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Book ; Online ; E-Book: Valuing health

Phelps, Charles E. / Lakdawalla, Darius

the generalized and risk-adjusted cost-effectiveness (GRACE) model

2024

Abstract: Valuing Health uses the generalized risk-adjusted cost-effectiveness (GRACE) model to demonstrate the economic value of improving the quality of life for individuals with disability or severe illness. ...

Author's details	Charles E. Phelps and Darius N. Lakdawalla
Abstract	Valuing Health uses the generalized risk-adjusted cost-effectiveness (GRACE) model to demonstrate the economic value of improving the quality of life for individuals with disability or severe illness.
Keywords	Medical economics ; Medical care/Cost effectiveness ; Value analysis (Cost control)
Subject code	338.473621
Language	English
Size	1 online resource (329 pages)
Publisher	Oxford University Press
Publishing place	New York, NY
Document type	Book ; Online ; E-Book
Remark	Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
ISBN	0-19-768630-3 ; 9780197686287 ; 978-0-19-768630-0 ; 0197686281
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Species-specific enhancement of enterohemorrhagic E. coli pathogenesis mediated by microbiome metabolites.

Tovaglieri, Alessio / Sontheimer-Phelps, Alexandra / Geirnaert, Annelies / Prantil-Baun, Rachelle / Camacho, Diogo M / Chou, David B / Jalili-Firoozinezhad, Sasan / de Wouters, Tomás / Kasendra, Magdalena / Super, Michael / Cartwright, Mark J / Richmond, Camilla A / Breault, David T / Lacroix, Christophe / Ingber, Donald E

Microbiome

2019 Volume 7, Issue 1, Page(s) 43

Abstract: Background: Species-specific differences in tolerance to infection are exemplified by the high susceptibility of humans to enterohemorrhagic Escherichia coli (EHEC) infection, whereas mice are relatively resistant to this pathogen. This intrinsic ... ...

Abstract	Background: Species-specific differences in tolerance to infection are exemplified by the high susceptibility of humans to enterohemorrhagic Escherichia coli (EHEC) infection, whereas mice are relatively resistant to this pathogen. This intrinsic species-specific difference in EHEC infection limits the translation of murine research to human. Furthermore, studying the mechanisms underlying this differential susceptibility is a difficult problem due to complex in vivo interactions between the host, pathogen, and disparate commensal microbial communities. Results: We utilize organ-on-a-chip (Organ Chip) microfluidic culture technology to model damage of the human colonic epithelium induced by EHEC infection, and show that epithelial injury is greater when exposed to metabolites derived from the human gut microbiome compared to mouse. Using a multi-omics approach, we discovered four human microbiome metabolites-4-methyl benzoic acid, 3,4-dimethylbenzoic acid, hexanoic acid, and heptanoic acid-that are sufficient to mediate this effect. The active human microbiome metabolites preferentially induce expression of flagellin, a bacterial protein associated with motility of EHEC and increased epithelial injury. Thus, the decreased tolerance to infection observed in humans versus other species may be due in part to the presence of compounds produced by the human intestinal microbiome that actively promote bacterial pathogenicity. Conclusion: Organ-on-chip technology allowed the identification of specific human microbiome metabolites modulating EHEC pathogenesis. These identified metabolites are sufficient to increase susceptibility to EHEC in our human Colon Chip model and they contribute to species-specific tolerance. This work suggests that higher concentrations of these metabolites could be the reason for higher susceptibility to EHEC infection in certain human populations, such as children. Furthermore, this research lays the foundation for therapeutic-modulation of microbe products in order to prevent and treat human bacterial infection.
MeSH term(s)	Animals ; Bacteria/metabolism ; Benzoates/pharmacology ; Caproates/pharmacology ; Cells, Cultured ; Enterohemorrhagic Escherichia coli/metabolism ; Enterohemorrhagic Escherichia coli/pathogenicity ; Escherichia coli Infections/microbiology ; Escherichia coli Infections/pathology ; Female ; Gastrointestinal Microbiome ; Heptanoic Acids/pharmacology ; Humans ; Intestines/cytology ; Intestines/microbiology ; Male ; Mice ; Microchip Analytical Procedures ; Organ Culture Techniques/methods ; Species Specificity
Chemical Substances	Benzoates ; Caproates ; Heptanoic Acids ; hexanoic acid (1F8SN134MX)
Language	English
Publishing date	2019-03-20
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2697425-3
ISSN	2049-2618 ; 2049-2618
ISSN (online)	2049-2618
ISSN	2049-2618
DOI	10.1186/s40168-019-0650-5
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Article ; Online: Species-specific enhancement of enterohemorrhagic E. coli pathogenesis mediated by microbiome metabolites

Alessio Tovaglieri / Alexandra Sontheimer-Phelps / Annelies Geirnaert / Rachelle Prantil-Baun / Diogo M. Camacho / David B. Chou / Sasan Jalili-Firoozinezhad / Tomás de Wouters / Magdalena Kasendra / Michael Super / Mark J. Cartwright / Camilla A. Richmond / David T. Breault / Christophe Lacroix / Donald E. Ingber

Microbiome, Vol 7, Iss 1, Pp 1-

2019 Volume 21

Abstract: Abstract Background Species-specific differences in tolerance to infection are exemplified by the high susceptibility of humans to enterohemorrhagic Escherichia coli (EHEC) infection, whereas mice are relatively resistant to this pathogen. This intrinsic ...

Abstract	Abstract Background Species-specific differences in tolerance to infection are exemplified by the high susceptibility of humans to enterohemorrhagic Escherichia coli (EHEC) infection, whereas mice are relatively resistant to this pathogen. This intrinsic species-specific difference in EHEC infection limits the translation of murine research to human. Furthermore, studying the mechanisms underlying this differential susceptibility is a difficult problem due to complex in vivo interactions between the host, pathogen, and disparate commensal microbial communities. Results We utilize organ-on-a-chip (Organ Chip) microfluidic culture technology to model damage of the human colonic epithelium induced by EHEC infection, and show that epithelial injury is greater when exposed to metabolites derived from the human gut microbiome compared to mouse. Using a multi-omics approach, we discovered four human microbiome metabolites—4-methyl benzoic acid, 3,4-dimethylbenzoic acid, hexanoic acid, and heptanoic acid—that are sufficient to mediate this effect. The active human microbiome metabolites preferentially induce expression of flagellin, a bacterial protein associated with motility of EHEC and increased epithelial injury. Thus, the decreased tolerance to infection observed in humans versus other species may be due in part to the presence of compounds produced by the human intestinal microbiome that actively promote bacterial pathogenicity. Conclusion Organ-on-chip technology allowed the identification of specific human microbiome metabolites modulating EHEC pathogenesis. These identified metabolites are sufficient to increase susceptibility to EHEC in our human Colon Chip model and they contribute to species-specific tolerance. This work suggests that higher concentrations of these metabolites could be the reason for higher susceptibility to EHEC infection in certain human populations, such as children. Furthermore, this research lays the foundation for therapeutic-modulation of microbe products in order to prevent and treat ...
Keywords	Microbial ecology ; QR100-130
Subject code	572
Language	English
Publishing date	2019-03-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
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Article ; Online: Transgenic expression of human leukocyte antigen-E attenuates GalKO.hCD46 porcine lung xenograft injury.

Laird, Christopher T / Burdorf, Lars / French, Beth M / Kubicki, Natalia / Cheng, Xiangfei / Braileanu, Gheorghe / Sun, Wenji / O'Neill, Natalie A / Cimeno, Arielle / Parsell, Dawn / So, Edward / Bähr, Andrea / Klymiuk, Nikolai / Phelps, Carol J / Ayares, David / Azimzadeh, Agnes M / Pierson, Richard N

Xenotransplantation

2017 Volume 24, Issue 2

Abstract: ... inhibitory ligand HLA-E and β2 microglobulin inhibits GalTKO.hCD46 pig cell injury or prolongs lung function ... and GalTKO.hCD46.HLA-E (n=5) were harvested and perfused with human blood until failure or elective ... cytotoxicity assays using human NK cells.: Results: HLA-E expression on GalTKO.hCD46 PAECs was associated ...

Abstract	Background: Lung xenografts remain susceptible to loss of vascular barrier function within hours in spite of significant incremental advances based on genetic engineering to remove the Gal 1,3-αGal antigen (GalTKO) and express human membrane cofactor protein (hCD46). Natural killer cells rapidly disappear from the blood during perfusion of GalTKO.hCD46 porcine lungs with human blood and presumably are sequestered within the lung vasculature. Here we asked whether porcine expression of the human NK cell inhibitory ligand HLA-E and β2 microglobulin inhibits GalTKO.hCD46 pig cell injury or prolongs lung function in two preclinical perfusion models. Methods: Lungs from pigs modified to express GalTKO.hCD46 (n=37) and GalTKO.hCD46.HLA-E (n=5) were harvested and perfused with human blood until failure or elective termination at 4 hours. Airway pressures and pulmonary artery hemodynamics were recorded in real time. Blood samples were also collected throughout the experiment for analysis. Porcine aortic endothelial cells (PAECs) from each genotype were cultured in monolayers in microfluidic channels and used in fluorescent cytotoxicity assays using human NK cells. Results: HLA-E expression on GalTKO.hCD46 PAECs was associated with significantly decreased antibody-dependent and antibody-independent NK-mediated cytotoxicity under in vitro conditions simulating physiologic shear stress. Relative to GalTKO.hCD46 pig lungs perfused with human blood on an ex vivo platform, additional expression of HLA-E increased median lung survival (>4 hours, vs 162 minutes, P=.012), and was associated with attenuated rise in pulmonary vascular resistance, and decreased platelet activation and histamine elaboration. As expected, HLA-E expression was not associated with a significant difference in NK cell adhesion to endothelial cells in vitro, or NK cell and neutrophil sequestration during organ perfusion. Conclusions: We conclude human NK cell activation contributes significantly to GalTKO.hCD46 pig endothelial injury and lung inflammation and show that expression of HLA-E is associated with physiologically meaningful protection of GalTKO.hCD46 cells and organs exposed to human blood.
MeSH term(s)	Animals ; Animals, Genetically Modified ; Cytotoxicity, Immunologic/immunology ; Endothelial Cells/immunology ; Galactosyltransferases/genetics ; Graft Survival/genetics ; Graft Survival/immunology ; HLA Antigens/genetics ; HLA Antigens/immunology ; Heterografts/immunology ; Humans ; Killer Cells, Natural/immunology ; Leukocytes/immunology ; Lung Injury/immunology ; Lung Injury/therapy ; Membrane Cofactor Protein/genetics ; Membrane Cofactor Protein/immunology ; Swine ; Transplantation, Heterologous/methods
Chemical Substances	HLA Antigens ; Membrane Cofactor Protein ; Galactosyltransferases (EC 2.4.1.-)
Language	English
Publishing date	2017-03
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	1236298-0
ISSN	1399-3089 ; 0908-665X
ISSN (online)	1399-3089
ISSN	0908-665X
DOI	10.1111/xen.12294
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Article ; Online: P- and E-selectin receptor antagonism prevents human leukocyte adhesion to activated porcine endothelial monolayers and attenuates porcine endothelial damage.

Laird, Christopher T / Hassanein, Wessam / O'Neill, Natalie A / French, Beth M / Cheng, Xiangfei / Fogler, William E / Magnani, John L / Parsell, Dawn / Cimeno, Arielle / Phelps, Carol J / Ayares, David / Burdorf, Lars / Azimzadeh, Agnes M / Pierson, Richard N

Xenotransplantation

2018 Volume 25, Issue 2, Page(s) e12381

Abstract: ... and rPSGL1.Fc were tested as E- and P- selectin antagonists, respectively. Cellular adhesion and ... rolled and tethered. Both E-and P-selectin antagonism significantly reduced the number of neutrophils ...

Abstract	Background: Alongside the need to develop more effective and less toxic immunosuppression, the shortage of human organs available for organ transplantation is one of the major hurdles facing the field. Research into xenotransplantation, as an alternative source of organs, has unveiled formidable challenges. Porcine lungs perfused with human blood rapidly sequester the majority of circulating neutrophils and platelets, which leads to inflammation and organ failure within hours, and is not significantly attenuated by genetic modifications to the pig targeted to diminish antibody binding and complement and coagulation cascade activation. Methods: Here, we model the interaction of freshly isolated human leukocytes with xenotransplanted vasculature under physiologic flow conditions using microfluidic channels coated with porcine endothelial cells. Both isolated human neutrophils and whole human blood were perfused over transgenic pig aortic endothelial cells that had been activated with rhTNF-α or rhIL-4 using the BioFlux system. Novel compounds GMI-1271 and rPSGL1.Fc were tested as E- and P- selectin antagonists, respectively. Cellular adhesion and rolling events were tracked using FIJI (imageJ). Results: Porcine endothelium activated with either rhTNF-α or rhIL-4 expressed high amounts of selectins, to which isolated human neutrophils readily rolled and tethered. Both E-and P-selectin antagonism significantly reduced the number of neutrophils rolling and rolling distance in a dose-dependent manner, with near total inhibition at higher doses (P < .001). Similarly, with whole human blood, selectin blocking compounds exhibited dose-dependent inhibition of prevalent leukocyte adhesion and severe endothelial injury (Untreated: 394 ± 97 PMNs/hpf, 57 ± 6% loss EC; GMI1271+rPSGL1.Fc: 23 ± 9 PMNs/hpf, 8 ± 6% loss EC P < .01). Conclusions: Selectin blockade may be useful as part of an integrated strategy to prevent neutrophil-mediated organ xenograft injury, especially during the early time points following reperfusion.
MeSH term(s)	Animals ; Animals, Genetically Modified ; Cell Adhesion/physiology ; E-Selectin/metabolism ; Endothelial Cells/immunology ; Humans ; Leukocytes/immunology ; Neutrophils/immunology ; P-Selectin/metabolism ; Swine ; Transplantation, Heterologous/methods
Chemical Substances	E-Selectin ; P-Selectin ; SELE protein, human ; SELP protein, human
Language	English
Publishing date	2018-01-23
Publishing country	Denmark
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1236298-0
ISSN	1399-3089 ; 0908-665X
ISSN (online)	1399-3089
ISSN	0908-665X
DOI	10.1111/xen.12381
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Book ; Online: Beam Asymmetry $\mathbf{\Sigma}$ for the Photoproduction of $\mathbf{\eta}$ and $\mathbf{\eta^{\prime}}$ Mesons at $\mathbf{E_{\gamma}=8.8}$GeV

The GlueX Collaboration / Adhikari, S. / Ali, A. / Amaryan, M. / Austregesilo, A. / Barbosa, F. / Barlow, J. / Barnes, A. / Barriga, E. / Barsotti, R. / Beattie, T. D. / Berdnikov, V. V. / Black, T. / Boeglin, W. / Boer, M. / Briscoe, W. J. / Britton, T. / Brooks, W. K. / Cannon, B. E. /

Cao, N. / Chudakov, E. / Cole, S. / Cortes, O. / Crede, V. / Dalton, M. M. / Daniels, T. / Deur, A. / Dobbs, S. / Dolgolenko, A. / Dotel, R. / Dugger, M. / Dzhygadlo, R. / Egiyan, H. / Erbora, T. / Ernst, A. / Eugenio, P. / Fanelli, C. / Fegan, S. / Foda, A. M. / Foote, J. / Frye, J. / Furletov, S. / Gan, L. / Gasparian, A. / Gevorgyan, N. / Gleason, C. / Goetzen, K. / Goncalves, A. / Goryachev, V. S. / Guo, L. / Hakobyan, H. / Hamdi, A. / Huber, G. M. / Hurley, A. / Ireland, D. G. / Ito, M. M. / Jarvis, N. S. / Jones, R. T. / Kakoyan, V. / Kalicy, G. / Kamel, M. / Kourkoumelis, C. / Kuleshov, S. / Larin, I. / Lawrence, D. / Lersch, D. I. / Li, H. / Li, W. / Liu, B. / Livingston, K. / Lolos, G. J. / Lyubovitskij, V. / Mack, D. / Marukyan, H. / Mattione, P. / Matveev, V. / McCaughan, M. / McCracken, M. / McGinley, W. / Meyer, C. A. / Miskimen, R. / Mitchell, R. E. / Nerling, F. / Ng, L. / Ostrovidov, A. I. / Papandreou, Z. / Patsyuk, M. / Paudel, C. / Pauli, P. / Pedroni, R. / Pentchev, L. / Peters, K. J. / Phelps, W. / Pooser, E. / Qin, N. / Reinhold, J. / Ritchie, B. G. / Robison, L. / Romanov, D. / Romero, C. / Salgado, C. / Schertz, A. M. / Schumacher, R. A. / Schwiening, J. / Semenov, A. Yu. / Semenova, I. A. / Seth, K. K. / Shen, X. / Shepherd, M. R. / Smith, E. S. / Sober, D. I. / Somov, A. / Somov, S. / Soto, O. / Staib, M. / Stevens, J. R. / Strakovsky, I. I. / Suresh, K. / Tarasov, V. V. / Taylor, S. / Teymurazyan, A. / Thiel, A. / Vasileiadis, G. / Whitlatch, T. / Wickramaarachchi, N. / Williams, M. / Xiao, T. / Yang, Y. / Zarling, J. / Zhang, Z. / Zhao, G. / Zhou, Q. / Zhou, X. / Zihlmann, B.

2019

Abstract: We report on the measurement of the beam asymmetry $\Sigma$ for the reactions $\vec{\gamma}p\rightarrow p\eta$ and $\vec{\gamma}p \rightarrow p\eta^{\prime}$ from the GlueX experiment, using an 8.2--8.8 GeV linearly polarized tagged photon beam incident ... ...

Abstract	We report on the measurement of the beam asymmetry $\Sigma$ for the reactions $\vec{\gamma}p\rightarrow p\eta$ and $\vec{\gamma}p \rightarrow p\eta^{\prime}$ from the GlueX experiment, using an 8.2--8.8 GeV linearly polarized tagged photon beam incident on a liquid hydrogen target in Hall D at Jefferson Lab. These measurements are made as a function of momentum transfer $-t$, with significantly higher statistical precision than our earlier $\eta$ measurements, and are the first measurements of $\eta^{\prime}$ in this energy range. We compare the results to theoretical predictions based on $t$--channel quasi-particle exchange. We also compare the ratio of $\Sigma_{\eta}$ to $\Sigma_{\eta^{\prime}}$ to these models, as this ratio is predicted to be sensitive to the amount of $s\bar{s}$ exchange in the production. We find that photoproduction of both $\eta$ and $\eta^{\prime}$ is dominated by natural parity exchange with little dependence on $-t$. Comment: 18 pages, 7 figures
Keywords	Nuclear Experiment ; High Energy Physics - Experiment
Subject code	551
Publishing date	2019-08-15
Publishing country	us
Document type	Book ; Online
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Article ; Online: Values Beyond "Health" in Budget-Constrained Healthcare Systems.

Phelps, Charles E

Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research

2024

Abstract: Objectives: Most current methods to value healthcare treatments only incorporate measures such as quality-adjusted life-years, combining gains in health-related quality of life and life expectancy in specific ways. Failure of these methods to recognize ... ...

Abstract	Objectives: Most current methods to value healthcare treatments only incorporate measures such as quality-adjusted life-years, combining gains in health-related quality of life and life expectancy in specific ways. Failure of these methods to recognize other dimensions of value has led to calls for methods to include additional values that are associated with the healthcare treatments but not captured directly by quality-adjusted life-years. This article seeks to provide methodologically sound ways to incorporate additional health-related outcomes, focusing on budget-constrained healthcare systems, in which using standard welfare economics methods are often eschewed. Methods: The analysis develops standard extra-welfarist approaches to maximizing aggregate health, subject to fixed-budget constraints, using Lagrange multiplier methods. Then, additional valuable health-related outcomes, eg, reduced caregiver burden, real option value, and market- and non-market productivity are introduced. The article also introduces a social welfare function approach to illuminate how disability, disease severity and other equity-related issues can be incorporated into complete welfare measures. Results: Resulting analysis, fully developed in an Appendix in Supplemental Materials found at https://doi.org/10.1016/j.jval.2024.02.005 and summarized in the main text, show that understanding how average and marginal healthcare costs increase with output and how health augments "additional values" provides ways to assess willingness to pay for them in these fixed-budget situations. Conclusions: In budget-constrained healthcare systems, only from actual budget allocations can values both of health itself and "additional values" be inferred. These methods, combined with methodologically sound social welfare functions, demonstrate how to move from "health" to "welfare" in measuring the value of increased healthcare use.
Language	English
Publishing date	2024-02-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	1471745-1
ISSN	1524-4733 ; 1098-3015
ISSN (online)	1524-4733
ISSN	1098-3015
DOI	10.1016/j.jval.2024.02.005
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Zs.A 5904: Show issues

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Article ; Online: Can Escherichia coli fly? The role of flies as transmitters of E. coli to food in an urban slum in Bangladesh.

Lindeberg, Yrja Lisa / Egedal, Karen / Hossain, Zenat Zebin / Phelps, Matthew / Tulsiani, Suhella / Farhana, Israt / Begum, Anowara / Jensen, Peter Kjaer Mackie

Tropical medicine & international health : TM & IH

2017 Volume 23, Issue 1, Page(s) 2–9

Abstract: ... microbiologically and molecularly analysed for the presence of Escherichia coli and genes of diarrhoeagenic E. coli ... and Shigella strains.: Results: Rice was at greater risk (P < 0·001) of being contaminated with E ... per fly landing was >0·6 × 103 CFU. Genes of diarrhoeagenic E. coli and Shigella species were detected ...

Abstract	Objective: To investigate the transmission of faecal bacteria by flies to food under natural settings. Methods: Over a period of 2 months, paired (exposed and non-exposed) containers with cooked rice were placed on the ground in kitchen areas in an urban slum area in Dhaka, Bangladesh, and the numbers of flies landing on the exposed rice were counted. Following exposure, the surface of the rice was microbiologically and molecularly analysed for the presence of Escherichia coli and genes of diarrhoeagenic E. coli and Shigella strains. Results: Rice was at greater risk (P < 0·001) of being contaminated with E. coli if flies landed on the rice than if no flies landed on the rice (odds ratio 5·4 (P < 0·001, 95% CI: 2·5-11·7). Mean contamination in exposed rice samples (n = 60) was 3·1 × 103 CFU/g (95% CI: 2·2 × 103-4·0 × 103). Furthermore, for approximately half of the observed fly landings, the average CFU per fly landing was >0·6 × 103 CFU. Genes of diarrhoeagenic E. coli and Shigella species were detected in 39 of 60 (65%) of exposed rice samples. Two fly species were identified: the common housefly (Musca domestica) and the oriental latrine fly (Chrysomya megacephala). Conclusion: Flies may transmit large quantities of E. coli to food under field settings. The findings highlight the importance of implementing control measures to minimise exposure of food to flies to ensure food safety. Fly control measures should be considered for the prevention of diarrhoeal diseases caused by E. coli.
MeSH term(s)	Animals ; Bangladesh ; Colony Count, Microbial ; Diptera ; Escherichia coli/isolation & purification ; Escherichia coli Infections/transmission ; Food Contamination ; Houseflies/microbiology ; Humans ; Insect Vectors/microbiology ; Poverty Areas
Language	English
Publishing date	2017-12-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1314080-2
ISSN	1365-3156 ; 1360-2276
ISSN (online)	1365-3156
ISSN	1360-2276
DOI	10.1111/tmi.13003
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Article ; Online: Deep Learning Based on Standard H&E Images of Primary Melanoma Tumors Identifies Patients at Risk for Visceral Recurrence and Death.

Clinical cancer research : an official journal of the American Association for Cancer Research

2019 Volume 26, Issue 5, Page(s) 1126–1134

Abstract: Purpose: Biomarkers for disease-specific survival (DSS) in early-stage melanoma are needed to select patients for adjuvant immunotherapy and accelerate clinical trial design. We present a pathology-based computational method using a deep neural network ... ...

Abstract	Purpose: Biomarkers for disease-specific survival (DSS) in early-stage melanoma are needed to select patients for adjuvant immunotherapy and accelerate clinical trial design. We present a pathology-based computational method using a deep neural network architecture for DSS prediction. Experimental design: The model was trained on 108 patients from four institutions and tested on 104 patients from Yale School of Medicine (YSM, New Haven, CT). A receiver operating characteristic (ROC) curve was generated on the basis of vote aggregation of individual image sequences, an optimized cutoff was selected, and the computational model was tested on a third independent population of 51 patients from Geisinger Health Systems (GHS). Results: Area under the curve (AUC) in the YSM patients was 0.905 ( Conclusions: The novel method presented is applicable to digital images, obviating the need for sample shipment and manipulation and representing a practical advance over current genetic and IHC-based methods.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Algorithms ; Area Under Curve ; Biopsy/methods ; Deep Learning/standards ; Disease Progression ; Female ; Follow-Up Studies ; Humans ; Image Processing, Computer-Assisted/methods ; Image Processing, Computer-Assisted/standards ; Male ; Melanoma/mortality ; Melanoma/pathology ; Middle Aged ; Neoplasm Recurrence, Local/mortality ; Neoplasm Recurrence, Local/pathology ; Neural Networks, Computer ; Retrospective Studies ; Risk Factors ; Staining and Labeling/methods ; Survival Rate ; Young Adult
Language	English
Publishing date	2019-10-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-19-1495
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Article ; Online: On the (Near) Equivalence of Welfarist and Extra-Welfarist Methods to Value Healthcare With Implications for Assessing Equity.

Phelps, Charles E

Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research

2023 Volume 26, Issue 11, Page(s) 1601–1607

Abstract: Objectives: While welfarist economics (WE) methods rely wholly on individuals' valuations, extra-welfarist (EW) methods seek alternative measures of value. Major reviews of the EW literature conclude that EW studies almost universally replace "utility" ... ...

Abstract	Objectives: While welfarist economics (WE) methods rely wholly on individuals' valuations, extra-welfarist (EW) methods seek alternative measures of value. Major reviews of the EW literature conclude that EW studies almost universally replace "utility" with "health" as the maximand. This analysis seeks to understand what conclusions are necessary and sufficient to make EW and WE methods concurrent and discusses implications for measuring social value. Methods: Using standard WE methods, I demonstrate that EW is equivalent to WE with 2 key restrictions-individuals have constant returns to health in producing utility and health budgets are fixed. Fixing budgets removes a key WE step, determining the marginal rate of substitution between consumption and health, the willingness to pay for health gains. Results: Because EW methods equate with WE with these 2 restrictions, I show how formal models to construct aggregated social welfare functions (SWFs) in WE frameworks lead directly to SWF models using EW models of value. I also show that, in fixed-budget health systems, when SWFs place different values for improving health of different subpopulations, aggregate health output fails as a SWF criterion. I demonstrate how different societal values can and should enter EW SWF models using WE criteria. I also discuss the implications when either of these key restrictions does not properly represent people's preferences. Conclusions: Once EW methods are shown to be a restricted form of WE methods, those WE methods can illuminate how best to measure SWFs in EW environments.
MeSH term(s)	Humans ; Cost-Benefit Analysis ; Delivery of Health Care ; Social Welfare
Language	English
Publishing date	2023-08-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	1471745-1
ISSN	1524-4733 ; 1098-3015
ISSN (online)	1524-4733
ISSN	1098-3015
DOI	10.1016/j.jval.2023.08.001
Database	MEDical Literature Analysis and Retrieval System OnLINE

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