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Article ; Online: Association of measured quality with financial health among U.S. hospitals.

Enumah, Samuel J / Resnick, Andrew S / Chang, David C

2022 Volume 17, Issue 4, Page(s) e0266696

Abstract: Background: High-quality care is a clear objective for hospital leaders, but hospitals must balance investing in quality with financial stability. Poor hospital financial health can precipitate closure, limiting patients' access to care. Whether ... ...

Abstract	Background: High-quality care is a clear objective for hospital leaders, but hospitals must balance investing in quality with financial stability. Poor hospital financial health can precipitate closure, limiting patients' access to care. Whether hospital quality is associated with financial health remains poorly understood. The objective of this study was to compare financial performance at high-quality and low-quality hospitals. Methods: We performed a retrospective observational cohort study of U.S. hospitals using the American Hospital Association and Hospital Compare datasets for years 2013 to 2018. We used multilevel mixed-effects linear and logistic regression models with fixed year effects and random intercepts for hospitals to identify associations between hospitals' measured quality outcomes-30-day hospital-wide readmission rate and the patient safety indicator-90 (PSI-90)-and their financial margins and risk of financial distress in the same year and the subsequent year. Our sample included 20,919 observations from 4,331 unique hospitals. Results: In 2018, the median 30-day readmission rate was 15.2 (interquartile range [IQR] 14.8-15.6), the median PSI-90 score was 0.96 (IQR 0.89-1.07), the median operating margin was -1.8 (IQR -9.7-5.9), and 750 (22.7%) hospitals experienced financial distress. Hospitals in the best quintile of readmission rates experienced higher operating margins (+0.95%, 95% CI [0.51-1.39], p < .001) and lower odds of distress (odds ratio [OR] 0.56, 95% CI [0.45-0.70], p < .001) in the same year as compared to hospitals in the worst quintile. Hospitals in the best quintile of PSI-90 had higher operating margins (+0.62%, 95% CI [0.17-1.08], p = .007) and lower odds of financial distress (OR 0.70, 95% CI [0.55-0.89], p = .003) as compared to hospitals in the worst quintile. The results were qualitatively similar for the same-year and lag-year analyses. Conclusion: Hospitals that deliver high-quality outcomes may experience superior financial performance compared to hospitals with poor-quality outcomes.
MeSH term(s)	Hospitals ; Humans ; Patient Readmission ; Patient Safety ; Quality of Health Care ; Retrospective Studies ; United States
Language	English
Publishing date	2022-04-20
Publishing country	United States
Document type	Journal Article ; Observational Study ; Research Support, N.I.H., Extramural
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0266696
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Association of measured quality with financial health among U.S. hospitals

Samuel J. Enumah / Andrew S. Resnick / David C. Chang

PLoS ONE, Vol 17, Iss

2022 Volume 4

Abstract: Background High-quality care is a clear objective for hospital leaders, but hospitals must balance investing in quality with financial stability. Poor hospital financial health can precipitate closure, limiting patients’ access to care. Whether hospital ... ...

Abstract	Background High-quality care is a clear objective for hospital leaders, but hospitals must balance investing in quality with financial stability. Poor hospital financial health can precipitate closure, limiting patients’ access to care. Whether hospital quality is associated with financial health remains poorly understood. The objective of this study was to compare financial performance at high-quality and low-quality hospitals. Methods We performed a retrospective observational cohort study of U.S. hospitals using the American Hospital Association and Hospital Compare datasets for years 2013 to 2018. We used multilevel mixed-effects linear and logistic regression models with fixed year effects and random intercepts for hospitals to identify associations between hospitals’ measured quality outcomes—30-day hospital-wide readmission rate and the patient safety indicator-90 (PSI-90)—and their financial margins and risk of financial distress in the same year and the subsequent year. Our sample included 20,919 observations from 4,331 unique hospitals. Results In 2018, the median 30-day readmission rate was 15.2 (interquartile range [IQR] 14.8–15.6), the median PSI-90 score was 0.96 (IQR 0.89–1.07), the median operating margin was -1.8 (IQR -9.7–5.9), and 750 (22.7%) hospitals experienced financial distress. Hospitals in the best quintile of readmission rates experienced higher operating margins (+0.95%, 95% CI [0.51–1.39], p < .001) and lower odds of distress (odds ratio [OR] 0.56, 95% CI [0.45–0.70], p < .001) in the same year as compared to hospitals in the worst quintile. Hospitals in the best quintile of PSI-90 had higher operating margins (+0.62%, 95% CI [0.17–1.08], p = .007) and lower odds of financial distress (OR 0.70, 95% CI [0.55–0.89], p = .003) as compared to hospitals in the worst quintile. The results were qualitatively similar for the same-year and lag-year analyses. Conclusion Hospitals that deliver high-quality outcomes may experience superior financial performance compared to hospitals with ...
Keywords	Medicine ; R ; Science ; Q
Subject code	027
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article ; Online: Association of measured quality with financial health among U.S. hospitals.

Samuel J Enumah / Andrew S Resnick / David C Chang

PLoS ONE, Vol 17, Iss 4, p e

2022 Volume 0266696

Abstract	Background High-quality care is a clear objective for hospital leaders, but hospitals must balance investing in quality with financial stability. Poor hospital financial health can precipitate closure, limiting patients' access to care. Whether hospital quality is associated with financial health remains poorly understood. The objective of this study was to compare financial performance at high-quality and low-quality hospitals. Methods We performed a retrospective observational cohort study of U.S. hospitals using the American Hospital Association and Hospital Compare datasets for years 2013 to 2018. We used multilevel mixed-effects linear and logistic regression models with fixed year effects and random intercepts for hospitals to identify associations between hospitals' measured quality outcomes-30-day hospital-wide readmission rate and the patient safety indicator-90 (PSI-90)-and their financial margins and risk of financial distress in the same year and the subsequent year. Our sample included 20,919 observations from 4,331 unique hospitals. Results In 2018, the median 30-day readmission rate was 15.2 (interquartile range [IQR] 14.8-15.6), the median PSI-90 score was 0.96 (IQR 0.89-1.07), the median operating margin was -1.8 (IQR -9.7-5.9), and 750 (22.7%) hospitals experienced financial distress. Hospitals in the best quintile of readmission rates experienced higher operating margins (+0.95%, 95% CI [0.51-1.39], p < .001) and lower odds of distress (odds ratio [OR] 0.56, 95% CI [0.45-0.70], p < .001) in the same year as compared to hospitals in the worst quintile. Hospitals in the best quintile of PSI-90 had higher operating margins (+0.62%, 95% CI [0.17-1.08], p = .007) and lower odds of financial distress (OR 0.70, 95% CI [0.55-0.89], p = .003) as compared to hospitals in the worst quintile. The results were qualitatively similar for the same-year and lag-year analyses. Conclusion Hospitals that deliver high-quality outcomes may experience superior financial performance compared to hospitals with ...
Keywords	Medicine ; R ; Science ; Q
Subject code	027
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article ; Online: Molecular and clinicopathologic characteristics of gliomas with EP300::BCOR fusions.

Wu, Zhichao / Rajan, Sharika / Chung, Hye-Jung / Raffeld, Mark / Panneer Selvam, Pavalan / Schweizer, Leonille / Perry, Arie / Samuel, David / Giannini, Caterina / Ragunathan, Aditya / Frosch, Matthew P / Marshall, Michael S / Boué, Daniel R / Donev, Kliment / Neill, Stewart G / Fernandes, Igor / Resnick, Adam / Rood, Brian / Cummings, Thomas J /

Buckley, Anne F / Szymanski, Linda / Neto, Osorio Lopes Abath / Zach, Leor / Colman, Howard / Cheshier, Samuel / Ziskin, Jennifer / Tyagi, Manoj / Capper, David / Abdullaev, Zied / Cimino, Patrick J / Quezado, Martha / Pratt, Drew / Aldape, Kenneth

Acta neuropathologica

2022 Volume 144, Issue 6, Page(s) 1175–1178

MeSH term(s)	Humans ; Glioma/genetics ; Proto-Oncogene Proteins ; Repressor Proteins ; E1A-Associated p300 Protein
Chemical Substances	BCOR protein, human ; Proto-Oncogene Proteins ; Repressor Proteins ; EP300 protein, human (EC 2.3.1.48) ; E1A-Associated p300 Protein (EC 2.3.1.48)
Language	English
Publishing date	2022-10-06
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1079-0
ISSN	1432-0533 ; 0001-6322
ISSN (online)	1432-0533
ISSN	0001-6322
DOI	10.1007/s00401-022-02508-2
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Article ; Online: Inhibitors of Coronavirus 3CL Proteases Protect Cells from Protease-Mediated Cytotoxicity.

Resnick, Samuel J / Iketani, Sho / Hong, Seo Jung / Zask, Arie / Liu, Hengrui / Kim, Sungsoo / Melore, Schuyler / Lin, Fang-Yu / Nair, Manoj S / Huang, Yaoxing / Lee, Sumin / Tay, Nicholas E S / Rovis, Tomislav / Yang, Hee Won / Xing, Li / Stockwell, Brent R / Ho, David D / Chavez, Alejandro

Journal of virology

2021 Volume 95, Issue 14, Page(s) e0237420

Abstract: We describe a mammalian cell-based assay to identify coronavirus 3CL protease (3CLpro) inhibitors. This assay is based on rescuing protease-mediated cytotoxicity and does not require live virus. By enabling the facile testing of compounds across a range ... ...

Abstract	We describe a mammalian cell-based assay to identify coronavirus 3CL protease (3CLpro) inhibitors. This assay is based on rescuing protease-mediated cytotoxicity and does not require live virus. By enabling the facile testing of compounds across a range of 15 distantly related coronavirus 3CLpro enzymes, we identified compounds with broad 3CLpro-inhibitory activity. We also adapted the assay for use in compound screening and in doing so uncovered additional severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CLpro inhibitors. We observed strong concordance between data emerging from this assay and those obtained from live-virus testing. The reported approach democratizes the testing of 3CLpro inhibitors by developing a simplified method for identifying coronavirus 3CLpro inhibitors that can be used by the majority of laboratories, rather than the few with extensive biosafety infrastructure. We identified two lead compounds, GC376 and compound 4, with broad activity against all 3CL proteases tested, including 3CLpro enzymes from understudied zoonotic coronaviruses.
MeSH term(s)	COVID-19/drug therapy ; COVID-19/enzymology ; Coronavirus 3C Proteases/antagonists & inhibitors ; Coronavirus 3C Proteases/chemistry ; Coronavirus 3C Proteases/metabolism ; Cysteine Proteinase Inhibitors/chemistry ; Cysteine Proteinase Inhibitors/pharmacology ; HEK293 Cells ; Humans ; SARS-CoV-2/enzymology
Chemical Substances	Cysteine Proteinase Inhibitors ; Coronavirus 3C Proteases (EC 3.4.22.28)
Language	English
Publishing date	2021-06-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.02374-20
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Article ; Online: Understanding health-related quality of life in adult women with metastatic cancer who have dependent children.

Park, Eliza M / Deal, Allison M / Yopp, Justin M / Edwards, Teresa / Resnick, Samuel J / Song, Mi-Kyung / Nakamura, Zev M / Rosenstein, Donald L

Cancer

2018 Volume 124, Issue 12, Page(s) 2629–2636

Abstract: Background: Cancer is a leading cause of death among women of parenting age in the United States. Women living with advanced or incurable cancer who have dependent children experience high rates of depression and anxiety as well as unique parenting ... ...

Abstract	Background: Cancer is a leading cause of death among women of parenting age in the United States. Women living with advanced or incurable cancer who have dependent children experience high rates of depression and anxiety as well as unique parenting challenges. To the authors' knowledge, few studies to date have examined the parenting factors associated with health-related quality of life (HRQOL) in women with advanced cancer. Methods: The authors conducted a cross-sectional, Web-based survey of the psychosocial concerns of 224 women with a tumor-node-metastasis staging system of the AJCC stage IV solid tumor malignancy who had at least 1 child aged <18 years. Participants completed validated measures of HRQOL (Functional Assessment of Cancer Therapy-General [FACT-G]); depression and anxiety symptom severity; functional status; parenting concerns; and investigator-designed questions to assess demographic, communication, and parenting characteristics. Multiple linear regression models were estimated to identify factors associated with FACT-G total and subscale scores. Results: The mean FACT-G score was 66 (standard deviation, 16). The mean Emotional Well-Being subscale scores were particularly low (13; standard deviation, 5). In multivariable linear regression models, parenting variables explained nearly 40% of the HRQOL model variance. In the fully adjusted model, parenting concerns and the absence of parental prognostic communication with children both were found to be significantly associated with HRQOL scores. For each 1-point increase in parenting concern severity, FACT-G scores decreased by 4 points (P = .003). Conclusions: Women with metastatic cancer who are parents of dependent children are at risk of high psychological distress and low HRQOL. Parenting factors may have a negative influence on HRQOL in this patient population. Cancer 2018;124:2629-36. © 2018 American Cancer Society.
MeSH term(s)	Adolescent ; Adult ; Anxiety/diagnosis ; Anxiety/psychology ; Child ; Cross-Sectional Studies ; Depression/diagnosis ; Depression/psychology ; Female ; Humans ; Karnofsky Performance Status ; Middle Aged ; Mothers/psychology ; Mothers/statistics & numerical data ; Neoplasms/diagnosis ; Neoplasms/pathology ; Neoplasms/psychology ; Parenting/psychology ; Quality of Life ; Self Report/statistics & numerical data ; Stress, Psychological/diagnosis ; Stress, Psychological/psychology
Language	English
Publishing date	2018-05-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.31330
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Article ; Online: Identification of potentially oncogenic alterations from tumor-only samples reveals Fanconi anemia pathway mutations in bladder carcinomas.

Madubata, Chioma J / Roshan-Ghias, Alireza / Chu, Timothy / Resnick, Samuel / Zhao, Junfei / Arnes, Luis / Wang, Jiguang / Rabadan, Raul

NPJ genomic medicine

2017 Volume 2, Page(s) 29

Abstract: Cancer is caused by germline and somatic mutations, which can share biological features such as amino acid change. However, integrated germline and somatic analysis remains uncommon. We present a framework that uses machine learning to learn features of ... ...

Abstract	Cancer is caused by germline and somatic mutations, which can share biological features such as amino acid change. However, integrated germline and somatic analysis remains uncommon. We present a framework that uses machine learning to learn features of recurrent somatic mutations to (1) predict somatic variants from tumor-only samples and (2) identify somatic-like germline variants for integrated analysis of tumor-normal DNA. Using data from 1769 patients from seven cancer types (bladder, glioblastoma, low-grade glioma, lung, melanoma, stomach, and pediatric glioma), we show that "somatic-like" germline variants are enriched for autosomal-dominant cancer-predisposition genes (
Language	English
Publishing date	2017-10-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2813848-X
ISSN	2056-7944 ; 2056-7944
ISSN (online)	2056-7944
ISSN	2056-7944
DOI	10.1038/s41525-017-0032-5
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Article: A simplified cell-based assay to identify coronavirus 3CL protease inhibitors.

Resnick, Samuel J / Iketani, Sho / Hong, Seo Jung / Zask, Arie / Liu, Hengrui / Kim, Sungsoo / Melore, Schuyler / Nair, Manoj S / Huang, Yaoxing / Tay, Nicholas E S / Rovis, Tomislav / Yang, Hee Won / Stockwell, Brent R / Ho, David D / Chavez, Alejandro

bioRxiv : the preprint server for biology

2020

Abstract: We describe a mammalian cell-based assay capable of identifying coronavirus 3CL protease (3CLpro) inhibitors without requiring the use of live virus. By enabling the facile testing of compounds across a range of coronavirus 3CLpro enzymes, including the ... ...

Abstract	We describe a mammalian cell-based assay capable of identifying coronavirus 3CL protease (3CLpro) inhibitors without requiring the use of live virus. By enabling the facile testing of compounds across a range of coronavirus 3CLpro enzymes, including the one from SARS-CoV-2, we are able to quickly identify compounds with broad or narrow spectra of activity. We further demonstrate the utility of our approach by performing a curated compound screen along with structure-activity profiling of a series of small molecules to identify compounds with antiviral activity. Throughout these studies, we observed concordance between data emerging from this assay and from live virus assays. By democratizing the testing of 3CL inhibitors to enable screening in the majority of laboratories rather than the few with extensive biosafety infrastructure, we hope to expedite the search for coronavirus 3CL protease inhibitors, to address the current epidemic and future ones that will inevitably arise.
Keywords	covid19
Language	English
Publishing date	2020-08-29
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.08.29.272864
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Article ; Online: Development of optimized drug-like small molecule inhibitors of the SARS-CoV-2 3CL protease for treatment of COVID-19.

Liu, Hengrui / Iketani, Sho / Zask, Arie / Khanizeman, Nisha / Bednarova, Eva / Forouhar, Farhad / Fowler, Brandon / Hong, Seo Jung / Mohri, Hiroshi / Nair, Manoj S / Huang, Yaoxing / Tay, Nicholas E S / Lee, Sumin / Karan, Charles / Resnick, Samuel J / Quinn, Colette / Li, Wenjing / Shion, Henry / Xia, Xin /

Daniels, Jacob D / Bartolo-Cruz, Michelle / Farina, Marcelo / Rajbhandari, Presha / Jurtschenko, Christopher / Lauber, Matthew A / McDonald, Thomas / Stokes, Michael E / Hurst, Brett L / Rovis, Tomislav / Chavez, Alejandro / Ho, David D / Stockwell, Brent R

Nature communications

2022 Volume 13, Issue 1, Page(s) 1891

Abstract: The SARS-CoV-2 3CL protease is a critical drug target for small molecule COVID-19 therapy, given its likely druggability and essentiality in the viral maturation and replication cycle. Based on the conservation of 3CL protease substrate binding pockets ... ...

Abstract	The SARS-CoV-2 3CL protease is a critical drug target for small molecule COVID-19 therapy, given its likely druggability and essentiality in the viral maturation and replication cycle. Based on the conservation of 3CL protease substrate binding pockets across coronaviruses and using screening, we identified four structurally distinct lead compounds that inhibit SARS-CoV-2 3CL protease. After evaluation of their binding specificity, cellular antiviral potency, metabolic stability, and water solubility, we prioritized the GC376 scaffold as being optimal for optimization. We identified multiple drug-like compounds with <10 nM potency for inhibiting SARS-CoV-2 3CL and the ability to block SARS-CoV-2 replication in human cells, obtained co-crystal structures of the 3CL protease in complex with these compounds, and determined that they have pan-coronavirus activity. We selected one compound, termed coronastat, as an optimized lead and characterized it in pharmacokinetic and safety studies in vivo. Coronastat represents a new candidate for a small molecule protease inhibitor for the treatment of SARS-CoV-2 infection for eliminating pandemics involving coronaviruses.
MeSH term(s)	Antiviral Agents/chemistry ; Antiviral Agents/therapeutic use ; COVID-19/drug therapy ; Coronavirus 3C Proteases/antagonists & inhibitors ; Humans ; Molecular Docking Simulation ; Pandemics ; Protease Inhibitors/chemistry ; Protease Inhibitors/pharmacology ; Protease Inhibitors/therapeutic use ; SARS-CoV-2
Chemical Substances	Antiviral Agents ; Protease Inhibitors ; 3C-like proteinase, SARS-CoV-2 (EC 3.4.22.-) ; Coronavirus 3C Proteases (EC 3.4.22.28)
Language	English
Publishing date	2022-04-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-29413-2
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Article ; Online: Identification of potentially oncogenic alterations from tumor-only samples reveals Fanconi anemia pathway mutations in bladder carcinomas

Chioma J Madubata / Alireza Roshan-Ghias / Timothy Chu / Samuel Resnick / Junfei Zhao / Luis Arnes / Jiguang Wang / Raul Rabadan

npj Genomic Medicine, Vol 2, Iss 1, Pp 1-

2017 Volume 10

Abstract: Cancer: Analytic tool reveals inherited and non-inherited tumor-causing alterations Bladder cancer cells often harbor DNA mutations that occur after tumor development, including some mutations that affect DNA repair. Raul Rabadan, Jiguang Wang, and ... ...

Abstract	Cancer: Analytic tool reveals inherited and non-inherited tumor-causing alterations Bladder cancer cells often harbor DNA mutations that occur after tumor development, including some mutations that affect DNA repair. Raul Rabadan, Jiguang Wang, and colleagues from Columbia University in New York, USA, developed an analytic framework for identifying genetic variants, both inherited and newly arisen, that contribute to tumor development. The machine-learning tool—known as Tumor-Only Boosting Identification, or TOBI—learns what’s a cancer-associated mutation from a small training set of tumor samples and matched healthy controls. The researchers then fed the algorithm data from the tumors of 1769 patients with cancers of the bladder, brain, lungs, stomach and skin. They found that TOBI pinpointed many inherited and non-inherited mutations known to contribute to cancer growth. In bladder cancer samples, the tool also revealed a previously unknown role for inherited mutations in BRCA2 and other DNA repair genes in the so-called Fanconi anemia pathway.
Keywords	Medicine ; R ; Genetics ; QH426-470
Subject code	616
Language	English
Publishing date	2017-10-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
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