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2.
Ann Intern Med ; 162(5): 380-3, 2015 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-25732280

RESUMO

This article applies major economic concepts, such as supply, demand, monopoly, monopsony, adverse selection, and moral hazard, to central features of U.S. health care. These illustrations help explain some of the principal problems of health policy-high cost and the uninsured-and why solutions are difficult to obtain.


Assuntos
Atenção à Saúde/economia , Política de Saúde/economia , Financiamento Governamental , Reforma dos Serviços de Saúde/economia , Gastos em Saúde , Humanos , Pessoas sem Cobertura de Seguro de Saúde , Estados Unidos
6.
J Org Chem ; 78(8): 3592-615, 2013 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-23544787

RESUMO

The development of zinc-mediated and -catalyzed asymmetric propargylations of trifluoromethyl ketones with a propargyl borolane and the N-isopropyl-l-proline ligand is presented. The methodology provided moderate to high stereoselectivity and was successfully applied on a multikilogram scale for the synthesis of the Glucocorticoid agonist BI 653048. A mechanism for the boron-zinc exchange with a propargyl borolane is proposed and supported by modeling at the density functional level of theory. A water acceleration effect on the zinc-catalyzed propargylation was discovered, which enabled a catalytic process to be achieved. Reaction progress analysis supports a predominately rate limiting exchange for the zinc-catalyzed propargylation. A catalytic amount of water is proposed to generate an intermediate that catalyzes the exchange, thereby facilitating the reaction with trifluoromethyl ketones.


Assuntos
Ácidos Borônicos/química , Hidrocarbonetos Fluorados/química , Cetonas/química , Pargilina/análogos & derivados , Pargilina/química , Prolina/análogos & derivados , Prolina/química , Zinco/química , Catálise , Estrutura Molecular , Estereoisomerismo
7.
J Org Chem ; 78(8): 3616-35, 2013 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-23544738

RESUMO

The development of a large scale synthesis of the glucocorticoid agonist BI 653048 BS H3PO4 (1·H3PO4) is presented. A key trifluoromethyl ketone intermediate 22 containing an N-(4-methoxyphenyl)ethyl amide was prepared by an enolization/bromine-magnesium exchange/electrophile trapping reaction. A nonselective propargylation of trifluoromethyl ketone 22 gave the desired diastereomer in 32% yield and with dr = 98:2 from a 1:1 diastereomeric mixture after crystallization. Subsequently, an asymmetric propargylation was developed which provided the desired diastereomer in 4:1 diastereoselectivity and 75% yield with dr = 99:1 after crystallization. The azaindole moiety was efficiently installed by a one-pot cross coupling/indolization reaction. An efficient deprotection of the 4-methoxyphenethyl group was developed using H3PO4/anisole to produce the anisole solvate of the API in high yield and purity. The final form, a phosphoric acid cocrystal, was produced in high yield and purity and with consistent control of particle size.


Assuntos
Amidas/química , Benzamidas/química , Glucocorticoides/agonistas , Glucocorticoides/química , Piridinas/química , Pirróis/química , Estrutura Molecular , Estereoisomerismo
11.
J Econ Perspect ; 26(3): 137-156, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-25076810

RESUMO

The share of increases in life expectancy realized after age 65 was only about 20 percent at the beginning of the 20th century for the US and 16 other countries at comparable stages of development; but that share was close to 80 percent by the dawn of the 21st century, and is almost certainly approaching 100 percent asymptotically. This new demographic transition portends a diminished survival effect on working life. For high-income countries at the forefront of the longevity transition, expected lifetime labor force participation as a percent of life expectancy is declining. Innovative policies are needed if societies wish to preserve a positive relationship running from increasing longevity to greater prosperity.

16.
Ann Intern Med ; 150(7): 493-5, 2009 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-19258550

RESUMO

The coverage, cost, and quality problems of the U.S. health care system are evident. Sustainable health care reform must go beyond financing expanded access to care to substantially changing the organization and delivery of care. The FRESH-Thinking Project (www.fresh-thinking.org) held a series of workshops during which physicians, health policy experts, health insurance executives, business leaders, hospital administrators, economists, and others who represent diverse perspectives came together. This group agreed that the following 8 recommendations are fundamental to successful reform: 1. Replace the current fee-for-service payment system with a payment system that encourages and rewards innovation in the efficient delivery of quality care. The new payment system should invest in the development of outcome measures to guide payment. 2. Establish a securely funded, independent agency to sponsor and evaluate research on the comparative effectiveness of drugs, devices, and other medical interventions. 3. Simplify and rationalize federal and state laws and regulations to facilitate organizational innovation, support care coordination, and streamline financial and administrative functions. 4. Develop a health information technology infrastructure with national standards of interoperability to promote data exchange. 5. Create a national health database with the participation of all payers, delivery systems, and others who own health care data. Agree on methods to make de-identified information from this database on clinical interventions, patient outcomes, and costs available to researchers. 6. Identify revenue sources, including a cap on the tax exclusion of employer-based health insurance, to subsidize health care coverage with the goal of insuring all Americans. 7. Create state or regional insurance exchanges to pool risk, so that Americans without access to employer-based or other group insurance could obtain a standard benefits package through these exchanges. Employers should also be allowed to participate in these exchanges for their employees' coverage. 8. Create a health coverage board with broad stakeholder representation to determine and periodically update the affordable standard benefit package available through state or regional insurance exchanges.


Assuntos
Reforma dos Serviços de Saúde/organização & administração , Cobertura Universal do Seguro de Saúde/organização & administração , Regulamentação Governamental , Reforma dos Serviços de Saúde/economia , Humanos , Reembolso de Seguro de Saúde/economia , Gestão da Qualidade Total/economia , Estados Unidos , Cobertura Universal do Seguro de Saúde/economia
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