia Haller, Allen C. Ho, Jason Hsu, Richard Kaiser, John Pitcher, Carl Regillo, Rajiv Shah, Marc Spirn, William Tasman, James Vander, Noga Senderowitsch, Michele Formoso, Michelle Markun, Cedric George, Christina Centinaro, Lisa Grande, Stefanie Carey, Elaine Liebenbaum, Mark Humayun, Rachel Sierra, Elizabeth Corona, Margaret Padilla, Moonseok Nu, Sylvia Ramos, Cullen Barnett, Glenn Currie, Cornelia Gottlieb, Richard Garfinkel, Daniel Berinstein, Marcus Colyer, William Deegan, Michael Min-Shyue Lai, Robert Murphy, Michael Osman, Michael Rivers, Reginald Sanders, Manfred A. von Fricken, Debbie Oliver, Jeanne Kirshon, Tanya Alexander Snowden, Thomas Blondo, Alysia Cronise, Vanessa Denny, Kylie Mendez, Janine Newgen, Justin Davis, Mike Flory, Robert Frantz, Bryan Murphy, Steve Rauch, Judy E. Kim, Jane Bachman, Thomas B. Connor, Dennis P. Han, Kimberly Stepian, David V. Weinberg, William J. Wirostko, Krissa Packard, Tracy Kaczanowski, Vesper Williams, Vicki Barwick, Judy Flanders, Dennis Backes, Joe Beringer, Kristy Keller, Kathy Selchert, Paul Bernstein, Michael Teske, Albert Vitale, Susan Allman, Bonnie Carlstrom, Kimberley Wegner, Anne Haroldsen, Deborah Harrison, Cyrie Fry, James Gilman, Glen Jenkins, Paula Morris, Michael Rauser, Joseph Fan, Mukesh Suthar, Gisela Santiago, Kara Rollins Halsey, Christy Quesada, William Kiernan, Jesse Knabb, Richard Alan Lewis, Cindy Dorenbach, Steven Spencer, Dana Barnett, Joseph Morales, Barron C. Fishburne, Jeffrey G. Gross, Michael A. Magee, Amy Flowers, Angie McDowell, Randall Price, Suber Huang, Johnny Tang, Shawn Wilker, Cherie Hornsby, Lisa Ferguson, Kirk Krogstad, Riva Adamovsky, Peggy Allchin, Kathleen Carlton, Claudia Clow, Kelly Sholtis, Stephanie Burke, Mark Harrod, Stacie Hrvatin, Geoffrey Pankhurst, Nelson R. Sabates, Michael Cassell, Komal Desai, Abraham Poulose, Felix Sabates, Yin Chen, Gary Gallimore, Yolanda Konior, Nicola Kim, Sami Uwaydat, Deborah Troillett, Karen Aletter, Robert N. Frank, Gary Abrams, James Puklin, Asheesh Tewari, Cheryl Milanovic, Melanie Bailey, David Griffith, Dena McDonald, Kit Morehead, Zlatan Sadikovic, Lisa Schillace, Elizabeth Silvis, Brian Joondeph, Nancy Christmas, Alan Kimura, Mimi Liu, Stephen Petty, John Zilis, Jenny Benitez, Cassandra Berryman Catlett, Eric Fluegel, Shane Mowry, Hoang Nguyen, David Reflow, Odette M. Houghton, Seema Garg, Maurice B. Landers, Travis Meredith, Sandy Barnhart, Megha Karmalkar, Debra Cantrell, Rona Lyn Esquejo-Leon, Linda Manor, Sue Pope, David Stines, Amelia Stokely, Dean Hainsworth, Dyann Helming, Debbie Eichelberger, Mary Paige Leaton, Chuck Hamm, Edward Chaum, Alessandro Iannaccone, Barbara Jennings, Tracy Murray, Joe Mastellone, Robert Millay, Brian Kim, Theresa Goddard, Liza Jarrett Beaudette, Nina Changelian-Aitken, Fernando Corrada, Jason Dubuque, Raymond Iezzi, Sophie J. Bakri, Jose S. Pulido, Diane Vogen, Rebecca Nielsen, Karin Berg, Jean Burrington, Shannon Howard, Joan Overend, Zbigniew Krason, Denise Lewison, Thomas Link, Kevin J. Blinder, Nicholas E. Engelbrecht, M. Gilbert Grand, Daniel P. Joseph, Gaurav K. Shah, Bradley Smith, Matthew Thomas, Rhonda Weeks, Lynda Boyd, Dana Gabel, Ron Adelman, John Huang, James Kempton, Aaron Parnes, Jennifer Dupont, Elizabeth Perotti, Victoria Donaldson, Kenneth Fong, Pamela Ossorio, Anita Agarwal, Paul Sternberg, Sandy Owings, Tony Adkins, Elaine Lok, Garvin Munn, Buddy Skellie, Neelakshi Bhagat, Monique S. Roy, Marco Zarbin, Catherine Fay, Michael Lazar, Beth Malpica, Tatiana Mikheyav, Lawrence Ulanski, Jennifer Lim, Marcia Niec, Tametha Johnson, Yesenia Ovando, Catherine Nail Carroll, Mark Janowicz, Steven Schwartz, David Cupp, Michael Gorin, Gad Heilweil, Hamid Hosseini, Jean-Pierre Hubschman, Allan Kreiger, Tara Young McCannel, Carolyn Pan, David Sarraf, Irena Tsui, Joshua Udoetek, Vinad Voleti, Logan Hitchcock, Rosaleen Ostrick, Melissa Chun, Jennie Kageyama, Nilo Davila, Kristin Lipka, Christina Shin, Cynthia Owsley, Michael Albert, Richard Feist, John Mason, Martin Thomley, Angelia Johnson, Tracy Emond, Joanna Hamela, Angela Marsh, Karen Searcey, Kia Rookard, Yu-Guang He, Rafael L. Ufret-Vincenty, Mike Molai, William Anderson, John Horna, Alan Letson, Colleen Cebulla, Susie Chang, Fred Davidorf, Jill Salerno, Laura Sladoje, Christina Stetson, Jeri Perry, Scott Savage, Cynthia Toth, Glenn Jaffe, Stefanie Schuman, Neeru Sarin, Jim Crowell, Tiffanie Keaton, Michael Kelly, Brian Lutman, Marriner Skelly, Lauren Welch, Lawrence Morse, Allan Hunter, Susanna Soon-Chun Park, Cynthia Wallace, Ember Dhillon, Marisa Salvador, Barbara Holderreed, Karishma Chandra, Sashi Kaur, Ellen Redenbo, Smiley Hom, Michael Cooney, Irene Barbazetto, James M. Klancnik, John A. Sorenson, Lawrence Yannuzzi, Maria Scolaro, Eugene Agresta, Nancy Gonzalez, Sandeep Grover, K.V. Chalam, Shailesh Gupta, Christopher Lyons, Wenhua Li, Chirag Patel, Jose Carrion, Henry Ferreyra, Amberly Rodriguez, Iliana Molina, Gabriel Balea, Pam Emory, Marlene Rico, Giorgio Siqueiros, Alexander J. Brucker, Joshua Dunaief, Juan Grunwald, Benjamin Kim, Albert M. Maguire, Brian VanderBeek, Sheri Drossner, Joan DuPont, Rebecca Salvo, Jim Berger, Cheryl Devine, Bill Nyberg, Laurel Weeney, David DiLoreto, Mina Chung, Valerie Davis, Peter MacDowell, George O. Gara, Daniel Castillo, Andrea Czubinski, Melissa Keim, Brandi Hardy, Rachel Grunhaus Hollar, Lynn Schueckler, Alice T. Lyon, Aaron Weinberg, Mira Shiloach, Nicole Pelkofer, Qin Zhou, Laura McPoland, Rajendra Apte, P. Kumar Rao, Sam Pistorius, Jamie Kambarian, Eve Adcock, Sarah Gould, Melanie Quinn, Rhonda Curtis, Amy Frost, Charla Meyer, and Greg Rathert
- Subjects
0301 basic medicine ,medicine.medical_specialty ,genetic structures ,business.industry ,Eye disease ,Incidence (epidemiology) ,Fundus (eye) ,Macular degeneration ,medicine.disease ,eye diseases ,Confidence interval ,Geographic atrophy ,03 medical and health sciences ,Ophthalmology ,030104 developmental biology ,0302 clinical medicine ,Age related ,030221 ophthalmology & optometry ,medicine ,sense organs ,Prospective cohort study ,business - Abstract
Purpose To analyze the prevalence, incidence, and clinical characteristics of eyes with geographic atrophy (GA) in age-related macular degeneration (AMD), including clinical and genetic factors affecting enlargement. Design Prospective cohort study within a controlled clinical trial. Participants Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50–85 years. Methods Baseline and annual stereoscopic color fundus photographs were evaluated for GA presence and area. Analyses included GA prevalence and incidence rates, Kaplan-Meier rates, mixed-model regression, and multivariable analysis of the square root of GA, area adjusted for covariates, including clinical/imaging characteristics and genotype. Main Outcome Measures (1) Presence or development of GA; (2) change in the square root of GA area over time. Results At baseline, 517 eyes (6.2%) of 411 participants (9.8%) had pre-existing GA (without neovascular AMD), with the following characteristics: 33% central, 67% noncentral; and the following configurations: 36% small, 26% solid/unifocal, 24% multifocal, 9% horseshoe/ring, and 6% indeterminate. Of the remaining 6530 eyes at risk, 1099 eyes (17.3%) of 883 participants developed incident GA without prior neovascular disease during mean follow-up of 4.4 years. The Kaplan-Meier rate of incident GA was 19% of eyes at 5 years. In eyes with incident GA, 4-year risk of subsequent neovascular AMD was 29%. In eyes with incident noncentral GA, 4-year risk of central involvement was 57%. GA enlargement rate (following square root transformation) was similar in eyes with pre-existing GA (0.29 mm/year; 95% confidence interval 0.27–0.30) and incident GA (0.28 mm/year; 0.27–0.30). In the combined group, GA enlargement was significantly faster with noncentrality, multifocality, intermediate baseline size, and bilateral GA (P Conclusions Analyses of AREDS2 data on natural history of GA provide representative data on GA evolution and enlargement. GA enlargement, which was influenced by lesion features, was relentless, resulting in rapid central vision loss. The genetic variants associated with faster enlargement were partially distinct from those associated with risk of incident GA. These findings are relevant to further investigations of GA pathogenesis and clinical trial planning.
- Published
- 2018
45. Life-Threatening Gastrointestinal Bleeding in an Immunocompromised Patient
- Author
-
Jeffrey A. Berinstein, Sami El-Dalati, and William D. Chey
- Subjects
medicine.medical_specialty ,Gastrointestinal bleeding ,Text mining ,Hepatology ,business.industry ,Colonic mass ,Gastroenterology ,medicine ,Immunocompromised patient ,business ,Intensive care medicine ,medicine.disease - Published
- 2021
46. 356 Baseline PD-L1 expression and tumor immune infiltration is associated with clinical response in patients with r/r DLBCL treated with DPX-Survivac, low-dose cyclophosphamide and pembrolizumab
- Author
-
Iran Rashedi, Nick Forward, Neil L. Berinstein, Gail Klein, Isabelle Bence-Bruckler, Douglas A. Stewart, Rebekah Conlon, Pierre Laneuville, Irina Amitai, Kim Roos, Nancy Pennell, Joy Mangel, and Yogesh Bramhecha
- Subjects
Oncology ,medicine.medical_specialty ,education.field_of_study ,Intention-to-treat analysis ,business.industry ,medicine.medical_treatment ,T cell ,Population ,Pembrolizumab ,Immunotherapy ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lcsh:RC254-282 ,Clinical trial ,medicine.anatomical_structure ,Internal medicine ,Cohort ,Medicine ,business ,education ,CD8 - Abstract
Background Treatment of recurrent/refractory (r/r) DLBCL remains an unmet clinical need, and new effective and well-tolerated treatments are required. DPX-Survivac is a unique T cell activation therapy that targets survivin-expressing tumor cells and has shown anti-tumor activity in clinical trials. This trial is evaluating a novel immunotherapy combination with DPX-Survivac, intermittent low dose CPA and pembrolizumab. Methods ‘SPiReL’ is a Phase 2 non-randomized, open label, efficacy and safety study of a novel immunotherapy combination with DPX-Survivac (a unique T cell activation therapy that targets survivin-expressing tumor cells), intermittent low dose CPA and pembrolizumab, treatment regimen as described in figure 1. Subjects with r/r incurable DLBCL and survivin expression are eligible for participation. This study was approved by the Ontario Cancer Research Ethics Board, approval number 0981.ORR is assessed by modified Cheson criteria. For translational analyses, baseline and on-treatment PBMCs, along with tumor biopsy samples are collected from each subject. Survivin-specific systemic T cell responses are assessed using IFNγ-ELISPOT assay and tumour immune-infiltrate profile by multiplex-IHC. Results Twenty-two subjects have been enrolled to date, 19 are included in the intent to treat (ITT) population and 11 subjects are evaluable in the per protocol (PP) population. In the PP, the ORR is 63.6% including 3 CRs (27.3%), 4 PRs (36.4%) and the DCR is 81.8% (9/11). In the ITT, the ORR is 35% (7/19), and DCR is 52.0% (10/19). Preliminary results show that non-GCB subjects had a higher proportion of clinical response (4/8, 50%), compared to 3/10 (30%) in GCB subjects.DPX-Survivac-induced T cell responses were observed in 8/19 subjects (42.1%) including 6 subjects with clinical response (PR, CR), one SD and one PD. Multiplex-IHC analyses demonstrated baseline tumor PD-L1 expression in 6/7 subjects with a clinical response (85.7%, p Conclusions DPX-Survivac, intermittent low-dose CPA and pembrolizumab is generally well tolerated and can induce clinical responses in subjects with r/r DLBCL (7/11, 63.6% of evaluable subjects), including subjects with both non-GCB and GCB subtypes. Pre-treatment biopsies of clinical responders were characterized by higher baseline tumor PD-L1 expression and CD4 and CD8 infiltration. Extending this exploratory data in a larger cohort may define a r/r DLBCL patient population with a higher likelihood to respond to this novel combination immunotherapy. Trial Registration NCT03349450 Ethics Approval This study was approved by the Ontario Cancer Research Ethics Board, approval number 0981.
- Published
- 2020
47. Hepatic Steatosis Is Associated with Increased Disease Severity and Liver Injury in Coronavirus Disease-19
- Author
-
Ihab Kassab, Naresh T Gunaratnam, Jeffrey A. Berinstein, Vincent L. Chen, Jeremy Louissaint, Calen A. Steiner, Pratima Sharma, Kevin D. Platt, Fadi Hawa, Chia-Yang Hsu, and Chanakyaram A. Reddy
- Subjects
medicine.medical_specialty ,Physiology ,medicine.medical_treatment ,Disease ,Outcomes ,Gastroenterology ,Severity of Illness Index ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,NAFLD ,Prevalence ,Acute liver injury ,Medicine ,Humans ,Dialysis ,Cardiopulmonary disease ,business.industry ,SARS-CoV-2 ,COVID-19 ,Hepatology ,Jaundice ,medicine.disease ,Fatty Liver ,Liver ,030220 oncology & carcinogenesis ,Transaminitis ,030211 gastroenterology & hepatology ,Original Article ,Steatosis ,medicine.symptom ,business ,Cohort study - Abstract
Background Coronavirus disease-2019 (COVID-19) is a global pandemic. Obesity has been associated with increased disease severity in COVID-19, and obesity is strongly associated with hepatic steatosis (HS). However, how HS alters the natural history of COVID-19 is not well characterized, especially in Western populations. Aims To characterize the impact of HS on disease severity and liver injury in COVID-19. Methods We examined the association between HS and disease severity in a single-center cohort study of hospitalized COVID-19 patients at Michigan Medicine. HS was defined by either hepatic steatosis index > 36 (for Asians) or > 39 (for non-Asians) or liver imaging demonstrating steatosis > 30 days before onset of COVID-19. The primary predictor was HS. The primary outcomes were severity of cardiopulmonary disease, transaminitis, jaundice, and portal hypertensive complications. Results In a cohort of 342 patients, metabolic disease was highly prevalent including nearly 90% overweight. HS was associated with increased transaminitis and need for intubation, dialysis, and vasopressors. There was no association between HS and jaundice or portal hypertensive complications. In a sensitivity analysis including only patients with liver imaging > 30 days before onset of COVID-19, imaging evidence of hepatic steatosis remained associated with disease severity and risk of transaminitis. Conclusions HS was associated with increased disease severity and transaminitis in COVID-19. HS may be relevant in predicting risk of complications related to COVID-19.
- Published
- 2020
48. Valuing the labour of midwives in Ontario, Canada and New Zealand
- Author
-
Juana Berinstein, Ellen Blais, and Karen Guilliand
- Subjects
Geography ,Socioeconomics ,Ontario canada - Published
- 2020
49. Variations in Health Care Utilization Patterns Among Inflammatory Bowel Disease Patients at Risk for High Medical Service Utilization Enrolled in High Deductible Health Plans
- Author
-
John I. Allen, Mohamed Noureldin, Peter D.R. Higgins, Jeffrey A. Berinstein, Jeffrey T. Kullgren, Megan McLeod, Akbar K. Waljee, Shirley Cohen-Mekelburg, and Calen A. Steiner
- Subjects
medicine.medical_specialty ,Colonoscopy ,Deductible ,Inflammatory bowel disease ,03 medical and health sciences ,0302 clinical medicine ,Service utilization ,Clinical Research ,Health care ,Deductibles and Coinsurance ,Immunology and Allergy ,Medicine ,Humans ,030212 general & internal medicine ,Retrospective Studies ,Insurance, Health ,medicine.diagnostic_test ,business.industry ,Gastroenterology ,Retrospective cohort study ,Emergency department ,Patient Acceptance of Health Care ,medicine.disease ,Inflammatory Bowel Diseases ,Emergency medicine ,Chronic Disease ,Cost sharing ,030211 gastroenterology & hepatology ,business - Abstract
Background High-deductible health plans (HDHPs) are increasing in prevalence as a cost control device for slowing health care cost growth by reducing nonessential medical service utilization. High cost-sharing associated with HDHPs can lead to significant financial distress and worse disease outcomes. We hypothesize that chronic disease patients are delaying or foregoing necessary medical care due to health care costs. Methods A retrospective cohort analysis of IBD patients at risk for high medical service utilization with continuous enrollment in either an HDHP or THP from 2009 to 2016 were identified using the MarketScan database. Health care costs were compared between insurance plan groups by Kruskal-Wallis test. Temporal trends in office visits, colonoscopies, emergency department (ED) visits, and hospitalizations were evaluated using additive decomposition time series analysis. Results Of 605,862 patients with a diagnosis of IBD, we identified 13,052 eligible patients. Annual out-of-pocket costs were higher in the HDHP group (n = 524) than the THP group (n = 12,458) ($2870 vs $1,864; P < 0.001) without any difference in total health care expenses ($23,029 vs $23,794; P = 0.583). Enrollment in an HDHP influenced colonoscopy, ED visit, and hospitalization utilization timing. Colonoscopies peaked in the fourth quarter, ED visits peaked in the first quarter, and hospitalizations peaked in the third and fourth quarter. Conclusions High-deductible health plan enrollment does not change the cost of care; however, it shifts health care costs onto patients and changes the timing of the care they receive. High-deductible health plans are incentivizing delays in obtaining health care with a potential to cause worse disease outcomes and financial distress. Further evaluation is warranted.
- Published
- 2020
50. Improving Detection Rates of Giardia Using Duodenal Biopsy PCR: Is the Juice Worth the Squeeze?
- Author
-
Krishna Rao and Jeffrey A. Berinstein
- Subjects
Diarrhea ,Giardiasis ,medicine.medical_specialty ,Physiology ,Duodenal biopsy ,Biopsy ,Gastroenterology ,Polymerase Chain Reaction ,law.invention ,Transplant surgery ,law ,Internal medicine ,Medicine ,Humans ,Polymerase chain reaction ,biology ,medicine.diagnostic_test ,business.industry ,Giardia ,Hepatology ,biology.organism_classification ,Detection rate ,medicine.symptom ,business - Published
- 2020
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.