RESUMO
From the inception of the Medicare program there have been questions regarding whether and how to pay for durable medical equipment, prosthetics, orthotics, and supplies. In 2011 the Centers for Medicare and Medicaid Services (CMS) implemented a competitive bidding program to reduce spending on durable medical equipment and similar items. Previously, CMS had used prices in an administrative fee schedule to reimburse for these items. We compared prices from Round 1 of the Medicare competitive bidding program, which were established for the periods 2011-13 and 2014-16, to prices paid by national commercial insurers for the same types of items in 2011-14. Our results suggest that the initial years of the program produced prices comparable to those obtained, on average, by large commercial insurers-sophisticated purchasers that presumably were able to negotiate prices with suppliers of durable medical equipment and similar items.
Assuntos
Proposta de Concorrência/métodos , Custos e Análise de Custo/economia , Equipamentos Médicos Duráveis/economia , Renda , Medicare/economia , Humanos , Estados UnidosRESUMO
The P2Y12/ADP receptor plays a central role in platelet activation. Characterization of this receptor is mandatory for studying disorders associated with a P2Y12 receptor defect and for evaluating P2Y12 receptor agonists and antagonists. In the absence of suitable anti-P2Y12 antibodies, radioligand binding assays are the only way to conduct such studies. While various radioligands were employed in the past for this purpose, none were found to be suitable for routine use. Described in this unit are protocols for quantitatively and qualitatively assessing P2Y12 receptors with [³H]PSB-0413, a selective antagonist for this site. The saturation and competition assays described herein make possible the determination of P2Y12 receptor density on cells, as well as the potencies and affinities of test agents at this site.
Assuntos
Monofosfato de Adenosina/análogos & derivados , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Receptores Purinérgicos P2Y12/metabolismo , Receptores Purinérgicos P2/metabolismo , Tionucleosídeos/farmacologia , Monofosfato de Adenosina/farmacologia , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Proposta de Concorrência/métodos , Humanos , Ensaio Radioligante/métodosRESUMO
The traditional Medicare fee-for-service program may be able to purchase clinical laboratory test services at a lower cost through competitive bidding. Demonstrations of competitive bidding for clinical laboratory tests have been twice mandated or authorized by Congress but never implemented. This article provides a summary and review of the final design of the laboratory competitive bidding demonstration mandated by the Medicare Modernization Act of 2003. The design was analogous to a sealed bid (first price), clearing price auction. Design elements presented include covered laboratory tests and beneficiaries, laboratory bidding and payment status under the demonstration, composite bids, determining bidding winners and the demonstration fee schedule, and quality under the demonstration. Expanded use of competitive bidding in Medicare, including specifically for clinical laboratory tests, has been recommended in some proposals for Medicare reform. The presented design may be a useful point of departure if Medicare clinical laboratory competitive bidding is revived in the future.
Assuntos
Serviços de Laboratório Clínico/economia , Proposta de Concorrência/economia , Custos de Cuidados de Saúde/tendências , Medicare Part B/economia , Mecanismo de Reembolso/economia , Serviços de Laboratório Clínico/legislação & jurisprudência , Proposta de Concorrência/legislação & jurisprudência , Proposta de Concorrência/métodos , Controle de Custos/legislação & jurisprudência , Controle de Custos/métodos , Tabela de Remuneração de Serviços/economia , Tabela de Remuneração de Serviços/legislação & jurisprudência , Tabela de Remuneração de Serviços/tendências , Custos de Cuidados de Saúde/legislação & jurisprudência , Humanos , Medicare Part B/legislação & jurisprudência , Mecanismo de Reembolso/legislação & jurisprudência , Mecanismo de Reembolso/tendências , Estados UnidosRESUMO
Healthcare is an important social and economic component of modern society, and the effective use of information technology in this industry is critical to its success. As health insurance premiums continue to rise, competitive bidding may be useful in generating stronger price competition and lower premium costs for employers and possibly, government agencies. In this paper, we assess an endeavor by several Fortune 500 companies to reduce healthcare procurement costs for their employees by having HMOs compete in open electronic auctions. Although the auctions were successful in generating significant cost savings for the companies in the first year, i.e., 1999, they failed to replicate the success and were eventually discontinued after two more years. Over the past decade since the failed auction experiment, effective utilization of information technologies have led to significant advances in the design of complex electronic markets. Using this knowledge, and data from the auctions, we point out several shortcomings of the auction design that, we believe, led to the discontinuation of the market after three years. Based on our analysis, we propose several actionable recommendations that policy makers can use to design a sustainable electronic market for procuring health insurance.
Assuntos
Proposta de Concorrência/economia , Proposta de Concorrência/métodos , Contratos/economia , Seguro Saúde/economia , Internet , Custos e Análise de Custo , Sistemas Pré-Pagos de Saúde/economia , Humanos , Satisfação do Paciente , Garantia da Qualidade dos Cuidados de Saúde , Estados UnidosRESUMO
Leadership within community nursing needs to be embraced and red to ensure it is inherent within the profession, not just adopted by a few. As healthcare organisations continue to change and develop to meet new political agendas, meeting the needs of patients and associated improvements to service will be shaped by those who are willing to take ideas forward. This article looks at ways all community nurses can develop their leadership skills in order to affect change.
Assuntos
Enfermagem em Saúde Comunitária/organização & administração , Liderança , Melhoria de Qualidade , Proposta de Concorrência/métodos , Reforma dos Serviços de Saúde , Humanos , Estudos de Casos Organizacionais , Inovação Organizacional , Medicina Estatal/organização & administração , Reino UnidoRESUMO
Leucine-rich repeat transmembrane neuronal proteins (LRRTMs) were recently found to instruct presynaptic and mediate postsynaptic glutamatergic differentiation. In a candidate screen, here we identify neurexin-1beta lacking an insert at splice site 4 (-S4) as a ligand for LRRTM2. Neurexins bind LRRTM2 with a similar affinity but distinct code from the code for binding neuroligin-1 (the predominant form of neuroligin-1 at glutamate synapses, containing the B splice site insert). Whereas neuroligin-1 binds to neurexins 1, 2, and 3 beta but not alpha variants, regardless of insert at splice site 4, LRRTM2 binds to neurexins 1, 2, and 3 alpha and beta variants specifically lacking an insert at splice site 4. We further show that this binding code is conserved in LRRTM1, the family member linked to schizophrenia and handedness, and that the code is functional in a coculture hemisynapse formation assay. Mutagenesis of LRRTM2 to prevent binding to neurexins abolishes presynaptic inducing activity of LRRTM2. Remarkably, mutagenesis of neurexins shows that the binding face on neurexin-1beta (-S4) is highly overlapping for the structurally distinct LRRTM2 and neuroligin-1 partners. Finally, we explore here the interplay of neuroligin-1 and LRRTM2 in synapse regulation. In neuron cultures, LRRTM2 is more potent than neuroligin-1 in promoting synaptic differentiation, and, most importantly, these two families of neurexin-binding partners cooperate in an additive or synergistic manner. Thus, we propose a synaptic code hypothesis suggesting that neurexins are master regulators of the cooperative activities of LRRTMs and neuroligins.
Assuntos
Moléculas de Adesão Celular Neuronais/metabolismo , Ácido Glutâmico/metabolismo , Moléculas de Adesão de Célula Nervosa/metabolismo , Neurônios/fisiologia , Sinapses/fisiologia , Processamento Alternativo/genética , Animais , Cálcio/metabolismo , Moléculas de Adesão Celular Neuronais/genética , Diferenciação Celular , Células Cultivadas , Chlorocebus aethiops , Proposta de Concorrência/métodos , Embrião de Mamíferos , Proteínas de Fluorescência Verde/genética , Hipocampo/citologia , Humanos , Mutagênese/genética , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Moléculas de Adesão de Célula Nervosa/genética , Ligação Proteica , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Ratos , Transfecção/métodosRESUMO
PURPOSE: We assessed the anticonvulsant potential of the phytocannabinoid Δ9-tetrahydrocannabivarin (Δ9-THCV) by investigating its effects in an in vitro piriform cortex (PC) brain slice model of epileptiform activity, on cannabinoid CB1 receptor radioligand-binding assays and in a generalized seizure model in rats. METHODS: Δ9-THCV was applied before (10 µm Δ9-THCV) or during (10-50 µm Δ9-THCV) epileptiform activity induced by Mg²(+) -free extracellular media in adult rat PC slices and measured using multielectrode array (MEA) extracellular electrophysiologic techniques. The actions of Δ9-THCV on CB1 receptors were examined using [³H]SR141716A competition binding and [³5S]GTPγS assays in rat cortical membranes. Effects of Δ9-HCV (0.025-2.5 mg/kg) on pentylenetetrazole (PTZ)-induced seizures in adult rats were also assessed. RESULTS: After induction of stable spontaneous epileptiform activity, acute Δ9 -THCV application (≥ 20 µm) significantly reduced burst complex incidence and the amplitude and frequency of paroxysmal depolarizing shifts (PDSs). Furthermore, slices pretreated with 10 µm Δ9-THCV prior to induction of epileptiform activity exhibited significantly reduced burst complex incidence and PDS peak amplitude. In radioligand-binding experiments, Δ9-THCV acted as a CB1 receptor ligand, displacing 0.5 nm [³H]SR141716A with a Kiâ¼290 nm, but exerted no agonist stimulation of [³5S]GTPγS binding. In PTZ-induced seizures in vivo, 0.25 mg/kg Δ9-THCV significantly reduced seizure incidence. DISCUSSION: These data demonstrate that Δ9-THCV exerts antiepileptiform and anticonvulsant properties, actions that are consistent with a CB1 receptor-mediated mechanism and suggest possible therapeutic application in the treatment of pathophysiologic hyperexcitability states.
Assuntos
Córtex Cerebral/efeitos dos fármacos , Dronabinol/análogos & derivados , Epilepsia/tratamento farmacológico , Epilepsia/fisiopatologia , Potenciais Evocados/efeitos dos fármacos , Animais , Córtex Cerebral/fisiologia , Proposta de Concorrência/métodos , Modelos Animais de Doenças , Dronabinol/farmacologia , Dronabinol/uso terapêutico , Interações Medicamentosas , Epilepsia/induzido quimicamente , Feminino , Guanosina 5'-O-(3-Tiotrifosfato)/metabolismo , Técnicas In Vitro , Masculino , Pentilenotetrazol , Isótopos de Fósforo/metabolismo , Piperidinas/farmacocinética , Pirazóis/farmacocinética , Ratos , Receptor CB1 de Canabinoide/agonistas , Receptor CB1 de Canabinoide/antagonistas & inibidores , RimonabantoRESUMO
The cannabinoid CB1 receptor (CB1) is one of the most abundant G protein-coupled receptors in the brain, but little is known about the mechanisms that modulate CB1 receptor signaling. Here, we show that inhibition or null mutation of the epsilon isozyme of protein kinase C (PKCepsilon) selectively enhances behavioral responses to the CB1 agonist WIN55,212-2 in mice, but not to the structurally unrelated CB1 agonist CP55,940. Binding affinity for [(3)H] WIN55,212-2 was increased in brain membranes from PKCepsilon(-/-) mice compared with PKCepsilon(+/+) mice. There was no difference in binding of the inverse agonist [(3)H] SR141716A. In addition, repeated administration of WIN55,212-2 produced greater analgesic and thermal tolerance in PKCvarepsilon(-/-) mice compared with PKCepsilon(+/+)mice. These results indicate that PKCvarepsilon selectively regulates behavioral sensitivity, CB1 receptor binding and tolerance to WIN55,212-2.
Assuntos
Comportamento Animal/efeitos dos fármacos , Benzoxazinas/farmacologia , Tolerância a Medicamentos/genética , Morfolinas/farmacologia , Naftalenos/farmacologia , Proteína Quinase C-épsilon/metabolismo , Receptor CB1 de Canabinoide/agonistas , Analgesia , Analgésicos/farmacologia , Animais , Comportamento Animal/fisiologia , Proposta de Concorrência/métodos , Cicloexanóis/farmacologia , Relação Dose-Resposta a Droga , Tolerância a Medicamentos/fisiologia , Inibidores Enzimáticos/farmacologia , Hipotermia/induzido quimicamente , Hipotermia/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Atividade Motora/efeitos dos fármacos , Atividade Motora/genética , Peptídeos/farmacologia , Ligação Proteica/efeitos dos fármacos , Proteína Quinase C-épsilon/deficiência , Serina/genética , Serina/metabolismo , Trítio/metabolismoRESUMO
The presence of beta-amyloid plaques in brain is a hallmark of Alzheimer's disease (AD) and serves as a biomarker for confirmation of diagnosis postmortem. Positron emission tomography (PET) radioligands such as Pittsburgh compound B ([(11)C]-2-(3-fluoro-4-methylamino-phenyl)-benzothiazol-6-ol) (PIB) binds selectively to beta-amyloid and are promising new tools supporting the clinical diagnoses of AD. In addition, such methodology may be useful for evaluation of new drugs aiming at reduction of amyloid plaque load. The objective of this study is to develop a new amyloid selective PET radioligand with higher signal-to-background ratio when compared with existing amyloid PET ligands. The lead compound, AZD2184, (2-[6-(methylamino)pyridin-3-yl]-1,3-benzothiazol-6-ol) was found to have high affinity for amyloid fibrils in vitro (K(d): 8.4 +/- 1.0 nM). Two minutes after i.v. administration in rats, about 1% of the dose was in brain. In vitro autoradiography on cortical brain sections from amyloid-beta precursor protein/presenilin 1 (APP/PS1) mice and AD patients showed that while [(3)H]AZD2184 and [(3)H]PIB are mutually displaceable, [(3)H]AZD2184 displays a higher signal-to-background ratio primarily by virtue of lower background binding levels. The ratio of binding ability in prefrontal cortex (high plaque load) to subcortical white matter (background) was 4.5 for [(3)H]AZD2184 and 0.8 for [(3)H]PIB at 1 nM. In adjacent cortical sections from APP/PS1 mouse as well as from AD cortical tissue, [(3)H]AZD2184 and antibodies to human beta-amyloid labeled identical structures. In vivo administration of [(3)H]AZD2184 to APP/PS1 mice further showed that [(3)H]AZD2184 labels amyloid deposits with low non-specific background binding. Taken together, the pre-clinical profile of AZD2184 in relation to the reference ligand PIB, suggests that (11)C-labeled AZD2184 is a potential radioligand for PET-visualization of beta-amyloid deposits in the living human brain.
Assuntos
Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Placa Amiloide/diagnóstico por imagem , Doença de Alzheimer/patologia , Aminopiridinas/metabolismo , Precursor de Proteína beta-Amiloide/genética , Compostos de Anilina/química , Compostos de Anilina/metabolismo , Animais , Autorradiografia , Benzotiazóis/metabolismo , Encéfalo/diagnóstico por imagem , Radioisótopos de Carbono/metabolismo , Proposta de Concorrência/métodos , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Mutação/genética , Tomografia por Emissão de Pósitrons/métodos , Presenilina-1/genética , Ligação Proteica/efeitos dos fármacos , Ensaio Radioligante/métodos , Ratos , Ratos Sprague-Dawley , Tiazóis/química , Tiazóis/metabolismo , Trítio/metabolismoRESUMO
PURPOSE: The purpose of this paper is, for English acute NHS hospitals, to investigate how they operate their governance systems in the area of secondary care contracting and identify the key determinants of relationship building within the contacting/commissioning of secondary care focusing upon non-price competitive behaviour. DESIGN/METHODOLOGY/APPROACH: A survey instrument was designed and mailed to a sample of all acute NHS hospitals in England of whom 35 per cent responded. This survey was then analysed using logit techniques. FINDINGS: The analysis suggests that: those NHS Trusts offering volume discounts, non-price competitive incentives or having a strong belief in performance being by "payment by results" criteria are significantly more likely to offer augmented services to secondary care purchasers over and above contractual minima; those NHS Trusts strongly believing in the importance of non-price factors (such as contract augmentation or quality) in the contracting process are more likely to offer customisation of generic services; and those NHS Trusts using cost-sharing agreements to realign contracts when negotiating contracts or who strongly believe in the importance of service augmentation in strengthening relationships, or that increased hospital efficiency is the most important aspect of recent NHS reform are more likely to utilise default measures to help realign contracts. ORIGINALITY/VALUE: This paper fills a gap in the area of non-price competition in English NHS acute secondary care contracting.
Assuntos
Proposta de Concorrência/métodos , Contratos/economia , Serviços Terceirizados/métodos , Medicina Estatal/organização & administração , Proposta de Concorrência/economia , Inglaterra , Pesquisas sobre Atenção à Saúde , Hospitais Públicos , Serviços Terceirizados/organização & administraçãoRESUMO
Among numerous neurotransmitters involved in central cardiovascular control, glutamate is one of the most studied transmitters that are related to nicotine considering its release and its postsynaptic regulation. However, there are no conclusive studies about nicotine effects on glutamatergic system and its relevance on hypertension development, which can help to understand the role of these two systems in that pathology. In this context, the objective of the present study is to evaluate the effects of systemic chronic nicotine exposure on hypertension development as well as the interaction between nicotine and the glutamatergic system in normotensive and neurogenic hypertensive rats. By means of high performance liquid chromatograph, immunohistochemistry, in situ hybridization and binding techniques, glutamatergic system was evaluated in SHR and Wistar Kyoto (WKY) rats treated with nicotine, delivered subcutaneously through nicotine pellets, for 8 weeks. The most important findings in this study were that (1) moderate doses of nicotine accelerated the onset and increased blood pressure in SHR but not in WKY rats, (2) the nicotine dosage and time of treatment employed did not affect body weight, (3) chronic nicotine treatment differentially affected glutamatergic system in normotensive and hypertensive rats, and (4) spontaneously hypertensive rats seem to be more sensitive to peripherally administered nicotine than Wistar Kyoto rats considering blood pressure and glutamatergic neurotransmission changes. In conclusion, we have demonstrated that a moderate dose of nicotine accelerates the onset and exacerbates hypertension in the SHR and that might be, at least in part, related to the modulation of glutamatergic neurotransmission.
Assuntos
Ácido Glutâmico/metabolismo , Hipertensão/induzido quimicamente , Nicotina/efeitos adversos , Agonistas Nicotínicos/efeitos adversos , Análise de Variância , Animais , Pressão Sanguínea/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Cromatografia Líquida de Alta Pressão/métodos , Proposta de Concorrência/métodos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Esquema de Medicação , Agonistas de Aminoácidos Excitatórios/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hibridização In Situ/métodos , Masculino , Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Ligação Proteica/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
Laboratories entering into a discussion regarding automation of their facility have a number of key issues that need to be considered right away. What is the financial impact going to be? How do we know which processes we should automate and which ones we shouldn't? Which vendor is going to best align with the goals of our organization? Developing a thorough and robust plan at the start of the automation process is vital to the overall success of the project. It requires dedicated staff members who are willing to do the research, crunch the numbers, and present the data effectively. In Part II of this manuscript, issues such as cost analyses, business plans, and purchasing decisions are each covered thoroughly.
Assuntos
Automação/métodos , Laboratórios Hospitalares/organização & administração , Guias de Prática Clínica como Assunto , Desenvolvimento de Programas/métodos , Automação/economia , Proposta de Concorrência/métodos , Análise Custo-Benefício , Equipamentos e Provisões Hospitalares/economia , Administração Financeira de Hospitais/métodos , Humanos , Los Angeles , Pessoal de Laboratório Médico/organização & administração , Estudos de Casos Organizacionais , Técnicas de Planejamento , Serviço Hospitalar de Compras/métodos , Mecanismo de ReembolsoAssuntos
Técnicas de Laboratório Clínico/instrumentação , Equipamentos e Provisões/economia , Laboratórios/economia , Proposta de Concorrência/economia , Proposta de Concorrência/métodos , Análise Custo-Benefício/métodos , Administração Financeira/métodos , Aluguel de Propriedade/economia , Aluguel de Propriedade/métodosRESUMO
The formation and plasticity of synaptic connections rely on regulatory interactions between pre- and postsynaptic cells. We show that the Drosophila heparan sulfate proteoglycans (HSPGs) Syndecan (Sdc) and Dallylike (Dlp) are synaptic proteins necessary to control distinct aspects of synaptic biology. Sdc promotes the growth of presynaptic terminals, whereas Dlp regulates active zone form and function. Both Sdc and Dlp bind at high affinity to the protein tyrosine phosphatase LAR, a conserved receptor that controls both NMJ growth and active zone morphogenesis. These data and double mutant assays showing a requirement of LAR for actions of both HSPGs lead to a model in which presynaptic LAR is under complex control, with Sdc promoting and Dlp inhibiting LAR in order to control synapse morphogenesis and function.
Assuntos
Proteínas de Drosophila/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/fisiologia , Neurônios/citologia , Proteínas Tirosina Fosfatases/fisiologia , Proteoglicanas/metabolismo , Receptores de Superfície Celular/fisiologia , Sinapses/fisiologia , Animais , Western Blotting/métodos , Células Cultivadas , Proposta de Concorrência/métodos , Proteínas de Ligação a DNA/metabolismo , Drosophila , Potenciais Pós-Sinápticos Excitadores/fisiologia , Potenciais Pós-Sinápticos Excitadores/efeitos da radiação , Cones de Crescimento/metabolismo , Peroxidase do Rábano Silvestre/metabolismo , Imuno-Histoquímica/métodos , Larva/citologia , Microscopia Eletrônica de Transmissão/métodos , Modelos Biológicos , Morfogênese , Junção Neuromuscular/metabolismo , Junção Neuromuscular/ultraestrutura , Fosforilação/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/fisiologia , RNA de Cadeia Dupla/farmacologia , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores , Sinapses/ultraestrutura , Transmissão Sináptica/fisiologia , Sindecanas , Transfecção/métodosRESUMO
The purpose of this study was to examine the functional interaction between endogenous opioid and cannabinoid receptor systems in the caudate putamen and nucleus accumbens. We therefore examined by autoradiography the functional activity and density of micro-, kappa- and delta-opioid receptors in both brain regions of cannabinoid CB1 receptor knockout mice. Functional activity was estimated by measuring agonist-stimulated [35S]GTPgammaS binding. Results showed that deletion of the CB1 cannabinoid receptor markedly increased kappa-opioid (50%) and delta-opioid (42%) receptor activities whereas no differences were found in micro-opioid receptor in the caudate putamen. In contrast, binding autoradiography showed a similar density of micro-, kappa- and delta-opioid receptors between mutant and wild-type mice. No differences were found in densities or activities of micro-, kappa- and delta-opioid receptors between mutant and wild-type mice in the nucleus accumbens. Taken together, our results revealed that deletion of CB1 cannabinoid receptors produced a pronounced increase in the activity of kappa- and delta-opioid receptors in the caudate putamen. This endogenous interaction between opioid and cannabinoid receptors may be relevant to further understand a variety of neuroadaptative processes involving the participation of opioid receptors, such as motor behaviour, emotional responses and drug dependence.